Reference range for ADAMTS13 antigen, activity and anti-ADAMTS13 antibody in the healthy adult Singapore population
ADAMTS13 (a disintegrin-like and metalloproteinase with a thrombospondin Type 1 motif, member 13) plays a fundamental role in the regulation of haemostasis and thrombosis. Its deficiency leads to an accumulation of ultra-large von Willebrand multimers, inducing spontaneous platelet aggregation, thrombosis in the microvasculature, and thrombotic thrombocytopenic purpura (TTP), a condition with 90% mortality when left untreated. Prompt quantification of ADAMTS13 antigen, activity and autoantibody plays a crucial role in the diagnosis and management of TTP and can help differentiate it from other thrombotic microangiopathies (TMAs). Reference ranges for ADAMTS13 are generally derived from Caucasian patients. Given that polymorphism in the ADAMTS13 gene can be associated with variable ADAMTS13 levels, we aimed to establish the first reference range in Singapore and provide a crucial laboratory test for institutions here and elsewhere. 150 healthy voluntary donors (75 men, 75 women) aged 21-60 years, with an ethnic mix mirroring Singapore's population profile, were recruited. ADAMTS13 antigen, activity and autoantibody levels were measured using the fluorescence resonance energy transfer-vWF73 and enzyme-linked immunosorbent assay methodologies. Levels (activity 0.65-1.79 IU/mL, antigen 0.36-1.17 IU/mL, autoantibody 1.4-12.5 U/mL) were not statistically different between the genders and various age groups. TTP and TMAs are encountered in a wide range of specialties. The availability of new assays in Singapore will aid clinicians in the timely management of these conditions. Standardising reference ranges established for Singapore against World Health Organization standards allows harmonisation of measurements between laboratories and for future research collaborations.


More Declassified Evidence Implicates CIA Physicians in Unethical Research.
In 2010, in an article in this journal, I argued that declassified documents implicated Central Intelligence Agency (CIA) physicians in the conduct of unethical research on enhanced interrogation using detainee subjects. The focus, then as now, is upon physicians at the Office of Medical Services (OMS). The 2010 article highlighted the heavily redacted "Draft OMS Guidelines on Medical and Psychological Support to Detainee Interrogations" (the Draft). This commentary focuses upon the recently declassified final version of that document revealing further culpable evidence of unethical human subject research. The commentary locates that unethical research in historical context and the development of the Nuremberg Code. The commentary also locates enhanced interrogation in contemporary political context and considers how to hold OMS physicians accountable for the conduct of unethical human research using detainee subjects.


Five families with homozygous delta-thalassaemia in Japan.
Five families with delta-thalassaemia discovered in Ehime, Japan, are presented. The delta-thalassaemia was associated with a slight elevation of the level of Hb F in two families and with normal Hb F levels in three. Complete absence of HbA2 was found in the homozygous probands. No abnormal clinical or haematological findings were noted in the individuals with delta-thalassaemia.


The disproportionate high risk of HIV infection among the urban poor in sub-Saharan Africa.
The link between HIV infection and poverty in sub-Saharan Africa (SSA) is rather complex and findings from previous studies remain inconsistent. While some argue that poverty increases vulnerability, existing empirical evidence largely support the view that wealthier men and women have higher prevalence of HIV. In this paper, we examine the association between HIV infection and urban poverty in SSA, paying particular attention to differences in risk factors of HIV infection between the urban poor and non-poor. The study is based on secondary analysis of data from the Demographic and Health Surveys from 20 countries in SSA, conducted during 2003-2008. We apply multilevel logistic regression models, allowing the urban poverty risk factor to vary across countries to establish the extent to which the observed patterns are generalizable across countries in the SSA region. The results reveal that the urban poor in SSA have significantly higher odds of HIV infection than their urban non-poor counterparts, despite poverty being associated with a significantly lower risk among rural residents. Furthermore, the gender disparity in HIV infection (i.e. the disproportionate higher risk among women) is amplified among the urban poor. The paper confirms that the public health consequence of urban poverty that has been well documented in previous studies with respect to maternal and child health outcomes does apply to the risk of HIV infection. The positive association between household wealth and HIV prevalence observed in previous studies largely reflects the situation in the rural areas where the majority of the SSA populations reside.


The p.Ser267Phe variant in SLC10A1 is associated with resistance to chronic hepatitis B.
In the past 50 years there have been considerable efforts to identify the cellular receptor of hepatitis B virus (HBV). Recently, in vitro evidence from several groups has shown that the sodium-taurocholate cotransporting polypeptide (NTCP, which is encoded by SLC10A1 and transports bile acids into hepatic cells in enterohepatic recirculation) is a strong candidate. In particular, in vitro the p.Ser267Phe variation of SLC10A1 results in loss of HBV receptor function. We tested the role of NTCP as a receptor for HBV in chronic hepatitis B patients using a genetic association study. We selected SLC10A1 variants from 189 exomes. We used Sanger sequencing to follow up the association of the various SLC10A1 variants in a Han Chinese cohort of 1899 chronic hepatitis B patients and 1828 healthy controls. We further investigated the potential impact of the p.Ser267Phe variant on NTCP function using structural analysis. The p.Ser267Phe variant was associated with healthy status (P = 5.7 × 10(-23) , odds ratio = 0.36) irrespective of hepatitis B virus surface antibody status (P = 6.2 × 10(-21) and 1.5 × 10(-10) , respectively, when the cases were compared with hepatitis B virus surface antibody-positive and -negative controls). The variation was also associated with a lower incidence of acute-on-chronic liver failure (P = 0.007). The estimated heritability explained by this single variation was ∼3.2%. The population prevented fraction was around 13.0% among the southern Chinese. Our structural modeling showed that the p.Ser267Phe variant might interfere with ligand binding, thereby preventing HBV from cellular entry. The p.Ser267Phe NTCP variant is significantly associated with resistance to chronic hepatitis B and a lower incidence of acute-on-chronic liver failure. Our results support that NTCP is a cellular receptor for HBV in human infection.


Contraception and sexually transmitted infections.
Many women seek contraceptive advice from general practitioners. These consultations provide an opportunity to discuss the prevention of sexually transmitted infections (STIs) including human immunodeficiency virus (HIV). This article discusses the effect of various contraceptive methods on the transmission of STIs and HIV. It also highlights issues relevant to achieving both contraception and STI/HIV prevention, with a focus on younger women. There is no ideal method to achieve protection against both pregnancy and STIs/HIV. Counselling about risks of STIs/HIV, providing the option of being tested for bacterial STIs, hepatitis B and HIV at the start of new relationships and promoting condom use for casual sex and concurrent sexual relationships is to be encouraged.


Mass Spectrometric Characterization of Circulating Covalent Protein Adducts Derived from Epoxide Metabolites of Carbamazepine in Patients.
Carbamazepine (CBZ) is an effective antiepileptic drug that has been associated with hypersensitivity reactions. The pathogenesis of those reactions is incompletely understood but is postulated to involve a complex interplay between the drug's metabolism, genetic variation in human leukocyte antigens, and adverse activation of the immune system. Multiple T-cell activation mechanisms have been hypothesized including activation by drug-peptide conjugates derived from proteins haptenated by reactive metabolites. However, definitive evidence of the drug-protein adducts in patients has been lacking. In this study, mass spectrometry was used to characterize protein modifications by microsomally-generated metabolites of CBZ and in patients taking CBZ therapy. CBZ 10,11-epoxide (CBZE), a major electrophilic plasma metabolite of CBZ, formed adducts with glutathione-S-transferase pi (GSTP; Cys47) and human serum albumin (HSA; His146 and His338, but not Cys34) in vitro via notably divergent side-chain selectivity. Both proteins were adducted at the same residues by undefined monoxygenated metabolites ([O]CBZ) when they were incubated with human liver microsomes, NADPH and CBZ. There was also evidence for formation of a CBZ adduct at His146 and His338 of HSA derived via dehydration from an intermediate arene oxide adduct. Glutathione trapping of reactive metabolites confirmed microsomal production of CBZE and indicated simultaneous production of arene oxides. In 15 patients prescribed CBZ therapy, [O]CBZ-modified HSA (His146) was detected in all subjects. The relative amount of adduct was moderately positively correlated with plasma concentrations of CBZ (r2 = 0.44, p = 0.002) and CBZE (r2 = 0.35, p = 0.006). Our results have provided the first chemical evidence for microsomal production of [O]CBZ species that are able to escape the microsomal domain to react covalently with soluble proteins. This study has also demonstrated the presence of circulating [O]CBZ-modified HSA in patients without hypersensitivity reactions who were receiving standard CBZ therapy. The implications of those circulating adducts for susceptibility to CBZ hypersensitivity merit further immunological investigation in hypersensitive patients.


Investigation of altered retinal microvasculature in female patients with rheumatoid arthritis: optical coherence tomography angiography detection.
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder that primarily causes symmetrical polyarthritis and bone deformity. In RA patients, sight-threatening inflammatory eye complications would be expected. The objective of the study is to ascertain the macular retinal vessel density changes in RA patients and controls using optical coherence tomography angiography (OCTA), and to investigate the association between disease and microvascular density alterations. A total of 12 RA patients (24 eyes) and 12 age- and gender-matched control participants (24 eyes) were recruited to the study. We used the Early Treatment Diabetic Retinopathy Study partitioning, hemispheric quadrants and annular partitioning to segment each image into different subregions. The vascular density of superficial retina layer, deep retina layer and conjunctival capillary plexus was quantitatively measured by OCTA and compared with the control group. Correlation analysis was used to explore the relationship between STMI and conjunctival capillaries densities. In the superficial retinal layer, the vascular density of S, I, L, SL, SR, IL and C1-C5 were significantly decreased in the RA group compared with the control group (P<0.05). For the deep retinal layer, the vascular density of S, SL, SR, IL, C1, C2 and C4 also decreased in RA group. A significant positive correlation was indicated between conjunctival vascular and STMI densities (r = 0.713, P<0.05). OCTA results suggest that RA patients present with a reduced macular retinal vascular density. These subtle alterations of ocular microcirculation may precede severe eye involvements and may be a potential biomarker for early distinguishing abnormal eyes from healthy eyes.


