C/EBPα promotes triacylglycerol synthesis via regulating PPARG promoter activity in goat mammary epithelial cells.
CCAAT/enhancer binding protein α (C/EBPα) is the key transcription factor involved in lipid metabolism, however, the role of C/EBPα in milk fat synthesis of dairy goats remains unknown. The objective of the present research was to clarify the function of C/EBPα in goat mammary epithelial cells (GMECs) and its impact on peroxisome proliferator-activated receptor gamma (PPARG) promoter activity. In this study, C/EBPα overexpression increased its mRNA and protein levels by 42-fold and 6-fold, respectively. In contrast, transfecting siRNA targeting C/EBPα decreased its mRNA level to 20% and protein abundance to 80% of the basal level. The contents of lipid droplets, triacylglycerol (TAG), and cholesterol were increased (P < 0.05) in C/EBPα-overexpressing GMECs, and knockdown of C/EBPα led to the opposite results. Overexpression of C/EBPα significantly increased the expression levels of genes involved in TAG synthesis (AGPAT6, DGAT2, P < 0.01), lipid droplet formation (PLIN2, P < 0.01), and fatty acid synthesis (FADS2, P < 0.05; ELOVL6, P < 0.01). Knockdown of C/EBPα decreased (P < 0.05) the expression levels of AGPAT6, DGAT1, DGAT2, PLIN2, FADS2, and ELOVL6. C/EBPα upregulated the expression level of PPARG (P < 0.05), and four C/EBPα binding regions were identified in the PPARG promoter at -1,112 to -1,102 bp, -734 to -724 bp, -248 to -238 bp, and -119 to -109 bp. Knockdown of C/EBPα reduced (P < 0.05) the PPARG promoter activity when the C/EBPα binding regions were mutated at -1,112 to -1,102 bp, -734 to -724 bp, and -248 to -238 bp locations of the promoter. However, the promoter activity did not change when the mutation was located at -119 bp. In conclusion, our results suggest that C/EBPα can promote TAG synthesis in GMECs through its effects on mRNA abundance of genes related to lipid metabolism and regulation of the PPARG promoter activity via C/EBPα binding regions.


Efficacy of protracted temozolomide dosing is limited in MGMT unmethylated GBM xenograft models.
Temozolomide (TMZ) is important chemotherapy for glioblastoma multiforme (GBM), but the optimal dosing schedule is unclear. The efficacies of different clinically relevant dosing regimens were compared in a panel of 7 primary GBM xenografts in an intracranial therapy evaluation model. Protracted TMZ therapy (TMZ daily M-F, 3 wk every 4) provided superior survival to a placebo-treated group in 1 of 4 O(6)-DNA methylguanine-methyltransferase (MGMT) promoter hypermethylated lines (GBM12) and none of the 3 MGMT unmethylated lines, while standard therapy (TMZ daily M-F, 1 wk every 4) provided superior survival to the placebo-treated group in 2 of 3 MGMT unmethylated lines (GBM14 and GBM43) and none of the methylated lines. In comparing GBM12, GBM14, and GBM43 intracranial specimens, both GBM14 and GBM43 mice treated with protracted TMZ had a significant elevation in MGMT levels compared with placebo. Similarly, high MGMT was found in a second model of acquired TMZ resistance in GBM14 flank xenografts, and resistance was reversed in vitro by treatment with the MGMT inhibitor O(6)-benzylguanine, demonstrating a mechanistic link between MGMT overexpression and TMZ resistance in this line. Additionally, in an analysis of gene expression data, comparison of parental and TMZ-resistant GBM14 demonstrated enrichment of functional ontologies for cell cycle control within the S, G2, and M phases of the cell cycle and DNA damage checkpoints. Across the 7 tumor models studied, there was no consistent difference between protracted and standard TMZ regimens. The efficacy of protracted TMZ regimens may be limited in a subset of MGMT unmethylated tumors by induction of MGMT expression.


HL-1 cells express an inwardly rectifying K+ current activated via muscarinic receptors comparable to that in mouse atrial myocytes.
An inwardly rectifying K(+) current is present in atrial cardiac myocytes that is activated by acetylcholine (I(KACh)). Physiologically, activation of the current in the SA node is important in slowing the heart rate with increased parasympathetic tone. It is a paradigm for the direct regulation of signaling effectors by the Gbetagamma G-protein subunit. Many questions have been addressed in heterologous expression systems with less focus on the behaviour in native myocytes partly because of the technical difficulties in undertaking comparable studies in native cells. In this study, we characterise a potassium current in the atrial-derived cell line HL-1. Using an electrophysiological approach, we compare the characteristics of the potassium current with those in native atrial cells and in a HEK cell line expressing the cloned Kir3.1/3.4 channel. The potassium current recorded in HL-1 is inwardly rectifying and activated by the muscarinic agonist carbachol. Carbachol-activated currents were inhibited by pertussis toxin and tertiapin-Q. The basal current was time-dependently increased when GTP was substituted in the patch-clamp pipette by the non-hydrolysable analogue GTPgammaS. We compared the kinetics of current modulation in HL-1 with those of freshly isolated atrial mouse cardiomyocytes. The current activation and deactivation kinetics in HL-1 cells are comparable to those measured in atrial cardiomyocytes. Using immunofluorescence, we found GIRK4 at the membrane in HL-1 cells. Real-time RT-PCR confirms the presence of mRNA for the main G-protein subunits, as well as for M2 muscarinic and A1 adenosine receptors. The data suggest HL-1 cells are a good model to study IKAch.


PPI layouts: BioJS components for the display of Protein-Protein Interactions.
We present two web-based components for the display of Protein-Protein Interaction networks using different self-organizing layout methods: force-directed and circular. These components conform to the BioJS standard and can be rendered in an HTML5-compliant browser without the need for third-party plugins. We provide examples of interaction networks and how the components can be used to visualize them, and refer to a more complex tool that uses these components. http://github.com/biojs/biojs; http://dx.doi.org/10.5281/zenodo.7753.


Glutamatergic agents for schizophrenia: current evidence and perspectives.
Suboptimal outcomes in schizophrenia are a consequence of lacking insight into the etiology, biomarkers and treatment-relevant subgroups, the therapeutic restriction to dopaminergic-modulating antipsychotics that fail to significantly improve negative and cognitive symptoms, non-adherence, and, in the case of treatment-resistance, the underutilization of clozapine. Evidence suggests additional, extra-dopaminergic abnormalities in amino acid neurotransmission, particularly the glutamatergic system. Antidopaminergic antipsychotics modulate this system on several levels, as do mood stabilizers, including lamotrigine, topiramate and pregabaline. Recently, agonists at metabotropic glutamate receptors and glycine uptake inhibitors failed in large placebo-controlled trials for schizophrenia. Problems to overcome for successfully leveraging glutamatergic agents for schizophrenia are patient selection, focus on positive symptoms and late disease stages, and dose-response relationships. Because glutamate guides processes of brain development and maturation, clinical research should focus on the at-risk mental state or first-episode psychosis, address cognition and negative symptoms and use monotherapy designs in parallel to augmentation strategies.


Simulated Winter Incubation of Soil With Swine Manure Differentially Affects Multiple Antimicrobial Resistance Elements.
Gastrointestinal bacteria that harbor antibiotic resistance genes (ARG) become enriched with antibiotic use. Livestock manure application to cropland for soil fertility presents a concern that ARG and bacteria may proliferate and be transported in the environment. In the United States, manure applications typically occur during autumn with slow mineralization until spring planting season. A laboratory soil incubation study was conducted mimicking autumn swine manure application to soils with concentrations of selected ARG monitored during simulated 120-day winter incubation with multiple freeze-thaw events. Additionally, the effects of two soil moistures [10 and 30% water holding capacity (WHC)] and two manure treatments [raw versus hydrated lime alkaline stabilization (HLAS)] were assessed. Fourteen tetracycline resistance genes were evaluated; tet(D), tet(G), and tet(L) were detected in background soil while swine manure contained tet(A), tet(B), tet(C), tet(G), tet(M), tet(O), tet(Q), and tet(X). By day 120, the manure-borne tet(M) and tet(O) were still detected while tet(C), tet(D), tet(L), and tet(X) genes were detected less frequently. Other tet resistance genes were detected rarely, if at all. The sum of unique tet resistance genes among all treatments decreased during the incubation from an average of 8.9 to 3.8 unique tet resistance genes. Four resistance elements, intI1, bla ctx-m-32, sul(I), erm(B), and 16s rRNA genes were measured using quantitative PCR. ARG abundances relative to 16S abundance were initially greater in the raw manure compared to background soil (-1.53 to -3.92 log abundance in manure; -4.02 to <-6.7 log abundance in soil). In the mixed manure/soil, relative abundance of the four resistance elements decreased (0.87 to 1.94 log abundance) during the incubation largely because 16S rRNA genes increased by 1.21 log abundance. Throughout the incubation, the abundance of intI1, bla ctx-m-32, sul(I), and erm(B) per gram in soil amended with HLAS-treated manure was lower than in soil amended with raw manure. Under low initial soil moisture conditions, HLAS treatment reduced the abundance of intI1 and resulted in loss of bla ctx-m-32, sul(I), and erm(B)] compared to other treatment-moisture combinations. Although one might expect antibiotic resistance to be relatively unchanged after simulated winter manure application to soil, a variety of changes in diversity and relative abundance can be expected.


LINC01410 Knockdown Suppresses Cervical Cancer Growth and Invasion via Targeting miR-2467-3p/VOPP1 Axis.
Long noncoding RNAs have essential roles in human diseases, including cancer. Our work aims to assess the function and mechanisms of LINC01410 in cervical cancer (CC) development. Expression analyses were performed using qRT-PCR. Proliferation was determined through CCK8 and colony formation assays. Cell migration and invasion were determined by Transwell assay. The interactions among LINC01410, miR-2467-3p and VOPP1 were analyzed via luciferase reporter assay. LINC01410 was upregulated in CC tissues and cell lines. LINC01410 upregulation correlated with poor prognosis. LINC01410 silencing suppressed proliferation, migration and invasion of CC cells. LINC01410 was the sponge for miR-2467. And LINC01410 promoted VOPP1 expression through inhibiting miR-2467. Our findings demonstrated that LINC01410 contributed to CC progression through regulating miR-2467/VOPP1 axis and suggested that LINC01410/miR-2467/VOPP1 cascade may be a potential therapeutic target.


