[Post-menopausal hypertension: Detecting, treating, accompany, prevent].
Menopause is associated with a significant increase in arterial and metabolic risk. Systolic hypertension is common in post-menopausal women. Measurement of blood pressure should be repeated systematically at each visit. Ambulatory blood pressure measurements should be encouraged, especially to detect nocturnal hypertension and to prevent more efficiently women at risk. Self-testing of hypertension by home blood pressure should be encouraged at menopause. Antihypertensive treatment should be initiated after ambulatory blood pressure monitoring in association with reinforced lifestyle. Furthermore, global level of cardiovascular risk should take into account before starting antihypertensive treatment. There are no women specificities in the choice of the initial treatment except thiazide diuretics which should be preferred in osteoporotic women. In hypertensive women and with disabling climacteric symptoms under 60 and within 10 years after the onset of menopause, post-menopausal hormone therapy can be offered in absence of arterial or venous contraindications. A preliminary discussion between gynecologist, cardiologist and general practionner is necessary before deciding to treat a post-menopausal women for her climacteric symptoms. A clear information on the benefit-risk balance of post-menopausal hormone therapy should be given to the women. The information should be recorded in the medical file. Cooperation between cardiologists, gynecologists and general practionners should be promoted in France, to optimize the care pathways in these women at risk and to improve medical practices.


Effect of undernutrition on DNA and RNA synthesis in subcellular fractions from different regions of the developing rat brain.
The effect of undernutrition on the incorporation of [methyl-3H] thymidine into DNA and of 5-[3H] uridine into RNA of cerebral hemispheres, cerebellum, and brain stem was studied in vivo and in vitro in rats. The labeling of DNA from nuclei and mitochondria and of RNA from nuclei, mitochondria, microsomes, and soluble fractions, was also measured in vitro. The results demonstrate that nucleic acid synthesis is impaired and delayed during undernutrition. Specific effects were observed for the different brain regions and subcellular fractions: at 10 days nuclear and mitochondrial DNA and RNA synthesis was impaired, whereas at 30 days only the mitochondrial nucleic acid synthesis was affected. The delay of DNA and RNA labeling, caused by undernutrition, was most evident in the cerebellum, probably due to its intense cell proliferation during postnatal development. The specific sensitivity of mitochondria as compared to other subcellular fractions, may by due to the intense biogenesis and/or turnover of nucleic acids in brain mitochondria not only during postnatal development, but also in the adult animal.


Interfacial behaviour of sodium stearoyllactylate (SSL) as an oil-in-water pickering emulsion stabiliser.
The ability of a food ingredient, sodium stearoyllactylate (SSL), to stabilise oil-in-water (O/W) emulsions against coalescence was investigated, and closely linked to its capacity to act as a Pickering stabiliser. Results showed that emulsion stability could be achieved with a relatively low SSL concentration (≥0.1 wt%), and cryogenic-scanning electron microscopy (cryo-SEM) visualisation of emulsion structure revealed the presence of colloidal SSL aggregates adsorbed at the oil-water interface. Surface properties of SSL could be modified by altering the size of these aggregates in water; a faster decrease in surface tension was observed when SSL dispersions were subjected to high pressure homogenisation (HPH). The rate of SSL adsorption at the sunflower oil-water interface also increased after HPH, and a higher interfacial tension (IFT) was observed with increasing SSL concentration. Differential scanning calorimetry (DSC) enabled a comparison of the thermal behaviour of SSL in aqueous dispersions with SSL-stabilised O/W emulsions. SSL melting enthalpy depended on emulsion interfacial area and the corresponding DSC data was used to determine the amount of SSL adsorbed at the oil-water interface. An idealised theoretical interfacial coverage calculation based on Pickering emulsion theory was in general agreement with the mass of SSL adsorbed as predicted by DSC.


