The role of topogenic sequences in the movement of proteins through membranes.
Recent advances have led to considerable convergence in ideas of the way topogenic sequences act to translocate proteins across various intracellular membranes (Table 2). Whereas co-translational translocation and processing were previously considered the norm at the endoplasmic reticulum membrane, several instances of post-translational translocation into endoplasmic reticulum microsomes in vitro have now been described. However, it must be noted that post-translational translocation in vitro is much less efficient than when endoplasmic reticulum membranes are present during translation, and it is possible that in the intact cell translocation occurs during translation. Movement of proteins into chloroplasts and mitochondria occurs after translation. When translocation is post-translational, proteins may perhaps traverse the membrane as folded domains, and the conformational effects of topogenic sequences on these domains may be as envisaged in Wickner's 'membrane-trigger hypothesis'. Both signal and transit sequences possess amphipathic structures which are capable of interacting with phospholipid bilayers, and these interactions may disturb the bilayer sufficiently to allow entry of the following domains of protein. There is increasing evidence that GTP is required to bind ribosomes and their associated nascent chains to the endoplasmic reticulum membrane. Precisely how the cell's energy is applied to achieve translocation is not clear, but one possibility at the endoplasmic reticulum is that a GTP-hydrolysing transducing mechanism may exist to couple signal sequence receptor binding to movement of the nascent chain across the membrane. Electrochemical gradients are required for protein movement to the mitochondrial inner membrane and across the bacterial inner membrane. Cytoplasmic factors such as SRP, the secA gene product or a 40 kDa protein (for mitochondrial precursors) may act by binding to topogenic sequences and preventing precursor proteins as they are translated from folding into forms which cannot be translocated. Specificity in the cell may be achieved both by targetting interactions between these cytoplasmic factors and their receptors located in target membranes, and also by specific binding of the topogenic sequences to specific proteins integrated into the target membranes. Possible candidates for the latter are the protein of microsomal membranes that reacts with a photoreactive signal peptide to give a 45 kDa complex (Fig. 1), the secY gene product of the bacterial inner membrane, and receptors on the outer membranes of chloroplasts and mitochondria. Whether these aid translocation as well as recognition is not clear.(ABSTRACT TRUNCATED AT 400 WORDS)


The Influence of Cochlear Implantation on Tinnitus in Patients with Single-Sided Deafness: A Systematic Review.
This systematic review provides an overview of the available studies (published by January 29, 2018) with descriptive data analysis about the influence of cochlear implantation on tinnitus in patients with single-sided deafness (SSD). PubMed, EMBASE, Web of Science, Cochrane Library, and Google Scholar. Original studies about the influence of cochlear implantation on tinnitus, measured with different tinnitus questionnaires or visual analog scale, in patients with SSD were included. The pre- and postimplantation tinnitus scores of the included studies were extracted for the further systematic review. The systematic search yielded 1028 studies. After evaluating titles, abstracts, and full texts, 1011 of these were dismissed. From the remaining 17 studies, 4 showed a low directness of evidence or high risk of bias and were therefore excluded. Due to the nature of cochlear implantation in SSD, only cohort studies and no randomized trials exist, which limits the evaluation in a systematic review. Generally, the mean tinnitus questionnaire scores decreased after cochlear implantation in these 13 studies with a total of 153 patients. The most widely used tinnitus questionnaire was the Tinnitus Handicap Inventory. In these studies, 34.2% of patients demonstrated complete suppression, 53.7% an improvement, 7.3% a stable value, and 4.9% an increase of tinnitus, and none of the patients reported an induction of tinnitus. This review shows a clear improvement of tinnitus complaints after cochlear implantation in patients with SSD. Therefore, tinnitus might be considered as an additional indication for cochlear implantation in SSD.


Free energy rhythms in Saccharomyces cerevisiae: a dynamic perspective with implications for ribosomal biogenesis.
To describe the time course of cellular systems, we integrate ideas from thermodynamics and information theory to discuss the work needed to change the state of the cell. The biological example analyzed is experimental microarray transcription level oscillations of yeast in the different phases as characterized by oxygen consumption. Surprisal analysis was applied to identify groups of transcripts that oscillate in concert and thereby to compute changes in free energy with time. Three dominant transcript groups were identified by surprisal analysis. The groups correspond to the respiratory, early, and late reductive phases. Genes involved in ribosome biogenesis peaked at the respiratory phase. The work to prepare the state is shown to be the sum of the contributions of these groups. We paid particular attention to work requirements during ribosomal building, and the correlation with ATP levels and dissolved oxygen. The suggestion that cells in the respiratory phase likely build ribosomes, an energy intensive process, in preparation for protein production during the S phase of the cell cycle is validated by an experiment. Surprisal analysis thereby provided a useful tool for determining the synchronization of transcription events and energetics in a cell in real time.


Microtubules provide guidance cues for myofibril and sarcomere assembly and growth.
Muscle myofibrils and sarcomeres present exceptional examples of highly ordered cytoskeletal filament arrays, whose distinct spatial organization is an essential aspect of muscle cell functionality. We utilized ultra-structural analysis to investigate the assembly of myofibrils and sarcomeres within developing myotubes of the indirect flight musculature of Drosophila. A temporal sequence composed of three major processes was identified: subdivision of the unorganized cytoplasm of nascent, multi-nucleated myotubes into distinct organelle-rich and filament-rich domains; initial organization of the filament-rich domains into myofibrils harboring nascent sarcomeric units; and finally, maturation of the highly-ordered pattern of sarcomeric thick (myosin-based) and thin (microfilament-based) filament arrays in parallel to myofibril radial growth. Significantly, organized microtubule arrays were present throughout these stages and exhibited dynamic changes in their spatial patterns consistent with instructive roles. Genetic manipulations confirm these notions, and imply specific and critical guidance activities of the microtubule-based cytoskeleton, as well as structural interdependence between the myosin- and actin-based filament arrays. Our observations highlight a surprisingly significant, behind-the-scenes role for microtubules in establishment of myofibril and sarcomere spatial patterns and size, and provide a detailed account of the interplay between major cytoskeletal elements in generating these essential contractile myogenic units.


Vacuum-assisted closure for treatment of a deep shell abscess and osteomyelitis in a tortoise.
A female Aldabra tortoise (Geochelone gigantea) was evaluated because of focal necrosis of the carapace. Debridement revealed a 14.5 x 11.5-cm area of shell necrosis, deep abscess formation, and osteomyelitis involving bacterial (Klebsiella pneumoniae, Staphylococcus aureus, and Pseudomonas spp) and fungal pathogens. Following extensive debridement, vacuum-assisted closure incorporating silver-impregnated bandaging materials was used. The wound was considered healed after 55 days, at which time a layer of epidermal tissue with progressing keratinization was present, with smooth underlying ossification. Keratinization with normal pigmentation continued over the next 67 days. Findings suggested that vacuum-assisted closure with silver-impregnated bandaging materials may provide advantages over traditional methods in the treatment of shell lesions in chelonians, including faster wound healing, improved cosmetic appearance of the healed wound, superior control of microbial contamination, and lower overall treatment costs.


Ameliorative effect of probiotics (Lactobacillus paracaseii and Protexin®) and prebiotics (propolis and bee pollen) on clindamycin and propionic acid-induced oxidative stress and altered gut microbiota in a rodent model of autism.
Colonization by toxin-producing bacteria in the gut plays a major role in bowel problems in autistic patients. Prebiotics can inhibit the growth of these pathogenic microbes by nourishing beneficial bacteria, while probiotics--live microorganisms--can balance the gut bacteria; thus, both together can maintain healthy bacteria in the gut. The present study was conducted to find the effect of probiotics and prebiotics in balancing the gut flora in a rodent model of autism linked with a clindamycin-induced altered gut. The effects of probiotics and prebiotics on oxidative stress markers in the brain were also evaluated. Eight groups of hamsters were assigned, with Group I serving as the control; Group II, as the autistic model, was treated with 250 mg propionic acid/kg BW/day for 3 days; Group III was treated with clindamycin 30 mg/kg BW for 3 days; Groups IV and V were treated with bee pollen and propolis (supposed prebiotics) at a dose of 250 mg/kg BW/day for 28 days; Group VI and Group VII were treated with Lactobacillus paracaseii and Protexin® (supposed probiotics) for 28 days; and finally, Group VIII was anorectally transplanted with stool from normal animals for 5 days. Remarkable changes were measured in oxidative stress markers, primarily glutathione and vitamin C, in the brains of hamsters in the propionic acid- and clindamycin-treated group. All probiotic/prebiotic treatments showed ameliorative effects; however, lactobacillus had the strongest effect. We conclude that pro-and prebiotic supplements may be effective to revive healthy digestive system function in autistic patients. The disappointing results of the fecal transplants suggest that further study is needed to develop an appropriate technique.


[Impact of several illnesses on health related quality of life on workers].
FOUNDATION AND OBJECTIVE: To make a comparative study of the degree of impact of different diseases in the health related quality of life (HRQoL) of workers. A questionnaire including the measure of HRQoL SF-36, was sent by mail and fulfilled by employees of the Pfizer company in Spain. Differences in the impact in HRQoL between subjects with and without several characteristics, with less or more degree of work productivity and with and without antecedents of several diseases and current treatment, were assessed by means of statistical tests of U Mann-Whitney and Kruskal-Wallis. In a sample of 399 valuable subjects, 35.8+/-6.5 years (mean+/-standard deviation), with a 63.7% of men, worst HRQoL scores in the Physical Summary Component of SF-36 were observed among subjects with history of some disease (52.6+/-5.9 days versus 55.9+/-2.6), migraine (46.2+/-5.9 versus 54.7+/-4.1), musculoskeletal (49.7+/-7.2 versus 53.9+/-5.1) and digestive diseases (51.5+/-6.6 versus 54.1+/-4.9), and/or taking some current treatment (50.2+/-6.4 versus 55.0+/-4.4); p <0.05 for all comparisons. In the Physical Summary Component of SF-36 worst HRQoL scores were observed among subjects with history of some disease (51.4+/-7.1 versus 53.4+/-5.9), digestive (49.9+/-8.3 versus 52.5+/-6.3) and mental disorders (46.0+/-8.8 versus 52.4+/-6.4); p <0.05 for all comparisons. The impact of the disease in the HRQoL was associated to the type of pathological antecedents, being migraine that hit more negatively in the Physical Health, and mental disorders in the Mental Health.