Maternal Physical Health Symptoms in the First 8 Weeks Postpartum Among Primiparous Australian Women.
To describe prospectively the extent, onset, and persistence of maternal physical health symptoms (cesarean delivery pain, perineal pain, back pain, constipation, hemorrhoids, urinary incontinence, bowel incontinence, and fatigue) in the first 8 weeks postpartum. A prospective cohort of 229 primiparous women was recruited antenatally from a public and a private maternity hospital, Melbourne, Australia, between 2009 and 2011. Data were collected by self-report questionnaires at weeks 1, 2, 3, 4, and 8. Main outcome measures were a checklist of maternal health symptoms and a standardized assessment of fatigue symptoms. Birth-related pain was common at week 1 (n = 80/88, 91% cesarean delivery pain; n = 92/125, 74% perineal pain), and still present for one in five women who had a cesarean birth (n = 17, 18%) at week 8. Back pain was reported by approximately half the sample at each study interval, with 25 percent (n = 48) reporting a later onset at week 2 or beyond. Fatigue was not relieved between 4 and 8 weeks. Women experience significant morbidity in the early weeks postpartum, the extent of which may have been underestimated in previous research relying on retrospective recall. Findings contribute to the growing body of evidence that supports early identification, treatment, and support for women's physical health problems in the postpartum.


Cell-ECM contact-guided intracellular polarization is mediated via lamin A/C dependent nucleus-cytoskeletal connection.
Cell polarization plays a crucial role in dynamic cellular events, such as cell proliferation, differentiation, and directional migration in response to diverse extracellular and intracellular signals. Although it is well known that cell polarization entails highly orchestrated intracellular molecular reorganization, the underlying mechanism of repositioning by intracellular organelles in the presence of multiple stimuli is still unclear. Here, we show that front-rear cell polarization based on the relative positions of nucleus and microtubule organizing center is precisely controlled by mechanical interactions including cellular adhesion to extracellular matrix and nucleus-cytoskeletal connections. By modulating the size and distribution of fibronectin-coated adhesive spots located in the polarized cell shape mimicking micropatterns, we monitored the alterations in cell polarity. We found that the localization of individual adhesive spots is more dominant than the cell shape itself to induce intracellular polarization. Further, the degree of cell polarization was diminished significantly by disrupting nuclear lamin A/C. We further confirm that geometrical cue-guided intracellular polarization determines directional cell migration via local activation of Cdc42. These findings provide novel insights into the role of nucleus-cytoskeletal connections in single cell polarization under a combination of physical, molecular, and genetic cues, where lamin A/C acts as a critical molecular mediator in ECM sensing and signal transduction via nucleus-cytoskeletal connection.


Coronary arterial abnormalities in pulmonary atresia with intact ventricular septum diagnosed during fetal life.
To establish the prevalence of coronary arterial abnormalities in mid-trimester fetuses with pulmonary atresia with intact ventricular septum, and whether their presence correlates with right ventricular morphology. The presence of coronary arterial fistulas significantly alters the surgical options and prognosis for patients with pulmonary atresia with intact ventricular septum. The lesion can reliably be diagnosed using fetal echocardiography, and further definition of the prognosis is important for counselling parents. We examined the hearts of 39 pathological specimens diagnosed during fetal life, 3 of whom died postnatally. Coronary arterial abnormalities were defined as non-connection of the left or right coronary arteries to the aorta, ostial stenosis, marked tortuosity, dilation, thickening or abnormal myocardial branching. Mild tortuosity, or myocardial bridging, were considered normal. We measured the dimensions of the tricuspid valve along with the inlet and outlet portions of the ventricles. Ebstein's malformation, tricuspid valvar dysplasia, and the presence or absence of the infundibulum, were especially noted. We examined also 12 normal hearts as controls. Coronary arterial abnormalities were found in 14/39 (36%). The dimensions of the right ventricle and tricuspid valves, and the gestational ages of the fetuses, were compared for these 14 with the 25 having no abnormalities using independent t-tests. The gestational ages were similar, 21.9 vs 21.1 weeks. The mean dimensions of the tricuspid valve, median z-scores, and right ventricle were smaller, 2.9 vs 7.2 mm; p < 0.002; -4.46 vs 0.23; p < 0.03; and 6.9 vs 13.7 mm; p < 0.002, for those with coronary arterial abnormalities. Ebstein's malformation, or dysplasia of the tricuspid valve, was present in 4 of 14 with, vs 15 of 25 without, coronary arterial abnormalities. A patent infundibulum was noted in 34 of 39 specimens. Mid-trimester fetuses with pulmonary atresia with intact ventricular septum already exhibit coronary arterial abnormalities, with a prevalence of 36%. The presence of a patent infundibulum confirms that atresia of the pulmonary valve is an acquired process. Coronary arterial abnormalities are seen in 50% of those with hypoplastic right ventricles, but less frequently in the presence of well developed ventricles. This is important information for those involved in counselling parents.


Evaluating the use of blood cultures in the management of children hospitalized for community-acquired pneumonia.
Blood cultures are often recommended for the evaluation of community-acquired pneumonia (CAP). However, institutions vary in their use of blood cultures, and blood cultures have unclear utility in CAP management in hospitalized children. To identify clinical factors associated with obtaining blood cultures in children hospitalized with CAP, and to estimate the association between blood culture obtainment and hospital length of stay (LOS). We performed a multicenter retrospective cohort study of children admitted with a diagnosis of CAP to any of four pediatric hospitals in the United States from January 1, 2011-December 31, 2012. Demographics, medical history, diagnostic testing, and clinical outcomes were abstracted via manual chart review. Multivariable logistic regression evaluated patient and clinical factors for associations with obtaining blood cultures. Propensity score-matched Kaplan-Meier analysis compared patients with and without blood cultures for hospital LOS. Six hundred fourteen charts met inclusion criteria; 390 children had blood cultures obtained. Of children with blood cultures, six (1.5%) were positive for a pathogen and nine (2.3%) grew a contaminant. Factors associated with blood culture obtainment included presenting with symptoms of systemic inflammatory response syndrome (OR 1.78, 95% CI 1.10-2.89), receiving intravenous hydration (OR 3.94, 95% CI 3.22-4.83), receiving antibiotics before admission (OR 1.49, 95% CI 1.17-1.89), hospital admission from the ED (OR 1.65, 95% CI 1.05-2.60), and having health insurance (OR 0.42, 95% CI 0.30-0.60). In propensity score-matched analysis, patients with blood cultures had median 0.8 days longer LOS (2.0 vs 1.2 days, P < .0001) without increased odds of readmission (OR 0.94, 95% CI 0.45-1.97) or death (P = .25). Obtaining blood cultures in children hospitalized with CAP rarely identifies a causative pathogen and is associated with increased LOS. Our results highlight the need to refine the role of obtaining blood cultures in children hospitalized with CAP.


Molecular characterization and prevalence of antibiotic resistance in Helicobacter pylori isolates in Kuala Lumpur, Malaysia.
Helicobacter pylori has been classified as high priority pathogen by the WHO in 2017. The emergence of antibiotic-resistant strains is one of the main causes of treatment failure in H. pylori infection. This study determined and characterized primary and secondary resistances in H. pylori in Malaysia. Gastric biopsies from antrum (n=288) and corpus (n=283) were obtained from 288 patients who underwent endoscopy at Universiti Kebangsaan Malaysia Medical Center (UKMMC), Kuala Lumpur, Malaysia. Antibiotic susceptibility to six classes of antibiotics was determined by the E-test. Mutations conferring in resistance in functional genes were identified by PCR and sequencing. Overall resistance rates to metronidazole, clarithromycin and levofloxacin were 59.3% (35/59), 35.6% (21/59) and 25.4% (15/59), respectively. Secondary isolates showed significantly higher resistance rates to clarithromycin compared to the primary isolates. Mixed infection with susceptible and resistant isolates was observed in 16.2% (6/37) of cases, of which 83.3% (n=5) had infection with the same strain. 41% (18/44) of isolates were resistant to more than one class of antibiotics of which 50% (9/18) were multidrug-resistant, two being primary and seven being secondary isolates. Mutations in rdxA, 23S rRNA and gyrA genes were associated with resistance to metronidazole, clarithromycin and levofloxacin, respectively. The high level of resistance to metronidazole, clarithromycin and levofloxacin seen in H. pylori isolates in our setting warrants the need for continuous surveillance and highlights caution in use of antibiotics generally used as first-line therapy in H. pylori eradication regimen.


Obesity prevalence and unfavorable health risk behaviors among German kindergarten teachers: cross-sectional results of the kindergarten teacher health study.
The aim of the study was to investigate obesity status and associated health risk behaviors in a sample of German kindergarten teachers. At present, such data are not available, despite the fact that kindergarten teachers educate children at a formative time in their lives. Kindergarten teachers aged 18-62 years (n = 313) were invited to participate in the Kindergarten Teacher Health Study (KTHS) by completing a self-reported questionnaire. We analyzed their obesity status, health risk behaviors (i.e., habitual physical activity, screen time activities, eating behavior patterns, smoking), and their general ability to identify overweight children and the associated health risks of overweight and obesity based on special age- and sex-specific silhouettes. After adjusting for covariates, bivariate correlations were conducted for associations between body mass index (BMI) and health risk behaviors, while analyses of variance (ANOVAs) were used to analyze differences of health risk behaviors between BMI groups. Logistic regression analyses were conducted to predict determinants of kindergarten teachers who did not correctly identify the overweight silhouettes and their associated physical and mental health risks. Additionally, data regarding kindergarten teachers' weight status and smoking behavior were compared with nationally representative data from the 2009 Microcensus (n = 371310) using the Mann-Whitney U-test. The prevalence rates of overweight and obesity were 41.2% and 17.9%, respectively. The prevalence of obesity was significantly higher in kindergarten teachers (p < 0.001) compared to national Microcensus data. Only 44.6% of teachers were able to identify overweight children correctly. The fact that being overweight is associated with physical and mental health risks was only reported by 40.1% and 21.2% of teachers, respectively. Older kindergarten teachers were more likely to misclassify the overweight silhouettes, while younger, normal-weight, and overweight kindergarten teachers were more likely to underestimate the associated health risks. Obese kindergarten teachers reported spending more time in front of computer and television screens than their normal-weight counterparts, especially on weekends. In addition, obese kindergarten teachers reported eating less often with their families and more frequently reported watching television during meals. Advanced monitoring and multifaceted interventions to improve the health behaviors of kindergarten teachers should be given high priority. Because kindergarten teachers' behavioral modeling presumably mediates children's health behaviors, additional research is needed about kindergarten teachers' health and its proposed interaction with children's health.


