Characteristics and health care utilization of otherwise healthy commercially and Medicaid-insured preterm and full-term infants in the US.
This study examined health care utilization and costs during the first year of life for preterm and full-term infants in the US. Preterm (<37 weeks gestational age [GA]) and full-term infants born 2003 to 2012 without complex medical conditions were identified in the MarketScan® Commercial and Multi-State Medicaid claims databases using ICD-9-CM diagnosis and diagnosis-related grouping codes. Inpatient and outpatient claims from birth through the first year were analyzed for preterm and full-term subgroups. Results were stratified by payer. There were 1,692,935 commercially insured infants (12.5% preterm) and 1,873,324 Medicaid-insured infants (13.9% preterm). The majority (>75%) of preterm infants were admitted to the neonatal intensive care unit during their birth hospitalization. Generally, mean length of stay and costs for birth hospitalizations increased with decreasing GA. The average cost of a birth hospitalization was US $62,931 (SD $134,347) for commercially insured preterm infants and $43,858 (SD $115,412) for Medicaid-insured preterm infants compared to $2,401 (SD $7,399) and $1,894 (SD $5,444) for commercially insured and Medicaid-insured full-term infants, respectively. Post-neonatal hospitalization rates increased as GA decreased (in full-term to <29 weeks GA: commercial =3.3%-19.5%; Medicaid =6.1%-26.2%). Preterm infants had greater average numbers of outpatient office visits and pharmacy claims than full-term infants. Following birth discharge, mean monthly health care costs per infant increased as GA decreased (commercial = $334 to $3,126; Medicaid = $205 to $2,473). During the first year of life, post-neonatal hospitalization rates, outpatient office visits, pharmacy claims, and monthly costs increased as GA decreased.


Developmental Expression and Dysregulation of miR-146a and miR-155 in Down's Syndrome and Mouse Models of Down's Syndrome and Alzheimer's Disease.
miR-146a and miR-155 are key regulators of the innate immune response. We hypothesized that an inflammation-mediated dysregulation of these miRNAs may occur in patients with Down syndrome (DS) and Alzheimer's disease (AD). The miRNA expression patterns were investigated by in situ hybridization in developing hippocampus from controls, patients with DS and in adults with AD pathology (DS and sporadic AD; sAD). Quantitative real-time PCR was employed to evaluate the miRNA levels in the hippocampus of sAD and in mouse models of DS and AD. Both miRNAs were expressed in prenatal human hippocampus. In DS we detected increased miR-146a expression in reactive astrocytes. Increased expression of miR-146a was found in the hippocampus of sAD and negatively correlated with its target IRAK-1. APP/PS1 mice showed a significant increase in the expression of both miRNAs at 11-13 months of age as compared to WT and mice at 3 months. A negative correlation between miR-146a levels and its target TRAF6 was observed in both Ts65Dn and APP/PS1 mice. These findings suggest a possible involvement of miR-146a and miR-155 in brain development and neurodegeneration. In particular, we provide evidence of a dysregulation of these two immunomodulatory miRNAs in AD with a potential therapeutical implication, deserving further investigation.


A correlation analysis of HHV infection and its predictive factors in an HIV-seropositive population in Yunnan, China.
Human herpesviruses (HHVs) have a particularly high prevalence in certain high-risk populations and cause increased morbidity and mortality in patients with acquired immunodeficiency syndrome (AIDS). Screening and treating subclinical HHV infections reduce human immunodeficiency virus (HIV) infection incidence, disease progression, and transmission. However, there are few studies on HHVs, HIV coinfection rates, and their related risk factors. We aimed to clarify the prevalence of all eight HHVs in peripheral blood samples collected from HIV-positive patients, and explore the association of HHV infection in HIV-positive patients in an HIV-seropositive population in Yunnan. We recruited 121 HIV-positive patients with highly active antiretroviral therapy (HAART) and 45 healthy individuals. All the eight HHVs were detected using polymerase chain reaction and their epidemiological information and clinical data were collected and statistically analyzed. A high prevalence of HHVs (89.3%) was observed in individuals with HIV infections and with herpes simplex virus (HSV)-2 (65.3%), and HSV-1 (59.5%) being the most common. Coinfection with more than two different HHVs was more common in patients with HIV infections receiving HAART (72.7%) than in healthy controls. Older age, being married, higher HIV-1 plasma viral loads, and use of antiviral protease inhibitors were independently correlated with an increased frequency of HHVs, but we found no association with CD4 count, WHO HIV clinical stage, and HIV infection duration. Our findings are of great significance for the prevention of HHV opportunistic infection in patients with AIDS and their clinical treatment.


The contribution of genomic research to explaining racial disparities in cardiovascular disease: a systematic review.
After nearly a decade of genome-wide association studies, no assessment has yet been made of their contribution toward an explanation of the most prominent racial health disparities observed at the population level. We examined populations of African and European ancestry and focused on cardiovascular diseases, which are collectively the largest contributor to the racial mortality gap. We conducted a systematic search for review articles and meta-analyses published in 2007-2013 in which genetic data from both populations were available. We identified 68 articles relevant to this question; however, few reported significant associations in both racial groups, with just 3 variants meeting study-specific significance criteria. For most outcomes, there were too few estimates for quantitative summarization, but when summarization was possible, racial group did not contribute to heterogeneity. Most associations reported from genome-wide searches were small, difficult to replicate, and in no consistent direction that favored one racial group or another. Although the substantial investment in this technology might have produced clinical advances, it has thus far made little or no contribution to our understanding of population-level racial health disparities in cardiovascular disease.


Knockdown of vimentin reduces mesenchymal phenotype of cholangiocytes in the Mdr2-/- mouse model of primary sclerosing cholangitis (PSC).
Cholangiocytes are the target cells of cholangiopathies including primary sclerosing cholangitis (PSC). Vimentin is an intermediate filament protein that has been found in various types of mesenchymal cells. The aim of this study is to evaluate the role of vimentin in the progression of biliary damage/liver fibrosis and whether there is a mesenchymal phenotype of cholangiocytes in the Mdr2-/- model of PSC. In vivo studies were performed in 12 wk. Mdr2-/- male mice with or without vimentin Vivo-Morpholino treatment and their corresponding control groups. Liver specimens from human PSC patients, human intrahepatic biliary epithelial cells (HIBEpiC) and human hepatic stellate cell lines (HHSteCs) were used to measure changes in epithelial-to-mesenchymal transition (EMT). There was increased mesenchymal phenotype of cholangiocytes in Mdr2-/- mice, which was reduced by treatment of vimentin Vivo-Morpholino. Concomitant with reduced vimentin expression, there was decreased liver damage, ductular reaction, biliary senescence, liver fibrosis and TGF-β1 secretion in Mdr2-/- mice treated with vimentin Vivo-Morpholino. Human PSC patients and derived cell lines had increased expression of vimentin and other mesenchymal markers compared to healthy controls and HIBEpiC, respectively. In vitro silencing of vimentin in HIBEpiC suppressed TGF-β1-induced EMT and fibrotic reaction. HHSteCs had decreased fibrotic reaction and increased cellular senescence after stimulation with cholangiocyte supernatant with reduced vimentin levels. Our study demonstrated that knockdown of vimentin reduces mesenchymal phenotype of cholangiocytes, which leads to decreased biliary senescence and liver fibrosis. Inhibition of vimentin may be a key therapeutic target in the treatment of cholangiopathies including PSC. FUND: National Institutes of Health (NIH) awards, VA Merit awards.


Characterization of rabbit myocilin: Implications for human myocilin glycosylation and signal peptide usage.
Mutations in the gene encoding human myocilin (MYOC) have been shown to cause juvenile- and adult-onset glaucoma. In addition, myocilin has been associated with glucocorticoid-induced ocular hypertension and steroid-induced glaucoma. To better understand the role myocilin plays in steroid-induced glaucoma and open-angle glaucoma, we examined rabbit myocilin for use in the rabbit animal model of steroid-induced glaucoma. We have cloned the rabbit ortholog of human MYOC. Rabbit MYOC consists of three exons and an open reading frame encoding a 490 amino acid, 54,882-Da protein, which is 14 amino acids shorter at the N-terminus than human myocilin but 84% identical overall. Rabbit myocilin migrates as a single electrophoretic band, vs. double-banded human myocilin, by SDS-PAGE/immunoblot analysis. We determined that the differential migration exhibited is due to an N-glycosylation site that is present in human (Asn57), monkey and mouse myocilin but absent in rabbit (Ser43), rat and bovine myocilin. Rabbit myocilin is secreted in vitro in trabecular meshwork cell culture and in vivo in aqueous humor. Secretion of human myocilin is shown to be dependent on the signal peptide and independent of the extra 14 amino acids not found in rabbit myocilin. Many of the amino acids in myocilin that are mutated in glaucoma patients are conserved across species. We have cloned the rabbit MYOC cDNA and determined that rabbit myocilin is secreted but not N-linked glycosylated. Knowledge of the rabbit MYOC cDNA sequence will facilitate future studies in the rabbit animal model examining the role of myocilin in steroid-induced glaucoma and the gain-of-function hypothesis in open-angle glaucoma.


Bovine Papillomavirus Type 1 or 2 Virion-Infected Primary Fibroblasts Constitute a Near-Natural Equine Sarcoid Model.
Equine sarcoids are common, locally aggressive skin tumors induced by bovine papillomavirus types 1, 2, and possibly 13 (BPV1, BPV2, BPV13). Current in vitro models do not mimic de novo infection. We established primary fibroblasts from horse skin and succeeded in infecting these cells with native BPV1 and BPV2 virions. Subsequent cell characterization was carried out by cell culture, immunological, and molecular biological techniques. Infection of fibroblasts with serial 10-fold virion dilutions (2 × 106-20 virions) uniformly led to DNA loads settling at around 150 copies/cell after four passages. Infected cells displayed typical features of equine sarcoid cells, including hyperproliferation, and loss of contact inhibition. Neither multiple passaging nor storage negatively affected cell hyperproliferation, viral DNA replication, and gene transcription, suggestive for infection-mediated cell immortalization. Intriguingly, extracellular vesicles released by BPV1-infected fibroblasts contained viral DNA that was most abundant in the fractions enriched for apoptotic bodies and exosomes. This viral DNA is likely taken up by non-infected fibroblasts. We conclude that equine primary fibroblasts stably infected with BPV1 and BPV2 virions constitute a valuable near-natural model for the study of yet unexplored mechanisms underlying the pathobiology of BPV1/2-induced sarcoids.


