Phylogeography of Phytophagous Weevils and Plant Species in Broadleaved Evergreen Forests: A Congruent Genetic Gap between Western and Eastern Parts of Japan.
The Quaternary climate cycles played an important role in shaping the distribution of biodiversity among current populations, even in warm-temperate zones, where land was not covered by ice sheets. We focused on the Castanopsis-type broadleaved evergreen forest community in Japan, which characterizes the biodiversity and endemism of the warm-temperate zone. A comparison of the phylogeographic patterns of three types of phytophagous weevils associated with Castanopsis (a host-specific seed predator, a generalist seed predator, and a host-specific leaf miner) and several other plant species inhabiting the forests revealed largely congruent patterns of genetic differentiation between western and eastern parts of the main islands of Japan. A genetic gap was detected in the Kii Peninsula to Chugoku-Shikoku region, around the Seto Inland Sea. The patterns of western-eastern differentiation suggest past fragmentation of broadleaved evergreen forests into at least two separate refugia consisting of the southern parts of Kyushu to Shikoku and of Kii to Boso Peninsula. Moreover, the congruent phylogeographic patterns observed in Castanopsis and the phytophagous insect species imply that the plant-herbivore relationship has been largely maintained since the last glacial periods. These results reinforce the robustness of the deduced glacial and postglacial histories of Castanopsis-associated organisms.


Assessment of plasma and tissue fibronectin EIIIB splice variant expressions measured serially using RT-PCR in a wound model of rabbits.
Fibronectin (FN) is an indispensable part of the extracellular matrix. During regeneration or wound healing, the plasma form of FN is incorporated into the fibrin clots to form a temporary fibrin-FN matrix, and also locally synthesized cellular FN migrates to the clot to regenerate the injured tissue. We aimed to examine wound tissue FN EIIIB and plasma FN EIIIB expression levels in an experimental wound healing model in rabbits. Plasma and tissue EIIIB splice variant expressions were measured serially with RT-qPCR in a cutaneous wound model of rabbits. Tissue FN expression increased as beginning on day 3 and continued to increase on days 6 and 9, reaching maximum expression at day 12 before starting to decrease. On the contrary to the tissue levels, plasma FN levels gradually decreased until day 15 when expression returned to the initial values. The findings of the current study support that tissue EIIIB expression level increases during wound healing; and plasma EIIIB expression level decreases minimal changed. This is in contrast to reports where plasma FN provisionally helps ECM formation. Therefore, our data show an essential role of EIIIB at the tissue level in accelerating the wound healing process. The RT-qPCR method in our experimental setup can provide more accurate and precise results compared to the antibody-based methods.


Radially Electrospun Fibrous Membrane Incorporated with Copper Peroxide Nanodots Capable of Self-Catalyzed Chemodynamic Therapy for Angiogenesis and Healing Acceleration of Diabetic Wounds.
Vascular dysfunction severely hinders the healing process of diabetic wounds. Therefore, a radially structured fibrous membrane was fabricated through electrospinning by using a polycaprolactone (PCL) and polyvinylpyrrolidone (PVP) mixed solution containing copper peroxide nanoparticles (CPs) as the chemodynamic therapy (CDT) agents, aiming to simultaneously accelerate tissue regeneration and angiogenesis. The fabricated membrane allowed for the in situ H2O2 generation activated by the acidic diabetic microenvironment and the subsequent Fenton-type reactions to realize 99.4% elimination against Staphylococcus aureus. Besides, the released Cu2+ ions significantly enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells (HUVECs), and they showed enhanced in vitro angiogenesis. Interestingly, the CP-embedded membrane also guided cell spreading and orientated migration of L929 fibroblasts along the fiber distribution through the radially aligned topology. The in vivo implantation indicated that the raidally structured membrane modified by CPs not only dramatically accelerated wound healing of diabetic Sprague-Dawley (SD) rats in 14 days but also promoted angiogenesis in wound sites. The combination of the in situ CDT with the radially structured morphology of the functional membrane is highly promising in applications to promote diabetic wound healing through anti-infection and revascularization.


Type I persistent proatlantal artery associated with fusiform subclavian artery aneurysm: Report of one case.
We report a 61 years old male presenting with a right cerebral infarction, along with a type I persistent left proatlantal artery (PA), which is a form of primitive carotid-basilar anastomosis. The patient had an absence of the ipsilateral vertebral artery (VA) and hypoplasia of the contralateral VA, while the basilar artery was supplied by the PA. Other vascular anomalies present were a fusiform aneurysm of the right subclavian artery, and an A1 segment aplasia of the hypoplastic anterior right cerebral artery, which originated from the anterior communicating artery. To our knowledge these anomalies were not described previously.


A comparison of pre ICU admission SIRS, EWS and q SOFA scores for predicting mortality and length of stay in ICU.
The 2015 sepsis definitions suggest using the quick SOFA score for risk stratification of sepsis patients among other changes in sepsis definition. Our aim was to validate the q sofa score for diagnosing sepsis and comparing it to traditional scores of pre ICU admission sepsis outcome prediction such as EWS and SIRS in our setting in order to predict mortality and length of stay. This was a retrospective cohort study. We retrospectively calculated the q sofa, SIRS and EWS scores of all ICU patients admitted with the diagnosis of sepsis at our center in 2015. This was analysed using STATA 12. Logistic regression and ROC curves were used for analysis in addition to descriptive analysis. 58 patients were included in the study. Based on our one year results we have shown that although q SOFA is more sensitive in predicting LOS in ICU of sepsis patients, the EWS score is more sensitive and specific in predicting mortality in the ICU of such patients when compared to q SOFA and SIRS scores. In conclusion, we find that in our setting, EWS is better than SIRS and q SOFA for predicting mortality and perhaps length of stay as well. The q Sofa score remains validated for diagnosis of sepsis.


Predictors of death in patients with life-threatening pelvic hemorrhage after successful transcatheter arterial embolization.
The purpose of this study was to determine predictors of death in patients with pelvic fracture whose pelvic arterial hemorrhage is controlled successfully by transcatheter arterial embolization (TAE). From January 1996 to December 2000, 61 patients with a pelvic fracture who had pelvic arterial hemorrhage were treated at our Level I trauma center according to a protocol that assigns a high priority to diagnostic and therapeutic angiography within the algorithm. Angiography is performed before laparotomy in patients with hemoperitoneum, who can be stabilized by fluid resuscitation, and otherwise afterward. External fixation was performed immediately after TAE in the angiography suite. Predictors of outcome were determined retrospectively by univariate and multivariate analysis using anatomic and physiologic parameters. Forty-eight patients survived and 13 died. TAE successfully controlled pelvic arterial hemorrhage in all patients. Predictors of death included posterior pelvic arterial injury and an elevated Acute Physiology and Chronic Health Evaluation II score (odds ratio, 15.6 and 23.9, respectively). Need for fluid requirements to achieve hemodynamic stability were higher in nonsurvivors than in survivors. Outcome did not correlate with the type of fracture or the Injury Severity Score. Application of angiography as a therapeutic intervention in patients with pelvic arterial bleeding may reduce the need for surgery, thereby avoiding or minimizing this additional trauma.


A randomized controlled trial of early versus "traditional" postoperative oral intake after major abdominal gynecologic surgery.
The purpose of this study was to compare early oral intake and the traditional timing of feeding after major gynecologic surgery and the effects on the length of hospital stay. Gynecologic oncology and urogynecology patients who underwent major abdominal gynecologic surgery were prospectively randomized to 1 of 2 groups. The traditional feeding group (group A, 49 patients) received nothing by mouth until documentation of bowel function. They were then advanced slowly to solid diet. The patients allocated to the early feeding regimen (group B, 47 patients) began clear fluids on the first postoperative day. Once 500 mL of clear fluid was tolerated, they received a regular diet. The groups were compared with regard to length of hospital stay, postoperative day that solids were tolerated, and the incidence of adverse effects. Statistical analyses were performed with the chi(2) test, the Fisher exact test, the Student t test, and analysis of variance. The demographic characteristics of the 2 groups were similar. There was a statistically significant reduction in the length of hospital stay for those patients on the early feeding regimen. The median length of stay for group A was 6.0 days and for group B was 4.0 days (P =.0001). There was no difference in the incidence of emesis, ileus, or other postoperative complications between the 2 groups. Early postoperative dietary advancement after major abdominal gynecologic surgery results in a decreased length of hospital stay and appears to be safe, with no increased adverse effects.


The Effect of the Shikamana Peer-and-Provider Intervention on Depressive Symptoms, Alcohol Use, and Other Drug Use Among Gay, Bisexual, and Other Men Who Have Sex with Men in Kenya.
Kenyan gay, bisexual, and other men who have sex with men (GBMSM) face stigma and discrimination, which may adversely impact mental health and limit antiretroviral therapy (ART) adherence among GBMSM living with HIV. We evaluated whether the Shikamana peer-and-provider intervention, which improved ART adherence among participants in a small randomized trial, was associated with changes in mental health or substance use. The intervention was associated with a significant decrease in PHQ-9 score between baseline and month 6 (estimated change - 2.7, 95% CI - 5.2 to - 0.2, p = 0.037) compared to standard care. In an exploratory analysis, each one-point increment in baseline HIV stigma score was associated with a - 0.7 point (95% CI - 1.3 to - 0.04, p = 0.037) greater decrease in PHQ-9 score over the study period in the intervention group. Additional research is required to understand factors that influence this intervention's effects on mental health outcomes.


