[The role of "hemochromatosis alleles" in the pathogenesis of polyglobulia after renal transplantation].
43 kidney recipients were followed up for 12 months after renal transplantation. In 13 patients treated with cyclosporin A for 6 months polyglobulia was found, which subsided after conversion of immunosuppressive therapy. A highly significant correlation was found between the presence of the antigen A3 and the polyglobulia in kidney recipients treated by cyclosporin A. The serum ferritin level was not elevated in kidney recipients who were carriers of the "hemochromatosis alleles". Results obtained in this study seem to justify the following conclusions: 1. Kidney recipients who are carriers of "hemochromatosis alleles" show a threefold higher risk of posttransplant polyglobulia. 2. Presence of "hemochromatosis alleles" is not an absolute predictor of polyglobulia in patients after kidney transplantation. 3. Both etiology and pathogenesis of posttransplant polyglobulia do not seem to be homogeneous. Cyclosporin A, in contrast to azathioprine, seems to have a promoting effect on the development of posttransplant polyglobulia. Therefore treatment of kidney transplant patients with cyclosporin A, who are carriers of "hemochromatosis alleles", needs careful monitoring.


Common reactions to transfusions.
A blood transfusion is a special kind of transplantation, with the transfer of living tissue from one person to another. Reactions can occur with as little as 10 to 15 ml of incompatible blood. The onset of a reaction may be misleading or delayed, and its detection requires astute assessment. Responsibility for recognition of a transfusion reaction lies with the transfusionist, who is often a nurse. The following types of response can occur: hemolytic reactions, transfusion-induced graft-versus-host disease, hemoglobinuria, purpura, fever, circulatory overload, thrombophlebitis, urticaria, hyperkalemia, asymptomatic hemoglobinuria, pulmonary edema, and allergic and anaphylactic reactions. Critical care nurses need to be aware of the dangers of blood and blood product transfusions and to be prepared to react quickly.


Avian CD4 and CD8 interact with a cellular tyrosine protein kinase homologous to mammalian p56lck.
Functional as well as immunochemical studies have indicated that chicken T lymphocytes express surface antigens homologous to mammalian CD4 and CD8. The results presented in this report demonstrate that the avian CD4 and CD8 homologs are physically associated with a cellular tyrosine protein kinase related to mammalian p56lck. Furthermore, they show that engagement of either avian CD4 or CD8 is associated with a rapid intracellular tyrosine phosphorylation signal, suggesting that the function of these surface molecules may be mediated through alterations of the associated tyrosine protein kinase. Taken together, these findings demonstrate that the associations of CD4 and CD8 with an intracellular tyrosine protein kinase are evolutionarily conserved, further enhancing the likelihood that they are critical for normal immune functions.


Detection limits of matrix-assisted laser desorption/ionisation mass spectrometry coupled to chromatography--a new application of solvent-free sample preparation.
The detection limits of matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) by semi-online coupling with chromatography were investigated using various mixtures of polyethylene oxides (PEOs) with different end groups. In contrast to the common 'dried-droplet' sample preparation technique, which results in an inhomogeneous sample-to-matrix ratio within the MALDI spot, the used coupling technique offers a very high reproducibility combined with surpassing sensitivity of a few femtograms over a broad range of sample-to-matrix ratios. These results are in correlation with the results of the recently established solvent-free MALDI-TOFMS method utilising the grinding approach and are also of assistance towards the more theoretical aspect of MALDI that suggests that there is no necessity for an analyte incorporation into a matrix crystal for excellent matrix-assistance.


Prophylactic balloon occlusion of internal iliac arteries in women with placenta accreta: literature review and analysis.
To review the literature on the use of prophylactic balloon occlusion alone and in conjunction with arterial embolization of the internal iliac arteries in women with placenta accreta. The PubMed, MEDLINE, CINAHL, EMBASE, and Cochrane Library databases were searched for keywords related to this technique and its use in the avoidance of caesarean hysterectomy. The relevant published articles were selected and then searched for further references. The literature search found 15 case reports and five studies for a total of 20 articles. The use of balloon catheters to prevent post-partum haemorrhage in women with placenta accreta is controversial with some investigators reporting reduced blood loss and transfusion requirements while others reporting no benefit. This procedure does not appear to reduce operative time or hospital stay. Some groups have described catheter-related complications, such as maternal thromboembolic events and the need for stent placement and/or arterial bypass. Thus far, there is no reported maternal or foetal mortality related to this procedure. Current evidence is based upon case reports and small retrospective studies. Larger studies or randomized controlled trials are essential in order to demonstrate the safety and efficacy of bilateral iliac balloon occlusion. The creation of a data registry would also facilitate the reporting of this technique.


Emergency Computed Tomography: How Misinterpretations Vary According to the Periods of the Nightshift?
To evaluate the accuracy of initial computed tomography (CT) interpretations made by radiology residents during nightshifts in the emergency department. Preliminary CT reports performed by radiology residents during 120 consecutive nightshifts (08:30 pm to 08:30 am) were reviewed, attendings' final interpretation being the reference standard. Nightshifts were divided into four consecutive periods of 3 hours. Major misinterpretations were related to potentially life-threatening conditions if not treated immediately after CT. The rate of misinterpretations was calculated for all CT examinations, separately for nightshift's periods and for residents' training years. Misinterpretations were recorded in 155 (7.4%) of 2102 CT examinations, 0.6% (13/2102) were major. There were 2.2% (4/186) major misinterpretations that occurred during the last period of the nightshift versus 0.4% (9/1916) during the first periods of the night (P < 0.05). Of all misinterpretations, 8.5% (130/1526) were made by third- and fourth-year residents and 4.3% (25/576) by fifth-year residents (P < 0.005). Major misinterpretations occur at the end of the nightshift, which may be explained by the fatigue effect. The rate of misinterpretations is lower among fifth-year residents, which may be related to their prior experience in reading emergency cases.


[Latent and manifest acquired syphilis--clinical aspects, diagnosis and therapy].
The annual reported incidence of new syphilis infections in the FRG is decreasing; cases with atypical or oligosymptomatic forms of syphilis, however, show a relative increase. In contrast to the primary or secondary stage, the late stages of syphilis are very rare. Of great diagnostic importance is the serological examination which today can be limited to the VDRL and TPHA tests for screening and the FTA-ABS test for confirmation. In cases with an atypical clinical picture or history, the necessity for treatment can be verified with the 19S-IgM-FTA-ABS test and demonstration of treponemal IgM antibodies. Penicillin is still the drug of choice for the treatment of syphilis. In patients who are allergic to penicillin, the administration of erythromycin, tetracycline and, recently, of cephalosporins can be considered.


Protective effects of Tat-NQO1 against oxidative stress-induced HT-22 cell damage, and ischemic injury in animals.
Oxidative stress is closely associated with various diseases and is considered to be a major factor in ischemia. NAD(P)H:quinone oxidoreductase 1 (NQO1) protein is a known antioxidant protein that plays a protective role in various cells against oxidative stress. We therefore investigated the effects of cell permeable Tat-NQO1 protein on hippocampal HT-22 cells, and in an animal ischemia model. The Tat-NQO1 protein transduced into HT-22 cells, and significantly inhibited against hydrogen peroxide (H2O2)-induced cell death and cellular toxicities. Tat-NQO1 protein inhibited the Akt and mitogen activated protein kinases (MAPK) activation as well as caspase-3 expression levels, in H2O2 exposed HT-22 cells. Moreover, Tat-NQO1 protein transduced into the CA1 region of the hippocampus of the animal brain and drastically protected against ischemic injury. Our results indicate that Tat-NQO1 protein exerts protection against neuronal cell death induced by oxidative stress, suggesting that Tat-NQO1 protein may potentially provide a therapeutic agent for neuronal diseases. [BMB Reports 2016; 49(11): 617-622].


Is the short follicular phase in older women secondary to advanced or accelerated dominant follicle development?
This study sought to determine whether the shortened follicular phase in ovulatory older women is secondary to advanced (i.e. earlier) or accelerated (i.e. more rapid) folliculogenesis. Normal ovulatory women, aged 40-45 yr (n = 15) and 20-25 yr (n = 13), underwent daily venipuncture and transvaginal ultrasonography throughout the follicular phase of a spontaneous menstrual cycle (control cycle) and after pituitary down-regulation with a GnRH agonist (study cycle). As expected, the older subjects in the control cycles demonstrated an elevated d 3 FSH and a shortened follicular phase compared with the younger subjects. After release from hypothalamic-pituitary-ovarian axis suppression, the early follicular phase FSH peak occurred earlier (6.8 vs. 9.8 d; P < 0.01) and was of a greater magnitude (12.1 vs. 6.5 mIU/ml; P < 0.01) in the older subjects. The time from release of suppression until the subsequent LH surge was also shorter (17.5 vs. 20.8 d; P < 0.01) in the older group. However, the time from FSH peak to LH surge was similar in the older and younger groups (10.7 vs. 11.0 d; P = 0.74). Compared with younger women, older subjects had normal follicular phase levels of estradiol and inhibin A and lower levels of inhibin B in both control and study cycles. We conclude that the shortened follicular phase observed in older ovulatory women is due to earlier dominant follicle selection, independent of hormonal influences from the preceding luteal phase.


Analysis of a catalytic pathway via a covalent adduct of D52E hen egg white mutant lysozyme by further mutation.
We previously demonstrated by X-ray crystallography and electrospray mass spectrometry that D52E mutant hen lysozyme formed a covalent enzyme-substrate adduct on reaction with N-acetylglucosamine oligomer. This observation indicates that D52E lysozyme may acquire a catalytic pathway via a covalent adduct. To explain this pathway, the formation and hydrolysis reactions of the covalent adduct were investigated. Kinetic analysis indicated that the hydrolysis step was the rate-limiting step, 60-fold slower than the formation reaction. In the formation reaction, the pH dependence was bell-shaped, which was plausibly explained by the functions of the two catalytic pKas of Glu35 and Glu52. On the other hand, the pH dependence in the hydrolysis was sigmoidal with a transition at pH 4. 5, which was identical with the experimentally determined pKa of Glu35 in the covalent adduct, indicating that Glu35 functions as a general base to hydrolyze the adduct. To improve the turnover rate of D52E lysozyme, the mutation of N46D was designed and introduced to D52E lysozyme. This mutation reduced the activation energy in the hydrolysis reaction of the covalent adduct by 1.8 kcal/mol at pH 5.0 and 40 degrees C but did not affect the formation reaction. Our data may provide a useful approach to understanding the precise mechanism of the function of natural glycosidases, which catalyze via a covalent adduct.