An exploration of staff experience and participation in a perinatal and infant mental health network group.
Infant mental health (IMH), an area which focuses on the social and emotional development of infants in the context of the parent-infant relationship, has become an increasingly prominent field of both research and clinical practice worldwide. IMH network groups are initiatives which aim to facilitate continuous learning in the IMH approach, provide an opportunity for case discussion and encourage reflective practice. This study aimed to explore the experiences of staff working within an adult mental health (AMH) service and their participation in a perinatal IMH network group (PIMH-NG). This study had a qualitative research design and the data were collected using a focus group methodology. Participants were recruited from a PIMH-NG which aimed to provide staff working within an AMH setting with the opportunity for continuous development of IMH knowledge. The data were analysed using thematic analysis. The data gathered from the focus group indicated that staff participating in a PIMH-NG enhanced their clinical skill, reflective practice and supported the dissemination of IMH knowledge throughout their respective teams. The PIMH-NG facilitated this work by providing the opportunity for continuous learning, reflective group discussion and ongoing peer support. The findings of this study indicate that incorporating elements of an IMH model into AMH services can be beneficial for staff, service users and overall service delivery and development. These findings may be used to develop the structure and content of future network groups of this nature.


Jellyfish stings and their management: a review.
Jellyfish (cnidarians) have a worldwide distribution. Despite most being harmless, some species may cause local and also systemic reactions. Treatment of jellyfish envenomation is directed at: alleviating the local effects of venom, preventing further nematocyst discharges and controlling systemic reactions, including shock. In severe cases, the most important step is stabilizing and maintaining vital functions. With some differences between species, there seems to be evidence and consensus on oral/topical analgesics, hot water and ice packs as effective painkillers and on 30 s application of domestic vinegar (4%-6% acetic acid) to prevent further discharge of unfired nematocysts remaining on the skin. Conversely, alcohol, methylated spirits and fresh water should be carefully avoided, since they could massively discharge nematocysts; pressure immobilization bandaging should also be avoided, as laboratory studies show that it stimulates additional venom discharge from nematocysts. Most treatment approaches are presently founded on relatively weak evidence; therefore, further research (especially randomized clinical trials) is strongly recommended. Dissemination of appropriate treatment modalities should be deployed to better inform and educate those at risk. Adequate signage should be placed at beaches to notify tourists of the jellyfish risk. Swimmers in risky areas should wear protective equipment.


Liver involvement in celiac disease.
Celiac disease may present as a cryptogenic liver disorder being found in 5-10 % of patients with a persistent and cryptogenetic elevation of serum aminotransferase activity. In fact, a wide spectrum of liver injuries in children and adults may be related to CD and in particular: (1) a mild parenchymal damage characterised by absence of any clinical sign or symptom suggesting a chronic liver disease and by non-specific histological changes reversible on a gluten-free diet; (2) a chronic inflammatory liver injury of autoimmune mechanism, including autoimmune hepatitis, primary sclerosing cholangitis and primary biliary cirrhosis, that may lead to fibrosis and cirrhosis, generally unaffected by gluten withdrawal and necessitating an immunosuppressive treatment; (3) a severe liver failure potentially treatable by a gluten-free diet. Such different types of liver injuries may represent a spectrum of a same disorder where individual factors, such as genetic predisposition, precocity and duration of exposure to gluten may influence the reversibility of liver damage. A rigorous cross-checking for a asymptomatic liver damage in CD individuals and conversely, for CD in any cryptogenic liver disorder including end-stage liver failure is recommended.


Surveillance of Australian Hajj pilgrims for carriage of potentially pathogenic bacteria: Data from two pilot studies.
To estimate the pharyngeal carriage rate of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae) and Staphylococcus aureus (S. aureus) among Australian Hajj pilgrims. In 2014, surveillance was conducted in two phases among Australian Hajj pilgrims: The first phase during Hajj in Mina, and the second phase soon after returning home to Australia. Nasopharyngeal or oropharyngeal swabs were taken from participants then tested, firstly by nucleic acid testing, and also by standard culture. Of 183 participants recruited in the first phase, 26 (14.2%) tested positive for S. pneumoniae; 4 had received pneumococcal conjugate vaccine (PCV13). Only one tested positive for N. meningitidis (W). Of 93 2nd phase samples cultured, 17 (18.3%) grew S. aureus, all methicillin sensitive, 2 (2.2%) grew N. meningitidis (on subculture; one serotype B, one negative), and 1 (1%), from an unvaccinated pilgrim, grew S. pneumoniae. Relatively high carriage of S. pneumoniae and little meningococcal carriage was found. This indicates the importance of a larger study for improved infection surveillance and possible vaccine evaluation.


[Evaluation of the effects of immunotherapy and mesenchymal stem cells transplantation in the treatment of critically ill coronavirus disease 2019 patients].
To analyze the immunotherapy and clinical characteristics of coronavirus disease 2019 (COVID-19) patients, and focus on exploring the effects of immunotherapy and mesenchymal stem cells (MSC) transplantation in the critically ill patients' treatment. Fity-five COVID-19 patients were admitted to the Fifth People's Hospital of Wuxi from January 23rd to March 31st, 2020 as the research object. The demographic characteristics of the cases and the methods of immunotherapy were analyzed, focusing on the immunized indicators, positivity of pathogens and clinical indicators of critically ill COVID-19 patient, and the effects of immunotherapy and stem cell transplantation were evaluated. Aged, male and people with comorbidities were the main risk factors in the development of severe and critical COVID-19. All of confirmed COVID-19 cases (n = 55) had been treated with interferon-α (IFN-α), of which 81.8% (n = 45, mild and ordinary) of the patients were recovered, 14.6% (n = 8) of the patients were converted to severe, 3.6% (n = 2) of the patients were converted to critical, and some severe patients were treated with gamma globulin and albumin as adjuvant treatment. Critically ill patients were not only treated with IFN-α, gamma globulin and albumin, but also treated with convalescent plasma and MSC transplantation. Due to pulmonary hemorrhage and persistently low blood oxygen saturation, terminal lung transplantation therapy was implemented. The total number of lymphocytes, CD4+, CD8+ T lymphocytes, natural killer (NK) cells and B cells in peripheral blood of the two critical COVID-19 patients were significantly reduced, and the functions of lung, liver, and kidney were severely damaged on admission, manifested as significant increase of the levels of blood C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN), etc. and decrease of blood oxygen saturation, and type I respiratory failure, and the noninvasive assisted ventilation was needed to improve. After adjuvant immunotherapy such as gamma globulin, the nucleic acid of 2019 novel coronavirus (2019-nCoV) turned into negative. The CRP of one critically ill patient was significantly lower than the value at admission (minimum of 21 mg/L). But the lung inflammation progressed rapidly, and the pathological results of the lung tissue from the lung transplantation showed hemorrhage and irreversible fibrosis. The ability to secrete immunoglobulin A (IgA) was significantly reduced. Liver function had been significantly improved and stabilized after treatment with convalescent plasma during the recovery period. MSC transplantation treatment reduced the BUN level by > 50% compared with the previous period, and the total number of lymphocytes in the patient increased by more than 2 times (rose from 0.23×109/L to 0.57×109/L), but the total amount of lymphocytes was still lower than the normal reference value (< 1.1×109/L). The lung inflammation lesions were obviously absorbed, and the vital signs were stable. In addition to IFN, gamma globulin, antiserum and MSC transplantation therapy can help clear the virus and reduce inflammation. Although MSC transplantation fail to completely change the immunecompromised state of critically ill patients, it controlled the progression of inflammation in the liver and kidneys.


[Tasks and importance of the acute poisoning center at a multiprofile provincial hospital based on 10 years experience].
The thesis presents a short history and way of organization of acute poisoning centre functioning within the internal diseases department in multiprofile provincial hospital. The data show the number of patients treated in particular years as well as the types of toxic substances that caused poisoning, and the number of analyses carried out for the needs of the poisoning centre and other hospital departments, as well as for the local hospitals. Based on the said data the conclusions were presented referring to the role of the centre in helping the people suffering from acute poisoning in number 0.5 million population.


Surveillance for illness and injury after hurricane Katrina--New Orleans, Louisiana, September 8-25, 2005.
Hurricane Katrina struck the Gulf Coast on August 29, 2005, resulting in extensive structural damage and severe flooding from breached levees in and around New Orleans, Louisiana. The public health infrastructure of the Louisiana Department of Health and Hospitals (LDHH) was damaged extensively, limiting surveillance for illnesses, injuries, and toxic exposures. On September 9, 2005, LDHH, CDC, and functioning emergency treatment resources (i.e., hospitals, disaster medical assistance teams, and military aid stations) established an active surveillance system to detect outbreaks of disease and characterize post-hurricane injuries and illnesses. As of September 25, the system had monitored 7,508 reports of health-related events at participating facilities. Trends observed in the data prompted investigations of respiratory and rash illnesses, but no major outbreaks of disease or hazardous environmental exposures were detected. These data also were used to identify post-hurricane injury patterns and to guide prevention messages to residents and relief workers. A natural disaster of the magnitude of Hurricane Katrina requires a sustained response and a detailed plan for return to pre-hurricane surveillance activities.


Hemispheric mapping of secondary somatosensory cortex in the rat.
This study used high-resolution hemispheric mapping of somatosensory evoked potentials to determine the number and organization of secondary somatosensory areas (SII) in rat cortex. Two areas, referred to as SII and PV (parietoventral), revealed complete (SII) or nearly complete (PV) body maps. The vibrissa and somatic representation of SII was upright, rostrally oriented, and immediately lateral to primary somatosensory cortex (SI), with a dominant face representation. Vibrissa representations in SII were highly organized, with the rows staggered rostrally along the mediolateral axis. Area PV was approximately one fifth the size of SII, and located rostral and lateral to auditory cortex. PV had a rostrally oriented and inverted body representation that was dominated by the distal extremities, with little representation of the face or vibrissae. These data support the conclusion that in the rat, as in other species, SII and PV represent anatomically and functionally distinct areas of secondary somatosensory cortex.


