The orphan nuclear receptor estrogen-related receptor beta (ERRβ) in triple-negative breast cancer.
Triple-negative breast cancer (TNBC)/basal-like breast cancer (BLBC) is a highly aggressive form of breast cancer. We previously reported that a small molecule agonist ligand for the orphan nuclear receptor estrogen-related receptor beta (ERRβ or ESRRB) has growth inhibitory and anti-mitotic activity in TNBC cell lines. In this study, we evaluate the association of ESRRB mRNA, copy number levels, and protein expression with demographic, clinicopathological, and gene expression features in breast tumor clinical specimens. ESRRB mRNA-level expression and clinical associations were analyzed using RNAseq data. Array-based comparative genomic hybridization determined ESRRB copy number in African-American and Caucasian women. Transcription factor activity was measured using promoter-reporter luciferase assays in TNBC cell lines. Semi-automatic quantification of immunohistochemistry measured ERRβ protein expression on a 150-patient tissue microarray series. ESRRB mRNA expression is significantly lower in TNBC/BLBC versus other breast cancer subtypes. There is no evidence of ESRRB copy number loss. ESRRB mRNA expression is correlated with the expression of genes associated with neuroactive ligand-receptor interaction, metabolic pathways, and deafness. These genes contain G/C-rich transcription factor binding motifs. The ESRRB message is alternatively spliced into three isoforms, which we show have different transcription factor activity in basal-like versus other TNBC cell lines. We further show that the ERRβ2 and ERRβsf isoforms are broadly expressed in breast tumors at the protein level. Decreased ESRRB mRNA expression and distinct patterns of ERRβ isoform subcellular localization and transcription factor activity are key features in TNBC/BLBC.


Anti-mycobacterial screening of five Indian medicinal plants and partial purification of active extracts of Cassia sophera and Urtica dioica.
To find out the anti-mycobacterial potential of Cassia sophera (C. sophera), Urtica dioica (U. dioica), Momordica dioica, Tribulus terrestris and Coccinia indica plants against multi-drug resistant (MDR) strain of Mycobacterium tuberculosis (M. tuberculosis). Plant materials were extracted successively with solvents of increasing polarity. Solvent extracts were screened for anti-mycobacterial activity against fast growing, non-pathogenic mycobacterium strain, Mycobacterium semegmatis, by disk diffusion method. The active extracts were tested against MDR and clinical isolates of M. tuberculosis by absolute concentration and proportion methods. The active extracts were subjected to bio-autoassay on TLC followed by silica column chromatography for isolation of potential drug leads. Hexane extract of U. dioica (HEUD) and methanol extract of C. sophera (MECS) produced inhibition zone of 20 mm in disc diffusion assay and MIC of 250 and 125 μ g/mL respectively in broth dilution assay against Mycobacterium semegmatis. Semipurified fraction F2 from MECS produced 86% inhibition against clinical isolate and 60% inhibition against MDR strain of M. tuberculosis. F18 from HEUD produced 81% inhibition against clinical isolate and 60% inhibition against MDR strain of M. tuberculosis. Phytochemical analysis indicated that anti-mycobacterial activity of MECS may be due to presence of alkaloids or flavonoids and that of HEUD due to terpenoids. C. sophera and U. dioica plant extracts exhibited promising anti-mycobacterial activity against MDR strain of M. tuberculosis. This is the first report of anti-mycobacterial activity form C. sophera. This study showed possibility of purifying novel anti-mycobacterial compound(s) from C. sophera and U. dioica.


A meta-analysis of hippocampal atrophy rates in Alzheimer's disease.
Hippocampal atrophy rates are useful in both diagnosing and tracking Alzheimer's disease (AD). However, cohorts and methods used to determine such rates are heterogeneous, leading to differences in reported annualised rates. We performed a meta-analysis of hippocampal atrophy rates in AD patients and matched controls from studies reported in the peer-reviewed literature. Studies reporting longitudinal volume change in hippocampi in AD subjects together with controls were systematically identified and appraised. All authors were contacted either to confirm the results or to provide missing data. Meta-analysis and meta-regression were then performed on this data. Nine studies were included from seven centres, with data from a total of 595 AD and 212 matched controls. Mean (95% CIs) annualised hippocampal atrophy rates were found to be 4.66% (95% CI 3.92, 5.40) for AD subjects and 1.41% (0.52, 2.30) for controls. The difference between AD and control subject in this rate was 3.33% (1.73, 4.94).


Integration of an Expression Platform in the SELEX Cycle to Select DNA Aptamer Binding to a Disease Biomarker.
Aptamers can be developed for biosensors, diagnostic tools, and therapeutic reagents. These applications usually require a fusion of aptamers and expression platforms. However, the fusion process is usually time-consuming and laborious. In this study, we integrated the deoxyribozyme (I-R3) as an expression platform in the SELEX cycle (called Expression-SELEX) to select aptazymes that can sense diverse molecules. We used the Maple syrup urine disease (MSUD) biomarker L-allo-isoleucine to test the selection model. After five rounds of screening, the cleavage products were sufficiently enriched to be visualized on polyacrylamide gel electrophoresis (PAGE) gel. Through high-throughput sequencing analysis, several candidates were identified. One such candidate, IR3-I-DNA, binds L-allo-isoleucine with a dissociation constant (K D) of 0.57 mM. When the ligand was present, the cleavage fraction of IR3-I-DNA increased from 0.3 to 0.5, and its K obs value improved from 1.38 min-1 to 1.97 min-1. Our selection approach can also be applied to produce aptazymes that can bind to variable ligands and be used more directly as biosensors.


Congenital H-type rectourethral fistula.
An H-type rectourethal fistula was seen in a male child. The anus and anterior urethra were normal. The embryology and surgical management of this rare anomaly are discussed.


Favorable outcome of secondary axillary dissection in breast cancer patients with axillary nodal relapse.
Little evidence can be found about the long-term outcome of breast cancer patients after axillary lymph node recurrence (ALNR) and its survival benefit after different kinds of management. The present study intends to evaluate the risk factors associated with axillary recurrence after definite surgery for primary breast cancer. The prognosis after ALNR and particularly outcome of different management methods also were studied. We retrospectively reviewed data from 4,473 patients who were diagnosed with primary breast cancer and received surgical intervention in a single institute from January 1990 to December 2002. Medical files were reviewed and data on survival were updated annually. Risk factors and prognosis of patients with axillary recurrence were analyzed. Breast-cancer-specific survival of patients with ALNR and outcomes after different management methods also were studied. After a median follow-up of 70.2 months, axillary recurrence developed in 0.8% of patients. Factors associated with ALNR included: age younger than 40 years, medial tumor location, no initial standard level I & II axillary dissection, and not receiving hormonal therapy. The 5-year breast-cancer-specific survival after ALNR was 57.9%. For patients who received further axillary dissection, the 5-year survival rate was 82.5% compared with 44.9% for patients who did not receive further dissection. ALNR is a rare event in treating breast cancer. Young age at diagnosis and medially located tumor are associated with higher risk, but standardized initial axillary dissection to level II and adjuvant hormonal therapy is protective against ALNR. In patients with ALNR, the outcome is not dismal and survival may be improved if further axillary dissection is given.


Shared component modelling of early childhood anaemia and malaria in Kenya, Malawi, Tanzania and Uganda.
Malaria and anaemia contribute substantially to child morbidity and mortality. In this study, we sought to jointly model the residual spatial variation in the likelihood of these two correlated diseases, while controlling for individual-level, household-level and environmental characteristics. A child-level shared component model was utilised to partition shared and disease-specific district-level spatial effects. The results indicated that the spatial variation in the likelihood of malaria was more prominent compared to that of anaemia, for both the shared and specific spatial components. In addition, approximately 30% of the districts were associated with an increased likelihood of anaemia but a decreased likelihood of malaria. This suggests that there are other drivers of anaemia in children in these districts, which warrants further investigation. The maps of the shared and disease-specific spatial patterns provide a tool to allow for more targeted action in malaria and anaemia control and prevention, as well as for the targeted allocation of limited district health system resources.


On modelling the flow controls on macrophyte and epiphyte dynamics in a lowland permeable catchment: the River Kennet, southern England.
A new in-stream model of phosphorus (P) and macrophyte dynamics, the Kennet Model, was applied to a reach of the River Kennet to investigate the impacts of changing flow conditions on macrophyte growth. The investigation was based on the assessment of two flow change scenarios, which both included the simulation of decreasing total phosphorus concentrations from a sewage treatment works due to improved effluent treatment. In the first scenario, the precipitation and potential evaporation outputs from a climate change model (HadCM2 GGx) where input into the catchment model INCA to predict the mean daily flows in the reach. In the second scenario, the mean daily flows observed in a historically dry year were repeated as input to the in-stream model to simulate an extended low flow period over 2 years. The simulation results suggest that changes in the seasonal distribution of flow were not detrimental to macrophyte growth. However, the simulation of extended periods of low flow suggests that a proliferation of epiphytic algae occurs, even when the in-stream phosphorus concentrations are reduced due to effluent treatment. This epiphytic growth was predicted to reduce the macrophyte peak biomass within the reach by approximately 80%. Thus, the model simulations suggest that flow was more important in controlling the macrophyte biomass in the River Kennet, than the in-stream phosphorus concentrations, which are elevated due to agricultural diffuse sources.


[Analysis of two health attendance models for the non-hospital emergencies in Gipuzkoa: Retrospective study].
Out-of-hospital medical emergency services are defined as a functional organization that performs a set of sequential human and material activities. The objective of this study was to compare the mortality of patients attended by the out-of-hospital medical emergency services in 2 neighboring Spanish regions with different models of healthcare transport assistance for emergency care. Retrospective observational cohort study, done between June 1, 2007 and December 31, 2008 in 2 regions of Gipuzkoa, Alto Deba (AD) and Bajo Deba (BD). The study variables were age, sex and place of exposure (AD/BD), heart rate, blood pressure, initial reason for the call defined by the European Resuscitation Council, unconsciousness and digestive bleeding. 3452 subjects were analyzed. The risk of in situ mortality in BD was 1.31 times higher than in AD (P=.050), that of hospital mortality in BD was 0.71 times lower than in AD (P=.011) and the risk of mortality at one year between counties and the combined mortality (in situ+hospital) did not contribute significant differences. Mortality (in situ+in-hospital, and one year aftercare) of patients treated by the out-of-hospital emergency medical services in AD (non-medicalized healthcare transport model) was similar to that of the BD region (mixed healthcare transport model).