Characterizing white matter connectivity in Alzheimer's disease and mild cognitive impairment: An automated fiber quantification analysis with two independent datasets.
Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive dementia. Diffusion tensor imaging (DTI) has been widely used to show structural integrity and delineate white matter (WM) degeneration in AD. The automated fiber quantification (AFQ) method is a fully automated approach that can rapidly and reliably identify major WM fiber tracts and evaluate WM properties. The main aim of this study was to assess WM integrity and abnormities in a cohort of patients with amnestic mild cognitive impairment (aMCI) and AD as well as normal controls (NCs). For this purpose, we first used AFQ to identify 20 major WM tracts and assessed WM integrity and abnormalities in a cohort of 120 subjects (39 NCs, 34 aMCI patients and 47 AD patients) in a discovery dataset and 122 subjects (43 NCs, 37 aMCI patients and 42 AD patients) in a replicated dataset. Pointwise differences along WM tracts were identified in the discovery dataset and simultaneously confirmed in the replicated dataset. Next, we investigated the utility of DTI measures along WM tracts as features to distinguish patients with AD from NCs via multilevel cross validation using a support vector machine. Correlation analysis revealed the identified microstructural WM alterations and classification output to be highly associated with cognitive ability in the patient groups, suggesting that they may be a robust biomarker of AD. This systematic study provides a pipeline to examine WM integrity and its potential clinical application in AD and may be useful for studying other neurological and psychiatric disorders.


In knee OA, physical therapy reduced pain and improved function more than glucocorticoid injections at 1 year.
Deyle GD, Allen CS, Allison SC, et al. Physical therapy versus glucocorticoid injection for osteoarthritis of the knee. N Engl J Med. 2020;382:1420-9. 32268027.


Ochronotic arthropathy. A comparative scanning electron microscopic and light microscopic study of the synovium in ochronosis.
The synovium in two cases of ochronosis was studied by scanning electron microscopy and light microscopy. Several features not yet described were seen by scanning electron microscopic examination and correlated with the light microscopic findings. This is the first report in the English language literature comparing scanning electron microscopic findings with the light microscopic findings in ochronosis.


Antibiotic Duration, but Not Abscess Size, Impacts Clinical Cure of Limited Skin and Soft Tissue Infection After Incision and Drainage.
Antibiotics are frequently prescribed following incision and drainage of cutaneous abscesses. In subgroup analyses from a recent clinical trial, we observed higher likelihood of cure with antibiotic courses beyond 5 or 7 days (up to 10). Among this cohort, for abscesses ≤5 cm, size did not modify the antibiotic effect.


[Fetal genitourinary anomalies Perinatal and postnatal management with imaging techniques].
Improvements in ultrasound technology and the appropriate timing of antenatal ultrasound has led to refined prenatal diagnosis and enhanced accuracy of diagnosis of fetal renal anomalies and makes it possible to treat obstructive and/or refluxing uropathies before the onset of clinical symptoms. The third trimester renal sonography is the most important to detect hydronephrosis amenable to treatment.Classically, the prenatal diagnosis of hydronephrosis, unilateral renal agenesis, or MDKD initiates postnatal investigations, including sonography, voiding cystourethrography (VCUG), and isotopic renography. The exact degree of renal pelvic dilatation that requires full postnatal investigation is still not entirely resolved. Most authors accept the upper limit of 7 mm for the AP diameter of the renal pelvis. The US examination should be performed after the physiological dehydration period, namely 3-5 days after birth, in an urgent case on the 1st day. A meticulous ultrasound examination performed by a physician who is familiar with the renal abnormalities shows the whole extent of underlying pathology. The role of MR urography in the work-up of renal anomalies, particularly of hydronephrosis, is currently being investigated. Due to the close developmental relationship of the urinary and genital tracts, malformations frequently occur in both of these systems. Therefore in all patients, especially in girls with renal anomalies (unilateral renal agenesis, multicystic dysplastic kidney disease), the internal genitalia need to be evaluated.


New Framework for Computing a General Local Self-Diffusion Coefficient Using Statistical Mechanics.
Widely applicable, modified Green-Kubo expressions for the local diffusion coefficient (Dl) are obtained using linear response theory. In contrast to past definitions in use, these expressions are statistical mechanical results. Molecular simulations of systems with anisotropic diffusion and an inhomogeneous density profile confirm the validity of the results. Diffusion coefficients determined from different expressions in terms of currents and velocity correlations agree in the limit of large systems. Furthermore, they apply to arbitrarily small local regions, making them readily applicable to nanoscale and inhomogeneous systems where knowledge of Dl is important.