Stromal expression of Fer suppresses tumor progression in renal cell carcinoma and is a predictor of survival.
Fps/Fes related (Fer) is a non-receptor tyrosine kinase that is expressed in fibroblasts, immune cells and endothelial cells. Fer serves an important pathological role in cell survival, angiogenesis and the immune system. However, the pathological role of Fer expression in the stromal cells surrounding renal cell carcinoma (RCC) has not been previously investigated. In the present study, immunohistochemical analysis of Fer was performed using the formalin-fixed tissue samples of 152 patients with RCC. The proliferative and apoptotic indices were used to represent the percentage of proliferation marker protein Ki-67- and cleaved caspase-3-positive cells, respectively. The microvessel density was defined as the number of cluster of differentiation (CD) 31-positively stained vessels/mm2. In addition, CD57+ and CD68+ cells were counted using semi-quantification of natural killer (NK) cells and macrophages. Fer expression in stromal cells was negatively associated with Fuhrman grade, pathological tumor stage and metastasis (P<0.001). Fer expression in stromal cells was negatively associated with CD68+ macrophage density, whereas it was positively associated with CD57+ NK cell density. Kaplan-Meier estimators indicated that decreased stromal Fer expression was a predictive marker of decreased cause-specific survival rate (P<0.001). Furthermore, low expression of Fer was identified as being an independent marker of decreased cause-specific survival using multivariate analysis (hazard ratio, 7.4; 95% confidence interval, 1.7-33.0; P<0.001). The results of the present study suggested that low Fer expression in stromal cells is associated with increased malignant aggressiveness and decreased survival in patients with RCC. CD57+ NK cell and CD68+ macrophage regulation in cancer-stromal tissue is considered to affect RCC pathology.


Neisseria gonorrhoeae in asymptomatic prepubertal household contacts of children with gonococcal infection.
This report describes the occurrence of gonococcal infection among prepubertal household contacts of children younger than 12 years of age. The records of 14 index cases (12 females and 2 males) reported during the period January 1979 and June 1983 were reviewed. Among 31 asymptomatic contacts of 10 index cases, nine (29%) had positive cultures (5 females and 4 males). Three were siblings of the index cases, and six were other children in the index households. The predominant site of positive cultures was the throat (7/9). This high recovery rate of gonococci among young asymptomatic household contacts makes clear the need for aggressive surveillance of prepubertal household contacts of children with gonococcal infection, and the importance of culturing all three sites, e.g., vagina/urethra, rectum, and throat.


Changes of maternal transcripts in oocytes from persistent follicles in cattle.
A high incidence of early embryonic loss is associated with prolonged dominance of follicles. The objective of the present experiment was to determine if persistence of a follicle resulted in alterations in mRNA expression of important genes in the oocyte. Cows were assigned to four groups: growing follicles on day 6 (G0h) or day 8 (G48h) and persistent follicles on day 13 (P0h) or day 15 (P48h) of the estrous cycle (estrus = day 0). All cows were super-stimulated on day 1-4. Cows in G48h, P0h, and P48h groups received 25 mg prostaglandin (PG) F2alpha on day 6. Cows in P0h and P48h groups received progesterone from CIDR-B devices on day 5 through 13. Ovaries of cows in G0h, G48h, P0h, and P48h groups were removed on day 6, 8, 13, and 15, respectively. Oocytes were aspirated immediately after colpotomy and denuded of cumulus cells. Quantitative real-time PCR was used to measure the mRNA abundances of 10 selected genes important for early embryogenesis in oocytes obtained from growing and persistent follicles. Relative abundances of MSY2, PARN, and YY1 mRNA (P < 0.05) were significantly lower in oocytes from persistent than from growing follicles. Oocytes from persistent follicles, however, had greater abundances of PAP and eIF-4E transcripts (P < 0.05). The data indicate that persistence of a follicle leads to altered abundances of mRNA for genes important for regulation of transcription and protein translation in the oocyte, which could compromise development of early embryos in cows that ovulate a persistent follicle.


Flexible rectangular wave-breaking-free pulse generation in actively mode-locked ytterbium-doped fiber laser.
We demonstrate nanosecond scale rectangular wave-breaking-free pulse generation in an actively mode locked Yb-doped fiber laser based on a combined action of active periodic cavity loss modulation and nonlinear polarization rotation effect. The pulse width of the laser can be controlled in the range of 890 ps to above 124 ns instantaneously by adjusting the electrical signal applied on the modulator. As high as 19.8 nJ wave-breaking-free pulse is achieved with maximum available pump power. The output pulse temporal dynamics exhibit various distinct characteristics under different modulation and polarization control. The laser presents unusually flexible tunabilities in pulse width, pulse energy and pulse shape.


Ki67 score as a potential predictor in the selection of liver-directed therapies for metastatic neuroendocrine tumors: a single institutional experience.
Neuroendocrine tumors (NETs) metastatic to the liver are treated with transarterial radioembolization (TARE) using yttrium-90 (Y-90) microspheres or transarterial chemoembolization (TACE). However the criteria for patient selection are not well defined. We sought to determine if Ki67 score could help select patients for one therapy over the other in the management of hepatic neuroendocrine metastases. Single institution analysis of patients treated with Y-90 or TACE between 2001 and 2014. Pathologists blinded to clinical information performed Ki67 staining. Data were analyzed using multivariate association for survival outcomes. Amongst 72 patients (male: 39, female: 33, median age: 57 years) with metastatic NET, the most common site of origin was small bowel (n=35, 49%), while pancreas constituted 32% (n=23). Forty-four patients were treated with Y-90 (61%) and 28 patients received TACE (39%). Ki67 score was available in 28 patients (64%) treated with Y-90 and 16 patients (57%) with TACE. Within Y-90 group, there was greater use of Sandostatin (95% vs. 75%, P=0.02) and less number of total treatments completed (89% vs. 46%, P<0.001). There was no significant difference in overall survival (OS) between Y-90 and TACE when used without selection (median, 69 vs. 82 months, P=0.47). When adjusted for Ki67, patients with Ki67 score ≥3% had better OS with Y-90 compared to TACE (HR, 0.1; CI, 0.01-0.9), however for Ki67 <3%, OS was better when treated with TACE compared to Y-90 (HR, 13.5; CI, 1.22-148.87). There is significant interaction between Ki-67 score and liver-directed treatment benefit in patients with hepatic neuroendocrine metastases. Ki-67 score ≥3% predicts greater benefit with Y-90 and a Ki-67 score <3% predicts greater benefit with TACE.


New interpretation of alpha-particle-driven instabilities in deuterium-tritium experiments on the Tokamak Fusion Test Reactor.
The original description of alpha particle driven instabilities in the Tokamak Fusion Test Reactor in terms of toroidal Alfvén eigenmodes (TAEs) remained inconsistent with three fundamental characteristics of the observations: (i) the variation of the mode frequency with toroidal mode number, (ii) the chirping of the mode frequency for a given toroidal mode number, and (iii) the antiballooning density perturbation of the modes. It is now shown that these characteristics can be explained by observing that cylindrical-like modes can exist in the weak magnetic shear region of the plasma that then make a transition to TAEs as the central safety factor decreases in time.


Perceived orientation of axis of rotation in structure-from-motion.
Perceived orientation of axis of rotation and accuracy in discriminating fixed-axis from nonfixed-axis rotations were investigated for orthographic projections of three-dimensional rotating objects. The principal findings were (a) the slant of the axis of rotation was systematically misperceived; (b) in both two-view and multiview displays, the perceived slant of the axis of rotation was well-predicted by the ratio between the deformation (a property of the first-order optic flow) and the component parallel to the image plane of the global velocity vector; (c) if this ratio was kept constant in each frame transition of the stimulus sequence (or it was varied), then the stimuli tended to be judged as fixed-axis rotations (or as nonfixed-axis rotations), regardless of whether they simulated a fixed-axis rotation or not; and (d) the tilt of the axis of rotation was perceived in two-view displays with a very small error.


Pair formation, home range, and spatial variation in density, size and social status in blotched foxface Siganus unimaculatus on an Okinawan coral reef.
The present study examined pair formation, spatial pattern of home range and spatial variation in density, size and social status of blotched foxface Siganus unimaculatus (family Siganidae) on an Okinawan coral reef. Of 32 pairs sampled for sexing, 31 (96.9%) were heterosexual and showed size-assortative pairing. Developed ovaries were found in April and July, whereas oocytes were immature in August, September and February. Heterosexual pairing was found in both reproductive and non-reproductive periods. Home range size tended to be positively related to fork length (FL). The degree of home range overlap for same size class pairs was smaller than that for different size class pairs. The intraspecific behavior when two pairs approached each other was categorized as 'attack,' 'agonistic display' and 'no interactions,' and the frequency of agonistic behaviors ("attack" or "agonistic display") was significantly greater than "no interactions." Underwater observations at a seagrass bed, a rocky reef flat and a sheltered reef slope revealed that the mean FL was significantly smaller at the sheltered reef slope (4-13 cm) than at the rocky reef flat (>13 cm). No individuals were found in the seagrass bed. Most individuals less than 6 cm FL were solitary, whereas most individuals over 7 cm FL were paired. Density was significantly greater on the sheltered reef slope than on the rocky reef flat.


The role of alpha- and epsilon-amino groups in the glycation-mediated cross-linking of gammaB-crystallin. Study of three site-directed mutants.
In the previous report we demonstrated that gammaB-crystallin is glycated predominantly at the N-terminal alpha-amino group (Casey, E. B., Zhao, H. R., and Abraham, E. C. (1995) J. Biol. Chem. 270, 20781-20786). To investigate the possible role of alpha- and epsilon-amino groups of gammaB-crystallin in glycation-mediated cross-linking, Lys-2 or Lys-163, or both, were mutated to threonine by site-directed mutagenesis in bovine gammaB-crystallin cDNA. Wild type and mutant gammaB-crystallins were expressed in Escherichia coli cells. Cross-linking studies were performed by incubating wild type and mutant gammaB-crystallins with glyceraldehyde, ribose, and galactose followed by SDS-polyacrylamide gel electrophoresis under reducing conditions. When both of the lysines of gammaB-crystallin were mutated to threonines (gammaB-K2T/K163T), the quantity of cross-linked products was greatly reduced, indicating that, despite the fact that the alpha-amino group is a major glycated site, epsilon-amino groups play a predominant role in cross-linking. Therefore, cross-linking ability depends not only upon the level of glycation but also upon which amino group is glycated. Steric hindrance may decrease the cross-linking ability of the alpha-amino group. Our results also show that Lys-2 and Lys-163 play almost equal roles in cross-linking of gammaB-crystallin. By incubating carbonic anhydrase, a protein with a blocked N terminus, and our novel "no lysine" gammaB (gammaB-K2T/K163T) with sugar, we were able to show for the first time that significant cross-linking occurs between lysines and non-lysine sites. The fact that pentosidine and imidazolysine, formed from ribose and methylglyoxal, respectively, were present in the cross-linked gammaB-crystallins revealed the existence of Lys-Arg and Lys-Lys cross-linking.