Destruction and reorganization of the receptor membrane in labellar chemosensory cells of the blowfly. Long-lasting latent action of colchicine.
Electron micrographs of sections of the labellar chemosensilla of the blowfly, Phormia regina, showed that treatment with sodium deoxycholate (DOC; 7.2 mM for 2 min) destroyed the distal processes of the receptors from up to 10 microns from the tip of the sensillum, but these processes regenerated almost completely within 0.5 h. However, when DOC treatment was preceded by colchicine treatment (25 mM for 2 min), greater than 10 h was required for complete regeneration. Sugar receptor responses supported these findings and disclosed a more detailed time course of regeneration after DOC treatment: without colchicine pretreatment, the destroyed distal process completely regenerated in 0.3-1.0 h, but with pretreatment, regeneration began at 3 h and reached the chemosensillar tip at 8 h at the earliest. Hardly any depression of the response was observed for 8 h after treatment with colchicine alone, but a transient depression was detected at 12 h. Based on these results, the role of microtubules in the maintenance of the receptor membrane is discussed.


Storm events as key moments of microplastic contamination in aquatic ecosystems.
Microplastic (MP) pollution is an emerging issue in aquatic sciences. Rain and storm events are responsible for the mobilization and transport of a range of pollutants in aquatic systems, yet to date no study has examined how microplastic abundance changes in waterways during such events. The aim of this study was to determine how microplastic concentrations changed over the course of the storm event in an urban estuary. Sampling was conducted at high frequency before, during, and after a storm event that caused flooding in the Cooks River estuary, Australia. Microplastic abundance increased during two days of heavy rain from 400 particles m3 before storm event to up to 17,383 particles m3 after the event. Variation in microplastic abundance was positively related to five-day average antecedent rainfall. The results highlight the importance of rain and storm events as key moments of microplastic contamination in aquatic systems. The results have implications for considering the maximum number of microplastics that aquatic life may be exposed to and the importance of strategies to manage stormwater to minimize the input of microplastics to aquatic ecosystems.


Fox (forkhead) genes are involved in the dorso-ventral patterning of the Xenopus mesoderm.
Fox (forkhead/winged helix) genes encode a family of transcription factors that are involved in embryonic pattern formation, regulation of tissue specific gene expression and tumorigenesis. Several of them are transcribed during Xenopus embryogenesis and are important for the patterning of ectoderm, mesoderm and endoderm. We have isolated three forkhead genes that are activated during gastrulation and play an important role in the dorso-ventral patterning of the mesoderm. XFKH1 (FoxA4b), the first vertebrate forkhead gene to be implicated in embryonic pattern formation, is expressed in the Spemann-Mangold organizer region and later in the embryonic notochord. XFKH7, the Xenopus orthologue of the murine Mfh1(Foxc2), is expressed in the presomitic mesoderm, but not in the notochord or lateral plate mesoderm. Finally, XFD-13'(FoxF1b)1 is expressed in the lateral plate mesoderm, but not in the notochord or presomitic mesoderm. Expression pattern and functional experiments indicate that these three forkhead genes are involved in the dorso-ventral patterning of the mesoderm.


Network centrality in patients with acute unilateral open globe injury: A voxel‑wise degree centrality study.
The present study aimed to investigate functional networks underlying brain‑activity alterations in patients with acute unilateral open globe injury (OGI) and associations with their clinical features using the voxel‑wise degree centrality (DC) method. In total, 18 patients with acute OGI (16 males and 2 females), and 18 healthy subjects (16 males and 2 females), closely matched in age, sex and education, participated in the present study. Each subject underwent a resting‑state functional magnetic resonance imaging scan. The DC method was used to assess local features of spontaneous brain activity. Receiver operating characteristic curve analysis was used to distinguish OGIs from healthy controls (HCs). Correlation analysis was used to examine the association between the observed mean DC values of different brain areas and behavioral performance. Compared with HCs, patients with acute unilateral OGI had significantly increased DC values in the bilateral primary visual cortex (V1/V2) and left precuneus (PCUN), and significantly decreased DC values in the right insula, left insula, right inferior parietal lobule (IPL)/supramarginal gyrus (SMG), IPL/SMG, right supplementary motor area and right postcentral gyrus. Additionally, in the acute OGI group, it was observed that the duration of OGI was negatively correlated with the DC signal value of the bilateral V1/V2 (r=‑0.581; P=0.011) and left PCUN (r=‑0.508; P=0.031). Acute OGI led to brain functional network dysfunction in a number of brain regions, which may indicate impairment of the visual cortex and other vision‑associated brain regions in OGI.


Employee-benefit plans, 1975.
Despite the national decline in the number of employed workers in 1975, the number of workers covered lnder most types of employee-benefit plans increased slightly. Contributions and benefit payments underwent the greatest change. Total contributions increased 17 percent and benefit payments rose 14 percent. In part this change can be attributed to inflation, but it also reflects real growth in contributions and payments for most types of plans, particularly those for retirement and health care benefits. Review of the private pension plans shows that an increasing number were terminated in 1975, but the reason has not been determined; contributions to these retirement plans showed one of the largest annual increases ever.


Comparison of long-term survival of 1986 consecutive patients with breast cancer treated at the National Cancer Institute of Milano, Italy (1971 to 1972 and 1977 to 1978).
Long-term survival of 1986 consecutive patients with infiltrating duct carcinoma of the breast treated at the National Cancer Institute of Milano (Italy) in two periods of time (1971 to 1972 and 1977 to 1978) was comparatively evaluated to verify if the evolving concepts in the management of breast cancer had an impact on survival. The authors found that 10-year survival of our patients increased from 59.4% of the first period of time to 65% of the second (P = 0.005). Both node-negative (N-) and node-positive (N+) patients had an improvement of survival rates at 10 years of the same magnitude: 6.8% and 5.9% respectively. Taking into consideration both the maximum diameter of the primary tumor and the status of axillary nodes it was found that in (1) both N- and N+ patients with a primary tumor of no more than 2 cm in greatest diameter, the improvement of survival was not statistically significant; and (2) both N- and N+ patients with a primary greater than 2 cm in maximum diameter had a better chance of survival in the second time period.


Regulation of human cerebral cortical development by EXOC7 and EXOC8, components of the exocyst complex, and roles in neural progenitor cell proliferation and survival.
The exocyst complex is a conserved protein complex that mediates fusion of intracellular vesicles to the plasma membrane and is implicated in processes including cell polarity, cell migration, ciliogenesis, cytokinesis, autophagy, and fusion of secretory vesicles. The essential role of these genes in human genetic disorders, however, is unknown. We performed homozygosity mapping and exome sequencing of consanguineous families with recessively inherited brain development disorders. We modeled an EXOC7 splice variant in vitro and examined EXOC7 messenger RNA (mRNA) expression in developing mouse and human cortex. We modeled exoc7 loss-of-function in a zebrafish knockout. We report variants in exocyst complex members, EXOC7 and EXOC8, in a novel disorder of cerebral cortex development. In EXOC7, we identified four independent partial loss-of-function (LOF) variants in a recessively inherited disorder characterized by brain atrophy, seizures, and developmental delay, and in severe cases, microcephaly and infantile death. In EXOC8, we found a homozygous truncating variant in a family with a similar clinical disorder. We modeled exoc7 deficiency in zebrafish and found the absence of exoc7 causes microcephaly. Our results highlight the essential role of the exocyst pathway in normal cortical development and how its perturbation causes complex brain disorders.


Benchmarks of successful physician-hospital organizations.
In recent years, there have been a proliferation of physician-hospital organizations (PHOs) in the medical community across the country. To date, many of them have been ineffective with unproven track records. This article will explore some of the benchmarks of successful PHOs.


Reliability and validity of the functional assessment of cancer therapy-ovarian.
To report the reliability and validity of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) in a consecutive series of outpatients with epithelial ovarian cancer. Two hundred thirty-two ovarian cancer patients attending an outpatient gynecologic oncology clinic completed questionnaires at baseline. The patients' FACT-O scores were compared with their performance status, disease stage, treatment status, and other factors hypothesized to be related to quality of life. Patients received a second questionnaire either one week after baseline to assess the instrument's test-retest reliability and/or two months after baseline to evaluate its sensitivity to change in performance status. Internal consistency and test-retest reliability of the FACT-O were adequate. Overall, the scales correlated with other measures as expected; all correlations were in the hypothesized direction. Patients with advanced disease, poor performance status, and who were receiving active treatment had lower scores on physical, functional, and ovarian cancer-specific scales. The total FACT-O and emotional well-being scores were lower for patients with poor performance status and patients in active treatment. The FACT-O total and all subscale scores except emotional well-being were sensitive to decreases in performance status. Overall, the FACT-O provides a reliable and valid assessment of the quality of life of women with ovarian cancer, and is appropriate as a brief quality of life assessment in clinical trials and descriptive studies.


The iron-H2O2-iodide cytotoxic system.
A potent antimicrobial system is described which consists of ferrous sulfate (Fe2+), hydrogen peroxide (H2O2), and iodide in 0.02 M sodium acetate buffer pH 5.5. H2O2 could be replaced by the H2O2-generating system glucose + glucose oxidase. This system, unlike the myeloperoxidase-H2O2-halide system, was ineffective when iodide was replaced by bromide, chloride, or thyroxine, and was inhibited by EDTA, the hydroxyl radical scavengers mannitol and ethanol, and phosphate and lactate buffers at the same concentration and pH as the acetate buffer used. The acetate buffer, however, could be replaced by water. It is proposed that Fe2+ and H2O2 (Fenton's reagent) generate OH X (or a closely related substance), which interacts with iodide to form one or more toxic species.