[Ultrasound diagnosis of sternum fractures].
With the present study we wanted to examine the value of ultrasonography in the diagnosis of fractures of the sternum. Included in this study were 11 patients with pain in the sternal region and suspected fracture of this area according to case history and clinical examination. We exclusively used a 7.5 MHZ linear scanner. In all 11 cases the fracture was free of doubts diagnosed using ultrasound. A fragment dislocation could be visualized in 10 cases and 1 case showed a fissure of the sternum. The standard lateral X-ray as our reference method confirmed the sonographical diagnosis in all cases. The diagnostical value of ultrasonography of the sternum is at least as high as that of standard lateral X-ray. When a hypoechoic area over the sternum together with a hematoma, a disruption of the cortical bone or a step in the bony outline as a sign for fragment dislocation are found, sternal fracture is the definite diagnosis. Ultrasonography is quickly feasible, non-invasive and gives sufficient information in these cases without side effects.


The cyclic nucleotide-gated channel, AtCNGC10, influences salt tolerance in Arabidopsis.
Cyclic nucleotide-gated channels (CNGCs) in the plasma membrane transport K+ and other cations; however, their roles in the response and adaptation of plants to environmental salinity are unclear. Growth, cation contents, salt tolerance and K+ fluxes were assessed in wild-type and two AtCNGC10 antisense lines (A2 and A3) of Arabidopsis thaliana (L.) Heynh. Compared with the wild-type, mature plants of both antisense lines had altered K+ and Na+ concentrations in shoots and were more sensitive to salt stress, as assessed by biomass and Chl fluorescence. The shoots of A2 and A3 plants contained higher Na+ concentrations and significantly higher Na+/K+ ratios compared with wild-type, whereas roots contained higher K+ concentrations and lower Na+/K+ ratios. Four-day-old seedlings of both antisense lines exposed to salt stress had smaller Na+/K+ ratios and longer roots than the wild-type. Under sudden salt treatment, the Na+ efflux was higher and the K+ efflux was smaller in the antisense lines, indicating that AtCNGC10 might function as a channel providing Na+ influx and K+ efflux at the root/soil interface. We conclude that the AtCNGC10 channel is involved in Na+ and K+ transport during cation uptake in roots and in long-distance transport, such as phloem loading and/or xylem retrieval. Mature A2 and A3 plants became more salt sensitive than wild-type plants because of impaired photosynthesis induced by a higher Na+ concentration in the leaves.


Partial cambial mortality in high-elevation Pinus aristata (Pinaceae).
Partial cambial mortality is a growth form that is characteristic of Pinus aristata trees. To better elucidate their cambial death pattern, tree size and aspect of cambial death data were gathered from three Pinus aristata forests in central Colorado, USA. Stripping frequency tended to be higher for larger diameter classes. Partial cambial mortality exhibits significant directionality within each stand. Furthermore, cambial death was measured to be most frequent on the wind-exposed side of stripped trees in two of the three study sites and appeared to be at the third. Data presented here support the hypothesis that wind plays a role in the occurrence of partial cambial mortality in Pinus aristata. The mechanisms by which wind causes cambial mortality remain unclear.


[Severe aspiration pneumonia with the laryngeal mask].
The anaesthesia management of a 10-year old girl with a fracture to her distal arm is presented, using inhalational anaesthesia with a laryngeal mask and a supplementary axillary plexus block. Due to light anaesthesia the patient vomited during the course of surgery resulting in a severe pulmonary aspiration necessitating four days of mechanical ventilation in the ICU. The safety of the laryngeal mask airway for emergency surgery is discussed.


Combined biomarker analysis for risk of acute kidney injury in patients with ST-segment elevation myocardial infarction.
Acute kidney injury (AKI) complicating ST-segment elevation myocardial infarction (STEMI) increases subsequent morbidity and mortality. We combined the biomarkers of heart failure (HF; B-type natriuretic peptide [BNP] and soluble ST2 [sST2]) and renal injury (NGAL [neutrophil gelatinase-associated lipocalin] and cystatin C) in predicting the development of AKI in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). From March 2010 to September 2013, 189 STEMI patients were sequentially enrolled and serum samples were collected at presentation for BNP, sST2, NGAL and cystatin C analysis. 37 patients (19.6%) developed AKI of varying severity within 48 hours of presentation. Univariate analysis showed age, Killip class ≥2, hypertension, white blood cell counts, hemoglobin, estimated glomerular filtration rate, blood urea nitrogen, creatinine, and all the four biomarkers were predictive of AKI. Serum levels of the biomarkers were correlated with risk of AKI and the Acute Kidney Injury Network (AKIN) stage and all significantly discriminated AKI (area under the receiver operating characteristic [ROC] curve: BNP: 0.86, sST2: 0.74, NGAL: 0.75, cystatin C: 0.73; all P < 0.05). Elevation of ≥2 of the biomarkers higher than the cutoff values derived from the ROC analysis improved AKI risk stratification, regardless of the creatine level (creatinine < 1.24 mg/dL: odds ratio [OR] 11.25, 95% confidence interval [CI] 1.63-77.92, P = 0.014; creatinine ≥ 1.24: OR 15.0, 95% CI 1.23-183.6, P = 0.034). In this study of STEMI patients undergoing primary PCI, the biomarkers of heart failure (BNP and sST2) and renal injury (NGAL and cystatin C) at presentation were predictive of AKI. High serum levels of the biomarkers were associated with an elevated risk and more advanced stage of AKI. Regardless of the creatinine level, elevation of ≥2 of the biomarkers higher than the cutoff values indicated a further rise in AKI risk. Combined biomarker approach may assist in risk stratification of AKI in patients with STEMI.


Glutathione biosynthesis via activation of the nuclear factor E2-related factor 2 (Nrf2)--antioxidant-response element (ARE) pathway is essential for neuroprotective effects of sulforaphane and 6-(methylsulfinyl) hexyl isothiocyanate.
Oxidative stress plays pivotal roles in aging, neurodegenerative disease, and pathological conditions such as ischemia. We investigated the effect of sulforaphane and 6-(methysulfinyl) hexyl isothiocyanate (6-HITC), a naturally occurring isothiocyanate, on oxidative stress-induced cytotoxicity using primary neuronal cultures of rat striatum. Pretreatment with sulforaphane and 6-HITC significantly protected against H(2)O(2)- and paraquat-induced cytotoxicity in a concentration-dependent manner. Sulforaphane and 6-HITC induced the translocation of nuclear factor E2-related factor 2 (Nrf2) into the nucleus and increased the expression of γ-glutamylcysteine synthetase (γ-GCS), a rate-limiting enzyme in glutathione synthesis, and the intracellular glutathione content. Treatment with reduced glutathione (GSH) and N-acetyl-L-cysteine, a substance for glutathione synthesis, significantly prevented the cytotoxicity induced by H(2)O(2) and paraquat. Moreover, exposure to L-buthionine-sulfoximine, an irreversible inhibitor of γ-GCS, suppressed the protective effects of sulforaphane and 6-HITC. In contrast, sulforaphane and 6-HITC increased heme oxygenase-1 (HO-1) expression in neurons. However, zinc-protophorphyrin IX, a competitive inhibitor of HO-1, did not influence the protective effects of sulforaphane and 6-HITC. These results suggest that sulforaphane and 6-HITC prevent oxidative stress-induced cytotoxicity in rat striatal cultures by raising the intracellular glutathione content via an increase in γ-GCS expression induced by the activation of the Nrf2-antioxidant response element pathway.


Immunogenicity of the Ad26.COV2.S Vaccine for COVID-19.
Control of the global COVID-19 pandemic will require the development and deployment of safe and effective vaccines. To evaluate the immunogenicity of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in humans, including the kinetics, magnitude, and phenotype of SARS-CoV-2 spike-specific humoral and cellular immune responses. Twenty-five participants were enrolled from July 29, 2020, to August 7, 2020, and the follow-up for this day 71 interim analysis was completed on October 3, 2020; follow-up to assess durability will continue for 2 years. This study was conducted at a single clinical site in Boston, Massachusetts, as part of a randomized, double-blind, placebo-controlled phase 1 clinical trial of Ad26.COV2.S. Participants were randomized to receive 1 or 2 intramuscular injections with 5 × 1010 viral particles or 1 × 1011 viral particles of Ad26.COV2.S vaccine or placebo administered on day 1 and day 57 (5 participants in each group). Humoral immune responses included binding and neutralizing antibody responses at multiple time points following immunization. Cellular immune responses included immunospot-based and intracellular cytokine staining assays to measure T-cell responses. Twenty-five participants were randomized (median age, 42; age range, 22-52; 52% women, 44% male, 4% undifferentiated), and all completed the trial through the day 71 interim end point. Binding and neutralizing antibodies emerged rapidly by day 8 after initial immunization in 90% and 25% of vaccine recipients, respectively. By day 57, binding and neutralizing antibodies were detected in 100% of vaccine recipients after a single immunization. On day 71, the geometric mean titers of spike-specific binding antibodies were 2432 to 5729 and the geometric mean titers of neutralizing antibodies were 242 to 449 in the vaccinated groups. A variety of antibody subclasses, Fc receptor binding properties, and antiviral functions were induced. CD4+ and CD8+ T-cell responses were induced. In this phase 1 study, a single immunization with Ad26.COV2.S induced rapid binding and neutralization antibody responses as well as cellular immune responses. Two phase 3 clinical trials are currently underway to determine the efficacy of the Ad26.COV2.S vaccine. ClinicalTrials.gov Identifier: NCT04436276.


Initiation and termination of antibiotic regimens in Veterans Affairs hospitals.
To assess rates of starting or stopping antibiotics across different hospitals. We used barcode medication administration data to measure antibiotic use on acute-care wards in 128 Veterans Affairs medical centres (VAMCs) in 2010. A treatment day (TD) was defined as the administration of any antibiotic on a given day. A treatment period (TP) was defined as an interval of inpatient antimicrobial therapy with gaps of ≤1 day in TDs. The rate of starting antibiotics was calculated for inpatients who had not yet started antibiotics, as the number of start events divided by the 'person-time at risk'. The rate of stopping antibiotics was calculated analogously for inpatients that were on antibiotics. Once individuals had stopped antibiotics they were removed from further analysis. Per-day start and stop rates were also calculated for each day of hospitalization. The hospital mean rate of starting the first TP was 18.1 start events/100 days at risk (range 8.4-25.6/100 days at risk). The mean hospital stopping rate was 21.1 stop events/100 days at risk (range 13.3-29.5/100 days at risk). The ratio of a facility's starting and stopping rates was highly correlated with overall antibiotic use in TDs/1000 patient-days (rs=0.92, P<0.001), while starting and stopping rates individually were only moderately correlated (rs=0.39, P<0.001). VAMCs with similar antibiotic use showed marked differences in their starting and stopping rates of antibiotics. It may be useful to target empirical therapy when starting rates are high and definitive therapy when stopping rates are low.