Photo- and thermodegradation of anthocyanins from grape and purple sweet potato in model beverage systems.
Recently, interest in the application of natural pigments to replace synthetic dyes in beverages has grown. The present study investigates the stability of anthocyanin-rich grape and purple sweet potato (PSP) extracts to photo- and thermostresses in ready-to-drink (RTD) beverage models including hot fill beverages with various concentrations of ascorbic acid, a preserved beverage, and a vitamin-enriched water beverage. Thermo- and photostresses were induced at 40, 60, and 80 °C and 250, 500, and 750 W/m(2), respectively. Qualitative and quantitative data on anthocyanin content were collected by pH differential assay and LC-MS. Increasing concentration of ascorbic acid caused more rapid degradation through thermostress, but had a protective effect through photostress. Additionally, PSP was significantly less stable than grape extract in the vitamin-enriched water model beverage through photostress. Furthermore, photostress caused the formation of monoacylated peonidins from diacylated peonidins.


Practice parameter for the assessment and treatment of children and adolescents with reactive attachment disorder of infancy and early childhood.
This parameter reviews the current status of reactive attachment disorder with regard to assessment and treatment. Attachment is a central component of social and emotional development in early childhood, and disordered attachment is defined by specific patterns of abnormal social behavior in the context of "pathogenic care." Clinically relevant subtypes include an emotionally withdrawn/inhibited pattern and a socially indiscriminate/disinhibited pattern. Assessment requires direct observation of the child in the context of his/her relationships with primary caregivers. Treatment requires establishing an attachment relationship for the child when none exists and ameliorating disturbed attachment relationships with caregivers when they are evident. Coercive treatments with children with attachment disorders are potentially dangerous and not recommended.


Maintaining physical fitness and function in Alzheimer's disease: a pilot study.
Little is known about how aerobic exercise affects physical functioning in persons with Alzheimer's disease (AD). This pilot study used a 1-group repeated measures design to examine the feasibility and impact of a 6-month individualized moderate intensity cycling intervention on cardiorespiratory fitness and lower extremity function in 8 participants aged 81.4 ± 3.58. Cardiorespiratory fitness was measured using the shuttle walk and modified YMCA cycle ergometer tests, and lower extremity function was measured using the Short Physical Performance Battery (SPPB) at baseline, 3 months and 6 months. The YMCA test showed a significant reduction in heart rate at stage 2 (103.4 vs 90.9 vs 91.6; P = .01), while no significant changes were observed in the shuttle walk and SPPB tests. Persons with AD are able to improve cardiorespiratory conditioning from aerobic exercise. Randomized, controlled trials are needed to confirm these findings. Implications for future research are detailed.


Lupus anticoagulant, antiphospholipid syndrome and cardiac surgery.
The presence of lupus anticoagulant and the related condition antiphospholipid syndrome present a challenge in cardiac surgery where measured anticoagulation may not reflect the in vivo patient status of hypercoagulation. We report the successful management of a patient with lupus anticoagulant presenting for aortic valve replacement and coronary revascularisation. We used heparin for anticoagulation, specialised additional tests of anticoagulation and a reduced protamine dose. We also used tranexamic acid. The clinical problems with anticoagulation in patients with lupus anticoagulant include anticoagulant choice, measurement of adequate anticoagulation, antifibrinolytic usage, protamine dosing and blood product transfusion.


Stimulation of bone union with dynamic beams of Konzal's "R" external fixator.
Treatment of septic long bone non-union remains a complex therapeutic problem. External stabilisation with Konzal's "R" fixator has been used in the Orthopaedic Department of CPME for years and allows for rigid stabilisation of bone fragments and good mutual alignment. Tried and tested in the treatment of osteitis, the fixator, however, offers limited possibilities for dynamisation and interfragmental compression. The following article presents a modernised design of Konzal's "R" with dynamic beams. The efficacy of dynamisation of the fixator with the modernised design was compared with that of the earlier technique of eccentric shifting of static beams by assessing the time of bone union, the average number of pin restabilisations required, and the percentage of "partial unions" in two groups treated with the different methods. In the dynamic beam group, mean time to bone union was shorter by 5.1 months on average. This group also recorded a significantly lower percentage of "partial unions" (<50% of diaphysial circumference) as well as a lower count of necessary pin restabilisations per patient. There was no correlation between time to bone union and the duration of active inflammation prior to the surgical treatment or the presence of an open fistula. 1. The modernised design allows for dynamic load bearing by the bone tissue between the fragments rather than by the fixator's static beams. 2. The biomechanical principle of the fixator provides for optimal bone healing and shortens the time to bone union.


Seasonal variations in the onset of positive and negative renal ANCA-associated vasculitis in Spain.
The closure of long-standing gaps in our knowledge of aetiological factors behind anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a major challenge. Descriptive and analytical epidemiological studies can improve our understanding of environmental influences. Reported seasonal variations in AAV, mainly related to Wegener's disease, have shown an increasing number of cases in the winter months, which could be related to an extrinsic factor underlying infection. The objective of this paper was to study seasonal variations in AAV with respect to renal affectation diagnosed in Catalonia, Spain. Two hundred and thirty-four patients diagnosed for renal AAV between 2001 and 2014 in eight hospitals in Catalonia were included in the study. We used medical records to retrospectively analyse the date of the first symptoms attributed to the AAV, ANCA subtypes, the degree of renal impairment and renal histology. Of the 234 patients studied, 49.2% were male and 50.8% female. For ANCA status, 8.5% were positive, 15.9% were proteinase-3-positive and 75.6% were myeloperoxidase-positive. In relation to histological classification, 17.8% were sclerotic, 11.7% focal, 38.8% crescentic and 31.7% mixed. Regarding seasonal distribution, we observed a clear seasonal periodicity with a significantly higher incidence of cases in the winter. Applying an Eigen decomposition, we observed a periodic fluctuation of frequencies around the annual cycle with peaks every 10-12 months, and higher incidence of AAV cases in February. Our results confirm, in Catalonia, the seasonal periodicity of AAV with a higher incidence in the winter, as formerly described in the literature for other regions. An environmental factor, likely one that is infectious, may explain this finding.


Formation of two novel estrogen guanine adducts and HPLC/MS detection of 4-hydroxyestradiol-N7-guanine in human urine.
Estrogen-DNA adducts are potential biomarkers for assessing the risk of developing of a number of hormonally modified cancers, including breast cancer. Formation of the 4-hydroxyestradiol-N(7)-guanine (4-OHE2-N(7)-guanine) adduct from the reaction of estradiol-3,4-quinone with DNA and its detection in vivo has been established. With the ultimate goal of exploring estrogen-DNA adducts as biomarkers in experimental and human investigations, the 4-OHE2-N(7)-guanine was synthesized, and preliminary studies demonstrated that this adduct was detectable in all 10 female human urine samples examined. Therefore, more extensive investigations were conducted to study this compound's chemical-physical properties and to examine the stability of 4-OHE2-N(7)-guanine under a range of pH conditions that might influence biomarker measurement. Under neutral to alkaline conditions, 4-OHE2-N(7)-guanine could completely oxidize to an 8-oxo-guanine derivative. This derivative was isolated by HPLC, and mass spectrometry confirmed the oxidized compound by demonstrating the formation of an m/ z 168 fragment, generated by oxygen addition to guanine. Furthermore, investigation of the 4-OHE2-N(7)-2'-deoxyguanosine nucleoside adduct showed that under alkaline conditions a formamidopyrimidine analogue was produced. The formamidopyrimidine derivative forms from ring opening of the guanine imidazole ring following C-8 oxidation in the N(7), N(9) disubstituted guanine. Formation of both of these oxidized estrogen-guanine DNA adducts has precedent with other chemical agents that covalently bind to the N(7) position in guanine. Therefore, the development and application of methods to measure estrogen-guanine adducts will need to also consider these new adducts, and the biological implications of these compounds will need to be explored to determine their contribution to estrogen toxicology.


Comparison of bailout versus elective stenting: time to reassess our benchmarks of outcome.
The aim of this study was to compare the clinical outcome of elective and bailout stenting in an era of improved stent deployment techniques and antithrombotic therapy. We retrospectively analysed 136 consecutive patients undergoing stent implantation over a 15 mo period. There was no significant difference in the follow-up duration, length of hospital stay, or the total incidence of major complications between the two groups. Bailout stenting, as compared to elective stenting, was not associated with an increased incidence of in-hospital (no death vs. 1.4%, 4.6% non-Q myocardial infarction vs. 0%, 7.7% vascular complications vs. 7.0%) or late complications (no death vs. 1.4%, no non-Q myocardial infarction vs. 2.8%, 3.1% repeat angioplasty vs. 5.6%, 1.5% coronary artery bypass surgery vs. 1.4%). Stents can be implanted in cases of failed angioplasty with a success rate similar to that of elective stent implantation with a low incidence of complications and equivalent clinical outcome.


[Environmental management: critical analysis, scenarios and challenges].
This article discusses the limits, alternatives and challenges of environmental management in contemporary globalized capitalist societies. It is based on a critical analysis supported by authors from social sciences, political ecology and public health. To this end, we systematize the meaning of hegemonic environmental management in terms of eco-efficiency and its limits to tackle environmental risks and construct democratic processes and societies. We developed four ideal scenarios involving possible combinations of environmental management and democracy. This model served as a base, together with academic studies and the theoretical and militant experience of the authors, for a reflection on the current characteristics and future trends of environmental management and democracy, with emphasis on the reality of Latin America, specifically Brazil. Lastly, we discuss possibilities for social transformation taking into consideration the contradictions and emancipatory alternatives resulting from confrontations between hegemonic tendencies of the market and counter-hegemonic utopias and social movements. The latter assume principles of environmental justice, economic solidarity, agro-ecology and sustainability as well as the construction of new epistemologies.


Deconstructing Eurocentrism in skin pigmentation research via the incorporation of diverse populations and theoretical perspectives.
The evolution of skin pigmentation has been shaped by numerous biological and cultural shifts throughout human history. Vitamin D is considered a driver of depigmentation evolution in humans, given the deleterious health effects associated with vitamin D deficiency, which is often shaped by cultural factors. New advancements in genomics and epigenomics have opened the door to a deeper exploration of skin pigmentation evolution in both contemporary and ancient populations. Data from ancient Europeans has offered great context to the spread of depigmentation alleles via the evaluation of migration events and cultural shifts that occurred during the Neolithic. However, novel insights can further be gained via the inclusion of diverse ancient and contemporary populations. Here we present on how potential biases and limitations in skin pigmentation research can be overcome with the integration of interdisciplinary data that includes both cultural and biological elements, which have shaped the evolutionary history of skin pigmentation in humans.


