Development of UDP-glucuronosyltransferase activity toward digitoxigenin-monodigitoxoside in neonatal rats.
Glucuronidation is low or undetectable in embryonic and early fetal tissues and changes to adult levels at rates depending on the acceptor, tissue, and species. Because other data indicate there may be a specific UDP-glucuronosyltransferase (GT) in the liver of adult rats that glucuronidates digitoxigenin-monodigitoxoside (DIG), the development of GT activity in neonatal rats toward DIG was compared with that of other acceptors. Conjugation of p-nitrophenol and 1-naphthol was higher at birth and decreased to adult levels by 20 days of age. Glucuronidation of chloramphenicol, morphine, valproic acid, and bilirubin increased from birth to adult activity by 20 days of age. Conjugation of phenolphthalein, estrone, and diethylstilbestrol was low in 1-day-old rats and higher than adult in 20-day-old animals. In contrast, glucuronidation of DIG was barely detectable (9% of adult) in 20-day-old rats. The concentration of UDP-glucuronic acid was 50% of adult levels at birth and increased to adult values by 10 days of age. Administration of 3-methylcholanthrene on days 6 to 9 after birth significantly stimulated GT activity toward 1-naphthol, p-nitrophenol, and morphine, whereas phenobarbital precociously increased conjugation of chloramphenicol, valproic acid, morphine, and diethylstilbestrol. Pregnenolone-16 alpha-carbonitrile enhanced the development of GT activity toward morphine, chloramphenicol, valproic acid, bilirubin, diethylstilbestrol, and estrone. Glucuronidation of DIG was not increased after 3-methylcholanthrene or phenobarbital, but could be induced after pregnenolone-16 alpha-carbonitrile to 7% of adult values in 10-day-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)


In vitro assembly and GTP hydrolysis by bacterial tubulins BtubA and BtubB.
Arecent study identified genuine tubulin proteins, BtubA and BtubB, in the bacterial genus Prosthecobacter. We have expressed BtubA and BtubB in Escherichia coli and studied their in vitro assembly. BtubB by itself formed rings with an outer diameter of 35-36 nm in the presence of GTP or GDP. Mixtures of BtubB and BtubA formed long protofilament bundles, 4-7 protofilaments wide (20-30 protofilaments in the three-dimensional bundle). Regardless of the starting stoichiometry, the polymers always contained equal concentrations of BtubA and BtubB, suggesting that BtubA and B alternate along the protofilament. BtubA showed negligible GTP hydrolysis, whereas BtubB hydrolyzed 0.40 mol GTP per min per mol BtubB. This GTPase activity increased to 1.37 per min when mixed 1:1 with BtubA. A critical concentration of 0.4-1.0 microM was indicated by light scattering experiments and extrapolation of GTPase versus concentration, thus suggesting a cooperative assembly mechanism.


[Orbital hemorrhage as a sequela of heparin-induced thrombocytopenia].
Spontaneous orbital hemorrhage is a rare but sight threatening incident. Several causative factors are known. Infrequently, hemorrhagic ocular complications can be associated with heparin therapy. The mechanism can involve a immunologically caused thrombocytpenia. In every hemorrhagic ocular complication which occurs in patients treated with heparin Heparin-induced thrombocytopenia (HIT) must be taken into consideration. A 76-year-old woman who underwent hip surgery three weeks prior to a spontaneous orbital hemorrhage had been treated with subcutaneous heparin. CT scan of the right orbit showed peribulbar hemorrhage with the main focus retro-lateral of the bulbus. Retrobulbar expansion of the hemorrhage was only slight with no compression of the optic nerve. There was no sign of tumor or anomaly of blood vessels. Blood cell count revealed a marked thrombocytopenia with 8000/microliter. After discontinuation of heparin therapy, thrombocytes' cell counts rised rapidly with 114,000/microliter after three days. Parallel to the normalization of the thrombocytes' cell counts the clinical symptoms disappeared quickly. Heparin-induced thrombocytopenia as a cause for spontaneous orbital hemorrhage has never been reported before. For differential diagnosis in patients with hemorrhagic ocular complications, HIT must taken into account. The most important measure is counting thrombocytes. In thrombocytopenia, heparin therapy must be discontinued before hemorrhagic or thromboembolic complications occur.


Identifying socio-demographic risk factors for suicide using data on an individual level.
Suicide is a complex issue. Due to the relative rarity of the event, studies into risk factors are regularly limited by sample size or biased samples. The aims of the study were to find risk factors for suicide that are robust to intercorrelation, and which were based on a large and unbiased sample. Using a training set of 5854 suicides and 596,416 control cases, we fit a logistic regression model and then evaluate the performance on a test set of 1425 suicides and 594,893 control cases. The data used was micro-data of Statistics Netherlands (CBS) with data on each inhabitant of the Netherlands. Taking the effect of possible correlating risk factors into account, those with a higher risk for suicide are men, middle-aged people, people with low income, those living alone, the unemployed, and those with mental or physical health problems. People with a lower risk are the highly educated, those with a non-western immigration background, and those living with a partner. We confirmed previously known risk factors such as male gender, middle-age, and low income and found that they are risk factors that are robust to intercorrelation. We found that debt and urbanicity were mostly insignificant and found that the regional differences found in raw frequencies are mostly explained away after correction of correlating risk factors, indicating that these differences were primarily caused due to the differences in the demographic makeup of the regions. We found an AUC of 0.77, which is high for a model predicting suicide death and comparable to the performance of deep learning models but with the benefit of remaining explainable.


Acceptable outcome following resection of bilateral large popliteal space heterotopic ossification masses in a spinal cord injured patient: a case report.
Spinal cord injury is a well-known predisposing factor for development of heterotopic ossification around the joints especially hip and elbow. Heterotopic ossification about the knee is usually located medially, laterally or anteriorly; besides, the knee is generally fixed in flexion. There are only a few reports of heterotopic bone formation at the posterior aspect of the knee (popliteal space) and fixation of both knees in extension; so, there is little experience in operative management of such a problem.Here, we present a 39-years old paraplegic man who was referred to us five years after trauma with a request of above knee amputation due to sever impairment of his life style and adaptive capacity for daily living because of difficulties in using wheelchair. The principle reason for the impairment was fixed full extension of both knees as the result of bilateral large heterotopic ossification masses in popliteal fossae. The bony masses were surgically resected with acceptable outcome. The anatomic position of the ossified masses as well as ankylosis of both knees in full extension, and the acceptable functional outcome of surgery which was done after a long period of five years following injury makes this case unique.


Contrast expression patterns of JNK1 during sex reversal of the rice-field eel.
The c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase family. Their functions in regulating animal development have been well studied in both invertebrates and vertebrates. However, it remains to be determined whether they play a role in sex determination. Here we present first evidence to show that expression of JNK1 displays distinct patterns during sex reversal of rice-field eel. Molecular cloning reveals that JNK1 is well conserved among rice-field eel and other vertebrates. Both quantitative real-time polymerase chain reaction and Western blot analysis demonstrate that JNK1 is highly expressed in the ovary of the female individual and reduced to a substantial degree at the later stage of the intersex. However, when the intersex individual develops into the stage of male, expression of the JNK1 in the testis of the male individual is distinctly downregulated. Associated with the contrast JNK1 expression pattern in female and male gonads, several stem cell marker genes including Nanog, Oct-3/4, and Sox-2 were also differentially expressed in female and male germinal stem cells. Together, these results suggest it is possible that JNK1 plays an important role in sexual reversal of the rice-field eel.


Characterization of the promoter of Grapevine vein clearing virus.
Grapevine vein clearing virus (GVCV) is a recently discovered DNA virus in grapevine that is closely associated with the grapevine vein clearing syndrome observed in vineyards in Missouri and surrounding states. The genome sequence of GVCV indicates that it belongs to the genus Badnavirus in the family Caulimoviridae. To identify the GVCV promoter, we cloned portions of the GVCV large intergenic region in front of a GFP gene present in an Agrobacterium tumefaciens binary vector. GFP expression was assessed by ELISA 3 days after agroinfiltration of Nicotiana benthamiana leaves. We found that the GVCV DNA segment between nts 7332 and 7672 directed expression of GFP and this expression was stronger than expression using the Cauliflower mosaic virus 35S promoter. It was revealed by 5' and 3' RACE that transcription was initiated predominantly at nt 7571 and terminated at nt 7676.


Prospective study of the psychiatric disorders of childbirth.
A representative sample of 105 women were assessed by Goldberg's Standardised Psychiatric Interview (SPI) on two occasions during pregnancy and twice more in the puerperium. Total SPI scores increased significantly after childbirth. Thirteen of the sample had a severe postnatal depression and a further 17 women had milder depression, which in 15 lasted at four weeks. Marked deterioration of their martial relationships was reported by the depressed women but no other social or obstetric characteristics of postnatal depression were found. Women with severe postnatal blues were particularly at risk of developing persistent depressive symptoms subsequently. The only two women referred to a psychiatrist had personality disorders rather than depressive illnesses.


[Impact of a music therapy program on the stress level of health professionals].
The study aimed to assess the effects of a music therapy program on the level of stress for female professionals working in a private hospital in Rio de Janeiro-RJ, Brazil. Thirty four female volunteers with 33.3 ± 8.5 years of age from different levels of professional participated in the study. We used the Lipp's inventory of symptoms of stress for adults (ISSL) to evaluate the level of stress of participants before and after music therapy. The program consisted of twelve sessions using the techniques of music therapy Improvisation and Musical Re-creation held once a week with 50 minutes / session in a period of three months. The Wilcoxon test for repeated measures was used for statistical analysis. The study showed a statistically significant decrease (Δ = - 60%, p <0.001) in the level of stress professionals studied after the music therapy program. In conclusion, the present study that the music therapy program was effective in decrease the level of stress of women health professionals working in a private hospital in Rio de Janeiro-RJ, Brazil.