Effect of naloxone on the respiratory responses to hypoxia in chronic obstructive pulmonary disease.
Ventilatory and airway occlusion pressure responses to hypoxia were measured in 7 subjects with chronic obstructive pulmonary disease (COPD). Paired responses were obtained after the administration of saline or naloxone and, on separate days, in 5 of the 7 subjects, after 2 saline injections. Naloxone increased (p less than 0.05) the mean inspiratory flow and the ventilatory and airway occlusion pressure responses to hypoxia when compared with the saline responses. Resting ventilation and tidal volume also increased, but not significantly. Involvement of endogenously generated opioid substances in the control of breathing of patients with COPD is further suggested by this study.


Destruction of the hydration shell around tetraalkylammonium ions at the electrochemical interface.
The structure and behavior of the hydration shells around tetraethyl-, -propyl-, and -butylammonium ions (Et(4)N(+), Pr(4)N(+), and Bu(4)N(+), respectively) at a CO-covered Pt electrode was studied by surface-enhanced IR absorption spectroscopy. Selective concentration of cations at the electrochemical interface by controlling the applied potential facilitates the observation of the hydration shells without interference from hydrated anions. We report for the first time that the hydration shells around Pr(4)N(+) and Bu(4)N(+) are decomposed at sufficiently negative potentials because of the strong electrostatic attraction with the surface. On the other hand, the hydration shell around Et(4)N(+), the smallest ion, is more stable and does not decompose in the potential range examined. The difference in the stability can be ascribed to the difference in the size of the central cation. On the other hand, the hydration shells are easily deconstructed on a bare Pt surface because of the stronger interaction with the surface.


1,2-Dichloroethane Exposure Alters the Population Structure, Metabolism, and Kinetics of a Trichloroethene-Dechlorinating Dehalococcoides mccartyi Consortium.
Bioremediation of groundwater contaminated with chlorinated aliphatic hydrocarbons such as perchloroethene and trichloroethene can result in the accumulation of the undesirable intermediate vinyl chloride. Such accumulation can either be due to the absence of specific vinyl chloride respiring Dehalococcoides mccartyi or to the inhibition of such strains by the metabolism of other microorganisms. The fitness of vinyl chloride respiring Dehalococcoides mccartyi subpopulations is particularly uncertain in the presence of chloroethene/chloroethane cocontaminant mixtures, which are commonly found in contaminated groundwater. Therefore, we investigated the structure of Dehalococcoides populations in a continuously fed reactor system under changing chloroethene/ethane influent conditions. We observed that increasing the influent ratio of 1,2-dichloroethane to trichloroethene was associated with ecological selection of a tceA-containing Dehalococcoides population relative to a vcrA-containing Dehalococcoides population. Although both vinyl chloride and 1,2-dichloroethane could be simultaneously transformed to ethene, prolonged exposure to 1,2-dichloroethane diminished the vinyl chloride transforming capacity of the culture. Kinetic tests revealed that dechlorination of 1,2-dichloroethane by the consortium was strongly inhibited by cis-dichloroethene but not vinyl chloride. Native polyacrylamide gel electrophoresis and mass spectrometry revealed that a trichloroethene reductive dehalogenase (TceA) homologue was the most consistently expressed of four detectable reductive dehalogenases during 1,2-dichloroethane exposure, suggesting that it catalyzes the reductive dihaloelimination of 1,2-dichloroethane to ethene.


Maternal microbiota-derived metabolic profile in fetal murine intestine, brain and placenta.
The maternal microbiota affects the development of the offspring by microbial metabolites translocating to the fetus. To reveal the spectrum of these molecular mediators of the earliest host-microbe interactions, we compared placenta, fetal intestine and brain from germ-free (GF) and specific pathogen free (SPF) mouse dams by non-targeted metabolic profiling. One hundred one annotated metabolites and altogether 3680 molecular features were present in significantly different amounts in the placenta and/or fetal organs of GF and SPF mice. More than half of these were more abundant in the SPF organs, suggesting their microbial origin or a metabolic response of the host to the presence of microbes. The clearest separation was observed in the placenta, but most of the molecular features showed significantly different levels also in the fetal intestine and/or brain. Metabolites that were detected in lower amounts in the GF fetal organs included 5-aminovaleric acid betaine, trimethylamine N-oxide, catechol-O-sulphate, hippuric and pipecolic acid. Derivatives of the amino acid tryptophan, such as kynurenine, 3-indolepropionic acid and hydroxyindoleacetic acid, were also less abundant in the absence of microbiota. Ninety-nine molecular features were detected only in the SPF mice. We also observed several molecular features which were more abundant in the GF mice, possibly representing precursors of microbial metabolites or indicators of a metabolic response to the absence of microbiota. The maternal microbiota has a profound impact on the fetal metabolome. Our observations suggest the existence of a multitude of yet unidentified microbially modified metabolites which pass through the placenta into the fetus and potentially influence fetal development.


Mechanistic Approach to Understanding the Influence of USP Apparatus I and II on Dissolution Kinetics of Tablets with Different Operating Release Mechanisms.
This article provides an analysis of dissolution kinetics associated with formulations subjected to different dissolution methods with the purpose of revealing credible direction on selection of apparatus type and hydrodynamics on in vitro drug release profiles using three different formulations. The dissolution kinetics of immediate release (IR) and controlled release (CR) ibuprofen tablets under different hydrodynamic conditions were determined, and potential existence of any correlation between USP apparatus I and II were analyzed using adequate kinetic models. Two types of CR tablets based on PEO (polyethylene oxide-N80) and HPMC (hydroxypropyl methylcellulose- K100M) polymers were prepared. Marketed ibuprofen 200-mg IR tablets were also used. Dissolution studies were carried out using USP 34 apparatuses I and II methods at stirring speed of 100 and 50 rpm in 900 mL phosphate buffer, pH 7.2 at 37°C. The drug release profiles for each formulation was determined and statistically analyzed using model-dependent, model-independent (f 2 ), and ANOVA methods. No significant dissolution differences existed between IR tablets, whereas CR tablets were significantly impacted by apparatus types and hydrodynamics. PEO matrices displayed higher sensitivity to hydrodynamics relative to HPMC matrices, and differences in dissolution profiles were confirmed by ANOVA and boxplot analysis. It is concluded that in the case of CR systems, selection of apparatus type and adherence to the monograph specifications and hydrodynamic conditions is critical, while for IR tablets, both apparatus types and agitation rates had no significant impact on drug release rate, suggesting the possibility of apparatus interchangeability if desired.


Rate of Complications and Subsequent Shoulder Complaints for Non-operatively Managed Pediatric Proximal Humerus Fractures.
Purpose: The purpose of the study was to describe the early complications and delayed shoulder complaints of non-displaced or minimally displaced pediatric proximal humerus fractures treated non-operatively. Methods: Retrospective review of all pediatric proximal humerus fractures at a single institution from 2001 to 2016. Inclusion criteria were: AP and axillary radiographs upon presentation and final follow up, one follow up appointment, either a non-displaced or minimally displaced fracture, and open physis. Exclusion criteria were: pathologic fractures, re-fractures, bone metabolic disorders. Patient demographics, injury characteristics, radiographic measurements and clinical exam findings were reviewed. Delayed shoulder complaints were defined as a visit to any provider for an ipsilateral shoulder or arm complaint after final scheduled fracture appointment. Results: Sixty-nine of 177 total pediatric proximal humerus fractures met inclusion criteria. Mean age was 10 years (SD = 3.4). Sixty-five had angulation <20 degrees. Median time to last scheduled follow up was 1.4 months (Interquartile range 0.8-1.4). At last scheduled follow up, 9 (13.0%) fractures had an altered exam. One (1.4%) fracture had a complication of a fall and re-fracture. Extraphyseal fractures were more likely to increase in angulation at short term follow up, but had no association with short or long term complications. No patient initially treated with non-operative management subsequently underwent operative treatment. There were three presentations (4.3%) to health professionals for subsequent shoulder complaints; one was treated with short courses of physical therapy and the other two were simply observed. Conclusions: Non-displaced or minimally displaced proximal humerus fractures treated non-operatively sustain rare short or long term complications with no cross over to operative management. Once non-operative management is pursued, these fractures may be amenable to surveillance with primary care or allied orthopedic staff after initial evaluation by pediatric orthopedic providers. Level of Evidence: Level III retrospective cohort study.


Sublingual salivary gland enlargement.
When examining the mouth floor, sublingual salivary gland enlargement, or hypertrophy, is commonly seen by dentists. It represents an innocuous, asymptomatic lesion that tends to proliferate into edentulous areas. It is often mistaken for a pathologic entity. Recognition avoids concern, misdiagnosis and unnecessary surgery.


Late acute rejection after liver transplantation: the Western Canada experience.
Acute rejection usually occurs within 3 months posttransplantation. Most centers reduce immunosuppression over 6 to 12 months to minimize opportunistic infection, malignancy, and drug toxicity. Pretransplant disease and low immunosuppression have been reported in association with late acute rejection (LAR). The objective of this study was to determine the incidence, predictive factors, and outcomes of LAR via retrospective review of adult liver transplant recipients in Western Canada from 1989 to 2000. LAR was defined as biopsy-proven acute rejection occurring more than 180 days posttransplantation. Patient characteristics, immunosuppression, and outcome were determined. Both a univariate and multiple logistic regression analysis were performed. LAR occurred in 97 (23%) of 415 patients more than 180 days posttransplantation. Median follow-up was 402 days (range, 180 to 3137 days); 79% of LAR episodes were graded mild. At the time of LAR, 33% were on a steroid taper. A total of 73% of LAR episodes were treated with pulse intravenous steroids, and 5% were steroid-resistant. In the univariate analysis, patients undergoing transplantation for viral etiologies and older age were associated with less LAR. Immunosuppression was significant in a multiple logistic regression model, but not with a proportional hazards model. On multivariate analysis, only patients undergoing transplantation for viral etiologies remained resistant to LAR (hazard ratio, 0.52; range, 0.34 to 0.93, P = .02). There was a trend toward increased chronic rejection in patients who developed LAR (P = .04). LAR is common and occurs after more than 1 year posttransplantation. Patients undergoing transplantation for viral etiologies seem to have a lower risk of LAR. There may be an increased risk of chronic rejection in those developing LAR.