Metal emissions from brake linings and tires: case studies of Stockholm, Sweden 1995/1998 and 2005.
Road traffic has been highlighted as a major source of metal emissions in urban areas. Brake linings and tires are known emission sources of particulate matter to air; the aim of the current study was to follow the development of metal emissions from these sources over the period 1995/ 1998-2005, and to compare the emitted metal quantities to other metal emission sources. Stockholm, Sweden was chosen as a study site. The calculations were based on material metal concentrations, traffic volume, particle emission factors, and vehicle sales figures. The results for metal emissions from brake linings/tire tread rubber in 2005 were as follows: Cd 0.061/0.47 kg/year, Cu 3800/5.3 kg/year, Pb 35/3.7 kg/year, Sb 710/0.54 kg/year, and Zn 1000/4200 kg/ year. The calculated Cu and Zn emissions from brake linings were unchanged in 2005 compared to 1998, indicating that brake linings still remain one of the main emission sources for these metals. Further, brake linings are a source of antimony. In contrast, Pb and Cd emissions have decreased to one tenth compared to 1998. The results also showed that tires still are one of the main sources of Zn and Cd emissions in the city.


[A case of an asthma patient receiving omalizumab during pregnancy].
We describe the first report in Japan of a woman who received omalizumab during pregnancy and delivery. Her asthma was so severe that she had been taking systemic corticosteroids since 22 years old, but asthma was poorly controlled. She had been pregnant seven times before, but almost every time asthma control had worsened and spontaneous abortion resulted, so she had only one child. She confirmed that she was not intending to become pregnant, and initiated use of omalizumab in August 2009. However, pregnancy was identified after she had taken the drug 3 times. We explained the risks in detail, but the patient wanted to keep taking omalizumab, as her asthma control was improved and she thought she could continue the pregnancy. We therefore decided to continue with omalizumab therapy. In October, she caught a cold and experienced asthma exacerbation. Despite the risk, she decided to suspend omalizumab therapy after taking the drug 7 times, as she was not feeling any benefit from therapy. Threat of abortion was identified in February 2010, so a 544-g female baby was delivered at 26 weeks gestation by Cesarean section. The baby had to be hospitalized in the neonatal intensive care unit because of low birth weight, but she has been developing and growing without handicap. We report this case as the first known case of pregnancy and delivery for a woman receiving omalizumab in Japan. Omalizumab may be safe to use in pregnant women with difficult-to-control asthma.


The genetic basis of neurocranial size and shape across varied lab mouse populations.
Brain and skull tissues interact through molecular signalling and mechanical forces during head development, leading to a strong correlation between the neurocranium and the external brain surface. Therefore, when brain tissue is unavailable, neurocranial endocasts are often used to approximate brain size and shape. Evolutionary changes in brain morphology may have resulted in secondary changes to neurocranial morphology, but the developmental and genetic processes underlying this relationship are not well understood. Using automated phenotyping methods, we quantified the genetic basis of endocast variation across large genetically varied populations of laboratory mice in two ways: (1) to determine the contributions of various genetic factors to neurocranial form and (2) to help clarify whether a neurocranial variation is based on genetic variation that primarily impacts bone development or on genetic variation that primarily impacts brain development, leading to secondary changes in bone morphology. Our results indicate that endocast size is highly heritable and is primarily determined by additive genetic factors. In addition, a non-additive inbreeding effect led to founder strains with lower neurocranial size, but relatively large brains compared to skull size; suggesting stronger canalization of brain size and/or a general allometric effect. Within an outbred sample of mice, we identified a locus on mouse chromosome 1 that is significantly associated with variation in several positively correlated endocast size measures. Because the protein-coding genes at this locus have been previously associated with brain development and not with bone development, we propose that genetic variation at this locus leads primarily to variation in brain volume that secondarily leads to changes in neurocranial globularity. We identify a strain-specific missense mutation within Akt3 that is a strong causal candidate for this genetic effect. Whilst it is not appropriate to generalize our hypothesis for this single locus to all other loci that also contribute to the complex trait of neurocranial skull morphology, our results further reveal the genetic basis of neurocranial variation and highlight the importance of the mechanical influence of brain growth in determining skull morphology.


Development of a model to deliver primary health care in Qatar.
Healthcare providers around the world are seeking to manage the rising burden of chronic conditions against a backdrop of both growing and ageing populations as well as greater expectations of health services. This paper describes the development of an integrated primary care model 'the family medicine model (FMM)' to deliver primary healthcare in Qatar to better address some of the healthcare challenges faced. A developmental approach was adopted in defining an FMM for Qatar that could potentially address health needs of its population, while acknowledging local context and addressing complexities. A literature review was undertaken followed by field visits and setting up of a working group in order to identify, develop and adapt a model suitable for delivery of primary care in Qatar. Key principles of the proposed model and its component were defined. Components included primary care workforce and practice-based teams, service provision and practice-based services, health information and technology, access to care and information, care management, care coordination, practice management and quality and safety. The proposed model is an innovative approach which utilises and integrates these components to deliver holistic primary care. It is anticipated that its introduction will help redesign and integrate the way primary healthcare is delivered to the population of Qatar in helping patients manage their own health and reduce the numbers that need to be admitted to secondary care, improving patients' independence and well-being as well as dramatically reducing the cost to the overall health system.


Effect of predischarge interventions on aftercare attendance: process and outcome.
A widely recognized problem in the mental health services delivery system is that of patients' early discontinuance of therapy. But less attention has been given to the high rate of nonattendance at initial appointments in outpatient mental health settings. The purpose of the study discussed in this article was to determine if particular predischarge interventions had an effect on whether psychiatric patients attended their initial aftercare appointments at a Veterans Administration mental health clinic. Two groups of patients were given predischarge interventions and one was not (a control group). Results showed a trend of greater attendance at initial aftercare appointments by those who received a predischarge intervention; however, the differences were not statistically significant. Suggestions for clinicians and researchers are provided.


NIR-Sensitized Activated Photoreaction between Cyanines and Oxime Esters: Free-Radical Photopolymerization.
Cyanines comprising either a benzo[e]- or benzo[c,d]indolium core facilitate initiation of radical photopolymerization combined with high power NIR-LED prototypes emitting at 805 nm, 860 nm, or 870 nm, while different oxime esters function as radical coinitiators. Radical photopolymerization followed an initiation mechanism based on the participation of excited states, requiring additional thermal energy to overcome an existing intrinsic activation barrier. Heat released by nonradiative deactivation of the sensitizer favored the system, even under conditions where a thermally activated photoinduced electron transfer controls the reaction protocol. The heat generated internally by the NIR sensitizer promotes generation of the initiating reactive radicals. Sensitizers with a barbiturate group at the meso-position preferred to bleach directly, while sensitizers carrying a cyclopentene moiety unexpectedly initiated the photosensitized mechanism.


[AMP-activated protein kinase--the key role in metabolic regulation].
AMP-activated protein kinase (AMPK) is the central component of a protein kinase cascade that acts as an energy sensor maintaining the energy balance at the cellular as well as at the whole body level. Within the healthy cell, metabolic stress leading to an increase in AMP concentration results in AMPK activation. Once activated, AMPK "switches off" many anabolic pathways e.g. fatty acid and protein synthesis while "switches on" catabolic pathways such as fatty acid oxidation or glycolysis which serve to restore intracellular ATP level. Adipocyte derived hormones leptin and adiponectin activate AMPK in peripheral tissues increasing energy expenditure. AMPK also regulates food intake due to response to hormonal and nutrient signals in hypothalamus. Antidiabetic drugs that mimic the action of insulin activate the AMPK signaling pathways. Further studies are needed to clarify the importance of the AMPK activation for therapeutic effects of this drugs.


Patient-targeted googling and psychiatric professionals.
This is a pilot study which assesses the beliefs of psychiatric professionals regarding obtaining patient information via the Internet as well as the frequency with which they do it in a variety of clinical settings. Psychiatry faculty and residents were asked to participate in an anonymous online survey about their use of the search engine Google to find information about their patients. Data were analyzed with Microsoft Excel. The participants included 48 faculty and 34 residents (118 faculty and 44 residents were surveyed) with response rates of 41% and 77%, respectively. Majority of attending physicians and residents reported engaging in patient-targeted googling with no significant difference between the groups. Residents were most likely to search for patient information online in the psychiatric emergency room (45%). Psychiatric emergency room (36.8%) and private practice (31.6%) were notable clinical settings for obtaining further patient information on the Internet for the faculty. When describing reasons for engaging in patient-targeted googling, "patient care" was cited about twice as often as "curiosity" in the psychiatric emergency room, whereas "curiosity" and "patient care" were reasons mentioned in other clinical settings. In general, neither faculty nor residents report informing their patients of their Internet searches either before or after engaging in patient-targeted googling. This study raises important questions about education for trainees and faculty regarding patient-targeted googling.


Rotational Osteotomy for Hallux Valgus. A New Technique for Primary and Revision Cases.
More than 200 different surgical techniques exist for hallux valgus (HV). Some of them are designed for mild, moderate, or severe deformities depending on their correction power. Nevertheless, they all correct only the coronal and/or sagittal plane deformity. Just a handful of them correct the known axial malrotation that exists in most HV cases. This malrotation is one possible factor that could be the source of recurrence of an operated HV as it has been described. We describe a new technique which simultaneously corrects the metatarsal internal rotation and varus deformity by rotating the metatarsal through an oblique plane osteotomy. This is performed with no bone wedge resection. Also, there is a broader bone surface contact than on a transverse proximal osteotomy. This technique is easy to remember and relatively simple to perform in primary and revision cases. The authors results show that it is as safe and effective as other procedures, with some advantages to be discussed. Diagnostic Level 5. See Instructions for Authors for a complete description of levels of evidence.