Air pollution and hospital admissions for diseases of the circulatory system in three U.S. metropolitan areas.
Generalized additive models were used to analyze the time series of daily hospital admissions for cardiovascular and cerebrovascular diseases over the period of 1987-1995 in three major metropolitan areas--Cook County, IL; Los Angeles County, CA; and Maricopa County, AZ--in the United States. In Cook and Maricopa Counties, admissions information was only available for the elderly (ages 65 and over), while in Los Angeles County, admissions information was available for all ages. In Cook County, daily monitoring information was available on PM10, CO, SO2, NO2, and O3. In Los Angeles and Maricopa Counties, monitoring information was available daily on the gases, and information on PM10 was available every sixth day. In Los Angeles County, information on PM2.5 was also available every sixth day. In Cook and Los Angeles Counties, associations were found between each pollutant, with the exception of O3, and admissions for cardiovascular disease, with the gases showing the strongest associations. In two-pollutant models with PM and one of the gases, the effect of the gases remained stable, while the effect of PM became unstable and insignificant. In Maricopa County, the gases, with the exception of O3, were weakly associated with hospital admissions for cardiovascular disease, while PM was not. In two-pollutant models with two of CO, SO2, and NO2, the pattern of results is heterogeneous in the three counties. In all three counties, only weak evidence of any association between air pollution and cerebrovascular admissions was found.


Effects of phosphatidylserine on membrane incorporation and surface protection properties of exchangeable poly(ethylene glycol)-conjugated lipids.
Liposomes containing the acidic phospholipid phosphatidylserine (PS) have been shown to avidly interact with proteins involved in blood coagulation and complement activation. Membranes with PS were therefore used to assess the shielding properties of poly(ethylene glycol 2000)-derivatized phosphatidylethanolamine (PE-PEG(2000)) with various acyl chain lengths on membranes containing reactive lipids. The desorption of PE-PEG(2000) from PS containing liposomes was studied using an in vitro assay which involved the transfer of PE-PEG(2000) into multilamellar vesicles, and the reactivity of PS containing liposomes was monitored by quantifying interactions with blood coagulation proteins. The percent inhibition of clotting activity of PS liposomes was dependent on the PE-PEG(2000) content. 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-PEG(2000) which transferred out slowly from PS liposomes was able to abolish >80% of clotting activity of PS liposomes at 15 mol%. This level of DSPE-PEG(2000) was also able to extend the mean residence time of PS liposomes from 0.2 h to 14 h. However, PE-PEG(2000) with shorter acyl chains such as 1,2-dimyristyl-sn-glycero-3-phosphoethanolamine-PEG(2000) were rapidly transferred out from PS liposomes, which resulted in a 73% decrease in clotting activity inhibition and 45% of administered intravenously liposomes were removed from the blood within 15 min after injection. Thus, PS facilitates the desorption of PE-PEG(2000) from PS containing liposomes, thereby providing additional control of PEG release rates from membrane surfaces. These results suggest that membrane reactivity can be selectively regulated by surface grafted PEGs coupled to phosphatidylethanolamine of an appropriate acyl chain length.


Percent of cancer in the biopsy set predicts pathological findings after prostatectomy.
The ability to use pretreatment variables to identify patients with organ confined prostate cancer continues to challenge physicians. We examined information available preoperatively, including prostate needle biopsy, clinical stage and preoperative prostate specific antigen (PSA), and evaluated these data based on pathological variables after radical retropubic prostatectomy. We reviewed results in 135 consecutive patients who underwent radical retropubic prostatectomy at a single institution. Needle biopsy information, such as the number of cores, percent of tumor per biopsy set, laterality of positive cores and Gleason sum, were compared with pathological data on the radical retropubic prostatectomy specimen, including pathological stage, Gleason sum and tumor volume. Clinical data, including biopsy information and pathological findings, were compared using univariate and multivariate models. Overall total PSA, percent of tumor in the biopsy and bilateral positive cores directly correlated with tumor volume (p <0.01). Also, increasing PSA, increasing percent of tumor in the biopsy and bilateral positive cores were associated with increased risks of extracapsular extension (p <0.01). From the information readily available from prostate needle biopsy these results suggest that percent of tumor in the biopsy is a useful predictor of pathological stage and tumor volume. Furthermore, including percent of tumor in the biopsy set and bilateral disease with traditional variables such as serum PSA and clinical stage may improve pretreatment tumor staging. This finding adds additional credence to the inclusion of percent of tumor in the biopsy set in models for the preoperative prediction of pathological stage and should be factored into discussions with patients on treatment options.


Quantum cryptographic resource distillation and entanglement.
We look into multipartite quantum states on which quantum cryptographic protocols including quantum key distribution and quantum secret sharing can be perfectly performed, and define the quantum cryptographic resource distillable rate as the asymptotic rate at which such multipartite state can be distilled from a given multipartite state. Investigating several relations between entanglement and the rate, we show that there exists a multipartite bound entangled state whose quantum cryptographic resource distillable rate is strictly positive, that is, there exists a multipartite entangled state which is not distillable, but can be useful for quantum cryptography such as quantum key distribution and quantum secret sharing.


Role of mitochondrial dysfunction and oxidative stress in sensorineural hearing loss.
Sensorineural hearing loss (SNHL) can either be genetically inherited or acquired as a result of aging, noise exposure, or ototoxic drugs. Although the precise pathophysiological mechanisms underlying SNHL remain unclear, an overwhelming body of evidence implicates mitochondrial dysfunction and oxidative stress playing a central etiological role. With its high metabolic demands, the cochlea, particularly the sensory hair cells, stria vascularis, and spiral ganglion neurons, is vulnerable to the damaging effects of mitochondrial reactive oxygen species (ROS). Mitochondrial dysfunction and consequent oxidative stress in cochlear cells can be caused by inherited mitochondrial DNA (mtDNA) mutations (hereditary hearing loss and aminoglycoside-induced ototoxicity), accumulation of acquired mtDNA mutations with age (age-related hearing loss), mitochondrial overdrive and calcium dysregulation (noise-induced hearing loss and cisplatin-induced ototoxicity), or accumulation of ototoxic drugs within hair cell mitochondria (drug-induced hearing loss). In this review, we provide an overview of our current knowledge on the role of mitochondrial dysfunction and oxidative stress in the development of SNHL caused by genetic mutations, aging, exposure to excessive noise, and ototoxic drugs. We also explore the advancements in antioxidant therapies for the different forms of acquired SNHL that are being evaluated in preclinical and clinical studies.


Clinical, angiographic, and procedural predictors of angiographic restenosis after sirolimus-eluting stent implantation in complex patients: an evaluation from the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) study.
The factors associated with the occurrence of restenosis after sirolimus-eluting stent (SES) implantation in complex cases are currently unknown. A cohort of consecutive complex patients treated with SES implantation was selected according to the following criteria: (1) treatment of acute myocardial infarction, (2) treatment of in-stent restenosis, (3) 2.25-mm diameter SES, (4) left main coronary stenting, (5) chronic total occlusion, (6) stented segment >36 mm, and (7) bifurcation stenting. The present study population was composed of 238 patients (441 lesions) for whom 6-month angiographic follow-up data were obtained (70% of eligible patients). Significant clinical, angiographic, and procedural predictors of post-SES restenosis were evaluated. Binary in-segment restenosis was diagnosed in 7.9% of lesions (6.3% in-stent, 0.9% at the proximal edge, 0.7% at the distal edge). The following characteristics were identified as independent multivariate predictors: treatment of in-stent restenosis (OR 4.16, 95% CI 1.63 to 11.01; P<0.01), ostial location (OR 4.84, 95% CI 1.81 to 12.07; P<0.01), diabetes (OR 2.63, 95% CI 1.14 to 6.31; P=0.02), total stented length (per 10-mm increase; OR 1.42, 95% CI 1.21 to 1.68; P<0.01), reference diameter (per 1.0-mm increase; OR 0.46, 95% CI 0.24 to 0.87; P=0.03), and left anterior descending artery (OR 0.30, 95% CI 0.10 to 0.69; P<0.01). Angiographic restenosis after SES implantation in complex patients is an infrequent event, occurring mainly in association with lesion-based characteristics and diabetes mellitus.


Saxagliptin reduces renal tubulointerstitial inflammation, hypertrophy and fibrosis in diabetes.
In addition to lowering blood glucose in patients with type 2 diabetes mellitus, dipeptidyl peptidase 4 (DPP4) inhibitors have been shown to be antifibrotic and anti-inflammatory. We have previously shown that DPP4 inhibition in human kidney proximal tubular cells exposed to high glucose reduced fibrotic and inflammatory markers. Hence, we wanted to demonstrate renoprotection in an in vivo model. We used a type 1 diabetic animal model to explore the renoprotective potential of saxagliptin independent of glucose lowering. We induced diabetes in enos -/- mice using streptozotocin and matched glucose levels using insulin. Diabetic mice were treated with saxagliptin and outcomes compared with untreated diabetic mice. We provide novel data that saxagliptin limits renal hypertrophy, transforming growth factor beta-related fibrosis and NF-κBp65-mediated macrophage infiltration. Overall, there was a reduction in histological markers of tubulointerstitial fibrosis. There was no reduction in albuminuria or glomerulosclerosis. Our findings highlight the potential of DPP4 inhibition as additional therapy in addressing the multiple pathways to achieve renoprotection in diabetic nephropathy.


Does identity disturbance contribute to inhibition in borderline personality? A preliminary report.
A research protocol was developed to test a theoretical model regarding impulsivity in borderline personality (BP) disorder. It was hypothesized that the impact of identity disturbance of individuals with BP features on their response-inhibition functions could be explained by the disposition of their self-concept to increase the intensity of negative emotions. Participants with different levels of BP features were assigned to a self-description condition (N=29) that had the potential to manipulate the identity coherence, or a control condition (N=27) prior to a response inhibition task with high and low arousal emotional stimuli. We also explored the relationship between participants' self-description and their performance on the inhibition task. The results showed a significant interaction between condition, level of BP features, valence, and stimulus intensity on commission errors. Post-hoc analysis did not reveal significant differences. In addition, a moderate correlation was found between a lesser differentiated description of the self and a higher mean of errors of commission. This preliminary study highlights the relevance of studying the relationship between the self-concept and inhibition regarding borderline impulsivity. The findings should be replicated with a larger sample and with individuals who meet the diagnostic criteria.