Functional Outcomes of Hip Arthroscopy for Pediatric and Adolescent Hip Disorders.
There is a paucity of literature on the use of hip arthroscopy for pathologic conditions in skeletally immature patients. Thus, the indications and safety of the procedure are still unclear. The purpose of this study was to investigate the safety and functional outcomes of hip arthroscopy for pediatric and adolescent hip disorders. We further attempted to characterize arthroscopic findings in each disease. We retrospectively reviewed 32 children and adolescents with hip disorders who underwent 34 hip arthroscopic procedures at a tertiary care children's hospital from January 2010 to December 2016. We evaluated functional limitations and improvement after operation by using the modified Harris hip score (HHS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), subjective pain assessment with a visual analog scale (VAS), and range of hip motion as well as the complications of hip arthroscopy. Arthroscopic findings in each disease were recorded. Hip arthroscopy was performed for Legg-Calvé-Perthes disease (n = 6), developmental dysplasia of the hip (n = 6), slipped capital femoral epiphysis (n = 5), idiopathic femoroacetabular impingement (n = 6), sequelae of septic arthritis of the hip (n = 3), hereditary multiple exostosis (n = 2), synovial giant cell tumor (n = 3), idiopathic chondrolysis (n = 2), and posttraumatic osteonecrosis of the femoral head (n = 1). Overall, there was a significant improvement in the modified HHS, WOMAC, VAS, and range of hip motion. Symptom improvement was not observed for more than 18 months in four patients who had dysplastic acetabulum with a labral tear (n = 2) or a recurrent femoral head bump (n = 2). There were no complications except transient perineal numbness in five patients. Our short-term follow-up evaluation shows that hip arthroscopy for pediatric and adolescent hip disorder is a less invasive and safe procedure. It appears to be effective in improving functional impairment caused by femoroacetabular impingement between the deformed femoral head and acetabulum or intra-articular focal problems in pediatric and adolescent hip disorders.


Integrative analysis of the microbiome and metabolome of the human intestinal mucosal surface reveals exquisite inter-relationships.
Consistent compositional shifts in the gut microbiota are observed in IBD and other chronic intestinal disorders and may contribute to pathogenesis. The identities of microbial biomolecular mechanisms and metabolic products responsible for disease phenotypes remain to be determined, as do the means by which such microbial functions may be therapeutically modified. The composition of the microbiota and metabolites in gut microbiome samples in 47 subjects were determined. Samples were obtained by endoscopic mucosal lavage from the cecum and sigmoid colon regions, and each sample was sequenced using the 16S rRNA gene V4 region (Illumina-HiSeq 2000 platform) and assessed by UPLC mass spectroscopy. Spearman correlations were used to identify widespread, statistically significant microbial-metabolite relationships. Metagenomes for identified microbial OTUs were imputed using PICRUSt, and KEGG metabolic pathway modules for imputed genes were assigned using HUMAnN. The resulting metabolic pathway abundances were mostly concordant with metabolite data. Analysis of the metabolome-driven distribution of OTU phylogeny and function revealed clusters of clades that were both metabolically and metagenomically similar. The results suggest that microbes are syntropic with mucosal metabolome composition and therefore may be the source of and/or dependent upon gut epithelial metabolites. The consistent relationship between inferred metagenomic function and assayed metabolites suggests that metagenomic composition is predictive to a reasonable degree of microbial community metabolite pools. The finding that certain metabolites strongly correlate with microbial community structure raises the possibility of targeting metabolites for monitoring and/or therapeutically manipulating microbial community function in IBD and other chronic diseases.


Targeting TARP, a novel breast and prostate tumor-associated antigen, with T cell receptor-like human recombinant antibodies.
MHC class I molecules are important components of immune surveillance. There are no available methods to directly visualize and determine the quantity and distribution of MHC/peptide complexes on individual cells or to detect such complexes on antigen-presenting cells in tissues. MHC-restricted recombinant antibodies with the same specificity of T cell receptors (TCR) may become a valuable tool to address these questions. They may also serve as valuable targeting molecules that mimic the specificity of cytotoxic T cells. We isolated by phage display a panel of human recombinant Fab antibodies with peptide-specific, MHC-restricted TCR-like reactivity directed toward HLA-A2-restricted T cell epitopes derived from a novel antigen termed TCRgamma alternative reading frame protein (TARP) which is expressed on prostate and breast cancer cells. We have characterized one of these recombinant antibodies and demonstrated its capacity to directly detect specific HLA-A2/TARP T cell epitopes on antigen-presenting cells that have complexes formed by naturally occurring active intracellular processing of the antigen, as well as on the surface of tumor cells. Moreover, by genetic fusion we armed the TCR-like antibody with a potent toxin and demonstrated that it can serve as a targeting moiety killing tumor cells in a peptide-specific, MHC-restricted manner similar to cytotoxic T lymphocytes.


Factors influencing publication rates of abstracts presented at the ADEA annual session & exhibition.
Factors related to the path of abstracts from presentation at a conference to publication as a full article have been analyzed in the medical field, but only a few studies have been performed in dentistry. This study investigated the rate of publication of articles based on abstracts presented at the American Dental Education Association (ADEA) Annual Session & Exhibition in 2002 and 2003 and the time lag to publication. This study also aimed to characterize the abstracts and subsequent articles and determine if there were any significant factors related to expansion of an abstract into a full manuscript. A total of 370 abstracts met the inclusion criteria and were examined for this study. Subsequent published articles were located using a standard PubMed search. Descriptive statistics and bivariate analyses were used to analyze the data collected (α=0.05). Results suggest that there was a low (19 percent) publication rate for articles based on abstracts presented at the meetings studied. The median time between abstract presentation and article publication was ten months. Factors that showed significant correlation to likelihood of article publication were multiple affiliations, presence of analytical statistics, and, to a lesser extent, funding. We suggest that presenters at these meetings should expand their abstracts into full manuscripts and seek to publish them in peer-reviewed journals for the benefit of the profession.


Recessive Inheritance of Congenital Hydrocephalus With Other Structural Brain Abnormalities Caused by Compound Heterozygous Mutations in ATP1A3.
ATP1A3 encodes the α3 subunit of the Na+/K+ ATPase, a fundamental ion-transporting enzyme. Primarily expressed in neurons, ATP1A3 is mutated in several autosomal dominant neurological diseases. To our knowledge, damaging recessive genotypes in ATP1A3 have never been associated with any human disease. Atp1a3 deficiency in zebrafish results in hydrocephalus; however, no known association exists between ATP1A3 and human congenital hydrocephalus (CH). We utilized whole-exome sequencing (WES), bioinformatics, and computational modeling to identify and characterize novel ATP1A3 mutations in a patient with CH. We performed immunohistochemical studies using mouse embryonic brain tissues to characterize Atp1a3 expression during brain development. We identified two germline mutations in ATP1A3 (p. Arg19Cys and p.Arg463Cys), each of which was inherited from one of the patient's unaffected parents, in a single patient with severe obstructive CH due to aqueductal stenosis, along with open schizencephaly, type 1 Chiari malformation, and dysgenesis of the corpus callosum. Both mutations are predicted to be highly deleterious and impair protein stability. Immunohistochemical studies demonstrate robust Atp1a3 expression in neural stem cells (NSCs), differentiated neurons, and choroid plexus of the mouse embryonic brain. These data provide the first evidence of a recessive human phenotype associated with mutations in ATP1A3, and implicate impaired Na+/K+ ATPase function in the pathogenesis of CH.


Describing and predicting the possession of assistive devices among persons with multiple sclerosis.
This study describes the types of assistive devices in the possession of persons with multiple sclerosis (MS) and identifies factors that best predicted the probability of possessing these devices. A secondary analysis using frequency distributions and logistic regression of existing cross-sectional data was completed. Data were from an anonymous mail survey of members of the Multiple Sclerosis Society of Canada (Atlantic Division) (N = 906). Mobility aids and grab bars were the most commonly reported assistive devices. Seeing an occupational therapist, not working, having a progressive type of MS, having more activity limitations and more symptoms, and having MS for a longer period were found to increase the probability of possessing assistive devices. The descriptive results of this study are similar to studies of assistive technology use by older adults and persons with other chronic conditions. Type of MS and seeing an occupational therapist were the two strongest predictors of possessing assistive devices among respondents.


The relationship among circulating insulin-like growth factor (IGF)-I, IGF-binding proteins-1 and -2, and birth anthropometry: a prospective study.
Fetal IGF-I is a determinant of birth weight, but whether maternal IGF-I plays a significant role is controversial. We sought to examine the relationships among maternal IGF-I, IGF-binding protein (IGFBP)-1, and IGFBP-2, with maternal and newborn anthropometry, in a cohort of 325 nondiabetic pregnant women of African origin. Blood was collected for IGF-I, IGFBP-1, and IGFBP-2 at 9, 25, and 35 wk gestation and in cord blood at delivery. In the second and third trimesters, maternal IGF-I was significantly correlated (P < 0.005) with maternal body mass index and triceps skinfold thickness. Maternal IGFBP-1 and -2 had an inverse correlation (P < 0.0001), with maternal anthropometry. Maternal IGF-I at 35 wk, and fetal IGF-I by cord blood were significantly correlated with birth weight (P = 0.001 and 0.048, respectively). IGFBP-1 in the third trimester and cord blood were negatively correlated with birth weight (P = 0.012 and 0.002). In multiple regression analyses, maternal IGF-I at 35 wk, fetal IGF-I, maternal weight at the first antenatal visit, gender, and gestational age were significant independent factors in the determination of birth weight. In conclusion, maternal IGF-I levels, especially during late pregnancy, positively influence birth weight.


Molecular pathogenesis of precursor lesions of pancreatic ductal adenocarcinoma.
Precursor lesions are assuming greater importance in the study of pancreatic ductal adenocarcinoma. As pancreatic cancer is almost universally fatal due to late clinical presentation and biological aggressiveness, characterisation of its precursor lesions may create scope for early diagnosis and improved outcome with conventional therapies as well as the development of novel therapeutic and preventative strategies. Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous tumours (IPMTs) are thought to be precursor lesions of ductal adenocarcinoma of the pancreas. Recent work has focused on the molecular aberrations associated with these lesions leading to the formulation of a progression model for pancreatic cancer. Progressive histopathological changes along the progression model are associated with aberrations of cell cycle regulatory and growth factor signalling molecules that occur in pancreatic cancer at high frequency and are common to many cancers. Characterisation of these molecular aberrations provides scope for the development of novel diagnostic and treatment strategies that will ultimately impact on the outcome for people who develop pancreatic cancer.


