Adenovirus 5 and 35 vectors expressing Plasmodium falciparum circumsporozoite surface protein elicit potent antigen-specific cellular IFN-gamma and antibody responses in mice.
Falciparum malaria vaccine candidates have been developed using recombinant, replication-deficient serotype 5 and 35 adenoviruses (Ad5, Ad35) encoding the Plasmodium falciparum circumsporozoite surface protein (CSP) (Ad5.CS, Ad35.CS) (Crucell Holland BV, Leiden, The Netherlands). To evaluate the immunogenicity of these constructs, BALB/cJ mice were immunized twice with either Ad5.CS, Ad35.CS, empty Ad5-vector (eAd5), empty Ad35 vector (eAd35), or saline. Another group received the CSP-based RTS,S malaria vaccine formulated in the proprietary Adjuvant System AS01B (GlaxoSmithKline Biologicals, Rixensart, Belgium). Here we report that Ad5.CS, Ad35.CS, and RTS,S/AS01B, elicited both cellular and serologic CSP antigen-specific responses in mice. These adenoviral vectors induce strong malaria-specific immunity and warrant further evaluation.


The implicit health-related self-concept in somatoform disorders.
Dual-process theories stress the importance of explicit as well as implicit cognitive processes for the development of somatoform disorders (SFDs).(1) In particular, the self-concept has been demonstrated to be a key factor in SFD. Yet, the self-concept in SFDs has been studied only on an explicit but not on an implicit level. The present study empirically examined the implicit health-related self-concept in SFDs by using the Implicit Association Test (IAT). Twenty-two patients with SFDs (according to DSM-IV) and 27 healthy control participants (CG) completed an IAT to assess associations of the self with illness- versus health-related words. (a) Patients with an SFD associated themselves more with illness-related words than patients in the CG, (b) this implicit self-concept was connected to self-reported bodily weakness in the SFD group, and (c) both the explicit and implicit health-related self-concepts were significantly related to the number and severity of bodily symptoms. However, the implicit measure had no incremental predictive value for symptom reports over the explicit self-concept measure. Due to the small sample size and the failure to match the SFD group and CG on education, further confirming evidence including other clinical control groups is needed. These findings are consistent with existing dual-process models of SFDs and could be of clinical relevance as they bring into focus implicit cognitive processes that may be targeted more directly for an effective treatment of SFDs.


Continuous and Rapid Solution Exchange in a Lipid Bilayer Perfusion System Based on Droplet-Interface Bilayer.
Because of the high sensitivity of lipid bilayers to external pressure fluctuations, a major challenge in functional studies of biological pores or ion channels is the difficulty in exchanging solutions rapidly while maintaining the stability of the lipid bilayer in a model membrane. Here we describe a droplet-interface bilayer-based perfusion system that has been routinely used in our research and is currently the most robust and stable perfusion system that provides prompt solution exchange surrounding a lipid bilayer. In this model membrane system, solutions can be completely exchanged within 1-2 s to obtain prompt responses of a lipid bilayer or membrane pores to the membrane environments. Also, our system is stable enough to sustain continuous perfusions up to at least dozens of minutes. To demonstrate, we show that acidification-induced protein channel insertion, substrate binding to protein channels, and pH gradient-driven protein translocation of anthrax toxin can be sequentially initiated by continuous perfusions in our system. Moreover, by rapidly switching the solutions, the protein translocation based on ratchet mechanisms can be paused and reinitiated iteratively in our system. Overall, this perfusion system provides a controllable and reliable solution exchange platform for investigations of pores and translocations on lipid bilayers.


Amplification by hyperoxia of coronary vasodilation induced by propofol.
We tested the hypothesis that in vitro coronary and myocardial effects of propofol (10-300 microM) should be significantly modified in an isolated and erythrocyte-perfused rabbit heart model in the absence (PaO(2) = 137 +/- 16 mm Hg, n = 12) or in the presence (PaO(2) = 541 +/- 138 mm Hg, n = 12) of hyperoxia. The induction of hyperoxia provoked a significant coronary vasoconstriction (-13% +/- 7%). Propofol induced increased coronary vasodilation in the presence of hyperoxia. Because high oxygen tension has been reported to induce a coronary vasoconstriction mediated by the closure of adenosine triphosphate-sensitive potassium channels, we studied the effects of propofol in 2 additional groups of hearts (n = 6 in each group) pretreated by glibenclamide (0.6 microM) and cromakalim (0.5 microM) in the absence and presence of hyperoxia, respectively. The pretreatment by glibenclamide induced a coronary vasoconstriction (-16% +/- 7%) which did not affect propofol coronary vasodilation. The pretreatment by cromakalim abolished the amplification of propofol coronary vasodilation in the presence of hyperoxia. Propofol induced a significant decrease in myocardial performance for a concentration >100 micro M both in the absence and presence of hyperoxia. We conclude that propofol coronary vasodilation is amplified in the presence of hyperoxia. This phenomenon is not explained by the previous coronary vasoconstriction induced by glibenclamide. However, the pretreatment of hearts by cromakalim abolished the amplification of propofol coronary vasodilation in the presence of hyperoxia. The myocardial effects of propofol were not affected by the presence of hyperoxia. Propofol induced a coronary vasodilation that was amplified in the presence of hyperoxia. This phenomenon does not seem to be related to previous coronary vasoconstriction. The myocardial effects of propofol were not significantly modified in the presence of hyperoxia.


Meta-Analysis Comparing Complete or Culprit Only Revascularization in Patients With Multivessel Disease Presenting With Cardiogenic Shock.
The optimal strategy for patients with an acute myocardial infarction (MI) and multivessel (MV) coronary artery disease complicated by cardiogenic shock (CS) remains unknown. We conducted a meta-analysis of all randomized controlled trials and observational studies that reported adjusted effect measures to evaluate the association of MV-PCI (percutaneous coronary intervention), compared with culprit only (C)-PCI, with cardiovascular events in patients admitted for CS and MV disease. We identified 12 studies (n = 1 randomized controlled trials, n = 11 observational) that included 7,417 patients (n = 1,809 treated with MV-PCI and n = 5,608 with C-PCI). When compared with C-PCI, MV-PCI was not associated with an increased risk of short-term death (odds ratio [OR] 1.14, 95% confidence interval [CI] 0.87 to 1.48, p = 0.35 and adjusted OR [ORadj] 1.00, 95% CI 0.70 to 1.43, p = 1.00). In-hospital and/or short-term mortality tended to be higher with MV-PCI, when compared with C-PCI, for CS patients needing dialysis (ß 0.12, 95% CI from 0.049 to 0.198; p= 0.001), whereas MV-PCI was associated with lower in-hospital and/or short-term mortality in patients with an anterior MI (ß -0.022, 95% CI -0.03 to -0.01; p <0.001). MV-PCI strategy was associated with a more frequent need for dialysis or contrast-induced nephropathy after revascularization (OR 1.36, 95% CI 1.06 to 1.75, p = 0.02). In conclusion, MV-PCI seems not to increase risk of death during short- or long-term follow-up when compared with C-PCI in patients admitted for MV coronary artery disease and MI complicated by CS. Furthermore, it appears a more favorable strategy in patients with anterior MI, whereas the increased risk for AKI and its negative prognostic impact should be considered in decision-making process. Further studies are needed to confirm our hypothesis on in these subpopulations of CS patients.


Human cortical networking by probabilistic and frequency-specific coupling.
Large-scale cortical networking patterns have been established based on the correlation of slow fluctuations of resting fMRI signals. However, the electrophysiological mechanism of cortical networking remained to be elucidated. With large-scale human ECoG recording, we developed a novel approach for functional network parcellation on the basis of probabilistic co-activation of cortical sites in spatio-temporal microstates. The parcellated networks were verified by electrical cortical stimulation (ECS) and somatosensory evoked potentials recording, which showed significantly higher accuracy than the traditional long-term correlation method. This provides direct electrophysiological evidence supporting the dynamic nature of cortical networking. Further analysis revealed that the brain-wide connectivity is likely established on the coupling of ECoG power envelop over a common carrier frequency ranging from alpha to low-beta (8-32Hz). Surprisingly, the cortical networking pattern over this specific frequency was found to be consistent across various tasks, which resembles the resting networks. The high similarity between the above functional network parcellation and the fMRI resting network atlas in individuals also suggested the slow power-envelope coupling of band-limited neural oscillations as the electrophysiological basis of spontaneous BOLD signals. Collectively, our findings on direct human recording revealed a probabilistic and frequency specific coupling mechanism for large-scale cortical networking shared by task and resting brain.


Structural evaluation of child physical abuse in trauma: Social determinants of health at the population level.
Child physical abuse (CPA) is closely linked to social factors like insurance status with limited evaluation at a structural population-level. This study evaluates the role of social determinants of health within the built environment on CPA. A single-institution retrospective review of pediatric trauma patients was conducted between January 2016 and December 2020. Patient address was geocoded to the census-tract level. Socioeconomic metrics, including poverty rate, supermarket access and Social Vulnerability Index (SVI) were estimated from the Food Access Research Atlas. Univariate and multivariable regression analyses were conducted to compare demographics and outcomes. Of 3,540 patients, 317 (9.0%) had concern for physical abuse reported in the registry. CPA patients were younger (7.5 vs 9.6 years, p<0.0001) and more often Black (37.0%, N = 117 vs 23.5%, N = 753; p<0.0001). CPA had higher injury severity scores (ISS) (7.9 vs 5.8, p<0.0001) and longer length of stay (5.3 vs 2.9 days, p<0.0001). CPA had higher Medicaid (73.0%, N = 232 vs 53.8%, N = 1748, p<0.0001) and SVI (0.65 vs 0.59, p<0.0001) with lower median income ($52,100 vs $56,100, p<0.0001) and more low-food access tracts (59.6% vs 53.6%, p = 0.06). Combined low-income and low-food access populations showed widened disparities (40.0% vs 28.9%, p = 0.0002). On multivariate analysis, CPA was associated with poverty (OR 2.3, 95% CI [0.979, 3.60], p = 0.0006), low-access Black share (OR 3.3, 95% CI [1.18, 5.47], p = 0.002) and urban designation (OR 1.5, 95% CI [1.13, 1.87], p = 0.004). The built-environment and population-level social determinants of health are related to child physical abuse and should influence advocacy and prevention. Level III. Retrospective.