Effects of Anti-IL-17 on Inflammation, Remodeling, and Oxidative Stress in an Experimental Model of Asthma Exacerbated by LPS.
Inflammation plays a central role in the development of asthma, which is considered an allergic disease with a classic Th2 inflammatory profile. However, cytokine IL-17 has been examined to better understand the pathophysiology of this disease. Severe asthmatic patients experience frequent exacerbations, leading to infection, and subsequently show altered levels of inflammation that are unlikely to be due to the Th2 immune response alone. This study estimates the effects of anti-IL-17 therapy in the pulmonary parenchyma in a murine asthma model exacerbated by LPS. BALB/c mice were sensitized with intraperitoneal ovalbumin and repeatedly exposed to inhalation with ovalbumin, followed by treatment with or without anti-IL-17. Twenty-four hours prior to the end of the 29-day experimental protocol, the two groups received LPS (0.1 mg/ml intratracheal OVA-LPS and OVA-LPS IL-17). We subsequently evaluated bronchoalveolar lavage fluid, performed a lung tissue morphometric analysis, and measured IL-6 gene expression. OVA-LPS-treated animals treated with anti-IL-17 showed decreased pulmonary inflammation, edema, oxidative stress, and extracellular matrix remodeling compared to the non-treated OVA and OVA-LPS groups (p < 0.05). The anti-IL-17 treatment also decreased the numbers of dendritic cells, FOXP3, NF-κB, and Rho kinase 1- and 2-positive cells compared to the non-treated OVA and OVA-LPS groups (p < 0.05). In conclusion, these data suggest that inhibition of IL-17 is a promising therapeutic avenue, even in exacerbated asthmatic patients, and significantly contributes to the control of Th1/Th2/Th17 inflammation, chemokine expression, extracellular matrix remodeling, and oxidative stress in a murine experimental asthma model exacerbated by LPS.


Evaluation of resources and environmental carrying capacity of 36 large cities in China based on a support-pressure coupling mechanism.
Resource and environmental carrying capacity (RECC) is an important foundation for the long-term development of cities. The accurate evaluation of the RECC of cities is of great significance to China, which is rapidly urbanizing. This paper constructs a support index and pressure index to calculate the level of support resources and the level of environmental pressure that human activities induce in 36 municipalities, provincial capitals and subprovincial cities in China from 2010 to 2016; in addition, this paper analyzes the factors affecting RECC. The results show that (1) the support index of most cities (32) is greater than the pressure index, demonstrating that the resource and environmental carrying capacity of most cities is stronger than the pressure of human social activities. (2) The RECC of first-line, super large cities is of concern; the RECCs of Beijing, Shanghai, Guangzhou and Shenzhen have already been exceeded. (3) The resources, the environmental services and the pressure of human activities on those services in most cities are average, while the resource, the environmental services and the pressure of human activities on those services are greater in a few developed cities (such as Beijing, Shanghai, Guangzhou, Shenzhen, etc.). (4) The ability of resources and the environment to support human activities in China's large cities exhibited a downward trend. The pressure of human social activities on urban resources and the environment is increasing, but the growth rate of that pressure has slowed. (5) Area of land used for urban construction, the area of urban green space and length of city sewage pipes and other resource indicators are common obstacles to the improvement of most cities' pressure indexes. Water shortage is a common problem faced by first-tier cities in China. This study supports a comprehensive understanding of China's large-scale RECC status and provides a reference for the formulation of a scientific and pragmatic urban development strategy.


Clinical Audit on the Practice of Documentation at Preanesthetic Evaluation in a Specialized University Hospital.
Performing preanesthetic evaluation, documenting, and keeping readily accessible record are responsibilities of anesthetists. Documentation can improve overall patient outcome. It also has an irreplaceable role in medico-legal aspects. Documentation is one of the challenges of providing quality care. The aim of this study was to evaluate the quality of documentation practice during preanesthetic visits. This clinical audit was conducted in the University of Gondar Hospital. Predefined 22 practice quality indicators were prepared according to modified global quality index. Descriptive statistics was performed using SPSS version 20. A total of 122 preanesthetic evaluation tools (PAETs) were reviewed. None of PAETs found fully completed according to the indicators. Trends differ between elective and emergency conditions. Indicators with high completion rate (>90%) were signed a consent, medical history, history of medication, allergy, anesthesia and surgery, cardiopulmonary examination, airway examination, preoperative diagnosis, and planned procedure. Anesthetic plan, vital signs, a name, per-oral status, premedication, and age were found with below average (<50%) completion rate. Documentation practice during the preanesthetic visit was below the standard. Unclear instructions should be replaced with standardized contents. Providing regular trainings on clinical documentation for students and staffs, and introducing modern electronic-based documentation system and preanesthetic clinics may improve the practice.


Metabolite fingerprinting in transgenic lettuce.
Metabolite fingerprinting has been achieved using direct atmospheric pressure chemical ionization-mass spectrometry (APCI-MS) and linked gas chromatography (GC-APCI/EI-MS) for transgenic lettuce (Lactuca sativa L. cv. Evola) plants expressing an IPT gene under the control of the senescence-specific SAG12 promoter from Arabidopsis thaliana (P(SAG12)-IPT). Mature heads of transgenic lettuce and their azygous controls were maintained under defined conditions to assess their shelf life. Transgenic lettuce plants exhibited delayed senescence and significant increases (up to a maximum of threefold) in the concentrations of three volatile organic compounds (VOCs), corresponding to molecular masses of 45, 47 and 63, when compared with heads from azygous plants. These VOCs were identified as acetaldehyde (45), ethanol (47) and dimethyl sulphide (63). The increase in dimethyl sulphide was paralleled by an accumulation of reactive oxygen species (ROS) in the heads of transgenic plants. These results demonstrate the applicability of metabolic fingerprinting techniques to elucidate the underlying pleiotropic responses of plants to transgene expression.


Prognostic impact of serum CYFRA 21-1 in patients with advanced lung adenocarcinoma: a retrospective study.
Serum CYFRA 21-1 is one of the most important serum markers in the diagnosis of non-small cell lung cancer (NSCLC), especially squamous-cell carcinoma. However, it remains unknown whether pretreatment serum CYFRA 21-1 values (PCV) may also have prognostic implications in patients with advanced lung adenocarcinoma. We retrospectively reviewed the data of 284 patients (pts) who were diagnosed as having advanced lung adenocarcinoma and had received initial therapy. Of the study subjects, 121 pts (43%) had activating epidermal growth factor receptor (EGFR) mutations (Mt+), while the remaining 163 pts (57%) had wild-type EGFR (Mt-). Univariate analysis identified gender (male/ female), ECOG performance status (PS) (0-1/ ≥2), PCV (<2.2 ng/ml/ ≥2.2 ng/ml), EGFR mutation status (Mt+/ Mt-), pretreatment serum CEA values (<5.0 ng/ml/ ≥5.0 ng/ml), smoking history (yes/ no) and EGFR-TKI treatment (yes/ no) as prognostic factors (p = .008, p < .0001, p < .0001, p < .0001, p = .036, p = .0012, p < .0001 respectively). Cox's multivariate regression analysis identified PCV < 2.2ng/ml as the only factor significantly associated with prolonged survival (p < .0001, hazard ratio: 0.43, 95% CI 0.31-0.59), after adjustments for PS (p < .0001), EGFR mutation status (p = .0069), date of start of initial therapy (p = .07), gender (p = .75), serum CEA level (p = .63), smoking history (p = .39) and EGFR-TKI treatment (p = .20). Furthermore, pts with Mt+ and PCV of <2.2 ng/ml had a more favorable prognosis than those with Mt+ and PCV of ≥2.2 ng/ml (MST: 67.0 vs. 21.0 months, p < .0001), and patients with Mt- and PCV of <2.2 ng/ml had a more favorable prognosis than those with Mt- and PCV of ≥2.2 ng/ml (MST: 24.1 vs. 10.2 months, p < .0001). PCV may be a potential independent prognostic factor in both Mt+ and Mt- patients with advanced lung adenocarcinoma.


Lepirudin in patients with heparin-induced thrombocytopenia - results of the third prospective study (HAT-3) and a combined analysis of HAT-1, HAT-2, and HAT-3.
To assess efficacy and safety of lepirudin in patients with heparin-induced thrombocytopenia (HIT) in a prospective study (HAT-3) as well as in a combined analysis of all HAT study data. Patients with laboratory-confirmed HIT were treated with lepirudin in three different aPTT-adjusted dose regimen and during cardiopulmonary bypass (CPB). Endpoints were new thromboembolic complications (TEC), limb amputations, and death and major bleeding. A historical control group (n = 120) was used for comparison. After start of lepirudin in 205 patients treated in HAT-3, the combined endpoint occurred in 43 (21.0%). Thirty (14.6%) patients died, 10 (4.9%) underwent limb amputation, and 11 (5.4%) new TECs occurred. Major bleeding occurred in 40 patients (19.5%) (seven during CPB surgery). Combining all prospective HAT trials (n = 403), after start of lepirudin treatment, the combined endpoint occurred in 82 patients (20.3%), with 47 deaths (11.7%), 22 limb amputations (5.5%), 30 new TECs (7.4%), and 71 (17.6%) major bleedings. Compared with the historical control group (log-rank test), the combined endpoint after start of treatment was reduced (29.7% vs. 52.1%, P = 0.0473), primarily because of reduction in new thromboses (11.9% vs. 32.1%, P = 0.0008). Mean lepirudin maintenance doses ranged from 0.07 to 0.11 mg kg(-1) h(-1). Major bleeding was more frequent in the lepirudin-treated patients (29.4% vs. 9.1%, P = 0.0148). The rate of new TECs in HIT patients is low after start of lepirudin treatment. The rate of major bleeding of 17.6% might be reduced by reducing the starting dose to 0.1 mg kg(-1) h(-1).


Thyroid function during pregnancy and the postpartum period: iodine metabolism and disease states.
To review various aspects of thyroid function during and early after pregnancy. We discuss biochemical and potential pathologic changes in the thyroid associated with the gestational and postpartum periods. Urinary iodine excretion during the last trimester of gestation in healthy euthyroid women shows that, in areas with mild iodine intake, iodine supplementation is necessary during pregnancy and the postpartum period. This measure should be considered in iodine-sufficient areas as well. Thyroglobulin is the main biochemical marker of persistent thyroidal stimulation. Alterations in thyroid volume during pregnancy can persist after delivery, especially in breast-feeding mothers. In most patients, the goitrogenic stimulus of pregnancy can be suppressed with iodine supplementation. Autoimmune thyroid disease during pregnancy and the postpartum period is reflected by monitoring of thyroid peroxidase antibodies (TPO-Ab). Women with positive test results for TPO-Ab early in gestation showed a highly significant decrease in free thyroxine and increased thyroid-stimulating hormone levels late in gestation. The main marker of Graves' disease during pregnancy is thyroid-stimulating antibodies. Nonautoimmune gestational hyperthyroidism differs from Graves' disease in that thyroid-stimulating antibodies are not detectable. Clinicians should be alert to the fact that pregnancy can induce thyroidal pathologic conditions.