Enhancing glycolysis attenuates Parkinson's disease progression in models and clinical databases.
Parkinson's disease (PD) is a common neurodegenerative disease that lacks therapies to prevent progressive neurodegeneration. Impaired energy metabolism and reduced ATP levels are common features of PD. Previous studies revealed that terazosin (TZ) enhances the activity of phosphoglycerate kinase 1 (PGK1), thereby stimulating glycolysis and increasing cellular ATP levels. Therefore, we asked whether enhancement of PGK1 activity would change the course of PD. In toxin-induced and genetic PD models in mice, rats, flies, and induced pluripotent stem cells, TZ increased brain ATP levels and slowed or prevented neuron loss. The drug increased dopamine levels and partially restored motor function. Because TZ is prescribed clinically, we also interrogated 2 distinct human databases. We found slower disease progression, decreased PD-related complications, and a reduced frequency of PD diagnoses in individuals taking TZ and related drugs. These findings suggest that enhancing PGK1 activity and increasing glycolysis may slow neurodegeneration in PD.


Positive and negative correlations between confidence and accuracy for the same events in recognition of categorized lists.
Different researchers have reported positive, null, and negative relationships between confidence and accuracy in reports from memory. One possible reason for this paradox is the variety of materials used across experiments, but the two experiments reported in this article show that positive and negative confidence-accuracy correlations can be observed using a single procedure and the same materials. Subjects studied words from semantic categories and then took a recognition test while making confidence ratings. For previously studied items, positive correlations between confidence and accuracy were obtained using three different measures. Yet when confidence-accuracy correlations were assessed for unstudied items from studied categories, the correlations were zero or negative. The critical factors in determining when negative correlations will be found are the similarity of lures to presented items and the type of analysis used. These results indicate that one should be cautious about relying on confidence of recognition when rememberers must decide among highly similar events.


Characteristics of acute ischemic stroke in patients with Nephrotic syndrome.
The incidence of ischemic stroke (IS) is higher in nephrotic syndrome (NS) patients compared to general population. However, there is limited information on the specific characteristics to stroke patients with NS. In this study, we aimed to examine the clinical manifestations of acute IS in a large group of NS patients, comparing to those without NS. We conducted a retrospective cohort study to compare the clinical presentations of acute IS in patients with and without NS. This study was a multi-institutional study and used data from Chang Gung Research Database of Taiwan from 1 January 2001, to 31 December 2017. A total of 233 IS patients with NS and 1358 IS patients without NS were enrolled. The median age of participants was 68 (range: 59-79) years. The risk of dependent functional status (modified Rankin Scale score≧3) after IS was higher in NS patients compared to those without NS (Odd ratio (OR) 4.02, 95% confidence interval (CI) 2.39 to 6.76, p < 0.001), particularly in stroke subtypes as small-artery occlusion (OR 8.02, 95% CI 3.94 to 16.32, p < 0.001), and stroke of undetermined etiology (OR 2.47, CI 1.06 to 5.76, p = 037). The risks of mortality or stroke recurrence within 30 days were similar between the two groups for all stroke subtypes. In conclusion, NS was associated with a higher risk of functional dependence following IS. Intensive treatment and rehabilitation should be considered for IS patients with NS.


Stress fractures in the Israeli defense forces from 1995 to 1996.
This study, encompassing 2591 Israeli soldiers, characterized Israeli soldiers with stress fractures to profile individuals who are prone to experience stress fractures: 318 with clinically and scintigraphically proven high grade stress fractures; 237 soldiers with symptoms but with normal scintigraphy; and 2036 soldiers with no symptoms. Soldiers with high grade stress fractures weighed less (68.4 +/- 7.9 kg versus 70.5 +/- 12.4 kg), smoked less, and reported fewer previous stress fractures, had fewer reports of stress fractures in their family histories, and had fewer incidences of bone diseases than did control subjects. Serum levels of bone specific alkaline phosphatase and osteocalcin were elevated in patients with high grade stress fractures compared with control subjects with no symptoms: 37.6 versus 26.2 units/L, and 10.8 versus 8.8 ng/mL, respectively. Levels of 25-hydroxy vitamin D were lower in patients with high grade stress fractures (25.3 ng/mL) than in control subjects (29.8 ng/mL). This study revealed that several parameters can distinguish soldiers with high grade stress fractures, but their predictive value and precise pathogenetic role remain unclear.


The RecQ helicase WRN is required for normal replication fork progression after DNA damage or replication fork arrest.
Werner syndrome is an autosomal recessive genetic instability and cancer predisposition syndrome with features of premature aging. Several lines of evidence have suggested that the Werner syndrome protein WRN plays a role in DNA replication and S-phase progression. In order to define the exact role of WRN in genomic replication we examined cell cycle kinetics during normal cell division and after methyl-methane-sulfonate (MMS) DNA damage or hydroxyurea (HU)-mediated replication arrest following acute depletion of WRN from human fibroblasts. Loss of WRN markedly extended the time cells needed to complete the cell cycle after either of these genotoxic treatments. Moreover, replication track analysis of individual, stretched DNA fibers showed that WRN depletion significantly reduced the speed at which replication forks elongated in vivo after MMS or HU treatment. These results establish the importance of WRN during genomic replication and indicate that WRN acts to facilitate fork progression after DNA damage or replication arrest. The data provide a mechanistic basis for a better understanding of WRN-mediated maintenance of genomic stability and for predicting the outcomes of DNA-targeting chemotherapy in several adult cancers that silence WRN expression.


Head and neck cancers: post-therapy changes in muscles with FDG PET-CT.
FDG PET-CT plays a critical role in the management of head and neck cancer patients. After therapy, many patterns of altered physiologic FDG uptake have been recognized. In our institution, we noticed patterns of head and neck muscle uptake that were unique in the post-therapy scans of head and neck cancer patients. A total of 32 patients with head and neck cancers who had both pretherapy and posttherapy FDG PET-CT scans were retrospectively analyzed. Regional anatomic muscle groups that had increased PET uptake on either pretherapy or post-therapy scans were identified. On the pretherapy scans, the majority of patients (24/32 patients) did not have increased PET activity in the predefined muscle groups. On the post-therapy scans, the majority of patients (25/32 patients) demonstrated increased uptake in at least 1 head and neck muscle group, with an average of 3 muscle groups per patient. The muscle groups with the greatest frequencies were the prevertebral (50%), the accessory neck (47%), the posterior paravertebral (47%), and the scalene muscles (38%). Relative to pretherapy scans, the mean intensity of the post-therapy elevations corresponded to greater SUVs. FDG PET-CT scan commonly depicts an elevated FDG muscle uptake in all regional anatomic muscle groups in the post-therapy head and neck cancer patient. This uptake should be considered as a consequence of treatment and perhaps changes in altered biomechanics, and not be confused with residual or recurrent neoplastic activity.


Profile of oritavancin and its potential in the treatment of acute bacterial skin structure infections.
Oritavancin, a semisynthetic derivative of the glycopeptide antibiotic chloroeremomycin, received the US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections caused by susceptible Gram-positive bacteria in adults in August 2014. This novel second-generation semisynthetic lipoglycopeptide antibiotic has activity against a broad spectrum of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant Enterococcus. Oritavancin inhibits bacterial cell wall synthesis and is rapidly bactericidal against many Gram-positive pathogens. The long half-life of this drug enables a single-dose administration. Oritavancin is not metabolized in the body, and the unchanged drug is slowly excreted by the kidneys. In two large Phase III randomized, double-blind, clinical trials, oritavancin was found to be non-inferior to vancomycin in achieving the primary composite end point in the treatment of acute Gram-positive skin and skin structure infections. Adverse effects noted were mostly mild with nausea, headache, and vomiting being the most common reported side effects. Oritavancin has emerged as another useful antimicrobial agent for treatment of acute Gram-positive skin and skin structure infections, including those caused by MRSA and VISA.


Insulin resistance and beta-cell dysfunction in people with prediabetes according to criteria based on glycemia and glycosylated hemoglobin.
Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are well-known conditions of risk for diabetes. Recently, 1h-hyperglycemia (1h-HG), i.e., glycemia > 8.6 mmol/L, has been suggested as further condition of diabetes risk. Moreover, in 2010 the American Diabetes Association included the measurement of glycosylated hemoglobin (HbA1c) among the criteria of diabetes risk (5.7-6.4%). Aim of this study was investigating all these different conditions of diabetes risk, with specific focus on possible insulin sensitivity and beta-cell function changes, when 1h-HG, and further HbA1c-prediabetes, are added to the already deeply studied condition of IFG/IGT. In this study, we retrospectively analysed 744 participants that underwent 2h-OGTT and HbA1c measurement. Participants were stratified into groups: (i) normal glucose tolerance, NGT (n=178); (ii) IFG and/or IGT (n=88); (iii) IFG/IGT plus 1h-HG (n=342); (iv) IFG/IGT plus 1h-HG plus HbA1c-prediabetes (n=136). We calculated several indices of insulin sensitivity and beta-cell function, as well as an index considering both aspects (disposition index). We found that progressing from group (i) to group (iv) both insulin sensitivity and beta-cell function tended to further deteriorate; the parameter providing more evidence was the disposition index (p<0.008 in any group comparison). In conclusion, for appropriate assessment of the level of diabetes risk (especially in people already known to be at high risk), it may be convenient to measure all the indicated parameters, that is, glycemia at fasting, at one hour and two hours during OGTT, and glycosylated hemoglobin.


Spanish adaptation of the scale of psychological empowerment in the workplace.
The objective of this study is to adapt and translate into Spanish Spreitzer's Psychological Empowerment Scale (1995a). A process of translation and reverse-translation was applied to the scale's items, whose psychometric properties were then examined using a sample of 272 professional nurses at public hospitals in the province of Seville. The data were subjected to confirmatory factor analysis. The significance of the factor loadings demonstrated the need to create a new model eliminating one item. The 11-item model was shown to possess adequate construct validity and internal consistency. The results confirm the original, four-factor structure obtained by Spreitzer, with the exception of item 10, and support the utilization of the Spanish version of this scale in the workplace. Future research should more extensively investigate its construct validity, and test the nomological network of the operationalized construct within the field of psychological well-being and in the context of the workplace.