Electrochemically deposition of metal-organic framework onto carbon fibers for online in-tube solid-phase microextraction of non-steroidal anti-inflammatory drugs.
Electrochemical deposition has been proposed as a promising approach for in situ immobilization of metal-organic framework (MOF) on conductive surfaces. It is favorable as it is time-saving, green, and does not require vigorous reaction conditions, which can be applied to the synthesis and immobilization of extraction materials for fiber in-tube solid phase microextraction. In this work, PPF-1 was immobilized on the surface of the carbon fibers by electrochemical method. The novel method overcame the problems including strict conditions and time-consuming operation. The modified carbon fibers were packed into the PEEK tube for extraction and analysis of three non-steroidal anti-inflammatory drugs (NSAIDs), which performed good extraction efficiency due to strong hydrogen bonding, hydrophobic interaction and π-π interaction between PPF-1 and analytes. The established method obtained good enrichment performance (enrichment factor between 230-540), low limits of detection (between 0.01-0.03 ng/mL), good linearity and good reproducibility (RSDs≤4.93%), which was successfully applied for the quantitative analysis of NSAIDs in human plasma samples.


Identification of the novel HLA-A*23:91N allele in a Saudi individual.
HLA-A*23:91N differs from HLA-A*23:01:01 by a single-nucleotide substitution (G → A) at position 369.


Combined PD-L1/TGFβ blockade allows expansion and differentiation of stem cell-like CD8 T cells in immune excluded tumors.
TGFβ signaling is associated with non-response to immune checkpoint blockade in patients with advanced cancers, particularly in the immune-excluded phenotype. While previous work demonstrates that converting tumors from excluded to inflamed phenotypes requires attenuation of PD-L1 and TGFβ signaling, the underlying cellular mechanisms remain unclear. Here, we show that TGFβ and PD-L1 restrain intratumoral stem cell-like CD8 T cell (TSCL) expansion and replacement of progenitor-exhausted and dysfunctional CD8 T cells with non-exhausted T effector cells in the EMT6 tumor model in female mice. Upon combined TGFβ/PD-L1 blockade IFNγhi CD8 T effector cells show enhanced motility and accumulate in the tumor. Ensuing IFNγ signaling transforms myeloid, stromal, and tumor niches to yield an immune-supportive ecosystem. Blocking IFNγ abolishes the anti-PD-L1/anti-TGFβ therapy efficacy. Our data suggest that TGFβ works with PD-L1 to prevent TSCL expansion and replacement of exhausted CD8 T cells, thereby maintaining the T cell compartment in a dysfunctional state.


Prostate-specific antigen flare induced by cabazitaxel-based chemotherapy in patients with metastatic castration-resistant prostate cancer.
A prostate-specific antigen (PSA) flare occurs in about 15% of metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel. This flare has no standard definition. Its impact on treatment efficacy is unclear. We sought to evaluate the incidence and characteristics of PSA flare on cabazitaxel, and its impact on survival. Multicentre retrospective review of consecutive patients treated with cabazitaxel second-line chemotherapy for mCRPC. Collection of baseline characteristics, disease history and PSA levels before and during cabazitaxel therapy. Overall survival (OS) and radiological/clinical progression-free survival (PFS) for patient groups corresponding to different definitions of PSA flare estimated by the Kaplan-Meier method and compared using the log-rank test. Overall, 125 patients were included. Median PFS and OS were 6.5 and 13.3 months, respectively. Depending upon the definition used, flare incidence ranged from 8.3% to 30.6%. The flare lasted <2.6 months. A PSA flare followed by a ⩾ 50% decrease was associated with a median PFS and OS of 11.2 and 25.2 months, respectively. Median PFS and OS for a ⩾ 30% rather than ⩾ 5 0% decrease were 10.4 and 16.5 months. These outcomes were not significantly different from those in patients with immediate PSA decreases of ⩾ 50% or ⩾ 30% from baseline, but were significantly better than in patients experiencing no PSA decrease (p = 0.006 and 0.015, respectively, for OS). The PSA response to cabazitaxel, with or without initial flare, was associated with a strong survival benefit. The taxane-induced flare during the first 12 weeks of therapy can be ignored when evaluating PSA response.


Association between serum uric acid and muscle strength in older adults with or without gout diagnosis: NHANES 2011-2014.
Increased oxidative stress seems to be one of the causes of muscle strength loss during aging. Uric acid (UA) is an important antioxidant that has been positively associated with muscle strength in older adults. However, UA is also a prerequisite for gout, which is a type of arthritis that increases inflammation. The association between UA and muscle strength in individuals with gout is unknown. The aim of the study was to associate muscle strength with UA in older adults with or without gout diagnosis. The present study evaluated older adults aged from 60 to 80 years from National Health and Nutrition Examination Survey (NHANES) 2011-2012 and 2013-2014. A total of 2529 individuals (1249 men and 1280 women) were evaluated, with (n = 201) or without (n = 2328) gout diagnosis. Muscle strength was measured using a handgrip dynamometer. The combined grip strength (sum of highest values of both hands) was evaluated. Linear regression analysis was performed to evaluate the association between UA and strength adjusting for confounders. Evaluating the individuals without gout, UA was positively associated with muscle strength [(β = 0.66 (CI = 0.08; 1.24); p = 0.028)]. However, this association was not significant in individuals with gout [(β = 0.20 (CI = - 1.18; 1.58); p = 0.774)]. Serum UA is positively associated with handgrip strength only in older adults without gout diagnosis. These results suggest that the presence of gout may avoid a positive association between UA and muscle strength in older adults.


Direct and indirect costs and resource use in dementia care: A cross-sectional study in patients living at home.
Due to the high prevalence of dementia, health care needs are increasing beyond existing formal resources. In Spain, it is the family that takes care of this disease. To analyze the direct (health and non-health) and indirect economic costs related to care of people with dementia living with their informal caregiver in the home care/community environment, from the perspective of illness severity, associated comorbidity and social impact. Multicentric, descriptive study. Three primary care public health centers associated with Hospital Clínic, Barcelona (Spain). Patients over 65 years old with a diagnosis of dementia, and included in a home care program. People with a diagnosis of dementia made by a specialist neurologist; aged 65 years or older; a score ≤ 24 on the Mini-Mental State Examination, and identification of an informal caregiver. Patients unable to identify an informal caregiver, and those with primary psychiatric pathology or Korsakoff's syndrome. Use of Resources in Dementia to assess costs; Mini-Mental State Examination to evaluate cognitive capacity; Katz-Index to measure functional capacity; Neuropsychiatric Index for neuropsychiatric symptoms, and the Charlson-Index for comorbidity. Data collection took place between November, 2010 and April, 2012. The average estimated monthly care costs for people with dementia in the home setting are 1956.2€ (SD 1463.9). Informal care was the major contributor to this with a mean estimated cost of 1214.86 (SD 902.68)€/month. Greater illness severity, dependency in activities of daily living, comorbidity and behavioral disturbance are associated with higher costs. Behavioral disturbance appeared as the only factor independently associated with cost in dementia care. The group of people with dementia with severe behavioral disturbance requires the most care resources with an average cost of 2545.2 (SD 1753.2)€/month. There is a direct association between dementia severity and increased costs. In addition, informal caregivers looking after people with dementia in Spain represent an important social cost. The independent factor associated with an increase in the total costs of patient care was neuropsychiatric symptoms.


Cortical thickness and cognition in older people with multiple sclerosis.
The structural changes associated with cognitive performance in older people with multiple sclerosis (PwMS; age ≥ 50 years old) remain unknown. To determine the relationship between whole-brain (WBV), thalamus as the largest deep gray matter nuclei, and cortex-specific volume measurements with both cognitive impairment and numerical performance in older PwMS. The main hypothesis is that cognitive impairment (CI) in older PwMS is explained by cortical thinning in addition to global and thalamic neurodegenerative changes. A total of 101 older PwMS underwent cognitive and neuroimaging assessment. Cognitive assessment included tests established as sensitive in MS samples (Minimal Assessment of Cognitive Function in MS; MACFIMS), as well as those tests often utilized in Alzheimer's dementia studies (Wechsler's Memory Scale, Boston Naming Test, Visual Motor Integration and language). Cognitive impairment (CI) was based on -1.5 standard deviations in at least 2 cognitive domains (executive function, learning and memory, spatial processing, processing speed and working memory and language) when compared to healthy controls. WBV and thalamic volume were calculated using SIENAX/FIRST and cortical thickness using FreeSurfer. Differences in cortical thickness between CI and cognitively preserved (CP) were determined using age, sex, education, depression and WBV-adjusted analysis of covariance (ANCOVA). The relationship between domain-specific cognitive performance and cortical thickness was analyzed by linear regression models adjusted for age, sex, education, depression, WBV and thalamic volume. Benjamini-Hochberg-adjusted p-values lower than 0.05 were considered significant. The average age of the study population was 62.6 (5.9) years old. After adjustment, CI PwMS had significantly thinner left fusiform (p = 0.0003), left inferior (p = 0.0032), left transverse (p = 0.0013), and bilateral superior temporal gyri (p = 0.002 and p = 0.0011) when compared to CP PwMS. After adjusting for age, sex, education, depression WBV, and thalamic volume, CI status was additionally predicted by the thickness of the left fusiform (p = 0.001) and left cuneus gyri (p = 0.004). After the adjustment, SDMT scores were additionally associated with left fusiform gyrus (p < 0.001) whereas letter-based verbal fluency performance with left pars opercularis gyrus (p < 0.001). In addition to global and thalamic neurodegenerative changes, the presence of CI in older PwMS is additionally explained by the thickness of multiple cortical regions.


Prevalence and Risk Factors for School-Associated Transmission of SARS-CoV-2.
School-associated SARS-CoV-2 transmission is described as uncommon, although the true transmission rate is unknown. To identify the SARS-CoV-2 secondary attack rate (SAR) in schools and factors associated with transmission. This cohort study examined the risk of school-based transmission of SARS-CoV-2 among kindergarten through grade 12 students and staff in 10 Massachusetts school districts during 2 periods: fall 2020/spring 2021 (F20/S21) and fall 2021 (F21). School staff collected data on SARS-CoV-2 index cases and school-based contacts, and SAR was defined as the proportion of contacts acquiring SARS-CoV-2 infection. SARS-CoV-2. Potential factors associated with transmission, including grade level, masking, exposure location, vaccination history, and Social Vulnerability Index (SVI), were analyzed using univariable and multivariable logistic regression models. For F20/S21, 8 school districts (70 schools, >33 000 students) were included and reported 435 index cases (151 staff, 216 students, and 68 missing role) with 1771 school-based contacts (278 staff, 1492 students, and 1 missing role). For F21, 5 districts (34 schools, >18 000 students) participated and reported 309 index cases (37 staff, 207 students, and 65 missing role) with 1673 school-based contacts (107 staff and 1566 students). The F20/S21 SAR was 2.2% (lower bound, 1.6%; upper bound, 26.7%), and the F21 SAR was 2.8% (lower bound, 2.6%; upper bound, 7.4%). In multivariable analysis, during F20/S21, masking was associated with a lower odds of transmission compared with not masking (odds radio [OR], 0.12; 95% CI, 0.04-0.40; P < .001). In F21, classroom exposure vs out-of-classroom exposure was associated with increased odds of transmission (OR, 2.47; 95% CI, 1.07-5.66; P = .02); a fully vaccinated vs unvaccinated contact was associated with a lower odds of transmission (OR, 0.04; 95% CI, 0.00-0.62; P < .001). In both periods, a higher SVI was associated with a greater odds of transmission. In this study of Massachusetts schools, the SAR for SARS-CoV-2 among school-based contacts was low during 2 periods, and factors associated with transmission risk varied over time. These findings suggest that ongoing surveillance efforts may be essential to ensure that both targeted resources and mitigation practices remain optimal and relevant for disease prevention.