Do other components of bedding dust affect sensitisation to house dust mites?
Bedding dust is a mixture of many components, of which the house dust mite (HDM) allergen, Der p 1, is the most allergenic. There has been little work to investigate the effect of other bedding dust components on HDM sensitisation. The objective of the study was to determine the effect of endotoxin in bedding dust on the allergic response in HDM-sensitised individuals. Twenty-nine house dust mite-sensitised adults were skin prick and allergen patch tested against a sterile solution of their own bedding dust and against a solution containing the same concentration of Der p 1 as the bedding solution for comparison. There was no significant difference in wheal size between the diluted house dust mite solution and the bedding dust in spite of their high levels of endotoxin. Symptomatic subjects had larger, but not statistically significant, responses to commercial house dust mite solution than asymptomatic subjects. Allergen patch test responses were negative in 22/29 of subjects using either bedding dust solutions or comparable diluted house dust mite solutions. An individual's own bedding dust does not appear to contain factors that enhance skin prick test or atopy patch test responses to house dust mites.


Targeted apoptosis of myofibroblasts with the BH3 mimetic ABT-263 reverses established fibrosis.
Persistent myofibroblast activation distinguishes pathological fibrosis from physiological wound healing, suggesting that therapies selectively inducing myofibroblast apoptosis could prevent progression and potentially reverse established fibrosis in diseases such as scleroderma, a heterogeneous autoimmune disease characterized by multiorgan fibrosis. We demonstrate that fibroblast-to-myofibroblast differentiation driven by matrix stiffness increases the mitochondrial priming (proximity to the apoptotic threshold) of these activated cells. Mitochondria in activated myofibroblasts, but not quiescent fibroblasts, are primed by death signals such as the proapoptotic BH3-only protein BIM, which creates a requirement for tonic expression of the antiapoptotic protein BCL-XL to sequester BIM and ensure myofibroblast survival. Myofibroblasts become particularly susceptible to apoptosis induced by "BH3 mimetic" drugs inhibiting BCL-XL such as ABT-263. ABT-263 displaces BCL-XL binding to BIM, allowing BIM to activate apoptosis on stiffness-primed myofibroblasts. Therapeutic blockade of BCL-XL with ABT-263 (navitoclax) effectively treats established fibrosis in a mouse model of scleroderma dermal fibrosis by inducing myofibroblast apoptosis. Using a BH3 profiling assay to assess mitochondrial priming in dermal fibroblasts derived from patients with scleroderma, we demonstrate that the extent of apoptosis induced by BH3 mimetic drugs correlates with the extent of their mitochondrial priming, indicating that BH3 profiling could predict apoptotic responses of fibroblasts to BH3 mimetic drugs in patients with scleroderma. Together, our findings elucidate the potential efficacy of targeting myofibroblast antiapoptotic proteins with BH3 mimetic drugs in scleroderma and other fibrotic diseases.


Sexual Dysfunctions in Women with Posttraumatic Stress Disorder Following Childhood Sexual Abuse: Prevalence Rates According to DSM-5 and Clinical Correlates.
Many women with posttraumatic stress disorder (PTSD) after child sexual abuse (CSA) suffer from sexual problems. However, little is known about the frequency of female sexual dysfunctions (FSD) as defined by DSM-5 among women with PTSD due to CSA. Furthermore, factors related to FSD in this patient population are understudied. To assess prevalence rates and clinical correlates of FSD according to DSM-5 criteria in women with PTSD after CSA, a structured clinical interview for sexual dysfunctions according to DSM-5 criteria was administered in a sample of 137 women with PTSD after CSA. Participants also completed measures for PTSD, depression symptoms, and borderline personality disorder symptoms. The association between FSD, severity of abuse, PTSD-, depression-, borderline symptom severity, and age was examined. In a second step, the association between FSD and PTSD-clusters was assessed. Diagnostic criteria of female sexual interest/arousal disorder (FSIAD) were met by 2.6% of women in our sample. 5.2% met criteria of female orgasmic disorder (FOD), and 11.8% those of genito-pelvic pain/penetration disorder (GPPPD). PTSD symptom severity predicted number of fulfilled criteria of FSIAD and FOD, the cluster "negative alterations in cognition and mood," was associated with more fulfilled criteria in FSIAD and FOD. The majority of women reported sexual problems, but diagnostic criteria of FSD were met by only a small number of participants. PTSD symptoms, especially the cluster "negative alterations in cognition and mood," seem to be related to female sexual functioning after CSA.


NH3-Sensing Mechanism Using Surface Acoustic Wave Sensor with AlO(OH) Film.
In this study, AlO(OH) (boehmite) film was deposited onto a surface acoustic wave (SAW) resonator using a combined sol-gel and spin-coating technology, and prepared and used as a sensitive layer for a high-performance ammonia sensor. The prepared AlO(OH) film has a mesoporous structure and a good affinity to NH3 (ammonia gas) molecules, and thus can selectively adsorb and react with NH3. When exposed to ammonia gases, the SAW sensor shows an initial positive response of the frequency shift, and then a slight decrease of the frequency responses. The sensing mechanism of the NH3 sensor is based on the competition between mass-loading and elastic-loading effects. The sensor operated at room temperature shows a positive response of 1540 Hz to 10 ppm NH3, with excellent sensitivity, selectivity and stability.


Ophthalmic manifestations of visceral larva migrans.
Two patients had ocular manifestations of infestation with visceral larva migrans. In neither case did the eye involvement improve despite thiabendazole, local and systemic steroids, and cryotherapy. The lack of ocular response to treatment may be assumed to be because of organisms were already dead. Thiabendazole therapy is probably worth trying for early ophthalmic involvement with visceral larva migrans if the organism is still alive. In most cases the diagnosis of visceral larva migrans can be made with the help of the ELISA serum antigen determination so that enucleation of the eye will not be necessary for diagnostic purposes.


Contributions of sensation and perception studies to the design of artificial environments.
It is argued that knowledge of cognitive psychology, and hence also of sensation and perception, one of its branches, is indispensable when one aims at improving our artificial environment. Four examples of sensation and perception studies are described. Firstly, an experiment was discussed to design a postal code format that can be used accurately in terms of the capacity of short-term visual memory. The second example describes a perceptual conflict between visual and bodily (kinesthetic/proprioceptive) sensations that arises as a result of wrongly designing buildings. In the third example it is shown that vibrotactual displays should present frequencies that trigger the Pacinian system in the skin if people have to make quick and accurate decisions. Finally, a study of a simple acoustic orientation system that can promote indoor travel and activity by blind people was described.


Locus heterogeneity, anticipation and reduction of the chromosome 2p minimal candidate region in autosomal dominant familial spastic paraplegia.
We examined 11 Caucasian pedigrees with autosomal dominant 'uncomplicated' familial spastic paraplegia (SPG) for linkage to the previously identified loci on chromosomes 2p, 14q and 15q. Chromosome 15q was excluded for all families. Five families showed evidence for linkage to chromosome 2p, one to chromosome 14q, and five families remained indeterminate. Homogeneity analysis of combined chromosome 2p and 14q data gave no evidence for a fourth as yet unidentified SPG locus. Recombination events reduced the chromosome 2p minimum candidate region (MCR) to a 3 cM interval between D2S352 and D2S367 and supported the previously reported 7 cM MCR for chromosome 14q. Age of onset (AO) was highly variable, indicating that subtypes of SPG are more appropriately defined on a genetic basis than by AO. Comparison of AO in parent-child pairs was suggestive of anticipation, with a median difference of 9.0 years (p<0.0001).


Effects of a Head-Cooling Cap on 5-Km Running Performance in the Heat.
Cooling the head region during exercise can enhance running performance, but this observation is limited to intermittent cooling. This study investigated the effects of continuous head cooling on 5-km running time-trial (TT) performance in hot conditions. Six male and four female triathletes completed two experimental sessions consisting of two 10-minute runs at 50% and 70% V̇O2max followed by a 5-km TT in the heat (32.0±0.3 °C, 50.1±1.2% RH). In a randomized crossover design, either an ice-filled cooling cap or no cooling cap was provided prior to the 10-minute run at 70%V̇O2max. Performance time, rectal, forehead and mean skin temperature, RPE, thermal comfort, fluid loss, blood lactate and heart rate were recorded. Performance time was faster with a cooling cap (1175±80 s) compared to no cooling cap (1189±76 s, P = 0.034; d = 0.18). The cooling cap reduced forehead temperature (P <0.001) and improved thermal comfort (P = 0.004) but had no effect on any other variable (P > 0.05). Continuously cooling the head with an ice-filled cap enhanced 5-km TT performance in the heat. Participants reported an improved thermal comfort with no change in core temperature. Continuously cooling the head may be a practical strategy to enhance running performance in hot conditions.


Stimulation of normal rat bone marrow fibroblast proliferation by sera from leukemic Fischer rats.
Fibroblast hyperplasia and accumulation of fibrous material in the bone marrow of patients with idiopathic (primary) or secondary myelofibrosis (MF) is believed to result from a reaction by marrow fibroblasts to an altered marrow microenvironment, the alteration being potentiated by abnormal hemic cells. We investigated the hypothesis that humoral factors might contribute to fibroblast overgrowth in MF by using an animal model, aged Fischer rats, where MF frequently occurs with leukemia. Sera from leukemic rats and leukemic cell conditioned media (CM) were assayed for enhancement of normal rat marrow fibroblast proliferation in a culture system where fibroblasts form discrete, adherent colonies. Our results demonstrated that: leukemic sera induced a 170% increase in total fibroblast colony numbers and a 325% increase in colonies containing more than 80 cells, stimulation of fibroblast growth was leukemia related since sera from rats with transplanted leukemia enhanced marrow fibroblast proliferation, leukemic cell CM did not contain a growth factor for marrow fibroblasts, sera from leukemic rats and 2-mercaptoethanol were additive in enhancing marrow fibroblast proliferation and probably act by different mechanisms, and leukemic rat sera was less effective as a colony-stimulating factor than normal rat sera, a condition mimicked when leukemic and normal spleen CM were compared. This is the first time that a serum component has been implicated in the pathogenesis of MF; our work may contribute to understanding the mechanism involved when MF occurs as a complication of leukemia.