Effects of hyperthermia and X-irradiation on mouse stromal tissue.
The sensitivity of normal stroma to heat, irradiation and heat combined with irradiation has been studied using the tumour bed effect (TBE) assay. Irradiation before implantation led to a TBE. This TBE was dose dependent below 15 Gy, the TBE remaining relatively constant above 15 Gy. The interval (0-90 days) between irradiation and tumour implantation did not influence the magnitude of the TBE. Hyperthermia with large heat doses (45-60 min at 44 degrees C) before implantation may lead to a TBE. The interval between hyperthermia and tumour implantation proved to be very important. Our results show that the recovery from heat-induced stromal damage is very rapid. When the interval between hyperthermia and tumour implantation is 10 days or longer, no TBE could be observed. Irradiation combined with large heat doses (30-60 min at 44 degrees C) decreased the radiation-induced TBE. However, the combination of irradiation with mild heat treatments (15 min at 44 degrees C) could lead to a larger TBE than after irradiation alone. When hyperthermia was given prior to irradiation, the interval between heat and irradiation proved to be very important. With large intervals (21 days or longer) the TBE values were about the same as with irradiation alone. When heat was given after irradiation it always reduced the irradiation-induced TBE.


Low-level plasticizer exposure and all-cause and cardiovascular disease mortality in the general population.
Plasticizers, also called phthalates, are a group of chemicals widely used in daily life. A previous report showed no significant association between phthalate metabolite concentrations and mortality. We investigated the association of urinary phthalate levels and individual phthalate metabolite levels with all-cause and cardiovascular disease (CVD) mortality after standardizing the phthalate concentration. A total of 6,625 participants were recruited from a nationally representative sample of adults aged 40 years or older who were enrolled in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2014 and were followed up through December 31, 2015. Data were analyzed from January 2021 to June 2021. NHANES-linked updated National Death Index public access files were used to acquire information on mortality status and cause of death. The present study conducted extended follow-up of an earlier analysis. Cox proportional hazard models were performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of covariate-adjusted creatinine standardization urinary phthalate concentrations with all-cause and CVD mortality after adjusting for demographics, lifestyle factors and comorbidity variables. The mean ± standard deviation age of all participants in the final study was 59.9±12.6 years old, and 49.6% of the participants were male. The median follow-up time was 73 months (range 1-157 months). At the censoring date of December 31, 2015, 3,023 participants were identified as deceased (13.4%). A fully adjusted Cox model showed that a urinary di(2-ethylhexyl) phthalate (DEHP) concentration >= 83.4 ng/mL was associated with a slight increase in all-cause mortality (HR 1.27, 95% CI 1.03, 1.57, P for trend= 0.014) and CVD mortality (HR 2.19, 95% CI 1.35, 3.54, P for trend= 0.002). Similarly, urinary mono-2-ethyl-5-carboxypentyl phthalate (MECPP) levels >= 39.2 ng/mL were associated with increased CVD mortality (HR 2.33, 95% CI 1.45, 3.73, P for trend < 0.001). Restricted cubic spline analyses suggested linear associations of DEHP and MECPP levels with all-cause and CVD mortality. In this large nationally representative sample of American adults, high urinary DEHP and MECPP were significantly associated with all-cause and CVD mortality after adjusting for demographics, lifestyle factors and comorbidity variables.


Closed traumatic rupture of the flexor pulleys of a long finger associated with avulsion of the flexor digitorum superficialis.
We report a closed rupture of the second, third and fourth annular pulleys associated with avulsion of the flexor digitorum superficialis tendon in the ring finger of a healthy, 48-year-old patient. It was caused by sudden and violent flexion of the finger and led to a serious impairment of the proximal interphalangeal joint motion, despite physiotherapy and dynamic splinting. The patient was treated surgically, 3 months after the injury, with reconstruction of the second (A2) and fourth (A4) annular pulleys and excision of the distal portion of the superficialis tendon. The final functional result was satisfactory.


BDNF serum concentrations in 2053 participants of the Berlin Aging Study II.
Serum BDNF concentrations in 2053 participants of the Berlin Aging Study II (BASE-II; 1572 individuals from the older age group [60-85 years], 481 individuals from the younger-age reference group [22-37 years]) were studied. There was no effect of age, sex, body mass index, self-reported depression, or BDNF Val66Met variant on serum BDNF concentrations. Multiple linear regression analysis failed to detect significant relationships of Digit Symbol Substitution Test score and Consortium to Establish a Registry for Alzheimer's Disease memory score to BDNF levels. However, we detected a positive correlation between platelet counts and BDNF levels (r = 0.303, p < 0.001). Our findings do not support an effect of aging, self-reported depression, or the Val66Met variant on serum BDNF concentrations. The role of thrombocytes in the biology of serum BDNF merits further study.


Association of Birth Weight with Central and Peripheral Corneal Thickness in Adulthood-Results from the Population-Based German Gutenberg Health Study.
Purpose: Low birth weight (BW) is associated with altered ocular geometry such as a steeper corneal shape in adulthood. However, it is unclear whether low birth weight affects corneal thickness development in the center or periphery in adulthood which may contribute to ocular disease. The purpose of this study was to investigate corneal thickness in former low birth weight individuals in adulthood. Methods: The German Gutenberg Health Study is a prospective, population-based study in which every participant (age range 40-80 years) was measured with Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany). BW was collected by self-reports. The relationship between birth weight and corneal thickness at different locations were assessed. Linear regression models were carried out including uni- and multivariable analyses with adjustment for age, sex, mean corneal radius, and white-to-white distance. Main outcome measures were corneal thickness at the apex, at the pupil center, and at the corneal periphery. Results: Overall, 5657 participants were successfully measured (3019 females, aged 56.0 ± 10.3 years). In multivariable analyses a lower BW was associated with a thinner corneal thickness at the apex (B = 1.71 µm/500 g, p < 0.001) and at the pupil (B = 1.69 µm/500 g, p < 0.001). These effects diminished towards the corneal periphery resulting in no differences in the perilimbal regions. Conclusion: The present study provides evidence that lower birth weight goes along with corneal thickness alterations even into adult ages of 40 to 80 years. Thinner measurements of the cornea were particularly found in the corneal center and diminished in the periphery. This indicates that there may be fetal origins affecting corneal thickness development particularly in the corneal center.


[Bunyavirus and its ecology].
The family Bunyaviridae consists of over 300 virus species and strains that are divided into 5 genera: orthobunyavirus, hantavirus, nairovirus, phlebovirus, and tospovirus. All members of family Bunyaviridae possess a negative-sense, single stranded tripartite RNA genome, consisting of large (L), medium (M) and small (S) segments, which encode an RNA-dependent RNA polymerase, two envelope glyoproteins (Gn and Gc) and nucleocapsid (N) protein, respectively. Insects and arthropods serve as vectors of viruses in the Bunyaviridae, except for hantviruses, which instead are harbored by rodents. However, phylogenetically distinct soricomorph-associated hantaviruses have been discovered in widely separated geographical regions spanning four continents. This new finding strongly suggests that evolutionary record of hantaviruses is far more complex and ancient than originally expected. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease recently described in northeast and central China. The causative agent of SFTS is phylogenetically classified to genus phlebivirus, but unlike to other member in genus phlebovirus, SFTV transmit by ticks. This review provides a brief overview of hantavirus and hantavirus infection and describes about two newly appeared viruses in the family Bunyaviridae.


Optical techniques for the intraoperative assessment of nodal status.
The lymphatic system is an important pathway in the metastatic spread of many malignancies and a key prognostic indicator. Nondestructive assessment of the nodal status during surgery could limit the amount of lymph nodes that need to be resected and allow for immediate regional lymphadenectomy during sentinel lymph node biopsy procedures. This review looks into the possibilities of conventional medical imaging methods that are capable of intraoperative nodal assessment and discusses multiple newly developed optical techniques. The physical background behind these techniques is reviewed and a concise overview of their main advantages and disadvantages is provided. These recent innovations show that while the application of optical modalities for intraoperative nodal staging is not yet applied routinely, there is reason enough to expect their introduction in the near future.


[In vitro transformation of human amniotic fluid cells in the presence of fecalase. Method for detecting environmental chemicals with oncogenic potential].
A short-term method for detecting potential environmental carcinogens is described using in vitro transformation assay of human epithelial-like amniotic fluid cells. According to Styles, after a short exposition to the carcinogen, only transformed cells grow and form large colonies when cultured in semi-solid agar. In our assay addition of liver homogenate was not necessary to activate the carcinogens. Nevertheless adjunction to the exposure medium of human fecalase (after Ames) is advised for studying carcinogenicity of food glycosides. Fecalase efficiency in metabolic activation of glycosidic compounds has been demonstrated in the use of 8-hydroxyquinoline-beta-D-glycopyranoside.


Relapsing acute pancreatitis induced by re-exposure to the cholesterol lowering agent bezafibrate.
We report a 75-yr-old patient, who presented three times with acute pancreatitis, accompanied by high temperature, shock, and multiorgan involvement and associated each time with exposure to the cholesterol lowering agent bezafibrate. Extensive workup excluded other possible causes for recurrent pancreatitis in this patient, further supporting bezafibrate as the cause of the patient's acute illness. Based on the short time elapsing between rechallenge and development of manifestations and the specific features of the attacks, we proposed hypersensitivity to bezafibrate as the underlying mechanism. The present report includes, for the first time, bezafibrate among definite causes of acute pancreatitis.