Medicare Program; Advancing Care Coordination Through Episode Payment Models (EPMs); Cardiac Rehabilitation Incentive Payment Model; and Changes to the Comprehensive Care for Joint Replacement Model (CJR); Delay of Effective Date. Final rule; delay of effective date.
This final rule finalizes May 20, 2017 as the effective date of the final rule titled "Advancing Care Coordination Through Episode Payment Models (EPMs); Cardiac Rehabilitation Incentive Payment Model; and Changes to the Comprehensive Care for Joint Replacement Model (CJR)" originally published in the January 3, 2017 Federal Register. This final rule also finalizes a delay of the applicability date of the regulations at 42 CFR part 512 from July 1, 2017 to January 1, 2018 and delays the effective date of the specific CJR regulations listed in the DATES section from July 1, 2017 to January 1, 2018.


Metabolic profiling of liver from hypercholesterolemic pigs fed rye or wheat fiber and from normal pigs. High-resolution magic angle spinning 1H NMR spectroscopic study.
This study presents the first application of a high-resolution magic angle spinning 1H NMR approach to elucidate the metabolic effects of a hypercholesterolemic condition and two high-fiber diets based on rye and wheat bread, respectively, in intact pig liver biopsy samples. Standard 1D and spin-echo 1H spectra were acquired on a total of 20 biopsy samples, and 2D total correlation spectroscopy experiments were carried out on selected samples for assignment of the observed resonances. Principal component analyses and partial least-squares regression discriminant analysis revealed differences in the hepatic lipid content and choline-containing compounds between normal and hypercholesterolemic pigs. In addition, the results demonstrated that the liver metabolite profile of hypercholesterolemic pigs fed a high-fiber rye bread differed from that of pigs fed high-fiber wheat bread with respect to both the lipoprotein fractions and the choline-containing compounds. These findings suggest that earlier reports on high-fiber rye diet-induced effects on plasma HDL/LDL content partially can be ascribed to effects on liver cholesterol metabolism and that the hepatic phospholipase pathways of phosphatidylcholine breakdown are affected by the high-fiber rye diet.


Drosophila Trap1 protects against mitochondrial dysfunction in a PINK1/parkin model of Parkinson's disease.
Mitochondrial dysfunction caused by protein aggregation has been shown to have an important role in neurological diseases, such as Parkinson's disease (PD). Mitochondria have evolved at least two levels of defence mechanisms that ensure their integrity and the viability of their host cell. First, molecular quality control, through the upregulation of mitochondrial chaperones and proteases, guarantees the clearance of damaged proteins. Second, organellar quality control ensures the clearance of defective mitochondria through their selective autophagy. Studies in Drosophila have highlighted mitochondrial dysfunction linked with the loss of the PTEN-induced putative kinase 1 (PINK1) as a mechanism of PD pathogenesis. The mitochondrial chaperone TNF receptor-associated protein 1 (TRAP1) was recently reported to be a cellular substrate for the PINK1 kinase. Here, we characterise Drosophila Trap1 null mutants and describe the genetic analysis of Trap1 function with Pink1 and parkin. We show that loss of Trap1 results in a decrease in mitochondrial function and increased sensitivity to stress, and that its upregulation in neurons of Pink1 mutant rescues mitochondrial impairment. Additionally, the expression of Trap1 was able to partially rescue mitochondrial impairment in parkin mutant flies; and conversely, expression of parkin rescued mitochondrial impairment in Trap1 mutants. We conclude that Trap1 works downstream of Pink1 and in parallel with parkin in Drosophila, and that enhancing its function may ameliorate mitochondrial dysfunction and rescue neurodegeneration in PD.


Diversity analysis of agronomic and nutritional traits of hybrid offspring of forage bermudagrass.
Because of its excellent stress resistance and forage quality, the forage bermudagrass hybrid population had attracted the attention of scientific researchers in recent years. Studying its diversity could promote the breeding of desirable varieties. The variability in agronomic traits including fresh weight, dry weight, ash content, crude protein content, crude fat, phosphorus content, and relative feed value for 56 bermudagrass was investigated using Wrangler as an experimental reference. Grey correlation analysis and cluster analysis were employed to screen bermudagrass with high yield and superior quality. WCF-34 had the highest 2-year fresh weight (109,773.3 kg/ha), WCF-37 had the highest 2-year dry weight (31,951.6 kg/ha), WCF-24 had the lowest Ash content (7.46%), WCF-26 had the highest crude protein content (16.27%), WCF-27 had the highest curde fat content (3.58%), WCF-13 had the highest P content (0.45%), and WCF-42 had the highest relative feed value (95.32). Combining the results of grey relational analysis and cluster analysis, WCF-42, WCF-34, WCF-38, WCF-37, and WCF-40 were selected as high-quality bermudagrass. Through comprehensive analysis of the agronomic characters of bermudagrass, five bermudagrass were selected, the outcomes of this study would provide a theoretical basis for the breeding and genetic enhancement of bermudagrass.


Control of Spin-Orbit Torques by Interface Engineering in Topological Insulator Heterostructures.
(Bi1-xSbx)2Te3 topological insulators (TIs) are gathering increasing attention owing to their large charge-to-spin conversion efficiency and the ensuing spin-orbit torques (SOTs) that can be used to manipulate the magnetization of a ferromagnet (FM). The origin of the torques, however, remains elusive, while the implications of hybridized states and the strong material intermixing at the TI/FM interface are essentially unexplored. By combining interface chemical analysis and spin-transfer ferromagnetic resonance (ST-FMR) measurements, we demonstrate that intermixing plays a critical role in the generation of SOTs. By inserting a suitable normal metal spacer, material intermixing is reduced and the TI properties at the interface are largely improved, resulting in strong variations in the nature of the SOTs. A dramatic enhancement of a field-like torque, opposing and surpassing the Oersted-field torque, is observed, which can be attributed to the non-equilibrium spin density in Rashba-split surface bands and to the suppression of spin memory loss. These phenomena can play a relevant role at other interfaces, such as those comprising transition metal dichalcogenides.


An Equivalent Circuit of Longitudinal Vibration for a Piezoelectric Structure with Losses.
Equivalent circuits of piezoelectric structures such as bimorphs and unimorphs conventionally focus on the bending vibration modes. However, the longitudinal vibration modes are rarely considered even though they also play a remarkable role in piezoelectric devices. Losses, especially elastic loss in the metal substrate, are also generally neglected, which leads to discrepancies compared with experiments. In this paper, a novel equivalent circuit with four kinds of losses is proposed for a beamlike piezoelectric structure under the longitudinal vibration mode. This structure consists of a slender beam as the metal substrate, and a piezoelectric patch which covers a partial length of the beam. In this approach, first, complex numbers are used to deal with four kinds of losses-elastic loss in the metal substrate, and piezoelectric, dielectric, and elastic losses in the piezoelectric patch. Next in this approach, based on Mason's model, a new equivalent circuit is developed. Using MATLAB, impedance curves of this structure are simulated by the equivalent circuit method. Experiments are conducted and good agreements are revealed between experiments and equivalent circuit results. It is indicated that the introduction of four losses in an equivalent circuit can increase the result accuracy considerably.


Associations between biochemical parameters and referral centre in pet rabbits with urolithiasis.
To determine the association between signalment, selected haematologic and biochemical parameters and referral centre in pet rabbits with imaging evidence of urolithiasis presented to two veterinary teaching hospitals in North America. The medical record database of two veterinary teaching hospitals was searched from 2009 to 2019 for records of pet rabbits that received both imaging studies and plasma biochemistry profiles. Information regarding signalment, bodyweight, packed cell volume, total solids, and plasma biochemistry profiles was obtained. Univariable and multivariable logistic regression models were performed to identify statistically significant parameters associated with imaging evidence of urolithiasis. Of the 324 examined rabbits, 33 (10.2%) had confirmed evidence of urolithiasis on imaging. Increasing plasma calcium and sodium concentrations and referral centre were significantly associated with the presence of urolithiasis on the univariable logistic regression model. However, only plasma calcium concentration and the referral centre demonstrated significant associations on the multivariable logistic regression model. Results indicate that urolithiasis in pet rabbits that receive imaging is associated with mildly increasing plasma calcium concentration and referral centre. The association with referral centre may indicate there are geographic influences on urolithiasis or on imaging. However, the identified associations have low predictive value for the diagnosis of urolithiasis, indicating the need for additional diagnostic modalities.


A Different Path for Harnessing TRAIL.
Two studies show that the apoptosis-inducing protein TRAIL also induces release of cytokines that promote tumor growth. TRAIL triggers formation of a signaling complex that activates NF-κB. Loss of one component of the signaling complex, the adaptor protein FADD, reduces the number of lung tumors in mice.


The Role of Social Influences on Pro-Environment Behaviors in the San Diego Region.
From a social psychological perspective, addressing the threats of climate change involves not only education, which imparts objective facts upon a passive individual, but also a socializing process. The Tripartite Integration Model of Social Influence (TIMSI) provides a theoretical framework that connects acquiring climate change knowledge with integration into a community, which results in greater engagement in climate friendly behaviors. Survey data were collected from 1000 residents in San Diego County. Measures included (a) knowledge about climate change; (b) self-efficacy, what pro-environmental actions they felt they could do; (c) identity, to what extent they identified as part of a community that is concerned about climate change; (d) values, endorsement of values of the community that is concerned about climate change; and (e) pro-environmental behavior, engagement in conservation behaviors. Results indicated that self-efficacy and values mediated the relationship between knowledge and pro-environmental behavior.


Surveillance nursing diagnoses, ongoing assessment and outcomes on in-patients who suffered a cardiorespiratory arrest.
Objective The purposes of this study were to examine the frequency of surveillance-oriented nursing diagnoses and interventions documented in the electronic care plans of patients who experienced a cardiac arrest during hospitalization, and to observe whether differences exist in terms of patients' profiles, surveillance measurements and outcomes. Method A descriptive, observational, retrospective, cross-sectional design, randomly including data from electronic documentation of patients who experienced a cardiac arrest during hospitalization in any of the 107 adult wards of eight acute care facilities. Descriptive statistics were used for data analysis. Two-tailed p-values are reported. Results Almost 60% of the analyzed patients' e-charts had surveillance nursing diagnoses charted in the electronic care plans. Significant differences were found for patients who had these diagnoses documented and those who had not in terms of frequency of vital signs measurements and final outcomes. Conclusion Surveillance nursing diagnoses may play a significant role in preventing acute deterioration of adult in-patients in the acute care setting.