High-performance liquid chromatography of proteins: purification of alpha-fetoprotein from fetal calf serum.
High-performance liquid chromatography was utilized for the purification of bovine alpha-fetoprotein (BAFP) from fetal calf serum (FCS). An initial step in the purification involved absorption of charcoal delipidated FCS on Cibacron Blue F3GA gel. The Cibacron Blue pre-purified FCS was then chromatographed on a Polyanion SI weak anion-exchange column. The BAFP isolated had a purity of greater than 93% with an overall yield of 48% from FCS. The procedure was applicable for semi-preparative scale purification of BAFP.


Acute metabolic effects of melatonin-A randomized crossover study in healthy young men.
Melatonin regulates circadian rhythm, but may also have effects on glucose homeostasis. A common G-allele in the MTNR1B locus has been associated with an increased risk of type 2 diabetes (T2DM). We aimed to examine acute effects of high doses of melatonin on glucose metabolism with attention to MTNR1B genotype. Twenty men were examined in a double-blinded, randomized crossover study on two nonconsecutive days with four doses of 10 mg oral melatonin or placebo. Insulin sensitivity and insulin secretion were assessed by an intravenous glucose tolerance test (IVGTT) and a hyperinsulinaemic-euglycaemic clamp (HEC). Blood samples were drawn to determine the metabolic profile and MTNR1B rs10830963 genotype. Indirect calorimetry and blood pressure measurements were also performed. Insulin sensitivity index was significantly reduced on the melatonin day (P = .028) in the whole group and in homozygous carriers of the rs10830963 C-allele (P = .041). Glucose during the IVGTT was unaffected, but there was a tendency towards lower insulin and C-peptide levels in the first minutes after glucose administration in G-allele carriers. Systolic blood pressure decreased and lipid oxidation increased significantly on the melatonin day in rs10830963 G-allele carriers. Overall, our study reports that acute administration of melatonin in supra-physiological doses may have a negative impact on insulin sensitivity. Clinical trial registration number (clinicaltrial.gov): NCT03204877.


Cell differentiation and matrix organization are differentially affected during bone formation in osteogenesis imperfecta zebrafish models with different genetic defects impacting collagen type I structure.
Osteogenesis imperfecta (OI) is a family of rare heritable skeletal disorders associated with dominant mutations in the collagen type I encoding genes and recessive defects in proteins involved in collagen type I synthesis and processing and in osteoblast differentiation and activity. Historically, it was believed that the OI bone phenotype was only caused by abnormal collagen type I fibrils in the extracellular matrix, but more recently it became clear that the altered bone cell homeostasis, due to mutant collagen retention, plays a relevant role in modulating disease severity in most of the OI forms and it is correlated to impaired bone cell differentiation. Despite in vitro evidence, in vivo data are missing. To better understand the physiopathology of OI, we used two zebrafish models: Chihuahua (Chi/+), carrying a dominant p.G736D substitution in the α1 chain of collagen type I, and the recessive p3h1-/-, lacking prolyl 3-hydroxylase (P3h1) enzyme. Both models share the delay of collagen type I folding, resulting in its overmodification and partial intracellular retention. The regeneration of the bony caudal fin of Chi/+ and p3h1-/- was employed to investigate the impact of abnormal collagen synthesis on bone cell differentiation. Reduced regenerative ability was evident in both models, but it was associated to impaired osteoblast differentiation and osteoblastogenesis/adipogenesis switch only in Chi/+. On the contrary, reduced osteoclast number and activity were found in both models during regeneration. The dominant OI model showed a more detrimental effect in the extracellular matrix organization. Interestingly, the chemical chaperone 4-phenylbutyrate (4-PBA), known to reduce cellular stress and increase collagen secretion, improved bone formation only in p3h1-/- by favoring caudal fin growth without affecting bone cell markers expression. Taken together, our in vivo data proved the negative impact of structurally abnormal collagen type I on bone formation but revealed a gene mutation-specific effect on bone cell differentiation and matrix organization in OI. These, together with the distinct ability to respond to the chaperone treatment, underline the need for precision medicine approaches to properly treat the disease.


Fault diagnosis method based on FFT-RPCA-SVM for Cascaded-Multilevel Inverter.
Thanks to reduced switch stress, high quality of load wave, easy packaging and good extensibility, the cascaded H-bridge multilevel inverter is widely used in wind power system. To guarantee stable operation of system, a new fault diagnosis method, based on Fast Fourier Transform (FFT), Relative Principle Component Analysis (RPCA) and Support Vector Machine (SVM), is proposed for H-bridge multilevel inverter. To avoid the influence of load variation on fault diagnosis, the output voltages of the inverter is chosen as the fault characteristic signals. To shorten the time of diagnosis and improve the diagnostic accuracy, the main features of the fault characteristic signals are extracted by FFT. To further reduce the training time of SVM, the feature vector is reduced based on RPCA that can get a lower dimensional feature space. The fault classifier is constructed via SVM. An experimental prototype of the inverter is built to test the proposed method. Compared to other fault diagnosis methods, the experimental results demonstrate the high accuracy and efficiency of the proposed method.


'What does good look like'-exploring access to healthcare for the homeless population in Gateshead, England.
individuals who are homeless encounter extreme health inequalities and as a result often suffer poor health. This study aims to explore ways in which access to healthcare could be improved for individuals who are homeless in Gateshead, UK. twelve semi-structured interviews were conducted with people working with the homeless community in a non-clinical setting. Transcripts were analysed using thematic analysis. six themes were identified under the broad category of 'what does good look like', in terms of improving access to healthcare. These were: facilitating GP registration; training to reduce stigma and to provide more holistic care; joined-up working in which existing services communicate rather than work in isolation; utilising the voluntary sector as support workers could actively support access to healthcare and provide advocacy; specialised roles such as specialised clinicians, mental health workers or link workers; and specialised bespoke services for the homeless community. the study revealed issues locally for the homeless community accessing healthcare. Many of the proposed actions to facilitate access to healthcare involved building upon good practice and enhancing existing services. The feasibility and cost-effectiveness of interventions suggested requires further assessment.


Association between Q192R PON1 genetic polymorphism and major adverse cardiovascular events in patients treated with clopidogrel: an updated meta-analysis.
Clopidogrel's responsiveness may be affected by the paraoxonase-1 (PON1) enzyme encoded by the Q192R PON1 genetic variant. We aimed to determine the aggregated risk of MACEs associated with carrying Q192R PON1 genetic variant in patients taking clopidogrel. Different databases were searched systematically for eligible studies, and risk ratio (RR) was measured using RevMan software where P <0.05 was set statistically significant. Nineteen studies were included consisting of 17,815 patients. It was found that patients carrying either homozygous or a combination of heterozygous and homozygous variants were not significantly associated with increased risk of MACEs compared to the non-carriers (QQ vs. RR: RR=0.99, 95% CI 0.69-1.42, P=0.96; QQ+QR vs RR; RR=1.05, 95% CI 0.82-1.35, P=0.70). The risk of MACEs was also not significantly different in other genetic model (QQ vs QR+RR) (RR=1.09, 95% CI 0.93-1.27, P=0.30). Further, bleeding events were not significantly different in different genetic models (QQ vs RR; RR=1.13, 95% CI 0.58-2.21, P=0.71; QQ+QR vs RR; RR=1.09, 95% CI 0.66-1.81, P=0.73; QQ vs QR+RR; RR=1.08, 95% CI 0.76-1.55, P=0.66). The results suggest that the Q192R PON1 genetic polymorphism has no significant impact on the risk of MACEs or bleeding events in patients treated with clopidogrel.


Human skeletal dysplasia causing L596P-mutant alters the conserved amino acid pattern at the lipid-water-Interface of TRPV4.
TRPV4 is a polymodal and non-selective cation channel that is activated by multiple physical and chemical stimuli. >50 naturally occurring point-mutation of TRPV4 have been identified in human, most of which induce different diseases commonly termed as channelopathies. While, these mutations are either "gain-of-function" or "loss-of-function" in nature, the exact molecular and cellular mechanisms behind such diverse channelopathies are largely unknown. In this work, we analyze the evolutionary conservation of individual amino acids present in the lipid-water-interface (LWI) regions and the relationship of TRPV4 with membrane cholesterol. Our data suggests that the positive-negative charges and hydrophobic-hydrophilic amino acids form "specific patterns" in the LWI region which remain conserved throughout the vertebrate evolution and thus suggesting for the specific microenvironment where TRPV4 remain functional. Notably, Spondylometaphyseal Dysplasia, Kozlowski (SMDK) disease causing L596P mutation disrupts this pattern significantly at the LWI region. L596P mutant also sequesters Caveolin-1 differently, especially in partial cholesterol-depleted (~40 % reduction) conditions. L596P shows altered localization in membrane and enhanced Ca2+-influx properties in cell as well as in filopodia-like structures. We propose that conserved pattern of amino acids is an important parameter for proper localization and functions of TRPV4 in physiological conditions. These findings also offer a new paradigm to analyze the channelopathies caused by mutations in LWI regions of other channels as well.


The role of 2-methyl-6-phytylbenzoquinone methyltransferase in determining tocopherol composition in Synechocystis sp. PCC6803.
A putative 2-methyl-6-phytylbenzoquinone (MPBQ) methyltransferase gene, SLL0418, was identified from the Synechocystis PCC6803 genome based on its homology to previously characterized gamma-tocopherol methyltransferases. Genetic and biochemical evidence confirmed open reading frame (ORF) SLL0418 encodes a MPBQ methyltransferase. An SLL0418 partial knockout mutant accumulated beta-tocopherol with no effect in the overall tocopherol content of the cell. In vitro assays of the SLL0418 gene expressed in Escherichia coli showed the enzyme efficiently catalyzes methylation of ring carbon 3 of MPBQ. In addition, the enzyme also catalyzes the methylation of ring carbon 3 of 2-methyl-6-solanylbenzoquinol in the terminal step of plastoquinone biosynthesis.