Genetic variation modifies risk for neurodegeneration based on biomarker status.
While a great deal of work has gone into understanding the relationship between Cerebrospinal fluid (CSF) biomarkers, brain atrophy, and disease progression, less work has attempted to investigate how genetic variation modifies these relationships. The goal of this study was two-fold. First, we sought to identify high-risk vs. low-risk individuals based on their CSF tau and Aβ load and characterize these individuals with regard to brain atrophy in an AD-relevant region of interest. Next, we sought to identify genetic variants that modified the relationship between biomarker classification and neurodegeneration. Participants were categorized based on established cut-points for biomarker positivity. Mixed model regression was used to quantify longitudinal change in the left inferior lateral ventricle. Interaction analyses between single nucleotide polymorphisms (SNPs) and biomarker group status were performed using a genome wide association study (GWAS) approach. Correction for multiple comparisons was performed using the Bonferroni procedure. One intergenic SNP (rs4866650) and one SNP within the SPTLC1 gene (rs7849530) modified the association between amyloid positivity and neurodegeneration. A transcript variant of WDR11-AS1 gene (rs12261764) modified the association between tau positivity and neurodegeneration. These effects were consistent across the two sub-datasets and explained approximately 3% of variance in ventricular dilation. One additional SNP (rs6887649) modified the association between amyloid positivity and baseline ventricular volume, but was not observed consistently across the sub-datasets. Genetic variation modifies the association between AD biomarkers and neurodegeneration. Genes that regulate the molecular response in the brain to oxidative stress may be particularly relevant to neural vulnerability to the damaging effects of amyloid-β.


Treating Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck Unsuitable to Receive Cisplatin-Based Therapy.
Concurrent chemoradiotherapy with high-dose cisplatin (100 mg/m2 every 3 weeks) is the preferred regimen with curative intent for patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). This treatment is associated with acute and late toxicities, including myelosuppression, severe nausea/vomiting, irreversible renal failure, hearing loss, and neurotoxicity. Because of cisplatin's safety profile, treatment adherence to high-dose cisplatin can be suboptimal. Patients commonly receive less than the total cumulative target dose of 300 mg/m2 or the minimum recommended dose of 200 mg/m2, which can have a negative impact on locoregional control and survival. Alternatively, cetuximab plus radiotherapy may be most suitable for patients at high risk of non-adherence to high-dose cisplatin. We discuss the baseline characteristics dictating the unsuitability/borderline unsuitability of cisplatin and the available alternative evidence-based treatment regimens for patients with LA SCCHN. We non-systematically reviewed published phase II and III trials and retrospective analyses of high-dose cisplatin-based chemoradiation in LA SCCHN conducted between 1987 and 2018, focusing on recent key phase III studies. We defined the baseline characteristics and associated prescreening tests to determine unsuitability and borderline unsuitability for high-dose cisplatin in combination with radiotherapy in patients with LA SCCHN. Patients with any pre-existing comorbidities that may be exacerbated by high-dose cisplatin treatment can be redirected to a non-cisplatin-based option to minimize the risk of treatment non-adherence. High-dose cisplatin plus radiotherapy remains the preferred treatment for fit patients with unresected LA SCCHN; patients who are unsuitable or borderline unsuitable for high-dose cisplatin could be identified using available tests for potential comorbidities and should be offered alternative treatments, such as cetuximab plus radiotherapy.


The role of emotion regulation and core autism symptoms in the experience of anxiety in autism.
Many children with autism spectrum disorder have problems with managing their emotions (emotion regulation) and anxiety. In this study, over 1000 parents completed an online survey which showed that emotion regulation and anxiety are closely linked. Although emotion regulation and anxiety are inter-connected, the results also show that autism symptoms play an important role in anxiety in autism spectrum disorder. Emotion regulation problems may be an important target for the treatment of anxiety in autism.


Analysis of Longitudinal Data with Semiparametric Estimation of Covariance Function.
Improving efficiency for regression coefficients and predicting trajectories of individuals are two important aspects in analysis of longitudinal data. Both involve estimation of the covariance function. Yet, challenges arise in estimating the covariance function of longitudinal data collected at irregular time points. A class of semiparametric models for the covariance function is proposed by imposing a parametric correlation structure while allowing a nonparametric variance function. A kernel estimator is developed for the estimation of the nonparametric variance function. Two methods, a quasi-likelihood approach and a minimum generalized variance method, are proposed for estimating parameters in the correlation structure. We introduce a semiparametric varying coefficient partially linear model for longitudinal data and propose an estimation procedure for model coefficients by using a profile weighted least squares approach. Sampling properties of the proposed estimation procedures are studied and asymptotic normality of the resulting estimators is established. Finite sample performance of the proposed procedures is assessed by Monte Carlo simulation studies. The proposed methodology is illustrated by an analysis of a real data example.


Associations between Global DNA Methylation and Telomere Length in Healthy Adolescents.
Emerging evidence suggests that epigenetics regulates telomere dynamics in adults. However, the relationship between these pathways in children and youth remains unknown. Thus, we examined this association in 542 healthy adolescents aged 14 to 18 years old (44.8% African Americans; 55.2% females). Global DNA methylation level (%5-mC) was quantified using ELISA method. Leukocyte telomere length (LTL) was defined as relative telomere to single copy gene (T/S) ratio. Multiple linear regression models, adjusted for age, gender, ethnicity, Tanner stage, BMI, PA, and batch effect, revealed that %5 mC was associated with LTL (adjusted β = 0.17, p < 0.01). %5 mC accounted for 5.0% of the variation for LTL. A significant gender interaction was identified (p < 0.01). There was an association between %5 mC and LTL in females (all ps < 0.01), but not in males. Further sensitivity analyses by race revealed similar associations in African Americans and whites (all ps < 0.03). The present study, for the first time, shows that lower levels of global DNA methylation are associated with shorter telomere lengths in youth, which may decrease genome stability and augment the susceptibility to diseases. Longitudinal studies are warranted to establish the effects of global DNA methylation on LTL maintenance over time.


Psilocybin: crystal structure solutions enable phase analysis of prior art and recently patented examples.
Psilocybin {systematic name: 3-[2-(dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate} is a zwitterionic tryptamine natural product found in numerous species of fungi known for their psychoactive properties. Following its structural elucidation and chemical synthesis in 1959, purified synthetic psilocybin has been evaluated in clinical trials and has shown promise in the treatment of various mental health disorders. In a recent process-scale crystallization investigation, three crystalline forms of psilocybin were repeatedly observed: Hydrate A, Polymorph A, and Polymorph B. The crystal structure for Hydrate A was solved previously by single-crystal X-ray diffraction. This article presents new crystal structure solutions for the two anhydrates, Polymorphs A and B, based on Rietveld refinement using laboratory and synchrotron X-ray diffraction data, and density functional theory (DFT) calculations. Utilizing the three solved structures, an investigation was conducted via Rietveld method (RM) based quantitative phase analysis (QPA) to estimate the contribution of the three different forms in powder X-ray diffraction (PXRD) patterns provided by different sources of bulk psilocybin produced between 1963 and 2021. Over the last 57 years, each of these samples quantitatively reflect one or more of the hydrate and anhydrate polymorphs. In addition to quantitatively evaluating the composition of each sample, this article evaluates correlations between the crystal forms present, corresponding process methods, sample age, and storage conditions. Furthermore, revision is recommended on characterizations in recently granted patents that include descriptions of crystalline psilocybin inappropriately reported as a single-phase `isostructural variant.' Rietveld refinement demonstrated that the claimed material was composed of approximately 81% Polymorph A and 19% Polymorph B, both of which have been identified in historical samples. In this article, we show conclusively that all published data can be explained in terms of three well-defined forms of psilocybin and that no additional forms are needed to explain the diffraction patterns.


Ligand binding and phagocytosis by CD16 (Fc gamma receptor III) isoforms. Phagocytic signaling by associated zeta and gamma subunits in Chinese hamster ovary cells.
CD16, the low affinity Fc gamma receptor III for IgG (Fc gamma RIII), exists as a polypeptide-anchored form (Fc gamma RIIIA or CD16A) in human natural killer cells and macrophages and as a glycosylphosphatidylinositol-anchored form (Fc gamma RIIIB or CD16B) in neutrophils. CD16A requires association of the gamma subunit of Fc epsilon RI or the zeta subunit of the TCR-CD3 complex for cell surface expression. The CD16B is polymorphic and the two alleles are termed NA1 and NA2. In this study, CD16A and the two alleles of CD16B have been expressed in Chinese hamster ovary (CHO) cells and their ligand binding and phagocytic properties analyzed. The two allelic forms of CD16B showed a similar affinity toward human IgG1. However, the NA1 allele showed approximately 2-fold higher affinity for the IgG3 than the NA2 allele. Although all three forms of CD16 efficiently bound rabbit IgG-coated erythrocytes (EA), only CD16A coexpressed with the gamma subunit phagocytosed EA. The phagocytosis mediated by CD16A expressed on CHO cells was independent of divalent cations but dependent on intact microfilaments. CHO cells expressing CD16A-gamma and CD16A-zeta chimeras also phagocytosed EA. The phagocytosis was specifically inhibited by tyrphostin-23, a tyrosine kinase inhibitor. In summary, our results demonstrate that glycosylphosphatidylinositol-anchored CD16B alleles differ from CD16A in their ability to mediate phagocytosis. Furthermore, since studies with other Fc gamma Rs have shown that CHO cells lack the phagocytic pathway mediated by the cytoplasmic domain of Fc gamma Rs, the phagocytosis of EA by CHO cells stably transfected with CD16A and CD16A-subunit chimera provides an ideal system to dissect the phagocytic signaling pathways mediated by these Fc gamma R-associated subunits.