'Le Roi est mort, vive le Roi': New Roles of Radiotherapy in the Treatment of Lymphomas in Combination With Immunotherapy.
immunotherapy (IT), including checkpoint inhibitors (CIs) and Chimeric Antigen Receptor T cell therapy (CAR-T) revolutionized the treatment of relapsing or refractory (r/r) lymphoma. Several preliminary experiences evaluated concomitant administration of radiotherapy and IT. we performed a systematic review of current literature as of March 30, 2020. A total of 1090 records was retrieved, 42 articles were selected on the basis of title and abstract and, after the removal of analyses with no original data or insufficient clinical information, 28 papers were included in the review. previous studies were mostly represented by case reports/series or small cohorts. Nonetheless, combination of radiotherapy and CIs or CAR-T led to promising outcomes, resulting in extremely high rates of complete response and improving progression free and overall survival compared with data from recent clinical trials. Combination of RT and CIs had a fair toxicity profile with no reports of severe side effects. Within the limits of the small cohorts retrieved, RT seems a superior option compared with systemic treatment as a 'bridge' to CAR-T and could as well reduce severe complications rates. Radiotherapy could elicit immune response against lymphoma, as demonstrated by multiple cases of abscopal effect and its inclusion in anti-neoplastic vaccines protocols. The results of this review warrant the evaluation of combination of RT and immunotherapy in larger and preferably prospective and randomized cohorts to confirm these preliminary impressive outcomes. The optimal dose, fractionation and timing of RT still have to be clarified.


Importance of residue 248 in Escherichia coli RNase P RNA mediated cleavage.
tRNA genes are transcribed as precursors and RNase P generates the matured 5' end of tRNAs. It has been suggested that residue - 1 (the residue immediately 5' of the scissile bond) in the pre-tRNA interacts with the well-conserved bacterial RNase P RNA (RPR) residue A248 (Escherichia coli numbering). The way A248 interacts with residue - 1 is not clear. To gain insight into the role of A248, we analyzed cleavage as a function of A248 substitutions and N-1 nucleobase identity by using pre-tRNA and three model substrates. Our findings are consistent with a model where the structural topology of the active site varies and depends on the identity of the nucleobases at, and in proximity to, the cleavage site and their potential to interact. This leads to positioning of Mg2+ that activates the water that acts as the nucleophile resulting in efficient and correct cleavage. We propose that in addition to be involved in anchoring the substrate the role of A248 is to exclude bulk water from access to the amino acid acceptor stem, thereby preventing non-specific hydrolysis of the pre-tRNA. Finally, base stacking is discussed as a way to protect functionally important base-pairing interactions from non-specific hydrolysis, thereby ensuring high fidelity during RNA processing and the decoding of mRNA.


Unmet need for medical care and safety net accessibility among Birmingham's homeless.
Although homeless individuals often experience health problems requiring care, there are limitations to available research concerning the scale of their needs and the accessibility of safety net agencies to meet them. Traditional access-to-care surveys calculate unmet need among all persons queried (rather than persons needing care), making it difficult to calculate what percentage of persons requiring care actually obtain it. Additionally, no research has compared the relative accessibility of safety net programs to homeless persons in need. This cross-sectional, community-based survey assessed the prevalence of unmet need for several specific types of health care and compared the accessibility of agencies in Birmingham, AL. Substantial proportions of respondents reported unmet needs for general medical care (46 %), specialty care (51 %), mental health care (51 %), dental care (62 %), medications (57 %), and care of a child (23 %). The most commonly mentioned sites where care was sought included a federally funded Health Care for the Homeless (HCH) program (59 %), a religious free clinic (31 %), and a public hospital emergency department (51 %). The HCH program was most commonly cited as the location where care, once sought, could not be obtained (15 %), followed by the county hospital primary care clinics (13 %). In this survey, unmet need was common for all types of care queried, including primary care. Key components of the safety net, including a federally funded homeless health care program, had suboptimum accessibility.


Difficulties in nutritional counseling and child growth follow-up: from a professional perspective.
Nutritional counseling and growth follow-up are priorities when providing care to children; however, these have not been completely incorporated into primary health care. To know the difficulties for providing nutritional counseling and child growth follow-up, from a professional healthcare perspective. Qualitative study, using Donabedian as theoretical framework, developed by 53 professionals in the field of primary health care. Data was obtained from focal groups and submitted to content analysis. The main difficulties for nutritional counseling were clustered in the category of 'perceptions and beliefs related to child feeding'. The 'problems of infrastructure and healthcare' and 'maintenance of the hegemonic medical model' are the main difficulties for following-up growth. Besides investments in infrastructure, healthcare training is indispensable considering beliefs and professional experiences, so in fact, nutritional counseling and child growth follow-up are incorporated in primary health care. Aconselhamento nutricional e acompanhamento do crescimento são prioritários na assistência à criança, porém, ainda não estão plenamente incorporados na atenção básica. Conhecer as dificuldades para realizar aconselhamento nutricional e acompanhamento do crescimento infantil, na perspectiva de profissionais de saúde. Estudo qualitativo, fundamentado no referencial de Donabedian, desenvolvido com 53 profissionais de saúde da atenção básica. Dados foram obtidos por grupos focais e submetidos à análise de conteúdo. As principais dificuldades para o aconselhamento nutricional reuniram-se na categoria 'percepções e crenças relacionadas à alimentação infantil'. Para o acompanhamento do crescimento, as categorias 'problemas de infraestrutura e funcionamento dos serviços de saúde' e 'manutenção do modelo médico hegemônico' representaram as principais dificuldades. Além de investimentos na infraestrutura, é imprescindível que capacitações em serviço considerem crenças e experiências dos profissionais para que, de fato, o aconselhamento nutricional e acompanhamento do crescimento infantil sejam incorporados na atenção básica.


Prevalence and cognitive underpinnings of isolated apathy in young healthy subjects.
Apathy is well described in neurodegenerative conditions, however to date there is no evidence of significant isolated apathy in subjects free from other neurological and psychiatric co-morbidites. Identifying isolated apathy in subjects free from neuropsychiatric conditions could contribute to refining current concepts of apathy and reevaluate its nosological classification as an independent clinical syndrome. We assessed apathy and perceived quality of life in a group of 2751 adults (age 19-40 years) free from neuropsychiatric or medical conditions. Subjects with and without elevated apathy were compared on measures of depression, self-efficacy, behavioral inhibition, and behavioral activation. Observed prevalence of isolated elevated apathy was 1.45%. Subjects with apathy presented with reduced quality of life and lower behavioral activation compared to apathy-free subjects, while there was no difference between the two groups on measures of depression, self-efficacy, and perceived social skills. The main limitation of this study is the use of self-report questionnaires. Isolated, ecologically-relevant apathy can be found in adults independently from the presence of subclinical depression or of concurrent medical conditions. Apathy screening should be considered in the evaluation of young non-depressed subjects with reduced perceived quality of life.


Crystal structure of the S. cerevisiae D-ribose-5-phosphate isomerase: comparison with the archaeal and bacterial enzymes.
Ribose-5-phosphate isomerase A has an important role in sugar metabolism by interconverting ribose-5-phosphate and ribulose-5-phosphate. This enzyme is ubiquitous and highly conserved among the three kingdoms of life. We have solved the 2.1 A resolution crystal structure of the Saccharomyces cerevisiae enzyme by molecular replacement. This protein adopts the same fold as its archaeal and bacterial orthologs with two alpha/beta domains tightly packed together. Mapping of conserved residues at the surface of the protein reveals strong invariability of the active site pocket, suggesting a common ligand binding mode and a similar catalytic mechanism. The yeast enzyme associates as a homotetramer similarly to the archaeal protein. The effect of an inactivating mutation (Arg189 to Lys) is discussed in view of the information brought by this structure.


Conformational heterogeneity of the aspartate transporter Glt(Ph).
Glt(Ph) is a Pyrococcus horikoshii homotrimeric Na(+)-coupled aspartate transporter that belongs to the glutamate transporter family. Each protomer consists of a trimerization domain involved in subunit interaction and a transporting domain with the substrate-binding site. Here, we have studied the conformational changes underlying transport by Glt(Ph) using EPR spectroscopy. The trimerization domains form a rigid scaffold, whereas the transporting domains sample multiple conformations, consistent with large-scale movements during the transport cycle. Binding of substrates changed the occupancies of the different conformational states, but the domains remained heterogeneous. The membrane environment favored conformations different from those observed in detergent micelles, but the transporting domain remained structurally heterogeneous in both environments. We conclude that the transporting domains sample multiple conformational states with substantial occupancy regardless of the presence of substrate and coupling ions, consistent with equilibrium constants close to unity between the observed transporter conformations.


Extraction and Verification of Mouse and Human Mucins from Tissue and Fecal Material.
Gel-forming mucins are highly O-glycosylated polymeric glycoproteins which have critical roles in tissue protection from environmental insult. To understand their biochemical properties, these samples must be extracted and enriched from biological samples. Here we describe how to extract and semi-purify human and murine mucins from intestinal scrapings or fecal material. As mucins have high molecular weights, traditional gel electrophoresis methods are unable to effectively separate these glycoproteins for analysis. We describe the procedure for making composite sodium dodecyl sulfate urea agarose-polyacrylamide (SDS-UAgPAGE) gels, which allows for accurate verification and band separation of extracted mucins.


Brucella canis in Commercial Dog Breeding Kennels, Ontario, Canada.
We evaluated the prevalence of Brucella canis seropositivity in a convenience sample of dogs from commercial breeding kennels in Ontario, Canada. Overall, 127/1,080 (11.8%) dogs from 23/63 (37%) kennels were seropositive. The prevalence of positive dogs within kennels with >1 positive dog ranged from 3.9% to 100% (median 33%).


A Simplified Method to Minimize Systematic Bias of Single-Optimized Intraocular Lens Power Calculation Formulas.
To provide a simplified method to optimize lens constants to zero the mean prediction error (ME) of an intraocular lens (IOL) calculation formula, without the need to program the formula itself, by exploring the influence of IOL and corneal power on the refractive impact of variations in effective lens position. Theoretical development of an optimized formula and retrospective clinical evaluation on documented datasets. Retrospective data from 8878 patients with cataracts with pre- and postoperative measurements available using 4 IOL models and 6 IOL power calculation formulas were examined. A schematic eye model was used to study the impact of small variations in effective lens position (ELP) on the postoperative spherical equivalent (SE) refraction. The impact of keratometry (K) and IOL power (P) on SE was investigated. A theoretical thick lens model was used to devise a formula to zero the average prediction error of an IOL power calculation formula. This was achieved by incrementing the predicted ELP, which could then be translated into an increment in the IOL constant. This method was tested on documented real-life postoperative datasets, using different IOL models and single-constant optimized IOL calculation formulas. For small variations in ELP, there was an exponential relationship between IOL power and the resultant postoperative refractive variation. The ELP adjustment necessary to zero the ME equated to a ratio between the ME and the mean of the following expression: 0.0006*(P2+2K*P) on the considered datasets. The accuracy of the values obtained using this formula was confirmed on documented postoperative datasets, and on published and nonpublished formulas. The proposed method allows surgeons without special expertise to optimize an IOL constant to nullify the ME on a documented dataset without coding the different formulas. The influence of individual eyes is proportional to the squared power of the implanted IOL.