Association between visual acuity loss and optical coherence tomography findings in patients with late solar retinopathy.
To describe optical coherence tomography findings in patients with late solar retinopathy and their association with visual loss. Twenty-one eyes of 21 patients who had a history of watching a solar eclipse in 1999 with or without visual loss were evaluated with colored and red-free fundus photography and optical coherence tomography analysis using the macular thickness protocol. Ten of the eyes (47.6%) had no visual acuity loss and 11 eyes (52.4%) had visual acuities ranging from 0.3 to 0.8. There was a strong correlation between central foveal thickness and visual acuity. Empty spaces involving the full thickness of the photoreceptor layer band of the entire fovea were observed in 10 eyes and found to be associated with visual acuity loss. Signal defects in the outer and inner segments of the photoreceptors were identified in 12 and 15 eyes, respectively, and were not associated with visual acuity loss. Decreased central foveal thickness and full-thickness empty spaces beneath the fovea in optical coherence tomography analysis can be associated with permanent visual acuity loss in patients with a history of watching a solar eclipse.


Differentiation of the basal cell epithelioma-like changes overlying dermatofibroma.
Epidermis overlying dermatofibroma rarely displays basal cell epithelioma-like changes (BCE-like changes). Based on the histopathological findings, whether BCE-like changes are induced by dermal lesion or adnexal regression secondary to the solid fibrotic growth remains to be explored. From the standpoint of differentiation, we examined the BCE-like changes overlying dermatofibroma, normal epidermis, and hair follicles. PNA and two kinds of anti-keratin monoclonal antibodies were used to detect markers for epidermal differentiation. When PNA and anti-keratin monoclonal antibody (34betaB4) were used, no difference was observed in the staining patterns among BCE-like changes, hair follicles or normal basal cells. With the other anti-keratin antibody (34betaE12), BCE-like changes and normal basal cells were recognized, though the hair matrix was not. Thus the results obtained indicate that normal basal cells show the most similar differentiation to BCE-like changes.


Spatial characterization of glutathione depletion in the KHT sarcoma using flow cytometry.
Intravenous administration of the fluorescent DNA stain Hoechst 33342 to tumour-bearing mice was used to label cells proportionally to their proximity from the vasculature. Flow cytometry was used to sort cells from the tumour into populations based on their Hoechst 33342-derived fluorescence. The cell populations were then assayed for their glutathione (GSH) content and their radiosensitivity. Tumours from mice pretreated with buthionine sulphoximine (BSO) were compared with untreated animals. The major findings of this study suggest that the cellular GSH concentration within tumours decreases with distance from the vasculature, and that the GSH concentration within cells from all locations in the tumour can be depleted by enzymatically inhibiting its synthesis using BSO. This depletion of GSH resulted in a small degree of hypoxic radiosensitization of cells both distal and proximal to the vasculature.


Characterization of oscillations of intracellular calcium concentration in ferret ventricular muscle.
The photoprotein aequorin was injected into superficial cells of ferret papillary muscles. Tension and aequorin light (a function of intracellular [Ca2+]) were monitored. Increasing intracellular Ca concentration ([Ca2+]i), either by decreasing extracellular Na, or by inhibiting the Na pump with strophanthidin, produced spontaneous oscillations of [Ca2+]i and tension. Fourier analysis showed that these oscillations had frequencies of up to 3-4 Hz. If the muscle was stimulated in these conditions the Ca transient associated with the twitch was followed by a series of damped oscillations of [Ca2+]i which were accompanied by after-contractions. Under a given set of conditions the frequency of the stimulated oscillations was similar to that of the spontaneous oscillations. Manoeuvres which increase [Ca2+]i increased the frequency of both spontaneous and stimulated oscillations. Drugs which inhibit the function of the sarcoplasmic reticulum (caffeine and ryanodine) abolished both stimulated and spontaneous oscillations. The spontaneous oscillations during a Na-free contracture were unaffected by the Ca channel blocker D-600. When repetitive stimulation was begun the frequency and magnitude of the stimulated oscillations increased over several minutes. Increasing the frequency of stimulation increased the magnitude of the stimulated oscillations. It is concluded that the spontaneous oscillations of [Ca2+]i may be due to oscillatory Ca release from the sarcoplasmic reticulum. The similar properties of the spontaneous and stimulated oscillations suggest that the latter may be due to a synchronization of the former.


Effects of stimulus-response variables on the choice reaction time of mildly retarded adults.
Nonretarded and mildly retarded adults were compared in two experiments on an 8-choice reaction time (RT) task. Stimulus lights were either distant or close. Both groups responded more slowly when stimuli were distant, this effect being more marked for retarded subjects. Patterns of latencies suggested that, compared with nonretarded subjects, retarded subjects inspected information input for longer periods of time and made more inspections before responding. Faster RTs to stimuli nearest the ends and midline of the display and to stimulus repetitions indicated that retarded subjects were more reliant upon more discriminable cues in the stimulus display.


Ligation of Soluble but Unreactive Peptide Segments in the Chemical Synthesis of Haemophilus Influenzae DNA Ligase.
During the total chemical synthesis of the water-soluble globular Haemophilus Influenzae DNA ligase (Hin-Lig), we observed the surprising phenomenon of a soluble peptide segment that failed to undergo native chemical ligation. Based on dynamic light scattering and transmission electron microscopy experiments, we determined that the peptide formed soluble colloidal particles in a homogeneous solution containing 6 m guanidine hydrochloride. Conventional peptide performance-improving strategies, such as installation of a terminal/side-chain Arg tag or O-acyl isopeptide, failed to enable the reaction, presumably because of their inability to disrupt the formation of soluble colloidal particles. However, a removable backbone modification strategy recently developed for the synthesis of membrane proteins did disrupt the formation of the colloids, and the desired ligation of this soluble but unreactive system was eventually accomplished. This work demonstrates that an appropriate solution dispersion state, in addition to good peptide solubility, is a prerequisite for successful peptide ligation.


Hypophyseal development in vertebrates from amphibians to mammals.
Classically, it has been widely accepted that epithelial hypophysis develops from the stomodeal ectoderm. This notion was based on purely morphological observation of normal specimens. Recently, evidence is being accumulated that indicates another lineage for the developmental origin of adenohypophysis. This minireview focuses on several series of experimental works that have demonstrated a neuroectodermal origin of the hypophysis in vertebrates from amphibians to mammals. Phylogenetic consideration of the pituitary-like structures of prechordal animals is also presented.


Changes in interventional treatment--from the viewpoint of percutaneous ethanol injection therapy.
The environment surrounding secondary hyperparathyroidism treatment has changed and the transition of the guidelines on selective percutaneous ethanol injection therapy (PEIT) for secondary hyperparathyroidism from 2000 to 2006 has been made. The new guidelines emphasize the point that PEIT is best indicated for patients with one enlarged gland. Among treatments, including local vitamin D injection, selective PEIT and parathyroidectomy, cinacalcet is a potent medical treatment and will be a very effective new post-treatment intervention. However, it is expected that some patients will require active intervention based on morphological examination even if biochemical control is possible with cinacalcet administration.


[Low transcartilage incision: an advantage for submucosal dissection in rhinoplasty].
The authors recall the advantages of low transcartilage incision in rhinoplasty and, by means of several technical details, illustrate the value of this approach in submucosal dissection. They emphasise the anatomical clarity, safety and rapidity of the technique.


Immunoreactive substance P in human plasma: response to changes in posture and sodium balance.
1. In healthy volunteers plasma concentrations of immunoreactive substance P were measured in response to changes in posture and dietary salt intake. 2. In 14 subjects plasma immunoreactive substance P was 168 +/- 31 pmol/l when subjects were supine and 401 +/- 51 pmol/l (P less than 0.001) when they were ambulant. 3. Measurement of supine plasma immunoreactive substance P at 6 h intervals gave a mean value of 240 +/- 39 pmol/l at 14.00 hours and a lowest value of 76 +/- 9 pmol/l at 02.00 hours. 4. In eight healthy subjects plasma immunoreactive substance P rose only slightly from 169 +/0 41 pmol/l, on a sodium intake ad lib., to 244 +/- 45 pmol/l by day 4 of dietary sodium restriction (35 mmol/day) and significantly fell to 51 +/- 20 pmol/l (P less than 0.001) by day 4 of high sodium intake (350 mmol/day). 5. Although exogenous substance P was shown to be natriuretic in dog and rat, the present results do not favour a role of endogenous substance P as a circulating natriuretic factor in man.


Hemochromatosis: an endocrine liver disease.
This review acknowledges the recent and dramatic advancement in the field of hemochromatosis and highlights the surprising analogies with a prototypic endocrine disease, diabetes. The term hemochromatosis should refer to a unique clinicopathologic subset of iron-overload syndromes that currently includes the disorder related to the C282Y homozygote mutation of the hemochromatosis protein HFE (by far the most common form of hemochromatosis) and the rare disorders more recently attributed to the loss of transferrin receptor 2, HAMP (hepcidin antimicrobial peptide), or hemojuvelin or to certain ferroportin mutations. The defining characteristic of this subset is failure to prevent unneeded iron from entering the circulatory pool as a result of genetic changes compromising the synthesis or activity of hepcidin, the iron hormone. Like diabetes, hemochromatosis results from the complex, nonlinear interaction between genetic and acquired factors. Depending on the underlying mutation, the coinheritance of modifier genes, the presence of nongenetic hepcidin inhibitors, and other host-related factors, the clinical manifestation may vary from simple biochemical abnormalities to severe multiorgan disease. The recognition of the endocrine nature of hemochromatosis suggests intriguing possibilities for new and more effective approaches to diagnosis and treatment.


How successful is the fitting of digital hearing aids? Implications for the allocation of resources within national health systems.
We conducted a retrospective study to determine the success rate of initial fittings in digital hearing aid (DHA) users. We also addressed the implications of national health systems' continuing to provide access to these devices. We identified 1,597 consecutively presenting adults who had undergone a first fitting or a new fitting (i.e., an upgrade from an analogue hearing aid in the first or second ear) of a behind-the-ear DHA during the previous year. We further sought to identify all nominal reprogram appointments that had taken place within 6 months after the first or new fitting; we found 460 such appointments (28.8%). Of these, 419 appointments had been for typical reasons other than patient dissatisfaction with the fitting itself-for example, poor hearing, a further hearing loss, an uncomfortably loud hearing aid level, difficulty with speech in noise, an imbalance between bilateral hearing aids, and a faulty or lost hearing aid. Only 41 of the 1,597 first or new fittings (2.6%) were considered unsatisfactory by patients and necessitated a follow-up reprogramming appointment. Overall, DHA fittings were generally successful, as most patients (1,137/1,597 [71.2%]) did not require any follow-up appointment during the study period. Principles of cost-effectiveness demand the maximum practicable efficiency in the utilization of resources to ensure the continuous delivery of high-quality audiologic services through national health systems. This can be achieved by scheduling group appointments to reduce costs and to increase the time allocated to fitting and training patients.