Influence of smoking and plasma factors on patency of femoropopliteal vein grafts.
To determine the effects of smoking, plasma lipids, lipoproteins, apolipoproteins, and fibrinogen on the patency of saphenous vein femoropopliteal bypass grafts at one year. Prospective study of patients with saphenous vein femoropopliteal bypass grafts entered into a multicentre trial. Surgical wards, outpatient clinics, and home visits coordinated by two tertiary referral centres in London and Birmingham. 157 Patients (mean age 66.6 (SD 8.2) years), 113 with patent grafts and 44 with occluded grafts one year after bypass. Cumulative percentage patency at one year. Markers for smoking (blood carboxyhaemoglobin concentration (p less than 0.05) and plasma thiocyanate concentration (p less than 0.01) and plasma concentrations of fibrinogen (p less than 0.001) and apolipoproteins AI (p less than 0.04) and (a) (p less than 0.05) were significantly higher in patients with occluded grafts. Serum cholesterol concentrations were significantly higher in patients with grafts that remained patent one year after bypass (p less than 0.005). Analysis of the smoking markers indicated that a quarter of patients (40) were untruthful in their claims to have stopped smoking. Based on smoking markers, patency of grafts in smokers was significantly lower at one year by life table analysis than in non-smokers (63% v 84%, p less than 0.02). Patency was significantly higher by life table analysis in patients with a plasma fibrinogen concentration below the median than in those with a concentration above (90% v 57%, p less than 0.0002). Surprisingly, increased plasma low density lipoprotein cholesterol concentration was significantly associated with improved patency at one year (85%) at values above the median compared with patency (only 68%) at values in the lower half of the range (p less than 0.02). Plasma fibrinogen concentration was the most important variable predicting graft occlusion, followed by smoking markers. A more forceful approach is needed to stop patients smoking; therapeutic measures to improve patency of vein grafts should focus on decreasing plasma fibrinogen concentration rather than serum cholesterol concentration.


Vitex agnus castus: a systematic review of adverse events.
Vitex agnus castus L. (VAC) [Verbenaceae] is a deciduous shrub that is native to Mediterranean Europe and Central Asia. Traditionally, VAC fruit extract has been used in the treatment of many female conditions, including menstrual disorders (amenorrhoea, dysmenorrhoea), premenstrual syndrome (PMS), corpus luteum insufficiency, hyperprolactinaemia, infertility, acne, menopause and disrupted lactation. The German Commission E has approved the use of VAC for irregularities of the menstrual cycle, premenstrual disturbances and mastodynia. Clinical reviews are available for the efficacy of VAC in PMS, cycle disorders, hyperprolactinaemia and mastalgia, but so far no systematic review has been published on adverse events or drug interactions associated with VAC. Therefore, this review was conducted to evaluate all the available human safety data of VAC monopreparations. Literature searches were conducted in six electronic databases, in references lists of all identified papers and in departmental files. Data from spontaneous reporting schemes of the WHO and national drug safety bodies were also included. Twelve manufacturers of VAC-containing preparations and five herbalist organisations were contacted for additional information. No language restrictions were imposed. Combination preparations including VAC or homeopathic preparations of VAC were excluded. Data extraction of key data from all articles reporting adverse events or interactions was performed independently by at least two reviewers, regardless of study design. Data from clinical trials, postmarketing surveillance studies, surveys, spontaneous reporting schemes, manufacturers and herbalist organisations indicate that the adverse events following VAC treatment are mild and reversible. The most frequent adverse events are nausea, headache, gastrointestinal disturbances, menstrual disorders, acne, pruritus and erythematous rash. No drug interactions were reported. Use of VAC should be avoided during pregnancy or lactation. Theoretically, VAC might also interfere with dopaminergic antagonists. Although further rigorous studies are needed to assess the safety of VAC, the data available seem to indicate that VAC is a safe herbal medicine.


Molecular cloning and pharmacological characterization of a molluscan octopamine receptor.
We describe the cloning and functional expression of a cDNA encoding a novel G protein-coupled receptor, which was isolated from the central nervous system of the pond snail Lymnaea stagnalis. The amino acid sequence predicted by this cDNA shows highest similarity with the sequence of the Locusta tyramine receptor, the Drosophila tyramine/octopamine receptor, and the mammalian alpha-adrenergic receptors. On expression in mammalian cells, [3H]rauwolscine, an alpha2-adrenergic receptor antagonist, binds with high affinity (K(D) = 2.9 x 10(-9) M) to the receptor. Of several tested neurotransmitters, octopamine (which is considered to be the invertebrate counterpart of norepinephrine) showed the highest affinity (1.9 x 10(-6) M) for the receptor. Therefore, we consider this receptor to be the first true octopamine receptor to be cloned. The ligand binding properties of the novel receptor, designated Lym oa1, seem to be distinct from any of the binding profiles described for octopamine receptors in tissue preparations. Although the pharmacological profile of Lym oa1 shows some similarity with that of Tyr/Oct-Dro and Tyr-Loc, there are also clear differences. In particular, phentolamine, chlorpromazine, and mianserine display markedly higher affinities for Lym oa1 than for the insect receptors. As far as the vertebrate adrenergic receptors are concerned, the ligand binding properties of Lym oa1 resemble alpha2-adrenergic receptors more than they do alpha- or beta-adrenergic receptors. Octopaminergic stimulation of Lym oa1 induces an increase in both inositol phosphates and cAMP (EC50 = 9.1 x 10(-7) M and 5.1 x 10(-6) M, respectively). This is in contrast to the signal transduction pathways described for the related tyramine- and alpha2-adrenergic receptors, which couple in an inhibitory way to adenylyl cyclase.


Flaps for the repair of bladder exstrophy.
From April 1986 to March 1992, flaps were used in the surgical treatment of 17 patients with congenital bladder exstrophy. Eleven of these patients had had surgery in other hospitals but all failed. Using the flap method for the repair all of them had procured a functional bladder except one who could not have a complete control of urination. The longest follow-up period was 3 years, and the renal and bladder functions were completely normal. The immediate result in 14 patients was good in the control of urination right after the removal of the catheter. The follow-up results were good in 16 cases. The flaps used included 8 types of skin flaps, fasciae and vascular pedicles. Provided with the central vascular supply, the new series of procedures were suitable for the treatment of a variety of exstrophy deformities.


Resistance and Resilience of Soil Nitrogen Cycling to Drought and Heat Stress in Rehabilitated Urban Soils.
In the context of climate change and biodiversity loss, rehabilitation of degraded urban soils is a means of limiting artificialization of terrestrial ecosystems and preventing further degradation of soils. Ecological rehabilitation approaches are available to reinitiate soil functions and enhance plant development. However, little is known about the long-term stability of rehabilitated soils in terms of soil functions when further natural or anthropogenic perturbations occur. Based on rehabilitated urban soils, the present study sought to evaluate the resistance and resilience of soil functions linked to carbon cycling and phosphate dynamics in addition to nitrogen cycling and related microbial communities after a heat and drought stress. A laboratory experiment was conducted in microcosms under controlled temperature conditions, with four contrasted soils collected from a rehabilitated urban brownfield; an initial, non-rehabilitated soil (IS), a technosol with a high organic matter level (HO), and two technosols with less organic matter (LO1 and LO2), together with their respective controls (no stress). Changes in potential denitrification (PDR), nitrification (PNR) rates, and their interactive relationships with soil microbial activities and soil physicochemical properties were determined following a combined heat (40°C) and drought stress period of 21 days. Measurements were carried out immediately after the stress (resistance), and then also 5, 30, and 92 days after soil rewetting at 60% water holding capacity (resilience). Microbial activities involved in soil functions such as carbon cycling and phosphate dynamics proved to be of low resistance in all soils except for IS; however, they were resilient and recovered rapidly after rewetting. On the other hand, the microbial activities and gene abundances that were measured in relation to nitrogen cycling processes showed that for denitrification, activities were more rapidly resilient than gene abundances whereas for nitrification the activities and gene abundances were resilient in the same way. Results suggest that, unless the soils contain high amounts of organic matter, microbial communities in imported soils can be more vulnerable to environmental pressures such as drought and heat than communities already present. This should be considered when rehabilitating degraded soils.


Mapping global trends in vaccine confidence and investigating barriers to vaccine uptake: a large-scale retrospective temporal modelling study.
There is growing evidence of vaccine delays or refusals due to a lack of trust in the importance, safety, or effectiveness of vaccines, alongside persisting access issues. Although immunisation coverage is reported administratively across the world, no similarly robust monitoring system exists for vaccine confidence. In this study, vaccine confidence was mapped across 149 countries between 2015 and 2019. In this large-scale retrospective data-driven analysis, we examined global trends in vaccine confidence using data from 290 surveys done between September, 2015, and December, 2019, across 149 countries, and including 284 381 individuals. We used a Bayesian multinomial logit Gaussian process model to produce estimates of public perceptions towards the safety, importance, and effectiveness of vaccines. Associations between vaccine uptake and a large range of putative drivers of uptake, including vaccine confidence, socioeconomic status, and sources of trust, were determined using univariate Bayesian logistic regressions. Gibbs sampling was used for Bayesian model inference, with 95% Bayesian highest posterior density intervals used to capture uncertainty. Between November, 2015, and December, 2019, we estimate that confidence in the importance, safety, and effectiveness of vaccines fell in Afghanistan, Indonesia, Pakistan, the Philippines, and South Korea. We found significant increases in respondents strongly disagreeing that vaccines are safe between 2015 and 2019 in six countries: Afghanistan, Azerbaijan, Indonesia, Nigeria, Pakistan, and Serbia. We find signs that confidence has improved between 2018 and 2019 in some EU member states, including Finland, France, Ireland, and Italy, with recent losses detected in Poland. Confidence in the importance of vaccines (rather than in their safety or effectiveness) had the strongest univariate association with vaccine uptake compared with other determinants considered. When a link was found between individuals' religious beliefs and uptake, findings indicated that minority religious groups tended to have lower probabilities of uptake. To our knowledge, this is the largest study of global vaccine confidence to date, allowing for cross-country comparisons and changes over time. Our findings highlight the importance of regular monitoring to detect emerging trends to prompt interventions to build and sustain vaccine confidence. European Commission, Wellcome, and Engineering and Physical Sciences Research Council.