Evolution, revolution or saltation scenario for the emergence of modern cultures?
Crucial questions in the debate on the origin of quintessential human behaviours are whether modern cognition and associated innovations are unique to our species and whether they emerged abruptly, gradually or as the result of a discontinuous process. Three scenarios have been proposed to account for the origin of cultural modernity. The first argues that modern cognition is unique to our species and the consequence of a genetic mutation that took place approximately 50 ka in Africa among already evolved anatomically modern humans. The second posits that cultural modernity emerged gradually in Africa starting at least 200 ka in concert with the origin of our species on that continent. The third states that innovations indicative of modern cognition are not restricted to our species and appear and disappear in Africa and Eurasia between 200 and 40 ka before becoming fully consolidated. We evaluate these scenarios in the light of new evidence from Africa, Asia and Europe and explore the mechanisms that may have led to modern cultures. Such reflections will demonstrate the need for further inquiry into the relationship between climate and demographic/cultural change in order to better understand the mechanisms of cultural transmission at work in Neanderthals and early Homo sapiens populations.


Clinical Practice of Cataract Special Care Standards in Nonophthalmic Wards.
Cataract is a lens metabolism disease, which is caused by various factors, and leads to metamorphic lens proteins turbidity. Cataract commonly occurs in elderly patients, and majority of these patients have clinical manifestations of blurred vision and other symptoms. In this study, we explored the clinical practice and observations of cataract care criteria in nonophthalmic wards. To realize this, a total of one hundred and twenty (120) cataract patients, admitted to the East Department of Ophthalmology, Shanghai Sixth People's Hospital, particularly from April 2019-2020, were divided into the control and observation groups, where 60 cases were added to each group. The control group received routine nursing, and observation group was treated with cataract care criteria based on the control group. The complication rate, health cognition, and patient's satisfaction were compared with existing approaches. The incidence of corneal edema, anterior chamber hemorrhage, endophthalmitis, and incision infection, specifically in the observation group, was lower than that in the control group (P < 0.05). Likewise, the number of hospitalization days and expenses, specifically in the observation group, were lower than those in the control group (P < 0.05). Health knowledge and satisfaction scores of the observation group were higher than the control group (P < 0.05). Active service, service attitude, psychological support, caring patients, and health education dissatisfaction rate of the observation group were lower than the control group (P < 0.05). Finally, the standard of cataract care in nonophthalmic wards reduces the incidence of complications, improve health awareness of patients, and help to improve satisfaction of patients with nurses. Furthermore, it is worthy of promotion and application particularly in traditional hospitals.


Area-Level Clustering of Shiga Toxin-Producing Escherichia coli Infections and Their Socioeconomic and Demographic Factors in Ontario, Canada: An Ecological Study.
Shiga toxin-producing Escherichia coli (STEC) infections are an important health burden for human populations in Ontario and worldwide. We assessed 452 STEC cases that were reported to Ontario's reportable disease surveillance system between 2015 and 2017. A retrospective scan statistic using a Poisson model was used to detect high-rate STEC clusters at the forward sortation area (FSA; the first three digits of a postal code) level. A significant spatial cluster in the southwest region of Ontario was identified. A case-case logistic regression analysis was applied to compare FSA-level socioeconomic and demographic characteristics among STEC cases included inside the spatial cluster with cases outside of the cluster. Cases included in the spatial cluster had higher odds of living in FSAs with a low median family income, low proportion of lone-parent families, and low proportion of the visible minority population. In addition, STEC cases inside the cluster had higher odds of coming from rural FSAs. Our study demonstrated that STEC cases were spatially clustered in Ontario and their clustering was associated with FSA-level socioeconomic and demographic determinants of cases.


Social aspects of dementia and dementia practice.
Social aspects of dementia are becoming increasingly important as part of a wider shift in emphasis from cure to care. This is partly because approaches based on finding a cure have proved far more difficult and complex than originally imagined (WHO, 2016). New evidence on the effectiveness of public health measures, that while incidence is growing as the proportion of older people in society increases its prevalence amongst older adults is actually falling, has also lead to increased interest in social dimensions of prevention, lifestyle change, and practical intervention in community settings (Prince et al., 2016; Kivipelto et al., 2017). This, in turn, has led to a rediscovery of the role of supports to people living with dementia in their daily lives, the needs of informal carers, and professional activities that can maintain the social engagement of each party (Winblad et al., 2016). The expansion of practice around person-centered care, beyond traditional institutional settings, has also contributed to a socialized view of how interactions in dementia care are thought about (Bartlett et al., 2017), as has an increased awareness of the effects of the social construction of dementia in the public mind (Biggs, 2018). Most recently, people living with dementia, and particularly with respect to younger onset dementia, have begun to find a voice and to make connections to the wider disability movement (Dementia Alliance International, 2017). Each of these developments, in their different ways, have led to a re-emphasis on psycho-social elements of dementia, its experience, and how that might translate into clinical practice and service delivery.


Association of statins and statin discontinuation with poor outcome and survival after intracerebral hemorrhage.
Studies suggest a protective role for statins after intracerebral hemorrhage, but many failed to assess statin discontinuation, did not include postdischarge outcomes, or did not account for withdrawal of care. We studied the relationship between preintracerebral hemorrhage statin use and in-hospital statin discontinuation on stroke severity and 30-day mortality. We analyzed data from the Registry of the Canadian Stroke Network and determined the adjusted ORs for statin use and outcomes, controlling for stroke severity and other covariates. We analyzed 2466 consecutive patients with intracerebral hemorrhage from 2003 to 2008: median age was 71 years, 53.6% were male, and 30-day mortality rate was 36.5%. Overall, 537 (21.7%) were taking statins before presentation. Compared with nonusers, statin users were less likely to have severe strokes on presentation (54.7% versus 63.3%) but had similar rates of poor outcome (70% versus 67%) and 30-day mortality (36% versus 37%). Statins were discontinued on admission in 158 of 537 (29.4%); these patients were more likely to have severe stroke (65% versus 27%, P<0.01), poor outcome (90% versus 62%, P<0.01), and to have died by 30 days (71% versus 21%, P<0.01). After adjusting for stroke severity, statin discontinuation was still associated with poor outcome (adjusted OR, 2.4; 95% CI, 1.13-4.56) and higher mortality (adjusted OR, 2.0; 95% CI, 1.30-3.04). However, these associations were attenuated and no longer significant after excluding patients treated palliatively. We found no association between preadmission statin use and outcomes in intracerebral hemorrhage. Statin discontinuation may worsen outcomes or may simply be a marker of worse underlying prognosis.


Intracellular Salmonella delivery of an exogenous immunization antigen refocuses CD8 T cells against cancer cells, eliminates pancreatic tumors and forms antitumor immunity.
Immunotherapies have shown great promise, but are not effective for all tumors types and are effective in less than 3% of patients with pancreatic ductal adenocarcinomas (PDAC). To make an immune treatment that is effective for more cancer patients and those with PDAC specifically, we genetically engineered Salmonella to deliver exogenous antigens directly into the cytoplasm of tumor cells. We hypothesized that intracellular delivery of an exogenous immunization antigen would activate antigen-specific CD8 T cells and reduce tumors in immunized mice. To test this hypothesis, we administered intracellular delivering (ID) Salmonella that deliver ovalbumin as a model antigen into tumor-bearing, ovalbumin-vaccinated mice. ID Salmonella delivers antigens by autonomously lysing in cells after the induction of cell invasion. We showed that the delivered ovalbumin disperses throughout the cytoplasm of cells in culture and in tumors. This delivery into the cytoplasm is essential for antigen cross-presentation. We showed that co-culture of ovalbumin-recipient cancer cells with ovalbumin-specific CD8 T cells triggered a cytotoxic T cell response. After the adoptive transfer of OT-I CD8 T cells, intracellular delivery of ovalbumin reduced tumor growth and eliminated tumors. This effect was dependent on the presence of the ovalbumin-specific T cells. Following vaccination with the exogenous antigen in mice, intracellular delivery of the antigen cleared 43% of established KPC pancreatic tumors, increased survival, and prevented tumor re-implantation. This response in the immunosuppressive KPC model demonstrates the potential to treat tumors that do not respond to checkpoint inhibitors, and the response to re-challenge indicates that new immunity was established against intrinsic tumor antigens. In the clinic, ID Salmonella could be used to deliver a protein antigen from a childhood immunization to refocus pre-existing T cell immunity against tumors. As an off-the-shelf immunotherapy, this bacterial system has the potential to be effective in a broad range of cancer patients.


Ubiquitination of PCNA and its essential role in eukaryotic translesion synthesis.
Ubiquitin and ubiquitin-like proteins (Ubls) are now at the center stage of molecular and cell biology because of their diverse functions in many fundamentally important cellular processes. Besides the celebrated role of ubiquitin in the 26S proteasome-mediated protein degradation pathway, the non-proteolytic functions of ubiquitin are being uncovered at a fast pace. The prominent examples include membrane trafficking, innate immunity, kinase signaling, chromatin dynamics and DNA damage response. Researchers in the area of DNA damage response have witnessed rapid progress within the past decade, largely stimulated by the seminal findings that ubiquitination and SUMOylation of a key DNA replication/repair protein, proliferating cell nuclear antigen (PCNA), controls precisely how eukaryotic cells respond to different types of DNA damage, and how cellular DNA damage repair or tolerance pathways are selected to cope with damage in the DNA genome. Here, we will review the recent findings on translesion synthesis (TLS) and its regulation by PCNA ubiquitination in eukaryotes. We will discuss two prevalent models, i.e., the postreplicative gap-filling and the polymerase switch, which have been invoked to account for eukaryotic cells' ability to overcome DNA damage associated replication blockade through TLS. Results from both in vitro reconstitution and from genetic systems will be discussed. We will also summarize the recent findings revealing the crosstalk between two major human DNA damage response pathways (the TLS and the Fanconi anemia pathways), and the ATR and ATM-independent regulation of PCNA ubiquitination. Lastly, new methods of preparing ubiquitinated PCNA will be reviewed. The availability of milligram levels of ubiquitinated PCNA will help our understanding of the molecular details in eukaryotic TLS.