Correlates and contexts of US injection drug initiation among undocumented Mexican migrant men who were deported from the United States.
Preventing the onset of injection drug use is important in controlling the spread of HIV and other blood borne infections. Undocumented migrants in the United States face social, economic, and legal stressors that may contribute to substance abuse. Little is known about undocumented migrants' drug abuse trajectories including injection initiation. To examine the correlates and contexts of US injection initiation among undocumented migrants, we administered quantitative surveys (N = 309) and qualitative interviews (N = 23) on migration and drug abuse experiences to deported male injection drug users in Tijuana, Mexico. US injection initiation was independently associated with ever using drugs in Mexico pre-migration, younger age at first US migration, and US incarceration. Participants' qualitative interviews contextualized quantitative findings and demonstrated the significance of social contexts surrounding US injection initiation experiences. HIV prevention programs may prevent/delay US injection initiation by addressing socio-economic and migration-related stressors experienced by undocumented migrants.


Rectoanal reflex induced by H2O thermal stimulation.
To obtain clear evidence of the rectoanal reflex, cold water was injected into the rectum. All patients with a normal reflex had a rectoanal reflex when the water was either 4 degrees C or 17 degrees C. The same reflex was seen when a balloon was used for distention. No reflex was evident when the water was 37 degrees C. At 27 degrees C or 45 degrees C, the reflex was evident occasionally. In patients with Hirschsprung's disease, the rectoanal reflex was absent with balloon distention, and when water at any temperature was injected. As cold water will induce the rectoanal reflex safely and without rectal distention, measurement of the reflex using cold water is useful when the presence or absence of the reflex is doubtful. The authors' results suggest that the receptor related to the reflex is neuronal in origin and not muscular, and that the receptor locates near the mucosa.


Safety of dietary supplements use among patients with cancer: A systematic review.
Dietary supplements (DS) are commonly taken by patients with cancer, but safety of DS use remains unclear. A systematic literature search was conducted using PubMed, ClinicalTrials.gov, International Pharmaceutical Abstracts and Alt HealthWatch databases from inception through October 12, 2018. Included studies were limited to clinical trials including patients with cancer, DS products as interventions, evaluation of safety endpoints of DS use, and published in English. Sixty-five studies were included to evaluate 20 different DS among patients with 12 types of cancer. Botanical DS (n = 13), vitamins (n = 8), and probiotics/synbiotics (n = 7) were the top 3 types of DS evaluated in these trials. Majority of studied DS appeared safe. Among 19 trials including patients with cancer undergoing chemotherapy, most (n = 18) of studied DS (e.g., vitamins, botanical, omega-3 fatty acid) were found to be safe. Evaluation of DS use and its safety should be regularly incorporated in clinical trials among patients with cancer.


A cancer cell membrane coated nanoparticles-based gene delivery system for enhancing cancer therapy.
Gene therapy is a superior therapeutic means in cancer therapy. However, the instability of nucleic acid and the lack of suitable delivery carrier greatly restricts its further development and application. Herein, we coupled low molecular weight polyethyleneimine (LMW PEI) through disulfide bonds, then modified it with manganese dioxide (MnO2) nanosheets and nuclear localization signal peptide (NLS), as a p53 gene carrier, and finally coated it with B16F10 cell membrane to construct a novel gene-carrier system CM@MnO2-PEI-NLS-ss/p53 (M@MPNs/p53). Tumor cell membrane coating endows nanoparticles with homotypic targeting and immune escape capabilities, disulfide-crosslinked LMW-PEI has high transfection efficiency and low toxicity, and NLS peptides enhance nuclear delivery and improve p53 gene delivery efficiency; meanwhile, MnO2 nanosheets oxidize high intracellular concentration of glutathione (GSH), sensitizing p53 gene-mediated antitumor therapy. The results showed that the novel biofilm-camouflaged M@MPNs/p53 nanoparticles had a highly specific targeting effect on homologous cancer cells and could effectively inhibit tumor growth in vitro and in vivo. Besides, MnO2 loading improved p53-mediated tumor regression. This novel gene delivery platform is of great significance in improving gene delivery efficiency and enhancing anti-tumor therapy.


Bile salts in breast milk.
Breast milk was studied for the presence of bile salts. Cholate and chenodeoxycholate were found in all samples examined. In both colostrum and milk there was a predominance of cholate. Their biological activity remains to be determined.


An insect-inspired asymmetric hinge in a double-layer membrane.
Insect wings are deformable airfoils, in which deformations are mostly achieved by complicated interactions between their structural components. Due to the complexity of the wing design and technical challenges associated with testing the delicate wings, we know little about the properties of their components and how they determine wing response to flight forces. Here, we report an unusual structure from the hind-wing membrane of the beetle Pachnoda marginata. The structure, a transverse section of the claval flexion line, consists of two distinguishable layers: a bell-shaped upper layer and a straight lower layer. Our computational simulations showed that this is an effective one-way hinge, which is stiff in tension and upward bending but flexible in compression and downward bending. By systematically varying its design parameters in a computational model, we showed that the properties of the double-layer membrane hinge can be tuned over a wide range. This enabled us to develop a broad design space, which we later used for model selection. We used selected models in three distinct applications, which proved that the double-layer hinge represents a simple yet effective design strategy for controlling the mechanical response of structures using a single material and with no extra mass. The insect-inspired, one-way hinge is particularly useful for developing structures with asymmetric behavior, exhibiting different responses to the same load in two opposite directions. This multidisciplinary study not only advances our understanding of the biomechanics of complicated insect wings but also informs the design of easily tunable engineering hinges.


The human brain GLUT1 glucose transporter: ultrastructural localization to the blood-brain barrier endothelia.
Immunogold electron microscopy was used to examine human brain resections to localize the GLUT1 glucose transporter. The tissue examined was obtained from a patient undergoing surgery for treatment of seizures, and the capillary profiles examined had characteristics identical to those described previously for active, epileptogenic sites (confirmed by EEG analyses). A rabbit polyclonal antiserum to the full-length human erythrocyte glucose transporter (GLUT1) was labeled with 10-nm gold particle-secondary antibody conjugates and localized immunoreactive GLUT1 molecules in human brain capillary endothelia, with < 0.25% of the particles beyond the capillary profile. Erythrocyte membranes were also highly immunoreactive, whereas macrophage membranes were GLUT1-negative. The number of immunoreactive sites per capillary profile was observed to be 10-fold greater in humans than in previous studies of rat and rabbit brain capillaries. In addition, half of the total number of immunoreactive gold particles were localized to the luminal capillary membrane. We suggest that the blood-brain barrier GLUT1 glucose transporter is up-regulated in seizures, and this elevated transporter activity is characterized by increased GLUT1 transporters, particularly on the luminal capillary membranes. In addition, acute modulation of glucose transporter activity is presumed to involve translocation of GLUT1 from cytoplasmic to luminal membrane sites, demonstrable with quantitative immunogold electron microscopy.


Clinical implication of cellular vaccine in glioma: current advances and future prospects.
Gliomas, especially glioblastomas, represent one of the most aggressive and difficult-to-treat human brain tumors. In the last few decades, clinical immunotherapy has been developed and has provided exceptional achievements in checkpoint inhibitors and vaccines for cancer treatment. Immunization with cellular vaccines has the advantage of containing specific antigens and acceptable safety to potentially improve cancer therapy. Based on T cells, dendritic cells (DC), tumor cells and natural killer cells, the safety and feasibility of cellular vaccines have been validated in clinical trials for glioma treatment. For TAA engineered T cells, therapy mainly uses chimeric antigen receptors (IL13Rα2, EGFRvIII and HER2) and DNA methylation-induced technology (CT antigen) to activate the immune response. Autologous dendritic cells/tumor antigen vaccine (ADCTA) pulsed with tumor lysate and peptides elicit antigen-specific and cytotoxic T cell responses in patients with malignant gliomas, while its pro-survival effect is biased. Vaccinations using autologous tumor cells modified with TAAs or fusion with fibroblast cells are characterized by both effective humoral and cell-mediated immunity. Even though few therapeutic effects have been observed, most of this therapy showed safety and feasibility, asking for larger cohort studies and better guidelines to optimize cellular vaccine efficiency in anti-glioma therapy.


Maladaptation of renal hemodynamics contributes to kidney dysfunction resulting from thoracic spinal cord injury in mice.
Renal dysfunction is a hallmark of spinal cord injury (SCI). Several SCI sequalae are implicated; however, the exact pathogenic mechanism of renal dysfunction is unclear. Herein, we found that T3 (T3Tx) or T10 (T10Tx) complete thoracic spinal cord transection induced hypotension, bradycardia, and hypothermia immediately after injury. T3Tx-induced hypotension but not bradycardia or hypothermia slowly recovered to levels in T10Tx SCI and uninjured mice ∼16 h after injury as determined by continuous radiotelemetry monitoring. Both types of thoracic SCI led to a marked decrease in albuminuria and proteinuria in all phases of SCI, whereas the kidney injury marker neutrophil gelatinase-associated lipocalin rapidly increased in the acute phase, remaining elevated in the chronic phase of T3Tx SCI. Renal interstitial and vascular elastin fragmentation after SCI were worsened during chronic T3Tx SCI. In the chronic phase, renal vascular resistance response to a step increase in renal perfusion pressure or a bolus injection of angiotensin II or norepinephrine was almost completely abolished after T3Tx SCI. Bulk RNA-sequencing analysis showed enrichment of genes involved in extracellular matrix remodeling and chemokine signaling in the kidney from T3Tx SCI mice. The serum level of interleukin-6 was elevated in the acute but not chronic phase of T3Tx and T10Tx SCI, whereas the serum amyloid A1 level was elevated in both acute and chronic phases. We conclude that tissue fibrosis and hemodynamic impairment are involved in renal dysfunction resulting from thoracic SCI; these pathological alterations, exacerbated by high thoracic-level injury, is mediated at least partly by renal microvascular extracellular matrix remodeling.NEW & NOTEWORTHY Urinary complications resulting from thoracic spinal cord injury (SCI) greatly affects quality of life and contributes to morbidity and mortality in patients with SCI. Herein, we showed that thoracic SCI initiates changes in the structure and function of the renal microvasculature that leads to autoregulation failure in the chronic phase of high thoracic-level injury. Our study identified extracellular matrix regulators and cytokine/chemokine signaling as potential targets for developing novel therapeutics for restoring renal function following SCI.