Studies on periodontitis and analyses of individuals at risk for periodontal diseases.
Periodontal disease is an infectious disease initiated by microbial plaque, which accumulates on the tooth surface at the gingival margin and induces an inflammatory reaction. The function of the inflammatory process is to protect the host, however the process may also contribute to tissue destruction. Most individuals show gingival inflammation, but only a limited number suffer from periodontitis i.e. loss of attachment. Without treatment, periodontitis will result in tooth mobility and subsequent tooth mortality. Independent of ethnicity, 10%-15% of an adult population will develop severe periodontitis The aim of this thesis has been to analyse individuals at risk for periodontal disease. Four studies have been conducted in 2 different groups of individuals with: Recurrent periodontitis kept in a maintenance care program--studies I-III. Type 2 diabetes (T2D)--study IV. In study I, the clinicaleffect of local periodontitis treatment with an antibiotic gel was investigated. In study II, the microbiologicaleffect of periodontitis treatment with the same antibiotic gel as in study I was investigated. In study III, it was investigated whether the interleukin-l (IL-1alpha and beta) and interleukin-6 (IL-6) gene polymorphisms were associated with the susceptibility of chronic periodontitis. In study IV, the prevalence of periodontitis in individuals with T2D was investigated, together with the prevalence of diabetic complications in relation to periodontal disease. We also studied whether there was a difference in dental care habits and knowledge of oral health between T2D subjects with and without periodontal disease. In conclusion, this thesis did not find any significant clinical and microbiological differences between subjects with recurrent periodontal disease treated with a locally delivered metronidazole gel compared to a placebo gel. Neither could we find an association between genetic variants in the IL-lalpha, IL-beta and IL-6 genes in individuals with or without periodontal disease. The prevalence of severe periodontitis, according to radiographic criteria, was almost 20% in subjects with T2D. This was further confirmed by clinical parameters. T2D individuals with periodontal disease demonstrated a higher HbAlc level, a higher prevalence of cardiovascular complications and a higher proportion of smokers compared to periodontally healthy T2D subjects. Finally, T2D individuals seem to lack sufficient knowledge about oral health.


Human Papillomavirus (HPV) Genotype Distribution in Patients with Recurrent Respiratory Papillomatosis (RRP) in Iran
Background: Currently, recurrent respiratory papillomatosis (RRP), common laryngeal warts in the upper airway systems of children and adults are on the increase. Human papillomaviruses (HPVs) are suspected as causative agents. This study concerned HPV incidence and genotype distribution in Iranian RRP patients. Methods: Specimens were collected from RRP patients referred to hospitals affiliated with Iran University of Medical Sciences, Tehran, Iran, from Dec 2014 to Feb 2016 in a cross sectional study. After DNA extraction with an QIAamp® DNA FFPE Tissue Kit, conventional PCR was performed and products were sequenced. INNO-LiPA HPV Genotyping Extra assays as another method for genotyping were conducted. CLC Main Workbench 5 and MEGA6 software as well as SPSS v.20 were used for further analysis. Results: Of the total of 12 patients, 6 (50%) were male. Total mean age (y) ± SD was 9.8±6.3. All RRP patients suffered from HPV infection, with HPV-6 found in 75% (9/12) and HPV-11 in 16.7% (2/12) and one co-infection by both HPV-6 and 11. Statistically, there were no correlations between demographic variables and HPV infection. Conclusion: The major cause of RRP is HPV genotypes 6 and 11 increasing the risk of a requirement for medical interventions. Broader studies are needed to clarify the major risk factors in RRP patients.


Homeopathy in the treatment of fibromyalgia--a comprehensive literature-review and meta-analysis.
Coping with the complex nature of fibromyalgia symptoms (FMS) still remains a challenge for patients. Taking into account the possible adverse events of pharmacological treatments patients often seek additional treatments for the management of fibromyalgia and turn towards complementary and alternative medicine (CAM). In this review, we aimed to investigate the current state of literature of homeopathy in the treatment of FMS. We searched Medline, the Cochrane Register of Controlled Trials, Embase, AMED, PsycInfo and CAMbase for the terms "fibromyalgia AND homeopath$" through February 2013. In addition we searched Google Scholar, the library of the Carstens Foundation and that of the Deutsche Homöopathische Union (DHU). Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated and meta-analyzed using the generic inverse variance method. We found 10 case-reports, 3 observational studies, 1 non-randomized and 4 randomized controlled trials (RCTs) on homeopathy for fibromyalgia. Both case reports and observational studies are naturally predominated by the use of qualitative and not validated outcome measures. Meta-analyses of CCTs revealed effects of homeopathy on tender point count (SMD=-0.42; 95%CI -0.78, -0.05; P=0.03), pain intensity (SMD=-0.54; 95%CI -0.97, -0.10; P=0.02), and fatigue (SMD=-0.47; 95%CI -0.90, -0.05; P=0.03) compared to placebo. The results of the studies as well as the case reports define a sufficient basis for discussing the possible benefits of homeopathy for patients suffering from fibromyalgia syndrome although any conclusions based on the results of this review have to be regarded as preliminary.


Development of Risk-Taking, Perspective-Taking, and Inhibitory Control During Adolescence.
Structural and functional brain development is thought to lead to different developmental progressions of cognitive control, risk/reward processing, and social cognition during adolescence. We compared these abilities in a cross-sectional sample of 90 adolescents aged 12, 15, or 17 years old, using computerized measures of inhibitory control (Go/No-Go task), risk-taking (Balloon Analogue Risk task), and social perspective-taking (Director task). Fifteen-year-olds exhibited better inhibitory control than 12-year-olds, while 17-year-olds exhibited greater perspective-taking than younger adolescents. Risk-taking was greater in older adolescents than 12-year-olds when controlling for inhibitory control. These findings are consistent with earlier findings obtained in separate samples.


Prevalence and Predictors of Postictal Confusion After Electroconvulsive Therapy.
To investigate the prevalence and predictors of postictal confusion (PIC) in patients who received electroconvulsive therapy (ECT). We conducted chart reviews for 79 patients who were receiving inpatient ECT. Subjects with PIC were identified. PIC was defined by confusion, disorientation, motor restlessness, purposeless movement, and nonresponse to verbal commands following ECT within an hour, intravenous benzodiazepine was necessary to manage disturbed behavior. Multivariable logistic regression analysis was used to examine the association of PIC with demographic and clinical variables. Prevalence of PIC was 36.7%. In 912 ECT sessions, the occurrence of PIC was 86 times. Patients with PIC (n = 29) had significant higher body mass index (BMI) (27 ± 6.6 kg/m2 vs 24.1 ± 5.2 kg/m2, t = -2.22, df = 77, p = 0.029) than patients without PIC (n = 50). PIC associated with BMI (Pearson correlation = 0.25, p = 0.029). BMI was significant predictor of PIC after adjusting for other covariates (odds ratio = 0.91, 95% CI= 0.83-0.99, p < 0.035). PIC was not uncommon in patients receiving ECT. BMI was an independent predictor of PIC. Psychiatrists should be aware of the risks of PIC in patients with high BMI receiving ECT.


The use of BoneWelding® technology in spinal surgery: an experimental study in sheep.
The innovative BoneWelding(®) technology, where ultrasound energy bonds bioresorbable implants to bone, was tested for its feasibility in spine surgery and its local thermal effects. The three tested concepts consisted of implementation of a resorbable plating system, two converging polymer pins and suture anchors to the cervical vertebral bodies. Bioresorbable polylactide implants (PLDLLA 70/30) were inserted ventrally into the third and fourth vertebral body of seven sheep, of which six were sacrificed at 2 months and one sheep immediately after temperature measurements during implant insertion. Polymer screws were used as controls. Qualitative, semi-quantitative histological, and quantitative histomorphometrical evaluation showed excellent anchorage of the implants, new mineralized bone at the implant-bone interface, no inflammatory cell reaction or thermal damage to the adjacent bone in response to the novel insertion technology. The application of two converging pins, parallel inserted polymer pins, or fusion of the implant to the polymer plates did not affect the overall excellent tissue tolerance of the technology. Temperature increase during insertion was noticed but never exceeded 47°C for less than 1 s. The BoneWelding(®) technology was proven to be safe and easy to apply.


Prevention of Neonatal Hypoglycemia With Oral Glucose Gel for High-Risk Newborns.
Neonatal hypoglycemia (glucose <47) is the most common metabolic problem in newborns (incidence 5% - 15%) and can cause adverse outcomes, even in the absence of noticeable symptoms. Oral glucose gel (OGG) is safe and effective for treatment of neonatal hypoglycemia. In order to reduce interventions such as intravenous (IV) dextrose administration and neonatal intensive care unit (NICU) transfer, in October 2017, we implemented a protocol in our Level 1 rural community hospital to identify newborns with asymptomatic hypoglycemia based on risk factors and treat them with OGG. Risk factors include large or small size for gestational age, maternal gestational diabetes, preterm and late preterm birth, and newborns requiring resuscitation. Chart review was performed for all infants born at our hospital from October 1, 2016 through September 30, 2018. Data for year 1-the period before protocol implementation (October 2016- September 2017)-was compared to post implementation data from year 2 (October 2017-September 2018). There was a significant risk reduction in newborns requiring interventions due to hypoglycemia after protocol implementation (P = 0.029, Student t test). In year one, 7 of 310 total newborns required IV dextrose or NICU transfer related to neonatal hypoglycemia. In year two, 108 out of 250 total newborns were tested for asymptomatic hypoglycemia based on risk factors identified in the protocol. Of those tested, 31 newborns demonstrated hypoglycemia and received OGG. None of the 250 newborns required further associated interventions. Protocol-based hypoglycemia testing based on risk factors with subsequent OGG administration was effective in reducing the need for IV dextrose and NICU transfer from our Level 1 rural community hospital.


Protein losing enteropathy: comprehensive review of the mechanistic association with clinical and subclinical disease states.
Protein losing enteropathy (PLE) has been associated with more than 60 different conditions, including nearly all gastrointestinal diseases (Crohn's disease, celiac, Whipple's, intestinal infections, and so on) and a large number of non-gut conditions (cardiac and liver disease, lupus, sarcoidosis, and so on). This review presents the first attempt to quantitatively understand the magnitude of the PLE in relation to the associated pathology for three different disease categories: 1) increased lymphatic pressure (e.g., lymphangiectasis); 2) diseases with mucosal erosions (e.g., Crohn's disease); and 3) diseases without mucosal erosions (e.g., celiac disease). The PLE with lymphangiectasis results from rupture of the mucosal lymphatics, with retrograde drainage of systemic lymph into the intestinal lumen with the resultant loss of CD4 T cells, which is diagnostic. Mucosal erosion PLE results from macroscopic breakdown of the mucosal barrier, with the epithelial capillaries becoming the rate-limiting factor in albumin loss. The equation derived to describe the relationship between the reduction in serum albumin (CP) and PLE indicates that gastrointestinal albumin clearance must increase by at least 17 times normal to reduce the CP by half. The strengths and limitations of the two quantitative measures of PLE (51Cr-albumin or α1-antitrypsin [αAT] clearance) are reviewed. αAT provides a simple quantitative diagnostic test that is probably underused clinically. The strong, unexplained correlation between minor decreases in CP and subsequent mortality in seemingly healthy individuals raises the question of whether subclinical PLE could account for the decreased CP and, if so, could the mechanism responsible for PLE play a role in the increased mortality? A large-scale study correlating αAT clearance with serum albumin concentrations will be required in order to determine the role of PLE in the regulation of the serum albumin concentration of seemingly healthy subjects.