Pulmonary Embolism as a Rare Complication of Liver Hydatid Cyst: Report of Two Cases.
Hydatid cyst is a helminth infection. The rupture of a hepatic hydatid cyst in inferior vena cava is a rare and lethal complication. Pulmonary embolism is the commonest manifestation. The diagnosis of hydatid cyst is made by histopathological or serological examination, and imaging may suggest the probability of hydatid cyst. Surgical treatment should be performed with caution and always under vascular control. We present two cases of hydatid cyst ruptured into the inferior vena cava. The patients also presented with dyspnea, hemoptysis, and intermittent cough at the time of admission. This presentation will be accompanied by a brief review of the literature. The radiological findings suggested the diagnosis. The first patient had a fatal hydatid pulmonary embolism and death occurred on the second day of hospitalization. The second patient refused surgery. These cases also exemplify the clinical and radiographic findings as well as the management of this complication.


Improvement of Euglena gracilis Paramylon Production through a Cocultivation Strategy with the Indole-3-Acetic Acid-Producing Bacterium Vibrio natriegens.
We investigated the putative effects on the growth and paramylon production of Euglena gracilis of cocultivation with Vibrio natriegensE. gracilis heterotrophically cocultivated with V. natriegens displayed significant increases in biomass productivity and paramylon content. In addition, the effects of the bacterial inoculum density and the timing of inoculation on the growth of E. gracilis were examined, to determine the optimal conditions for cocultivation. With the optimal deployment of V. natriegens, biomass productivity and paramylon content were increased by more than 20% and 35%, respectively, compared to those in axenic E. gracilis cultures. Interestingly, indole-3-acetic acid biosynthesized by V. natriegens was responsible for these enhancements of E. gracilis The morphology of cocultured E. gracilis cells was assessed. Paramylon granules extracted from the cocultivation were significantly larger than those from axenic culture. Our study showed that screening for appropriate bacteria and subsequent cocultivation with E. gracilis represented an effective way to enhance biomass and metabolite production.IMPORTANCEEuglena gracilis has attracted special interest due to its ability to excessively accumulate paramylon. Paramylon is a linear β-1,3-glucan polysaccharide that is the principal polymer for energy storage in E. gracilis The polysaccharide features high bioactive functionality in the immune system. This study explored a new method to enhance the production of paramylon by E. gracilis, through cocultivation with the indole-3-acetic acid-producing bacterium Vibrio natriegens The enhanced production was achieved indirectly with the phytohormone-producing bacteria, instead of direct application of the hormone. The knowledge obtained in this study furthers the understanding of the effects of V. natriegens on the growth and physiology of E. gracilis.


Clinical and endoscopic findings in the mucosae of the upper respiratory and digestive tracts in post-treatment follow-up of paracoccidioidomycosis patients.
Systematic examination of the upper respiratory and digestive tracts (URDT) was performed in a group of 80 paracoccidioidomycosis (PCM) patients submitted to post-treatment follow-up ranging from 8 months to 17 years. Mucosae of the URDT had been involved prior to specific treatment in 74 patients, distributed as follows: oropharynx, 50 (41 alone, 7 in association with the larynx, and 2 with the nasal mucosa); larynx, 30 (23 alone and 7 in association); and nasal mucosa, 3 (1 alone and 2 in association). Inactive lesions were observed in all the 50 patients with lesions of the oropharynx, 3 of whom with deforming scars (1 with retraction of the tongue and 2 with narrowing of the oral orifice). One case presented a destructive lesion, with perfuration of the palate. Of the other 46 cases, examination showed nacreous white striated scars which were nearly imperceptible in some cases and in others displayed partial retraction of anatomical structures without any alteration of their features. Patients presented a high rate of missing teeth. In 3 patients with involvement of the nasal mucosa, none of whom presented active PCM lesions, 2 still had nasal voices. In 30 patients with lesions of the larynx, 1 suffered a relapse of PCM and 2 developed epidermoid carcinoma. Of the other 27 cases, none of whom had active PCM lesions, 15 presented dysphonia, 3 were tracheotomized, and 9 were asymptomatic.


Identification of RNA editing sites in chloroplast transcripts from the maternal and paternal progenitors of tobacco (Nicotiana tabacum): comparative analysis shows the involvement of distinct trans-factors for ndhB editing.
RNA editing alters genomic nucleotide sequences at the transcript level. In higher plant chloroplasts, C-to-U conversion is known to occur at around 30 specific sites. The tobacco cultivar Nicotiana tabacum is an amphidiploid derived from ancestors of N. sylvestris (maternal) and N. tomentosiformis (paternal). The chloroplast genome of N. tabacum is believed to originate from an ancestor of N. sylvestris. To study the evolution of RNA editing in higher plant chloroplasts, editing sites in the two likely progenitors have first been identified based on those found in N. tabacum. Altogether 34, 33, and 32 editing sites have been found in the chloroplast transcripts from N. tabacum, N. sylvestris, and N. tomentosiformis, respectively. Thirty-one sites are conserved among the three species, whereas remarkable differences are observed in the editing of ndhB and ndhD transcripts. Sites 7 and 8 in ndhB mRNAs are separated only by five nt, and both are edited in N. tabacum and N. sylvestris. However, site 8 is not edited in N. tomentosiformis, indicating that distinct trans-factors are involved in the two editing events. The first site in ndhD mRNAs is edited to produce an AUG start codon in N. sylvestris as well as in N. tabacum but not in N. tomentosiformis, suggesting that a distinct mechanism operates for the translational initiation of N. tomentosiformis ndhD mRNAs. Four to six sites are edited partially in green leaves. Some of these sites may represent evolutionary intermediates in the process of losing editing events.


Keratosis lichenoides chronica: proposal of a concept.
It has been a subject of controversy whether keratosis lichenoides chronica (KLC) is a distinctive inflammatory disease of the skin or whether it represents a manifestation of another well-known disease, such as lichen planus, lupus erythematosus, or lichen simplex chronicus. In search of clear criteria for diagnosis of KLC the entire literature pertinent to the subject was studied and findings clinical and histopathologic as they were telegraphed in them were compared with a patient of my own experience. Review of the literature reveals more than 60 patients in whom the diagnosis of KLC was made. Three categories emerge based on whether the findings presented in a particular article (1) do not permit any diagnosis to be rendered; (2) do allow a diagnosis specific to be made, such as of lichen simplex, lichen planus, or lupus erythematosus; or (3) do not correspond to any disease well defined, such as lichen simplex, lichen planus, lupus erythematosus, but seem to show attributes morphologic, clinically and histopathologically, that are repeatable. Patients diagnosed as having KLC obviously represent a potpourri of different diseases, the most common of them being lichen simplex chronicus, lichen planus, and lupus erythematosus. Fewer than 25 patients reported on, however, presented themselves with lesions very similar to one another clinically, namely, an eruption that involved the face in a manner reminiscent of seborrheic dermatitis and with tiny papules on the trunk and extremities, which assumed linear and reticulate shapes by way of confluence of lesions. Individual papules were infundibulocentric and acrosyringocentric. Findings histopathologic were those of a lichenoid interface dermatitis affiliated with numerous necrotic keratocytes and covered by parakeratosis housing neutrophils in staggered fashion. These patients seem to have an authentic and distinctive condition that is exceedingly rare. In conclusion, the diagnosis of KLC should be made only for patients who present themselves with features clinical and findings histopathologic that resemble closely those of what is summarized in this article under category 3.


Lesbian phobia among BSN educators: a survey.
This exploratory study identified the attitudes of BSN educators in a midwestern state towards lesbians. A 50% (N100) return rate of mailed questionnaires elicited responses to 48 statements about lesbians and lesbianism on a modified Likert scale. The questionnaire included general demographic data and responses to statements seeking information about topics of lesbianism or lesbian issues. Specific areas addressed included moral and ethical responses, knowledge statements, sexuality or sex related statements, normalness of lesbians and lesbian behavior, and social contact with lesbians. Notable findings revealed that BSN educators were not personally fearful of sexual advances from lesbians; however, they did indicate concern about lesbians molesting and caring for children as well as lesbians in the role of educators. More than half believed that lesbianism is not a natural expression of human sexuality.


Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses.
Tuberculosis (TB) remains a major public health problem and we lack a comprehensive understanding of how Mycobacterium tuberculosis (M. tb) infection impacts host immune responses. We compared the induced immune response to TB antigen, BCG and IL-1β stimulation between latently M. tb infected individuals (LTBI) and active TB patients. This revealed distinct responses between TB/LTBI at transcriptomic, proteomic and metabolomic levels. At baseline, we identified a novel immune-metabolic association between pregnane steroids, the PPARγ pathway and elevated plasma IL-1ra in TB. We observed dysregulated IL-1 responses after BCG stimulation in TB patients, with elevated IL-1ra responses being explained by upstream TNF differences. Additionally, distinct secretion of IL-1α/IL-1β in LTBI/TB after BCG stimulation was associated with downstream differences in granzyme mediated cleavage. Finally, IL-1β driven signalling was dramatically perturbed in TB disease but was completely restored after successful treatment. This study improves our knowledge of how immune responses are altered during TB disease, and may support the design of improved preventive and therapeutic tools, including host-directed strategies.


Sun-protective Properties of Technical Sportswear Fabrics 100% Polyester: The Influence of Moisture and Sweat on Protection against Different Biological Effects of Ultraviolet (UV) Radiation.
The use of technical sportswear is now widespread, but the degree of protection these fabrics offer against UV radiation is not known. We have analyzed the capacity of different types of technical sportswear fabrics to protect against different UV biological effects. A sample of 34 100% polyester t-shirts from different manufactures was classified by color, fabric structure, cover factor, and due to different tonalities, dark, and clear color. Ultraviolet protection factor was calculated according to UNE-EN13758. The protection factor for other biological effects as pre-vitamin D3 production, non-melanoma skin cancer, photoimmunosuppression, and photoaging was analyzed. The effects of moisture and sweat in protection were also evaluated. From the analyzed sample garments, more than 75% achieved an excellent protection value (protection factor 40-50+). Higher values were found in double-layer type (P < 0.05). Cover factor was the main determinant of biological protection factors with correlation coefficients of 0.81 for UPF (erythema), 0.77 for NMSC, and 0.63 for photoimmunosuppression. Water or sweat humidity saturation increased biological protection factors over a 20% (P < 0.05). The 83% of the fabrics analyzed showed less than 5% of transmittance with labeling as UVA protective elements. No effect of fabric color was found related to biological protection factors. The 100% polyester sports T-shirts of the analyzed sample offer general protection against UV for different biological effects that can be increased by humidity but no affected by fabric color.