Release of Entropic Spring Reveals Conformational Coupling Mechanism in the ABC Transporter BtuCD-F.
Substrate translocation by ATP-binding cassette (ABC) transporters involves coupling of ATP binding and hydrolysis in the nucleotide-binding domains (NBDs) to conformational changes in the transmembrane domains. We used molecular dynamics simulations to investigate the atomic-level mechanism of conformational coupling in the ABC transporter BtuCD-F, which imports vitamin B12 across the inner membrane of Escherichia coli. Our simulations show how an engineered disulfide bond across the NBD dimer interface reduces conformational fluctuations and hence configurational entropy. As a result, the disulfide bond is under substantial mechanical stress. Releasing this entropic spring, as is the case in the wild-type transporter, combined with analyzing the pairwise forces between individual residues, unravels the coupling mechanism. The identified pathways along which force is propagated from the NBDs via the coupling helix to the transmembrane domains are composed of highly conserved residues, underlining their functional relevance. This study not only reveals the details of conformational coupling in BtuCD-F, it also provides a promising approach to other long-range conformational couplings, e.g., in ABC exporters or other ATP-driven molecular machines.


Sphingosine kinase-1 activation causes acquired resistance against Sunitinib in renal cell carcinoma cells.
Multi-target tyrosine kinase inhibitor Sunitinib has been widely used in cancer treatment, including metastatic renal cell carcinoma. However, most patients who initially benefit from Sunitinib develop resistance with extended usage of Sunitinib, which is referred to as "acquired resistance". The molecular mechanisms contributing to this acquired resistance remain poorly understood. In this present study, we established Sunitinib-resistant cell lines from human renal cell lines (786-O, A498, ACHN and CAKI1) by continuous treatment with Sunitinib to explore the molecular mechanism leading to Sunitinib resistance. We found that PDGFR-β expression in cell seems to be a protective factor against Sunitinib resistance formation. In addition, we found that both SK1 and ERK were activated in Sunitinib-resistance cell lines and SK1 and ERK inhibitors could resensitize Sunitinib-resistant cell lines. In conclusion, our observations suggest that SK1 and ERK activation is a feature of resistant cell lines, which serves as an alternative pathway evading anti-tumor activity of Sunitinib.


Disparities in Pediatric Provider Availability by Insurance Type After the ACA in California.
To examine insurance-based disparities in provider-related barriers to care among children in California in the wake of changes to the insurance market resulting from the Affordable Care Act. Our sample included 6514 children (ages 0 to 11 years) from the 2014-2016 California Health Interview Survey. We examined parent reports in the past year of 1) having trouble finding a general provider for the child, 2) the child not being accepted by a provider as a new patient, 3) the child's health insurance not being accepted by a provider, or 4) any of the above. Multivariable models estimated the associations of insurance type-Medi-Cal (Medicaid), employer-sponsored insurance, or privately purchased coverage-and parent reports of these problems. Approximately 8% of parents had encountered at least one of these problems. Compared with parents of children with employer-sponsored insurance, parents of children with Medi-Cal or privately purchased coverage had over twice the odds of experiencing at least one of the barriers. Parents of children with Medi-Cal had over twice the odds of being told a provider would not accept their children's coverage or having trouble finding a general provider and 3times the odds of being told a provider would not accept their children as new patients. Parents of children with privately purchased coverage had over 3times the odds of being told a provider would not accept their children's coverage. Our study found significant disparities in provider-related barriers by insurance type among children in California.


Acute lymphoblastic leukemia in adult identical twins.
The development of acute lymphoblastic leukemia (c-ALL) in identical twins is reported. The first born had ALL in 1982 and bone marrow transplantation was performed in first complete remission (CR) from his healthy twin-brother the same year. The bone marrow donor developed ALL in 1985; he received an autologous bone marrow transplantation in first CR in 1986. Unfortunately, both patients relapsed in 1986. Cytogenetic studies of the first born revealed multiple chromosomal abnormalities and a marker chromosome whereas the second patient had a Philadelphia chromosome. Genetic reasons or exposure to leukemogenic agents may be responsible for the onset of these leukemias.


Stimulatory effect of interleukin-1beta on growth hormone gene expression and growth hormone release from rat GH3 cells.
Our previous studies demonstrated that interferon gamma increases the human (h) growth hormone (GH) gene promoter activity in rat pituitary GH3 cells, and its regulatory mechanism may be different from the classical GH-releasing hormone-induced regulatory mechanism. Interleukin-1beta (IL-1beta) is thought to induce the release of GH by pituitary cells, but whether or not and by which mechanisms IL-1beta regulates GH synthesis remains unclear. The purpose of our study was thus to investigate the effect of IL-1beta on the hGH gene expression in GH3 rat pituitary tumor cells using stable transfection of the hGH promoter fused to a luciferase reporter gene. Our results showed that IL-1beta (10-10(4) U/ml) increased GH secretion and synthesis and that 10(2) to 10(4) U/ml IL-1beta promoted the luciferase expression in stable GH3 cells, with a maximal action of 1.61 times over that of controls. Among inhibitors of intracellular signaling transduction pathways, mitogen-activated protein kinase kinase (MAPKK/MEK) inhibitor PD98059 (40 microM) and p38 MAPK inhibitor SB203580 (5 microM)blocked completely the stimulatory effect of IL-1beta, and the phosphoinositide 3-kinase inhibitor LY294002 (10 microM) blocked partially the induction of IL-1beta. Western blot analysis demonstrated that IL-1beta increased the activation of phosphorylated MEK and p38 MAPK in GH3 cells. Neither overexpression of Pit-1 nor inhibiting Pit-1 expression affected IL-1beta induction of hGH promoter activity. To identify the DNA sequence that mediated the effect of IL-1beta, six deletion constructs of hGH promoter were created. The stimulatory effect of IL-1beta was abolished following deletion of the -196- to -132-bp fragment. In conclusion, our data show that IL-1beta promotes GH secretion and synthesis by rat pituitary GH3 cells. The stimulatory effect of IL-1beta on the hGH gene promoter appears to require the activation of MEK, p38 MAPK, and phosphoinositide 3-kinase and a fragment of promoter sequence that spans the -196- to -132-bp fragment of the gene, but is unrelated to the Pit-1 protein.


Effect of danshen extract on pharmacokinetics of theophylline in healthy volunteers.
Danshen extract is widely used for the treatment and prevention of coronary heart disease and other diseases of senility in Asia. Danshen extract and theophylline may be prescribed together to treat patients with asthma. In human, theophylline with low therapeutic index is mainly metabolized by CYP1A2. In vitro findings have shown that human CYP1A2 is inhibited by the ethyl acetate extract of danshen and danshen pharmaceutical product. There may be drug interactions between danshen extract and theophylline (CYP1A2 substrate). This study concerned drug interactions between danshen extract and theophylline in Chinese volunteers. Long-term oral intake of danshen extract does not change the basic pharmacokinetic parameters of theophylline. Dose adjustment of theophylline thus may not be necessary in patients receiving concomitant therapy with danshen extract. To examine the potential effect of danshen extract on the pharmacokinetics of theophylline. In a sequential cross-over study with two phases, 12 volunteers took 100 mg theophylline on day 1 and day 15. From day 2 to day 15, volunteers received danshen extract tablets three times daily, four tablets each time for 14 days. On day 15, they received four danshen extract tablets with 100 mg theophylline. Plasma concentrations of theophylline were measured on days 1 and 15 periodically for 24 h. The 90% confidence interval of C(max), t(1/2) and CL/F of theophylline with 14-day danshen extract tablets vs. without comedication were (101.42, 121.36) (84.57, 106.72) and (88.82, 105.72), respectively. The time to peak plasma theophylline concentration was unchanged by danshen (P > 0.05). The pharmacokinetics parameter of theophylline was unaffected by danshen extract. Danshen extract does not influence the metabolism of theophylline in healthy volunteers. Dose adjustment of theophylline thus may not be necessary in patients receiving concurrent therapy with danshen extract tablets.


Management and outcomes of adnexal masses during pregnancy: a 6-year experience.
To demonstrate adnexal masses detected during gestations in a 6-year period. A retrospective study of pregnancy with adnexal masses requiring surgery over a 6-year period at the Selcuk University Hospital, a tertiary referral center, between June 2000 and June 2006. We detected 36 pregnancies with adnexal masses. The mean age of the patients was 26.6 years (range, 18-42). The mean gestational age at which adnexal masses were detected was 17 weeks (range, 5-36), and the mean gestational age at the time of surgery was 24 weeks (range, 6-41). Postoperative pathology results of the patients were functional ovarian cysts in 14 cases (41.1%), endometrioma in eight cases (23.5%), dermoid cyst in six cases (17.6%), serous cystadenoma in two cases (5.8%), mucinous cystadenoma in one case (2.9%), para-ovarian cyst in one case (2.9%), and borderline serous tumor in two cases (5.8%). Two patients operated on during the second trimester developed preterm birth risk (5.8%). Miscarriage occurred in only one patient (2.9%). In this report, we demonstrate a high rate of surgical intervention of adnexal masses at pregnancy which is secondary to the fact that our center works as a tertiary referral center. Most masses at pregnancies were benign in character and our malignity rate was low. We detected an acceptable complication rate due to surgery in pregnant women.


Regeneration and characterization of adult mouse hippocampal neurons in a defined in vitro system.
Although the majority of human illnesses occur during adulthood, most of the available in vitro disease models are based upon cells obtained from embryonic/fetal tissues because of the difficulties involved with culturing adult cells. Development of adult mouse neuronal cultures has a special significance because of the abundance of transgenic disease models that use this species. In this study a novel cell culture method has been developed that supports the long-term survival and physiological regeneration of adult mouse hippocampal cells in a serum-free defined environment. In this well-defined, controlled system, adult mouse hippocampal cells survived for up to 21 days in culture. The cultured cells exhibited typical hippocampal neuronal morphology and electrophysiological properties after recovery from the trauma of dissociation, and stained positive for the expected neuronal markers. This system has great potential as an investigative tool for in vitro studies of adult diseases, the aging brain or transgenic models of age-associated disorders.


Early phase microvascular interactions in rat jejunum between nitric oxide and vasopressin following indomethacin administration.
The involvement of endogenous vasopressin in the actions of indomethacin following the concurrent administration of the nitric oxide (NO) synthase inhibitor, NG -nitro-l-arginine methyl ester (l-NAME), on acute intestinal microvascular permeability has been investigated in the rat. Administration of indomethacin (10mg/kg, s.c.) or L-NAME (10mg/kg, s.c.) alone did not affect jejunal and ileal vascular permeability after 1 h, as determined by the leakage of radiolabelled serum albumin. In contrast, when indomethacin (10mg/kg, s.c.) was injected concurrently with L-NAME (2-10mg/kg, s.c), significant dose-dependent plasma leakage occurred in the jejunum. Pretreatment with l-arginine (300 mg/kg s.c.) 15 min prior to l-NAME prevented these changes in microvascular permeability. Moreover, pretreatment with the vasopressin pressor-receptor antagonist, d(CH2 )5 Tyr(Me)AVP (0.01-0.2m̈g/kg, s.c.) dose-dependently attenuated such damage. These findings suggest that following indomethacin administration, the early inhibition of NO synthase leads to acute microvascular injury involving vasopressin in the rat jejunum. This suggests a protective role of NO, formed by constitutive NO synthase, counteracting effectively the deleterious actions of endogenous vasopressin.