Common carp Cyprinus carpio responses to sub-chronic exposure to perfluorooctanoic acid.
Perfluorooctanoic acid (PFOA) is an important and diffuse perfluorinated alkylated substance, but knowledge of the toxicological effects of this endocrine disrupter in fish is limited. Adult common carp Cyprinus carpio, L. were exposed to 200 ng/l (a concentration reported in impacted aquatic ecosystems) and 2 mg/l PFOA solutions in a flow-through system for 56 days to determine tissue accumulation and histological alterations of the primary target organs. PFOA was extracted from blood, gill, liver, muscle, kidney, gonad, and brain by an ion-pairing liquid extraction procedure and quantified using high performance liquid chromatography with electrospray ionization tandem mass spectrometry. The limit of detection (LOD) was 0.4 ng/g wet weight (ww). PFOA was not detectable in unexposed fish or in fish exposed to 200 ng/l, but was >LOD in most samples of carp exposed to 2 mg/l. Mean PFOA concentration ranged from 0.5 to 65 ng/g ww, depending on the tissue, with highest levels in the blood and liver. There were no significant differences in condition factor, hepato-somatic index, or gonado-somatic index among the fish of the three groups. Histological, histochemical, and immunohistochemical staining was performed on sections of liver and gonad. Occurrence of atretic oocytes and a paucity of spermatozoa were documented in carp treated with 2 mg/l PFOA. Exposed fish did not show gross hepatic anomalies, but there was enhancement of hepatocytes in proliferation (positive to anti-PCNA antibody) compared to controls.


Walnuts (Juglans regia) Chemical Composition and Research in Human Health.
Walnuts are among the most widely consumed commercially grown tree nuts in the world. Many health benefits have been claimed for the consumption of these, including reduced risk of cardiovascular disease, coronary heart disease, type II diabetes treatment, and prevention and treatment of certain cancers, and the lessening of symptoms attributed to age-related and other neurological disorders. The health-promoting benefits of walnut consumption are ascribed to its fatty acid profile, which is rich in polyunsaturated fatty acids with a particularly high ω3:ω6 ratio-the highest among all the tree nuts. The content of polyphenols and other phytochemicals in walnuts, with their claimed cytotoxic properties, also make them an attractive candidate for research for the prevention of free radical-induced nucleic acid damage. Research of walnut consumption in humans and animals employing a range of data sets and statistical methods suggest that walnuts may be considered a safe potential nutraceutical or possibly pharmaceutical substance. Nevertheless, few reviews of scientific research on the proposed benefits of these nuts exist, in spite of the numerous claims attributed to them in the lay media. This brief review article attempts to disseminate much of the information surrounding walnut consumption, and human health benefits, to other scientists and the interested general reader.


Magnetic resonance and the human brain: anatomy, function and metabolism.
The introduction and development, over the last three decades, of magnetic resonance (MR) imaging and MR spectroscopy technology for in vivo studies of the human brain represents a truly remarkable achievement, with enormous scientific and clinical ramifications. These effectively non-invasive techniques allow for studies of the anatomy, the function and the metabolism of the living human brain. They have allowed for new understandings of how the healthy brain works and have provided insights into the mechanisms underlying multiple disease processes which affect the brain. Different MR techniques have been developed for studying anatomy, function and metabolism. The primary focus of this review is to describe these different methodologies and to briefly review how they are being employed to more fully appreciate the intricacies associated with the organ, which most distinctly differentiates the human species from the other animal forms on earth.


An Automated Nanowell-Array Workflow for Quantitative Multiplexed Single-Cell Proteomics Sample Preparation at High Sensitivity.
Multiplexed and label-free mass spectrometry-based approaches with single-cell resolution have attributed surprising heterogeneity to presumed homogenous cell populations. Even though specialized experimental designs and instrumentation have demonstrated remarkable advances, the efficient sample preparation of single cells still lags. Here, we introduce the proteoCHIP, a universal option for single-cell proteomics sample preparation including multiplexed labeling up to 16-plex with high sensitivity and throughput. The automated processing using a commercial system combining single-cell isolation and picoliter dispensing, the cellenONE, reduces final sample volumes to low nanoliters submerged in a hexadecane layer simultaneously eliminating error-prone manual sample handling and overcoming evaporation. The specialized proteoCHIP design allows direct injection of single cells via a standard autosampler resulting in around 1500 protein groups per TMT10-plex with reduced or eliminated need for a carrier proteome. We evaluated the effect of wider precursor isolation windows at single-cell input levels and found that using 2 Da isolation windows increased overall sensitivity without significantly impacting interference. Using the dedicated mass spectrometry acquisition strategies detailed here, we identified on average close to 2000 proteins per TMT10-plex across 170 multiplexed single cells that readily distinguished human cell types. Overall, our workflow combines highly efficient sample preparation, chromatographic and ion mobility-based filtering, rapid wide-window data-dependent acquisition analysis, and intelligent data analysis for optimal multiplexed single-cell proteomics. This versatile and automated proteoCHIP-based sample preparation approach is sufficiently sensitive to drive biological applications of single-cell proteomics and can be readily adopted by proteomics laboratories.


Risk factors for resistance to ciprofloxacin in community-acquired urinary tract infections due to Escherichia coli in an elderly population.
Antimicrobial resistance to ciprofloxacin is rising worldwide, especially in bacteria causing urinary tract infections (UTIs). Prudent use of current antibiotic drugs is therefore necessary. We analysed (modifiable) risk factors for ciprofloxacin-resistant Escherichia coli. Urinary cultures of UTIs caused by E. coli were collected from participants in the Rotterdam Study, a prospective cohort study in an elderly population, and analysed for susceptibility to ciprofloxacin. Multivariate logistic regression was performed to investigate several possible risk factors for resistance. Ciprofloxacin resistance in 1080 E. coli isolates was 10.2%. Multivariate analysis showed that higher age (OR 1.03; 95% CI 1.00-1.05) and use of two (OR 5.89; 95% CI 3.45-10.03) and three or more (OR 3.38; 95% CI 1.92-5.97) prescriptions of fluoroquinolones were associated with ciprofloxacin resistance, while no association between fluoroquinolone use more than 1 year before culture and ciprofloxacin resistance could be demonstrated. Furthermore, a high intake of pork (OR 3.68; 95% CI 1.36-9.99) and chicken (OR 2.72; 95% CI 1.08-6.85) and concomitant prescription of calcium supplements (OR 2.51; 95% CI 1.20-5.22) and proton pump inhibitors (OR 2.04; 95% CI 1.18-3.51) were associated with ciprofloxacin resistance. Ciprofloxacin resistance in community-acquired UTI was associated with a high intake of pork and chicken and with concomitant prescription of calcium supplements and proton pump inhibitors. Modification of antibiotic use in animals as well as temporarily stopping the prescription of concomitant calcium and proton pump inhibitors need further evaluation as strategies to prevent ciprofloxacin resistance.


Bioremediation of Dichlorodiphenyltrichloroethane (DDT)-Contaminated Agricultural Soils: Potential of Two Autochthonous Saprotrophic Fungal Strains.
DDT (dichlorodiphenyltrichloroethane) was used worldwide as an organochlorine insecticide to control agricultural pests and vectors of several insect-borne human diseases. It was banned in most industrialized countries; however, due to its persistence in the environment, DDT residues remain in environmental compartments, becoming long-term sources of exposure. To identify and select fungal species suitable for bioremediation of DDT-contaminated sites, soil samples were collected from DDT-contaminated agricultural soils in Poland, and 38 fungal taxa among 18 genera were isolated. Two of them, Trichoderma hamatum FBL 587 and Rhizopus arrhizus FBL 578, were tested for tolerance in the presence of 1-mg liter-1 DDT concentration by using two indices based on fungal growth rate and biomass production (the tolerance indices Rt:Rc and TI), showing a clear tolerance to DDT. The two selected strains were studied to evaluate catabolic versatility on 95 carbon sources with or without DDT by using the Phenotype MicroArray system and to investigate the induced oxidative stress responses. The two strains were able to use most of the substrates provided, resulting in both high metabolic versatility and ecological functionality in the use of carbon sources, despite the presence of DDT. The activation of specific metabolic responses with species-dependent antioxidant enzymes to cope with the induced chemical stress has been hypothesized, since the presence of DDT promoted a higher formation of reactive oxygen species in fungal cells than the controls. The tested fungi represent attractive potential candidates for bioremediation of DDT-contaminated soil and are worthy of further investigations.IMPORTANCE The spread and environmental accumulation of DDT over the years represent not only a threat to human health and ecological security but also a major challenge because of the complex chemical processes and technologies required for remediation. Saprotrophic fungi, isolated from contaminated sites, hold promise for their bioremediation potential toward toxic organic compounds, since they might provide an environment-friendly solution to contamination. Once we verified the high tolerance of autochthonous fungal strains to high concentrations of DDT, we showed how fungi from different phyla demonstrate a high metabolic versatility in the presence of DDT. The isolates showed the singular ability to keep their functionality, despite the DDT-induced production of reactive oxygen species.


Clinically meaningful reduction in pruritus in patients with cutaneous T-cell lymphoma treated with romidepsin.
Patients with cutaneous T-cell lymphoma (CTCL) frequently experience severe pruritus that can significantly impact their quality of life. Romidepsin is approved by the US Food and Drug Administration (FDA) for the treatment of patients with CTCL who have received at least one prior systemic therapy, with a reported objective response rate of 34%. In a phase 2 study of romidepsin in patients with CTCL (GPI-04-0001), clinically meaningful reduction in pruritus (CMRP) was evaluated as an indicator of clinical benefit by using a patient-assessed visual analog scale. To determine the effect of romidepsin alone, confounding pruritus treatments including steroids and antihistamines were prohibited. At baseline, 76% of patients reported moderate-to-severe pruritus; 43% of these patients experienced CMRP, including 11 who did not achieve an objective response. Median time to CMRP was 1.8 months, and median duration of CMRP was 5.6 months. Study results suggest that the clinical benefit of romidepsin may extend beyond objective responses.