Is there a place for traditional midwives in the provision of community-health services?
Traditional midwives (TM) have been involved in delivering babies, and providing a broad range of other services to women, for hundreds of years. They are usually local women with little formal education. As they are well known in their communities they are often called to assist women at the time of delivery. Two opposite views persist about the continuation of their role; some health workers would like to see them trained better and incorporated into the formal health system. Other health workers feel that all deliveries should be attended by either a nurse/midwife or a doctor, and that TM should eventually be phased out. Traditional midwives currently perform > 60% of deliveries in some developing countries and have had their role expanded in some places. Recruiting nurse/midwives and doctors to work in remote areas remains difficult and, even if they were recruited, there is no guarantee that their obstetric services would be used. The evaluation of training programmes has not produced any clear-cut answers in the debate about the long-term role or existence of TM. Rather, the studies have shown that the success of the programmes depends on the resources available, the people involved in the training and how the training is carried out. Some of the lessons learnt from working with TM apply to any two groups of people working together. If TM are going to be offered training, and this must be a local decision made after consultation and an evaluation of prevailing resources and conditions, the training should be a two-way process, with both parties learning from each other.


TGF beta 1 inhibits Ca2+-calcineurin-mediated activation in thymocytes.
TGFbeta1 is a polypeptide growth modulatory and differentiation factor involved in many biological processes including immune homeostasis and self-tolerance. Tgfb1 knockout mice die around weaning age due to severe inflammation in most major organ systems, but the mechanism underlying this disease is not understood. In this study we demonstrate that Tgfb1(-/-) CD4(+)CD8(+) and CD4(+)CD8(-) thymocytes are hyperresponsive to receptor-mediated and receptor-independent mitogenic stimulation. A suboptimal concentration of ionomycin in the presence of PMA fully activates Tgfb1(-/-) thymocytes, whereas the inhibitors of Ca(2+) influx and calcineurin, EGTA and FK506, eliminate the hyperresponsiveness. Hence, the hypersensitivity of Tgfb1(-/-) thymocytes is due to a lowered threshold for Ca(2+)-dependent activation. Further, we demonstrate that the hypersensitivity of thymocytes results from the absence of TGFbeta1 and not from the inflammatory environment because the thymocytes are hyperresponsive in preinflammatory-stage Tgfb1(-/-) mice. Our results suggest for the first time that TGFbeta1 functions to inhibit aberrant T cell expansion by maintaining intracellular calcium concentration levels low enough to prevent a mitogenic response by Ca(2+)-independent stimulatory pathways alone. Consequently, TGFbeta1 prevents autoimmune disease through a Ca(2+) regulatory pathway that maintains the activation threshold above that inducible by self-MHC-TCR interactions.


Tabletop versus microcomputer-assisted speech management: response evocation phase.
This is the third in a series of studies on the use of microcomputers with speech-delayed children. Two repeated-measures designs (n = 15) and five case studies were completed to compare tabletop management at early and late stages of the response development phase with two comparable, computer-assisted drill-and-practice activities. Discrimination of correct articulatory responses was mediated by the clinician in all modes, rather than by speech recognition hardware, but all contingent reinforcement in the computer modes was presented by animation graphics. The two computer modes were identical except for the addition of fantasy involvement in one of the modes. Findings indicated that the three modes of intervention were equally effective, efficient, and engaging. Subject-level analyses suggested that microcomputer software has excellent potential to engage children in drill-and-practice for late-phase response evocation, when the target sound is stimulable, but limited usefulness with young children at early-phase response evocation, when specific articulatory behaviors need to be cued. Discussion considers learning, child, and hardware/software factors in microcomputer-assisted speech management.


Comparison of trend detection algorithms in the analysis of physiological time-series data.
This paper presents a comparative performance analysis of various trend detection methods developed using fuzzy logic, statistical, regression, and wavelet techniques. The main contribution of this paper is the introduction of a new method that uses noise rejection fuzzy clustering to enhance the performance of trend detection methodologies. Furthermore, another contribution of this work is a comparative investigation that produced systematic guidelines for the selection of a proper trend detection method for different application requirements. Examples of representative physiological variables considered in this paper to examine the trend detection algorithms are: 1) blood pressure signals (diastolic and systolic); and 2) heartbeat rate based on RR intervals of electrocardiography signal. Furthermore, synthetic physiological data intentionally contaminated with various types of real-life noise has been generated and used to test the performance of trend detection methods and develop noise-insensitive trend-detection algorithms.


Nanobubble Technologies Offer Opportunities To Improve Water Treatment.
Since first hypothesizing the existence of nanobubbles (NBs) in 1994, the empirical study of NB properties and commercialization of NB generators have rapidly evolved. NBs are stable spherical packages of gas within liquid and are operationally defined as having diameters less than 1000 nm, though they are typically in the range of 100 nm in one dimension. While theories still lack the ability to explain empirical evidence for formation of stable NBs in water, numerous NB applications have emerged in different fields, including water and wastewater purification where NBs offer the potential to replace or improve efficiency of current treatment processes. The United Nations identifies access to safe drinking water as a human right, and municipal and industrial wastewaters require purification before they enter water bodies. These protections require treatment technologies to remove naturally occurring (e.g., arsenic, chromium, fluoride, manganese, radionuclides, salts, selenium, natural organic matter, algal toxins), or anthropogenic (e.g., nitrate, phosphate, solvents, fuel additives, pharmaceuticals) chemicals and particles (e.g., virus, bacteria, oocysts, clays) that cause toxicity or aesthetic problems to make rivers, lakes, seawater, groundwater, or wastewater suitable for beneficial use or reuse in complex and evolving urban and rural water systems. NBs raise opportunities to improve current or enable new technologies for producing fewer byproducts and achieving safer water. This account explores the potential to exploit the unique properties of NBs for improving water treatment by answering key questions and proposing research opportunities regarding (1) observational versus theoretical existence of NBs, (2) ability of NBs to improve gas transfer into water or influence gas trapped on particle surfaces, (3) ability to produce quasi-stable reactive oxygen species (ROS) on the surface of NBs to oxidize pollutants and pathogens in water, (4) ability to improve particle aggregation through intraparticle NB bridging, and (5) ability to mitigate fouling on surfaces. We conclude with key insights and knowledge gaps requiring research to advance the use of NBs for water purification. Among the highest priorities is to develop techniques that measure NB size and surface properties in complex drinking and wastewater chemistries, which contain salts, organics, and a wide variety of inorganic and organic colloids. In the authors' opinion, ROS production by NB may hold the greatest promise for usage in water treatment because it allows movement away from chemical-based oxidants (chlorine, ozone) that are costly, dangerous to handle, and produce harmful byproducts while helping achieve important treatment goals (e.g., destruction of organic pollutants, pathogens, biofilms). Because of the low chemical requirements to form NBs, NB technologies could be distributed throughout rapidly changing and increasingly decentralized water treatment systems in both developed and developing countries.


The Caribbean experience with the diabetic foot management of the diabetic foot.
The foot complications of diabetic patients are one of the commonest and most devastating of medical problems that occurs in the Caribbean. The scale of the problem is reflected in the fact that, on average, 75% of the beds in the general surgical wards of the Queen Elizabeth Hospital in Barbados are occupied by patients with this problem. Of the patients admitted, a third lose a limb by amputation and another third of the patients lose toes or part of their feet and remain in hospital an average of two months as doctors struggle to prevent them losing their limbs. Half of the patients are in their 70s when they are admitted to hospital but 4 per cent are as young as thirty to forty years. It is clear to the surgeons who struggle to save the limbs of these patients that preventive care and early and aggressive intervention, when problems occur, are the best way to avoid prolonged hospitalization and loss of limb. The events that precipitate the problems often appear trivial to most people. a little nick cutting a nail or a callus, a crack under the toe, an ingrowing nail, stepping on a rock in the yard or, even more devastating, on a dirty or rusty nail. The diabetic's foot is more susceptible to injury, sepsis and gangrene because of an altered inflammatory response and an increased incidence of occlusive vascular disease and neuropathy. Injuries normally considered minor can threaten the limb in diabetics by rapid progression of necrosis along tissue planes. Prevention is of primary importance and patients need to be educated and to remind themselves over and over again to clean their feet daily, paying particular attention to the interdigital areas: looking at them to make sure that there is no swelling or cuts or change in colour. Looking is important since diabetics, especially those with neuropathy, cannot rely-on pain as a symptom of injury. Patients have to be trained to recognise and respond to the signs of injury and infection without relying on the signal of pain that they and the health care workers usually rely upon to assess the seriousness of most conditions. Diabetics should wear something on their feet at all times, in and out of the house. What is worn should have a good firm sole to prevent penetration. If a sandal is worn, it should be strapped on so that it does not slip off easily. If something goes wrong, or is noticed to be wrong with the feet, professional help should be sought the same day. Treatment and observation are needed on a daily basis. In order to try and save a limb, patients may need to have a series of minor operations and for those who are seen by surgeons early enough, four out of every five persons will have their limbs preserved. However, after the limb is saved, it is in greater danger for further problems and patients may require special shoes to prevent recurrence. The area of rehabilitation and prevention needs a great deal of improvement in the Caribbean for specialist orthotic advice and skills are scarce. Team work is essential for, by working together, patients, doctors, nurses, chiropodists and orthotic technicians can improve outcomes for the diabetic patient.