Effects of prenatal exposure to coal-burning pollutants on children's development in China.
Environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs), lead, and mercury are released by combustion of coal and other fossil fuels. In the present study we evaluated the association between prenatal exposure to these pollutants and child development measured by the Gesell Developmental Schedules at 2 years of age. The study was conducted in Tongliang, Chongqing, China, where a seasonally operated coal-fired power plant was the major source of ambient PAHs and also contributed lead and mercury to the air. In a cohort of nonsmoking women and their newborns enrolled between March 2002 and June 2002, we measured levels of PAH-DNA adducts, lead, and mercury in umbilical cord blood. PAH-DNA adducts (specifically benzo[a]pyrene adducts) provided a biologically relevant measure of PAH exposure. We also obtained developmental quotients (DQs) in motor, adaptive, language, and social areas. Decrements in one or more DQs were significantly associated with cord blood levels of PAH-DNA adducts and lead, but not mercury. Increased adduct levels were associated with decreased motor area DQ (p = 0.043), language area DQ (p = 0.059), and average DQ (p = 0.047) after adjusting for cord lead level, environmental tobacco smoke, sex, gestational age, and maternal education. In the same model, high cord blood lead level was significantly associated with decreased social area DQ (p = 0.009) and average DQ (p = 0.038). The findings indicate that exposure to pollutants from the power plant adversely affected the development of children living in Tongliang; these findings have implications for environmental health policy.


Measuring the impact of health research data in terms of data citations by scientific publications.
Health is a representative domain data-driven research since health research data are growingly generated at a massive scale. There is an intuitive logic that the degree to which disease burden and the number of data resources align. In order to figure out disease-specific data sharing and reuse level, we took the number of data records and their citations in the scientific literature in the Data Citation Index platform as approximate indicators. The results indicated that only a small percentage (7.5%) of health data records had received documented citations by scientific publications. We find the level of data sharing and reuse varies across diseases. Our study suggested that the more socioeconomic burden and the more research funding, the more likely scientific data for diseases will be produced and made available. But such a correlation could not be observed for the activity of data reuse. Secondary reuse of scientific data is a complex behavior.


Immunogenic and antigenic properties of the COOH-terminal hexapeptide of substance P.
Substance P (SP) and its COOH-terminal fragment (6-11) were coupled to bovine serum albumin by glutaraldehyde and used to elicit antibodies. Anti-SP and anti-SP6-11 antibodies bound to the same extent 125I-[Tyr8]-SP and 125I-[T-Lys6]-SP6-11. The latter was obtained after conjugation of the [Lys6]-SP6-11 with cold Bolton-Hunter reagent and then labelling by the chloramine-T method. In contrast to 125I-[Tyr8]-SP, 125I-[Tyr8]-SP6-11 was poorly bound by both anti-SP and anti-SP6-11 antibodies. Synthetic fragments of SP shorter than SP7-11 did not react with anti-SP6-11 antibodies. It is concluded that the antigenic determinant is within the COOH-terminal pentapeptide, and that Phe7, Phe8, Leu10 and Met11 contribute significantly to both anti-SP and anti-SP6-11 immunoreactivity.


Lymphocyte glucocorticoid receptor expression level and hormone-binding properties differ between war trauma-exposed men with and without PTSD.
Posttraumatic stress disorder (PTSD) has been shown to be associated with altered glucocorticoid receptor (GR) activity. We studied the expression and functional properties of the receptor in peripheral blood mononuclear cells (PBMCs) from non-traumatized healthy individuals (healthy controls; n=85), and war trauma-exposed individuals with current PTSD (n=113), with life-time PTSD (n=61) and without PTSD (trauma controls; n=88). The aim of the study was to distinguish the receptor alterations related to PTSD from those related to trauma itself or to resilience to PTSD. Functional status of the receptor was assessed by radioligand binding and lysozyme synthesis inhibition assays. The level of GR gene expression was measured by quantitative PCR and immunoblotting. Current PTSD patients had the lowest, while trauma controls had the highest number of glucocorticoid binding sites (Bmax) in PBMCs. Hormone-binding potential (Bmax/KD ratio) of the receptor was diminished in the current PTSD group in comparison to all other study groups. Correlation between Bmax and KD that normally exists in healthy individuals was decreased in the current PTSD group. Contrasting Bmax data, GR protein level was lower in trauma controls than in participants with current or life-time PTSD. Current PTSD is characterized by reduced lymphocyte GR hormone-binding potential and by disturbed compensation between Bmax and hormone-binding affinity. Resilience to PTSD is associated with enlarged fraction of the receptor molecules capable of hormone binding, within the total receptor molecule population in PBMCs.


Quality of life in ALS depends on factors other than strength and physical function.
To study patients with ALS to determine the following: 1) the relationship between physical function and quality of life (QOL); 2) the instruments that best reflect patients' own ratings of QOL; and 3) whether spiritual/religious factors play a role in determining QOL. The authors prospectively studied 96 patients with ALS using several instruments, including the McGill Quality of Life (MQOL) instrument, the Idler Index of Religiosity, the Sickness Impact Profile (SIP)/ALS-19, and several measures of strength and physical function. QOL as assessed by patients (MQOL single item score) did not correlate with measures of physical function and strength, but correlated with the total MQOL score (p < 0.0005), the psychological and existential subscores of MQOL (p < 0. 0005), the support subscore of MQOL (p = 0.001), and the total Idler score (p = 0.001). In contrast, correlations between SIP/ALS-19 and these measures were not significant, although SIP/ALS-19 correlated with measures of physical function and strength. QOL, as assessed by the patient with ALS, does not correlate with measures of strength and physical function, but appears to depend on psychological and existential factors, and thus may be measured well by the MQOL scale. Spiritual factors and support systems appear to play roles as well. SIP/ALS-19 is a good measure of physical function, but not of overall QOL.


Biofeedback treatment of fecal incontinence incorporating a mental variable without instrumentation: a prospective pilot study in Hispanic population.
The long-established approaches utilized to treat fecal incontinence always require instrumentation with some type of electronic equipment. This equipment is not always available in every institutions. In addition, no studied protocol principally used as coordination, sensory, or strength training has reached the level of gold standard. The purpose of this study was to describe a simple biofeedback technique that incorporating a mental variable and not requiring electronic equipment with prior adequate training could be used at any medical institution. A particular modality of an operant conditioning technique was given once and a home trainer program was established. Forty-eight patients (mean age 37.1 +/- 3.7 years) were recruited. Patients had suffered from total incontinence for a period of 55 +/- 7.5 months, all used two to three pads per day and suffered 2.4 +/- 0.2 episodes of incontinence per day. Patients underwent clinical history recording, laboratory tests, recto-sigmoidoscopy, and double-contrast barium enema. Manometry and rectal sensitivity were performed in 7 and 27 patients, respectively. For physiologic comparisons, 21 healthy volunteers were used. A total of 79.1% of patients became continent in a median period of 3.9 +/- 0.5 months. An average of 3.85 +/- 0.55 sessions was required. Follow-up continued for 3-11 years. Patients with incontinence showed lower basal mean resting pressure, maximum squeeze pressure and rectal sensitivity (p <0. 01) and spontaneous rectoanal inhibitory reflex was absent in 57%. This biofeedback approach does not employ any type of electronic equipment and can be easily reproduced in any type of medical center. Additionally, this is the first report in which a methodology for biofeedback therapy successfully incorporates a mental variable in addition to sensory and strength training.


Continued Counseling for the Relationship Between State-Level Medicine and Public Health.
Public health and organized medicine have operated somewhat independently of each other since the early 1900s. In the wake of the COVID-19 pandemic, the necessity of healing any divide between organized medicine and state and local health officials seems self-evident. Using the recommendations abstracted from a 2005 article by Dr. Ronald Davis, "Marriage Counseling for Medicine and Public Health," this cross-sectional study explores the formal relationships that existed between state-level public health and medical practice across the U.S. at the end of 2019. A questionnaire was distributed to every state's senior public health official and medical society executive (N=104) between August and December 2019 to examine the extent of these entities' partnerships. Analysis was completed in January 2020. Among the respondents, 40%-63.1% (n=65) currently engage in the recommended activities, with 1 exception: state health departments infrequently invite medical society executives to speak at major conferences or meetings (26.2%). The majority of respondents (71.1%-85.9%) judged that each recommended activity would improve the practices of medicine and public health. Survey results illustrate a desire for reconciliation, but poor implementation of recommended strategies aimed at building a healthy marriage between the 2 sectors. More formal efforts are needed among state medical and public health organizations to capitalize on the current climate of rapprochement. The burden of COVID-19 on the national health system could provide a worthy cause around which these efforts would coalesce.


Dose-response in stereotactic irradiation of lung tumors.
The dose-response for local tumor control after stereotactic radiotherapy of 92 pulmonary tumors (36 NSCLC and 56 metastases) was evaluated. Short course irradiation of 1-8 fractions with different fraction doses was used. After a median follow-up of 14 months (2-85 months) 11 local recurrences were observed with significant advantage for higher doses. When normalization to a biologically effective dose (BED) is used a dose of 94Gy at the isocenter and 50Gy at the PTV-margin are demonstrated to give 50% probability of tumor control (TCD50). Multivariate analysis revealed the dose at the PTV-margin as the only significant factor for local control.


Protective anti-outer membrane protein immunity against Pasteurella pneumotropica infection of mice.
The ability of recombinant outer membrane proteins of Pasteurella pneumotropica to vaccinate against the infections of mice was studied. The proteins examined were the homologues of the P4, P6, P26, and D15 proteins of Haemophilus influenzae. Intranasal vaccination with P4 and P6 produced protection against pneumonia. P6 vaccination, which was most studied, reduced the peak bacteria load in lungs by 50-fold and caused a rapid resolution of an infection that lasted for at least 5 days in unvaccinated animals. Protection could be partially transferred with CD4(+) T cells and pulmonary challenge with the P6 antigen induced interferon-γ and the Th17 cytokine IL-21. This is the first demonstration of the ability of a recombinant P6 to mediate protective immunity to a pathogen in its natural host and it is proposed that it would not only have utility for mouse breeding but also for investigating how to improve the efficacy of vaccination with homologous proteins for related species.