Characterization of the frameshift stimulatory signal controlling a programmed -1 ribosomal frameshift in the human immunodeficiency virus type 1.
Synthesis of the Gag-Pol protein of the human immunodeficiency virus type 1 (HIV-1) requires a programmed -1 ribosomal frameshifting when ribosomes translate the unspliced viral messenger RNA. This frameshift occurs at a slippery sequence followed by an RNA structure motif that stimulates frameshifting. This motif is commonly assumed to be a simple stem-loop for HIV-1. In this study, we show that the frameshift stimulatory signal is more complex than believed and consists of a two-stem helix. The upper stem-loop corresponds to the classic stem-loop, and the lower stem is formed by pairing the spacer region following the slippery sequence and preceding this classic stem-loop with a segment downstream of this stem-loop. A three-purine bulge interrupts the two stems. This structure was suggested by enzymatic probing with nuclease V1 of an RNA fragment corresponding to the gag/pol frameshift region of HIV-1. The involvement of the novel lower stem in frameshifting was supported by site-directed mutagenesis. A fragment encompassing the gag/pol frameshift region of HIV-1 was inserted in the beginning of the coding sequence of a reporter gene coding for the firefly luciferase, such that expression of luciferase requires a -1 frameshift. When the reporter was expressed in COS cells, mutations that disrupt the capacity to form the lower stem reduced frameshifting, whereas compensatory changes that allow re-formation of this stem restored the frameshift efficiency near wild-type level. The two-stem structure that we propose for the frameshift stimulatory signal of HIV-1 differs from the RNA triple helix structure recently proposed.


Suitability of near-total laryngopharyngectomy in piriform carcinoma.
The surgical specimens from total laryngectomy and partial pharyngectomy in 20 consecutive cases of piriform sinus carcinoma were studied by whole-organ serial sectioning in the horizontal plane. There had been gross clinical involvement or fixation of the vocal cord in 19 of these cases. Histopathologic evidence of cartilage invasion or piriform apex involvement was found in 17 specimens. In 13 cases, it appeared, retrospectively, that the cancer could have been adequately encompassed without resecting the entire contralateral side of the larynx. When this element is spared, a sphincteric speaking shunt can be made. Careful preoperative assessment would have correctly predicted the suitability or danger of this approach in 18 of the 20 cases; the two indeterminate cases would have required intraoperative quick section. These findings have meaningful implications regarding the scope of conservation surgery in piriform carcinoma.


Associations of Mental Health and Physical Function with Colonoscopy-related Pain.
Objective To clarify the effects of mental health and physical function in association with colonoscopy-related pain. Methods The mental health and physical function were evaluated using the Japanese version of the SF-8 Health Survey questionnaire. Poor physical status was defined as a physical component summary (PCS) <40 and poor mental status as a mental component summary (MCS) <40. Pain was assessed using a visual analogue scale (VAS), with significant pain defined as VAS ≥70 mm and insignificant pain as VAS <70 mm. The background and colonoscopic findings were compared in patients with significant and insignificant pain. Patients This study evaluated consecutive Japanese patients who were positive on fecal occult blood tests and underwent total colonoscopy. Results Of the 100 patients, 23 had significant and 77 had insignificant colonoscopy-related pain. A multiple logistic regression analysis showed that MCS <40 [odds ratio (OR) 6.03; 95% confidence interval (CI) 1.41-25.9, p=0.0156], PCS <40 (OR 5.96; 95% CI 1.45-24.5, p=0.0133), and ≥300 seconds to reach the cecum (OR 4.13; 95% CI 1.16-14.7, p=0.0281) were independent risk factors for colonoscopy-related pain. Conclusion The mental health and physical function are important determinants of colonoscopy-related pain. Evaluating the mental health and physical function of patients prior to colonoscopy may effectively predict the degree of colonoscopy-related pain.


Gibbs free energy of liquid water derived from infrared measurements.
Infrared spectra of pure liquid water were recorded from 20 cm(-1) to 4000 cm(-1) at temperatures ranging from 263 K to 363 K. The evolution of connectivity, libration, bending and OH stretching bands as a function of temperature follows the evolution of the inter-molecular dynamics, and so gives insight into the internal energy averaged over the measurement time and space. A partition function, which takes into account the inter-molecular and intra-molecular modes of vibration of water, all variable with the molecular networking, was developed to convert this vibrational absorption behavior of water into its macroscopic Gibbs free energy, assuming the vibrational energy to feature most of the water energy. Calculated Gibbs free energies along the thermal range are in close agreement with the literature values up to 318 K. Above this temperature, contributions specific to the non H-bonded molecules must be involved to closely fit the thermodynamics of water. We discussed this temperature threshold in relation to the well-known isosbestic point. Generally speaking, our approach is valuable to convert the IR molecular data into mean field properties, a quantitative basis to predict how water behaves in natural or industrial settings.


Sevoflurane and propofol increase 11C-flumazenil binding to gamma-aminobutyric acidA receptors in humans.
Based on in vitro studies and animal data, most anesthetics are supposed to act via gamma-aminobutyric acid type A (GABA(A)) receptors. However, this fundamental characteristic has not been extensively investigated in humans. We studied (11)C-flumazenil binding to GABA(A) receptors during sevoflurane and propofol anesthesia in the living human brain using positron emission tomography (PET). Fourteen healthy male subjects underwent 2 60-min dynamic PET studies with (11)C-labeled flumazenil, awake and during anesthesia. Anesthesia was maintained with 2% end-tidal sevoflurane (n = 7) or propofol at a target plasma concentration of 9.0 +/- 3.0 (mean +/- sd) microg/mL (n = 7). The depth of anesthesia was measured with bispectral index (BIS). Values of regional distribution volumes (DV) of (11)C-flumazenil were calculated in several brain areas using metabolite-corrected arterial plasma curves and a two-compartment model. Separate voxel-based statistical analysis using parametric DV images was performed for detailed visualization. The average BIS index was 35 +/- 6 in the sevoflurane group and 28 +/- 8 in the propofol group (P = 0.02). Sevoflurane increased the DV of (11)C-flumazenil significantly (P < 0.05) in all brain areas studied except the pons and the white matter. In the propofol group the increases were significant (P < 0.05) in the caudatus, putamen, cerebellum, thalamus and the frontal, temporal, and parietal cortices. Furthermore, the DV increases in the frontal, occipital, parietal, and temporal cortical areas and in the putamen were statistically significantly larger in the sevoflurane than in the propofol group. Our findings support the involvement of GABA(A) receptors in the mechanism of action of both anesthetics in humans.


Epidemiology of cryptosporidiosis in North American travelers to Mexico.
We studied 1,179 North American travelers who visited Mexico from 2005 to 2007. Travelers' diarrhea (TD) was reported by 521 (44%) participants. Among subjects with TD, 218 cases were examined for cryptosporidiosis by polymerase chain reaction (PCR) and enzyme-linked immunoassays (ELISA). There were 14 (6%) cases of cryptosporidiosis and 141 cases (64%) of bacterial diarrhea. Compared with bacterial diarrhea, a longer stay in Mexico was a risk factor for cryptosporidiosis. Additionally, Cryptosporidium cases passed greater number of watery stools (P < 0.05), suffered more episodes of diarrhea (P < or = 0.05), and were more likely to experience tenesmus (P < or = 0.05) compared with bacterial causes of TD. ELISA detected seven (3%) cases of Cryptosporidium, whereas PCR identified an additional seven cases (6%). Speciation by 18SrRNA sequencing showed that 13 cases were caused by C. parvum and only 1 case was caused by C. hominis. ELISA showed a sensitivity of 50% and specificity of 100% compared with PCR.


Predictors of mortality in the Amsterdam cohort of human immunodeficiency virus (HIV)-positive and HIV-negative drug users.
The impact of human immunodeficiency virus (HIV) infection and other risk factors on mortality was studied in a cohort of Dutch injection drug users and drug users who did not inject. Participants were recruited between 1985 and 1992 and followed up through 1993. Vital status was ascertained through repeat visit information, supplemented by population register data. A total of 77 deaths were recorded among 632 drug users, for a mortality rate per 1,000 person-years of 7 for HIV-negative noninjection drug users, 18 for HIV-negative injection drug users, and 64 for HIV-positive injection drug users. In multivariate analyses, limited to injection drug users, a positive HIV serostatus, age above 40 years, and using benzodiazepines several times daily were significantly associated with an elevated risk of death, both for death from all causes and for death preceding acquired immunodeficiency syndrome (AIDS) diagnosis (pre-AIDS). For pre-AIDS death, the adjusted relative risk associated with HIV infection was 2.2 (95% confidence interval 1.3-3.7). Only 38% of HIV-infected injection drug users who died were diagnosed with AIDS. However, 76% of HIV-infected injection drug users who died without AIDS diagnosis had evidence of immunosuppression (CD4 count < 500/microliters). Daily use of methadone and participation in needle and syringe exchange schemes were not associated with lower mortality rates. This study illustrates in a group of injection drug users with a 30% HIV seroprevalence and a high background mortality the profound influence on mortality that HIV infection has gained.


[Multiple lentigines syndrome. Apropos of 2 cases. Critical study of the leopard syndrome].
With regard to 2 cases of a same family associating: multiple lentigos, osseous signs and impairment of E.C.G., the authors recall the differents visceral manifestations which can be associated to lentigos and the relative frequency of every one of them. The authors report 38 indisputable observations of the literature that associated the 2 criterions: multiple lentigos symmetrical in their distribution and histological confirmation of sun spots. The authors perfer the term: multiple lentigos syndrome to the LEOPARD syndrome. The last term (LEOPARD), in spite of his attractive character contains a part of possible associated signs (osseous signs, primordial in our observations, are not present in that syndrome). But another way, contrary to, not any observation, up to now, allowed all the symptomes present in the acrostic LEOPARD. Through it should appear difficult to define actually the scope of the multiple lentigos syndrome, the knowledge of that entity offers a real interest for the dermopath: the discovery of a symmetrical lentiginosis, extensive or not, must lead to the exploration, as well as possible, of organs susceptible to be out of order: heart, nervous system and hearing, skeleton and facial malformations, genital-organs, and also to a family inquiry.