Easy and Hard Auditory Tasks Distinguished by Otoacoustic Emissions and Event-related Potentials: Insights into Efferent System Activity.
The medial olivocochlear (MOC) system is thought to be responsible for modulation of peripheral hearing through descending (efferent) pathways. This study investigates the connection between peripheral hearing function and auditory attention tasks of different degrees of difficulty. Peripheral hearing function was evaluated by analyzing the amount of change in otoacoustic emissions (OAEs) by contralateral acoustic stimulation (CAS), a well-known effect of the MOC system. Simultaneously, levels of attention were evaluated by event-related potentials (ERPs). The ERPs showed clear differences in processing tasks of different difficulty, but paradoxically there was no difference in the amount of OAE change brought about by CAS. There was also no effect on OAE latency, nor was there any difference in noise level or number of rejected trials. However, we observed that the changes in OAEs by CAS for easy and hard tasks were correlated with the magnitude of the P3 wave in the ERP. This suggests there might be some sort of mutual compensation mechanism - presently unknown - between periphery and cortex.


Precise identification of immunotherapeutic targets for solid malignancies using clues within the tumor microenvironment-Evidence to turn on the LIGHT.
Targeted immunotherapy for solid gastrointestinal malignancies is challenging due to a lack of identified tumor antigens. Therefore, a strategy that supports and expands tumor infiltrating lymphocytes in the tumor microenvironment may allow these tumor-reactive T-cells to incite an antitumor response. Gene expression analysis of colon metastases has identified specific immunotherapeutic targets for this malignancy.


[Malignant pleural mesothelioma: diagnosis and treatment].
Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor issued from the mesothelial surface of the pleural space. A previous exposure to asbestos is the main risk factor of mesothelioma. Clinical signs are most of the time late and unspecific. Chest CT-scan, a key imaging procedure, usually shows a (unilateral) pleurisy associated with pleural nodular thickening. PET-scan associated with CT-scan may help to differenciate MPM from pleural benign tumors but it is not recommended for the diagnosis of MPM, as well as chest resonance magnetic imaging and blood or pleural fluid biomarkers, including soluble mesothelin still under investigation. The diagnosis of MPM is based on histology using essentially immunohistochemistry on pleural biopsies best obtained by thoracoscopy. The treatment of MPM relies mostly on chemotherapy. Surgery, pleurectomy/decortication or extrapleural pneumonectomy, is not recommended outside a clinical trial, as well as adjuvant chest radiotherapy. Prophylactic irradiation of chest scars and drains, validated by the French guidelines in 2005, is however highly discussed at the international level. Finally, numerous research studies presently assess the value of targeted therapies and biomarkers in MPM, opening new perspectives in the management of this cancer.


[Convulsions and encephalopathy as initial manifestations of cyanocobalamin deficiency, without hematologic changes].
A case of deficiency of cobalamin coenzyme synthesis whose first manifestation was encephalopathy with seizures and no trace of megaloblastic anemia is presented. After a while, signs of posterior cord and polyneural disfunction were detected. We highlight the rareness of the case and the difficulty of the diagnosis because of the discrepancy between neurologic and hematologic signs, as well as the need for early diagnosis which is an important factor for observing therapeutic response.


The Ring Study: an international comparison of PD-L1 diagnostic assays and their interpretation in non-small cell lung cancer, head and neck squamous cell cancer and urothelial cancer.
PD-L1 immunohistochemistry has been approved as a diagnostic assay for immunotherapy. However, an international comparison across multiple cancers is lacking. This study aimed to assess the performance of PD-L1 diagnostic assays in non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC) and urothelial cancer (UC). The excisional specimens of NSCLC, HNSCC and UC were assayed by Ventana SP263 and scored at three sites in each country, including Australia, Brazil, Korea, Mexico, Russia and Taiwan. All slides were rotated to two other sites for interobserver scoring. The same cohort of NSCLC was assessed with Dako 22C3 pharmDx PD-L1 for comparison. The PD-L1 immunopositivity was scored according to the approved PD-L1 scoring algorithms which were the percentage of PD-L1-expressing tumour cell (TC) and tumour proportion score (TPS) by Ventana SP263 and Dako 22C3 staining, respectively. In NSCLC, the comparison demonstrated the comparability of the SP263 and 22C3 assays (cut-off of 1%, κ=0.71; 25%, κ=0.75; 50%, κ=0.81). The interobserver comparisons showed moderate to almost perfect agreement for SP263 in TC staining at 25% cut-off (NSCLC, κ=0.72 to 0.86; HNSCC, κ=0.60 to 0.82; UC, κ=0.68 to 0.91) and at 50% cut-off for NSCLC (κ=0.64 to 0.90). Regarding the immune cell (IC) scoring in UC, there was a lower correlation (concordance correlation coefficient=0.10 to 0.68) and poor to substantial agreements at the 1%, 5%, 10% and 25% cut-offs (κ= -0.04 to 0.76). The interchangeability of SP263 and 22C3 in NSCLC might be acceptable, especially at the 50% cut-off. In HNSCC, the performance of SP263 is comparable across five countries. In UC, there was low concordance of IC staining, which may affect treatment decisions. Overall, the study showed the reliability and reproducibility of SP263 in NSCLC, HNSCC and UC.


Macrophage Activation Syndrome.
Macrophage activation syndrome (MAS) is a potentially life-threatening complication of rheumatic disorders that occurs most commonly in systemic juvenile idiopathic arthritis. In recent years, there have been several advances in the understanding of the pathophysiology of MAS. Furthermore, new classification criteria have been developed. Although the place of cytokine blockers in the management of MAS is still unclear, interleukin-1 inhibitors represent a promising adjunctive therapy, particularly in refractory cases.


Highly improved dechlorination of 2,4-dichlorophenol in aqueous solution by Fe/Ni nanoparticles supported by polystyrene resin.
2,4-dichlorophenol (2,4-DCP) is a typical chlorophenol that has been widely used in industrial production and caused serious pollution to the environment. In this study, the performance of Fe/Ni bimetallic nanoparticles supported on polystyrene cation exchange resin (Fe/Ni-D072) to remove 2,4-DCP was evaluated. The effects including the doping amount of Ni, the dosage of Fe/Ni-DCP, the initial concentration of 2,4-DCP, and pH value of the solution on the removal efficiency were also investigated. The results showed that when the initial concentration of 2,4-DCP was 20 mg/L and pH = 7.3, 90% of 2,4-DCP could be dechlorinated by Fe/Ni-D072 (Ni% = 30 wt%, dosage: 6.7 g/L) after 12 h reaction. The dechlorination process followed a pseudo-first-order model, and the reaction constant was 0.252 h-1. In addition, the effects of humic acid and common coexisting ions on dechlorination were studied. The results showed that humic acid with a low concentration (5 mg/L) and CO32- restrained the degradation of 2,4-DCP. The dechlorination products of 2,4-DCP were identified by HPLC and the result showed phenol was the main product with a slight amount of 2-CP as the dechlorination intermediate, and 4-CP was barely detected. These results suggest that Fe/Ni-D072 was a promising catalytic material for the removal of chlorophenol and has great application prospects in groundwater remediation.


Deflector designs for fish habitat restoration.
Paired current deflectors are structures that are installed on each bank of a river to locally reduce the width of the channel, thereby creating flow acceleration and promoting scouring. These instream habitat structures have been used extensively in restoration projects to create pool habitat for fish, but there are many discrepancies in deflector design recommendations in terms of orientation, height, and length. Our objectives were to (1) examine how the angle, height, and length of paired deflectors affect scour hole dimensions and potential for bank erosion; and (2) test the applicability to paired deflectors of existing equations for scour hole depth and volume. Three deflector angles (45 degrees, 90 degrees, and 135 degrees), two deflector heights (with flow under and over the deflector height), and two lengths (reducing the width by 25% and 50%) were investigated using uniform sand in a laboratory flume. Results showed a 26-30% smaller scour depth resulting from 45 degrees deflectors than from 90 degrees deflectors and a 5-10% smaller scour depth for 135 degrees deflectors compared to 90 degrees deflectors. The volume of scour and the potential for bank erosion were greater when flow was under the height of the deflectors rather than overtopping and when the length of deflector was increased. When flow was under the deflector height, 135 degrees deflectors had the highest amount of bank erosion; whereas during overtopping flow conditions, 90 degrees deflectors had the greatest bank erosion potential. Values predicted by the model of Kuhnle and others were closest to observed scour depth and volume measurements. The assumption that upstream-oriented deflectors always generate the largest scour should be revised.


Removal of surface adherent Staphylococcus aureus in the determination of phagocytosis and intracellular killing by the use of lysostaphin.
Use of lysostaphin to remove non-phagocytized, granulocyte-adherent bacteria allows more precise calculation of the percentage of the ingested as well as killed bacteria in the process of phagocytosis.


Occurrence and distribution of microplastics in sediments of a man-made lake receiving reclaimed water.
Microplastics have been widely detected in the effluent discharged from wastewater treatment plants. However, few studies have focused on the occurrence of microplastics in the sediments of waterbodies receiving reclaimed water. The present study investigated the microplastics distribution in the sediments of such a lake in Tianjin, China receiving reclaimed water and determined the factors affecting the settlement of microplastics in the sediment column. Nine sediment cores were collected and the abundance, shape, size, and color of the microplastics were determined. The polymers of microplastics were identified and the mass concentrations of polyethylene terephthalate (PET) and polycarbonate (PC) were analyzed. Large amount of microplastics were found to accumulate in the sediments of the lake receiving reclaimed water. Eighteen polymers were found in the sediments and PA, PET, PP, PSF, and PU are much more than others. In surface sediments, PET and PC ranged from 2.43 to 10.62 mg/kg and 0.03 to 0.77 mg/kg, respectively. Fragment and fiber are the most common shapes, accounting for 67.5% and 24.8% of all the microplastics. The distribution of microplastics was influenced by polymer type, size, shape, and grain size of the sediments. Microplastic morphological diversities decreased with increasing depth of the sediments. Our findings provide evidence that the sediments of receiving waterbodies are important sinks of the microplastics in reclaimed water.