Towards effective outbreak detection: a qualitative study to identify factors affecting nurses' early warning surveillance practice in Solomon Islands.
Intelligence generated by a surveillance system is dependent on the quality of data that are collected. We investigated the knowledge, attitudes and practices of nurses responsible for outbreak early warning surveillance data collection in Solomon Islands to identify factors that influence their ability to perform surveillance-related tasks with rigour. We interviewed 12 purposively selected surveillance nurses and conducted inductive analysis on resulting data. Interviewees were knowledgeable and willing to contribute to the surveillance system. Constraining factors included the perception that surveillance was less important than patient care and could be 'deferred' during busy periods and wide variability in the application of case definitions. Motivating factors were frequent in-clinic training, formal recognition for good performance, incentives and designation of a focal point. Nurses held mixed views about the effect of mobile technologies on surveillance practice. This study identified several challenges to consistent and accurate data collection and reporting. Engagement of different parts of the health system, including human resources and health facilities' management, is needed to address these challenges.


Kinetics and mechanism of G-quadruplex formation and conformational switch in a G-quadruplex of PS2.M induced by Pb²⁺.
DNA sequences with guanine repeats can form G-quartets that adopt G-quadruplex structures in the presence of specific metal ions. Using circular dichroism (CD) and ultraviolet-visible (UV-Vis) spectroscopy, we determined the spectral characteristics and the overall conformation of a G-quadruplex of PS2.M with an oligonucleotide sequence, d(GTG(3)TAG(3)CG(3)TTG(2)). UV-melting curves demonstrate that the Pb(2+)-induced G-quadruplex formed unimolecularly and the highest melting temperature (T(m)) is 72°C. The analysis of the UV titration results reveals that the binding stoichiometry of Pb(2+) ions to PS2.M is two, suggesting that the Pb(2+) ions coordinate between adjacent G-quartets. Binding of ions to G-rich DNA is a complex multiple-pathway process, which is strongly affected by the type of the cations. Kinetic studies suggest that the Pb(2+)-induced folding of PS2.M to G-quadruplex probably proceeds through a three-step pathway involving two intermediates. Structural transition occurs after adding Pb(NO(3))(2) to the Na(+)- or K(+)-induced G-quadruplexes, which may be attributed to the replacement of Na(+) or K(+) by Pb(2+) ions and the generation of a more compact Pb(2+)-PS2.M structure. Comparison of the relaxation times shows that the Na(+)→Pb(2+) exchange is more facile than the K(+)→Pb(2+) exchange process, and the mechanisms for these processes are proposed.


Misexpression Approaches for the Manipulation of Flower Development.
The generation of dominant gain-of-function mutants through activation tagging is a forward genetic approach that can be applied to study the mechanisms of flower development, complementing the screening of loss-of-function mutants. In addition, the functions of genes of interest can be further analyzed through reverse genetics. A commonly used method is gene overexpression, where ectopic expression can result in an opposite phenotype to that caused by a loss-of-function mutation. When overexpression is detrimental, the misexpression of a gene using tissue-specific promoters can be useful to study spatial-specific function. As flower development is a multistep process, it can be advantageous to control gene expression, or its protein product activity, in a temporal and/or spatial manner. This has been made possible through several inducible promoter systems as well as inducible proteins by constructing chimeric fusions between the ligand-binding domain of the glucocorticoid receptor (GR) and the protein of interest. The recently introduced CRISPR-Cas9-based platform provides a new way of bioengineering transcriptional regulators in plants. By fusing a catalytically inactive dCas9 with functional activation or repression domains, the CRISPR-Cas9 module can achieve transcriptional activation or repression of endogenous genes. All these methods allow us to genetically manipulate gene expression during flower development. In this chapter, we describe methods to produce the expression constructs, method of screening, and more general applications of the techniques.