Hemodialysis Tunneled Catheter-Related Infections.
Catheter-related bloodstream infections, exit-site infections, and tunnel infections are common complications related to hemodialysis central venous catheter use. The various definitions of catheter-related infections are reviewed, and various preventive strategies are discussed. Treatment options, for both empiric and definitive infections, including antibiotic locks and systemic antibiotics, are reviewed.


Metastable superconducting qubit.
We propose a superconducting qubit design, based on a tunable rf SQUID and nanowire kinetic inductors, which has a dramatically reduced transverse electromagnetic coupling to its environment, so that its excited state should be metastable. If electromagnetic interactions are in fact responsible for the current excited-state decay rates of superconducting qubits, this design should result in a qubit lifetime orders of magnitude longer than currently possible. Furthermore, since accurate manipulation and readout of superconducting qubits is currently limited by spontaneous decay, much higher fidelities may be realizable with this design.


Pelvic Ultrasound Findings in Women with Obstetric Fistula: A Cross-Sectional Study of Cases and Controls.
Obstetric fistula (OF) is a morbid condition caused by prolonged obstructed labor. Women with OF experience profound injury and have high rates of infertility and poor obstetric outcomes. We examined endovaginal ultrasound parameters in women with and without OF. This cross-sectional study enrolled women evaluated at the Fistula Care Centre in Lilongwe, Malawi. Eligibility criteria included age 18-45, prior pregnancy, and a uterus on ultrasound. Participants underwent endovaginal ultrasound with measurement of cervical dimensions. Comparisons were done using t-tests and Fisher's exact test. Among women with OF, linear regression was used to assess whether fistula stage was associated with cervical length. We enrolled 98 cases and 12 controls. Women with OF had shorter cervical lengths (18.8 mm versus 27.3 mm, p < 0.01), as well as shorter anterior (7.0 mm versus 9.3 mm, p < 0.01) and posterior (9.5 mm versus 11.0 mm, p < 0.04) cervical stroma, compared to controls. Women with OF have shorter cervical lengths and anterior and posterior cervical stroma, when compared to women without OF. This may offer a partial explanation for subfertility and poor obstetric outcomes in OF patients. Additional studies to clarify the role of ultrasound in OF patients and prediction of future fertility are warranted.


Ultraviolet spectroscopy of pyrene in a supersonic jet and in liquid helium droplets.
In a series of experiments devoted to the study of polycyclic aromatic hydrocarbons for astrophysical applications, the S(2)<--S(0) transition of jet-cooled pyrene (C(16)H(10)) at 321 nm has been studied by an absorption technique for the first time. The spectra observed by cavity ring-down spectroscopy closely resemble the excitation spectra obtained earlier by laser-induced fluorescence (LIF) and show the same band clusters arising from the vibronic interaction of S(2) with S(1). We have also investigated pyrene when it was incorporated into 380 mK cold helium droplets. These spectra which were recorded employing LIF and molecular beam depletion spectroscopy are broadened and redshifted by 0.94 nm but retain the essential features of the gas phase spectra.


Placental hormone profiles as predictors of preterm birth in twin pregnancy: A prospective cohort study.
The objective of the study was to analyse placental hormone profiles in twin pregnancies to determine if they could be used to predict preterm birth. Progesterone, estradiol, estriol and corticotropin-releasing hormone were measured using competitive immunoassay and radioimmunoassay in serum and saliva samples of 98 women with twin pregnancies,at 3 or more gestational timepoints. Hormone profiles throughout gestation were compared between very preterm (<34 weeks; n = 8), preterm (<37 weeks; n = 40) and term (37+ weeks; n = 50) deliveries. No significant differences were found between preterm and term deliveries in either absolute hormone concentrations or ratios. Estimated hormone concentrations and ratios at 26 weeks did not appear to predict preterm delivery. Salivary and serum hormone concentrations were generally poorly correlated. Our results suggest that serial progesterone, estradiol, estriol and corticotropin-releasing hormone measurements in saliva and serum are not robust biomarkers for preterm birth in twin pregnancies.


Accuracy of CT perfusion-predicted core in the late window.
Recent endovascular trials have spurred a paradigm shift toward routine use of CT perfusion (CTP) for decision-making in acute ischemic stroke. CTP use in the late window, however, remains under evaluation. Our objective was to assess the accuracy of CTP-predicted core in the late window. In a retrospective review of our prospectively identified stroke registry at a single, comprehensive stroke center, we included patients with anterior large vessel occlusions presenting within the 6-24 h window who underwent baseline CTP evaluation and achieved TICI2b or TICI3 reperfusion on endovascular treatment. We recorded baseline CTP-predicted core volumes at relative cerebral blood flow (CBF) thresholds of <30% <34%, and <38% using RAPID software. Final infarct volumes (FIV) were calculated using follow up MRI and CT, obtained within 72 h after stroke onset. Of the eligible patients, 134 met our inclusion criteria. Mean FIV was 39.5 (SD 49.6). Median CTP to reperfusion time was 93.5 min. Median absolute differences between CTP-predicted core and FIV were 14.7, 14.9, and 16.0 ml at <30%, <34%, and <38%, respectively. Correlation between CTP-predicted ischemic cores and FIV was moderate and statistically significant at all thresholds: r = 0.43 (p <0.001), r = 0.43 (p <0.001), and r = 0.42 (p <0.001) at the <30%, <34%, and <38% cutoffs, respectively. CTP cores in the 6-24 h period underestimate FIV, especially with larger infarcts. CTP-predicted core volumes in the late window show moderate positive correlation with FIV.


Effects of intravenous anesthetics on the contraction and response of rat trachea to phosphatidylinositol.
Some intravenous anaesthetics have significant effects on the tonicity of airway smooth muscle. There are evidences for a direct relationship between airway smooth muscle contraction and phosphatidylinositol (PI) response. The aims of this study were to clarify 1) the effects of anaesthetics on the cholinergically induced contraction, and 2) the relationship between the effects on the PI response and the contraction. Rat tracheal rings or slices were incubated in Krebs-Henseleit solution containing 5.5 microM carbachol (CCh) in the presence of varying doses of anaesthetics. Thiamylal, fentanyl, ketamine and midazolam all attenuated the CCh-induced contraction. On the other hand, thiamylal augmented inositol monophosphate (IP1) accumulation, whilst ketamine, midazolam and morphine did not have the effect, and fentanyl significantly attenuated IP1 accumulation. These data suggest that airway smooth muscle can be relaxed by intravenous anaesthetics, and that the relaxing effects are not always dependent on the PI system.


Autoradiographic localization of arginine vasopressin binding sites in the brain of adult and developing Brazilian opossums.
We are utilizing the Brazilian short-tailed opossum, Monodelphis domestica, to study the development of the vasopressinergic system. Earlier studies demonstrated that arginine vasopressin-like immunoreactivity was present very early in the Brazilian opossum brain, suggesting a role for vasopressin in the developing central nervous system of mammals. In this study, we have utilized [3H]arginine vasopressin autoradiography to describe the distribution of arginine vasopressin binding sites in adult and developing Brazilian opossum brains. In general, arginine vasopressin binding patterns in adult opossum brains resembled those of other species. However, we found very few labelled areas in neonatal Brazilian opossum brains. At birth, only the ventral tegmental area and the nucleus of the solitary tract were labelled. Binding was not evident in the forebrain until 25 days of postnatal age. The anterior pituitary was heavily labelled from birth onward, but binding in the brain itself remained at low levels until 35 days postnatal. Heavy binding was observed in only a few areas of the brain in adults, including the dorsal part of the lateral septal nucleus, the suprachiasmatic nucleus, the dorsal and median raphe, the nucleus of the solitary tract, and the caudal part of the spinal trigeminal nucleus. Surprisingly, arginine vasopressin binding sites in the Brazilian opossum appeared much later than arginine vasopressin immunoreactivity and, in many cases, after neurogenesis was complete. These findings suggest that the arginine vasopressin binding sites are not playing a developmental role in opossums, although the peptide is present at an early age.


[A dose-effect curve in the range of biological and therapeutic action of the radon treatment].
Optimal dose regimen for radon treatment in different diseases should be estimated with dose-effect curve in the range of a stimulating action of moderate doses. The range of therapeutic doses is situated on the ascending part of the resultant curve between minimal and maximal levels of the factor effect.


Clinical Features of Benign Essential Blepharospasm in Korean Patients.
To analyze the clinical features of benign essential blepharospasm in Korean patients. Patients diagnosed with benign essential blepharospasm in Kim's Eye Hospital from November 2014 to December 2016 were evaluated using a clinical examination and questionnaire. The questionnaire reviewed personal medical history, demographic factors, risk factors for blepharospasm development, and relieving and aggravating factors. Of the 101 patients enrolled, 78 (77.2%) were women. The mean age was 64.9 years old. Hypertension was the most common medical disorder (42.6%), followed by diabetes mellitus. The majority of the patients were non-smokers (83.2%) and drank less than a cup of a caffeinated beverage a day (30.7%). Fifty-seven percent of patients reported no stressful events immediately prior to symptom development. Fatigue and stress were aggravating factors in more than 55% of patients; rest was the most common relieving factor (35.6%). Here, we report the clinical features of benign essential blepharospasm in Korean patients for the first time. The results were consistent with previous reports showing that the majority of benign essential blepharospasm patients are women and non-smokers. In contrast to previous reports though, fatigue and stress were aggravating factors, and the most common relieving factor was rest. No stressful events had immediately preceded the development of blepharospasm in 57.4% of patients. This report may aid in treating and counseling patients with benign essential blepharospasm.


Among- and within-population variability in tolerance to cadmium stress in natural populations of Daphnia magna: implications for ecological risk assessment.
Previous attempts to test the hypothesis that laboratory selection of isogenetic populations can produce test organisms with a significantly increased mean tolerance to toxic substances have failed. One possible explanation for such failure is that the tolerance of laboratory populations is largely constrained by their origins (were the source populations composed of tolerant genotypes?). To address this question, among- and within-population variability in stress tolerance was assessed by calculating the variance in individual fitness and longevity across a cadmium gradient (0-10 microg/L). The study employed Daphnia magna clones from four geographically separate European populations. Results revealed significant differences in tolerance to lethal levels of toxic stress among populations. The distribution of tolerances within two of the studied populations showed high amounts of genetic variation in tolerance. Genetic relationships between tolerance traits and life history performance under nonstressful environments differed among the studied populations. One population showed significant but low costs associated with tolerance, whereas no costs were associated with tolerance in the other population. These results suggest that laboratory selection will favor individuals with high fitness or reproductive performance under optimal laboratory conditions resulting in laboratory populations with similar or lower tolerance to toxic stress than their original field populations. Given that populations can exhibit high levels of genetic variability in tolerance to toxic stress, minimizing genetic diversity in toxicity tests will increase the uncertainty attendant in extrapolating from the lab to the field.