Garcinia mangostana Linn displays antidepressant-like and pro-cognitive effects in a genetic animal model of depression: a bio-behavioral study in the Flinders Sensitive Line rat.
There is abundant evidence for both disorganized redox balance and cognitive deficits in major depressive disorder (MDD). Garcinia mangostana Linn (GM) has anti-oxidant activity. We studied the antidepressant-like and pro-cognitive effects of raw GM rind in Flinders Sensitive Line (FSL) rats, a genetic model of depression, following acute and chronic treatment compared to a reference antidepressant, imipramine (IMI). The chemical composition of the GM extract was analysed for levels of α- and γ-mangostin. The acute dose-dependent effects of GM (50, 150 and 200 mg/kg po), IMI (20 mg/kg po) and vehicle were determined in the forced swim test (FST) in FSL rats, versus Flinders Resistant Line (FRL) control rats. Locomotor testing was conducted using the open field test (OFT). Using the most effective dose above coupled with behavioral testing in the FST and cognitive assessment in the novel object recognition test (nORT), a fixed dose 14-day treatment study of GM was performed and compared to IMI- (20 mg/kg/day) and vehicle-treated animals. Chronic treated animals were also assessed with respect to frontal cortex and hippocampal monoamine levels and accumulation of malondialdehyde. FSL rats showed significant cognitive deficits and depressive-like behavior, with disordered cortico-hippocampal 5-hydroxyindole acetic acid (5-HIAA) and noradrenaline (NA), as well as elevated hippocampal lipid peroxidation. Acute and chronic IMI treatment evoked pronounced antidepressant-like effects. Raw GM extract contained 117 mg/g and 11 mg/g α- and γ-mangostin, respectively, with acute GM demonstrating antidepressant-like effects at 50 mg/kg/day. Chronic GM (50 mg/kg/d) displayed significant antidepressant- and pro-cognitive effects, while demonstrating parity with IMI. Both behavioral and monoamine assessments suggest a more prominent serotonergic action for GM as opposed to a noradrenergic action for IMI, while both IMI and GM reversed hippocampal lipid peroxidation in FSL animals. Concluding, FSL rats present with cognitive deficits and depressive-like behaviors that are reversed by acute and chronic GM treatment, similar to that of IMI.


Lack of evidence for HIV type 1-related SIVcpz infection in captive and wild chimpanzees (Pan troglodytes verus) in West Africa.
Serum from 387 chimpanzees (Pan troglodytes verus), caught in the wild or bred in captivity, was tested for antibody to HIV-1 and HIV-2, using second- and third-generation enzyme immunoassays. Six samples were repeatedly positive; however, only one of these was Western blot positive. Serial sera drawn before and after the Western blot-positive samples were seronegative, and thus we conclude that this sample represented specimen contamination, or mislabeling. Thus, none of the 387 Pan troglodytes verus from West Africa were spontaneously infected with SIVcpz. Chimpanzees are known to be exquisitely susceptible to infection with HIV-1 when experimentally inoculated, and thus our findings suggest that HIV-1-related viruses do not exist in Pan troglodytes verus in the wild. As it has been convincingly shown that SIVcpz exists in wild Pan troglodytes troglodytes in Central Africa, this suggests that HIV-1 arose in Central Africa, but not in West Africa.


Management of malignant hyperthermia susceptible parturients.
The management of eleven women susceptible to malignant hyperthermia during twenty deliveries is presented. These women were managed over a six-year period following guidelines that were established in 1990. Initial problems identified were the management of labour and caesarean section, the use of sympathomimetics and potential problems for the newborn, viz placental transfer of drugs and the possibility of a stress-induced malignant hyperthermia reaction in the newborn. There was little evidence that the stress of labour produced hypermetabolic responses in either mother or neonates and the use of sympathomimetics increased throughout the six-year period with no evidence of adverse effects. A caesarean section using general anaesthesia was not required but the management of this situation is described in both the protocol and discussion sections of this paper.


Antifungal Susceptibility Profiles and Drug Resistance Mechanisms of Clinical Lomentospora prolificans Isolates.
Lomentospora prolificans is an opportunistic fungal pathogen with low susceptibility to current antifungal drugs. Here, we tested the in vitro susceptibility of 8 drugs against 42 clinical L. prolificans isolates. All isolates showed high MICs to voriconazole (MIC90>16 μg/ml), itraconazole (MIC90>16 μg/ml), posaconazole (MIC90>16 μg/ml), isavuconazole (MIC90>16 μg/ml), amphotericin B (MIC90>16 μg/ml), and terbinafine (MIC90>64 μg/ml) and high minimum effective concentrations (MECs) to micafungin (MEC90>8 μg/ml), with the exception of miltefosine showing an MIC90 value of 4 μg/ml. We examined six different in vitro drug combinations and found that the combination of voriconazole and terbinafine achieved the most synergistic effort against L. prolificans We then annotated the L. prolificans whole genome and located its Cyp51 and Fks1 genes. We completely sequenced the two genes to determine if any mutation would be related to azole and echinocandin resistance in L. prolificans We found no amino acid changes in Cyp51 protein and no tandem repeats in the 5' upstream region of the Cyp51 gene. However, we identified three intrinsic amino acid residues (G138S, M220I, and T289A) in the Cyp51 protein that were linked to azole resistance. Likewise, two intrinsic amino acid residues (F639Y, W695F) that have reported to confer echinocandin resistance were found in Fks1 hot spot regions. In addition, three new amino acid alterations (D440A, S634R, and H1245R) were found outside Fks1 hot spot regions, and their contributions to echinocandin resistance need future investigation. Overall, our findings support the notion that L. prolificans is intrinsically resistant to azoles and echinocandins.


Computing Mathematical Functions using DNA via Fractional Coding.
This paper discusses the implementation of mathematical functions such as exponentials, trigonometric functions, the sigmoid function and the perceptron function with molecular reactions in general, and DNA strand displacement reactions in particular. The molecular constructs for these functions are predicated on a novel representation for input and output values: a fractional encoding, in which values are represented by the relative concentrations of two molecular types, denoted as type-1 and type-0. This representation is inspired by a technique from digital electronic design, termed stochastic logic, in which values are represented by the probability of 1's in a stream of randomly generated 0's and 1's. Research in the electronic realm has shown that a variety of complex functions can be computed with remarkably simple circuitry with this stochastic approach. This paper demonstrates how stochastic electronic designs can be translated to molecular circuits. It presents molecular implementations of mathematical functions that are considerably more complex than any shown to date. All designs are validated using mass-action simulations of the chemical kinetics of DNA strand displacement reactions.


Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss.
DNA methyltransferase 1 (DNMT1) is crucial for maintenance of methylation, gene regulation and chromatin stability. DNA mismatch repair, cell cycle regulation in post-mitotic neurons and neurogenesis are influenced by DNA methylation. Here we show that mutations in DNMT1 cause both central and peripheral neurodegeneration in one form of hereditary sensory and autonomic neuropathy with dementia and hearing loss. Exome sequencing led to the identification of DNMT1 mutation c.1484A>G (p.Tyr495Cys) in two American kindreds and one Japanese kindred and a triple nucleotide change, c.1470-1472TCC>ATA (p.Asp490Glu-Pro491Tyr), in one European kindred. All mutations are within the targeting-sequence domain of DNMT1. These mutations cause premature degradation of mutant proteins, reduced methyltransferase activity and impaired heterochromatin binding during the G2 cell cycle phase leading to global hypomethylation and site-specific hypermethylation. Our study shows that DNMT1 mutations cause the aberrant methylation implicated in complex pathogenesis. The discovered DNMT1 mutations provide a new framework for the study of neurodegenerative diseases.


A task-dependent causal role for low-level visual processes in spoken word comprehension.
It is well established that the comprehension of spoken words referring to object concepts relies on high-level visual areas in the ventral stream that build increasingly abstract representations. It is much less clear whether basic low-level visual representations are also involved. Here we asked in what task situations low-level visual representations contribute functionally to concrete word comprehension using an interference paradigm. We interfered with basic visual processing while participants performed a concreteness task (Experiment 1), a lexical-decision task (Experiment 2), and a word class judgment task (Experiment 3). We found that visual noise interfered more with concrete versus abstract word processing, but only when the task required visual information to be accessed. This suggests that basic visual processes can be causally involved in language comprehension, but that their recruitment is not automatic and rather depends on the type of information that is required in a given task situation. (PsycINFO Database Record


[Steps towards a symptom-based diagnosis of fibromyalgia syndrome. Symptom profiles of patients from different clinical settings].
A symptom-based diagnosis of fibromyalgia syndrome (FMS) without tender point examination is helpful for primary medical care. We tested whether a symptom-based diagnosis of FMS can be based on the symptoms of musculoskeletal pain and fatigue. The most frequent and severe symptoms in FMS patients from four different settings (n= 464 from a self-help organization, n=162 from medical expertise, n= 33 from a private rheumatology practice, n=36 from a tertiary-care pain department) were assessed using the Giessen Subjective Complaints List GBB 24. The most frequent and severe symptoms were assessed and compared to those of a representative German population sample. A k-means cluster analysis was performed to identify sub-groups with and without additional vegetative symptoms within the total sample of FMS patients. The most frequent and severe symptoms in all four sub-samples were low back pain, limb pain and fatigue. The greatest mean differences between FMS patients and the general population were found in the subscales "limb pain" and "fatigue". Cluster analysis identified three sub-groups of patients which were all characterized by severe limb pain and fatigue, as well as varying degrees of vegetative symptoms. Following the exclusion of inflammatory rheumatoid, endocrinological and neurological diseases, a symptom-based clinical diagnosis of FMS can be based on of the key symptoms of chronic widespread musculoskeletal pain, as well as chronic fatigue.


The extracellular matrix: not just pretty fibrils.
The extracellular matrix (ECM) and ECM proteins are important in phenomena as diverse as developmental patterning, stem cell niches, cancer, and genetic diseases. The ECM has many effects beyond providing structural support. ECM proteins typically include multiple, independently folded domains whose sequences and arrangement are highly conserved. Some of these domains bind adhesion receptors such as integrins that mediate cell-matrix adhesion and also transduce signals into cells. However, ECM proteins also bind soluble growth factors and regulate their distribution, activation, and presentation to cells. As organized, solid-phase ligands, ECM proteins can integrate complex, multivalent signals to cells in a spatially patterned and regulated fashion. These properties need to be incorporated into considerations of the functions of the ECM.