Isolated tricuspid valve surgery: impact of aetiology and clinical presentation on outcomes.
The aim of this study was to identify determinants of in-hospital and mid-term outcomes after isolated tricuspid valve surgery (ITVS) and more specifically the impact of tricuspid regurgitation (TR) mechanism and clinical presentation. Among 5661 consecutive adult patients who underwent a tricuspid valve (TV) surgery at 12 French tertiary centres in 2007-2017 collected from a mandatory administrative database, we identified 466 patients (8% of all tricuspid surgeries) who underwent an ITVS. Most patients presented with advanced disease [47% in New York Heart Association (NYHA) III/IV, 57% with right-sided heart failure (HF) signs]. Tricuspid regurgitation was functional in 49% (22% with prior left-sided heart valve surgery and 27% isolated) and organic in 51% (infective endocarditis in 31% and other causes in 20%). In-hospital mortality and major complications rates were 10% and 31%, respectively. Rates of survival and survival free of HF readmission were 75% and 62% at 5 years. Patients with functional TR incurred a worse in-hospital mortality than those with organic TR (14% vs. 6%, P = 0.004), but presentation was more severe. Independent determinants of outcomes were NYHA Class III/IV [odd ratios (OR) = 2.7 (1.2-6.1), P = 0.01], moderate/severe right ventricular dysfunction [OR = 2.6 (1.2-5.8), P = 0.02], lower prothrombin time [OR = 0.98 (0.96-0.99), P = 0.008], and with borderline statistical significance, right-sided HF signs [OR = 2.4 (0.9-6.5), P = 0.06] while TR mechanism was not [OR = 0.7 (0.3-1.8), P = 0.88]. Isolated TV surgery was associated with high mortality and morbidity, both in hospital and during follow-up, predicted by the severity of the presentation but not by TR mechanism. Our results suggest that TV intervention should be performed earlier in the course of the disease.


Inflammation plays a critical role in damage to the bronchiolar epithelium induced by Trueperella pyogenes in vitro and in vivo.
Trueperella pyogenes can cause severe pulmonary disease in swine, but the mechanism of pathogenesis is not well defined. T. pyogenes-induced damage to porcine bronchial epithelial cells (PBECs), porcine precision-cut lung slices (PCLS), and respiratory epithelium of mice remains unknown. In this study, we used T. pyogenes 20121 to infect PBECs in air-liquid interface conditions and porcine PCLS. T. pyogenes could adhere to, colonize, and induce cytotoxic effect on PBECs and the luminal surface of bronchi in PCLS, which damaged the bronchiolar epithelium. Moreover, bronchiolar epithelial cells showed extensive degeneration in the lungs of infected mice. Furthermore, western blot showed that the NOD-like receptor (NLR)/C-terminal caspase recruitment domain (ASC)/caspase-1 axis and nuclear factor-kappa B pathway were involved in inflammation in PCLS and lungs of mice, which also confirms that porcine PCLS provide a platform to analyze the pulmonary immune response. Meanwhile, the levels of p-c-Jun N-terminal kinase, p-extracellular signal-regulated kinase, and p-protein kinase B (AKT) were increased significantly, which indicated the mitogen-activated protein kinase and Akt pathways were also involved in inflammation in T. pyogenes-infected mice. In addition, we used T. pyogenes 20121 to infect tumor necrosis factor-alpha (tnf-α-/-) mice, and the results indicated that apoptosis and injury in respiratory epithelium of infected tnf-α-/- mice were alleviated. Thus, the pro-inflammatory cytokine TNF-α played a role in apoptosis and the respiratory epithelium injury in mouse lungs. Collectively, our study provides insight into the inflammatory injury induced by T. pyogenes and suggests that blocking NLR may be a potential therapeutic strategy against T. pyogenes infection.


Monitoring metabolic side effects of atypical antipsychotics in people with an intellectual disability.
This audit was undertaken prospectively to examine the compliance of a group of psychiatrists against guidelines they developed for monitoring the onset of metabolic syndrome, a potential side effect of antipsychotic medication, especially second generation or atypical ones. Phase 1 of the audit was to set standards by a questionnaire survey of participating psychiatrists against Consensus Guidelines on monitoring (American Diabetic Association, 2004), which they favoured. The results led to modifying these guidelines to develop minimum acceptable standards against which their practice was audited in Phase 2. Although in Phase 1, 77% of the psychiatrists felt that they did some baseline recording, Phase 2 finding did not corroborate this--only 53.8% of the notes recorded the assessment of risk factors in personal history; 37.5% risk factors in family history; 31.7% baseline weight and 26.4% baseline blood sugar/lipid levels. In Phase 1, 85% of the psychiatrists thought that they carried out some of the recommended monitoring; our audit found the records of weight monitoring in 69.7% of the notes and blood sugar and lipids monitoring in 44.2%. People with intellectual disability have a shorter life expectancy and increased risk of early death when compared with the general population. Obesity is already a health issue for people with intellectual disability. We discuss the challenges faced by psychiatrists in implementing their own minimum acceptable standards and suggest measures to reduce the metabolic risk associated with antipsychotic medication through increasing awareness--use of information leaflets in accessible format, health promotion and use of side effect checklists and improving access--by working collaboratively with general practitioners utilising the forum of annual health checks.


Tumor-derived exosomes in the regulation of macrophage polarization.
This review focuses on exosomes derived from various cancer cells. The review discusses the possibility of differentiating macrophages in alternatively activated anti-inflammatory pro-tumorigenic M2 macrophage phenotypes and classically activated pro-inflammatory, anti-tumorigenic M1 macrophage phenotypes in the tumor microenvironment (TME). The review is divided into two main parts, as follows: (1) role of exosomes in alternatively activating M2-like macrophages-breast cancer-derived exosomes, hepatocellular carcinoma (HCC) cell-derived exosomes, lung cancer-derived exosomes, prostate cancer-derived exosomes, Oral squamous cell carcinoma (OSCC)-derived exosomes, epithelial ovarian cancer (EOC)-derived exosomes, Glioblastoma (GBM) cell-derived exosomes, and colorectal cancer-derived exosomes, (2) role of exosomes in classically activating M1-like macrophages, oral squamous cell carcinoma-derived exosomes, breast cancer-derived exosomes, Pancreatic-cancer derived modified exosomes, and colorectal cancer-derived exosomes, and (3) exosomes and antibody-dependent cellular cytotoxicity (ADCC). This review addresses the following subjects: (1) crosstalk between cancer-derived exosomes and recipient macrophages, (2) the role of cancer-derived exosome payload(s) in modulating macrophage fate of differentiation, and (3) intracellular signaling mechanisms in macrophages regarding the exosome's payload(s) upon its uptake and regulation of the TME. Under the electron microscope, nanoscale exosomes appear as specialized membranous vesicles that emerge from the endocytic cellular compartments. Exosomes harbor proteins, growth factors, cytokines, lipids, miRNA, mRNA, and DNAs. Exosomes are released by many cell types, including reticulocytes, dendritic cells, B-lymphocytes, platelets, mast cells, and tumor cells. It is becoming clear that exosomes can impinge upon signal transduction pathways, serve as a mediator of signaling crosstalk, thereby regulating cell-to-cell wireless communications. Based on the vesicular cargo, the molecular constituents, the exosomes have the potential to change the fate of macrophage phenotypes, either M1, classically activated macrophages, or M2, alternatively activated macrophages. In this review, we discuss and describe the ability of tumor-derived exosomes in the mechanism of macrophage activation and polarization.


Design of a lens-to-channel waveguide system as a solar concentrator structure.
We present a lens-to-channel waveguide solar concentrator, where the lens array and the channel waveguide act as the primary and the secondary concentrator. Sunlight collected by the lens array is coupled into channel waveguides and exits from one end of the tapered waveguide directly onto photovoltaic cells. A 45°coupler is placed at each lens focal point to couple light into the waveguides. This configuration eliminates any inherent decoupling losses. We provide a detailed math model and simulation results using exemplar system parameters, showing that this structure can achieve 800x concentration at 89.1% optical efficiency under ±0.7° incidence angle.


The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration.
Parkinson's disease (PD) is characterized by the accumulation of misfolded and aggregated α-synuclein (α-syn) into intraneuronal inclusions named Lewy bodies (LBs). Although it is widely believed that α-syn plays a central role in the pathogenesis of PD, the processes that govern α-syn fibrillization and LB formation remain poorly understood. In this work, we sought to dissect the spatiotemporal events involved in the biogenesis of the LBs at the genetic, molecular, biochemical, structural, and cellular levels. Toward this goal, we further developed a seeding-based model of α-syn fibrillization to generate a neuronal model that reproduces the key events leading to LB formation, including seeding, fibrillization, and the formation of inclusions that recapitulate many of the biochemical, structural, and organizational features of bona fide LBs. Using an integrative omics, biochemical and imaging approach, we dissected the molecular events associated with the different stages of LB formation and their contribution to neuronal dysfunction and degeneration. In addition, we demonstrate that LB formation involves a complex interplay between α-syn fibrillization, posttranslational modifications, and interactions between α-syn aggregates and membranous organelles, including mitochondria, the autophagosome, and endolysosome. Finally, we show that the process of LB formation, rather than simply fibril formation, is one of the major drivers of neurodegeneration through disruption of cellular functions and inducing mitochondria damage and deficits, and synaptic dysfunctions. We believe that this model represents a powerful platform to further investigate the mechanisms of LB formation and clearance and to screen and evaluate therapeutics targeting α-syn aggregation and LB formation.


13C and 31P NMR study of gluconeogenesis: utilization of 13C-labeled substrates by perfused liver from streptozotocin-diabetic and untreated rats.
The metabolism of 13C-labeled substrates was followed by 13C and 31P NMR in perfused liver from the streptozotocin-treated rat model of insulin-dependent diabetes. Comparison was made with perfused liver from untreated littermates, fasted either 24 or 12 h. The major routes of pyruvate metabolism were followed by a 13C NMR approach that provided for the determination of the metabolic fate of several substances simultaneously. The rate of gluconeogenesis was 2-4-fold greater and beta-hydroxybutyrate production was 50% greater in liver from the chronically diabetic rats as compared with the control groups. Large differences in the distribution of 13C label in hepatic alanine were measured between diabetic and control groups. The biosyntheses of 13C-labeled glutathione and N-carbamoylaspartate were monitored in time-resolved 13C NMR spectra of perfused liver. Assignments for the resonances of glutathione and N-carbamoylaspartate were made with the aid of 13C NMR studies of perchloric acid extracts of the freeze-clamped livers. 13C NMR spectroscopy of the perfusates provided a convenient, rapid assay of the rate of oxidation of [2-13C]ethanol, the hepatic output of [2-13C]acetaldehyde, and the accumulation of [2-13C]acetate in the perfusate. By 31P NMR spectroscopy, carbamoyl phosphate was measured in all diabetic livers and an unusual P,P'-diesterified pyrophosphate was observed in one-fourth of the diabetic livers examined. Neither of these phosphorylated metabolites was detected in control liver. Both 13C and 31P NMR were useful in defining changes in hepatic metabolism in experimental diabetes.