A probable case of congenital syphilis from pre-Columbian Austria.
This study examines the skeletal remains of a subadult from an archeological site in Austria. Radiocarbon dating and archeological attribution indicate that this individual is of pre-Columbian origin. Most of the skeleton was recovered, and only the teeth and the orbital roofs show changes. Dental defects such as the mulberry molar and a tapered, fang-like canine suggest a diagnosis of congenital syphilis. This is the first probable case of congenital syphilis from pre-Columbian Central Europe. Our findings contribute to the pre-Columbian theory, offering counter evidence to the assumption that syphilis was carried from Columbus' crew from the New to the Old World.


Conflict-related trauma and bereavement: exploring differential symptom profiles of prolonged grief and posttraumatic stress disorder.
Exposure to trauma and bereavement is common in conflict-affected regions. Previous research suggests considerable heterogeneity in responses to trauma and loss with varying symptom representations. The purpose of the current study was to (1) identify classes of prolonged grief disorder (PGD) and posttraumatic stress disorder (PTSD) symptom profiles among individuals who were exposed to both trauma and loss due to the Colombian armed conflict and (2) to examine whether sociodemographic, loss and trauma-related characteristics could predict class membership. Three hundred eight victims of internal displacement who had experienced trauma and loss were assessed through measures of PGD (PG-13), PTSD (PCL-C), and social support (DUKE-UNC). Latent class analysis (LCA) was performed to analyze differential profiles by symptoms of PGD and PTSD and multinomial logistic regression was used to analyze predictors of class membership. LCA revealed a four-class solution: a resilient class (23.6%), a PTSD-class (23.3%), a predominately PGD class (25.3%) and a high distress-class with overall high values of PGD and PTSD (27.8%). Relative to the resilient class, membership to the PGD class was predicted by the loss of a close family member and the exposure to a higher number of assaultive traumatic events, whereas membership to the PTSD class was predicted by the perception of less social support. Compared to the resilient class, participants in the high distress-class were more likely to be female, to have lost a close relative, experienced more accidental and assaultive traumatic events, and perceived less social support. Specific symptom profiles emerged following exposure to trauma and loss within the context of the Colombian armed conflict. Profiles were associated with distinct types of traumatic experiences, the degree of closeness to the person lost, the amount of social support perceived, and gender. The results have implications for identifying distressed subgroups and informing interventions in accordance with the patient's symptom profile.


Two differentially regulated phosphate transporters from the symbiotic fungus Hebeloma cylindrosporum and phosphorus acquisition by ectomycorrhizal Pinus pinaster.
Ectomycorrhizal symbiosis markedly improves plant phosphate uptake, but the molecular mechanisms underlying this benefit are still poorly understood. We identified two ESTs in a cDNA library prepared from the ectomycorrhizal basidiomycete Hebeloma cylindrosporum with significant similarities to phosphate transporters from the endomycorrhizal fungus Glomus versiforme and from non-mycorrhizal fungi. The full-length cDNAs corresponding to these two ESTs complemented a yeast phosphate transport mutant (Deltapho84). Measurements of (33)P-phosphate influx into yeast expressing either cDNA demonstrated that the encoded proteins, named HcPT1 and HcPT2, were able to mediate Pi:H(+) symport with different affinities for Pi (K(m) values of 55 and 4 mum, respectively). Real-time RT-PCR showed that Pi starvation increased the levels of HcPT1 transcripts in H. cylindrosporum hyphae grown in pure culture. Transcript levels of HcPT2 were less dependent on Pi availability. The two transporters were expressed in H. cylindrosporum associated with its natural host plant, Pinus pinaster, grown under low or high P conditions. The presence of ectomycorrhizae increased net Pi uptake rates into intact Pinus pinaster roots at low or high soil P levels. The expression patterns of HcPT1 and HcPT2 indicate that the two fungal phosphate transporters may be involved in uptake of phosphate from the soil solution under the two soil P availability conditions used.


A new breakthrough: ESD using a newly developed grasping type scissor forceps for early gastrointestinal tract neoplasms.
Endoscopic submucosal dissection (ESD) has allowed the achievement of histologically curative en bloc resection of gastrointestinal neoplasms regardless of size, permitting the resection of previously non-resectable tumors. The ESD technique for treatment of early gastric cancer has spread rapidly in Japan and a few other Asian countries due to its excellent eradication rate compared to endoscopic mucosal resection. Although numerous electrosurgical knives have been developed for ESD, technical difficulties and high complication rates (bleeding and perforation) have limited their use worldwide. We developed the grasping type scissor forceps (GSF) to resolve such ESD-related problems. Our animal and preliminary clinical studies showed that ESD using GSF is a safe (no intraoperative complication) and technically efficient (curative en bloc resection rate 92%) method for dissection of early gastrointestinal tumors. The use of GSF is a promising option for performing ESD on early stage GI tract tumors both safely and effectively.


Exploring Subjective Frames of Patients on Hemodialysis on Acquiring Resilience: A Q Methodology Study.
This study explored subjectivity frames of reference of resilience of patients on hemodialysis by using Q methodology. Participants included 35 patients on hemodialysis. Data were obtained from October to December 2016 and were analyzed by the PQ method. Five factors were identified: 1) finding the value of life by focusing on the meaning of a new life through hemodialysis, 2) compromising actively with the situation of hemodialysis, 3) internalizing sadness and emphasizing the meaning of life itself, 4) finding a support system to help overcome hemodialysis, and 5) building the will to live by getting strength from family. The common theme of the five factors was overcoming hemodialysis and moving forward with their lives. This study can help nurses understand the resilience of patients on hemodialysis and presents strategies that can be used to develop an intervention program to improve the resilience of patients on hemodialysis.


An adult case of relapsing human herpesvirus-6 encephalitis.
Human herpesvirus-6 (HHV-6) is the main etiologic agent of exanthema subitum in young children. Central nervous system (CNS) infections in children due to HHV-6 have been described on many occasions. HHV-6 is also a common cause of infections in immunocompromised individuals. However, little is known concerning the impact of HHV-6 on the CNS in immunocompetent adults. We report the first case of relapsing HHV-6 encephalitis in a healthy 73-year-old female.


[Malakoplakia at 3 sites: the bladder, urethra and kidney. Isolation and ultrastructural study of blood monocytes].
We studied the blood mononuclear cells in a seventy-four-year old man who had urinary tract malacoplakia located to bladder, ureter and kidney. The blood mononuclear cells were isolated as described by Boyum [2] and studied by electron microscopy. They did not show bacilliform bodies or bacteria in the phagolysosomes. The microfilaments and the microtubules were not easily identifiable in the mononuclear cells of the patient. In the control, the internal skeleton of the mononuclear cells was normal. This ultrastructural finding may suggest that there is a relation between microfilaments and microtubules lesion and the low level of cyclic G.M.P. described by Abdou et al.


Effect of Cerebral Ischemic Strokes in Different Cerebral Artery Regions on Left Ventricular Function.
The relationship between cerebral ischemic stroke and left ventricular function evaluated by echocardiography has been emphasized. Whether lesions in different cerebral artery regions would result in left ventricular dysfunction remains uncertain. Patients were divided into middle cerebral artery (MCA) (n = 79), posterior cerebral artery (PCA) (n = 64), basilar artery (BA) regions (n = 66), and no-ischemic stroke group (n = 209). We retrospectively collected demographic characteristics, hematologic parameters, and ECG results, and a comparison of echocardiographic parameters was performed to determine the relationship between ischemic stroke and left ventricular function. A total of 418 patients were included. Demographic characteristics did not significantly differ between the ischemic stroke and non-ischemic stroke groups, except for a history of drinking (p < 0.001). Homocysteine levels in the MCA group were higher than those in the PCA and BA groups (p < 0.05). The highly sensitive C-reactive protein (hs-CRP) level was higher in the ischemic stroke group than in the non-ischemic stroke one (p = 0.001). A higher incidence of ST-T changes in the ECG and lower levels of potassium and magnesium in the ischemic stroke group were found. Significant differences in diastolic function between groups were noted, and the early mitral inflow velocity, annular early diastolic velocity, and ratio between the mitral annular early diastolic velocity and mitral annulus atrial inflow velocity in the MCA group were lower than those in the BA group (p < 0.05). Ischemic strokes exhibited a negative effect on left ventricular diastolic function by echocardiography, especially in MCA region infarcts. These results are of great importance for neurologists as they highlight the need for left ventricular function evaluation after stroke to regulate therapy strategies in time.


Associations of Health Literacy and Health Outcomes Among Populations with Limited Language Proficiency: A Scoping Review.
Populations with limited language proficiency (LLP) experience difficulties understanding health information and accessing care. This study aimed to explore health literacy and LLP by examining the published literature on the barriers and facilitators to health care. A scoping review of studies with populations in countries and regions where they have LLP in the locally dominant language was conducted. One-hundred and forty-three (143) articles met eligibility criteria. Most studies were conducted in North America (n = 99, 69.2%) and the primary language of study participants was Spanish (n = 32; 22.4%). Limited language proficiency was associated with low health literacy. Age was a consistent predictor of LLP, while education was predictive of low health literacy. Low health literacy was associated with poorer health outcomes. This review synthesizes the existing research regarding populations with LLP and their health literacy, demonstrating the importance that the intersection between the two has on patient experiences and behaviors.


Overexertional lumbar and thoracic back pain among recruits: a prospective study of risk factors and treatment regimens.
A total of 395 male infantry recruits were evaluated in a prospective study of possible risk factors for overexertional back pain and the efficacy of drug treatment regimens for this syndrome. Recruits were classified into subgroups of lumbar or thoracic, and paraspinal or spinous process pain. Recruits were divided into three treatment groups: Ibuprofen, Paracetamol, and no drug treatment. Of the recruits, 18% were diagnosed as having overexertional back pain during the course of 14 weeks of training. By multivariate analysis low body mass index was found to be a risk factor for overexertional lumbar pain (p = 0.005) and increased lumbar lordosis a risk factor for overexertional thoracic pain (p = 0.005). Of recruits with overexertional back pain, 65% were asymptomatic by the end of basic training. There was no statistically significant difference between cure rates according to treatment groups.