Grey-matter abnormalities in clinical high-risk participants for psychosis.
The current study examined the presence of abnormalities in cortical grey-matter (GM) in a sample of clinical high-risk (CHR) participants and examined relationships with psychosocial functioning and neurocognition. CHR-participants (n = 114), participants who did not fulfil CHR-criteria (CHR-negative) (n = 39) as well as a group of healthy controls (HC) (n = 49) were recruited. CHR-status was assessed using the Comprehensive Assessment of At-Risk Mental State (CAARMS) and the Schizophrenia Proneness Interview, Adult Version (SPI-A). The Brief Assessment of Cognition in Schizophrenia Battery (BACS) as well as tests for emotion recognition, working memory and attention were administered. In addition, role and social functioning as well as premorbid adjustment were assessed. No significant differences in GM-thickness and intensity were observed in CHR-participants compared to CHR-negative and HC. Circumscribed abnormalities in GM-intensity were found in the visual and frontal cortex of CHR-participants. Moreover, small-to-moderate correlations were observed between GM-intensity and neuropsychological deficits in the CHR-group. The current data suggest that CHR-participants may not show comprehensive abnormalities in GM. We discuss the implications of these findings for the pathophysiological theories of early stage-psychosis as well as methodological issues and the impact of different recruitment strategies.


What is the response profile of deciduous pulp fibroblasts stimulated with E. coli LPS and E. faecalis LTA?
Oral fibroblast immunological responses to bacterial stimuli are well known. However, there are few studies about pulp fibroblasts from deciduous teeth (HDPF) responses, which are important for the treatment of pulp infections in children. The aim of this study was to evaluate expression and production of inflammatory cytokines and chemokines by HDPF when challenged with bacterial antigens normally present in advanced caries lesions. Triplicate HDPF from 4 children (n = 4; 2 boys and 2 girls) were cultured by explant technique and challenged or not with Escherichia coli lipopolysaccharide/1 μg/mL (EcLPS) or Enterococcus faecalis lipoteichoic acid/1 μg/mL (EfLTA) for 6 and 24 h. Most of published studies employed immortalized cells, i.e., without checking possible gender and genetic variables. mRNA expression and protein production were evaluated by RT-qPCR and ELISA MILLIPLEX®, respectively, for Interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, Chemokine C-C motif ligand 2/monocyte chemoattractant protein 1 (CCL2/MCP-1), Chemokine C-C motif ligand 3/macrophage inflammatory protein 1-alpha (CCL3/MIP1-α), Chemokine C-C motif ligand 5/ regulated on activation, normal T cell expressed and secreted (CCL5/RANTES), C-X-C motif chemokine 12/ stromal cell-derived factor 1 (CXCL12/SDF-1), Tumor Necrosis Factor-alpha (TNF-α), Interferon-gamma (IFN γ), Vascular Endothelial Growth Factor (VEGF), Colony stimulating factor 1 (CSF-1) and Macrophage colony-stimulating factor (M-CSF). EcLPS increased IL-1α, IL-1β, IL-8, CCL2, CCL5, TNF-α and CSF-1 mRNA and protein levels while EfLTA was only able to positively regulate gene expression and protein production of IL-8. The results of the present study confirmed our hypothesis, since pulp fibroblasts from deciduous teeth are capable of increasing gene expression and protein production after being stimulated with EcLPS and EfLTA.


Adenovector 26 encoded prefusion conformation stabilized RSV-F protein induces long-lasting Th1-biased immunity in neonatal mice.
While RSV is a major cause of respiratory morbidity in infants, vaccine development is hindered by the immaturity and Th2-bias of the infant immune system and the legacy of enhanced respiratory disease (ERD) after RSV infection following immunization with formalin inactivated (FI)-RSV vaccine in earlier clinical trials. Preclinical studies have demonstrated that an adenoviral vector-based RSV F vaccine candidate (Ad26.RSV.FA2) induces Th1-biased protective immune responses, without signs of ERD upon subsequent RSV challenge. We here developed an Ad26 vector encoding the RSV F protein stabilized in its prefusion conformation (Ad26.RSV.preF). In adult mice, Ad26.RSV.preF induced superior, Th1-biased IgG2a-dominated humoral responses as compared to Ad26.RSV.FA2, while maintaining the strong Th1-biased cellular responses. Similar to adult mice, Ad26.RSV.preF induced robust and durable humoral immunity in neonatal mice, again characterized by IgG2a-dominated RSV F-binding antibodies, and high and stable virus-neutralizing titers. In addition, vaccine-elicited cellular immune responses were durable and characterized by IFN-γ-producing CD4+ and CD8+ T cells, with a profound Th1 bias. In contrast, immunization of neonatal mice with FI-RSV resulted in IgG1 RSV F-binding antibodies associated with a Th2 phenotype, no detectable virus-neutralizing antibodies, and a Th2-biased cellular response. These results are supportive for the clinical development of Ad26.RSV.preF for use in infants.


Maternal pemphigus vulgaris with in vivo bound antibodies in the stillborn fetus.
A 42-year-old black woman, gravida V, para IV, developed a recurrence of pemphigus vulgaris in the third trimester of pregnancy. She delivered a 2,056-gm stillborn female fetus in the seventh month, 2 days after ultrasonography had demonstrated absence of fetal cardiac activity and other evidence of intrauterine fetal death. The macerated fetus had peeling of its skin and an intact bulla on the foot. Fetal cardiac blood, obtained after delivery, showed the presence of pemphigus antibodies at a titer of 20. Direct immunofluorescence of fetal skin demonstrated IgG in the epidermal intercellular spaces. Autolytic changes of the skin, however, precluded definitive histologic documentation of acantholytic disease.


Complement: a novel factor in basal and ischemia-induced neurogenesis.
Through its involvement in inflammation, opsonization, and cytolysis, the complement protects against infectious agents. Although most of the complement proteins are synthesized in the central nervous system (CNS), the role of the complement system in the normal or ischemic CNS remains unclear. Here we demonstrate for the first time that neural progenitor cells and immature neurons express receptors for complement fragments C3a and C5a (C3a receptor (C3aR) and C5a receptor). Mice that are deficient in complement factor C3 (C3(-/-)) lack C3a and are unable to generate C5a through proteolytic cleavage of C5 by C5-convertase. Intriguingly, basal neurogenesis is decreased both in C3(-/-) mice and in mice lacking C3aR or mice treated with a C3aR antagonist. The C3(-/-) mice had impaired ischemia-induced neurogenesis both in the subventricular zone, the main source of neural progenitor cells in adult brain, and in the ischemic region, despite normal proliferative response and larger infarct volumes. Thus, in the adult mammalian CNS, complement activation products promote both basal and ischemia-induced neurogenesis.


Open versus robot-assisted partial nephrectomy: A longitudinal comparison of 880 patients over 10 years.
Most comparisons between robot-assisted partial nephrectomy (RAPN) and open partial nephrectomy (OPN) indicate the superiority of RAPN, but the learning curve is often not considered. All consecutive partial nephrectomies from the very first RAPN at a single tertiary referral centre (n = 818, 500 RAPN vs. 313 OPN) were retrospectively analyzed. Complications, success rates and surgical outcomes were compared. Inequalities between cohorts and the inherent learning curve were controlled by subgroup comparisons, regression analyses, and propensity score matching. Overall, RAPN had fewer complications, less blood loss, and shorter length of stay. However, an inherent learning curve caused higher complications for the first 4 years. Thereafter, perioperative outcomes clearly favoured RAPN, even for more complex tumours. In one of the largest monocentric cohorts over more than 10 years, RAPN was found to be superior to OPN. However, not all advantages of RAPN are immediate because a learning curve must be passed.


Chemical composition and biological activity of Mentha citrata Ehrh., essential oils growing in southern Algeria.
Three techniques, hydro distillation, steam distillation and microwave-assisted distillation, was used in this work to extract volatile secondary metabolites essential oils (EOs), from the aerial part of Mentha citrata Ehrh., plant (steams, leaves and flowers). The plant material was collected from a location called El-kobna in El-Oued province, southern Algeria during June 2018. The extracted Mentha citrata EOs, were analyzed using both gas chromatography coupled with flame ionization detector and gas chromatography attached with mass spectrometry detector techniques. The antioxidant activity of these EOs were evaluated in vitro using DPPH (2,2-diphenyl-1-picrylhydrazyl) free radicals scavenging activity and cytotoxic test. The results of the EOs analysis showed large variability of the chemical compositions for all techniques. Moreover, a promising cytotoxic activity on colon cancer cells was found.


Dentin hypersensitivity: etiology, diagnosis and treatment; a literature review.
The objective of this review is to inform practitioners about dentin hypersensitivity (DH); to provide a brief overview of the diagnosis, etiology and clinical management of dentin hypersensitivity and to discuss technical approaches to relieve sensitivity. This clinical information is described in the context of the underlying biology. The author used PUBMED to find relevant English-language literature published in the period 1999 to 2010. The author used combinations of the search terms "dentin*", "tooth", "teeth", "hypersensit*", "desensitiz*". Abstracts and also full text articles to identify studies describing etiology, prevalence, clinical features, controlled clinical trials of treatments and relevant laboratory research on mechanisms of action were used.


Nasal flow, volumes, and minimal cross sectional areas in asthmatics.
The Unified Airways hypothesis suggests an involvement of the upper airways in asthma. Critical parameters of the nasal airway can be quantified objectively with acoustic rhinometry (AR) and peak nasal inspiratory flow (PNIF). We aimed to investigate nasal airway patency in asthmatics compared to non-asthmatic controls. Nasal volume, cross sectional area and flow were measured using acoustic rhinometry (AR) and peak nasal inspiratory flow (PNIF) in 87 asthmatics and 93 non-asthmatic controls before and after decongestion with xylometazoline. Nasal congestion index (NCI) was calculated, and allergy status was assessed by skin prick test or specific IgE. We found significantly smaller minimum cross sectional area and nasal cavity volume in asthmatics than controls, and the cross sectional area is at its minimum at 2-3 cm from the nasal orifice in both groups. AR and PNIF measurements are not different in allergic and non allergic subjects in either group. The effect of xylometazoline is not significantly different between the 2 groups with regard to AR, but there is a significant improvement in PNIF for the asthmatics when assessed by the NCI. The present study demonstrates a significantly smaller nasal airway when assessed by minimum cross sectional area and nasal cavity volume in asthmatics than controls, and these findings apply to asthmatics and controls irrespective of allergy status.