New inspection procedures for bloodborne pathogens take effect.
In summary, this directive provides guidance for enforcement of the Bloodborne Pathogens Standard. The agency's application of this policy in any particular manner will, however, depend upon all relevant circumstances. For purposes of providing information and guidance, this directive also restates, clarifies, and explains the provisions of the standard.


Recurrent use of the Emergency Department in patients with anxiety disorder.
Panic disorder is characterized by the spontaneous and unexpected occurrence of panic attacks. During panic attacks, patients (pts) refer to the Emergency Department (ED). The diagnostic work-up for any panic attack is expensive since symptoms at presentation mimic other diseases such acute coronary syndrome or neurological emergencies. The aim of the present study was to describe a 10 years cohort of pts diagnosed with panic disorder in the ED in terms of ED visit recurrence. Case-control study, in a tertiary care, involving pts presenting to the ED and diagnosed with panic attack according to the International Classification of Diseases 9nt Revision (ICD-9). From January 2001 to Dec 2009 were extracted from the electronic clinical database 469 pts and were divided into "recurrent ED visit" (multiple ED access for panic attack) (N=361) and "no recurrent ED visit" (only one ED access for panic attack in 9 years) (N=108). At univariate analysis cases and controls differed for male prevalence (p < 0.01), neurological symptoms at presentation (p = 0.02) and history of other psychiatry disorder (p < 0.01). In multivariate analysis independent predictors were male gender, age under 40 year old, palpitations at presentations, 1 or more cardiovascular risk factors and previous other psychiatry conditions. Male under 40 years old with palpitations or cardiovascular risk and other psychiatric diseases, have a higher recurrence of panic attacks. General psychiatric evaluation and treatment with benzodiazepine in ED is not useful to prevent recurrences. Identifying those patients at high risk of panic attack and ED visit recurrence might be useful to establish ad-hoc interventions, improve patients' morbidity and save precious resources.


Exploiting Particle Mutual Interactions To Enable Challenging Dielectrophoretic Processes.
Dielectrophoresis (DEP) is the motion of particles under the influence of a nonuniform electric field. In insulator-based dielectrophoresis (iDEP), the required nonuniform electric fields are generated with insulating structures embedded in a microchannel. These structures distort the electric field distribution when an electric potential is applied. This contribution presents an experimental characterization of the electrokinetic (EK) and DEP velocities of a set of target particles, under DC potentials, when additional innocuous particles are used as fillers. Streak-based particle velocimetry in a tapered channel was used to assess particle motion. Filler particles of various sizes were added at different volume fractions (ϕ) to suspending media containing the target particles/cells. The presence of the filler particles resulted in electric field distortions and dissimilar particle behaviors caused by particle-particle interactions. These particle mutual interactions were exploited to improve the enrichment of low-abundance yeast cells in an iDEP channel. It was shown that the smallest studied filler particles (500 nm) have the potential to aid the enrichment of low-abundance yeast cells when filler volume fractions ∼1 × 10-5 v/v are used. Enrichment factors of ∼115 were achieved by applying electric potentials as low as 500 V.


Polybia occidentalis and Polybia fastidiosa venom: a cytogenotoxic approach of effects on human and vegetal cells.
The venoms of wasps are a complex mixture of biologically active compounds, such as low molecular mass compounds, peptides, and proteins. The aim of the study was to evaluate the action of wasp venoms, Polybia occidentalis and Polybia fastidiosa, on the DNA of human leukocytes and on the cell cycle and genetic material of the plant model Lactuca sativa L. (lettuce). The cultured leukocytes were treated with the venoms and then evaluated by the comet assay. On another assay, seeds were exposed to a venom solution; the emitted roots were collected and the occurrence of cell cycle alterations (CCAs) and DNA fragmentation were evaluated by agarose gel electrophoresis and TUNEL assay. The results demonstrated that the venom of both wasps induces several CCAs and reduces the mitotic index (MI) on treated cells. They induced damage on human leukocytes DNA. High frequencies of fragments were observed in cells exposed to P. occidentalis venom, while those exposed to P. fastidiosa showed a high frequency of non-oriented chromosome. Both venoms induced the occurrence of various condensed nuclei (CN). This alteration is an excellent cytological mark to cell death (CD). Additionally, CD was evidenced by positive signals in TUNEL assay, by DNA fragmentation in agarose gel electrophoresis with vegetal cells, and by DNA fragmentation of the human leukocytes evaluated. Furthermore, human leukocytes exposed to the venom of P. fastidiosa had high rate of damage. The data demonstrate that both vegetal and human cells are adequate to evaluate the genotoxicity induced by venoms.


[Disruption of blood-brain barrier in multiple sclerosis and neuromyelitis optica].
Pathological destruction of the blood-brain barrier(BBB) has been considered to be the initial key step of disease process in multiple sclerosis (MS) and neuromyelitis optica (NMO). The pathological findings using autopsy brain section from patients with secondary progressive (SP) MS or relapsing MS demonstrated a leaky BBB in active lesions and our recent data also showed that the sera from patients with relapsing MS or SPMS can induce the BBB breakdown. Recently, the disease-specific autoantibody "anti-aquaporin 4(AQP4) antibodies" was detected in the sera of NMO patients. Because the circulating anti-AQP4 antibodies need to pass through BBB in order to reach the astrocytic endfeets, where AQP4 localized, our recent studies demonstrated the detailed molecular mechanism of the BBB disruption in NMO.


Micro-brushing-based technique to gain fresh urothelial cells for gene expression analysis.
The gold standard of saving fresh tissue in liquid nitrogen has some serious disadvantages in that this process is not available in daily medical routine practices even in many tumor centers. Our approach of a new minimally invasive technique is obtaining urothelial cells via micro-brushing the urinary bladder on the occasion of urological routine methods such as transurethral resection (TUR). Urothelial cells were obtained from 25 patients via two different micro-brushes from tumor tissue and from macroscopically healthy tissue during TUR. These cells were immediately transferred into RNA stabilization reagent and stored at -20°C. Later, mRNA was isolated, transcribed into cDNA, and amplified. cDNA was stored at -20°C until analysis. The mean RNA quantity was 99.5 ng/μl from tumor tissues and 66.3 ng/μl from macroscopically tumor-free tissue, enabling a considerable number of analyses. The quality of the gained cDNA allowed semi-quantitative PCR analysis of GSTM1 expression as well as quantitative PCR analysis of c-Myc expression. The new technique presents several important advantages. First, staging and grading of the stained tumor sample can be examined immediately, whereas fresh frozen sample is not examined until some days later. Further, this method can be applied in hospitals with no access to liquid nitrogen or without capability to provide an additional examination of frozen tumor sample by a pathologist. This presented minimally invasive method enables investigation of gene expression in the urinary bladder without disadvantages of the need for storage of fresh tissues in liquid nitrogen.


Release of glutamate and gamma-aminobutyric acid in the ovine fetal hippocampus: ontogeny and effect of hypoxia.
The effects of increased potassium ion concentration (50 mM) and hypoxia on the efflux of glutamate and gamma-aminobutyric acid (GABA) were studied in ovine fetal hippocampal slices using the static-pool-interface superfusion method at three selected gestational ages (85 days, 105 days, 135 days; term, about 147 days). There was no difference in spontaneous efflux of either amino acid across the three gestational ages. Potassium ion stimulated the efflux of glutamate in the hippocampus of the 85-days-old fetus only, and this efflux of glutamate was not calcium-ion dependent. Potassium ion stimulated the efflux of GABA in the ovine fetal hippocampus at days 85 and 105 only; this efflux was calcium-ion dependent. A ten-minute period of hypoxia did not enhance the efflux of either glutamate or GABA. The data indicate that both glutamate and GABA are present in the ovine fetal hippocampus, and can be released by depolarizing concentrations of potassium ion in the immature fetus. The lack of potassium ion-evoked efflux of glutamate and GABA in the mature fetal hippocampus may reflect a toxic response to this stimulus. The lack of calcium ion regulation of glutamate efflux compared with GABA efflux indicates either a difference in maturation of glutamatergic synaptic mechanisms compared with GABAergic mechanisms, or is indicative of glial release of glutamate. Prolonged, severe hypoxia (greater than 10 min) may be required to evoke efflux of glutamate in the developing fetal hippocampus.


Leiomyoma With Massive Lymphoid Infiltration: 2 Cases With Lymphocytic Vasculopathy and Angiocentric Germinal Centers.
Uterine leiomyoma with massive lymphoid infiltration is characterized by a dense lymphoid infiltrate and germinal centers sparing the adjacent myometrium. Only few reports describe this entity and its etiology is unknown. This rare lesion may also exhibit lymphocytic vasculopathy but this has only been reported in the setting of GnRH agonist exposure. We report 2 cases of uterine leiomyoma with massive lymphoid infiltration in which only 1 patient was exposed to GnRH agonists. In both cases, histopathologic analysis showed thick-walled vessels with swollen endothelial cells showing evidence of intramural lymphocytic infiltration, red blood cell extravasation, and medial edema. This constellation of findings represented frank vascular damage and lymphocytic vasculopathy. Our findings suggest that lymphocytic vasculopathy in these lesions may be secondary to factors other than GnRH agonists. Furthermore, both cases showed an angiocentric disposition of germinal centers that has scarcely been alluded to in prior reports. This finding may provide a clue in accurately recognizing leiomyoma with massive lymphoid infiltration. Recognition of this lesion will allow one to avoid mistaking it for mimickers such as inflammatory myofibroblastic tumor, lymphoid malignancies, or other inflammatory processes.