[Diffusion sampling of benzene present in the urine].
Benzene is a widely diffuse solvent; in the industrial environment benzene is currently present at concentrations of ppm. A valid method of biological monitoring that is easy to perform is need for assessing occupational and non-occupational exposures. A new method has been developed to evaluate low concentrations of benzene in urine samples by means of a diffusion sampling. The solvent is absorbed from the urine surface and concentrated on an absorbent substrate (Tenax) that is placed inside the vial. The solvent is thermically desorbed from Tenax and injected into a column (Thermal Tube Desorber-Supelco; 250 degrees C thermal flash; borosilicate capillary glass-column SPB-I 60 m length, 0.75 mm I.D., 1 micron film thickness; GC Dani 8580-FID). The method, which had not been previously employed for the determination of volatile organic substances in biological fluids, has a linear range which extends up to 40 micrograms/l, and gives results in excellent agreement with the conventional Head Space method, except in the low concentration region: the new method permits the quantitative determination of benzene quantities smaller than the detection limit of Head Space method connected with mass spectrometer (approximately 1 microgram/l). The detection limit was not exactly determined, but is estimated to be of 100 ng/l with 25 ml of urine sample.


Knockdown of Placental Major Facilitator Superfamily Domain Containing 2a in Pregnant Mice Reduces Fetal Brain Growth and Phospholipid Docosahexaenoic Acid Content.
Docosahexaenoic acid (DHA) is an n-3 long chain polyunsaturated fatty acid critical for fetal brain development that is transported to the fetus from the mother by the placenta. The lysophosphatidylcholine (LPC) transporter, Major Facilitator Superfamily Domain Containing 2a (MFSD2a), is localized in the basal plasma membrane of the syncytiotrophoblast of the human placenta, and MFSD2a expression correlates with umbilical cord blood LPC-DHA levels in human pregnancy. We hypothesized that placenta-specific knockdown of MFSD2a in pregnant mice reduces phospholipid DHA accumulation in the fetal brain. Mouse blastocysts (E3.5) were transduced with an EGFP-expressing lentivirus containing either an shRNA targeting MFSD2a or a non-coding sequence (SCR), then transferred to pseudopregnant females. At E18.5, fetuses were weighed and their placenta, brain, liver and plasma were collected. MFSD2a mRNA expression was determined by qPCR in the brain, liver and placenta and phospholipid DHA was quantified by LC-MS/MS. MFSD2a-targeting shRNA reduced placental mRNA MFSD2a expression by 38% at E18.5 (n = 45, p < 0.008) compared with SCR controls. MFSD2a expression in the fetal brain and liver were unchanged. Fetal brain weight was reduced by 13% (p = 0.006). Body weight, placenta and liver weights were unaffected. Fetal brain phosphatidyl choline and phosphatidyl ethanolamine DHA content was lower in fetuses with placenta-specific MFSD2a knockdown. Placenta-specific reduction in expression of the LPC-DHA transporter MFSD2a resulted in reduced fetal brain weight and lower phospholipid DHA content in the fetal brain. These data provide mechanistic evidence that placental MFSD2a mediates maternal-fetal transfer of LPC-DHA, which is critical for brain growth.


Microwave beamforming for non-invasive patient-specific hyperthermia treatment of pediatric brain cancer.
We present a numerical study of an array-based microwave beamforming approach for non-invasive hyperthermia treatment of pediatric brain tumors. The transmit beamformer is designed to achieve localized heating-that is, to achieve constructive interference and selective absorption of the transmitted electromagnetic waves at the desired focus location in the brain while achieving destructive interference elsewhere. The design process takes into account patient-specific and target-specific propagation characteristics at 1 GHz. We evaluate the effectiveness of the beamforming approach using finite-difference time-domain simulations of two MRI-derived child head models from the Virtual Family (IT'IS Foundation). Microwave power deposition and the resulting steady-state thermal distribution are calculated for each of several randomly chosen focus locations. We also explore the robustness of the design to mismatch between the assumed and actual dielectric properties of the patient. Lastly, we demonstrate the ability of the beamformer to suppress hot spots caused by pockets of cerebrospinal fluid (CSF) in the brain. Our results show that microwave beamforming has the potential to create localized heating zones in the head models for focus locations that are not surrounded by large amounts of CSF. These promising results suggest that the technique warrants further investigation and development.


Sensorineural Hearing Loss in Non-depressed Essential Tremor Cases and Controls: A Clinical and Audiometric Study.
Patients with essential tremor (ET) have an increased prevalence of hearing loss, and depression is a confounding issue for both conditions. We assessed hearing loss in non-depressed ET patients and controls using a questionnaire and audiometric tests. The study included 34 patients with ET and 45 volunteers were included. Both groups were asked if they had hearing loss, and pure tone audiometry, speech recognition threshold, tympanogram, short increment sensitivity index (SISI), tone decay, and otoacoustic emission audiological tests were conducted. Seventeen subjects (50.0%) in the patient group answered "yes" to the question "Do you have hearing loss?" compared to one (2.2%) subject in the control group (p<0.001). The tone decay values of the right ear at 4,000 Hz were higher in the patient group. The number of subjects in which the otoacoustic emissions could not be obtained in the right ear was higher in the ET patients (p = 0.005). The results support the presence of a cochlear pathology in ET and may indicate that ET and sensorineural hearing loss may be components of a common disease process.


Inflammatory Stroke Extracellular Vesicles Induce Macrophage Activation.
Extracellular vesicles (EVs) are protein-lipid complexes released from cells, as well as actively exocytosed, as part of normal physiology, but also during pathological processes such as those occurring during a stroke. Our aim was to determine the inflammatory potential of stroke EVs. EVs were quantified and analyzed in the sera of patients after an acute stroke (<24 hours; OXVASC [Oxford Vascular Study]). Isolated EV fractions were subjected to untargeted proteomic analysis by liquid chromatography mass-spectrometry/mass-spectrometry and then applied to macrophages in culture to investigate inflammatory gene expression. EV number, but not size, is significantly increased in stroke patients when compared to age-matched controls. Proteomic analysis reveals an overall increase in acute phase proteins, including C-reactive protein. EV fractions applied to monocyte-differentiated macrophage cultures induced inflammatory gene expression. Together these data show that EVs from stroke patients are proinflammatory in nature and are capable of inducing inflammation in immune cells.


Diabetes Mellitus and Hyperglycemia and the Risk of Aseptic Loosening in Total Joint Arthroplasty.
It is unknown to what extent diabetes mellitus modifies the long-term risk of aseptic loosening in total hip arthroplasty (THA) and total knee arthroplasty (TKA). We examined the association between diabetes mellitus, perioperative hyperglycemia, and the likelihood of revisions for aseptic loosening. We studied 16,085 primary THA and TKA procedures performed at a large tertiary care hospital between 2002 and 2009. All blood glucose values around the time of surgery (within 1 week) were retrieved. Subsequent revision surgeries and the reasons for revision were ascertained through the institutional joint registry. Multivariate Cox models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for aseptic loosening associated with diabetes mellitus and hyperglycemia adjusting for age, gender, body mass index, and surgery type. A total of 2911 (18%) surgeries had a diagnosis of diabetes mellitus at the time of surgery. Glucose testing was performed at least once in 7055 (44%) procedures within ±1 week of surgery. Although diabetic patients did not experience a higher risk of revision for aseptic loosening (HR, 0.87; 95% CI, 0.55-1.38), higher preoperative glucose values on the day before surgery were significantly associated with both the overall risk of revisions (HR, 2.80; 95% CI, 1.00-7.85) and revisions for aseptic loosening (HR, 4.95; 95% CI, 1.26-19.54). High preoperative hyperglycemia is a potential risk factor for aseptic loosening in THA and TKA.


Quality-of-life and quality-adjusted survival (Q-TWiST) in patients receiving lapatinib in combination with paclitaxel as first-line treatment for metastatic breast cancer.
In a phase 3 randomized, multicenter, double-blind, placebo-controlled study, first-line therapy with lapatinib plus paclitaxel significantly improved clinical outcomes based on a pre-planned analysis of ErbB2+ metastatic breast cancer patients (GSK Study #EGF30001; ClinicalTrials.gov identifier: NCT00075270). Patients with ErbB2- or untested did not significantly benefit. This article focuses on the quality of life (QOL) and quality-adjusted survival outcomes (Q-TWiST) in the study. QOL was assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B). Changes from baseline were analyzed using ANCOVAs, repeated measures and pattern mixture modeling. The Q-TWiST method was used to examine the trade-off between toxicities and delayed progression. The study included 579 subjects, of whom 86 were ErbB2+. In the ITT population, no significant differences in QOL or Q-TWiST scores were observed. In the ErbB2+ subgroup, the lapatinib plus paclitaxel (L + P) arm demonstrated stable FACT-B scores over the first year, while average scores for patients on P + placebo (P + pla) monotherapy decreased (change from baseline: L + P, p = 0.99; P + pla, p = 0.01). Clinically meaningful differences were observed between treatment arms on the FACT-B, Trial Outcome Index and breast cancer subscale scores. Pattern mixture models suggested more QOL differentiation between treatments among patients who progressed or withdrew early. Q-TWiST differences between the arms in the ErbB2+ subgroup ranged from 2 to 15 weeks with an L + P advantage across all utility weight combinations. In the ITT population, results provide no evidence of QOL differences between treatment groups. In a small, prospectively-defined subgroup of ErbB2+ patients, L + P resulted in more stable QOL and more quality-adjusted survival than paclitaxel monotherapy, representing clinically important differences between treatments.


A Multidimensional Approach to Measuring Economic Insecurity: The Case of Chile.
This paper proposes a strategy to measure economic insecurity in countries in the Global South. It builds a 'Multidimensional Economic Insecurity Index' (MEII) that combines four indicators of economic vulnerability that cause stress and anxiety: unexpected economic shocks, unprotected employment or non-workers in the household, over-indebtedness and asset poverty. The index offers a measure that directly relates economic uncertainty to stress and anxiety due to the lack of protection and buffers to face an unexpected economic shock. The MEII is applied to Chile using Survey of Household Finances (SHF) cross-sectional data (2007, 2011, 2014 and 2017). The results show that (i) about half of the Chilean households experienced, on average, two or more economic vulnerabilities during the last decade with an intensity of 2.3 vulnerabilities, and (ii) economic insecurity affects households on the entire income distribution, even in the highest income deciles groups. By identifying the groups of households most affected by economic insecurity and its trend in recent years, applying the MEII in countries such as Chile provides relevant information to monitor, evaluate and improve social safety nets besides labour market regulations.