A study of the reliability and validity of the Chinese version of the Nociception Coma Scale-Revised.
The aim of the study was to check on the reliability and validity of the translated version of Nociception Coma Scale-Revised. Prospective psychometric study. Rehabilitation and neurology unit in hospital. Patients with prolonged disorders of consciousness. None. The original English version of the Nociception Coma Scale-Revised was translated into Chinese. The reliability and validity were undertaken by trained raters. Intraclass correlation coefficients were used to assess inter-rater reliability and test-retest reliability. Cronbach's alpha test was used to investigate internal consistency. Spearman's correlation was used to calculate concurrent validity. The Coma Recovery Scale-revised was used to assess the consciousness of patients. Eighty-four patients were enrolled in the study. Inter-rater reliability of the Chinese version of Nociception Coma Scale-Revised was high for total scores and motor and verbal subscores and good for facial subscores. Test-retest reliability was high for total score and for all subscores. Analysis revealed a moderate internal consistency for subscores. For the concurrent validity, a strong correlation was found between the Nociception Coma Scale-Revised and the Face, Legs, Activity, Cry, and Consolability behavioral scale for all patients. A moderate correlation was found between the Nociception Coma Scale-Revised and the Coma Recovery Scale-revised scores for all patients. The Chinese version of Nociception Coma Scale-Revised has good reliability and validity data for assessing responses to pain in patients with prolonged disorders of consciousness.


Time-resolved fluorescence of apoferritin and its subunits.
The decay of the intrinsic fluorescence of the apoferritin polymer and its subunits has been studied by pulse and phase shift techniques. Both techniques show that the fluorescence decay of all the samples tested cannot be described by a single exponential function. The fluorescence decay data of the apoferritin subunits obtained with either technique can be fitted satisfactorily with a function resulting from the sum of two exponential components. However, the polymer data obtained with the high resolution phase shift technique operated either by synchrotron radiation or by a mode-locked argon ion laser can be fitted better using a bimodal gaussian continuous distribution of lifetime components. The molecular basis for this distribution of lifetime values may lie in the heterogeneity of the tryptophan environment generated by the assembly of the subunits into the polymer. The binding of the first 100 irons to apoferritin quenches the intrinsic fluorescence without affecting the lifetimes in a proportional way. This finding may be taken as an indication that the quenching of the tryptophan fluorescence induced by the binding of iron has both static and dynamic components.


Flavones and flavonols exert cytotoxic effects on a human oesophageal adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis.
Dietary flavonoids have been shown to exert specific cytotoxicity towards some cancer cells, but the precise molecular mechanisms are still not completely understood. In our study, cytotoxic effects of structurally related flavones and flavonols on a human oesophageal adenocarcinoma cell line (OE33) were compared, and the molecular mechanisms responsible for their cytotoxic effects were explored. The results of MTT assay showed that flavones (luteolin, apigenin, chrysin) and flavonols (quercetin, kaempferol, myricetin) were all able to induce cytotoxicity in OE33 cells in a dose- and time-dependent manner, and the cytotoxic potency of these compounds was in the order of quercetin>luteolin>chrysin>kaempferol>apigenin>myricetin. Flow cytometry and DNA fragmentation analysis indicated that the cytotoxicity induced by flavones and flavonols was mediated by G2/M cell cycle arrest and apoptosis. Furthermore, the expression of genes related to cell cycle arrest and apoptosis was assessed by oligonucleotide microarray, real-time RT-PCR and Western blot. It was found that the treatment of OE33 cells with flavones and flavonols caused G2/M arrest through up-regulation of GADD45beta and 14-3-3sigma and down-regulation of cyclin B1 at the mRNA and protein levels, and induced p53-independent mitochondrial-mediated apoptosis through up-regulation of PIG3 and cleavage of caspase-9 and caspase-3. The results of western blot analysis further showed that increases of p63 and p73 protein translation or stability might be contribute to the regulation of GADD45beta, 14-3-3sigma, cyclin B1 and PIG3.


Correlating notch signaling with thymocyte maturation.
The Notch receptor and its ligands are involved in many developmental processes. They are highly expressed in the thymus and have been implicated in the CD4 versus CD8 lineage decision. We identified the constitutively active intracellular fragment of murine Notch-1 as capable of rendering thymomas resistant to glucocorticoid-induced apoptosis. This effect was confirmed in other T cell lines and in CD4+ CD8+ DP thymocytes. Activation of the Notch signaling pathway also upregulated a number of other markers that, like steroid resistance, correlate with DP maturation into both the CD4 and CD8 lineages. These results suggest that Notch signaling is critically involved in the maturation of DP thymocytes into both CD4+ and CD8+ SP thymocytes.


Trs20 is required for TRAPP II assembly.
The modular TRAPP complexes act as nucleotide exchangers to activate the Golgi Ypt/Rab GTPases, Ypt1 and Ypt31/Ypt32. In yeast, TRAPP I acts at the cis-Golgi and its assembly and structure are well characterized. In contrast, TRAPP II acts at the trans-Golgi and is poorly understood. Especially puzzling is the role of Trs20, an essential TRAPP I/II subunit required neither for the assembly of TRAPP I nor for its Ypt1-exchange activity. Mutations in Sedlin, the human functional ortholog of Trs20, cause the cartilage-specific disorder SEDT. Here we show that Trs20 interacts with the TRAPP II-specific subunit Trs120. Furthermore, the Trs20-Trs120 interaction is required for assembly of TRAPP II and for its Ypt32-exchange activity. Finally, Trs20-D46Y, with a single-residue substitution equivalent to a SEDT-causing mutation in Sedlin, interacts with TRAPP I, but the resulting TRAPP complex cannot interact with Trs120 and TRAPP II cannot be assembled. These results indicate that Trs20 is crucial for assembly of TRAPP II, and the defective assembly caused by a SEDT-linked mutation suggests that this role is conserved.


Prefeeding Oromotor Stimulation Program for Improving Oromotor Function in Preterm Infants - A Randomized Controlled Trial.
To determine effect of Premature Infant Oral Motor Intervention program on oro-motor function and time to full independent wati spoon feeds in preterm infants. 30 preterm infants between 28-32 weeks of gestation on full gavage feeds of 150 mL/kg/day were randomized to receive either pre-feed oro-motor stimulation using Premature Infant Oral Motor Intervention (structured stimulation) or sham intervention (unstructured stimulation). Improvement in mean (SD) Neonatal Oro-Motor Assessment Scale (NOMAS) over 7 days from baseline was significantly higher in the study group infants as compared to control group (9.25 (1.73) vs 4.79 (1.52), P=0.001). Infants in the study group reached full independent wati spoon feeds significantly earlier than the infants in control group (4.0 (0.8) d; vs 6.64 (1.0) d; P=0.001). There was significant increase in weight gain after enrolment in infants in study group compared to those in control group. Oral stimulation program improves the oro-motor skills and growth velocity in 28-32 week preterm infants. There is decreased transition time from gavage to full independent feeds by mouth.


Is the renal vasodilatation induced by beta-adrenoceptor stimulants in the dog mediated through dopamine receptor?
In chloralose-anaesthetized dogs the renal vasodilator effect of isoprenaline is depressed by blockade of either dopamine or beta-adrenoceptors but the renal vasodilator effect of dopamine is depressed only by blockade of dopamine receptors. This suggests that the vasodilatation induced by beta-stimulants within the canine kidney is due in part to activation of dopamine receptors.


Markovian approaches to modeling intracellular reaction processes with molecular memory.
Many cellular processes are governed by stochastic reaction events. These events do not necessarily occur in single steps of individual molecules, and, conversely, each birth or death of a macromolecule (e.g., protein) could involve several small reaction steps, creating a memory between individual events and thus leading to nonmarkovian reaction kinetics. Characterizing this kinetics is challenging. Here, we develop a systematic approach for a general reaction network with arbitrary intrinsic waiting-time distributions, which includes the stationary generalized chemical-master equation (sgCME), the stationary generalized Fokker-Planck equation, and the generalized linear-noise approximation. The first formulation converts a nonmarkovian issue into a markovian one by introducing effective transition rates (that explicitly decode the effect of molecular memory) for the reactions in an equivalent reaction network with the same substrates but without molecular memory. Nonmarkovian features of the reaction kinetics can be revealed by solving the sgCME. The latter 2 formulations can be used in the fast evaluation of fluctuations. These formulations can have broad applications, and, in particular, they may help us discover new biological knowledge underlying memory effects. When they are applied to generalized stochastic models of gene-expression regulation, we find that molecular memory is in effect equivalent to a feedback and can induce bimodality, fine-tune the expression noise, and induce switch.


Studies on sphingomyelinase activity in cultured cells and leucocytes.
Using both [3H]ceramide-sphingomyelin and [14C]methyl choline-sphingomyelin as substrate, enzyme activity was determined in skin fibroblasts, cultured amniotic fluid cells and leucocytes. Sphingomyelinase activities of fibroblasts from two patients with Niemann-Pick disease were about 1% of the mean control values (22.9 nmol/h/mg protein and 65.6 nmol/h/mg protein, with [3H]sphingomyelin and [14C]sphingomyelin respectively). Leucocyte sphingomyelinase activity is much lower than that of cultured cells. Optimum sphingomyelinase activity of cultured cells is at pH 5.0 and the apparent Km values are 58 mumol/1 and about 200 mumol/1 for [3H]sphingomyelin and [14C]sphingomyelin respectively. These properties are similar to those for residual sphingomyelinase activity in Niemann-Pick fibroblasts.


Ultrasound as pre-treatment for drying of pineapple.
Dehydration of fruits is an alternative to reduce post-harvest loss of fruits and also a process to produce dried fruits, which can be directly consumed or become part of foodstuffs like cakes, pastries and many others. The effect of ultrasonic pre-treatment and ultrasound-assisted osmotic dehydration, before air-drying, on dehydration of pineapple (Ananas comosus) was investigated. This study allowed estimating the water diffusivity in the air-drying process for pineapples submitted to ultrasound. Results showed that the water diffusivity increased after application of ultrasound and that the overall drying time was reduced by 8% (over 1h of air-drying time). During the ultrasonic treatment in distilled water the pineapples lost sugar (23.2% in 30 min), so in this condition the ultrasonic pre-treatment can be an interesting process to produce dried fruits with low sugar content. Results showed that the water loss increased with increasing soluble solids content of the osmotic solution and that the ultrasound-assisted osmotic dehydration incorporated more sugar than conventional osmotic dehydration. The water effective diffusivity of the pineapples during the air-drying process was influenced by the pre-treatment, increasing the water effective diffusivity when ultrasound was applied.