Retention and intracellular distribution of instilled iron oxide particles in human alveolar macrophages.
Bronchoalveolar lavage (BAL) was used to sample retention of particles within the alveolar macrophage (AM) compartment at various times from 1 to 91 d following intrapulmonary instillation of 2. 6-microm-diameter iron oxide (Fe2O3) particles in human subjects. Particles were cleared from the lavagable AM compartment in a biphasic pattern, with a rapid-phase clearance half-time of 0.5 d and long-term clearance half-time of 110 d, comparable to retention kinetics determined by more traditional methods. The intracellular distribution of particles within lavaged AMs was similar in bronchial and alveolar BAL fractions. AMs with high intracellular particle burdens disappeared from the lavagable phagocytic AM population disproportionately more rapidly (shorter clearance half-time) than did AMs with lower particle burdens, consistent with the occurrence of a particle redistribution phenomenon as previously described in similar studies in rats. The rates of AM disappearance from the various particle burden categories was generally slightly slower in bronchial fractions than in alveolar fractions. The instillation of particles induced a transient acute inflammatory response at 24 h postinstillation (PI), characterized by increased numbers of neutrophils and alveolar macrophages in BAL fluids. This response was subclinical and was resolved within 4 d PI.


Bremsstrahlung by a rapidly accelerating point charge.
The classical problem of radiation emitted by an accelerated charge in the relativistic case is considered. Only accelerations which occur in a short time interval are taken into account. We first discuss the one dimensional trajectories, for later extending the analysis to the two-dimensional case by means of a first-order approximation. We find an expression for the allowed radiated frequencies and we discuss the inconvenience of the concept of formation time of radiation. The results allow us to treat the case of successive collisions, in order to study the behavior of the interference terms.


Extracorporeal interferon therapy in malignant melanoma. Significant economies of interferon in an extracorporeal chamber.
A new method is described for interferon therapy. The procedure involves immobilization of interferon with maintained activity to the surfaces of an extracorporeal perfusion chamber made from polymethylmethacrylate, having a surface area of 0.5 m2 and housing 150 ml blood. The interferon activity remains for at least 3 weeks in a chamber used in patients. Three cases of malignant melanoma, stage II, were treated for 35 to 50 h. The treatment induced increased natural killer activity against melanoma target cells (cytotoxicity index +45--65%) which lasted even after cessation of therapy. the drastic reduction in costs for this type of interferon therapy is underlined.


The endocannabinoid system in bull sperm and bovine oviductal epithelium: role of anandamide in sperm-oviduct interaction.
Anandamide binds to cannabinoid receptors and plays several central and peripheral functions. The aim of this work was to study the possible role for this endocannabinoid in controlling sperm-oviduct interaction in mammals. We observed that bull sperm and bovine oviductal epithelial cells express cannabinoid receptors, CB1 and CB2, and fatty acid amide hydrolase, the enzyme that controls intracellular anandamide levels. A quantitative assay to determine whether anandamide was involved in bovine sperm-oviduct interaction was developed. R(+)-methanandamide, a non-hydrolysable anandamide analog, inhibited sperm binding to and induced sperm release from oviductal epithelia. Selective CB1 antagonists (SR141716A or AM251) completely blocked R(+)-methanandamide effects. However, SR144528, a selective CB2 antagonist, did not exert any effect, indicating that only CB1 was involved in R(+)-methanandamide effect. This effect was not caused by inhibition of the sperm progressive motility or by induction of the acrosome reaction. Overall, our findings indicate for the first time that the endocannabinoid system is present in bovine sperm and oviductal epithelium and that anandamide modulates the sperm-oviduct interaction, by inhibition of sperm binding and induction of sperm release from oviductal epithelial cells, probably by activating CB1 receptors.


123I-FP-CIT SPECT validation of nigro-putaminal MRI tractography in dementia with Lewy bodies.
Assessment of nigrostriatal degeneration is a key element to discriminate between dementia with Lewy bodies (DLB) and Alzheimer disease (AD), and it is often evaluated using ioflupane (123I-FP-CIT) single-photon emission computed tomography (SPECT). Given the limited availability of 123I-FP-CIT SPECT, we evaluated if a mask-based approach to nigroputaminal magnetic resonance imaging (MRI) diffusion-weighted tractography could be able to capture microstructural changes reflecting nigroputaminal degeneration in DLB. A nigroputaminal bundle mask was delineated on 12 healthy volunteers (HV) and applied to MRI diffusion-weighted data of 18 subjects with DLB, 21 subjects with AD and another group of 12 HV. The correlation between nigroputaminal fractional anisotropy (FA) values and 123I-FP-CIT SPECT findings was investigated. Shapiro-Wilk, ANOVA, ANCOVA, and parametric correlation statistics as well as receiver operating characteristic (ROC) analysis were used. DLB patients showed a higher nigroputaminal FA values compared with both AD and HV-controls groups (p = 0.001 for both comparisons), while no difference was observed between HV-controls and AD groups (p = 0.450); at ROC analysis, the area under the curve for the discriminating DLB and AD subjects was 0.820; FA values correlated with 123I-FP-CIT values (on the left, r = -0.670; on the right, r = -720). No significant differences were observed for the FA of the corticospinal tract across the three groups (p = 0.740). In DLB, nigroputaminal degeneration could be reliably assessed on MRI diffusion scans using a mask of nigroputaminal bundle trajectory. Nigroputaminal FA in DLB patients correlated with 123I-FP-CIT values data may allow to differentiate these patients from AD patients and HV-controls.


Efficacy of methylcobalamin on lowering total homocysteine plasma concentrations in haemodialysis patients receiving high-dose folic acid supplementation.
Hyperhomocysteinaemia, which is considered to be induced by impairment of the remethylation pathway in patients with chronic renal failure (CRF), cannot be cured solely by folic acid therapy. In the present study, we investigated the additional benefit of administration of methylcobalamin, which is a co-enzyme in the remethylation pathway, on lowering total homocysteine (tHcy) plasma concentrations in haemodialysis (HD) patients receiving high-dose folic acid supplementation. In order to assess the efficacy on lowering plasma tHcy levels (fasting concentration), 21 HD patients, were randomly assigned and provided folic acid supplementation: 15 mg/day orally (group I, n=7); methylcobalamin 500 mg intravenously after each HD, in addition to folic acid (group II, n=7); or vitamin B(6) (B(6)), 60 mg/day orally, in addition to folic acid and methylcobalamin (group III, n=7). All patients were treated for 3 weeks. A methionine-loading test was conducted before and after supplementation. The following measurements were also made before and after supplementation for each group: serum folic acid, B(6), and vitamin B(12) (B(12)) concentrations (including measurement of proportion of methylcobalamin fraction). Twelve HD patients receiving methylcobalamin alone served as the HD control group and seven healthy volunteers served as the normal control group for this study. In our randomized HD patients the proportions of methylcobalamin fraction (48.3+/-7.5%) and plasma vitamin B(6) concentration (2.9+/-1.1 ng/ml) were significantly lower than in the normal controls (methylcobalamin 58.7+/-2.2%, P<0.01; B(6) 20.1+/-10.8 ng/ml, P<0.01), while folic acid and vitamin B(12) were not significantly different from the normal controls. Mean percentage reduction in fasting tHcy was 17.3+/-8.4% in group I, 57.4+/-13.3% in group II, 59.9+/-5.6% in group III, and 18.7+/-7.5% in HD controls. The power of the test to detect a reduction of tHcy level was 99.6% in group II and 99.9% in group III when type I error level was set at 0.05. Groups II and III had normal results for the methionine-loading test after treatment. Treatment resulted in normalization of fasting tHcy levels (<12 ng/ml) in all 14 patients treated by the combined administration of methylcobalamin and supplementation of folic acid regardless of whether there was supplementation of vitamin B(6). The benefit of methylcobalamin administration on lowering plasma tHcy levels in HD patients was remarkable. Our study suggested that both supplementations of high-dose folic acid and methylcobalamin are required for the remethylation pathway to regain its normal activity. This method could be a therapeutic strategy to combat the risk associated with atherosclerosis and cardiovascular disease in patients with chronic renal failure.


Three-dimensional vascular and metabolic imaging using inverted autofluorescence.
Three-dimensional (3D) vascular and metabolic imaging (VMI) of whole organs in rodents provides critical and important (patho)physiological information in studying animal models of vascular network. Autofluorescence metabolic imaging has been used to evaluate mitochondrial metabolites such as nicotinamide adenine dinucleotide (NADH) and flavine adenine dinucleotide (FAD). Leveraging these autofluorescence images of whole organs of rodents, we have developed a 3D vascular segmentation technique to delineate the anatomy of the vasculature as well as mitochondrial metabolic distribution. By measuring fluorescence from naturally occurring mitochondrial metabolites combined with light-absorbing properties of hemoglobin, we detected the 3D structure of the vascular tree of rodent lungs, kidneys, hearts, and livers using VMI. For lung VMI, an exogenous fluorescent dye was injected into the trachea for inflation and to separate the airways, confirming no overlap between the segmented vessels and airways. The kidney vasculature from genetically engineered rats expressing endothelial-specific red fluorescent protein TdTomato confirmed a significant overlap with VMI. This approach abided by the "minimum work" hypothesis of the vascular network fitting to Murray's law. Finally, the vascular segmentation approach confirmed the vascular regression in rats, induced by ionizing radiation. Simultaneous vascular and metabolic information extracted from the VMI provides quantitative diagnostic markers without the confounding effects of vascular stains, fillers, or contrast agents.


Atomic mechanism of liquid-glass transition for Ca7Mg3 alloy.
The atomic mechanism of liquid-glass transition for Ca(7)Mg(3) alloy during the rapid quenching processes is studied by the molecular dynamics simulations. The temperature dependences of structural, thermodynamic, and dynamic properties during the liquid-glass transition have been investigated. It is found that onset temperatures where these different properties begin to deviate from the equilibrium liquid are identical and near the melting temperature T(m). The liquid-glass transition temperatures in structure (T(g)(Str)) and dynamics (T(g)(Dyn)) are identical and higher than the calorimetric one (T(g)(Cal)), which are consistent with many experiments and computer simulations. The solid- and liquid-like atoms are defined by the Debye-Waller factor. It reveals that the solid-like atoms hold lower potential and higher degree of local order. On the basis of the evolution of solid-like atoms, the atomic mechanisms in structure, thermodynamics, and dynamics transition are systematically elucidated, which are consistent with the potential energy landscape.