Patients' Preferences for Treatment for Dupuytren's Disease: A Discrete Choice Experiment.
Although in modern medicine, patients' preferences are important, these have never been defined for characteristics of Dupuytren treatment. This study determines these patients' preferences using a discrete choice experiment. A multicenter discrete choice experiment study was conducted among patients with Dupuytren's disease who had been treated previously. Patients were asked about their preferences for attributes of Dupuytren treatments using scenarios based on treatment method, major and minor complication rates, recurrence rates, convalescence, residual extension deficit after treatment, and aesthetic results. The relative importance of these attributes and the tradeoffs patients were willing to make between them were analyzed using a panel latent class logit model. Five-hundred six patients completed the questionnaire. All above-mentioned attributes proved to influence patients' preferences for Dupuytren treatment (p < 0.05). Preference heterogeneity was substantial. Men who stated they performed heavy labor made different tradeoffs than women or men who did not perform heavy labor. In general, recurrence rate (36 percent) and extension deficit (28 percent) were the most important attributes in making treatment choices, followed by minor complication rate (13 percent). Patients accepted an increase in recurrent disease of 11 percent if they could receive needle aponeurotomy treatment instead of limited fasciectomy. This study confirms the importance of low recurrence rates and complete contracture corrections, but also emphasizes the significance of low complication rates. Convalescence was not an attribute, which scored high. The preference heterogeneity shows that patient consultations need to be targeted differently, which may result in different treatment decisions, depending on patient characteristics and preferences.


Reduced in vitro doxycycline susceptibility in plasmodium falciparum field isolates from Kenya is associated with PfTetQ KYNNNN sequence polymorphism.
Doxycycline is widely used for malaria prophylaxis by international travelers. However, there is limited information on doxycycline efficacy in Kenya, and genetic polymorphisms associated with reduced efficacy are not well defined. In vitro doxycycline susceptibility profiles for 96 Plasmodium falciparum field isolates from Kenya were determined. Genetic polymorphisms were assessed in P. falciparum metabolite drug transporter (Pfmdt) and P. falciparum GTPase tetQ (PftetQ) genes. Copy number variation of the gene and the number of KYNNNN amino acid motif repeats within the protein encoded by PftetQ were determined. Reduced in vitro susceptibility to doxycycline was defined by 50% inhibitory concentrations (IC50s) of ≥35,000 nM. The odds ratio (OR) of having 2 PfTetQ KYNNNN amino acid repeats in isolates with IC50s of >35,000 nM relative to those with IC50s of <35,000 nM is 15 (95% confidence interval [CI], 3.0 to 74.3; P value of <0.0002). Isolates with 1 copy of the Pfmdt gene had a median IC50 of 6,971 nM, whereas those with a Pfmdt copy number of >1 had a median IC50 of 9,912 nM (P = 0.0245). Isolates with 1 copy of PftetQ had a median IC50 of 6,370 nM, whereas isolates with a PftetQ copy number of >1 had a median IC50 of 3,422 nM (P < 0.0007). Isolates with 2 PfTetQ KYNNNN motif repeats had a median IC50 of 26,165 nM, whereas isolates with 3 PfTetQ KYNNNN repeats had a median IC50 of 3,352 nM (P = 0.0023). PfTetQ sequence polymorphism is associated with a reduced doxycycline susceptibility phenotype in Kenyan isolates and is a potential marker for susceptibility testing.


Crystallization and preliminary X-ray crystallographic study of Streptomyces olivaceoviridis E-86 beta-xylanase.
beta-Xylanase from Streptomyces olivaceoviridis E-86 has been crystallized by the hanging drop vapor diffusion method from 25% saturated ammonium sulfate and 2% McIlvaine buffer, pH 5.7. The crystals diffract to at least 1.9 A resolution, and belong to space group P2(1)2(1)2(1), with unit-cell dimensions of a=79.6 A, b=95.2 A, and c=140.3 A. There are probably two xylanase molecules (MW=45 K) per asymmetric unit.


The complete mitochondrial genome of western painted turtle, Chrysemys picta bellii (Chrysemys, Emydidae).
In this study, we report the complete mitochondrial genome sequence of western painted turtle, Chrysemys picta bellii. The genome is found to be 16,875 bp in length and has a base composition of A (34.4%), G (13.0%), C (26.0%), and T (26.6%). Similar to other turtles, it contains a typically conserved structure including 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 control region (D-loop). Most of the genes are encoded on H-strand, except for the eight tRNA and ND6 genes. All protein-coding genes start with an ATN codon except for COX1 and ND4, which initiate with GTG instead, and terminate with the typical stop codon (TAA/TAG) or a single T (T-) or an unexpected codon of AGG. The complete mitochondrial genome sequence provided here would be useful for further phylogenetic analysis and conservation genetic studies in C. p. bellii.


Renal hemodynamics and electrolyte excretions after reserpine and ethanol.
The participation of the peripheral nervous system in the renal response to an acute ethanol administration was investigated in dogs. The animals received water or ethanol (3 g/kg), with and without 2 days pretreatment with reserpine. Each group was examined 18 hours after the water or ethanol administration. In comparison to water controls, both reserpine and ethanol produced similar increases with respect to renal hemodynamics. The combined treatment produced a further significant increase in effective renal plasma flow. Reserpine alone produced increases in the rates of filtration and reabsorption of sodium and chloride; ethanol and reserpine-ethanol treatments produced further increases but did not alter the excretory rates. Although all three treatments produced increases in the rate of filtration of potassium, only ethanol and reserpine-ethanol treatments increased the excretory rate. Magnesium excretion was decreased by reserpine and reserpine-ethanol in comparison to water and ethanol, respectively; but calcium excretion was elevated in all the treatment groups. Zinc excretion was increased in the ethanol group. The results suggest that the secondary action of ethanol to produce release and possible depletion of peripheral catecholamine stores is not primarily involved with its renal effects, except in the case of magnesium and zinc metabolism.


5-Year Survival in Gastric Adenocarcinoma with Epithelial and Stromal Versican Expression.
Gastric cancer is the second most frequent cause of cancer death worldwide, despite dif- ferences in incidence around the world. The majority of gastric cancer cases concern gastric adenocarcinoma, which has a fairly high 5-year survival rate when coupled with early-stage diagnosis. Versican, a member of the aggregating chondroitin sulfate proteoglycans family, is accumulated predominantly in the tumor stroma. The aim of our study was to investigate versican expression in gastric adenocarcinoma. In this study we investigated 80 patients with gastric adenocarcinoma who underwent gastrectomy. Each sample was obtained from paraffin-embedded resected specimens of the stomach after histopathological diagnosis. Patient follow-up was performed every 3 months after the beginning of data collection. Survival analysis was calcu- lated using the Kaplan-Meier method for univariate analysis. Out of 80 patients with gastric adenocarcinoma, 76 cases (76.3%males and 23.7% females) completed the follow-up period. Positive versican expression in tumor epithelial and stromal cells was found in 39.5% and 22.4% of tumors, respectively. Shorter survival was observed among patients whose gastric adenocarcinoma expressed epithelial or stromal versican. In summary, the present study suggests that versican is likely a prognostic biomarker that predicts a poor outcome in patients with gastric adenocarcinoma. Comprehensive studies with larger sample sizes are needed.


Incisal edge reattachment: the effect of preparation utilization and design.
This study evaluated the effect of preparation utilization and design, and addition of resin composite to the bonding interface, on the fracture resistance of reattached incisal fragments. Sixty bovine incisors were distributed among 1 control group and 5 experimental groups. Experimental specimens were sectioned 3.0 mm from the incisal edge with a 0.15-mm wafering blade at a 25-degree inclination apically in a faciolingual direction. Two groups received no further preparation. Specimens in the other 3 groups received either external bevels, internal bevels, or combined external and internal bevels. One preparationless group was reattached with dentin bonding agent alone. All other fragments were reattached with a dentin bonding agent-resin composite interface. After thermocycling and 4 weeks of bond weathering, specimens were sheared to failure in a universal testing machine. No significant differences in fracture strength were observed among any of the experimental groups, yet each displayed significantly less resistance to fracture than the control group. Reattachment of fragments in all groups restored approximately one half or one third the fracture strength of the control teeth for crown or root fractures, respectively. Compared to the simple, expedient regimen of using a dentin bonding agent alone, nonconservative tooth modification and the addition of resin composite to the bonding interface did not increase resistance to fracture and thus provided no retentive advantage.


Prevalence of homelessness among hospitalized patients: A point-in-time survey.
Although homelessness is associated with increased acute healthcare utilization and poorer health outcomes, the prevalence of homelessness and housing insecurity in hospitalized patients is poorly characterized. We conducted an in-person survey to determine the prevalence of housing insecurity and homelessness among hospitalized patients at two hospitals in metropolitan Denver in conjunction with the Housing and Urban Development point-in-time count on January 24, 2022. Of the 271 surveyed patients, 79 (29.2%) reported experiencing either housing insecurity (17.3%) or homelessness (11.8%). Of those experiencing housing insecurity or homelessness, 69.6% reported chronic health conditions, 55.7% reported multiple hospitalizations in the preceding year, 38% reported mental health concerns and 39.2% reported substance use. The prevalence of homelessness among a hospitalized patient population was over 20-fold higher than community prevalence estimates. Housing insecurity also impacted a substantial proportion of hospitalized patients and was associated with high rates of co-morbid conditions.


Automated discovery and phylogenetic analysis of new toxin-antitoxin systems.
Although often viewed as elements "at the service of" bacteria, plasmids exhibit replication and maintenance mechanisms that make them purely "selfish DNA" candidates. Toxin-antitoxin (TA) systems are a spectacular example of such mechanisms: a gene coding for a cytotoxic stable protein is preceded by a gene coding for an unstable antitoxin. The toxin being more stable than the antitoxin, absence of the operon causes a reduction of the amount of the latter relative to the amount of the former. Thus, a cell exhibiting a TA system on a plasmid is 'condemned' either not to loose it or to die. Different TA systems have been described and classified in several families, according to similarity and functional parameters. However, given the small size and large divergence among TA system sequences, it is likely that many TA systems are not annotated as such in the rapidly accumulating NCBI database. To detect these putative TA systems, we developed an algorithm that searches public databases on the basis of predefined similarity and TA-specific structural constraints. This approach, using a single starting query sequence for each of the ParE, Doc, and VapC families, and two starting sequences for the MazF/CcdB family, identified over 1,500 putative TA systems. These groups of sequences were analyzed phylogenetically for a better classification and understanding of TA systems evolution. The phylogenetic distributions of the newly uncovered TA systems are very different within the investigated families. The resulting phylogenetic trees are available for browsing and searching through a java program available at http://ueg.ulb.ac.be/tiq/.