Age related changes in metabolite concentrations in the normal spinal cord.
Magnetic resonance spectroscopy (MRS) studies have previously described metabolite changes associated with aging of the healthy brain and provided insights into normal brain aging that can assist us in differentiating age-related changes from those associated with neurological disease. The present study investigates whether age-related changes in metabolite concentrations occur in the healthy cervical spinal cord. 25 healthy volunteers, aged 23-65 years, underwent conventional imaging and single-voxel MRS of the upper cervical cord using an optimised point resolved spectroscopy sequence on a 3T Achieva system. Metabolite concentrations normalised to unsuppressed water were quantified using LCModel and associations between age and spinal cord metabolite concentrations were examined using multiple regressions. A linear decline in total N-Acetyl-aspartate concentration (0.049 mmol/L lower per additional year of age, p = 0.010) and Glutamate-Glutamine concentration (0.054 mmol/L lower per additional year of age, p = 0.002) was seen within our sample age range, starting in the early twenties. The findings suggest that neuroaxonal loss and/or metabolic neuronal dysfunction, and decline in glutamate-glutamine neurotransmitter pool progress with aging.


On the potential use of dynamic contrast-enhanced (DCE) MRI parameters as radiomic features of cervical cancer.
To evaluate whether the analysis of high-temporal resolution DCE-MRI by various tracer kinetic models could yield useful radiomic features in discriminating cervix carcinoma and normal cervix tissue. Forty-three patients (median age 51 yr; range 26-78 yr) diagnosed with cervical cancer based on postoperative pathology were enrolled in this study with informed consent. DCE-MRI data with temporal resolution of 2 s were acquired and analyzed using the Tofts (TOFTS), extended Tofts (EXTOFTS), conventional two-compartment (CC), adiabatic tissue homogeneity (ATH), and distributed parameter (DP) models. Ability of all kinetic parameters in distinguishing tumor from normal tissue was assessed using Mann-Whitney U test and receiver operating characteristic (ROC) curves. Repeatability of parameter estimates due to sampling of arterial input functions (AIFs) was also studied using intraclass correlation (ICC) analysis. Fractional extravascular, extracellular volume (Ve) of all models were significantly smaller in cervix carcinoma than normal cervix tissue, and were associated with large values of area under ROC curve (AUC 0.884-0.961). Capillary permeability PS derived from the ATH, CC, and DP models also yielded large AUC values (0.730, 0.860, and 0.797). Transfer constant Ktrans derived from TOFTS and EXTOFTS models yielded smaller AUC (0.587 and 0.701). Repeatability of parameters derived from all models was robust to AIF sampling, with ICC coefficients typically larger than 0.80. With the use of high-temporal resolution DCE-MRI, all tracer kinetic models could reflect pathophysiological differences between cervix carcinoma and normal tissue (with significant differences in Ve and PS) and potentially yield radiomic features with diagnostic value.


Thrombin receptor polymorphism in Chinese hamster.
We report the existence of a new Chinese hamster thrombin receptor allele, characterized by an in-frame insertion of three nucleotides at position 250 of the published sequence. As a consequence, an additional proline is inserted into a proline-rich region of the extracellular amino-terminal domain of the receptor. A corresponding proline at this position is also found in the rat thrombin receptor. A silent base-pair change is found in the cytoplasmic tail of the receptor gene. Single-strand conformation polymorphism and sequence analysis indicate this new receptor allele is present in several cell lines derived from different individual Chinese hamsters. Embryonic CHEF IIC9 cells and primary culture cells are homozygous for this new allele. In contrast, the CCL39 lung fibroblast cell line is heterozygous for both the new and old alleles. Both alleles are transcribed into mRNA and code for functional receptors. Given the allelic distribution and sequence alignment with thrombin receptors from other species, we propose that the new sequence represents the actual predominant allele in Chinese hamster.


The role of scientists in statutory interpretation of the U.S. Endangered Species Act.
Like many federal statutes, the U.S. Endangered Species Act (ESA) contains vague or ambiguous language. The meaning imparted to the ESA's unclear language can profoundly impact the fates of endangered and threatened species. Hence, conservation scientists should contribute to the interpretation of the ESA when vague or ambiguous language contains scientific words or refers to scientific concepts. Scientists need to know at least these 2 facts about statutory interpretation: statutory interpretation is subjective and the potential influence of normative values results in different expectations for the parties involved. With the possible exception of judges, all conventional participants in statutory interpretation are serving their own interests, advocating for their preferred policies, or biased. Hence, scientists can play a unique role by informing the interpretative process with objective, policy-neutral information. Conversely, scientists may act as advocates for their preferred interpretation of unclear statutory language. The different roles scientists might play in statutory interpretation raise the issues of advocacy and competency. Advocating for a preferred statutory interpretation is legitimate political behavior by scientists, but statutory interpretation can be strongly influenced by normative values. Therefore, scientists must be careful not to commit stealth policy advocacy. Most conservation scientists lack demonstrable competence in statutory interpretation and therefore should consult or collaborate with lawyers when interpreting statutes. Professional scientific societies are widely perceived by the public as unbiased sources of objective information. Therefore, professional scientific societies should remain policy neutral and present all interpretations of unclear statutory language; explain the semantics and science both supporting and contradicting each interpretation; and describe the potential consequences of implementing each interpretation. A review of scientists' interpretations of the phrase "significant portion of its range" in the ESA is used to critique the role of scientists and professional societies in statutory interpretation.


High-resolution time-of-flight terahertz tomography using a femtosecond fiber laser.
High-resolution tomographic imaging is demonstrated using a reflection-type terahertz time-domain spectroscopy. To realize a practical system for general use, a robust all-fiber laser was used as the pump light source. Broadband terahertz waves were generated with the combination of optical pulses compressed to 17 fs using optical fibers and a DAST crystal. Using deconvolution signal processing, the wideband spectrum of the generated terahertz waves provided high-axial resolution leading to successful imaging of a multilayered structure containing a 2-microm-thin GaAs layer. To our knowledge, this is the first demonstration of terahertz tomographic imaging of such a thin layer.


Two new sesquiterpene aryl esters from Armillaria gallica 012m.
Two new sesquiterpene aryl esters, armimelleolides A and B (1 and 2), and four known ones, were isolated from the EtOAc extract of Armillaria gallica 012 m by column chromatography on silica gel, reversed-phase C18 silica gel and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic methods, including extensive 1 D NMR, 2 D NMR and MS. All these compounds showed potential antitumor activities against at least one of the human cancer cell lines (A549, HCT-116, M231 and W256), with IC50 ranging from 2.57 to 19.94 μM.


The Ophthalmic Side Effects of Topiramate: A Review.
Topiramate (TPM) is a sulfonamide drug with multiple modes of action. It inhibits carbonic anhydrase, blocks sodium channels, enhances potassium channels, and stimulates postsynaptic gamma-aminobutyric acid (GABA) receptors. Pharmacists Joe Gardocki and Bruce Maryanoff synthesized TPM for the first time in 1979. The FDA did not approve it for medical use in the US until 1996. Around 2004, it was authorized for the prevention of migraine headaches. TPM, like any medication, has several side effects. Common aftermaths include weight loss, diarrhea, dizziness, sleepiness, fatigue, and coordination issues. Some people may experience mental health issues like memory problems, confusion, and speech or language difficulties. The most well-known ocular side effects of TPM are choroidal effusion syndrome, angle-closure glaucoma, and myopic shift. Aside from these, other ophthalmic adverse effects may arise in some people, including retinal problems, uveitis, visual field defects, myokymia, and neuro-ophthalmology complications. If such complications are not identified and treated promptly, they can be severe and vision-threatening, potentially leading to permanent blindness. TPM's application as a standalone and adjunctive therapy has increased over time. In 2019, more than 10 million prescriptions of TPM were issued. Due to its extensive use, medical professionals and patients must be aware of its potential repercussions, especially ophthalmic issues. The current review paper likewise makes a step in this direction. This article's primary purpose is to educate readers by providing a comprehensive assessment of the research on TPM's ocular side effects. All the information has been collected via a thorough search of the Google Search Engine and PubMed.


Edible aquatic Coleoptera of the world with an emphasis on Mexico.
Anthropoentomophagy is an ancient culinary practice wherein terrestrial and aquatic insects are eaten by humans. Of these species of insects, terrestrial insects are far more commonly used in anthropoentomophagy than aquatic insects. In this study we found that there are 22 genera and 78 species of edible aquatic beetles in the world. The family Dytiscidae hosts nine genera, Gyrinidae one, Elmidae two, Histeridae one, Hydrophilidae six, Haliplidae two and Noteridae one. Of the recorded species, 45 correspond to the family Dytiscidae, 19 to Hydrophilidae, three to Gyrinidae, four to Elmidae, two to Histeridae, four to Haliplidae and one to Noteridae. These beetles are the most prized organisms of lentic waters. The family that has the highest number of edible food insect genera and species is Dytiscidae. Here, the global geographic distribution of species in these organisms is shown, and a discussion is presented of its importance as a renewable natural resource widely used for food in various countries.


Similarities in the Etiology of Alcohol Use Among Native American and Non-Native Young Women.
This study examined social-and individual-level factors associated with alcohol use among young women and tested whether differences exist between Native American and non-Native young women. School-based surveys were conducted among 952 young women (ages 14-19) attending four high schools within the tribal jurisdictional service area of the Cherokee Nation in northeastern Oklahoma. Structural equation modeling using Mplus was used to assess the direct and indirect effects of social-and individual-level factors on subsequent alcohol use among Native and non-Native young women. We found no differences in the level of risk and protective factors among Native and non-Native young women. Among Native and non-Native young women, alcohol access, parental communication, and best friends' alcohol use had statistically significant direct and/or indirect effects on alcohol use. Indirect effects were mediated through alcohol expectancies and norms. A history of alcohol problems by an adult in the household and depression were not retained as independent risk factors in either model. We found more similarities than differences in level of and relations to alcohol use among social and individual risk and protective factors between Native American and non-Native young women from northeastern Oklahoma. The results provide support for universal prevention strategies, suggesting the importance of increasing perceptions that it is difficult to obtain alcohol and increasing parent-child communication.