Dupilumab therapy provides clinically meaningful improvement in patient-reported outcomes (PROs): A phase IIb, randomized, placebo-controlled, clinical trial in adult patients with moderate to severe atopic dermatitis (AD).
Moderate to severe atopic dermatitis (AD) is associated with substantial patient burden despite current therapies. We sought to evaluate dupilumab treatment on patient-reported outcomes in adults with moderate to severe AD. Adults (N = 380) with moderate to severe AD inadequately controlled by topical medications were randomized to 16 weeks of double-blind, subcutaneous treatment with dupilumab 100 mg every 4 weeks, 200 mg every 2 weeks, 300 mg every 2 weeks, 300 mg once weekly, or placebo. Patient-reported outcomes included pruritus numeric rating scale; patient-reported sleep item on Scoring AD scale; Patient-Oriented Eczema Measure; Hospital Anxiety and Depression Scale; Dermatology Life Quality Index; and 5-dimension 3-level EuroQol. Dupilumab reduced peak itch at 16 weeks relative to placebo by 1.1 to 3.2 points on numeric rating scale (P < .0001 all doses, except 100 mg every 4 weeks P < .05); improved sleep and health-related quality of life on Dermatology Life Quality Index and 5-dimension 3-level EuroQol (P < .05 all doses, except 100 mg every 4 weeks); and reduced anxiety and depression symptoms (P < .05 all doses). Dupilumab's effects appeared early and achieved clinically relevant improvements without significant safety concerns. There are potential cultural differences affecting patient-reported outcome responses. Outcomes were secondary or exploratory end points. Dupilumab produced early and sustained patient-reported and clinically relevant improvements in sleep, mental health, and health-related quality of life; the two 300-mg dose regimens resulted in greatest benefits.


Interaction between huntingtin exon 1 and HEAT repeat structure probed by chimeric model proteins.
Huntington disease (HD) is associated with aggregation of huntingtin (HTT) protein containing over 35 continuous Q residues within the N-terminal exon 1 encoded region. The C-terminal of the HTT protein consists mainly of HEAT repeat structure which serves as a scaffold for multiple cellular activities. Structural and biochemical analysis of the intact HTT protein has been hampered by its huge size (~300 kDa) and most in vitro studies to date have focused on the properties of the exon 1 region. To explore the interaction between HTT exon 1 and the HEAT repeat structure, we constructed chimeric proteins containing the N-terminal HTT exon 1 region and the HEAT repeat protein PR65/A. The results indicate that HTT exon 1 slightly destabilizes the downstream HEAT repeat structure and endows the HEAT repeat structure with more conformational flexibility. Wild-type and pathological lengths of polyQ did not show differences in the interaction between HTT exon 1 and the HEAT repeats. With the C-terminal fusion of PR65/A, HTT exon 1 containing pathological lengths of polyQ could still form amyloid fibrils, but the higher-order architecture of fibrils and kinetics of fibril formation were affected by the C-terminal fusion of HEAT repeats. This indicates that interaction between HTT exon 1 and HEAT repeat structure is compatible with both normal function of HTT protein and the pathogenesis of HD, and this study provides a potential model for further exploration.


Providing Tobacco Treatment in a Community Mental Health Setting: A Pilot Study.
Individuals with mental illnesses (MIs) are disproportionately affected by tobacco-related disease burden because of higher tobacco use prevalence and poor tobacco treatment outcomes. This pilot study examines the outcomes of delivering an evidence-based tobacco treatment program (the Cooper-Clayton program) in a community mental health setting. A prospective nonequivalent group design was used to assess outcomes. This study included 47 participants, of which 19 were in a community mental health setting and 28 were from two non-mental-health settings. Information on sociodemographic (gender, age, educational level, and current life stressors) and medical, MI, substance use, and tobacco use and cessation histories were obtained. Program completion and smoking cessation at the end of treatment (verified with expired carbon monoxide monitoring) were assessed. The program consists of combining behavioral counseling with nicotine replacement therapy for 12 weeks. Participants from the mental health setting were significantly less educated, had greater medical comorbidities, had greater psychiatric and mental health histories, and had greater perceived secondhand tobacco smoke exposure as compared with those from the non-mental-health settings. Thirty-two percent of the participants (6/19) completed the program in the mental health site as compared with 68% (19/28) from the non-mental-health site. None of those from the mental health site achieved cessation as compared with 68% of those from non-mental-health sites. The differential outcomes of evidence-based tobacco treatment programs in non-mental-health versus mental health settings may suggest the need to modify existing tobacco treatment approaches for those with MIs in community settings.


Effect of a hypocaloric diet on lipids and rheological profile in subjects with severe and morbid obesity. A follow-up study.
Discrepant results have been published regarding modifications of rheological parameters in obese subjects after a low caloric diet (LCD). In order to ascertain whether a decrease in BMI associated to a LCD, is accompanied by changes in the hemorheological parameters, we determined in 41 morbid obese subjects (32 female, 9 male aged 33+/-10 years) BMI, glucose, plasmatic lipids and apolipoproteins, fibrinogen, blood viscosity (Brookfield viscosimeter), plasma viscosity (Fresenius capillary viscosimeter), erythrocyte aggregation (Myrenne aggregometer), hematocrit and erythrocyte indexes, before starting on a LCD and 1 and 3 months after. During the first month obese subjects received a very low caloric diet (VLCD) (Modifast) providing 458 kcal per day. The second and third month they received a LCD providing 1500 kcal/day for men and 1200 kcal/day for women. One month after starting on a VLCD, a statistical significant decrease in glucose (p<0.001), Total-cholesterol (p<0.001), LDL-cholesterol (p<0.001), triglycerides (p=0.012), apoB (p<0.001) and erythrocyte aggregation (p<0.001) were observed together with a concomitant decrease in BMI (p<0.001). The expected decrease in HDL-cholesterol associated with a low fat diet was also noted in these individuals. No changes in fibrinogen, hematocrit, blood viscosity or plasma viscosity were observed. At 3 months only a slight increase in BMI was observed regarding the one month period, glucose being the only parameter which remained statistically lower. All the other significant parameters returned to their basal values at 3 months. VLCD (Modifast) is associated to a significant decrease in BMI with the corresponding improvement in glucose, lipids and erythrocyte aggregation at one month. However a LCD alone does not produce a further decrease in weight and both lipids and erythrocyte aggregation return to the basal situation at three months.


Characterization of a novel OTX2-driven stem cell program in Group 3 and Group 4 medulloblastoma.
Medulloblastoma (MB) is the most common malignant primary pediatric brain cancer. Among the most aggressive subtypes, Group 3 and Group 4 originate from stem/progenitor cells, frequently metastasize, and often display the worst prognosis, yet we know the least about the molecular mechanisms driving their progression. Here, we show that the transcription factor orthodenticle homeobox 2 (OTX2) promotes self-renewal while inhibiting differentiation in vitro and increases tumor initiation from MB stem/progenitor cells in vivo. To determine how OTX2 contributes to these processes, we employed complementary bioinformatic approaches to characterize the OTX2 regulatory network and identified novel relationships between OTX2 and genes associated with neuronal differentiation and axon guidance signaling in Group 3 and Group 4 MB stem/progenitor cells. In particular, OTX2 levels were negatively correlated with semaphorin (SEMA) signaling, as expression of 9 SEMA pathway genes is upregulated following OTX2 knockdown with some being potential direct OTX2 targets. Importantly, this negative correlation was also observed in patient samples, with lower expression of SEMA4D associated with poor outcome specifically in Group 4 tumors. Functional proof-of-principle studies demonstrated that increased levels of select SEMA pathway genes are associated with decreased self-renewal and growth in vitro and in vivo and that RHO signaling, known to mediate the effects of SEMA genes, is contributing to the OTX2 KD phenotype. Our study provides mechanistic insight into the networks controlled by OTX2 in MB stem/progenitor cells and reveals novel roles for axon guidance genes and their downstream effectors as putative tumor suppressors in MB.


Through the clinician's lens: objective and subjective views of disability.
In this study, we used recovery preference exploration (RPE) to explore how clinicians practicing in an inpatient medical rehabilitation facility assign meaning to alternative paths of recovery from profound disability. Through the RPE procedure, 33 clinicians ranked preference for recovery from 18 imagined activity limitations and provided narrative explanations for their choices. We used mixed methods, including grounded theory, to identify themes that expressed their recovery choices. Sixteen themes emerged that were classified into separate but linked procedural and conditional reasoning taxonomies. These theme taxonomies represented logical scientific inquiries vs. more phenomenological inquiries into lifeworld meanings, respectively. Just over two thirds (66.8%) of all quotes specified themes from the conditional reasoning taxonomy. The RPE procedure appeared to simulate a lived experience of imagined disability for the clinicians through which contexts and meanings began to emerge independent of the clinicians' scientific attitudes.


Solvent effect on palladium-catalyzed cross-coupling reactions and implications on the active catalytic species.
Suzuki coupling of the bifunctional substrate 1 using [Pd(2)(dba)(3)]/PtBu(3) gives selectivity for C-Cl in nonpolar solvents but for C-OTf in polar solvents. The results of computational and experimental studies suggest that the catalytically active species in polar solvents under conditions employing coordinating additives is inconsistent with monoligated [Pd(PtBu(3))]. Instead, the data are consistent with an anionic palladium complex as the active species.


[Preparation and antibacterial activity of quaternary ammonium salt monomers].
To prepare three quaternary ammonium salt (QAS) monomers, and to compare their antibacterial activities against four oral bacterial strains. Three antibacterial monomers [methacryloxyethyl benzyl dimethyl ammonium chloride (DMAE-BC), methacryloxyethyl m-chloro benzyl dimethyl ammonium chloride (DMAE-m-CBC), methacryloxyethyl cetyl dimethyl ammonium chloride (DMAE-CB)] were synthesized according to the general structure of target monomers. Their antibacterial effects were investigated using the broth dilution test on Gram-positive and Gram-negative bacterial strains (Streptococcus mutans, Streptococcus sanguis, Porphyromonas gingivalis, Prevotella melaninogenica ). Three different monomers were successfully obtained. All the tested bacterial strains were susceptible to the three monomers, among which DMAE-CB exhibited the lowest minimal inhibitory concentrations (MIC) ranging from 1.2 to 4.8 mg/L. All these three QAS monomers have different antibacterial activities against four oral bacteria strains. The data indicate that DMAE-CB may be a candidate antibacterial agent for oral infectious diseases.