Patient and Surgical Risk Factors for Surgical Site Infection in Lower-Extremity Oncological Endoprosthetic Reconstruction: A Secondary Analysis of the PARITY Trial Data.
The specific risk factors for surgical site infection (SSI) in orthopaedic oncology patients undergoing endoprosthetic reconstruction have not previously been evaluated in a large prospective cohort. In the current study, we aimed to define patient- and procedure-specific risk factors for SSI in patients who underwent surgical excision and endoprosthetic reconstruction for lower-extremity bone or soft-tissue tumors using the prospectively collected data of the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial. PARITY was a multicenter, blinded, randomized controlled trial with a parallel 2-arm design that aimed to determine the effect of a long duration (5 days) versus short duration (24 hours) of postoperative prophylactic antibiotics on the rate of SSI in patients undergoing surgical excision and endoprosthetic reconstruction of the femur or tibia. In this secondary analysis of the PARITY data, a multivariate Cox proportional hazards regression model was constructed to explore predictors of SSI within 1 year postoperatively. A total of 96 (15.9%) of the 604 patients experienced an SSI. Of the 23 variables analyzed in the univariate analysis, 4 variables achieved significance: preoperative diagnosis, operative time, volume of muscle excised, and hospital length of stay (LOS). However, only hospital LOS was found to be independently predictive of SSI in the multivariate regression analysis (hazard ratio per day = 1.03; 95% confidence interval = 1.01 to 1.05; p < 0.001). An omnibus test of model coefficients demonstrated that the model showed significant improvement over the null model (χ2 = 78.04; p < 0.001). No multicollinearity was found. This secondary analysis of the PARITY study data found that the only independent risk factor for SSI on multivariate analysis was hospital LOS. It may therefore be reasonable for clinicians to consider streamlined discharge plans for orthopaedic oncology patients to potentially reduce the risk of SSI. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.


Evaluation of cardiovascular ischemic event rates in dasatinib-treated patients using standardized incidence ratios.
With high survival rates for chronic myeloid leukemia (CML) patients treated with BCR-ABL1 tyrosine kinase inhibitors (TKIs), emerging consequences, such as arterial ischemic events, require consideration when evaluating treatment options. Cardiovascular ischemic event incidence in clinical trials was evaluated in 2712 dasatinib-treated patients with Philadelphia chromosome-positive (Ph+) leukemias from 11 first- and second-line trials (pooled), newly diagnosed CML patients treated with dasatinib or imatinib (DASISION), and prostate cancer patients treated with dasatinib or placebo plus docetaxel/prednisone (READY). Overall, 2-4% of dasatinib-treated patients had cardiovascular ischemic events. Most dasatinib-treated patients with an event had a history of and/or risk factor for atherosclerosis (pooled 77 with history/risk and event/96 with events; DASISION 8/10; READY 15/18). Most cardiovascular ischemic events occurred within 1 year of initiating dasatinib (pooled 69/96; DASISION 7/10; READY 16/18). Comparison of observed and expected event rates through standardized incidence ratios indicates that dasatinib does not increase risk for cardiovascular ischemic events compared with external reference populations.


Surgical and therapeutic management of a complete proximal hamstring avulsion after failed conservative approach.
Case report. After 2 attempts at conservative care for a diagnosis of hamstring strain, the patient had a surgical hamstring allograft reconstruction. The purpose of this report is to describe the physical therapy approach to postoperative management of a hamstring reconstruction. A 24-year-old female coach who sustained a complete avulsion of the proximal hamstring tendon while playing softball had a surgical hamstring reconstruction using an Achilles tendon allograft. Precautions concerning range of motion and stretching, weight-bearing status, and brace were followed to protect the surgical graft. Treatment incorporated cardiovascular, strength and proprioception exercises, and progressed with the focus on correct movement patterns and eccentric muscle control during functional movements. The patient attended 25 physical therapy sessions over 7 months. Muscle strength improved from 4/5 to 5/5. Straight-leg raise range of motion decreased from 145 degrees to 90 degrees . Lower Extremity Functional Scale (LEFS) scores improved from 15/80 to 70/80. A complete avulsion of the proximal insertion is rare. Conservative management of hamstring tears has traditionally focused on end-range passive stretching, modalities, and direct hamstring strengthening. New evidence recommends a program that is more protective of the injured tissue and includes exercises such as core stabilization; indirect hamstring strengthening may be beneficial in the treatment of hamstring injuries. This concept was taken into account when considering the rehabilitation protocol and progression for this patient. Therapy, level 4.


Lymphocytic infundibuloneurohypophysitis as a cause of central diabetes insipidus.
Central diabetes insipidus may be familial, secondary to hypothalamic or pituitary disorders, or idiopathic. Idiopathic central diabetes insipidus is characterized by selective hypofunction of the hypothalamic-neurohypophysial system, but its cause is unknown. We studied 17 patients with idiopathic diabetes insipidus, in whom the duration of the disorder ranged from 2 months to 20 years. Only four patients had been treated with vasopressin before the study began. All the patients underwent endocrinologic studies and magnetic resonance imaging (MRI) with a 1.5-T superconducting unit, and two patients had biopsies of the neurohypophysis or the pituitary stalk. Nine of the 17 patients had thickening of the pituitary stalk, enlargement of the neurohypophysis, or both and lacked the hyperintense signal of the normal neurohypophysis. In the remaining eight patients, the pituitary stalk and the neurohypophysis were normal, although the hyperintense signal was absent. The abnormalities of thickening and enlargement were seen on MRI only in the patients who had had diabetes insipidus for less than two years, and the abnormalities disappeared during follow-up, suggesting a self-limited process. In addition to vasopressin deficiency, two patients had mild hyperprolactinemia and nine had impaired secretory responses of growth hormone to insulin-induced hypoglycemia. The two biopsies revealed chronic inflammation, with infiltration of lymphocytes (mainly T lymphocytes) and plasma cells. Diabetes insipidus can be caused by lymphocytic infundibuloneurohypophysitis, which can be detected by MRI. The natural course of the disorder is self-limited.


"Is It My Responsibility?": A Qualitative Review of University Students' Perspectives on Bystander Behavior.
Bystander interventions focus on framing violence as a community problem and encourage all community members to act as prosocial bystanders if they witness a dangerous situation. Research has demonstrated there are multiple barriers and facilitators that might discourage or encourage an individual to act as a prosocial bystander. A qualitative interpretive meta-synthesis (QIMS) of existing literature was conducted to determine university students' perspectives on bystander facilitators and barriers. A systematic search of the literature was completed to identify articles that included university students' perspectives on bystander facilitators and barriers, utilized a qualitative methodology, and contained participant quotations in the published article. The search yielded 181 articles and after screening 10 articles were included in the QIMS. The original themes and participant quotations were qualitatively coded to develop five new themes: (1) the impact of alcohol, (2) beliefs about responsibility, (3) peer perceptions, (4) indicators and situational dilemmas, and (5) the role of friendship and group impact. The results of this synthesis reveal important implications for the continued development of bystander intervention programs for universities. By incorporating the perspectives of university students, bystander intervention programs may be more effective at encouraging students to be prosocial bystanders by confronting perceived barriers to intervention.


[Epilepsy in adults and elderly subjects. Epidemiological aspects, therapeutic strategies].
The important and quite amazing increase in frequency of epileptic seizures and epilepsy in patients older than 60 years is now recognized as a valid epidemiologic phenomenon. This has been emphasized in the last epidemiologic studies performed with an identical methodology in our industrialized countries. This could in part be explained by the growth of the aged population, by the ageing itself and by a larger exposition to the various risk factors existing at this age. The first is represented by cerebrovascular diseases, but cerebral involution--per se--is surely involved. Prescription of antiepileptic drugs in these patients has to be adapted to the individual cautiously. Pharmacokinetics and pharmacodynamic variations are more frequent than in other populations. On the other hand, drug interactions seem to be more frequent and severe because of the polytherapy prescribed for multiple other diseases. Intellectual or sensorial decline may explain the imperfect compliance observed in these patients.


Andrology.
Andrology is part of dermatology in Germany, as it arose from dermatology as a subspecialty. Accordingly training in andrology is part of the curriculum for specialty certification in dermatology. All dermatologists are required to "have experience in the diagnosis of andrologic disorders and their subsequent treatment". The specialty of andrology deals with male infertility problems including questions regarding fertility prophylaxis, contraception, erectile dysfunction, disturbance in libido, ejaculation and copulation, and primary and secondary hypogonadism, as well as male aging and diseases of the male breast. Evaluation and treatment of the partner may also be necessary. Ejaculate analysis is the most important laboratory tool and each dermatologist must be qualified in its performance.


Homozygosity for the HR2 Haplotype: Is It a Risk Factor for Thrombosis?
A4070G (His 1299 Arg) polymorphism in exon 13 of factor V gene can influence factor V levels and contribute to the activated protein C resistance. We are presenting our data concerning Turkish population and postulate that homozygosity for the HR2 haplotype may be an important risk factor for thrombosis.


The prevalence of the technocratic model in obstetric care from the perspective of health professionals.
to identify the reasons for the prevalence of the technocratic model in obstetric care from the perspective of health professionals. Grounded Theory. Study approved by two Research Ethics Committees and conducted by theoretical sampling, from July 2015 to June 2017. Twenty-nine interviews were conducted with health professionals from two maternity hospitals in the Southern Region of Brazil. Data collection and analysis was performed alternately; and analysis by open, axial, and selective coding/integration. the technocratic model still persists because the assistance is performed in a mechanized way, centered on the professionals. There is a lack of systematization of care, and under-dimensioning of the nursing staff. obstetric nurses need to review their performance in obstetric centers, the internal organization, the dimensioning of nursing professionals, and become protagonists of care. Investment in academic training/updating the knowledge of midwifery professionals, based on scientific evidence and user-centered care is necessary.


Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade.
The programmed death (PD)-1-PD-1 ligand (PD-L) pathway, which is part of the B7-CD28 family, consists of the PD-1 receptor and its two ligands PD-L1 and PD-L2. Engagement of PD-1 by its ligands inhibits immune responses, and recent work has shown that PD-1 is highly expressed on exhausted T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. Blockade of this pathway reinvigorates the exhausted T cells, allowing them to expand and produce effector cytokines, raising the issue of whether this pathway has been exploited by a variety of viruses during chronic infection. New studies now extend these observations to HIV infection and human disease.