Intestinal calcium waves coordinate a behavioral motor program in C. elegans.
Periodic behavioral motor patterns are normally controlled by neural circuits, such as central pattern generators. We here report a novel mechanism of motor pattern generation by non-neural cells. The defecation motor program in Caenorhabditis elegans consists of three stereotyped motor steps with precise timing and this behavior has been studied as a model system of a ultradian biological clock [J.H. Thomas, Genetic analysis of defecation in C. elegans, Genetics 124 (1990) 855-872; D.W. Liu, J.H. Thomas, Regulation of a periodic motor program in C. elegans, J. Neurosci. 14 (1994) 1953-1962; K. Iwasaki, D.W. Liu, J.H. Thomas, Genes that control a temperature-compensated ultradian clock in Caenorhabditis elegans, Proc. Natl. Acad. Sci. USA 92 (1995), 10317-10321]. It was previously implied that the inositol-1,4,5-trisphosphate (IP3) receptor in the intestine was necessary for this periodic behavior [P. Dal Santo, M.A. Logan, A.D. Chisholm, E.M. Jorgensen, The inositol trisphosphate receptor regulates a 50s behavioral rhythm in C. elegans, Cell 98 (1999) 757-767]. Therefore, we developed a new assay system to study a relationship between this behavioral timing and intestinal Ca(2+) dynamics. Using this assay system, we found that the timing between the first and second motor steps is coordinated by intercellular Ca(2+)-wave propagation in the intestine. Lack of the Ca(2+)-wave propagation correlated with no coordination of the motor steps in the CaMKII mutant. Also, when the Ca(2+)-wave propagation was blocked by the IP3 receptor inhibitor heparin at the mid-intestine in wild type, the second/third motor steps were eliminated, which phenocopied ablation of the motor neurons AVL and DVB. These observations suggest that an intestinal Ca(2+)-wave propagation governs the timing of neural activities that controls specific behavioral patterns in C. elegans.


[Monoclonal integration of simian T-cell leukemia virus in hamadryas with malignant lymphoma].
The association of simian T-cell leukemia virus with baboons malignant lymphoma was studied. Proviral DNA integrated in cells of lymphoid organs was detected in 19 of 21 sick animals examined. Only 4 of 10 monkeys from high risk colony without clinical manifestations had virus-specific sequences in their cellular DNAs. As a rule, S(H)TLV-I-infected cells monoclonally proliferated both in lymphomatous and healthy baboons. The restriction patterns with EcoRI, HindIII, PstI, BamHI of S(H)TLV-I provirus were similar but not identical to those of prototype HTLV-I and STLV-I isolates.


[Ileal endometriosis. A clinical case and a review of the literature].
Ileal localization of intestinal endometriosis is not extremely rare, but there are always problems related to the preoperative diagnosis. Symptoms of intestinal endometriosis offer often problems to the surgeon in the differential diagnosis with many more pregnant illnesses like appendicitis, diverticulitis, inflammatory bowel diseases and abdominal neoplasms. The authors report a case of endometriosis of the ileum clinically mimicking Crohn's disease. Crohn's disease of the ileum is the most frequently reported illness that is considered in the differential diagnosis. The review of the literature shows that a correct preoperative diagnosis of endometriosis of the ileum is very seldom done. All common diagnostic tools are not able to resolve diagnostic doubts. Also during explorative surgery the diagnosis of endometriosis is not easy. The authors conclude that endometriosis of the ileum has to be more often considered as possible cause of common intestinal symptoms mimicking inflammatory bowel disease and that this illness induces to reevaluate the importance for a correct diagnosis of an accurate clinical history.


[Serodiagnosis of Lyme borreliosis: antibody titer and specificity in the IFT and western blot].
Out of 334 sera from healthy persons from northern Bavaria 6% reacted positive in the indirect immunofluorescence test (IFT, titre greater than or equal to 1:64). The percentage of positive cases in patients with erythema chronicum migrans (ECM), meningoradiculitis (M. Bannwarth), or acrodermatitis chronica atrophicans (ACA) was 43, 83 and 78%, respectively. In other patients with less characteristic symptoms in which an infection with B. burgdorferi was suspected the number of positive cases was only about 20%. A positive IgM-IFT was most often associated with ECM and M. Bannwarth; however, even in these cases IgM was only found in 30%. The serodiagnosis of Lyme disease required simultaneous serum testing of T. pallidum antibodies (TPHA) to exclude a syphilis with cross-reacting antibodies. In cases with a positive B. burgdorferi-IFT and TPHA the final diagnosis of Lyme disease was possible on the basis of Western blot analysis. The prominent antigens detected by sera from patients with Lyme disease--but not with syphilis--had molecular weights of 18, 22, 41 and 60 K; IgM antibodies were mainly directed against the 22 K and 41 K antigens. The antigen pattern was not characteristic for different disease stages.


Social-bond strength influences vocally mediated recruitment to mobbing.
Strong social bonds form between individuals in many group-living species, and these relationships can have important fitness benefits. When responding to vocalizations produced by groupmates, receivers are expected to adjust their behaviour depending on the nature of the bond they share with the signaller. Here we investigate whether the strength of the signaller-receiver social bond affects response to calls that attract others to help mob a predator. Using field-based playback experiments on a habituated population of wild dwarf mongooses (Helogale parvula), we first demonstrate that a particular vocalization given on detecting predatory snakes does act as a recruitment call; receivers were more likely to look, approach and engage in mobbing behaviour than in response to control close calls. We then show that individuals respond more strongly to these recruitment calls if they are from groupmates with whom they are more strongly bonded (those with whom they preferentially groom and forage). Our study, therefore, provides novel evidence about the anti-predator benefits of close bonds within social groups.


Water ingestion during swimming activities in a pool: a pilot study.
Chloroisocyanurates are commonly added to outdoor swimming pools to stabilize chlorine disinfectants. The chloroisocyanurates decompose slowly to release chlorine and cyanuric acid. Studies conducted to determine if the chloroisocyanurates might be toxic to swimmers showed that they were not and that ingested cyanuric acid passed through the body unmetabolized. This fact was used to determine the amount of water swallowed during swimming activity. Fifty-three recreational swimmers, using a community swimming pool disinfected with cyanuric acid stabilized chlorine, participated in the study. The participants did not swim on the day before or after the test swim. The swimmers were asked to actively swim for at least 45 minutes and to collect their urine for the next 24 hours. Cyanuric acid was measured in pool water using high performance liquid chromatography and porous graphitic carbon columns with UV detection. The urine sample assay required a clean-up procedure to remove urinary proteins and interfering substances. Results of the study indicate that non-adults ingest about twice as much water as adults during swimming activity. The average amount of water swallowed by non-adults and adults was 37 ml and 16 ml, respectively. The design for this study and the analytical methodology used to assay cyanuric acid in swimming pool water and human urine were effective for measuring the volume of water swallowed during swimming activity.


Antibodies against deamidated gliadin peptides and tissue transglutaminase for diagnosis of pediatric celiac disease.
The aim of the present study was to evaluate diagnostic performance and actual costs in clinical practice of immumoglobulin (Ig)G/IgA deamidated gliadin peptide antibodies (DGP) as a complement to IgA antibodies against tissue transglutaminase (tTG) for the diagnosis of pediatric celiac disease (CD). All of the consecutive patients younger than 18 years tested for tTG and/or DGP, who underwent duodenal biopsy because of suspected CD in Stockholm and Gothenburg, Sweden, from 2008 to 2010, were included. Medical records were reviewed. Of 537 children who underwent duodenal biopsy, 278 (52%) had CD. A total of 71 (13%) were younger than 2 years and 16 (4%) had IgA deficiency. Sensitivity and specificity for tTG were 94% and 86%, respectively. Corresponding values for DGP were 91% and 26%. Positive predictive values (PPV) were 88% for tTG and 51% for DGP. There were 148 children who were tTG-negative and DGP-positive, of which only 5% (8/148) had villous atrophy. Among children younger than 2 years with normal IgA, PPV was 96% (25/26) for tTG and 48% (24/50) for DGP. In 16 IgA-deficient children, 11 were DGP positive, of which 5 had CD (PPV 45%). Eight of 278 cases of CD would possibly have been missed without DGP. The cost of adding DGP and consequently more biopsies to be able to detect 8 extra cases of CD was [Euro sign]399,520 or [Euro sign]49,940 per case. For diagnosing CD, tTG is superior to DGP, even in children younger than 2 years. Combining tTG and DGP does not provide a better tradeoff between number of missed cases of CD, number of unnecessary duodenal biopsies, and cost than tTG alone.


Is increased D2 receptor availability associated with response to stimulant medication in ADHD.
The purpose of this study was to estimate striatal dopamine (D2) receptor availability in non-drug treated children with attention-deficit-hyperactivity disorder (ADHD) before and after methylphenidate therapy, and to examine correlations between severity of symptoms and response rates to stimulant medication with levels of striatal D2 receptor binding. Nine children (six males, three females; mean age 9.8 years, SD 2.3 years) with ADHD participated. All underwent iodobenzamide (123I IBZM) brain SPECT within 2 hours following intravenous injection of 123I IBZM before and 3 months after methylphenidate therapy. A semiquantitative approach was used to generate indices of specific D2 receptor binding in the basal ganglia. Specific binding ratios at baseline were higher than the previously reported specific binding values obtained in studies using young healthy adults. D2 availability reduced significantly (paired t-test,p<0.05) as a function of methylphenidate therapy in patients with ADHD in all four regions of the striatum. When the relation between therapy response and D2 availability was investigated, we observed that the higher the baseline D2 levels were, the higher the response rate was (detected as the percentage reduction of hyperactivity scores and Conners Teacher Rating Scale scores), while no such trend was observed between the initial D2 binding levels and the response in attention-deficit scores. Results indicate that in non-drug treated children with ADHD, higher D2 receptor availability is observed at baseline which is down-regulated back to reported near-normal values after methylphenidate therapy. The effect of methylphenidate on D2 receptor levels in patients with ADHD is similar to that observed in healthy adults; a down-regulation phenomenon within 0 to 30%. In addition, initially higher values of D2 availability seem to indicate better response to methylphenidate therapy in ADHD.


Rewilding soil-disturbing vertebrates to rehabilitate degraded landscapes: benefits and risks.
Soil-disturbing animals are common globally and play important roles in creating and maintaining healthy functional soils and landscapes. Yet many of these animals are threatened or locally extinct due to habitat loss, predation by non-native animals or poaching and poisoning. Some reintroduction and rewilding programmes have as their core aims to increase animal populations and reinstate processes that have been lost due to their extirpation. Here we use a meta-analytical approach to review the effects of soil-disturbing vertebrates on ecosystem processes, and advance the argument that they can be used to rehabilitate degraded ecosystems by altering mainly composition and function, but with fewer positive effects on structure. We describe four examples where the loss or reintroduction of soil-disturbing vertebrates leads to ecosystem state changes and highlight the role of spatial scale, covarying management changes, and species co-occurrence in modulating their effects. We discuss the advantages and disadvantages of using soil-disturbing vertebrates over mechanized engineering approaches such as pitting and furrowing, considering some advantages to include more self-sustainable and heterogeneous disturbances, creation of new habitats and added recreational values. Finally, we identify key knowledge gaps in our understanding of the use of soil-disturbing vertebrates for rehabilitating degraded ecosystems.