Ignoring overdispersion in hierarchical loglinear models: Possible problems and solutions.
Poisson data frequently exhibit overdispersion; and, for univariate models, many options exist to circumvent this problem. Nonetheless, in complex scenarios, for example, in longitudinal studies, accounting for overdispersion is a more challenging task. Recently, Molenberghs et.al, presented a model that accounts for overdispersion by combining two sets of random effects. However, introducing a new set of random effects implies additional distributional assumptions for intrinsically unobservable variables, which has not been considered before. Using the combined model as a framework, we explored the impact of ignoring overdispersion in complex longitudinal settings via simulations. Furthermore, we evaluated the effect of misspecifying the random-effects distribution on both the combined model and the classical Poisson hierarchical model. Our results indicate that even though inferences may be affected by ignored overdispersion, the combined model is a promising tool in this scenario.


A cohort study on the association between psychotropics and hip fracture in Korean elderly women.
To test the hypothesis that the intake of psychotropics may increase the risk of hip fracture, a cohort study was conducted upon elderly Korean women. The Korean Elderly Pharmacoepidemiology Cohort was constructed from members of the Korea Medical Insurance Corporation over 65 yr of age who were living in Busan Metropolitan City in 1993. Study participants (n=6,043) were female respondents to a self-administered question survey. Information on the intake of psychotropics was obtained from the drug prescription database, which contained all psychotropic prescriptions during any hospital admission over the two-year period between January 1, 1993 and December 31, 1994. The cohort follow-up has been conducted with information on hip fracture being collected from the Korea Medical Insurance Corporation medical treatment claims database over the four year period between January 1, 1993 and December 31, 1996. Three hundred and three subjects had received 745 psychotropics prescriptions and 56 cases of hip fracture were found. After adjusting for age, body mass index, and drinking history, it was found that the intake of psychotropics significantly increased the risk of hip fracture (adjusted odds ratio, 4.24; 95% confidence interval, 1.89-9.52). This study suggests that the intake of psychotropics might be an important risk factor for hip fracture in elderly Korean women.


Underestimation of COVID-19 cases in Japan: an analysis of RT-PCR testing for COVID-19 among 47 prefectures in Japan.
Under the unique Japanese policy to restrict reverse transcriptase-polymerase chain reaction (RT-PCR) testing against severe acute respiratory syndrome coronavirus 2, a nationwide number of its confirmed cases and mortality remains to be low. Yet the information is lacking on geographical differences of these measures and their associated factors. Evaluation of prefecture-based geographical differences and associated predictors for the incidence and number of RT-PCR tests for coronavirus disease 2019 (COVID-19). Cross-sectional study using regression and correlation analysis. We retrieved domestic laboratory-confirmed cases, deaths and the number of RT-PCR testing for COVID-19 from 15 January to 6 April 2020 in 47 prefectures in Japan, using publicly available data by the Ministry of Health, Labour and Welfare. We did descriptive analyses of these three measures and identified significant predictors for the incidence and RT-PCR testing through multiple regression analyses and correlates with the number of deaths through correlation analysis. The median prefectural-level incidence and number of RT-PCR testing per 100 000 population were 1.14 and 38.6, respectively. Multiple regression analyses revealed that significant predictors for the incidence were prefectural-level population (P < 0.001) and the number of RT-PCR testing (P = 0.03); and those for RT-PCR testing were the incidence (P = 0.025), available beds (P = 0.045) and cluster infections (P = 0.034). Considering bidirectional association between the incidence and RT-PCR testing, there may have been an underdiagnosed population for the infection. The restraint policy for RT-PCR testing should be revisited to meet the increasing demand under the COVID-19 epidemic.