Personal protective equipment for preventing highly infectious diseases due to exposure to contaminated body fluids in healthcare staff.
In epidemics of highly infectious diseases, such as Ebola Virus Disease (EVD) or SARS, healthcare workers (HCW) are at much greater risk of infection than the general population, due to their contact with patients' contaminated body fluids. Contact precautions by means of personal protective equipment (PPE) can reduce the risk. It is unclear which type of PPE protects best, what is the best way to remove PPE, and how to make sure HCWs use PPE as instructed. To evaluate which type or component of full-body PPE and which method of donning or removing (doffing) PPE have the least risk of self-contamination or infection for HCWs, and which training methods most increase compliance with PPE protocols. We searched MEDLINE (PubMed up to 8 January 2016), Cochrane Central Register of Trials (CENTRAL up to 20 January 2016), EMBASE (embase.com up to 8 January 2016), CINAHL (EBSCOhost up to 20 January 2016), and OSH-Update up to 8 January 2016. We also screened reference lists of included trials and relevant reviews, and contacted NGOs and manufacturers of PPE. We included all eligible controlled studies that compared the effect of types or components of PPE in HCWs exposed to highly infectious diseases with serious consequences, such as EVD and SARS, on the risk of infection, contamination, or noncompliance with protocols. This included studies that simulated contamination with fluorescent markers or a non-pathogenic virus.We also included studies that compared the effect of various ways of donning or removing PPE, and the effects of various types of training in PPE use on the same outcomes. Two authors independently selected studies, extracted data and assessed risk of bias in included trials. We intended to perform meta-analyses but we did not find sufficiently similar studies to combine their results. We included nine studies with 1200 participants evaluating ten interventions. Of these, eight trials simulated the exposure with a fluorescent marker or virus or bacteria containing fluids. Five studies evaluated different types of PPE against each other but two did not report sufficient data. Another two studies compared different types of donning and doffing and three studies evaluated the effect of different types of training.None of the included studies reported a standardised classification of the protective properties against viral penetration of the PPE, and only one reported the brand of PPE used. None of the studies were conducted with HCWs exposed to EVD but in one study participants were exposed to SARS. Different types of PPE versus each otherIn simulation studies, contamination rates varied from 25% to 100% of participants for all types of PPE. In one study, PPE made of more breathable material did not lead to a statistically significantly different number of spots with contamination but did have greater user satisfaction (Mean Difference (MD) -0.46 (95% Confidence Interval (CI) -0.84 to -0.08, range 1 to 5, very low quality evidence). In another study, gowns protected better than aprons. In yet another study, the use of a powered air-purifying respirator protected better than a now outdated form of PPE. There were no studies on goggles versus face shields, on long- versus short-sleeved gloves, or on the use of taping PPE parts together. Different methods of donning and doffing procedures versus each otherTwo cross-over simulation studies (one RCT, one CCT) compared different methods for donning and doffing against each other. Double gloving led to less contamination compared to single gloving (Relative Risk (RR) 0.36; 95% CI 0.16 to 0.78, very low quality evidence) in one simulation study, but not to more noncompliance with guidance (RR 1.08; 95% CI 0.70 to 1.67, very low quality evidence). Following CDC recommendations for doffing led to less contamination in another study (very low quality evidence). There were no studies on the use of disinfectants while doffing. Different types of training versus each otherIn one study, the use of additional computer simulation led to less errors in doffing (MD -1.2, 95% CI -1.6 to -0.7) and in another study additional spoken instruction led to less errors (MD -0.9, 95% CI -1.4 to -0.4). One retrospective cohort study assessed the effect of active training - defined as face-to-face instruction - versus passive training - defined as folders or videos - on noncompliance with PPE use and on noncompliance with doffing guidance. Active training did not considerably reduce noncompliance in PPE use (Odds Ratio (OR) 0.63; 95% CI 0.31 to 1.30) but reduced noncompliance with doffing procedures (OR 0.45; 95% CI 0.21 to 0.98, very low quality evidence). There were no studies on how to retain the results of training in the long term or on resource use.The quality of the evidence was very low for all comparisons because of high risk of bias in studies, indirectness of evidence, and small numbers of participants. This means that it is likely that the true effect can be substantially different from the one reported here. We found very low quality evidence that more breathable types of PPE may not lead to more contamination, but may have greater user satisfaction. We also found very low quality evidence that double gloving and CDC doffing guidance appear to decrease the risk of contamination and that more active training in PPE use may reduce PPE and doffing errors more than passive training. However, the data all come from single studies with high risk of bias and we are uncertain about the estimates of effects.We need simulation studies conducted with several dozens of participants, preferably using a non-pathogenic virus, to find out which type and combination of PPE protects best, and what is the best way to remove PPE. We also need randomised controlled studies of the effects of one type of training versus another to find out which training works best in the long term. HCWs exposed to highly infectious diseases should have their use of PPE registered and should be prospectively followed for their risk of infection.


Preclinical studies of the novel vascular disrupting agent MN-029.
Vascular disrupting agents (VDAs) are designed to cause a rapid and selective shutdown of the established tumor vasculature, which leads to secondary ischemic tumor cell death. We examined the efficacy of a novel VDA, MN-029, in the rodent KHT sarcoma model. A significant reduction in the functional vessel number was observed after intraperitoneal injection of MN-029 at a dose of 100 mg/kg. Histological evaluation showed extensive necrosis (approximately 90%) by 24 h. MN-029 treatment to the tumor-bearing mice also resulted in a dose-dependent tumor cell killing. When used in combination with radiation or cisplatin chemotherapy, a 100 mg/kg dose of MN-029 significantly enhanced tumor killing compared to that seen with radiation or cisplatin alone. The results demonstrated that MN-029 could cause rapid vascular shutdown in solid tumors, dose-dependent secondary tumor cell killing, and effective enhancement of the antitumor effects of radiation and cisplatin chemotherapy.


The NMR blood flowmeter--applications.
Nuclear Magnetic Resonance (NMR) permits the noninvasive measurement of blood flow signals unimpaired by clothes, bandages, casts, etc. The cylindrical crossed-coil NMR blood flowmeter was used to measure blood flow through a cross-section of the human forearm. Two calibration procedures are described: one for pulsatile flows and the other for flows with a high non-pulsatile component. Flow measurements from normal arms, from limbs with arterial obstruction, arteriovenous hemodialysis fistulas or other conditions are reported. An application of the flow scanning technique for separation of flow signals from individual arteries (e.g., ulnar and radial) is described. The flat crossed-coil NMR flowmeter was applied to detect blood flow from individual arteries (e.g., brachial, popliteal, etc.). Applications of a ranging technique developed to detect signals at predetermined depths are described.


Method of leptin dosing, strain, and group housing influence leptin sensitivity in high-fat-fed weanling mice.
High-fat diets are reported to induce resistance to peripherally administered leptin. In an attempt to develop a model of juvenile diet-induced obesity, mice were weaned onto high-fat diet. Male and female, 35-day-old, C57BL/6J high-fat (45% kcal fat) diet-fed mice housed individually on grid floors did not decrease food intake or body weight in response to intraperitoneal (30 microg), lateral ventricle (5 microg), or third ventricle (0.5 microg) injections of leptin. Body weight and fat were significantly reduced by 13-day intraperitoneal infusions of 10 microg leptin/day, which doubled circulating leptin. Leptin infusion also reduced body fat in weanling, high-fat diet-fed NIH Swiss mice. Group housing mice on bedding prevented loss of fat in high-fat diet-fed male and female NIH Swiss and female C57BL/6J mice. These results indicate that peripherally infused leptin reduces fat in part by increasing thermogenesis and that inhibition of food intake in high-fat diet-fed mice requires either chronic activation of central leptin receptors or is independent of receptors that inhibit feeding in response to an acute central injection of leptin.


Genistein: mechanisms of action for a pleiotropic neuroprotective agent in stroke.
Genistein is a plant estrogen promoted as an alternative to post-menopausal hormone therapy because of a good safety profile and its promotion as a natural product. Several preclinical studies of cerebral ischemia and other models of brain injury support a beneficial role for genistein in protecting the brain from injury whether administered chronically or acutely. Like estrogen, genistein is a pleiotropic molecule that engages several different mechanisms to enhance brain health, including reduction of oxidative stress, promotion of growth factor signaling, and immune suppression. These actions occur in endothelial, glial, and neuronal cells to provide a coordinated beneficial action to ischemic challenge. Though many of these protective actions are associated with estrogen-like actions of genistein, additional activities on other receptors and intracellular targets suggest that genistein is more than a mere estrogen-mimic. Importantly, genistein lacks some of the detrimental effects associated with post-menopausal estrogen treatment and may provide an alternative to hormone therapy in those patients at risk for ischemic events.


From Ornstein-Uhlenbeck dynamics to long-memory processes and fractional Brownian motion.
This article establishes a natural physical path leading from "regular" Ornstein-Uhlenbeck dynamics to "anomalous" long-memory processes and, thereafter, to fractional Brownian motion. Considering a system composed of n different parts-each part conducting its own Ornstein-Uhlenbeck dynamics, and all parts being perturbed by a common external Lévy noise-we show that the collective system-dynamics, in the limit n-->infinity , converges to a temporal moving-average of the driving noise. The limiting moving-average process, in turn, can possess a long memory-in which case, when observed over large time scales, further yields fractional Brownian motion. The temporal correlation structure of the limiting moving-average process turns out to be determined by the structural statistical variability of the system's composing parts. Thus, the emergence of a long memory is a consequence of the intrinsic "quenched disorder" present at the system's formation epoch rather than the consequence of the external annealed disorder carried in continuously by the driving noise.


Nonlinear effects contributing to hand-stopping tones in a horn.
Hand stopping is a technique for playing the French horn while closing the bell relatively tightly using the right hand. The resulting timbre is called "penetrating" and "metallic." The effect of hand stopping on the horn input impedance has been studied, but the tone quality has hardly ever been considered. In the present paper, the dominant physical cause of the stopped-tone quality is discussed in detail. Numerical calculations of the transmission function of the stopped-horn model and the measurements of both sound pressure and wall vibration in hand stopping are carried out. They strongly suggest that the metallicness of the stopped tone is characterized by the generation of higher harmonics extending over 10 kHz due to the rapidly corrugating waveform and that the associated wall vibration on the bell may be responsible for this higher harmonic generation. However, excitation experiments and immobilization experiments performed to elucidate the relationship between sound radiation and wall vibration deny their correlation. Instead, the measurement result of the mouthpiece pressure in hand stopping suggests that minute wave corrugations peculiar to the metallic stopped tones are probably formed by nonlinear sound propagation along the bore.