Novel nanoemulsion gel containing triple natural bio-actives combination of curcumin, thymoquinone, and resveratrol improves psoriasis therapy: in vitro and in vivo studies.
Curcumin, resveratrol, and thymoquinone are the potential natural bio-actives reported with good anti-psoriatic activity. However, poor aqueous solubility and limited skin permeation of these natural bio-actives hinder their effective delivery and potential therapeutic outcome. In this regard, current research work focuses on the design and optimization of nanoemulsion (NE) gel formulation for the concurrent delivery of these three drugs. The NE system is consisting of oleic acid as oil phase, Tween 20 as surfactant, and PEG 200 as co-surfactant. The optimized formulation exhibited the droplet size 76.20 ± 1.67 nm, PDI of 0.12 ± 0.05, RI of 1.403 ± 0.007, and viscosity of 137.9 ± 4.07 mp. Carbopol 940 (0.5% w/v) was used as the gelling agent to prepare the NE gel which exhibited a good texture profile. The optimized formulation exhibited a higher % of growth inhibition on A-431 cells and demonstrated good anti-angiogenic activity in the HET-CAM test. Finally, in vivo studies in Balb/c mice model showed improved anti-psoriatic conditions which indicated that the triple natural bio-actives combination in nanoemulgel formulation is effective in the management of psoriasis.


Comorbidity between asthma attacks and internalizing disorders among Puerto Rican children at one-year follow-up.
Authors examined the association between internalizing disorders and asthma attacks at 1-year follow-up among a community sample of 1,789 children and adolescents ages 5-18 years living on the island of Puerto Rico. The Diagnostic Interview Schedule for Children was administered to assess DSM-IV internalizing disorders during the past year. Children with a lifetime history of asthma attacks at baseline had greater odds of having an internalizing disorder at 1-year follow-up, independent of socio-demographic measures. However, an association was not found between asthma attacks and persistence of internalizing disorders. These findings show that the association between internalizing disorders and asthma attacks was replicated 1 year later in the same sample.


Comparative evaluation of initial and new versions of the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test for direct detection of Mycobacterium tuberculosis in respiratory and nonrespiratory specimens.
We evaluated the initial version of the Amplified Mycobacterium Tuberculosis Direct Test (Gen-Probe) (AMTDT 1) and the new version of AMTDT (AMTDT 2) for the detection of Mycobacterium tuberculosis directly from respiratory and nonrespiratory samples and compared the results with those of culture and staining methods. The assays were applied to 410 respiratory and 272 nonrespiratory samples collected from 515 patients. The combination of the culture results and clinical diagnosis was considered to be the "gold standard." Ninety-five respiratory specimens were collected from 67 patients with a diagnosis of pulmonary tuberculosis (TB) and 68 nonrespiratory specimens were collected from 61 patients with a diagnosis of extrapulmonary TB. With respiratory specimens, the sensitivity, specificity, and positive and negative predictive values were 83, 100, 100, and 96%, respectively, for AMTDT 1 and 94.7, 100, 100, and 98.4%, respectively, for AMTDT 2. With nonrespiratory specimens, the sensitivity, specificity, and positive and negative predictive values were 83, 100, 100, and 94%, respectively, for AMTDT 1 and 86.8, 100, 100, and 98.4%, respectively, for AMTDT 2. The overall results of AMTDT 1 and AMTDT 2 were concordant for 97% (661 of 682) of the samples. Statistically significant differences in sensitivities were found between AMTDT 1 and AMTDT 2 with respiratory specimens. It was concluded that although both nucleic acid amplification methods are rapid, sensitive, and specific for the detection of M. tuberculosis complex in all types of clinical samples, AMTDT 2 appeared to be more sensitive than AMTDT 1 when applied to smear-negative specimens. In contrast AMTDT 2 is more susceptible than AMTDT 1 to inhibitory substances in the amplification reaction. The turnaround time of AMTDT 2 is shorter (3.5 h) than that for AMTDT 1 (5 h).


Immunoprophylaxis of perinatal transmission of the hepatitis B virus: efficacy of hepatitis B immune globulin and hepatitis B vaccine in a low-prevalence area.
One hundred eleven newborn infants born of Spanish hepatitis B surface antigen (HBsAg) carrier mothers were consecutively assigned to one of three treatment groups. Group A was treated with three or four doses of hepatitis B immune globulin (HBIG) in one of three different schedules. Group B received one dose of hepatitis B vaccine (Hevac-B, Pasteur) at birth and at 1, 2 and 12 months. Group C was treated with the same vaccination schedule as group B and in addition received a single dose of HBIG at birth. Comparisons were made in the 85 babies who had strictly completed the immunization schedule and had been followed for at least 12 months. The three immunization protocols were equally effective, since none of the children became a chronic HBsAg carrier or developed acute symptomatic infection. There were five transient and subclinical infections among children who received only HBIG (group A), one transient infection in group B, and one in group C. There seems to be some correlation between anti-HBs levels and degree of protection, since all transient infections in group A occurred in the subgroups who did not maintain protective antibodies during the first 6 months. Although the percentage of responders in the two vaccinated groups did not differ significantly, children who received only vaccine reached higher antibody levels than those who also received HBIG. Our results suggest that any immunization schedule able to maintain anti-HBs levels during the first 6 months of life would be useful to prevent mother-to-infant transmission of the hepatitis B virus in areas where most of the carrier women are expected to be anti-HBe positive and hence relatively less infectious.


Perioperative spontaneous bilateral suprachoroidal hemorrhage.
Suprachoroidal hemorrhage is a rare condition, occurring most commonly in the perioperative period, although cases of unilateral spontaneous hemorrhages have been reported. We report a case of bilateral spontaneous suprachoroidal hemorrhage and discuss the potential causative factors.


A global two component signal transduction system that integrates the control of photosynthesis, carbon dioxide assimilation, and nitrogen fixation.
Photosynthesis, biological nitrogen fixation, and carbon dioxide assimilation are three fundamental biological processes catalyzed by photosynthetic bacteria. In the present study, it is shown that mutant strains of the nonsulfur purple photosynthetic bacteria Rhodospirillum rubrum and Rhodobacter sphaeroides, containing a blockage in the primary CO2 assimilatory pathway, derepress the synthesis of components of the nitrogen fixation enzyme complex and abrogate normal control mechanisms. The absence of the Calvin-Benson-Bassham (CBB) reductive pentose phosphate CO2 fixation pathway removes an important route for the dissipation of excess reducing power. Thus the mutant strains develop alternative means to remove these reducing equivalents, resulting in the synthesis of large amounts of nitrogenase even in the presence of ammonia. This response is under the control of a global two-component signal transduction system previously found to regulate photosystem biosynthesis and the transcription of genes required for CO2 fixation through the CBB pathway and alternative routes. In addition, this two-component system directly controls the ability of these bacteria to grow under nitrogen-fixing conditions. These results indicate that there is a molecular link between the CBB and nitrogen fixation process, allowing the cell to overcome powerful control mechanisms to remove excess reducing power generated by photosynthesis and carbon metabolism. Furthermore, these results suggest that the two-component system integrates the expression of genes required for the three processes of photosynthesis, nitrogen fixation, and carbon dioxide fixation.


Vitamin A and interstitial retinol-binding protein in an eye with recessive retinitis pigmentosa.
The composition and amount of vitamin A stored in the retinal pigment epithelium and choroid (RPE-Ch) was evaluated in postmortem donor eyes from a patient with retinitis pigmentosa that was probably inherited by an autosomal recessive mode. Additionally, the soluble proteins in the neural retina and RPE-Ch cytosols and interphotoreceptor matrix were examined collectively for the presence of interstitial retinol-binding protein (IRBP). Although there was depletion of the amount of vitamin A stored in the RPE, this was commensurate with the histopathologic findings on the RPE extent and thickness. No evidence was found for an accumulation of free retinol. Nearly all of the vitamin A stored in the RPE was esterified. As in normal eyes, the retinyl esters consisted mainly of palmitate mixed with a small proportion of stearate. Eleven-cis retinyl esters were present, although their proportion was lower than that reported for normals. IRBP could not be detected in stained gels of the soluble proteins, or by autoradiography of these gels after treatment with 125I-concanavalin A. These findings suggest that depletion of stored vitamin A, accumulation of free retinol, or deficiency of 11-cis isomer are unlikely to be causative factors in the retinal degeneration examined here. Although the depletion of IRBP seen at this advanced stage might be secondary to the advanced loss of photoreceptors, the authors cannot rule out the possibility that a relative deficiency or abnormality in this protein at earlier disease stages may contribute to the pathogenesis of retinitis pigmentosa.


Correlation of miRNA expression profiling in surgical pathology materials, with Ki-67, HER2, ER and PR in breast cancer patients.
New molecular markers related to prognosis and/or clinical outcome have been extensively studied in breast cancer. In particular, microRNA (miRNA) has attracted the interest of both basic and clinical investigators as one of the promising molecular markers of breast cancer patients. MiRNAs are a class of short noncoding RNAs that regulate mRNAs at posttranscriptional level and are deregulated in various human malignancies. Previous studies have reported that miRNAs were stably conserved in 10% formalin-fixed paraffin-embedded tissues without significant degradation, in contrast to more fragile RNA. Therefore, in this study, we examined 21 surgical breast cancer specimens using the Human Cancer microRNA PCR Array system (QIAGEN) to explore potential molecular targets of miRNAs. Profiling of miRNA expression in archival materials demonstrated that a group of deregulated miRNAs was associated with clinicopathological parameters of the patients, such as Ki-67, HER2, ER and PR. For instance, an abundant expression of multiple let-7 miRNA family, also known as tumor suppressor, was detected in low Ki-67 and HER2 groups. Elevated expression of 8 miRNAs overlapped between Ki-67+/HER2+/ER+/PR+ groups, including several known oncogenic miRNAs such as miR-148b, miR-15b, miR-200c, miR-150, miR-191, miR-96, miR-25 and miR-21. These results all indicated that when analyzing miRNAs in surgical pathology specimens of breast cancer as a biomarker, they should be examined as a cluster through miRNA profiling, rather than relying on the analysis of a single miRNA.


The presence of 5-hydroxymethylcytosine in animal deoxyribonucleic acid.
A method is given for small-scale preparation of DNA from 1.0-1.5g of adult rat tissues. The product from brain or liver is characterized by base ratios and phosphorus content which accord with reported values for rat tissue. It is reasonably free of RNA, protein and glycogen. It contains 5-hydroxymethylcytosine at a content of about 15% of the total cytosine bases present. 5-Hydroxymethylcytosine is also demonstrable in mouse and frog brain DNA and in the crude cytidylic acid fractions obtained from RNA hydrolysates of rat brain and liver. 5-Hydroxymethylcytosine is identified by paper chromatography, u.v. spectra in acid and alkaline solutions and by its conversion into 5-hydroxymethyluracil.