The radiology of gastrointestinal Burkitt's lymphoma in children.
Four cases of Burkitt's lymphoma limited to the abdominal region are described. The sites of involvement included the duodenum, caecum, ascending colon, jejunum and ovaries. One case presented with an intussusception. The distribution of lesions in this series differs from the African cases described by Burkitt and from the small series reported from North America.


The role of ideology in creating new nations in the USSR and strengthening a centralised state-The example of the Dungans in central Asia.
This paper describes the role of the totalitarian state in changing ethnic identity. To solve the question of nationality, the Soviet Union drew upon the ideologies of ultra-radical theorists of the 19th century, whose goal was to change society by removing several major institutions - for example, through the liquidation of family or private property, in addition to creating a national group. Numerous paradoxes emerged when putting these initial theories into practice because they were full of internal contradictions. The example of the Dungans shows how the state created a new ethnic group, which it supported in every possible way, and then, in the next phase, it clearly persecuted this ethnic group. In the implementation of state interventions, it is clear that the main declared elements of ethnic identity are extremely volatile and their meaning varies considerably. Whereas earlier Soviet ideology sought to present the Dungans as a group vastly different from its ancestors in China, contemporary Chinese ideology emphasises the similarities between the two groups.


Celiac artery aneurysm: diagnosis by color Doppler sonography and three-dimensional CT angiography.
Celiac artery aneurysms are rare vascular lesions that are sometimes found incidentally during abdominal imaging. Their significance is in their potential to rupture, which can lead to death. We present the case of a celiac artery aneurysm diagnosed by color Doppler sonography and 3-dimensional CT angiography.


Intrinsic Heart Regeneration in Adult Vertebrates May be Strictly Limited to Low-Metabolic Ectotherms.
The heart has a high-metabolic rate, and its "around-the-clock" vital role to sustain life sets it apart in a regenerative setting from other organs and appendages. The landscape of vertebrate species known to perform intrinsic heart regeneration is strongly biased toward ectotherms-for example, fish, salamanders, and embryonic/neonatal ectothermic mammals. It is hypothesized that intrinsic heart regeneration is exclusively limited to the low-metabolic hearts of ectotherms. The biomedical field of regenerative medicine seeks to devise biologically inspired regenerative therapies to diseased human hearts. Falsification of the ectothermy dependency for heart regeneration hypothesis may be a crucial prerequisite to meaningfully seek inspiration in established ectothermic regenerative animal models. Otherwise, engineering approaches to construct artificial heart components may constitute a more viable path toward regenerative therapies. A more strict definition of regenerative phenomena is generated and several testable sub-hypotheses and experimental avenues are put forward to elucidate the link between heart regeneration and metabolism. Also see the video abstract here https://youtu.be/fZcanaOT5z8.


Constitutive cholesterol-dependent endocytosis of melanocortin-4 receptor (MC4R) is essential to maintain receptor responsiveness to α-melanocyte-stimulating hormone (α-MSH).
Melanocortin-4 receptor (MC4R) is a G-protein-coupled receptor expressed in the hypothalamus where it controls feeding behavior. MC4R cycles constitutively and is internalized at the same rate in the presence or absence of stimulation by the agonist, melanocyte-stimulating hormone (α-MSH). This is different from other G-protein-coupled receptors, such as β(2)-adrenergic receptor (β(2)AR), which internalizes more rapidly in response to agonist stimulation. Here, it is found that in immortalized neuronal Neuro2A cells expressing exogenous receptors, constitutive endocytosis of MC4R and agonist-dependent internalization of β(2)AR were equally sensitive to clathrin depletion. Inhibition of MC4R endocytosis by clathrin depletion decreased the number of receptors at the cell surface that were responsive to the agonist, α-MSH, by 75%. Mild membrane cholesterol depletion also inhibited constitutive endocytosis of MC4R by ∼5-fold, while not affecting recycling of MC4R or agonist-dependent internalization of β(2)AR. Reduced cholesterol did not change the MC4R dose-response curve to α-MSH, but it decreased the amount of cAMP generated per receptor number indicating that a population of MC4R at the cell surface becomes nonfunctional. The loss of MC4R function increased over time (25-50%) and was partially reversed by mutations at putative phosphorylation sites (T312A and S329A). This was reproduced in hypothalamic GT1-7 cells expressing endogenous MC4R. The data indicate that constitutive endocytosis of MC4R is clathrin- and cholesterol-dependent. MC4R endocytosis is required to maintain MC4R responsiveness to α-MSH by constantly eliminating from the plasma membrane a pool of receptors modified at Thr-312 and Ser-329 that have to be cycled to the endosomal compartment to regain function.


Time for Taste-A Review of the Early Cerebral Processing of Gustatory Perception.
The first successfully recorded event-related potential (ERP) for taste, one of our basic senses, was published nearly half a century ago. Despite this large time span, surprisingly little is known about the early neural processing of taste perception. Here, we are providing a comprehensive and critical overview of over four decades of research, with a focus on the temporal dimension of cerebral taste processing in healthy humans. For this purpose, we review studies using techniques that permit a high temporal resolution, namely, electroencephalography and magnetoencephalography, ERP, and event-related magnetic fields (ERF). Our current knowledge of taste ERP is interpreted in the context of our understanding of other, nonchemical senses. Gaps in the existing literature are identified and discussed. Finally, we suggest directions for future investigations using gustatory ERP/ERF.


The sensitization potential of some perfume ingredients tested using a modified draize procedure.
A modified Draize procedure was used to test 23 natural and 46 synthetic perfume ingredients for their potential to induce allergic contact dermatitis in guinea pigs. Fifty-three ingredients did not induce sensitization. Two synthetic ingredients showed a strong sensitization potential and 14 ingredients, 7 natural and 7 synthetic, showed a weak sensitization potential. The findings indicate that there is little risk of sensitization in man to most of these perfume ingredients.


Pulmonary macrophage growth factor.
Pulmonary macrophage growth factor (MCF) can be purified from the "used" serum-free medium of cultures of mouse lung cells by concentration and dialysis over a 30,000-dalton Amicon ultrafilter and subjecting the retentate to isoelectric focusing. This yields a protein fraction with an isolelectric point of pH 4.2, which contains all the MGF activity. Upon electrophoresis of this fraction in analytical gels, one large and four small bands could be visualized. All bands were biologically active. This same "heterogenous" fraction ran as one band (mol wt 68,000) in SDS analytical gel electrophoresis, suggesting the ordered aggregation of this monomer. This was confirmed by reelectrophoresis of the first (and largest) band demonstrating the same 5-banded pattern as the initial material.


Possible role of the stomach in enteroinsular axis in rats.
To elucidate the possible role of the stomach in enteroinsular axis, rats had both an inflow gastric cannula and an outflow diversion cannula and a duodenal inflow cannula. The effects of intragastric infusion of glucose (1 mL in 10% solution) or mannitol (1 mL in 10% solution) on blood and plasma insulin responses to subsequent intraduodenal glucose (1.5 g/kg in 10% solution) or amino acids (1.0 g/kg in 10% solution) infusion were investigated. Blood glucose and plasma insulin responses to intraduodenal amino acids were not altered by intragastric infusion of glucose or mannitol. However, higher blood glucose and lower plasma insulin responses to intraduodenal glucose were observed in the rat with intragastric infusion of glucose or mannitol compared with controls (intragastric infusion of distilled water). This phenomenon was abolished in the rat with preadministration of phentolamine. These results suggest that intragastric tonicity may suppress glucose-induced insulin secretion, probably through the alpha-adrenergic mechanism in the rat.


The influence of low fat, low lactose diet on diarrhoea during pelvic radiotherapy.
In a prospective clinical trial 143 women undergoing pelvic radiotherapy for gynaecological malignancies, were randomized to receive either a low-fat, low-lactose diet (intervention group) or a regular diet (control group) in order to evaluate the possible impact of diet therapy on radiation induced diarrhoea, nausea and vomiting. The daily number and consistency of stools, use of antidiarrhoeal agents, nausea and vomiting were recorded before radiotherapy was begun (week 0), in the last week of therapy (week 6) and 6 weeks after the end of therapy (week 12). The intervention group used half the amount of antidiarrhoeal agents in week 6, than used by the control group (mean 0.6 tablets per day versus 1.1, p < 0.01). 14 patients (23%) in the intervention group reported diarrhoea, versus 32 (48%) in the control group (p < 0.01). In week 12 there were no differences in the use of antidiarrhoeal agents and the prevalence of diarrhoea between the groups.


What have we learned from C5 palsy - A short communication.
A study group on C5 palsy retrospectively reviewed 1001 cervical operations at their institutions in order to understand the incidence, prognosticators, pathogenesis, and outcome of C5 palsy after cervical operations. Three studies are summarized. C5 palsy was higher after posterior versus anterior operations. C4-C5 foraminotomy and age were the strongest predictors of C5 palsy after posterior surgeries and anterior cervical decompression-fusion, respectively. Among patients undergoing C4-C5 posterior laminoforaminotomy with instrumented fusion, cord shift on postoperative imaging was thought to be implicated in the pathogenesis of C5 palsy. Among affected patients, 81.4% recovered. Median time to resolution of C5 palsy was between 6 months to 1 year.


Retropharyngeal lymph node metastasis in nasopharyngeal carcinoma detected by magnetic resonance imaging : prognostic value and staging categories.
Retropharyngeal lymph node (RLN) metastasis was not included in the current American Joint Committee on Cancer (AJCC) staging system (6th edition) for nasopharyngeal carcinoma (NPC). The object of the current study was to investigate the prognostic value and staging categories of RLN metastasis in NPC detected by magnetic resonance imaging (MRI). All 924 consecutive patients with newly diagnosed NPC were examined with MRI before treatment with definitive intent radiotherapy. The incidence of RLN metastasis was 73.5%. On multivariate analysis, RLN metastasis was found to be an independent prognostic factor for distant metastasis-free survival (DMFS) in all patients (P = .040). In patients with N0 disease, significant differences were observed between patients with and those without RLN metastasis after adjusting for T classification (P = .046). With regard to laterality, no significant differences were observed in DMFS between patients with unilateral and bilateral RLN metastasis in N0 disease (P = .734). No significant difference in the hazards ratios for either DMFS or disease-free survival (DFS) was found between patients with N0 disease with RLN metastasis and patients with N1 disease (P = .092 and P = .149, respectively). When RLN was classified as N1 disease, there was a better segregation of different N classifications in terms of DFS and DMFS curves, whereas the difference in hazards ratios for N0 and N1 disease was more obvious in DMFS (from 0.461 vs 0.785 to 0.317 vs 0.690). The results of the current MRI-based study demonstrate that RLN metastasis affects the DMFS rates of NPC. The authors propose that RLN metastasis be classified as N1 disease, regardless of its laterality.