Role of nonohmicity in the regulation of electron transport in plant mitochondria.
The relationship between the respiratory rate and the membrane ionic current on the protonmotive force has been investigated in percoll purified potato mitochondria. The dependence of the membrane ionic current on the membrane potential was monitored using a methyltriphenylphosphonium-sensitive electrode and determining the maximal net rate of depolarization following the addition of a respiratory inhibitor. We have confirmed that a nonohmic relationship exists between the ionic conductance and membrane potential. Addition of ATPase inhibitors markedly increased the initial rate of dissipation suggesting that in their absence the dissipation rate induced by respiratory inhibitors is partially offset by H(+)-efflux due to the hydrolysis of endogenous ATP. This was corroborated by direct measurement of endogenous ATP levels which decreased significantly following dissipation of the membrane potential. Results are discussed in terms of the regulation of electron transport in plant mitochondria in vivo.


Effects of an empowerment program on health behaviors and stroke risk reduction of at-risk group in Thai rural community.
Unhealthy behaviors such as being overweight, have hypertension, diabetes, and dyslipidemia increase the risks of stroke. Promoting healthy behaviors could reduce the incidence of stroke, death, and disabilities. Empowerment was used in this study to help people change their health behaviors. To determine the effects of an empowerment program on health behaviors and stroke risk factors reduction of people at-risk for stroke in a rural community in Thailand. A quasi-experimental study was conducted in sixty participants identified with moderate risk for stroke, according to the Standard Operation Procedure to Prevent and Control of Stroke 2007 of the Bureau of Non Communicable Disease, from two villages in Phitsanulok. Participants were enrolled in experimental (n = 30) and control (n = 30) groups using match pair for sex, age, blood pressure, and blood sugar. The experimental group received empowerment based on the Gibson's model of empowerment (discovering reality, critical reflection, taking charge, and holding on) at week 1, 4, and 8 while the control group received routine care. The study duration was 12 weeks. Instruments used were a questionnaire regarding health behaviors and a form for recording the BMI, blood pressure, blood sugar cholesterol, and triglyceride. Data analyses included the Analysis of Variance (ANOVA), repeated measure, and independent t-test. Following the implementation of the empowerment program, health behaviors of participants in the experimental group were significantly better than those of the control group (p < 0.001). Risk factors, body mass index, blood pressure, blood sugar, cholesterol, and triglyceride of participants in the experimental group were significantly lower than those in the control group (p < 0.01, p < 0.001). The empowerment program was effective in decreasing stroke risk behaviors and stroke risk factors. Future research using this empowerment intervention program should be conducted in high cardiovascular risk group and patients with other chronic diseases.


Anaplastic lymphoma kinase-positive large cell lymphoma of the anterior skull base: Report of an unusual case and review of the literature.
Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is a rare peripheral T-cell lymphoma, accounting for approximately 3% of adult non-Hodgkin lymphomas (NHL). In this report we describe an unusual case of an ALK(+) ALCL, which presented as an aggressive mass involving upper nasal cavity and anterior skull base. The pathogenesis, histopathology with radiologic correlations, and management of this case are reviewed. A 28-year-old Asian female presented with a 3-month history of nasal congestion culminating in epistaxis. Physical examination was notable for a tissue mass obstructing nasal cavity and the sphenoid sinus. Computed tomography (CT) and magnetic resonance (MR) imaging revealed a lesion primarily involving the upper nasal cavity extending intracranially through the cribriform plates into the anterior cranial fossa. Histologic and immunohistochemical analysis of the specimen obtained through a transnasal biopsy revealed an ALK(+) ALCL. The patient underwent two cycles of chemotherapy and focal radiation therapy, achieving minimal residual disease. The patient remained neurologically unchanged with stable minimal residual disease at the 1-year follow-up. To the best of our knowledge, this is the first case of an ALK(+) ALCL that presented as an aggressive upper nasal cavity and anterior skull base lesion. This case report highlights the importance of multi-modality approaches including preoperative imaging and tissue biopsy for definitive diagnosis.


A prospective investigation of dietary patterns and internalizing and externalizing mental health problems in adolescents.
Investigating protective and risk factors that influence mental health in young people is a high priority. While previous cross-sectional studies have reported associations between diet and mental health among adolescents, few prospective studies exist. The aim of this study was to examine prospective relationships between dietary patterns and mental health among adolescents participating in the Western Australian Pregnancy Cohort (Raine) Study. Self-report questionnaires were used to assess indicators of mental health (Youth Self-Report externalizing/internalizing T-scores) and Western and Healthy dietary patterns (identified using factor analysis) at 14 (2003-2005) and 17 years (2006-2008). Multivariate linear and logistic regression were used to assess relationships between dietary patterns and mental health. Complete data were available for 746 adolescents. In females only, the Western dietary pattern z-score at 14 years was positively associated with greater externalizing behaviors at 17 years (β = 1.91; 95% CI: 0.04, 3.78) and a greater odds of having clinically concerning externalizing behaviors at 17 years (OR = 1.90; 95% CI: 1.06, 3.41). No other statistically significant associations were observed. Overall our findings only lend partial support to a link between diet and mental health. We found it to be specific to females consuming a Western dietary pattern and to externalizing behaviors. Future research on dietary patterns and mental health needs to consider possible sex differences and distinguish between different mental health outcomes as well as between healthy and unhealthy dietary patterns.


Nonequilibrium temperature measurement in a thermal conduction process.
We identify the temperature being measured by a thermometer in a nonequilibrium scenario by studying heat conduction in a three-dimensional Lennard-Jones (LJ) system whose two ends are kept at different temperatures. It is accomplished by modeling the thermometer particles also with the LJ potential but with added tethers to prevent their rigid body motion. These models of the system and the thermometer mimic a real scenario in which a mechanical thermometer is "inserted" into a system and kept there long enough for the temperature to reach a steady value. The system is divided into five strips, and for each strip the temperature is measured using an embedded thermometer. Unlike previous works, these thermometers are small enough not to alter the steady state of the nonequilibrium system. After showing initial transients, the thermometers eventually show steady-state conditions with the subregions of the system and provide values of the different temperature definitions-kinetic, configurational, dynamical, and higher-order configurational. It is found that their kinetic and the configurational temperatures are close to the system's kinetic temperature except in the two thermostatted regions. In the thermostatted regions, where the system's kinetic and the configurational temperatures are significantly different, the thermometers register a temperature substantially different from either of these two values. With a decrease in the system density and size, these differences between the kinetic and the configurational temperatures of the thermometer become more pronounced.


Antibodies against the T61 antigen inhibit neuronal migration in the chick optic tectum.
Cell migration in the central nervous system depends, in part, on receptors and extracellular matrix molecules that likewise support axonal outgrowth. We have investigated the influence of T61, a monoclonal antibody that has been shown to inhibit growth cone motility in vitro, on neuronal migration in the developing optic tectum. Intraventricular injections of antibody-producing hybridoma cells or ascites fluid were used to determine the action of this antibody in an in vivo environment. To document alterations in tectal layer formation, a combination of cell-nuclei staining and axonal immunolabeling methods was employed. In the presence of T61 antibody, cells normally destined for superficial layers accumulated in the ventricular zone instead, leading to a reduction of the cell-dense layer in the tectal plate. Experiments with 5-bromo-2'-deoxyuridine labeling followed by antibody staining confirmed that the nonmigrating cells remaining in the ventricular zone were postmitotic and had differentiated. The structure of radial glial cells, as judged by staining with a glia-specific antibody and the fluorescent tracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), remained intact in these embryos. Our findings suggest that the T61 epitope is involved in a mechanism underlying axonal extension and neuronal migration, possibly by influencing the motility of the leading process.


In search of blood tests for thoracic aortic diseases.
A number of new diagnostic screening tools have been developed for the assessment of acute and chronic diseases of the thoracic aorta. Although standardized blood-based tests capable of detecting individuals at risk for aortic aneurysm and dissection disease are not yet available, our current knowledge is expanding at a rapid rate and the future is very promising. In this review, an update of the contemporary knowledge on blood tests for detecting thoracic aortic diseases in both preclinical and clinical settings is provided, offering the potential to predict adverse aortic events, such as enlargement, rupture, and dissection.


Prevalence of Behçet's disease in rural western Turkey: a preliminary report.
To study the prevalence of Behçet's disease (BD) in a rural area of Western Turkey. This study was conducted in seven villages in the rural Havsa region which has a total population of 5727. The physicians and medical students visited every household and distributed a questionnaire on the symptoms of rheumatic disorders. One of the questions was whether they had ever suffered from mouth ulcers. If the response was affirmative the proband was examined by a rheumatologist and a dermatologist for other symptoms. The individuals with true aphthous ulcerations had pathergy tests and were invited to the hospital for ophtalmic examinations. Of the 5203 individuals who participated in this survey, 4861 were 10 years or older. 124 out of 190 individuals who responded positively to the question regarding the presence of mouth ulcers had true aphthous ulcerations. 115/124 underwent a pathergy test and 4 showed positive reactions without any other stigmata of BD, except for folliculitis in one. Among the individuals with a negative pathergy test, 2 had acneiform skin lesions and 1 a genital ulcer. No individual exhibited any ocular symptoms or findings characteristic for BD. Only 1 person with aphthous ulceration, folliculitis and a positive pathergy test was considered to have BD. In this survey, the prevalence of BD was found to be 2: 10,000 (95% confidence interval 0 to 4.3: 10,000). This figure is lower than what has been reported in four previous studies from different regions in Turkey. This finding might be due to ethnic distribution and geographical differences.


Exploring the Role of Social Networks in Facilitating Health Service Access Among Low-Income Women in the Philippines: A Qualitative Study.
Despite efforts to implement universal health care coverage (UHC) in the Philippines, income poor households continue to face barriers to health care access and use. In light of recent UHC legislation, the aim of this study was to explore how gender and social networks shape health care access and use among women experiencing poverty in Negros Occidental, Philippines. Semi-structured interviews were conducted with women (n = 35) and health care providers (n = 15). Descriptive statistical analyses were performed to report demographic information. Interview data were analyzed thematically using a hybrid deductive-inductive approach and guided by the Patient-Centred Access to Health Care framework. Women's decisions regarding health care access were influenced by their perceptions of illness severity, their trust in health care facilities, and their available financial resources. Experiences of health care use were shaped by interactions with health professionals, resource availability at facilities, health care costs, and health insurance acquisition. Women drew upon social networks throughout their lifespan for social and financial support to facilitate healthcare access and use. These findings indicate that social networks may be an important complement to formal supports (eg, UHC) in improving access to health care for women experiencing poverty in the Philippines.