What is "Nonbinary" and What Do I Need to Know? A Primer for Surgeons Providing Chest Surgery for Transgender Patients.
Most transgender research focuses on patients who identify within the gender binary of either trans-male or trans-female. This largely omits understanding of the "nonbinary" gender identity as it pertains to surgical care. We sought to describe a single-institution experience of chest-affirming procedures performed in nonbinary patients, including patient characteristics, surgical techniques, practice pearls, and outcomes. This was an observational study of nonbinary patients who underwent "chest-affirming surgery" from 2012 to 2017. Demographic and surgical data were collected. A postoperative questionnaire assessing quality of life and body image outcomes was administered. A total of 458 patients with gender dysphoria underwent chest surgery; 58 (13%) patients were nonbinary. All nonbinary patients indicated female sex was assigned at their birth (100%). The most commonly performed procedure was the double incision technique with nipple grafts (72%), followed by the double incision technique without nipple grafts (19%). On a Likert scale, patients reported improved quality of life (4.88, SD ± 0.34), comfort with exercise (4.07, SD ± 0.98), sex life (4.02, SD ± 0.92), and comfort with physical appearance with (4.97, SD ± 0.18) and without clothes (4.69, SD ± 0.47). Chest surgery for nonbinary patients comprises a considerable proportion of transgender surgery practice, and surgeons who provide affirming care should be familiar with the unique characteristics and treatment options for this population.


Search for the invisible decay of neutrons with KamLAND.
The Kamioka Liquid scintillator Anti-Neutrino Detector is used in a search for single neutron or two-neutron intranuclear disappearance that would produce holes in the -shell energy level of (12)C nuclei. Such holes could be created as a result of nucleon decay into invisible modes (inv), e.g., n--> 3v or nn--> 2v. The deexcitation of the corresponding daughter nucleus results in a sequence of space and time-correlated events observable in the liquid scintillator detector. We report on new limits for one- and two-neutron disappearance: tau(n--> inv) > 5.8 x 10(29) years and tau (nn--> inv) > 1.4 x 10(30) years at 90% C.L. These results represent an improvement of factors of approximately 3 and >10(4) and over previous experiments.


Cloning and sequencing the endocarditis immunodominant antigen of Streptococcus sobrinus strain MUCOB 263.
Immunoblotting sera from cases of Streptococcus mutans or S. sobrinus endocarditis against an extract from S. sobrinus strain MUCOB 263 had identified three immunodominant antigenic bands at 190, 200 and 220 kDa. A lambda ZAPII DNA library was produced from the sheared genomic DNA of S. sobrinus MUCOB 263 and six identical positive clones were identified when this library was screened with serum from a patient with endocarditis caused by a bacterium from the mutans group of streptococci. On subcloning and sequencing, a protein containing 1548 amino acids was identified with a 99.2% homology to the SpaA antigen of S. sobrinus and 68.4% homology to the PAc antigen of S. mutans.


Evaluation of the Preservation and Digestion of Seal Meat Processed with Heating and Antioxidant Seal Meat Hydrolysates.
Seal meat is of high nutritive value but is not highly exploited for human food due to ethical issues, undesirable flavors, and loss of nutrients during the processing/cooking step. In this work, commercially available processed seal meat was treated with its hydrolysates as preservatives with the aim of improving nutrient bioavailability. The contents of the nutrients were analyzed after digestion using a simulated dynamic digestion model, and the effects of different processing conditions, i.e., low-temperature processing and storage (25 °C) and high-temperature cooking (100 °C), of seal meat were investigated. Hydrolysates with antioxidant activity decreased the amounts of the less desirable Fe3+ ions in the seal meat digests. After treatment with hydrolysates at room temperature, a much higher total Fe content of 781.99 mg/kg was observed compared to other treatment conditions. The release of amino acids increased with temperature and was 520.54 mg/g for the hydrolysate-treated sample versus 413.12 mg/g for the control seal meat sample treated in buffer. Overall, this study provides useful data on the potential use of seal meat as a food product with high nutritive value and seal meat hydrolysates with antioxidant activity as preservatives to control oxidation in food.


White light-emitting diodes based on ultrasmall CdSe nanocrystal electroluminescence.
We report white light-emitting diodes fabricated with ultrasmall CdSe nanocrystals, which demonstrate electroluminescence from a size of nanocrystals (<2 nm) previously thought to be unattainable. These LEDs have excellent color characteristics, defined by their pure white CIE color coordinates (0.333, 0.333), correlated color temperatures of 5461-6007 K, and color rendering indexes as high as 96.6. The effect of high voltage on the trap states responsible for the white emission is also described.


[Functional nutrients, digestive tract and potencial benefits for the child].
Widespread interest in the possibility that selected foods containing specifically physiologically active components might promote health has resulted in the coining of the term Functional Food. Recent studies have shown that modified foods or selected ingredients may provide health benefits. Benefits touted by these foods are known to prevent certain diseases, promote health or both; and by that promoting a state of well-being and better health; reducing the risk of disease. The gastrointestinal tract is an obvious target for the development of Functional Foods, acting as it does as the interface between diet and the metabolic events, which sustain life. The American Dietetic Association recommends cautious evaluation of the clinical efficacy of individual nutrients/ingredients before recommending their use to promote as specific health outcome. Identification of sensitive and reliable biomarkers will be key to adequate assessment of the true effect of foods and their components.


Whiteness theory and the (in)visible hierarchy in medical education.
The theory of whiteness in medical education has largely been ignored, yet its power continues to influence learners within our medical curricula and our patients and trainees within our health systems. Its influence is even more powerful given the fact that society maintains a 'possessive investment' in its presence. In combination, these (in)visible forces create environments that favour White individuals at the exclusion of all others, and as health professions educators and researchers, we have the responsibility to uncover how and why these influences continue to pervade medical education. To better understand how whiteness and the possessive investment in its presence create (in)visible hierarchies, we define and explore the origin of whiteness by examining whiteness studies and how we have come to have a possessive investment in its presence. Next, we provide ways in which whiteness can be studied in medical education so that it can be disruptive. We encourage health profession educators and researchers to collectively 'make strange' our current hierarchical system by not just recognising the privileges afforded to those who are White but also recognising how these privileges are invested in and maintained. As a community, we must develop and resist established power structures to transform the current hierarchy into a more equitable system that supports everyone, not just those who are White.


IMx (Abbott) Immunoassay of Insulin: A Practical Alternative to RIA Hyperinsulinemia Identification in Idiopathic Neurootology and Other Hyperinsulin Metabolic Disorders.
Hyperinsulinemia identification as defined by glucose/insulin tolerance has been established as the prime etiological factor in idiopathic neurootological disorders. Insulin assays by radioimmunoassay (RIA) and the IMx (Abbott) immunoassay yielded in 558 of 595 glucose/insulin tolerance a concurrence of 93.7%. The latter measures insulin without cross-reaction with proinsulin. The RIA methodology includes proinsulin. The IMx (Abbott), a micro-particle enzyme immunoassay (MEIA), gave lower values due to its nondetection of proinsulin. Based upon defined insulin values, the dynamic patterns of euinsulinemia, hyperinsulinemia with elevated fasting insulin levels and hyperinsulinemia with impaired and/or hyperglycemia glucose tolerance were concurred 100% by MEIA. All of the nonconcurrences were with normal glucose tolerances when the second and/or third hour insulin values were borderline. The limited utilization of RIA technology and the potential availability of enzymatic immunoassay which requires less technical skills presents MEIA as a practical and precise alternative to RIA hyperinsulinemia identification. The increasing world-wide significance of the clinical pathology of hyperinsulinemia becoming manifest in all disciplines of medicine, warrants the identification and/or exclusion of hyperinsulinemia by cost-effective technology.


Coccidioidomycosis during pregnancy. An analysis of ten cases among 47,120 pregnancies.
Previous studies have suggested that coccidioidomycosis during pregnancy is a devastating illness associated with high maternal mortality. However, this concept recently has been challenged. We examined the incidence of coccidioidomycosis during pregnancy in Tucson, Arizona, an area endemic for this infection. After reviewing the records of three separate health care facilities, we found ten cases of coccidioidomycosis among 47,120 pregnancies. Nine of the ten women had no underlying disease. Seven were diagnosed with coccidioidomycosis during either the first or second trimester. Illness resolved in all seven. Three other patients were diagnosed during the first ten days postpartum. While infection was self-limited in one woman, two others developed severe disseminated coccidioidomycosis associated with meningitis. Despite this, there were no maternal deaths. Of eight deliveries, all were uncomplicated and produced healthy infants. In summary, diagnosing coccidioidomycosis during pregnancy is rare. Although we observed no maternal death, our experience suggests that women who develop coccidioidomycosis late in pregnancy are at risk for developing severe disseminated infection.


Hypolithic and soil microbial community assembly along an aridity gradient in the Namib Desert.
The Namib Desert is considered the oldest desert in the world and hyperarid for the last 5 million years. However, the environmental buffering provided by quartz and other translucent rocks supports extensive hypolithic microbial communities. In this study, open soil and hypolithic microbial communities have been investigated along an East-West transect characterized by an inverse fog-rainfall gradient. Multivariate analysis showed that structurally different microbial communities occur in soil and in hypolithic zones. Using variation partitioning, we found that hypolithic communities exhibited a fog-related distribution as indicated by the significant East-West clustering. Sodium content was also an important environmental factor affecting the composition of both soil and hypolithic microbial communities. Finally, although null models for patterns in microbial communities were not supported by experimental data, the amount of unexplained variation (68-97 %) suggests that stochastic processes also play a role in the assembly of such communities in the Namib Desert.