A Novel Technique for Generating and Observing Chemiluminescence in a Biological Setting.
Intraoperative imaging techniques have the potential to make surgical interventions safer and more effective; for these reasons, such techniques are quickly moving into the operating room. Here, we present a new approach that utilizes a technique not yet explored for intraoperative imaging: chemiluminescent imaging. This method employs a ruthenium-based chemiluminescent reporter along with a custom-built nebulizing system to produce ex vivo or in vivo images with high signal-to-noise ratios. The ruthenium-based reporter produces light following exposure to an aqueous oxidizing solution and re-reduction within the surrounding tissue. This method has allowed us to detect reporter concentrations as low as 6.9 pmol/cm2. In this work, we present a visual guide to our proof-of-concept in vivo studies involving subdermal and intravenous injections in mice. The results suggest that this technology is a promising candidate for further preclinical research and might ultimately become a useful tool in the operating room.


Cadmium concentrations in German soybeans are elevated in conurbations and in regions dominated by mining and the metal industry.
Cadmium (Cd) is a mobile heavy metal and soybeans accumulate more of this element compared to other grain crops. Because vegan and vegetarian lifestyles are increasingly popular, plant-based diets should be free from contaminants. Cd minimization has recently been identified as a breeding aim in addition to protein and oil levels. It is also important to consider the regional variability of Cd in crops. A large sample collection (n = 602) was subjected to Cd analyses. Soybeans were grown using a standard protocol by private gardeners in a citizen science program. Some 12.5% of samples exceeded European Union limits, although Cd concentrations and exceedances showed regional variation around the national mean (0.13 mg kg-1 ). Contamination was higher in densely populated regions, possibly as a result of the long-term emissions of heavy metal loaded dusts from industry, traffic and energy production. Cd concentrations were also elevated in regions once characterized by mining and heavy industry. Values were low overall in rural areas and agricultural regions despite potential inputs via phosphate fertilizers. Grain Cd levels are highly variable across Germany. Soybean farming may be problematic in regions with a long history of mining and heavy metal deposition. © 2018 Society of Chemical Industry.


Drug consumption rooms are effective to reduce at-risk practices associated with HIV/HCV infections among people who inject drugs: Results from the COSINUS cohort study.
The primary aim of this study was to evaluate the impact of drug consumption rooms (DCRs) in France on injection equipment-sharing, while the secondary aims focused upon their impact on access to hepatitis C virus (HCV) testing and opioid agonist treatment (OAT). The COhort to identify Structural and INdividual factors associated with drug USe (COSINUS cohort) was a 12-month longitudinal study of 665 people who inject drugs (PWID), conducted in Bordeaux, Marseille, Paris and Strasbourg. We used data from face-to-face interviews at enrolment and at 6-month and 12-month visits. The participants were recruited in harm reduction programmes in Bordeaux and Marseille and in DCRs in Strasbourg and Paris. Participants were aged more than 18 years, French-speaking and had injected substances the month before enrolment. We measured the impact of DCR exposure on injection equipment sharing, HCV testing and the use of medications for opioid use disorder, after adjustment for significant correlates. We used a two-step Heckman mixed-effects probit model, which allowed us to take into account the correlation of repeated measures and to control for potential bias due to non-randomization between the two groups (DCR-exposed versus DCR-unexposed participants). The difference of declared injection equipment sharing between PWID exposed to DCRs versus non-exposed was 10% (1% for those exposed versus 11% for those non-exposed, marginal effect = -0.10; 95% confidence interval = -0.18, -0.03); there was no impact of DCRs on HCV testing and OAT. In the French context, drug consumption rooms appear to have a positive impact on at-risk practices for infectious diseases such as human immunodeficiency virus (HIV) and hepatitis C virus.


Mice lacking the norepinephrine transporter are supersensitive to psychostimulants.
The action of norepinephrine (NE) is terminated, in part, by its uptake into presynaptic noradrenergic neurons by the plasma-membrane NE transporter (NET), which is a target for antidepressants and psychostimulants. Disruption of the NET gene in mice prolonged the clearance of NE and elevated extracellular levels of this catecholamine. In a classical test for antidepressant drugs, the NET-deficient (NET-/-) animals behaved like antidepressant-treated wild-type mice. Mutants were hyper-responsive to locomotor stimulation by cocaine or amphetamine. These responses were accompanied by dopamine D2/D3 receptor supersensitivity. Thus altering NET expression significantly modulates midbrain dopaminergic function, an effect that may be an important component of the actions of antidepressants and psychostimulants.


Prevalence of respiratory symptoms among female flight attendants and teachers.
Potential health effects of the indoor environment in office buildings and aircraft have generated considerable concern in recent years. To analyse the prevalence of self reported respiratory symptoms and illnesses in flight attendants (FAs) and schoolteachers. Data were collected as part of a study of reproductive health among female FAs. The prevalences of work related eye, nose, and throat symptoms, wheezing, physician diagnosed asthma, chest illness, and cold or flu were calculated and stratified by smoking status in 1824 FAs and 331 schoolteachers. FAs and teachers were significantly more likely to report work related eye (12.4% and 7.4 %, respectively), nose (15.7% and 8.1%), and throat symptoms (7.5% and 5.7%) than were other working women (2.9% eye, 2.7% nose, and 1.3% throat symptoms). FAs were significantly more likely than teachers and referent working women to report chest illness during the prior three years (32.9%, 19.3%, 7.2%, respectively). Both study groups were more likely to report five or more episodes of cold or flu in the past year than were other working women (10.2% of FAs, 8.2% of teachers, 2.3% of referents), and both groups were more likely to report wheezing than other working women (22.8% of FAs, 28.4% of teachers, 16.4% of referents). FAs were significantly less likely than teachers and other working women to report ever having been diagnosed with asthma (8.2%, 13.3%, 11.8%, respectively). Overall, FAs and schoolteachers report a higher prevalence of work related upper respiratory symptoms, chest illness, and cold or flu than the general working population.


Right ventricular infarction: specific requirements of management.
The principal cause of right ventricular infarction is atherosclerotic proximal occlusion of the right coronary artery. Proximal occlusion of this artery leads to electrocardiographically identifiable right-heart ischemia and an increased risk of death in the presence of acute inferior infarction. Clinical recognition begins with the ventricular electrocardiographic manifestations: inferior left ventricular ischemia (ST segment elevation in leads II, III and aVF), with or without accompanying abnormal Q waves and right ventricular ischemia (ST segment elevation in right chest leads V3R through V6R and ST segment depression in anterior leads V2 through V4). Associated findings may include atrial infarction (PR segment displacement, elevation or depression in leads II, III and aVF), symptomatic sinus bradycardia, atrioventricular node block and atrial fibrillation. Hemodynamic effects of right ventricular dysfunction may include failure of the right ventricle to pump sufficient blood through the pulmonary circuit to the left ventricle, with consequent systemic hypotension. Management is directed toward recognition of right ventricular infarction, reperfusion, volume loading, rate and rhythm control, and inotropic support.


Evaluation of antimicrobial activities of sequential spray applications of decontamination treatments on chicken carcasses.
The objective of this study was to evaluate the effects of sequential applications of ɛ-polylysine (EPL) or lauramide arginine ethyl ester (LAE) sprays followed by an acidic calcium sulfate (ACS) spray on inoculated chicken carcasses to reduce Salmonella (Salmonella enterica serovars including Salmonella typhimurium and Salmonella enteritidis) contamination during 6 days of storage (4.4°C). Secondly, reductions of the resident microflora were studied on uninoculated chicken carcasses following the sequential application of the treatments, chilling and 10 days of storage at 4.4°C. The treatment of Salmonella inoculated carcasses with 300 mg/L EPL followed by 30% ACS (EPL300-ACS30) sprays reduced Salmonella counts initially by 1.5 log cfu/mL and then by 1.2 log cfu/mL (p<0.05) following 6 days of storage at 4.4°C. Likewise, 200 mg/L LAE followed by 30% ACS (LAE200-ACS30) treatment reduced initial Salmonella counts on poultry carcasses by 1.8, 1.4 and 1.8 log cfu/mL (p<0.05), respectively, after 0, 3, and 6 days storage. Immediately after the treatments, EPL300-ACS30 and LAE200-ACS30 both reduced Escherichia coli counts significantly by 2.6 and 2.9 log cfu/mL, respectively. EPL300-ACS30 and LAE200-ASC30 were effective in lowering psychrotroph counts by 1 log cfu/mL on day 10 when compared to the control and distilled water treatments. This study demonstrated that EPL300-ACS30 and LAE200-ACS30 were effective in reducing Salmonella on inoculated chicken carcasses both after treatment and during the storage at 4.4°C for up to 6 days. In addition, reductions in psychrotroph counts indicated that these treatments might have the potential to increase the shelf-life of poultry carcasses.


Electrical recordings from meningioma cells during cytolytic action of antibody and complement.
Resting membrane potential and total cell resistance of human meningioma cells in tissue culture have been measured with fine microelectrodes. Addition of either antiserum inactivated with heat or control serum from normal rabbits produced small depolarizations (2 to 4 millivolts) with no discernible ( 5 percent) change in resistance. Addition of antiserums with complement, however, produced larger depolarizations and decreases in resistance before any changes in cell morphology were visible with light microscopy; as cytoplasmic swelling progressed, membrane potential dropped close to zero, and resistance decreased five- to tenfold. The electrical recording technique may be useful in the study of sublethal as well as lethal damage to immune cells and, in particular, may permit temporal resolution of damaging events and repair mechanisms in a single cell.


Impact of health education on sexual risk behaviour of secondary school students in Jos, Nigeria.
Secondary school students are a high risk group for HIV transmission. They could also be easily reached with health education interventions. There is as yet no global consensus on the nature, content and effectiveness of this intervention among this group. It is also not known how effective this intervention is in reducing sexual risk behaviour among secondary school students in our environment. The aim of the study was to find out the impact of HIV/AIDS health education intervention on the sexual risk behaviour of secondary school students. This was an interventional follow-up study among senior secondary school students with controls selected from similar schools. The students' sexual risk behaviour was assessed at baseline followed by a HIV/AIDS health education intervention. The risk behaviour was then re-assessed 6 months after the intervention. Students who lived in urban areas and those who lived with both parents were less likely to have experienced sexual intercourse at baseline than those who lived in the rural areas (but school in Jos during school sessions), and those who lived with single parents and other relations. Health education delayed sexual debut among students who were sexually naïve but had no effect on the sexual activity of those who were already sexually experienced. Health Education intervention has a place in reducing secondary school students' sexual risk behaviourif commenced before their sexual debut.


The incidence of color blindness among some school children of Pokhara, Western Nepal.
The incidence of color blindness varies from race to race and different in different geographical area. Since, there is no such report about the prevalence of color blindness in the western part of Nepal, the present study had been conducted to find out the incidence of color blindness among school children of Pokhara city, western Nepal. Participant's (n=964, 474 boys, 490 girls, age group 10 to 19 years) color vision was tested by using Ishihara chart (38 plates). Among 474 boys, 18 boys were color blind with the prevalence of 3.8%. None of girls were found to be color blind. Out of 18 color blind boys, nine, six and three boys were the victims of deuteranopia, deuteranomaly and protanomaly respectively. The incidence of color blindness were more amongst the Darji (14.3%) and Newar (9.1%) ethnic groups.