Correlation between octanol/water and liposome/water distribution coefficients and drug absorption of a set of pharmacologically active compounds.
Absorption and consequent therapeutic action are key issues in the development of new drugs by the pharmaceutical industry. In this sense, different models can be used to simulate biological membranes to predict the absorption of a drug. This work compared the octanol/water and the liposome/water models. The parameters used to relate the two models were the distribution coefficients between liposomes and water and octanol and water and the fraction of drug orally absorbed. For this study, 66 drugs were collected from literature sources and divided into four groups according to charge and ionization degree: neutral; positively charged; negatively charged; and partially ionized/zwitterionic. The results show a satisfactory linear correlation between the octanol and liposome systems for the neutral (R²= 0.9324) and partially ionized compounds (R²= 0.9367), contrary to the positive (R²= 0.4684) and negatively charged compounds (R²= 0.1487). In the case of neutral drugs, results were similar in both models because of the high fraction orally absorbed. However, for the charged drugs (positively, negatively, and partially ionized/zwitterionic), the liposomal model has a more-appropriate correlation with absorption than the octanol model. These results show that the neutral compounds only interact with membranes through hydrophobic bonds, whereas charged drugs favor electrostatic interactions established with the liposomes. With this work, we concluded that liposomes may be a more-appropriate biomembrane model than octanol for charged compounds.


Stenting of coronary bifurcation lesions: a literature and technical review.
Newer generation drug-eluting stents have improved outcomes in various subsets of coronary lesions including bifurcation lesions. This article reviews the current literature on various issues in bifurcation percutaneous coronary intervention (PCI). Generally, the provisional approach of placing one stent in the main vessel is the preferred first-line treatment for most bifurcation lesions. However, some lesions require 2-stenting. It is unknown whether 2nd-generation DES have improved outcomes with 2-stenting. The use of fractional flow reserve (FFR) for the assessment of functional significance of the jailed side branch can help avoid unnecessary stenting in complex lesions. Skilled techniques in every step of the 2-stenting process and meticulous use of imaging techniques including IVUS or OCT are warranted to obtain optimal angiographic and clinical results. Dedicated bifurcation stents are feasible treatment options and may change future concepts in bifurcation PCI, although larger trials with control groups are required in order to widely apply these techniques into daily routine practice.


Correction: The impact of reducing dietary aflatoxin exposure on child linear growth: a cluster randomized controlled trial in Kenya.
[This corrects the article DOI: 10.1136/bmjgh-2018-000983.].


Interactions between climate warming, herbicides, and eutrophication in the aquatic food web.
Understanding the interactive effects of multiple environmental stressors on biological communities is crucial for effective environmental management and biodiversity conservation. Here, we present the results of an outdoor mesocosm experiment examining how an aquatic food web responds to the individual and combined effects of climate warming, heat waves, nutrient enrichment, and herbicide exposure. To assess ecosystem functioning, we examined energy flow, using stable isotope analysis integrated with the bioenergetics food web approach to quantify energy fluxes among trophic levels. Our results revealed that the combined effects of these stressors altered the pattern of energy fluxes within the food web. Under warming conditions, there was an increase in energy flux from producers and primary consumers to secondary consumers. However, we did not observe a significant increase in energy flux in primary consumers, potentially due to enhanced top-down control. Nutrient enrichment increased energy flux from producers to higher trophic levels while simultaneously decreasing detrital energy flux. Herbicide exposure did not significantly affect herbivory energy flux but did reduce detritivory energy flux, particularly from detritus to primary consumers. The interactive effects we observed were primarily antagonistic or additive, although we also detected reversed and synergistic effects. The responses to multiple stressors varied across different energy flow pathways, leading to an asymmetric response. Furthermore, our results also revealed significant differences in the effects of constant warming and heat waves, either alone or in combination with water pollution. The asymmetric response of energy flow pathways and the prevalence of antagonistic effects present significant challenges for ecosystem restoration. Together, our findings provide novel and clear evidence of the complex mechanisms by which the coexistence of stressors can differently affect the pathways of energy flux across trophic levels in aquatic ecosystems. Regulatory strategies for ecosystems should comprehensively consider responses at multi-trophic levels using a network perspective, especially in the face of combinations of global and local stressors.