Exploring the polymorphism, conformational dynamics and function of amyloidogenic peptides and proteins by temperature and pressure modulation.
Our understanding of amyloid structures and the mechanisms by which disease-associated peptides and proteins self-assemble into these fibrillar aggregates, has advanced considerably in recent years. It is also established that amyloid fibrils are generally polymorphic. The molecular structures of the aggregation intermediates and the causes of molecular and structural polymorphism are less understood, however. Such information is mandatory to explain the pathological diversity of amyloid diseases. What is also clear is that not only protein mutations, but also the physiological milieu, i.e. pH, cosolutes, crowding and surface interactions, have an impact on fibril formation. In this minireview, we focus on the effect of the less explored physical parameters temperature and pressure on the fibrillization propensity of proteins and how these variables can be used to reveal additional mechanistic information about intermediate states of fibril formation and molecular and structural polymorphism. Generally, amyloids are very stable and can resist harsh environmental conditions, such as extreme pH, high temperature and high pressure, and can hence serve as valuable functional amyloid. As an example, we discuss the effect of temperature and pressure on the catalytic activity of peptide amyloid fibrils that exhibit enzymatic activity.


Arsenic accumulation and speciation in rice grown in arsanilic acid-elevated paddy soil.
P-arsanilic acid (AsA) is a emerging but less concerned contaminant used in animal feeding operations, for it can be degraded to more toxic metabolites after being excreted by animals. Rice is the staple food in many parts of the world, and also more efficient in accumulating arsenic (As) compared to other cereals. However, the uptake and transformation of AsA by rice is unclear. This study aimed to evaluate the potential risk of using AsA as a feed additive and using the AsA contaminated animal manure as a fertilizer. Five rice cultivars were grown in soil containing 100mg AsA/kg soil, after harvest, As species and their concentrations in different tissues were determined. Total As concentration of the hybrid rice cultivar was more than conventional rice cultivars for whole rice plant. For rice organs, the highest As concentration was found in roots. AsA could be absorbed by rice, partly degraded and converted to arsenite, monomethylarsonic acid, dimethylarsinic acid, arsenate. The number of As species and their concentrations in each cultivar were related to their genotypes. The soil containing 100mg AsA/kg or more is unsuitable for growing rice. The use of AsA and the disposal of animal manure requires detailed attention.


The Use of Oral Disease-Modifying Therapies in Multiple Sclerosis.
Three oral disease-modifying drugs-fingolimod, teriflunomide, and dimethyl fumarate (DMF)-are available for treatment of relapsing forms of multiple sclerosis (MS). All three agents were approved in the last decade, primarily on the basis of a moderate to substantial reduction in the occurrence of MS relapses and central nervous system lesion formation detected by MRI. In the trials leading to approval, the first oral disease-modifying drug, fingolimod, reduced the annualized relapse rate (ARR) from 0.40 in placebo-treated patients to 0.18 (FREEDOMS) and from 0.33 in patients treated with interferon β1a intramuscularly to 0.16 (TRANSFORMS). Teriflunomide, approved on the basis of the two placebo-controlled trials TEMSO and TOWER, demonstrated a reduction in the ARR from 0.54 to 0.37 and from 0.50 to 0.32 respectively. The latest oral MS medication, approved in 2014, is DMF, which had been used in a different formulation for treatment of psoriasis for decades. In the 2-year DEFINE study, the proportion of patients with a relapse was reduced to 27 %, compared with 46 % in placebo arm, whereas in the CONFIRM trial, the ARR was reduced from 0.40 (placebo) to 0.22 in the DMF-treated group of patients. In this review, we will elucidate the mechanisms of action of these three medications and compare their efficacy, safety, and tolerability as a practical guideline for their use. We will further discuss effects other than relapse reduction these small molecules may exert, including potential activities within the central nervous system, and briefly summarize emerging data on new oral MS drugs in clinical development.


Detection of JC virus DNA in peripheral lymphocytes from patients with and without progressive multifocal leukoencephalopathy.
Progressive multifocal leukoencephalopathy (PML) results from lytic infection of oligodendrocytes by JC virus (JCV). Although JCV has been identified in mononuclear cells in bone marrow and hematogenous dissemination of the virus to the central nervous system has been suspected, JCV has never been clearly demonstrated in the peripheral circulation. Using polymerase chain reaction technology, we examined peripheral lymphocytes of 19 patients with brain biopsy-proven PML for the JCV genome. Two non-PML control groups, consisting of 26 patients seopositive for human immunodeficiency virus type 1 (HIV-1) and 30 immunocompetent patients with Parkinson's disease, were also examined for the presence of the JCV genome in lymphocytes. Cerebrospinal fluid from 10 patients with PML was examined for the presence of the JCV genome as well. The JCV genome was detected in the lymphocytes of 89% (17) of the patients with PML, 38% (10) of the HIV-1-seropositive patients without PML, and none of the patients with Parkinson's disease. Sequencing of the JCV regulatory region from the lymphocytes of three patients revealed the prototype MAD-1 strain of JCV in one patient with PML, a MAD-4 strain in a second patient with PML, and a slightly modified MAD-4 strain in an HIV-1-positive patient without PML. Only 3 of 10 patients with PML who had JCV detected in lymphocytes had the JCV genome in their cerebrospinal fluid. These results demonstrate that the JCV genome can be found in circulating lymphocytes from patients with PML and suggest that lymphocytes are an important vector for hematogenous dissemination of JCV to the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)


Trends of cardiovascular health in Asian American individuals: A national health and nutrition examination survey study.
Oversampling of Asian American individuals in the National Health and Nutrition Examination Survey (NHANES) provides a unique opportunity to assess the population-level cardiovascular health (CVH) in the fastest-growing racial group in the US. The Life's Essential 8 (LE8) score and its components were calculated in self-reported Asian American individuals ≥20 years of age and free of cardiovascular disease in the NHANES cycles from 2011-March 2020. Multivariable adjusted linear and logistic regression models were used for analysis. Among 2,059 Asian American individuals, the weighted mean LE8 score was 69.1 (0.4) with US-born [69.0 (0.8)] and foreign-born individuals [69.1 (0.4)] having similar CVH. From 2011 to March 2020, CVH in the overall population [69.7 (0.8) to 68.1 (0.8); Ptrend: 0.009] and foreign-born individuals [69.7 (0.8) to 67.7 (0.8); Ptrend: 0.005] declined. Decreasing trends were noted in the body mass index score irrespective of stratification and in the blood pressure scores in the overall population and foreign-born Asian American individuals. Compared with US-born individuals, the odds of ideal levels of smoking [ORadj:<5 years: 2.23 (95%CI: 1.45-3.44); 5-15 years: 1.97 (95%CI: 1.27-3.05); 15-30 years: 1.61 (95%CI: 1.11-2.34); ≥30 years: 1.69(95%CI:1.20-2.36)] and diet [ORadj: <5 years: 1.87 (95%CI: 1.26-2.79); 5-15 years: 2.00 (95%CI: 1.38-2.89); 15-30 years: 1.74 (95%CI: 1.14-2.68)] were higher in foreign-born individuals. Foreign-born individuals had lower odds of ideal physical activity levels [ORadj: 5-15 years: 0.55 (95%CI: 0.39-0.79); 15-30 years: 0.68 (95%CI: 0.49-0.95)] and ideal cholesterol levels [ORadj: 5-15 years: 0.59 (95%CI: 0.42-0.82); 15-30 years: 0.54 (95%CI :0.38-0.76); ≥30 years: 0.52 (95%CI: 0.38-0.76)]. The CVH in Asian American individuals declined from 2011 to March 2020. The odds of ideal CVH decreased with increasing duration of stay in the US, with foreign-born individuals residing in the US for ≥30 years having ∼28% lower odds of ideal CVH compared with US-born individuals.


In vitro and in vivo analysis of a rat bipotential O-2A progenitor cell line containing the temperature-sensitive mutant gene of the SV40 large T antigen.
Primary cultures from neonatal optic nerve contain pluripotential O-2A progenitor cells that are capable of differentiating into oligodendrocytes, type-2 astrocytes or adult O-2A progenitors (O-2Aadult). Since primary optic nerve cultures contain a mixture of glial cell types of which only a small number are O-2A progenitors, experiments on cell lineage and differentiation carried out using these cultures are both intrinsically limited and difficult to interpret. Ideally, cells from a clonal cell population would provide the optimal starting material for biological studies. In this paper we describe the creation of an O-2A progenitor cell line using a retrovirus carrying a temperature-sensitive mutant SV40 large T antigen gene. This cell line has provided sufficient numbers of cells to allow analysis of their in vitro properties and their behaviour following transplantation into an in vivo environment. At the non-permissive temperature (39 degrees C), these cells differentiate into oligodendrocytes and type-2 astrocytes in a similar fashion to O-2A progenitor cells from primary cultures (O-2Aprim). When grown in media containing platelet-derived growth factor and basic fibroblast growth factor, the cell numbers can be expanded in culture without differentiating, consistent with the behaviour of O-2Aprim progenitor cells. By exploiting this property, it has been possible to culture large numbers of O-2A progenitors for in vivo analysis. In this study we have shown that transplantation of this O-2A cell line into glia-free areas in adult rat spinal cord results in differentiation of a proportion of cells into oligodendrocytes which are capable of myelinating axons. Furthermore, differentiation of O-2A cells into astrocytes was also observed, indicating that the bipotentiality of these cells in vitro can also be demonstrated in vivo.


Involvement of serum factor(s) adsorbed to the dish in the response of cycloheximide-pretreated BP-A31 cells to serum pulses.
The mitogenic effect of serum pulses, observed previously in quiescent BP-A31 cells, is an artifact due to adsorption of (unknown) serum mitogens to the culture dish; the continuous presence of growth factors is necessary for these cells to traverse the G1 phase. When pretreated with cycloheximide (CH) during the last 8-24 h of quiescence, the BP-A31 cells are particularly sensitive to the adsorbed serum mitogens, as well as to low concentrations of fetal calf serum (less than 0.25%) and to basic fibroblast growth factor. In contrast, the mitogenic activity of insulin was not influenced by CH pretreatment. The expression of the "competence genes" c-myc and JE was only transiently elevated in quiescent BP-A31 cells during CH exposure and did not correlate with the enhancement of the cells' sensitivity to mitogens.