Chemokine receptors in the pathogenesis and therapy of psoriasis.
Chemokine receptors are G-protein-coupled, seven-transmembrane-spanning surface receptors that play key roles in cell trafficking, cell motility, and survival. These receptors are activated by small molecular weight chemotactic cytokines called chemokines. Chemokine receptors and their corresponding chemokine ligands play roles in the migration and localization of normal T cells (and other cells) during physiological responses in inflamed or infected skin. In psoriasis, the chemokine receptor CCR6 is expressed on the Th17 cells and γδ T cells, which produce a variety of cytokines (IL17 and IL22 among others), that play a role in the immunological activation. CCR6 and its ligand, CCL20, are highly expressed in psoriatic skin lesion and CCR6 is essential for the development of the psoriasiform phenotype following IL23 injection in mouse skin. In this review, we focus on the roles of chemokine receptors, particularly of CCR6, in the pathogenesis of psoriasis and discuss chemokine receptors as novel therapeutic targets for psoriasis.


Architecting Braided Porous Carbon Fibers Based on High-Density Catalytic Crystal Planes to Achieve Highly Reversible Sodium-Ion Storage.
Carbonaceous materials are considered strong candidates as anode materials for sodium-ion batteries (SIBs), which are expected to play an indispensable role in the carbon-neutral era. Herein, novel braided porous carbon fibres (BPCFs) are prepared using the chemical vapour deposition (CVD) method. The BPCFs possess interwoven porous structures and abundant vacancies. The growth mechanism of the BPCFs can be attributed to the polycrystalline transformation of the nanoporous copper catalyst in the early stage of CVD process. Density functional theory calculations suggest that the Na+ adsorption energies of the mono-vacancy edges of the BPCFs (-1.22 and -1.09 eV) are lower than that of an ideal graphene layer (-0.68 eV), clarifying in detail the adsorption-dominated sodium storage mechanism. Hence, the BPCFs as an anode material present an outstanding discharge capacity of 401 mAh g-1 at 0.1 A g-1 after 500 cycles. Remarkably, this BPCFs anode, under high-mass-loading of 5 mg cm-2, shows excellent long-term cycling ability with a reversible capacity of 201 mAh g-1 at 10 A g-1 over 1000 cycles. This study provided a novel strategy for the development of high-performance carbonaceous materials for SIBs.


Treatment-Resistant Juvenile Depression-A Quicksand?
Though research in juvenile depression is advancing, evidence examining effective treatments for Treatment-resistant juvenile depression remains at large limited. There is a dire need for more studies to help guide clinicians navigating these challenging cases.


Effect of Different Slopes of the Lower Leg during the Nordic Hamstring Exercise on Hamstring Electromyography Activity.
The purpose of this study was to examine whether the NHE with an increased lower leg slope angle would enhance hamstring EMG activity in the final phase of the descend. The hamstring EMG activity was measured, the biceps femoris long head (BFlh) and the semitendinosus (ST). Fifteen male volunteers participated in this study. Subjects performed a prone leg curl with maximal voluntary isometric contraction to normalize the hamstring EMG activity. Subsequently, subjects performed the NHE, with the help of a certified strength and conditioning specialist, while the lower leg slope angle were randomly set at 0° (NH), 20° (N20), and 40° (N40). To compare hamstring EMG activity during the NHE variations, the knee flexion angle was set in the range from 0° to 50°, divided into five phases (0-10°, 10-20°, 20-30°, 30-40° and 40-50°), where 0° indicated that the knee was fully extended. To calculate the knee extension angular velocity, the knee flexion angle divided by time, and break point angle (BPA) was the angle at which 10°/s was exceeded. In the statistical analysis, a two-way repeated measures ANOVA was used for the hamstring EMG activity and a one-way repeated measures ANOVA was used for the BPA. The EMG activity of the BFlh and the ST in N20 and N40 was significantly higher than in NH at knee flexion angle of 0-20° (p < 0.05). For the BPA, NH (57.75° ± 13.28°), N20 (36.27° ± 9.89°) and N40 (16.26° ± 9.58°) were significantly higher in that order (p < 0.05). The results of this study revealed that the NHE with an increased lower leg slope angle shifted the BPA to the lower knee flexion angle and enhanced the hamstring EMG activity in the final phase of the descent.


The effects of acute passive stretch on muscle protein synthesis in humans.
We examined the effect of an isolated bout of maximal tolerated passive stretch on fractional muscle protein synthetic rate in human soleus muscle. Eight healthy males performed two separate trials with the same leg: one session of passive stretch and one of intermittent active isometric contraction at a force equivalent to that which occurred during the passive stretch trial. This force was approximately 40% of maximum voluntary contraction force and produced volitional fatigue in approximately 27 min. Intermittent passive stretch, for the same duration, elicited a 6.1 degrees increase in joint angle (P<.0005) with silent electromyography. Fractional protein synthetic rate from experimental and control soleus in each trial was assessed from biopsy samples over the period 10-22 hr postexercise by the incorporation rate of L-[1-13C] leucine into muscle. Protein synthesis was elevated in the soleus of the exercised leg following the active contraction trial by 49% (P<.05) but not following the passive stretch trial. Results indicate that a single bout of maximal passive stretch does not significantly elevate fractional muscle protein synthetic rate in humans and thus suggests that muscle stretch per se is not the stimulus for the muscle hypertrophy that occurs with resistance training.


Development of vocal emotion recognition in school-age children: The EmoHI test for hearing-impaired populations.
Traditionally, emotion recognition research has primarily used pictures and videos, while audio test materials are not always readily available or are not of good quality, which may be particularly important for studies with hearing-impaired listeners. Here we present a vocal emotion recognition test with pseudospeech productions from multiple speakers expressing three core emotions (happy, angry, and sad): the EmoHI test. The high sound quality recordings make the test suitable for use with populations of children and adults with normal or impaired hearing. Here we present normative data for vocal emotion recognition development in normal-hearing (NH) school-age children using the EmoHI test. Furthermore, we investigated cross-language effects by testing NH Dutch and English children, and the suitability of the EmoHI test for hearing-impaired populations, specifically for prelingually deaf Dutch children with cochlear implants (CIs). Our results show that NH children's performance improved significantly with age from the youngest age group onwards (4-6 years: 48.9%, on average). However, NH children's performance did not reach adult-like values (adults: 94.1%) even for the oldest age group tested (10-12 years: 81.1%). Additionally, the effect of age on NH children's development did not differ across languages. All except one CI child performed at or above chance-level showing the suitability of the EmoHI test. In addition, seven out of 14 CI children performed within the NH age-appropriate range, and nine out of 14 CI children did so when performance was adjusted for hearing age, measured from their age at CI implantation. However, CI children showed great variability in their performance, ranging from ceiling (97.2%) to below chance-level performance (27.8%), which could not be explained by chronological age alone. The strong and consistent development in performance with age, the lack of significant differences across the tested languages for NH children, and the above-chance performance of most CI children affirm the usability and versatility of the EmoHI test.


Machine Learning and Artificial Intelligence Applications to Epilepsy: a Review for the Practicing Epileptologist.
Machine Learning (ML) and Artificial Intelligence (AI) are data-driven techniques to translate raw data into applicable and interpretable insights that can assist in clinical decision making. Some of these tools have extremely promising initial results, earning both great excitement and creating hype. This non-technical article reviews recent developments in ML/AI in epilepsy to assist the current practicing epileptologist in understanding both the benefits and limitations of integrating ML/AI tools into their clinical practice. ML/AI tools have been developed to assist clinicians in almost every clinical decision including (1) predicting future epilepsy in people at risk, (2) detecting and monitoring for seizures, (3) differentiating epilepsy from mimics, (4) using data to improve neuroanatomic localization and lateralization, and (5) tracking and predicting response to medical and surgical treatments. We also discuss practical, ethical, and equity considerations in the development and application of ML/AI tools including chatbots based on Large Language Models (e.g., ChatGPT). ML/AI tools will change how clinical medicine is practiced, but, with rare exceptions, the transferability to other centers, effectiveness, and safety of these approaches have not yet been established rigorously. In the future, ML/AI will not replace epileptologists, but epileptologists with ML/AI will replace epileptologists without ML/AI.


Natural human genetic variation determines basal and inducible expression of PM20D1, an obesity-associated gene.
PM20D1 is a candidate thermogenic enzyme in mouse fat, with its expression cold-induced and enriched in brown versus white adipocytes. Thiazolidinedione (TZD) antidiabetic drugs, which activate the peroxisome proliferator-activated receptor-γ (PPARγ) nuclear receptor, are potent stimuli for adipocyte browning yet fail to induce Pm20d1 expression in mouse adipocytes. In contrast, PM20D1 is one of the most strongly TZD-induced transcripts in human adipocytes, although not in cells from all individuals. Two putative PPARγ binding sites exist near the gene's transcription start site (TSS) in human but not mouse adipocytes. The -4 kb upstream site falls in a segmental duplication of a nearly identical intronic region +2.5 kb downstream of the TSS, and this duplication occurred in the primate lineage and not in other mammals, like mice. PPARγ binding and gene activation occur via this upstream duplicated site, thus explaining the species difference. Furthermore, this functional upstream PPARγ site exhibits genetic variation among people, with 1 SNP allele disrupting a PPAR response element and giving less activation by PPARγ and TZDs. In addition to this upstream variant that determines PPARγ regulation of PM20D1 in adipocytes, distinct variants downstream of the TSS have strong effects on PM20D1 expression in human fat as well as other tissues. A haplotype of 7 tightly linked downstream SNP alleles is associated with very low PMD201 expression and correspondingly high DNA methylation at the TSS. These PM20D1 low-expression variants may account for human genetic associations in this region with obesity as well as neurodegenerative diseases.