Relative sensitivity of postpartum gestational diabetic women to oral contraceptive agents and other metabolic stress.
Women who develop diabetes mellitus during pregnancy very often revert to normal carbohydrate metabolism after parturition. During this quiescent period, however, increased sensitivity to adverse metabolic stress is evident. Recurrence of impaired carbohydrate tolerance with greater frequency than in normal populations is observed following the administration of oral contraceptive agents, glucocorticoids, and certain placental hormones such as human chorionic somatomammotropin. Factors responsible for this vulnerability to adverse stress are unknown but, in part, may reside in subclinical defects in beta-cell function. Ultimately, the great majority of these individuals develop permanent disease, suggesting that diabetes initially manifested only during pregnancy is not transient but progresses to more severe forms later in life.


Clinical and laboratory features of rickettsioses in Yucatan, Mexico.
Rickettsia species are obligate intracellular bacteria that can cause mild to severe human disease. Based on phylogeny, clinical symptoms, and antigenic properties, rickettsiae are classified into four groups. Infections by these agents are characterized by clinical symptoms ranging from self-limited to severe and even fatal febrile illnesses, depending on the Rickettsia spp. involved, the patient's predisposition, and timely medical care. The present study aimed to characterize rickettsial diseases in Yucatan according to clinical and laboratory features appearing in medical records corresponding to 427 samples taken between 2015 and 2018. A study was conducted over the period 2015-2018 on 427 samples. Clinical and laboratory features were documented from the patients' medical records. For molecular diagnosis, blood was collected in 3.8 % sodium citrate as anticoagulant, and DNA was extracted. Single-step and nested PCR amplification was performed using genus-specific primers for the rickettsial 17kDa and ompB genes. The amplicons obtained were purified and sequenced. A total of 22.7 % (97/427) positive cases of Rickettsia spp. were identified by PCR from 14.15 % (15/106) of the municipalities in Yucatan. 75.2 % (73/97) of the cases were from the city of Merida during the autumn (September-December). The age groups with the highest frequency of confirmed cases were pediatric (5-14 years) (57.7 %) and adults (25-49 years) (42.2 %). There were six fatal cases in children, one associated with R. typhi and five with R. rickettsii. In non-fatal cases, 32.9 % (32/97) corresponded to the spotted fever group (SFG), and 60.8 % (59/97) to the typhus group (TG). Significant differences in signs, and laboratory data, were observed between the pediatric and adult populations. For the treatment of patients, oral and intravenous doxycycline was used in severe hospitalized cases. Typhus group and spotted fever group Rickettsiae are endemic pathological agents found in urban and rural areas of our region. Molecular identification allows for greater diagnostic accuracy and timely treatment and consequently a better prognosis. It is necessary to implement or reinforce measures focused on the dissemination of knowledge regarding rickettsial diseases and their prevention.


Does postoperative radiation therapy represent a contraindication to expander-implant based immediate breast reconstruction? An update 2012-2014.
Post-mastectomy radiotherapy (PMRT) is well known in the plastic surgery community for having a negative impact on expander-implant based immediate breast reconstruction (IBBR), although recently some technical improvements allow better results. Very recent papers would suggest that there is no difference in postoperative complications in patients receiving post-mastectomy radiotherapy using modern techniques. However, study results are often biased by small groups of patients and by heterogeneity of radiotherapy timing, different surgical techniques and measured outcomes. We have conducted a MEDLINE search to summarize the latest data (2012-2014) on the topic. Search was conducted using the following parameters: breast reconstruction AND implant AND expander AND post-mastectomy radiotherapy. The MEDLINE search showed 53 reports, demonstrating a great interest on this topic; among these 37 dealed specifically with post-mastectomy radiotherapy after breast reconstruction. In particular, 15 were amenable to plastic surgeons, 6 to breast surgeons, 9 to radiotherapists and 7 to oncologists. Papers amenable to plastic surgeons highlighted the highest rate of undesired results, although with recent advances such as delayed-immediate reconstruction or protective lipofilling. PMRT remains an undesired event when pursuing an implant-based breast reconstruction, although it does not represent an absolute contraindication. The higher rate of complications reported by plastic surgeons and not by other specialists can be explained with the greater attention to aesthetic details, such as capsular contractures, that our community has. Technical strategies to prevent complications described in this community now allow better results, should be well known and improved if possible in the future.


The heritability of reading and reading-related neurocognitive components: A multi-level meta-analysis.
Reading ability is a complex task requiring the integration of multiple cognitive and perceptual systems supporting language, visual and orthographic processes, working memory, attention, motor movements, and higher-level comprehension and cognition. Estimates of genetic and environmental influences for some of these reading-related neurocognitive components vary across reports. By using a multi-level meta-analysis approach, we synthesized the results of behavioral genetic research on reading-related neurocognitive components (i.e. general reading, letter-word knowledge, phonological decoding, reading comprehension, spelling, phonological awareness, rapid automatized naming, and language) of 49 twin studies spanning 4.1-18.5 years of age, with a total sample size of more than 38,000 individuals. Except for language for which shared environment seems to play a more important role, the causal architecture across most of the reading-related neurocognitive components can be represented by the following equation a² > e² > c². Moderators analysis revealed that sex and spoken language did not affect the heritability of any reading-related skills; school grade levels moderated the heritability of general reading, reading comprehension and phonological awareness.


Diarrhoea and malabsorption in acquired immune deficiency syndrome: a study of four cases with special emphasis on opportunistic protozoan infestations.
Chronic diarrhoea is frequent in acquired immune deficiency syndrome (AIDS) but has been poorly investigated so far. We report four patients with AIDS in whom diarrhoea and malabsorption were outstanding features, and who underwent extensive digestive investigations. Diarrhoea was a presenting symptom in all subjects and was of secretory type in three of them. D-xylose and vitamin B12 were malabsorbed in all cases; steatorrhea was found in the two patients who could ingest significant amounts of fat. Faecal alpha 1-antitrypsin clearance was increased in all subjects. Search for digestive pathogens showed unusual protozoans in all patients: in case 1, optical and electron microscopy revealed the presence in the cytoplasm of villous enterocytes of Microsporidia protozoans still unreported in AIDS. Stool and jejunal fluid examination showed Isospora belli in case 2 and Cryptosporidium in cases 3 and 4. On histological and ultrastructural study the former was localised in the cytoplasm of a few enterocytes and the latter was scattered throughout the villus and crypt brush border. Otherwise small intestinal histology only showed minor non-specific changes and the enterocytes were ultrastructurally normal. In patient 3 the slow marker intestinal perfusion technique showed a profuse fluid secretion in the duodenum and proximal jejunum. All patients needed prolonged total parenteral nutrition. Cryptosporidium and Microsporidia could not be eradicated despite multiple drug trials. Isospora belli was transiently cured by pyrimethamine-sulphadiazine. Only patient 2 is presently at home, and patients 1, 3, and 4 died after two, six, and nine months of total parenteral nutrition, respectively.


Urine interleukin-8 as a marker of vesicoureteral reflux in infants.
Vesicoureteral reflux (VUR) is a common finding in children presenting with urinary tract infection (UTI) and prenatally diagnosed urinary tract dilatation and in relatives of index patients. Children with VUR are at risk for ongoing renal damage with subsequent infections. Detecting VUR and renal scarring currently depends on imaging modalities with associated problems of radiation, invasiveness, and expense. Noninvasive methods would greatly facilitate diagnosis and would also help in identifying relatives of index cases who should be screened. Interleukin-8 (IL-8) is produced by epithelial cells of the renal tract in response to inflammatory stimuli and has been shown to increase during acute UTI. The objective of this study was to assess the urine levels of IL-8 as a noninvasive marker of VUR in infants in the absence of a recent UTI episode. We evaluated urine concentrations of IL-8 in 59 infants aged 1 month to 2 years. All infants were free of UTI for a minimum of 3 weeks before IL-8 evaluation. Infants were divided into 3 groups: group A, subjects with proven VUR (24 infants aged 0.15-1.95 years, median 0.43); group B, subjects with a history of UTI but negative investigation for VUR (14 infants aged 0.32-1.95 years, median 0.57); and group C, subjects without any history of acute or chronic condition that might impair renal function (21 infants aged 0.08-1.92 years, median 0.33). IL-8 concentrations were determined by a commercially available quantitative enzyme-linked immunosorbent assay. To avoid dilution effects, urinary levels of IL-8 were expressed as the ratio of cytokine-to-urinary creatinine. Results were presented as medians and ranges. The Kruskal-Wallis test, the Mann-Whitney rank sum U test, and the Spearman rank order correlation test were performed for the univariate analysis. Two-tailed P values were calculated and the conventional level of significance P < .05 was applied in all cases. Infants in groups A and B had been free of UTI for a period of 3 to 52 weeks (median, 5.0 weeks) and 3 to 78 weeks (median, 4.5 weeks), respectively, before IL-8 determination. No significant difference was noted in the length of the UTI-free period between groups A and B (P = .469). Urine creatinine concentrations did not differ among groups A, B, and C (medians 1.15, 2.25, and 1.15 micromol/mL, respectively; P = .080). The median urine IL-8/creatinine concentrations (pg/micromol) were 40.5 (range, 2.04-3874) in group A, 1.91 (range, 0.001-386) in group B, and 2.47 (range, 0.002-55.6) in group C. Urine IL-8/creatinine concentrations were significantly higher in group A than both in group B (P = .0003) and in group C (P < .0001). No significant difference was observed between groups B and C (P = .749). In group A, no significant correlation was shown between IL-8/creatinine concentrations and the presence of renal parenchymal damage (P = .506), reflux grade (P = .770), or time from UTI (P = .155). A receiver-operator characteristic curve was constructed by plotting the sensitivity versus the specificity for different cutoff concentrations of IL-8/creatinine. With a cutoff concentration of urinary IL-8/creatinine at 5 pg/micromol, the sensitivity of this marker in diagnosing VUR was 88%, the specificity 69%, the positive prognostic value 66%, and the negative prognostic value 89%. In higher cutoff concentrations, specificity of the marker increased but sensitivity rapidly decreased. We present evidence that urine IL-8 concentrations remain elevated in infants with VUR even in the absence of UTI and that a cutoff of 5 pg/micromol IL-8/creatinine is of high sensitivity and adequate specificity for diagnosing VUR. Elevated urine IL-8 levels in VUR and renal scarring have already been reported; however, the present study is, to our knowledge, the first to confirm significant differences between infants with VUR and infants with a history of UTI alone and healthy controls, and to suggest a reliable cutoff concentration for diagnosing VUR. Our findings additionally suggest that inflammatory process in VUR is ongoing even after UTI has resolved, pointing against the currently held belief that sterile reflux cannot harm kidneys. The chronic inflammatory cell infiltrate associated with reflux nephropathy rather than VUR itself might offer an explanation for the secretion of IL-8, which may well be independent of reflux grade. Using urine IL-8 for diagnosing VUR is not free of limitations, because IL-8 may be elevated as a result of urinary tract manipulation or undetected UTI. In addition, this study focused on infants and not in older children with longstanding VUR. Increased urine IL-8 concentrations after UTI has resolved is a promising noninvasive marker for an initial screening for VUR in infancy with high sensitivity and adequate specificity.