Sustentacular Cell Enwrapment of Olfactory Receptor Neuronal Dendrites: An Update.
The pseudostratified olfactory epithelium (OE) may histologically appear relatively simple, but the cytological relations among its cell types, especially those between olfactory receptor neurons (ORNs) and olfactory sustentacular cells (OSCs), prove more complex and variable than previously believed. Adding to the complexity is the short lifespan, persistent neurogenesis, and continuous rewiring of the ORNs. Contrary to the common belief that ORN dendrites are mostly positioned between OSCs, recent findings indicate a sustentacular cell enwrapped configuration for a majority of mature ORN dendrites at the superficial layer of the OE. After vertically sprouting out from the borderlines between OSCs, most of the immature ORN dendrites undergo a process of sideways migration and terminal maturation to become completely invaginated into and enwrapped by OSCs. Trailing the course of the dendritic sideways migration is the mesodendrite (mesentery of the enwrapped dendrite) made of closely apposed, cell junction connected plasma membrane layers of neighboring folds of the host sustentacular cell. Only a minority of the mature ORN dendrites at the OE apical surface are found at the borderlines between OSCs (unwrapped). Below I give a brief update on the cytoarchitectonic relations between the ORNs and OSCs of the OE. Emphasis is placed on the enwrapment of ORN dendrites by OSCs, on the sideways migration of immature ORN dendrites after emerging from the OE surface, and on the terminal maturation of the ORNs. Functional implications of ORN dendrite enwrapment and a comparison with myelination or Remak's bundling of axons or axodendrites in the central and peripheral nervous system are also discussed.


Quantification of maximum-entropy spectrum reconstructions.
Maximum-entropy spectrum reconstruction derives much of its power from its nonlinearity. This nonlinearity causes difficulties in several contexts, however, including computation of multidimensional spectra and quantification of reconstructed spectra. We describe two methods for avoiding these difficulties: a "Constant-lambda" algorithm for performing row-wise reconstructions, which uses a fixed weighting of the entropy and the experimental constraint in the objective function, and in situ error analysis, for calibrating the nonlinearity. These methods are applied to data from quantitative J-correlation and relaxation experiments.


[The regularity of changes on the CT images of accessory nasal cavity in patients with nasopharyngeal carcinoma after radiotherapy].
To analyze the CT findings of nasal sinusitis in patients with nasopharyngeal carcinoma post-radiotherapy and detect the regularity of their change in different periods. This is a study on 145 cases of nasopharygeal carcinoma, including 75 cases treated by gamma-ray and 70 cases by X-ray. CT examinations on the patients were carried out pre-radiotherapy and post-radiotherapy in different periods. The radioreactions in maxillary sinus and sphenoidal sinus might be classified as patch form, crescent form, ring form and polyform. The unit of radioreaction in ethmoidal sinus was ethmoidal cell. Several ethmoidal sinus cells were fused to patch in severe cases. The radioreactions in ethmoidal sinus, maxillary sinus and sphenoidal sinus were seen within three months, after three months and after one year respectively. And nasal sinus radioreactions of most cases were not absorbed spontaneously after one year. When the two kinds of radiotherapies were equal in dosing level, there was no obvious difference between them in respect to the radioreaction of accessory sinus, but when the dosing level was above 3182 GBq, the radioreaction of accessory sinus was remarkably increased, compared with those caused by lower-dose radiotherapies. CT plays an important role in yielding helpful information for the diagnosis and treatment of the nasal sinusitis of nasopharyngeal carcinoma post-radiotherpy. The patients' life quality can be improved.


Genetics Influence Neurocognitive Performance at Baseline but Not Concussion History in Collegiate Student-Athletes.
This study investigates 4 single-nucleotide polymorphisms [Apolipoprotein E (APOE), APOE promoter, catechol-O-methyl transferase (COMT), and dopamine D2 receptor] that have been implicated in concussion susceptibility and/or cognitive ability in collegiate student-athletes. Cross-sectional study. Neuroscience laboratory at Elon University. Two hundred fifty division I collegiate student-athletes (66 women, 184 men) from various sports. All participants completed Immediate Postconcussion Assessment and Cognitive Testing (ImPACT) testing at baseline concussion testing and had a buccal swab taken for DNA for genotyping. Self-reported history of concussions and neurocognitive performance were taken from ImPACT. Individuals carrying an ε4 allele in their APOE gene had a significantly slower reaction time (P = 0.001). Individuals homozygous for the Val allele of the COMT gene showed significantly worse impulse control scores (P = 0.014). None of the genotypes were able to predict self-reported concussion history in collegiate student-athletes. These results indicate that certain genotypes may influence performance on cognitive testing at baseline and that the APOE genotypes may not influence concussion susceptibility as suggested by past studies.


Early life influences on the development of chronic obstructive pulmonary disease.
There is increasing evidence that chronic obstructive pulmonary disease (COPD) is not simply a disease of old age that is largely restricted to heavy smokers, but may be associated with insults to the developing lung during foetal life and the first few years of postnatal life, when lung growth and development are rapid. A better understanding of the long-term effects of early life factors, such as intrauterine growth restriction, prenatal and postnatal exposure to tobacco smoke and other pollutants, preterm delivery and childhood respiratory illnesses, on the subsequent development of chronic respiratory disease is imperative if appropriate preventive and management strategies to reduce the burden of COPD are to be developed. The extent to which insults to the developing lung are associated with increased risk of COPD in later life depends on the underlying cause, timing and severity of such derangements. Suboptimal conditions in utero result in aberrations of lung development such that affected individuals are born with reduced lung function, which tends to remain diminished throughout life, thereby increasing the risk both of wheezing disorders during childhood and subsequent COPD in genetically susceptible individuals. If the current trend towards the ever-increasing incidence of COPD is to be reversed, it is essential to minimize risks to the developing lung by improvements in antenatal and neonatal care, and to reduce prenatal and postnatal exposures to environmental pollutants, including passive tobacco smoke. Furthermore, adult physicians need to recognize that lung disease is potentially associated with early life insults and provide better education regarding diet, exercise and avoidance of smoking to preserve precious reserves of lung function in susceptible adults. This review focuses on factors that adversely influence lung development in utero and during the first 5 years of life, thereby predisposing to subsequent COPD.


Eudragit S-100 coated sodium alginate microspheres of naproxen sodium: formulation, optimization and in vitro evaluation.
The aim of the study was to prepare site specific drug delivery of naproxen sodium using sodium alginate and Eudragit S-100 as a mucoadhesive and pH-sensitive polymer, respectively. Core microspheres of alginate were prepared by a modified emulsification method followed by cross-linking with CaCl2, which was further coated with the pH dependent polymer Eudragit S-100 (2.5 or 5 %) to prevent drug release in the upper gastrointestinal environment. Microspheres were characterized by FT-IR spectroscopy, X-ray diffraction, differential scanning calorimetry and evaluated by scanning electron microscopy, particle size analysis, drug loading efficiency, in vitro mucoadhesive time study and in vitro drug release study in different simulated gastric fluids. Stability studies of the optimized formulation were carried out for 6 months. SEM images revealed that the surface morphology was rough and smooth for core and coated microspheres, respectively. Core microspheres showed better mucoadhesion compared to coated microspheres when applied to the mucosal surface of freshly excised goat colon. The optimized batch of core microspheres and coated microspheres exhibited 98.42 ± 0.96 and 95.58 ± 0.74 % drug release, respectively. Drug release from all sodium alginate microsphere formulations followed Higuchi kinetics. Moreover, drug release from Eudragit S-100 coated microspheres followed the Korsmeyer-Peppas equation with a Fickian kinetics mechanism. Stability study suggested that the degradation rate constant of microspheres was minimal, indicating 2 years shelf life of the formulation.


[Clinical evaluation of continuous isoproterenol inhalation in adult patients with severe acute asthma].
The clinical efficacy and safety of continuous inhalation therapy using l-isoproterenol in adult acute severe asthma were retrospectively evaluated. Fifty adult patients (34 men and 16 women, mean age 47.5) with severe acute asthma, which was not improved by conventional therapy including intermittent inhalation of salbutamol, intravenous aminophylline, and corticosteroid, were given continuous l-isoproterenol inhalation treatment. Both the lowered PaO2/FiO2 and the elevated PaCO2 improved significantly within 4 hours later. Forty-seven patients (94.0%) showed clinical improvement whereas two (4.0%) did not respond and received mechanical ventilation. No obvious side effects were noted in 49 patients (98.0%), while an 81-year-old man showed an elevation of blood pressure, which recovered promptly after discontinuation of the treatment. Based on these observations, we conclude that continuous inhalation therapy using l-isoproterenol is a safe and possibly useful option in the treatment of severe adult acute asthma, especially in patients who do not respond to conventional therapy.


Diffusion characteristics of ethylene glycol in skeletal muscle.
Part of the optical clearing study in biological tissues concerns the determination of the diffusion characteristics of water and optical clearing agents in the subject tissue. Such information is sufficient to characterize the time dependence of the optical clearing mechanisms—tissue dehydration and refractive index (RI) matching. We have used a simple method based on collimated optical transmittance measurements made from muscle samples under treatment with aqueous solutions containing different concentrations of ethylene glycol (EG), to determine the diffusion time values of water and EG in skeletal muscle. By representing the estimated mean diffusion time values from each treatment as a function of agent concentration in solution, we could identify the real diffusion times for water and agent. These values allowed for the calculation of the correspondent diffusion coefficients for those fluids. With these results, we have demonstrated that the dehydration mechanism is the one that dominates optical clearing in the first minute of treatment, while the RI matching takes over the optical clearing operations after that and remains for a longer time of treatment up to about 10 min, as we could see for EG and thin tissue samples of 0.5 mm.


[Psychotherapeutic support for the elderly].
After recalling the need of explicit description of psychic disorders and the importance of the psychotherapeutic approach in the elderly subject, the author defines the function of support and the content of psychotherapeutic support. The authors consider the psychotherapeutic attitude of the clinician, which has an effect preceding that of psychotherapy using specific techniques. This attitude is not limited to support and empathy alone but brings into play complex interactive processes. The importance and the role of interactions between generations and the relationship of age in geriatric care leads to expanding psychotherapeutic support to the family circle as well as to volunteer and professional persons involved in care of the patient.