Anterior versus posterior procedure for surgical treatment of thoracolumbar tuberculosis: A retrospective analysis.
Approach for surgical treatment of thoracolumbar tuberculosis has been controversial. The aim of present study is to compare the clinical, radiological and functional outcome of anterior versus posterior debridement and spinal fixation for the surgical treatment of thoracic and thoracolumbar tuberculosis. 70 patients with spinal tuberculosis treated surgically between Jan 2005 and Dec 2009 were included in the study [corrected]. Thirty four patients (group I) with mean age 34.9 years underwent anterior debridement, decompression and instrumentation by anterior transthoracic, transpleural and/or retroperitoneal diaphragm cutting approach. Thirty six patients (group II) with mean age of 33.6 years were operated by posterolateral (extracavitary) decompression and posterior instrumentation. Various parameters like blood loss, surgical time, levels of instrumentation, neurological recovery, and kyphosis improvement were compared. Fusion assessment was done as per Bridwell criteria. Functional outcome was assessed using Prolo scale. Mean followup was 26 months. Mean surgical time in group I was 5 h 10 min versus 4 h 50 min in group II (P>0.05). Average blood loss in group I was 900 ml compared to 1100 ml in group II (P>0.05). In group I, the percentage immediate correction in kyphosis was 52.27% versus 72.80% in group II. Satisfactory bony fusion (grades I and II) was seen in 100% patients in group I versus 97.22% in group II. Three patients in group I needed prolonged immediate postoperative ICU support compared to one in group II. Injury to lung parenchyma was seen in one patient in group I while the anterior procedure had to be abandoned in one case due to pleural adhesions. Functional outcome (Prolo scale) in group II was good in 94.4% patients compared to 88.23% patients in group I. Though the anterior approach is an equally good method for debridement and stabilization, kyphus correction is better with posterior instrumentation and the posterior approach is associated with less morbidity and complications.


Mini puberty and its interpretation.
Gonadotropins which are high in the middle of the fetal life are measured to be considerably low in the cord blood and estrogen is found to be high in the cord blood. Gonodotropins are supressed by estrogen. After delivery, the hypothalamo-pituitary-gonadal axis is activated when estrogen is eliminated and a hormone profile which reaches pubertal levels is established. These changes are called mini puberty. In boys, long-term testicular functions and sperm production are regulated with mini puberty and mini puberty contributes to masculinization of the brain. The role of mini puberty in female newborns is not known. Central hypogonadism, Turner syndrome and ovarian hyperstimulation in preterm babies may be diagnosed with evaluation of mini puberty. In this article, mini puberty and related problems were reviewed and the importance of this issue was emphasized.


Elevated internal exposure of children in simulated acute inhalation of volatile organic compounds: effects of concentration and duration.
When deriving health-based exposure limits in recent years, increasing attention has been drawn to susceptible subpopulations, in particular to children. We investigated the differences in kinetics between children and adults during inhalation of styrene as a typical category-3 volatile organic compound (VOC), i.e., a gas with a low reactivity and low water solubility allowing a high rate of alveolar absorption. Internal exposure was simulated using a physiologically based kinetic model over a broad range of airborne concentrations (1-1000 ppm) and for an exposure time of up to 8 h according to the scenario in the acute exposure guideline level (AEGL) program. Age-specific anatomical and physiological parameters and compound-specific data was derived from the literature. The calculated concentrations in arterial blood are higher in children than in adults, and are highest in the newborn. For an 8-h exposure to low concentrations, the calculated arterial concentration in the newborn is higher by a factor of 2.3 than in the adult. This is due mainly to the relatively high ventilation rate and the immature metabolism. With increasing airborne concentration, the ratio of arterial concentrations (newborn/adult) increases to a maximum of 3.8 at 130 ppm in ambient air, and declines with further increments of concentration to a value of 1.7. This is because the metabolism of the newborn becomes non-linear at lower concentrations than in adults. At high concentrations, metabolism is saturated in both age groups. For shorter exposures, the dose dependency of the concentration ratios (newborn/adult) is less pronounced. This is the first article to show that the intraspecies assessment factor may vary with concentration and duration of exposure.


Effects of omega-3 fatty acids on patients undergoing surgery for gastrointestinal malignancy: a systematic review and meta-analysis.
Surgical resection remains the primary treatment for gastrointestinal (GI) malignancy including early-stage cancer. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to have beneficial clinical and immune-modulating effects in the prognosis of GI cancer patients undergoing surgery. We searched PubMed, Embase, EBSCO-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), CNKI and Wanfang to identify primary research reporting the effects of n-3 PUFAs compared with isocaloric nutrition on GI cancer patients who underwent surgery up to the end of June 30, 2016. Two authors independently reviewed and selected eligible randomized controlled trials (RCTs). A total of 9 RCTs (623 participants) were included. The n-3 PUFAs regime resulted in lower levels of C-reactive protein (CRP) (P < 0.05), interleukin-6 (IL-6) (P < 0.01), and higher levels of albumin (ALB), CD3+ T cells, CD4+ T cells and CD4+/CD8+ ratio (P < 0.05) compared with the isocaloric nutrition regime. However, there was no significant difference in the level of tumor necrosis factor-α (TNF-α) between the n-3 PUFAs regime and the isocaloric nutrition regime (P = 0.17). And the level of CD8 + T cells decreased compared with the isocaloric nutrition regime (P < 0.0001). Our meta-analysis revealed that n-3 PUFAs are effective in improving the nutritional status and immune function of GI cancer patients undergoing surgery as they effectively enhance immunity and attenuate the inflammatory response.


Evaluating the performance of the ORTEC® Detective™ for emergency urine bioassay.
The performance of the ORTEC(®) Detective™ as a field deployable tool for emergency urine bioassay of (137)Cs, (60)Co, (192)Ir, (169)Yb and (75)Se was evaluated against ANSI N13.30. The tested activity levels represent 10 % RL (reference level) and 1 % RL defined by [Li C., Vlahovich S., Dai X., Richardson R. B., Daka J. N. and Kramer G. H. Requirements for radiation emergency urine bioassay techniques for the public and first responders. Health Phys (in press, 99(5), 702-707 (2010)]. The tests were conducted for both single radionuclide and mixed radionuclides at two geometries, one conventional geometry (CG) and one improved geometry (IG) which improved the MDAs (minimum detectable amounts) by a factor of 1.6-2.7. The most challenging radionuclide was (169)Yb. The measurement of the mixture radionuclides for (169)Yb at the CG did not satisfy the ANSI N13.30 requirements even at 10 % RL. At 1 % RL, (169)Yb and (192)Ir were not detectable at either geometry, while the measurement of (60)Co in the mixed radionuclides satisfied the ANSI N13.30 requirements only at the IG.


The Gazayerli endoscopic retractor model 1.
A simple yet effective abdominal wall retractor for use in endoscopic surgery is described. It has been used in laparoscopic herniorrhaphy, laparoscopic cholecystectomy in the morbidly obese, and lysis of abdominal wall adhesions, and to control abdominal wall bleeding.


Clinical course and management of acute and chronic viral hepatitis during pregnancy.
Pregnancy is a para-physiologic condition, which usually evolves without any complications in the majority of women, even if in some circumstances moderate or severe clinical problems can also occur. Among complications occurring during the second and the third trimester very important are those considered as concurrent to pregnancy such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, HELLP syndrome and acute fatty liver of pregnancy. The liver diseases concurrent to pregnancy typically occur at specific times during the gestation and they may lead to significant maternal and foetal morbidity and mortality. Commonly, delivery of the foetus, even preterm, usually terminates the progression of these disorders. All chronic liver diseases, such as chronic viral hepatitis, autoimmune hepatitis, Wilson's disease, and cirrhosis of different aetiologies may cause liver damage, independently from pregnancy. In this review we will also comment the clinical implications of pregnancies occurring in women who received a orthotopic liver transplantation (OLT) Therefore, the management of immunosuppressive therapy before and after the delivery in women who received liver transplant is becoming a relevant clinical issue. Finally, we will focus on acute and chronic viral hepatitis occurring during pregnancy, on management of advanced liver disease and we will review the literature on the challenging issue regarding pregnancy and OLT.


Socioeconomic status, occupational characteristics, and sleep duration in African/Caribbean immigrants and US White health care workers.
o advance our understanding of the interplay of socioeconomic factors, occupational exposures, and race/ethnicity as they relate to sleep duration. We hypothesize that non Hispanic African/Caribbean immigrant employees in long term health care have shorter sleep duration than non Hispanic white employees, and that low education, low income, and occupational exposures including night work and job strain account for some of the African/Caribbean immigrant-white difference in sleep duration. Cross sectional Four extended care facilities in Massachusetts, United States 340 employees in extended care facilities Sleep duration was assessed with wrist actigraphy for a mean of 6.3 days. In multivariable regression modeling controlling for gender and age, African/Caribbean immigrants slept 64.4 fewer minutes (95% CI: -81.0, -47.9) per night than white participants; additional control for education and income reduced the racial gap to 50.9 minutes (-69.2, -32.5); additional control for the occupational factors of hours worked per week and working the night shift reduced the racial gap to 37.7 minutes (-57.8, -17.6). his study provides support for the hypothesis that socioeconomic and occupational characteristics explain some of the African/ Caribbean immigrant-white difference in sleep duration in the United States, especially among health care workers.


Soy protein, genistein, and daidzein improve serum paraoxonase activity and lipid profiles in rheumatoid arthritis in rats.
In this study, we investigated the effects of genistein, daidzein, and soy protein on paraoxonase and arylesterase activity, malondialdehyde (MDA) levels, and lipid profiles of arthritic rats in vivo and the results were compared with that of dexamethasone. Seventy-two female Sprague-Dawley rats were divided into six groups: healthy control, animals with collagen-induced arthritis (CIA), CIA-soy protein (7 g/kg)-treated rats, CIA-genistein (20 mg/kg)-treated animals, CIA-daidzein (20 mg/kg)-treated rats, and CIA-dexamethasone (1 mg/kg)-treated rats. Rheumatoid arthritis was induced using collagen type II and the treatments were carried out by daily gavages feedings for 50 days. The paraoxonase activity in serum was measured spectrophotometrically using paraoxon and phenylacetate as substrates. Serum MDA and lipids levels were determined using enzymatic colorimetric methods. Arthritis-induced decreases in paraoxonase and arylesterase activity was restored after treatment with soy protein and isoflavones (P<.05). MDA concentrations were lower after treatment with all tested compounds. However, only soy protein could partially improve the lipid profile.


Aortic septal defect and coronary-systemic micro-fistulae.
This report concerns a 32-year-old man, who at the age of 11, had an aortic septal defect with severe pulmonary hypertension. The defect was partially closed and the patient was left with a continuous murmur, an a-v shunt and marked diminution of pulmonary hypertension. Five years later he was asymptomatic, auscultation was normal and no shunt was found at cardiac catheterization. At 32 years of age, although asymptomatic he had abnormal "T" waves, and a selective coronary angiography demonstrated micro-fistulae involving the anterior descending coronary artery. It is suggested that these fistulae may be responsible for the abnormality of ventricular repolarization.