[Analysis of DSG2, TTN and GATA4 gene variants in patients with Brugada syndrome from Henan].
To explore the correlation between DSG2, TTN and GATA4 genes and Brugada syndrome in Henan Province of China. From February 2017 to February 2019, 100 patients with Brugada syndrome and 100 healthy individuals were selected as the study and the control groups, respectively. Electrocardiogram and echocardiography were carried out, and peripheral blood samples was collected. Coding regions of DSG2, TTN and GATA4 genes were amplified by PCR and sequenced. The results were compared with standard sequences from GenBank. Electrocardiogram showed that all patients from the study group had ventricular arrhythmia, 87 cases (87%) presented ventricular tachycardia (VT), 84 cases (84%) presented T wave inversion, and 51 cases (51%) presented Epsilon wave. Echocardiography showed that the right ventricle in the study group was enlarged with the inner diameter of the right ventricle being (40.0±13.3) mm, and the right ventricle showed various degree of abnormal systolic function. The enlargement of right atrium accounted for 64%, and the involvement of the left ventricle accounted for 27%. The right ventricular diameter and left ventricular diastolic diameter of the study group were significantly greater than those of the control group (P< 0.05). DNA sequencing showed that 60 patients carried DSG2 gene variants, among which 18 had missense variant of exon 8. Fifty patients carried TTN gene variants, including 8 in the A-band domain and 3 in the I-band domain. Twenty patients carried 3 variants of the GATA4 gene. Variants of the DSG2, TTN and GATA4 genes in Henan region are correlated with the onset of Brugada syndrome.


[Anaphylactic shock caused by ethyl alcohol ingestion].
This article reports an unusual case of a 34 years old female who developed a near fatal anaphylactic shock 15 minutes after drinking an alcoholic beverage. Six year before, with different kinds of alcoholic beverages she developed generalized urticaria cleared without medication. Although the precise mechanism of our patient reaction could not be elucidated, the wide variety of ethanol containing beverages suggest that ethanol or its metabolites was the offending allergen acting as hapten.


[Neurologic aspects of Ito's hypomelanosis].
Hypomelanosis of Ito (incontinentia pigmenti achromians) is a neurocutaneous syndrome consisting of bizarre, patterned, macular hypopigmentation over variable portions of the body surface. Associated defects in other systems occur, commonly in the central nervous system, in a significant percentage of affected individuals. Six children affected by hypomelanosis of Ito are presented. Similarities and differences between hypomelanosis and incontinentia pigmenti and systematized achromic nevus are discussed.


Insights into muscle degeneration from heritable inclusion body myopathies.
Muscle mass and function are gradually lost in age-related, degenerative neuromuscular disorders, which also reflect the clinical hallmarks of sarcopenia. The consensus definition of sarcopenia includes a condition of age-related loss of muscle mass, quality, and strength. The most common acquired muscle disease affecting adults aged over 50 years is sporadic inclusion body myositis (sIBM). Besides inflammatory effects and immune-mediated muscle injury, degenerative myofiber changes are characteristic features of the disease. Although the earliest triggering events in sIBM remain elusive, a plethora of downstream mechanisms are implicated in the pathophysiology of muscle wasting. Although it remains controversial whether hereditary forms of inclusion body myopathy (IBM) may be considered as degenerative sIBM disease models, partial pathophysiological aspects can mimic the much more frequent sporadic condition, in particular the occurrence of inclusion bodies in skeletal muscle. Various clinical aspects in genetically determined skeletal muscle disorders reflect age-related alterations observed in sarcopenia. Several intriguing clues from monogenic defects in heritable IBMs contributing to the molecular basis of muscle loss will be discussed with special emphasis on inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) and GNE myopathy. Finally, also the recently identified dominant multisystem proteinopathy will be considered, which may rarely present as IBM.


Batch map extensions of the kernel-based maximum entropy learning rule.
In this letter, two batch-map extensions are described for the kernel-based maximum entropy learning rule (kMER). In the first, the weights are iteratively set to weighted component-wise medians, while in the second the generalized median is used, enabling kMER to process symbolic data. Simulations are performed to illustrate the extensions.


Utilization of RAPD markers to assess genetic diversity of wild populations of North American ginseng (Panax quinquefolium).
The Catskill Mountains of New York State are an important source of wild-collected American ginseng (Panax quinquefolium) and, increasingly, of woods-cultivated ginseng. The objective of this study was to assess genetic diversity among 9 different wild ginseng populations in and adjacent to the Catskill Mountain region of New York State and to compare these to wild populations from other states including Kentucky, Tennessee, North Carolina, Pennsylvania, and Virginia, and one cultivated population from Wisconsin. Randomly amplified polymorphic DNA (RAPD) markers were used to estimate the genetic distance among samples from the 15 populations. Pooled DNA from 10 plants of each of 8 New York populations was initially screened with 64 random primers; subsequently, the 15 primers that exhibited the greatest number of reproducible polymorphic markers were selected for further experimentation. Gel electrophoresis with the selected 15 primers produced 124 highly reproducible polymorphic bands. The ratio of discordant bands to total bands scored was used to estimate the genetic distance within and among populations. Multidimensional scaling (MDS) of the relation matrix showed distinctly separate clusters between New York and non-New York populations, indicating separation between these two groupings. The MDS analysis was confirmed using pooled chi-square tests for fragment homogeneity. This study shows that RAPD markers can be used as population-specific markers for Panax quinquefolium, and may eventually be utilized as markers for ginsenoside assessment.


Grey nomads with diabetes: the experience of rural and remote diabetes educators in South Australia.
The phenomenon of grey nomads travelling in rural and remote regions of Australia is on the increase, and as this cohort is an older age group, they are often travelling with chronic conditions, such as diabetes. Seven rural and remote diabetes educators were interviewed about their experiences of grey nomad travellers with diabetes, to whom they provided services. The findings revealed problems associated with grey nomads with diabetes, including maintenance of equipment, medications, self-management, glycaemic control and unpredictable events. The problems highlighted by the participants were exacerbated when travelling long distances for extended periods, often with changes to their usual regime of self-management. The isolation and remoteness of some areas was a factor for the travellers who were often not prepared and often turned to pharmacists for help. The participants were able to enhance the care and self-management of the travellers with diabetes and identified several pathways travellers may undertake if they needed services related to their diabetes. The diabetes educators' capacity to provide services for travellers was stretched at times; however, this was viewed as positive in that it added diversity to their normal practice. Recommendations included a preparation checklist and information for travellers with diabetes and further education for pharmacists.


Genetic diversity, recombination, and divergence in animal associated Penicillium dipodomyis.
Penicillium dipodomyis is thought to be an exclusively asexual fungus associated with Kangaroo Rats, Dipodomys species, and is unique among Penicillium species in growing at 37°C but producing no known toxins. Lack of recombination within P. dipodomyis would result in limited adaptive flexibility but possibly enhance local adaptation and host selection via maintenance of favourable genotypes. Here, analysis of DNA sequence data from five protein-coding genes shows that recombination occurs within P. dipodomyis on a small spatial scale. Furthermore, detection of mating-type alleles supports outcrossing and a sexual cycle in P. dipodomyis. P. dipodomyis was a weaker competitor in in vitro assays with other Penicillium species found in association with Kanagaroo rats. Bayesian species level analysis suggests that the P. dipodomyis lineage diverged from closely related species also found in cheek pouches of Kangaroo Rats and their stored seeds about 11 million years ago, a similar divergence time as Dipodomys from its sister rodent taxa.


Goliath family E3 ligases regulate the recycling endosome pathway via VAMP3 ubiquitylation.
Diverse cellular processes depend on endocytosis, intracellular vesicle trafficking, sorting and exocytosis, processes regulated post-transcriptionally by modifications such as phosphorylation and ubiquitylation. In addition to sorting to the lysosome, cargo is recycled to the plasma membrane via recycling endosomes. Here, we describe a role of the goliath gene family of protease-associated (PA) domain E3 ligases in regulating recycling endosome trafficking. The two Drosophila members of this family--Goliath and Godzilla(CG10277)--are located on endosomes, and both ectopic expression and loss-of-function lead to the accumulation of Rab5-positive giant endosomes. Furthermore, the human homologue RNF167 exhibits similar behaviour. We show that the soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE) protein VAMP3 is a target of these ubiquitin ligases, and that recycling endosome trafficking is abrogated in response to their activity. Furthermore, mutation of the Godzilla ubiquitylation target lysines on VAMP3 abrogates the formation of enlarged endosomes induced by either Godzilla or RNF167. Thus, Goliath ubiquitin ligases play a novel role in regulating recycling endosome trafficking via ubiquitylation of the VAMP3 SNARE protein.