Recalcitrant periungual verrucae: the role of carbon dioxide laser vaporization.
Recalcitrant periungual verrucae (24 lesions) in 17 patients were vaporized with the carbon dioxide laser. The lesions had been present for 1 to 15 years and treated an average of nine times previously. Vaporization of these warts, in combination with partial or complete nail avulsion, resulted in complete cures in 71% of patients who had one or two treatments. The cure rate was 94% when the patients who had clearing after one or two laser treatments in combination with other therapies are included. Further follow-up indicates that infection and significant onychodystrophy are uncommon. Pain occurs, but in most cases it is short lived and manageable.


[Possibilites and limitations of retrospective research on cause of death within the framework of a nationwide epidemiological study].
Cause-specific mortality is an important endpoint in longitudinal epidemiological studies to research causal health links and carry out individual process analyses. As in Germany no national mortality register exists, state-specific data-protection conditions for and approaches to cause of death studies were researched and tested within the framework of a pilot project. The database was provided by a sample of deceased study participants from the 1998 nationwide health survey. Under the given conditions, cause of death research in a nationwide epidemiological study is possible in principle, but requires a great deal of time and effort. In Rhineland-Palatinate research needs to be carried out in a timely manner as the health authorities' retention period for death certificates is limited to minimum of 5 years. In Berlin the research situation is particularly difficult as, while the death certificates are held 3 years by the statistics bureau, this department cannot release any pseudonymous data. In Berlin it is possible to research the cause of death for some of the deceased through the doctors and hospitals that issued the death certificates and through the GKR Berlin-Brandenburg (in keeping with the special data protection measures of the cancer registry). In North Rhine Westphalia the written consent obtained during people's lifetimes, including an explicit release from medical confidentiality, is required to carry out cause of death research. In all other German states exceptions are possible, in all cases requiring the consent of the state's data protection commissioners. The results of the pilot project underline the need for a national mortality register. Until this is established the approach used in the pilot study can be used and, working together with the state and national data protection authorities and with the highest national health authorities, can be further optimized in order to avoid losing data and to use resources efficiently.


Lipid packing and transbilayer asymmetries of mixed lipid vesicles.
Predictions, based on a previously developed theory, of the radii and asymmetric lipid distribution of mixed phosphatidylcholine/lysophosphatidylcholine and phosphatidylcholine/cholesterol vesicles of variable composition are presented. The results compare well with available experimental data, except for cis-unsaturated phosphatidylcholine/cholesterol vesicles at high concentrations of cholesterol. It is concluded that specific lipid-lipid interactions need not be invoked for saturated and trans-unsaturated phosphatidylcholine mixed with lysophosphatidylcholine or cholesterol. A discussion of the effect of packing stresses on induced flip-flop and non-spherical vesicles is also presented.


Production, reproduction and size in mammals.
It is argued that birth rate, turnover rate and production/biomass ratios (P/B) are equivalent in stable populations. It is then shown from field data on 21 mammal species that production scales as a 2/3 power of body mass, suggesting that size rather than life history characteristics explain most interspecific variation. The relationship simolifies calculations of annual production in populations and energy flow through communities.


Acute Myocardial Infarction and Risk of Cognitive Impairment and Dementia: A Review.
Cognitive impairment (CI) shares common cardiovascular risk factors with acute myocardial infarction (AMI), and is increasingly prevalent in our ageing population. Whilst AMI is associated with increased rates of CI, CI remains underreported and infrequently identified in patients with AMI. In this review, we discuss the evidence surrounding AMI and its links to dementia and CI, including pathophysiology, risk factors, management and interventions. Vascular dysregulation plays a major role in CI, with atherosclerosis, platelet activation, microinfarcts and perivascular inflammation resulting in neurovascular unit dysfunction, disordered homeostasis and a dysfunctional neurohormonal response. This subsequently affects perfusion pressure, resulting in enlarged periventricular spaces and hippocampal sclerosis. The increased platelet activation seen in coronary artery disease (CAD) can also result in inflammation and amyloid-β protein deposition which is associated with Alzheimer's Dementia. Post-AMI, reduced blood pressure and reduced left ventricular ejection fraction can cause chronic cerebral hypoperfusion, cerebral infarction and failure of normal circulatory autoregulatory mechanisms. Patients who undergo coronary revascularization (percutaneous coronary intervention or bypass surgery) are at increased risk for post-procedure cognitive impairment, though whether this is related to the intervention itself or underlying cardiovascular risk factors is debated. Mortality rates are higher in dementia patients with AMI, and post-AMI CI is more prevalent in the elderly and in patients with post-AMI heart failure. Medical management (antiplatelet, statin, renin-angiotensin system inhibitors, cardiac rehabilitation) can reduce the risk of post-AMI CI; however, beta-blockers may be associated with functional decline in patients with existing CI. The early identification of those with dementia or CI who present with AMI is important, as subsequent tailoring of management strategies can potentially improve outcomes as well as guide prognosis.


Sickle cell anaemia: current therapies.
Tremendous progress has been made in the treatment of patients with sickle cell anaemia. This paper emphasises the benefit of early therapy with hydroxyurea, the indication for blood transfusions including iron chelation and the role of hematopoietic stem cell transplantation. In order to offer transplantation to a larger number of patients including adolescents and young adults, it is important to find less toxic, but still effective conditioning therapy and to evaluate the feasability of using alternative donors.


Cytokines and neurotrophic factors fail to affect Nogo-A mRNA expression in differentiated human neurones: implications for inflammation-related axonal regeneration in the central nervous system.
Nogo is a novel myelin-associated inhibitor of neurite outgrowth which regulates stable neuronal connections during axonal regeneration following injury in the adult mammalian central nervous system (CNS). Because cytokines and neurotrophic factors play a key role in inflammation-related axonal regeneration, we investigated: (i) the constitutive expression of Nogo and the Nogo receptor (NgR) mRNA in human neural cell lines; (ii) Nogo and NgR mRNA levels in the NTera2 human teratocarcinoma cell line during retinoic acid (RA)-induced neuronal differentiation; and (iii) their regulation in NTera2-derived differentiated neurones (NTera2-N) after exposure to a battery of cytokines and growth factors potentially produced by activated glial cells at post-traumatic inflammatory lesions in the CNS. By reverse transcriptase-polymerase chain reaction analysis, the constitutive expression of Nogo-A, the longest isoform of three distinct Nogo transcripts and NgR mRNA was identified in a wide variety of human neural and non-neural cell lines. By Northern blot analysis, the levels of Nogo-A mRNA were elevated markedly in NTera2 cells following RA-induced neuronal differentiation, accompanied by an increased expression of the neurite growth-associated protein GAP-43 mRNA. In contrast, Nogo-A, Nogo-B, NgR and GAP-43 mRNA levels were unaltered in NTera2-N cells by exposure to basic fibroblast growth factor, brain-derived neurotrophic factor, glia-derived neurotrophic factor, tumour necrosis factor-alpha, interleukin-1beta, dibutyryl cyclic AMP or phorbol 12-myristate 13-acetate. These results indicate that both Nogo-A and NgR mRNA are coexpressed in various human cell types, including differentiated neurones, where their expression is unaffected by exposure to a panel of cytokines and neurotrophic factors which might be involved in inflammation-related axonal regeneration in the CNS.


Erica multiflora extract rich in quercetin-3-O-glucoside and kaempferol-3-O-glucoside alleviates high fat and fructose diet-induced fatty liver disease by modulating metabolic and inflammatory pathways in Wistar rats.
The wide morbidity of obesity has heightened interest in providing natural and safe compounds to maintain optimal health. The present study was designed to determine the chemical constituents and the effects of methanol leaf extract from Erica multiflora (M-EML) on mitigating high-fat and high-fructose diet (HFFD)-induced metabolic syndrome (MS). LC-MS/MS characterization of M-EML allowed the identification of 14 secondary metabolites and showed that quercetin-3-O-glucoside and kaempferol-3-O-glucoside were the main compounds of our extract. In the in vivo study, the oral administration of M-EML (250 mg/kg) during the last 4 weeks of the experimentation alleviated HFFD-induced obesity, insulin resistance (IR) and cardiovascular diseases. Thus, M-EML treatment significantly normalized body and liver weight, allowed to a sharp decline in plasma levels of TC, TG and LDL-c by 32%, 35% and 66%, respectively. Moreover, hepatic enzymes, total and direct bilirubin, lipase and uric acid levels have been diminished in treated group. Histopathology of the liver confirmed the changes induced by HFFD and the hepatoprotective effect of M-EML. The supply of M-EML reduced NO production and cellular lysosomal enzyme activity by 44% and 60%, respectively compared to HFFD. Besides, M-EML showed decreased pro-inflammatory cytokines levels (259.5±47.35 pg/ml and 56.08±1.56 pg/ml) of TNF-α and IL-6, respectively. In addition, M-EML reduced liver malondialdehyde (MDA) content and enhanced superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. In contrast, these enzymatic activities have been disrupted in HFFD rats. Overall, M-EML prevented obesity through the modulation of metabolic syndrome, reducing inflammation and promoting antioxidant enzymes activities.


Radiation exposure in endovascular procedures.
The introduction of percutaneous techniques to treat patients with peripheral vascular disease has placed the vascular surgeon in the unique role as the fluoroscopy supervisor overseeing the radiation protection for patient, self, staff, and trainee. Since radiation is an invisible threat in endovascular interventions, attention to protection may be challenging for the surgeon to understand and enforce. General endovascular radiation considerations for endovascular aneurysm repair (EVAR) and peripheral interventions are reviewed. Peripheral atherectomy has the highest estimated skin doses of all endovascular procedures. Renal interventions, visceral balloon angioplasty and stenting, and embolization procedures are some of the procedures that have the highest peak skin doses. Patients with high body mass index (BMI) have been found to have up to three times higher peak skin doses than patients with normal BMI. The degree of radiation exposure is dependent on the type of endovascular procedure, the patient's body habitus, and also the safety habits of the surgeon. Radiation exposure needs addressed in an informed consent process as is required for other procedures. Radiation exposure risks also need monitoring just as a surgeon monitors individual morbidity and mortality.


Effect on aflatoxin production of competition between wild-type and mutant strains of Aspergillus parasiticus.
Co-cultivation of a strain of Aspergillus parasiticus, capable of making aflatoxins, with blocked mutant strains, capable of producing none or only a low level of aflatoxins, reduced the net yield of aflatoxins more than that expected based on spore recovery. Yields of aflatoxins were 8-fold less for a norsolorinic acid-producing strain, 14-fold less for an averantin-producing strain, 6-fold less for an averufin-producing strain, and 21-fold less for a versicolorin A-producing strain when co-cultured in equal amounts with a wild-type strain of Aspergillus parasiticus. Even when the wild-type strain was initially present in 100-fold excess, with two of the mutant strains, reduced aflatoxin production was still observed.