Investigating the energetic and entropic components of effective potentials across a glass transition.
By eliminating unnecessary details, coarse-grained (CG) models provide the necessary efficiency for simulating scales that are inaccessible to higher resolution models. However, because they average over atomic details, the effective potentials governing CG degrees of freedom necessarily incorporate significant entropic contributions, which limit their transferability and complicate the treatment of thermodynamic properties. This work employs a dual-potential approach to consider the energetic and entropic contributions to effective interaction potentials for CG models. Specifically, we consider one- and three-site CG models for ortho-terphenyl (OTP) both above and below its glass transition. We employ the multiscale coarse-graining (MS-CG) variational principle to determine interaction potentials that accurately reproduce the structural properties of an all-atom (AA) model for OTP at each state point. We employ an energy-matching variational principle to determine an energy operator that accurately reproduces the intra- and inter-molecular energy of the AA model. While the MS-CG pair potentials are almost purely repulsive, the corresponding pair energy functions feature a pronounced minima that corresponds to contacting benzene rings. These energetic functions then determine an estimate for the entropic component of the MS-CG interaction potentials. These entropic functions accurately predict the MS-CG pair potentials across a wide range of liquid state points at constant density. Moreover, the entropic functions also predict pair potentials that quite accurately model the AA pair structure below the glass transition. Thus, the dual-potential approach appears a promising approach for modeling AA energetics, as well as for predicting the temperature-dependence of CG effective potentials.


Blood-brain barrier permeability of 11C-labeled alcohols and 15O-labeled water.
The extraction of 11C-labeled methanol, ethanol, and isopropanol, as well as 15O-labeled water by the brain during a single capillary transit, was studied in vivo in six adult rhesus monkeys by external detection of the time course of these tracers subsequent to their internal carotid artery injection. The data demonstrate the feasibility of accurately measuring brain permeability of highly diffusible substances by this technique and show that neither water nor the alcohols studied freely equilibrate with brain when the cerebral blood flow exceeds 30 ml/100 g min-1. At a cerebral blood flow of 50 ml/100 g min-1 only about 93% of an injected bolus of labeled water freely exchanges with brain, compared with methanol (93%), ethanol (97%), and isopropanol (99%). The brain capillary permeability-surface area (PS) products computed from these data were 0.023 cm3/s g-1 (water), 0.024 cm3/s g-1 (methanol), 0.030 cm3/s g-1 (ethanol), and 0.062 cm3/s g-1 (isopropanol). This sequence of PS products is consistent with the individual lipid solubilities of the alcohols studied and underscores the unique brain permeability characteristics of lipid-insoluble water.


Depression and HIV risk among men who have sex with men in Tanzania.
Studies have shown high rates of depression among men who have sex with men (MSM) in developed countries. Studies have also shown association between depression and HIV risk among MSM. However, very little research has been done on depression among African MSM. We assessed depression and HIV risk among a sample of MSM in Tanzania. We reviewed data on 205 MSM who were recruited from two Tanzanian cities using the respondent driven sampling method. Demographic and behavioral data were collected using a structured questionnaire. HIV and sexually transmitted infections data were determined from biological tests. Depression scores were assessed using the Patient Health Questionnaire (PHQ-9). For the analysis, depression scores were dichotomized as depressed (PHQ > 4) and not depressed (PHQ ≤ 4). Bivariate and multivariable Poisson regression analyses were conducted to assess factors associated with depression. The prevalence of depression in the sample was 46.3%. The mean (±SD) age of the sample was 25 (±5) years. In bivariate analysis, depression was associated with self-identifying as gay (p = .001), being HIV positive (p < .001: <8% of MSM knew they were HIV infected) and having a high number of sexual partners in the last 6 months (p = .001). Depression was also associated with sexual (p = .007), physical (p = .003) and verbal (p < .001) abuse. In the Poisson regression analysis, depression was associated with verbal abuse (APR = 1.91, CI = 1.30-2.81). Depression rates were high among MSM in Tanzania. It is also associated with abuse, HIV and HIV risk behaviors. Thus, reducing the risk of depression may be helpful in reducing the risk of HIV among MSM in Africa. We recommend the colocation of mental health and HIV preventive services as a cost-effective means of addressing both depression and HIV risk among MSM in Africa.


The role of vision for online control of manual aiming movements in persons with autism spectrum disorders.
Recent studies suggest motor skills are not entirely spared in individuals with an autism spectrum disorder (ASD). Previous reports demonstrated that young adults with ASD were able to land accurately on a target despite increased temporal and spatial variability during their movement. This study explored how a group of adolescents and young adults with an ASD used vision and proprioception to land successfully on one of two targets. Participants performed eye movements and/or manual reaching movements, either with or without vision. Although eye movements were executed in a similar timeframe, participants with ASD took longer to plan and execute manual reaching movements. They also exhibited significantly greater variability during eye and hand movements, but were able to land on the target regardless of the vision condition. In general, individuals with autism used vision and proprioception. However, they took considerably more time to perform movements that required greater visual-proprioceptive integration.


Three-dimensional imaging of chemical phase transformations at the nanoscale with full-field transmission X-ray microscopy.
The ability to probe morphology and phase distribution in complex systems at multiple length scales unravels the interplay of nano- and micrometer-scale factors at the origin of macroscopic behavior. While different electron- and X-ray-based imaging techniques can be combined with spectroscopy at high resolutions, owing to experimental time limitations the resulting fields of view are too small to be representative of a composite sample. Here a new X-ray imaging set-up is proposed, combining full-field transmission X-ray microscopy (TXM) with X-ray absorption near-edge structure (XANES) spectroscopy to follow two-dimensional and three-dimensional morphological and chemical changes in large volumes at high resolution (tens of nanometers). TXM XANES imaging offers chemical speciation at the nanoscale in thick samples (>20 µm) with minimal preparation requirements. Further, its high throughput allows the analysis of large areas (up to millimeters) in minutes to a few hours. Proof of concept is provided using battery electrodes, although its versatility will lead to impact in a number of diverse research fields.


Color Doppler ultrasound guidance during renal angioplasty and stenting.
To investigate whether an imaging technique combining color Doppler ultrasonography and selective renal artery digital subtraction angiography reduces contrast requirements in patients with progressive renal insufficiency undergoing renal artery angioplasty and stenting. Eight patients (5 men; mean age 58 years) with renal artery stenosis and renal insufficiency underwent percutaneous transluminal angioplasty and stenting under color Doppler ultrasound guidance. Color Doppler ultrasound imaging yielded the information necessary for verifying catheter position, stent placement and expansion, and hemodynamics after revascularization. The combined imaging technique considerably reduced contrast requirements to only 10 mL in each case. No worsening of renal function was seen in any patient. The combined imaging procedure uses low doses of contrast agent and is especially suited to patients with renal dysfunction undergoing percutaneous renal revascularization.


Global prevalence and incidence of pressure injuries in hospitalised adult patients: A systematic review and meta-analysis.
Pressure injuries are frequently occurred adverse events in hospitals, affecting the well-being of patients and causing considerable financial burden to healthcare systems. However, the estimates of prevalence, incidence and hospital-acquired rate of pressure injury in hospitalised patients vary considerably in relevant published studies. To systematically quantify the prevalence and incidence of pressure injuries and the hospital-acquired pressure injuries rate in hospitalised adult patients and identify the most frequently occurring pressure injury stage(s) and affected anatomical location(s). Systematic review and meta-analysis. Medline, PubMed, Embase, Cochrane Library, CINAHL and ProQuest databases from January 2008 to December 2018. We included studies with observational, cross-sectional or longitudinal designs, reporting pressure injury among hospitalised adults (≥16 years) and published in English. Outcomes were point prevalence, incidence of pressure injuries and the hospital-acquired pressure injuries rate reported as percentages. Two reviewers independently appraised the methodological quality of included studies. Heterogeneity was assessed by using the I² statistic and random effects models were employed. Sources of heterogeneity were investigated by subgroup analysis and meta-regression. Of 7,489 studies identified, 42 were included in the systematic review and 39 of them were eligible for meta-analysis, with a total sample of 2,579,049 patients. The pooled prevalence of 1,366,848 patients was 12.8% (95% CI 11.8-13.9%); pooled incidence rate of 681,885 patients was 5.4 per 10,000 patient-days (95% CI 3.4-7.8) and pooled hospital-acquired pressure injuries rate of 1,893,593 was 8.4% (95% CI 7.6-9.3%). Stages were reported in 16 studies (132,530 patients with 12,041 pressure injuries). The most frequently occurred stages were Stage I (43.5%) and Stage II (28.0%). The most affected body sites were sacrum, heels and hip. Significant heterogeneity was noted across some geographic regions. Meta-regression showed that the year of data collection, mean age and gender were independent predictors, explaining 67% variability in the prevalence of pressure injuries. The year of data collection and age alone explained 93% of variability in hospital-acquired pressure injuries rate. This study suggested that the burden of pressure injuries remains substantial with over one in ten adult patients admitted to hospitals affected. Superficial pressure injuries, such as Stage I and II, are most common stages and are preventable. Our results highlight healthcare institutions' focus on pressure injuries globally and supports the need to dedicate resources to prevention and treatment on pressure injuries. Registration number: PROSPERO CRD42019118774.


Clinical and pathologic factors associated with subclinical spread of invasive melanoma.
Indications to treat invasive melanoma with Mohs micrographic surgery (MMS) or analogous techniques with exhaustive microscopic margin assessment have not been defined. Identify clinical and histologic factors associated with subclinical spread of invasive melanoma. This retrospective, cross-sectional study evaluated 216 invasive melanomas treated with MMS and melanoma antigen recognized by T cells 1 immunostaining. Logistic regression models were used to correlate clinicopathologic risk factors with subclinical spread and construct a count prediction model. Risk factors associated with subclinical spread by multivariate analysis included tumor localization on the head and neck (OR 3.28, 95% confidence interval [CI] 1.16-9.32), history of previous treatment (OR 4.18, 95% CI 1.42-12.32), age ≥65 (OR 4.45, 95% CI 1.29-15.39), and ≥1 mitoses/mm2 (OR 2.63, 95% CI 1.01-6.83). Tumor thickness and histologic subtype were not associated with subclinical spread. The probability of subclinical spread increased per number of risk factors, ranging from 9.22% (95% CI 2.57%-15.86%) with 1 factor to 80.32% (95% CI 68.13%-92.51%) with 5 factors. This study was conducted at a single academic institution with a small study population using a retrospective study design that was subject to potential referral bias. Clinical and histologic factors identify invasive melanomas that are at increased risk for subclinical spread and might benefit from MMS or analogous techniques prior to reconstruction.