Analysis of fuels via easy ambient sonic-spray ionization mass spectrometry.
The desorption and ionization of analytes directly from surfaces or natural matrices under ambient conditions has greatly simplified chemical analysis by mass spectrometry. Among the currently available set of such techniques, easy ambient sonic-spray ionization (EASI) is one of the simplest and most easily implemented. Fuels are among the most important and most complex classes of chemical mixtures and a challenge for fast and comprehensive chemical analysis. This review summarizes the applications of EASI-MS for fast, simple and nearly sample-preparation-free analysis of various fuels, focusing in typification, adulteration and quality control.


Effect of similarity between patterns in associative memory.
We study the stability of patterns in Hopfield networks in which a part of memorized patterns are similar. The similarity between patterns impacts the stability of these patterns, but the stability of other independent patterns is only changed slightly. We show that the stability of patterns is affected in different ways by similarity. For networks storing a number of patterns, the similarity between patterns enhances the pattern stability. However, the stability of patterns can be weakened by the similarity when networks store fewer patterns, and the relation between the stability of patterns and similarity is nonmonotonic. We present a theoretical explanation of the effect of similarity on stability using signal-to-noise-ratio analysis.


Interrogating a high-density SNP map for signatures of natural selection.
Identifying genomic regions that have been targets of natural selection remains one of the most important and challenging areas of research in genetics. To this end, we report an analysis of 26,530 single nucleotide polymorphisms (SNPs) with allele frequencies that were determined in three populations. Specifically, we calculated a measure of genetic differentiation, F(ST), for each locus and examined its distribution at the level of the genome, the chromosome, and individual genes. Through a variety of analyses, we have found statistically significant evidence supporting the hypothesis that selection has influenced extant patterns of human genetic variation. Importantly, by contrasting the F(ST) of individual SNPs to the empirical genome-wide distribution of F(ST), our results are not confounded by tenuous assumptions of population demographic history. Furthermore, we have identified 174 candidate genes with distribution of genetic variation that indicates that they have been targets of selection. Our work provides a first generation natural selection map of the human genome and provides compelling evidence that selection has shaped extant patterns of human genomic variation.


No place else to go: the changing role of state hospitals and forensic mental health services.
Current trends in forensic mental health services and how they are used are shaping the future of state hospitals and mental health systems.


Role of lymphangiography in staging testicular seminoma.
Bipedal lymphangiography (LAG) and abdominal/pelvic computerized tomography (CT) are both useful in evaluating retroperitoneal lymph nodes in early-stage testicular seminoma. Fifty-four patients who had both radiologic studies performed between 1982 and 1986 were identified, and their films were reviewed. Four patients had evidence of retroperitoneal lymph node metastases on both CT and LAG. Of the 50 patients who had normal findings on CT scan, 39 (78%) had a normal LAG and 11 (22%) had a positive LAG. All 11 patients had architectural abnormalities within normal-sized nodes. No patient had positive findings on CT with negative LAG. In addition to aiding in staging, LAG is very useful in designing radiation treatment portals. Therefore, we believe that LAG can continue to play an important role in the accurate staging and treatment of patients with testicular seminoma.


Genomic diversity, linkage disequilibrium and selection signatures in European local pig breeds assessed with a high density SNP chip.
Genetic characterization of local breeds is essential to preserve their genomic variability, to advance conservation policies and to contribute to their promotion and sustainability. Genomic diversity of twenty European local pig breeds and a small sample of Spanish wild pigs was assessed using high density SNP chips. A total of 992 DNA samples were analyzed with the GeneSeek Genomic Profiler (GGP) 70 K HD porcine genotyping chip. Genotype data was employed to compute genetic diversity, population differentiation and structure, genetic distances, linkage disequilibrium and effective population size. Our results point out several breeds, such as Turopolje, Apulo Calabrese, Casertana, Mora Romagnola and Lithuanian indigenous wattle, having the lowest genetic diversity, supported by low heterozygosity and very small effective population size, demonstrating the need of enhanced conservation strategies. Principal components analysis showed the clustering of the individuals of the same breed, with few breeds being clearly isolated from the rest. Several breeds were partially overlapped, suggesting genetic closeness, which was particularly marked in the case of Iberian and Alentejana breeds. Spanish wild boar was also narrowly related to other western populations, in agreement with recurrent admixture between wild and domestic animals. We also searched across the genome for loci under diversifying selection based on FST outlier tests. Candidate genes that may underlie differences in adaptation to specific environments and productive systems and phenotypic traits were detected in potentially selected genomic regions.


Cell culture-induced aberrant methylation of the imprinted IG DMR in human lymphoblastoid cell lines.
DNA methylation patterns are often poorly conserved through cell culturing. To determine the effect of cell immortalization and culture on DNA methylation profiles, we analyzed methylation in the differentially methylated regions (DMR) of five imprinted domains: the intergenic (IG) DMR on chromosome 14q32; potassium voltage-gated channel, KQT-like subfamily, member 1, (KCNQ1); small nuclear ribonucleoprotein polypeptide N (SNRPN), mesoderm specific transcript homolog (MEST); and H19 in lymphoblastoid cell lines (LCLs). In the IG DMR we found an aberrant methylation pattern that was consistent through all the cell lines tested and significantly different from that of noncultured peripheral blood cells. Using a generalized linear mixed model to compare methylation profiles, we show that recently derived LCLs significantly differ from the CEPH LCLs. This implies a gradual cell-culture related deterioration of DNA methylation in the IG DMR with at least two steps that may be identified: loss of methylation at CG sites 1 and 8; and loss of allelic differences in DNA methylation. The IG DMR methylation profile also confirms the high level of clonality of the CEPH LCLs. We conclude that non-transformed primary cells may be less susceptible to epigenetic anomalies and therefore may provide a more accurate reflection of gene expression in vivo.


Statistics: using regression models.
In a previous article, we asked the simple question "Are we related?" and used scatterplots and correlation coefficients to provide an answer. In this article, we will take this question and reword it to "How are we related?" and will demonstrate the statistical techniques required to reach a conclusion.


Evaluation of selected benzoquinones, naphthoquinones, and anthraquinones as replacements for phylloquinone in the A1 acceptor site of the photosystem I reaction center.
Selected substituted 1,4-benzoquinones, 1,4-naphthoquinones, and 9,10-anthraquinones were investigated as possible replacement quinones in spinach photosystem I (PSI) preparations that had been depleted of endogenous phylloquinone by extraction with hexane/methanol. As a criterion for successful biochemical reconstitution, the restoration of electron transfer was determined by measuring P-430 turnover at room temperature from flash-induced absorbance transients. Restoration of complete electron transfer between A0- and P-430 (terminal iron-sulfur centers, FAFB) was demonstrated by using phylloquinone, 2-methyl-3-decyl-1,4-naphthoquinone, 2-methyl-3-(isoprenyl)2-1,4-naphthoquinone, and 2-methyl-3-(isoprenyl)4-1,4-naphthoquinone. All other quinones tested did not restore P-430 turnover but acted as electron acceptors and oxidized A0-. It is concluded that the specificity of the replacement quinone for interaction with the primary acceptor, A0-, is low but additional structural constraints are required for the quinone occupying the A1 site to donate to the iron-sulfur center, Fx. It is suggested that the 3-phytyl side chain of phylloquinone and the 3-alkyl tails of the three naphthoquinones that restored P-430 turnover may be required for interaction with a hydrophobic domain of the A1 site in the PSI core to promote electron transfer to Fx and then to FAFB.


Ultraviolet Photodissociation of ESI- and MALDI-Generated Protein Ions on a Q-Exactive Mass Spectrometer.
The identification of molecular ions produced by MALDI or ESI strongly relies on their fragmentation to structurally informative fragments. The widely diffused fragmentation techniques for ESI multiply charged ions are either incompatible (ECD and ETD) or show lower efficiency (CID, HCD), with the predominantly singly charged peptide and protein ions formed by MALDI. In-source decay has been successfully adopted to sequence MALDI-generated ions, but it further increases spectral complexity, and it is not compatible with mass-spectrometry imaging. Excellent UVPD performances, in terms of number of fragment ions and sequence coverage, has been demonstrated for electrospray ionization for multiple proteomics applications. UVPD showed a much lower charge-state dependence, and so protein ions produced by MALDI may exhibit equal propensity to fragment. Here we report UVPD implementation on an Orbitrap Q-Exactive Plus mass spectrometer equipped with an ESI/EP-MALDI. UVPD of MALDI-generated ions was benchmarked against MALDI-ISD, MALDI-HCD, and ESI-UVPD. MALDI-UVPD outperformed MALDI-HCD and ISD, efficiently sequencing small proteins ions. Moreover, the singly charged nature of MALDI-UVPD avoids the bioinformatics challenges associated with highly congested ESI-UVPD mass spectra. Our results demonstrate the ability of UVPD to further improve tandem mass spectrometry capabilities for MALDI-generated protein ions. Data are available via ProteomeXchange with identifier PXD011526.


Pathophysiology of obesity.
Individuals weighing greater than 100 kg represent a small fraction of the population and yet pose a major health risk to themselves. It is proposed that individuals be classified according to their body mass index (BMI). Class 0 individuals have a BMI of 20-25 kg/m2 and are not obese; Class I individuals have a BMI of 25-30 kg/m2 and are at low risk from their obesity; Class II individuals have a BMI of 30-35 kg/m2 and have moderate risk; Class III individuals have a BMI of 35-40 kg/m2 and have high risk associated with their obesity; Class IV individuals have a BMI of greater than 40 kg/m2 and are at very high risk for illness. Class IV is the primary group for surgical consideration. The pathophysiologic consequences of excess weight result in large part from increased food intake and/or decreased physical activity. Individuals in Class IV have additional problems related to their weight, including cardiomyopathy, Pickwickian/sleep apnea syndrome, pituitary/gonadal dysfunction, acanthosis nigricans, and significant osteoarthritis.