DNA synthesis dependent on genetic recombination: characterization of a reaction catalyzed by purified bacteriophage T4 proteins.
To simulate a reaction that occurs in T4-infected cells, we have developed an in vitro DNA synthesis system that requires seven highly purified proteins encoded by this bacteriophage: the DNA polymerase "holoenzyme" (four proteins), gene 32 protein, dda DNA helicase, and uvsX protein - an enzyme that catalyzes homologous DNA pairing and is functionally homologous to the recA protein. In the reaction observed, the 3'OH end of one single-stranded DNA molecule primes DNA synthesis using a double-stranded DNA molecule of homologous sequence as the template. The uvsX protein continuously removes the new DNA chain from its template, so that DNA is synthesized by a conservative mechanism. This type of reaction, which requires the cooperation of recombination and replication enzymes, seems likely to be a general feature of DNA metabolism.


Attitudes and perceptions towards HPV vaccination among young women in Saudi Arabia.
Rising incidence of human papillomavirus (HPV) infection and cervical cancer can be reduced by effective vaccination. Saudi Food and Drug Administration approved prophylactic HPV vaccine in 2010 for females of 11-26 years. To determine the awareness of HPV infection, its health sequel and the attitude and barriers to the acceptance of HPV vaccine by young women in Saudi Arabia. Dynamics influencing the decision of patients and parents regarding vaccination were assessed to foster effective and strategically focused interventions. All patients of Family Medicine department, King Faisal Specialist Hospital and Research Center, Riyadh were invited to participate in this study from January 2012 to June 2014. A culturally sensitive and specially designed questionnaire was administered using an interview-based model to assess the knowledge, perception, and associated sociodemographic factors of HPV. A total of 325 patients participated as per the inclusion criteria: 87.4% were Saudis, 53.5% had university or higher education and 65.2% were adolescents (age 11-19 years). The questionnaire was answered by participants (50.8%) or guardians (49.2%). About 34.5% of the population was aware of HPV infection, and 27.4% were aware of its relation with cervical cancer. However, awareness of the HPV vaccine, perception of its prevention of cervical cancer and other HPV-related disease was relatively low (32.3%), Saudis (29.9%) versus non-Saudis (48.8%) (P = 0.016). More guardians (41.2%) were aware of the HPV vaccine and its impact than participants (27.9%) (P = 0.01). Higher educational background (43.1%) increased the knowledge of HPV compared to less than high school education (24.5%) (odds ratio: 2.33; 95% confidence interval: 1.44-3.76). Nearly 64.3% of participants agreed, and 35.7% refused to receive the HPV vaccine. Knowledge and perception of HPV infection as an sexually transmitted infections and its vaccine was significantly low in this cohort of patients. Higher age and educational levels directly correlated with increased knowledge of HPV infection and its complications. It is recommended that awareness should be raised, and access to HPV vaccination increased to help reduce the health care burden of HPV sequelae in the Kingdom.


[Cloning of human TRAIL cDNA and its expression in COS-7 cells].
The human TRAIL cDNA was amplified with the total RNA from the human acute promyelocytic leukemia cell line HL-60 by means of RT-PCR, and was cloned into the pGEM-T vector. The DNA sequence analysis showed that it was consistent with the published sequence. Then, the insert of human TRAIL cDNA was subcloned into the mammalian expression vector pcDNA3. The hybrid plasmid pcDNA3-hTRAIL was transformed into COS-7 cells, and transiently expressed in the COS-7 cells. The activity of the expressed product could induce apoptosis in U937 cell line.


GEP-NETS update: a review on surgery of gastro-entero-pancreatic neuroendocrine tumors.
The incidence of neuroendocrine tumors (NETs) has increased in the last decades. Surgical treatment encompasses a panel of approaches ranging from conservative procedures to extended surgical resection. Tumor size and localization usually represent the main drivers in the choice of the most appropriate surgical resection. In the presence of small (<2 cm) and asymptomatic nonfunctioning NETs, a conservative treatment is usually recommended. For localized NETs measuring above 2 cm, surgical resection represents the cornerstone in the management of these tumors. As they are relatively biologically indolent, an extended resection is often justified also in the presence of advanced NETs. Surgical options for NET liver metastases range from limited resection up to liver transplantation. Surgical choices for metastatic NETs need to consider the extent of disease, the grade of tumor, and the presence of extra-abdominal disease. Any surgical procedures should always be balanced with the benefit of survival or relieving symptoms and patients' comorbidities.


Electromyography of the quadriceps femoris muscles in subjects with normal knees and acutely effused knees.
The purpose of the study was to describe the electrical activity of the vastus medialis, rectus femoris, and vastus lateralis muscles in subjects with normal knees and acute, severely effused knees when contracting maximally at 30 degrees and 0 degrees of knee flexion. Two groups identified were 1) an effused group (n=8) with subjects having one effused knee and one normal knee and 2) a normal group (n = 8) with subjects having two normal knees. The results were evaluated on two occasions by an observer who has unfamiliar with the groups to which the subjects belonged. The repeated evaluation yielded a high reliability coefficient (Spearman Rho r = .91). Analysis revealed a marked decrease in electrical activity at 0 degrees knee flexion compared to 30 degrees knee flexion in all muscles monitored in the effused knees, while the electrical activity was about equal in both joint positions for the normal knees in both groups. A hypothesis was formed that suggests the decreased electrical activity at 0 degrees in the effused knees results from reflex inhibition caused by joint capsule distension and intra-articular pressures that change with joint position.


Patrolling monocytes promote the pathogenesis of early lupus-like glomerulonephritis.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with genetic and environmental contributions. Hallmarks of the disease are the appearance of immune complexes (IC) containing autoreactive Abs and TLR-activating nucleic acids, whose deposition in kidney glomeruli is suspected to promote tissue injury and glomerulonephritis (GN). Here, using a mouse model based on the human SLE susceptibility locus TNFAIP3-interacting protein 1 (TNIP1, also known as ABIN1), we investigated the pathogenesis of GN. We found that GN was driven by TLRs but, remarkably, proceeded independently of ICs. Rather, disease in 3 different mouse models and patients with SLE was characterized by glomerular accumulation of patrolling monocytes (PMos), a cell type with an emerging key function in vascular inflammation. Consistent with such function in GN, monocyte-specific deletion of ABIN1 promoted kidney disease, whereas selective elimination of PMos provided protection. In contrast to GN, PMo elimination did not protect from reduced survival or disease symptoms such as IC generation and splenomegaly, suggesting that GN and other inflammatory processes are governed by distinct pathogenic mechanisms. These data identify TLR-activated PMos as the principal component of an intravascular process that contributes to glomerular inflammation and kidney injury.


An Inductive Voltage/Current-Mode Integrated Power Management with Seamless Mode Transition and Energy Recycling.
An integrated power management (IPM) with the unique capabilities of seamless-voltage/current-mode (SVCM) operation and energy recycling is presented for robust inductive power delivery. Utilizing parasitic bulk diodes with lower voltage drop, this IPM seamlessly transitions between voltage mode (VM) and current mode (CM) in a safe and robust fashion, extending the input-voltage range (removing dead zone) and significantly improving power-conversion efficiency (PCE) in CM operation. The IPM first provides the required load power (PL) by one-step rectification/regulation, and then stores the surplus energy into a storage capacitor to extend the receiver (Rx) operation time via energy recycling when the input power is insufficient. The theory behind the energy recycling is presented. A proof-of-concept chip was fabricated in a 0.35 µm CMOS process. In measurements, the chip safely achieved a regulated voltage of 3 V for a wide input-voltage range (without dead zone) by switching the Rx LC-tank at 142 kHz. With zero input power, the chip extended the Rx operation time by 250% thanks to the energy recycling.


Defect-controlled softness, diffusive permeability, and mesh-topology of metallo-supramolecular hydrogels.
Hydrogels are polymer networks swollen in water; they are suitable materials for biomedical applications such as tissue engineering and drug delivery. In the latter, the controlled diffusion of small diffusants inside the network is essential, as it determines the release mechanism of the drug. In general, the diffusion inside a polymer network is controlled by its mesh-size. Here, we actively control the diffusivity and also the softness of metallo-supramolecular hydrogels via the network mesh-topology by introducing connectivity defects. A model polymer network is realized based on a 4-arm poly(ethylene glycol) (pEG) where each arm is capped with terpyridine moieties that are capable of forming metallo-supramolecular complexes with zinc ions. In this model network, we insert 8-arm pEG macromolecules that are functionalized with terpyridine at different ratios to create connectivity defects. With an increasing amount of 8-arm pEG, the polymer network forms more loops, as quantified by double quantum-NMR. This doped network shows an enhanced self-diffusivity of the building block molecules within the network, as examined by fluorescence recovery after photobleaching, and a higher softness, as investigated by oscillatory shear rheology. With these findings, we show that it is possible to tune the diffusivity and softness of hydrogels with defects in a rational fashion.


Lacrimal stenting versus three-snip punctoplasty for treatment of punctal stenosis or occlusion: an open- label, randomized clinical trial.
To compare the short-term anatomical and functional outcomes of, as well as patient satisfaction with, lacrimal stenting and three-snip punctoplasty for the treatment of punctal stenosis or occlusion. In this open-label, randomized clinical trial, we included 50 eyes of 30 patients diagnosed with punctal stenosis or occlusion. They were randomly allocated to two groups of 25 eyes each, using central telephone randomization. Group A underwent a lacrimal stenting procedure and was subdivided into two subgroups: Group A1 (13 eyes) received polyvinylpyrrolidone-coated perforated punctal plugs, and Group A2 (12 eyes) received closed intubation using a bicanalicular silicon tube. Group B included 25 eyes that underwent three- snip punctoplasty. All eyes were examined after 1 day, 1 week, 1 month, 3 months, and 6 months. Postoperative anatomical success assessing the punctum size, functional success using the fluorescein disappearance test (FDT), and patient satisfaction based on epiphora scoring were recorded. Both study groups were comparable in terms of sex and age distribution. Compared to Group B, Group A had a significantly larger punctum size at one, three, and 6-month postoperatively (P = 0.009, 0.01, and 0.02, respectively). The difference in FDT results was significant between the two groups at all follow-up visits (P = 0.008, 0.0001, 0.003, and 0.002, at postoperative one week, one-months, three-month, and si-month, respectively). Likewise, patient satisfaction was significantly different between both groups at all follow-up visits (P = 0.007, 0.001, 0.005, and 0.002, at postoperative one week, one-months, three-month, and si-month, respectively). Lacrimal stenting is an effective method for the treatment of punctal stenosis or occlusion. Overall, the FDT results and patient satisfaction outcomes were significantly better.