The effects of neighborhood social ties and networks on mental health and well-being: A qualitative case study of women residents in a middle-class Korean urban neighborhood.
Despite the general understanding of the significance of neighborhood social capital on mental health, our understanding of the mechanisms of these effects is limited. This study thus explores the characteristics of neighborhood social ties and networks experienced by women residents in their urban neighborhood in the Seoul metropolitan area, Korea, and how these social relationships contributed to their mental health and well-being. We draw on a phenomenological qualitative study conducted in 2016, which included interviews with 18 full-time or part-time housewives with children. The participants in this study experienced the neighborhood social networks and ties as unessential but supportive relationships, as an extension of mothering, and as a source of stressful social comparisons. With these characteristics, the social relationships had both positive and negative effects on the participants' mental health and well-being because they provided social support but also generated everyday stress. This study illustrates an example of the complex link between neighborhood social capital and mental health. It also contributes to our understanding of the everyday processes that influence the health and well-being of women, highlighting the possible oppressive attributes of neighborhood communities.


Weight gain since age of 20 as risk of metabolic syndrome even in non-overweight individuals.
Metabolic syndrome (MetS), regardless of the presence of obesity, is known as a risk of diabetes and cardiovascular disease. Weight gain after age 20 reported to be associated with these diseases. Impact of the difference between the body mass index (BMI) at examination and BMI at age 20 (ΔBMIexa-20y) on MetS, especially in non-overweight individuals, remains to be elucidated. We analyzed the data of 24,363 individuals (14,301 men and 10,062 women) in this cross-sectional study. The diagnosis of MetS was diagnosed when three or more of the following criteria were present: hypertension, hyperglycemia, hypertriglyceridemia, low HDL-cholesterol level, and abdominal obesity. Logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, alcohol, smoking, exercise, and BMI at examination. Compared to the lowest ΔBMIexa-20y tertile (ΔBMIexa-20y < 1.2 kg/m2 in men and ≤0 kg/m2 in women), the highest tertile (ΔBMIexa-20y ≥ 3.2 kg/m2 in men and ≥2.0 kg/m2 in women) was associated with the risk of the presence of MetS (multivariate OR = 1.80, 95%CI 1.53-2.11, p < 0.001 in men and OR = 3.27, 95%CI 2.22-4.96, p < 0.001 in women). This result was also applicable in non-overweight individuals (multivariate OR = 2.06, 95%CI 1.46-2.92, p < 0.001 in men and OR = 2.49, 95%CI 1.40-4.64, p < 0.001 in women). Our analyses showed that ΔBMIexa-20y is associated with the risk of the presence of MetS, even in non-overweight individuals. It is thus important to check weight changes from early adulthood, even in non-overweight individuals.


Proteomic analysis of amniotic fluid to identify potential targets predicting preterm delivery.
Preterm delivery is a common complication of pregnancy which leads to significant neonatal mortality and morbidity. Identifying predictive markers linked to spontaneous preterm delivery (SPTD) is important for effective treatment and prevention of PTD. To explore potential biomarkers related to SPTD, we performed proteomics analysis in amniotic fluid (AF). In total, we enrolled 30 pregnant women with singleton gestation who underwent clinically indicated amniocentesis at 15-24 weeks of gestation. LC-MS analysis was used to analyze the AF samples of 10 women with SPTD < 34 weeks after cervix cerclage (Preterm group), 10 women with term delivery (TD) ≥ 34 weeks after cervix cerclage (Term group), and 10 women who delivered at term (Normal group). ELISA validation was performed for candidate proteins in a second independent cohort. As a result, we identified 44 differentially expressed proteins (DEPs, P < 0.05) via proteomic analysis, and based on that, 9 primary pathways were also determined in SPTD. Results of the ELISA assay confirmed that the increased concentration of Serpin A1, decreased concentrations of Renin and IGFBP4 were significantly associated with SPTD at ≤34 weeks.


Empirical fear profiles among American youth.
Fears among children can range from relatively innocuous fears of simple objects to significant phobias that affect youths' everyday functioning in the home, school, or community environments. This study investigated empirically derived fear profiles among American youth ages 7-19 (N=556). Based upon youths' scores on the 5 factors of the Fear Survey Schedule for Children-II (FSSC-II; Burnham & Gullone (Behav Res Ther, 35, 1997)), multistage Euclidean grouping was applied and produced 5 replicable fear cluster profiles with unique contours. Logistic regression odds ratios revealed specific associations of profile group membership with demographic characteristics such as child age, sex, and ethnicity.


Benefit of pronase in image quality during EUS.
EUS is useful for diagnosis of GI disease. However, artifacts caused by gastric mucus may worsen visibility during EUS. To investigate the efficacy of premedication with pronase, the proteolytic enzyme, for improving imaging during EUS. Blinded, randomized, prospective study. Tertiary-care referral center. This study involved 183 patients scheduled for EUS. Patients were assigned to oral premedication with saline solution (group A), pronase and bicarbonate (group B), or pronase, bicarbonate, and simethicone (group C). Either conventional EUS or high-frequency catheter EUS (HFUS) was selected. Gastric cavity and gastric mucosal surface obscurity grades were assessed by using visibility scores from ultrasonographic images of each patient. Means of visibility scores and proportion of images with better visibility scores of the gastric cavity and gastric mucosal surface. Lower scores indicate better visibility of the gastric mucosal surface and fewer artifacts within the gastric cavity on conventional EUS and HFUS. Group B had significantly lower mean gastric cavity and gastric mucosal surface visibility scores than did groups A and C in both conventional EUS and HFUS. Group B also had a high proportion of images that had better gastric cavity and gastric mucosal surface visibility scores than did the other two groups in conventional EUS and HFUS. Small number of patients and no assessment of the amount of mucus before oral premedication. Premedication for conventional EUS and HFUS by using a mixture of pronase and bicarbonate seems to decrease the number of gastric wall and lumen hyperechoic artifacts observed in patients given either saline solution or pronase/bicarbonate/simethicone.


[Role of endocervical curettage in the screening for cervical cancer: apropos of a series of 31 cases].
We present a study of 31 cases of pathologic cervical smear with an inconclusive colposcopy. The aim of this study was to compare the results of the cervical smear, colposcopy, cervical biopsy, endocervical curettage and conization. The endocervical curettage is a valuable complement to the colposcopy, especially in the case of an inconclusive colposcopy.


The effect of anoxia on PolyP content of Phycomyces blakesleeanus mycelium studied by 31P NMR spectroscopy.
The effect of anoxia and the respiratory chain inhibitors azide and cyanide on the polyphosphate content of Phycomyces was studied by in vivo (31)P NMR spectroscopy. Anoxia was manifested by a decrease of core polyphosphates (PP(i)) and increase of intracellular inorganic phosphate (P(i)) signal. Normalized changes in PP(i)/P(i) ratio between control and nitrogen-purged mycelia suggest that the sensitivity to anoxia differs with growth phases. Azide acts in the same way as anoxia, by decreasing the PP(i)/P(i) ratio, while cyanide causes an increase of the PP(i)/P(i) ratio.


Urethral striated sphincter responses to electro-bulbocavernosus stimulation.
Electric stimuli of known strength, duration and frequency were applied to the glans penis, and the cystosphincterometric and electromyographic responses of the urethral striated sphincter were recorded. Studies performed on male subjects, including normal men, patients with a neurologic deficit and patients who had undergone prostatectomy, indicate the usefulness of this technique in evaluating the striated sphincter excitability via the pudendal reflex arc. The intravenous administration of diazepam produced a notable increase in the striated sphincter threshold, indicating the applicability of this technique to evaluate the effect of various neuropharmacologic agents on the striated sphincter activity. In addition, the transit time through the pudendal reflex arc was measured with this method to assess the somatic neural integrity of the lower urinary tract. Also, studies on patients with post-radical prostatectomy incontinence have suggested that our technique of striated sphincter evaluation could be applied to the prediction of postoperative urinary incontinence.


Environmental life cycle assessment of different domestic wastewater streams: policy effectiveness in a tropical urban environment.
To enhance local water security, the Singapore government promotes two water conservation policies: the use of eco-friendly toilets to reduce yellow water (YW) disposal and the installation of water efficient devices to minimize gray water (GW) discharge. The proposed water conservation policies have different impacts on the environmental performance of local wastewater management. The main purpose of this study is to examine and compare the impacts of different domestic wastewater streams and the effectiveness of two water conservation policies by means of life cycle assessment (LCA). LCA is used to compare three scenarios, including a baseline scenario (BL), YW-reduced scenario (YWR) and GW-reduced scenario (GWR). The BL is designed based on the current wastewater management system, whereas the latter two scenarios are constructed according to the two water conservation policies that are proposed by the Singapore government. The software SIMPARO 7.3 with local data and an eco-invent database is used to build up the model, and the functional unit is defined as the daily wastewater disposal of a Singapore resident. Due to local water supply characteristics, the system boundary is extended to include the sewage sludge management and tap water production processes. The characterization results indicate that the GWR has a significant impact reduction (22-25%) while the YWR has only a 2-4% impact reduction compared with the BL. The contribution analysis reveals that the GW dominates many impact categories except eutrophication potential. The tap water production is identified as the most influential process due to its high embodied energy demand in a local context. Life cycle costing analysis shows that both YWR and GWR are financially favorable. It is also revealed that the current water conservation policies could only achieve Singapore's short-term targets. Therefore, two additional strategies are recommended for achieving long-term goals. This study provides a comprehensive and reliable environmental profile of Singapore's wastewater management with the help of extended system boundary and local data. This work also fills the research gap of previous studies by identifying the contribution of different wastewater streams, which would serve as a good reference for source-separating sanitation system design.


Bcl-2 overexpression prevents apoptosis induced by ceramidase inhibitors in malignant melanoma and HaCaT keratinocytes.
We examined the biological effects of the ceramide analogues (1S,2R)-2-N-myristoylamino-1-phenyl-1-propanol (D-e-MAPP) and (1R,2R)-2-N-myristoylamino-1-(4-nitrophenyl)-1,3-propandiol (D-NMAPPD) on human HaCaT keratinocytes and human melanoma cells. We could demonstrate that D-e-MAPP and D-NMAPPD are able to suppress acid ceramidase activity. The elevation of the endogenous level of ceramide is followed by induction of apoptosis and suppression of proliferation in HaCaT keratinocytes. Moreover, we recently identified a group of human melanoma cell populations which are heterogeneously susceptible to C2-ceramide-mediated apoptosis. Studies with these melanoma cells revealed correlation between ceramide-mediated apoptosis and D-NMAPPD-induced apoptosis, confirming the effect of this inhibitor on ceramide signaling in human melanoma cells. These findings suggest ceramidase inhibitors as a potential new therapeutical class of antiproliferative and cytostatic drugs.