Technologically-assisted communication attenuates inter-brain synchrony.
The transition to technologically-assisted communication has permeated all facets of human social life; yet, its impact on the social brain is still unknown and the effects may be particularly intense during periods of developmental transitions. Applying a two-brain perspective, the current preregistered study utilized hyperscanning EEG to measure brain-to-brain synchrony in 62 mother-child pairs at the transition to adolescence (child age; M = 12.26, range 10-14) during live face-to-face interaction versus technologically-assisted remote communication. The live interaction elicited 9 significant cross-brain links between densely inter-connected frontal and temporal areas in the beta range [14-30 Hz]. Mother's right frontal region connected with the child's right and left frontal, temporal, and central regions, suggesting its regulatory role in organizing the two-brain dynamics. In contrast, the remote interaction elicited only 1 significant cross-brain-cross-hemisphere link, attenuating the robust right-to-right-brain connectivity during live social moments that communicates socio-affective signals. Furthermore, while the level of social behavior was comparable between the two interactions, brain-behavior associations emerged only during the live exchange. Mother-child right temporal-temporal synchrony linked with moments of shared gaze and the degree of child engagement and empathic behavior correlated with right frontal-frontal synchrony. Our findings indicate that human co-presence is underpinned by specific neurobiological processes that should be studied in depth. Much further research is needed to tease apart whether the "Zoom fatigue" experienced during technological communication may stem, in part, from overload on more limited inter-brain connections and to address the potential cost of social technology for brain maturation, particularly among youth.


Effect of exposure to lead on postural control in workers.
To examine the effect of lead on postural control of workers who have been exposed to lead. 63 Male, lead battery workers mean (SD) age 41.0 (7.4) were compared with 48 age matched male controls after excluding those with acute or chronic diseases. Exposed workers had mean (SD) past blood lead concentrations of 37.5 (9.2) micrograms/dl and 11.2 (5.7) years of employment. Postural control was measured with a computerised postural sway measurement system which measured both sway and total movements. Workers standing straight with eyes open on the bare plates had sway and total movements which were not notably different from controls. On the other hand increased movements were needed in the exposed workers to maintain stability (the general stability quotient 18.2 (5.4) v 15.4 (4.4) in controls, p < 0.01) when standing directly on the foot-plates with closed eyes,, and with the head tilted (15.0 (3.8) v 11.5 (3.0) in controls, p < 0.001). Exposed workers also had a trend for less ability to synchronize anterior posterior and lateral sway in the stress positions (0.0625) than had non-exposed workers. Significant but low correlations were found between the estimate of the chronic internal dose of lead and three of 10 of the postural control measurements, and present lead blood concentrations and only one of the 10 measurements and (r values ranged from 0.21 to 0.31, p < or = 0.03). These findings suggest that lead affects postural control in asymptomatic workers. Further studies are warranted to find whether workers with decreased postural control are at increased risk of accidents and the relation, if any, of these measurements with subsequent morbidity.


Collision tumor of primary laryngeal mucosal melanoma and invasive squamous cell carcinoma with IL-17A and CD70 gene over-expression.
The most common primary malignancy of the larynx is the squamous cell carcinoma (SCC). The primary malignant melanoma is quite rare in this location. Less than 60 cases of laryngeal melanomas have been reported to date. To our knowledge, collision primary malignant melanoma and invasive squamous cell carcinoma in the vocal cords has not been reported. We report a 53-year-old male patient who was diagnosed with a collision tumor of laryngeal melanoma and invasive SCC. Multiple Th17 pathway related genes including CTLA-4, IL-17A-F, PLZF, FoxP3, RorγT, CD27, and CD70 were analyzed by reverse transcriptase-polymerase chain reaction (Rt-PCR) in this case. Both IL-17A and CD70 genes were detected in this case of collision tumor. The results may define useful biomarkers for early diagnosis of mucosal melanoma and open an immunotherapeutic field for clinical management with the potential benefit from the immunomodulators that enhance both genes.


High-throughput genotyping for species identification and diversity assessment in germplasm collections.
Germplasm collections provide an extremely valuable resource for breeders and researchers. However, misclassification of accessions by species often hinders the effective use of these collections. We propose that use of high-throughput genotyping tools can provide a fast, efficient and cost-effective way of confirming species in germplasm collections, as well as providing valuable genetic diversity data. We genotyped 180 Brassicaceae samples sourced from the Australian Grains Genebank across the recently released Illumina Infinium Brassica 60K SNP array. Of these, 76 were provided on the basis of suspected misclassification and another 104 were sourced independently from the germplasm collection. Presence of the A- and C-genomes combined with principle components analysis clearly separated Brassica rapa, B. oleracea, B. napus, B. carinata and B. juncea samples into distinct species groups. Several lines were further validated using chromosome counts. Overall, 18% of samples (32/180) were misclassified on the basis of species. Within these 180 samples, 23/76 (30%) supplied on the basis of suspected misclassification were misclassified, and 9/105 (9%) of the samples randomly sourced from the Australian Grains Genebank were misclassified. Surprisingly, several individuals were also found to be the product of interspecific hybridization events. The SNP (single nucleotide polymorphism) array proved effective at confirming species, and provided useful information related to genetic diversity. As similar genomic resources become available for different crops, high-throughput molecular genotyping will offer an efficient and cost-effective method to screen germplasm collections worldwide, facilitating more effective use of these valuable resources by breeders and researchers.


Playful interaction: occupational therapy for all children on the school playground.
We examined the impact of an intervention on the playfulness of 5- to 7-year-old children who are developing typically. Materials that had no defined purpose were placed on a school playground for 11 weeks. The Test of Playfulness (ToP) was used to compare videotaped play segments pre- and postintervention. Teachers who did playground duty were interviewed regarding changes in play. ToP data were analyzed using a Wilcoxon signed-ranks test. Interview data were analyzed for themes. ToP scores were significantly higher after intervention (Z= -1.94; p = .025, one-tailed; Cohen's d = 0.55). Teachers reported that children were more social, creative, and resilient when the materials were on the playground. Children who were creative, rather than very physically capable, became leaders in activity. Our results revealed a potential role for occupational therapists with typically developing children in schools. This finding has clear implications for children with disability.


Neuronal connectome of a sensory-motor circuit for visual navigation.
Animals use spatial differences in environmental light levels for visual navigation; however, how light inputs are translated into coordinated motor outputs remains poorly understood. Here we reconstruct the neuronal connectome of a four-eye visual circuit in the larva of the annelid Platynereis using serial-section transmission electron microscopy. In this 71-neuron circuit, photoreceptors connect via three layers of interneurons to motorneurons, which innervate trunk muscles. By combining eye ablations with behavioral experiments, we show that the circuit compares light on either side of the body and stimulates body bending upon left-right light imbalance during visual phototaxis. We also identified an interneuron motif that enhances sensitivity to different light intensity contrasts. The Platynereis eye circuit has the hallmarks of a visual system, including spatial light detection and contrast modulation, illustrating how image-forming eyes may have evolved via intermediate stages contrasting only a light and a dark field during a simple visual task.


Patients' Experiences With a Digital Primary Health Care Concept Using Written Dialogues: A Pilot Study.
Background: The changing health care environment promotes the adoption of new information technologies to connect patients and health care providers. However, individuals greatly vary in their ability to use new digital systems, and in their feelings regarding integrity and validation. Caregivers in southern Sweden plan to implement a new digital primary health care (DPHC) service, and patients' experiences must be studied to guide the best possible implementation of this service. Purpose: To examine the patients' experiences with DPHC using written dialogues. Method: Patients were consecutively recruited from June 2018 to April 2019. This prospective pilot study used questionnaires with fixed response options, summarized as index values (IV, 0-1.0) in the following domains: communication, technical functionality, and general experience of DPHC. Results: Participants included 286 patients with a mean age of 40 ± 15 years. The response rate was 49% (n = 140), including 40 men (29%) and 100 women (71%). Communication using DPHC was experienced as fairly good (IV, 0.58), technical functionality was experienced as good (IV, 0.80), and the general experience of DPHC was positive with an IV of 0.76. The overall experience of the concept (IV, 0.71), corresponds to a median satisfaction value of 8.0 (interquartile range, 6-9). The patients felt well-prepared and experienced reasonable time aspects. Of the responding patients, 81% would recommend DPHC to others, and a notable reason for satisfaction was availability. However, patients expressed some uncertainty regarding the physician's ability to assess correct care needs. Conclusion: The patients in our pilot study described their satisfaction and expressed good experiences with the concept of DPHC using written dialogues.


A review of Internet-based home drug-testing products for parents.
To review home drug-testing products and the Internet-based recommendations intended for parents. A qualitative review of drug-testing products and structured analysis of information presented on company Internet sites were conducted. Eight Internet sites that sold home drug-testing products and contained a "parent's section" were identified by Ixquick using the search term "home drug testing." Description and prices of products sold by each Internet site and recommended indications for testing, consent, collection procedures, and follow-up of positive and negative test results were researched. A variety of drug-testing products were available, including breath and saliva tests for alcohol, a multidrug panel hair test, and a variety of laboratory and instant urine tests. Prices ranged from 2.75 dollars for a single alcohol test to 89.00 dollars for a multidrug combination urine/hair package. A total of 14 indications for home drug-testing were cited; all sites claimed that drug testing was a way to know with certainty whether a child has used drugs. Only 1 web site made a clear statement against testing an adolescent against his or her will. Little information was presented on valid specimen collection procedures and the risks of false-positive and false-negative tests. Only half of the sites recommended that parents consult a professional if a test is positive. Pediatricians should advise parents of the limitations and potential risks associated with home drug-testing products.