Remote ischemic conditioning for kidney protection: A meta-analysis.
Results from randomized controlled trials (RCTs) concerning kidney effect of remote ischemic conditioning (RIC) are inconsistent. We searched for relevant studies in Medline, Embase, the Cochrane Library, Google Scholar and Chinese database (SinoMed), as well as relevant references from their inception to November 2015. We performed a systematic review and meta-analysis of all eligible RCTs of RIC with kidney events. We included 37 RCTs from 2007 to 2015 involving 8168 patients. Pooled analyses of all RCTs showed RIC significantly reduced the incidence of investigator-defined acute kidney injury (AKI) compared with control groups (RR 0.84, 95% CI 0.73-0.96, P = .009) (I(2) = 25%). However, the difference was not significant when only RIFLE (Risk, Injury, Failure, Loss, End Stage), AKIN (Acute Kidney Injury Network), or KDIGO (Kidney Disease Improving Global Outcomes) criteria were applied to the definition of AKI (RR 0.87, 95% CI 0.74-1.02, P = .08) (I(2) = 22%). In subgroup analysis, RIC showed a significant benefit on reducing investigator-defined AKI in patients following percutaneous coronary intervention (RR 0.64, 95% CI 0.46-0.87), but not after cardiac surgery (RR 0.93, 95% CI 0.82-1.06). There was no difference for changes in the incidence of renal replacement therapy, estimated glomerular filtration rate or serum creatinine. RIC might be beneficial for the prevention of investigator-defined AKI; however, the effect is likely small. Moreover, due to lack of an effect on use of renal replacement therapy, estimated glomerular filtration rate, RIFLE, AKIN, or KDIGO-defined AKI, and serum creatinine, the evidence for RIC is not robust. Finally, recent large-scale RCTs of RIC focusing on patient-centered outcomes do not support the wider application of RIC.


UTIs and two new antibiotics in the elderly.
Of the new antimicrobials available for the treatment of urinary tract infections (UTIs), aztreonam and imipenem/cilastatin represent two structurally unique, but distinct, classes of beta-lactam antibiotics. Aztreonam has a directed spectrum of activity covering gram-negative bacilli usually associated with UTIs. In comparative clinical trials of patients with complicated UTIs, aztreonam is well-tolerated and is as effective as conventional control regimens, including aminoglycosides. On the other hand, the antimicrobial spectrum of imipenem/cilastatin includes not only gram-negative bacilli but also gram-positive cocci and anaerobes. As such, this broad-spectrum antibiotic should be reserved for the treatment of mixed infections.


Complete genome sequence of Lactobacillus acetotolerans RIB 9124 (NBRC 13120) isolated from putrefied (hiochi) Japanese sake.
Lactobacillus acetotolerans RIB 9124 (NBRC 13120) was isolated from putrefied (hiochi) Japanese sake. Here we report the complete genome sequence of this organism. This paper is the first report demonstrating the fully sequenced and completely annotated genome of a L. acetotolerans strain.


PD-L1 Immunohistochemistry Comparability and Their Correlation with Clinical Characteristics in NSCLC.
PD-L1 expression is an important predictive factor of response to therapy with immune checkpoint inhibitors (ICIs). This study was designed to retrospectively analyze the concordance of PD-L1 measurements using three different assays (Dako22C3, Dako28-8, and SP142) in NSCLC patients and to find possible predictors of high PD-L1 expression. Data of 144 patients with histologically confirmed NSCLC and available PD-L1 measurements treated at the Taoyuan General Hospital from 2018 to 2019 were retrospectively reviewed in the study. Patients' characteristics, including age, sex, clinical stage (T, N, and M) of NSCLC (AJCC, 8th edition), and EGFR/ALK alterations, were analyzed for association with PD-L1 expression. Measurements of PD-L1 expression levels with Dako22C3 and Dako28-8 were comparable while SP142 showed lower levels of PD-L1 expression. The overall agreement between Dako22C3 and Dako28-8 was 82.2% and 91.6% for both 1% and 50% TPS cut-offs, respectively. The above findings were confirmed by Cohen's kappa. In addition, we found that PD-L1 expression was significantly associated with advanced N stage but not with T and M stages. Dako22C3 and Dako28-8 showed comparable results in assessing PD-L1 levels. Future prospective studies are needed to validate these findings. N stage may be a good predictor for PD-L1 expression.


Prospective study of transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: an Asian cooperative study between Japan and Korea.
To evaluate the safety and efficacy of transcatheter arterial chemoembolization used for the treatment of unresectable hepatocellular carcinoma (HCC) with an Asian cooperative prospective study between Japan and Korea. Patients with unresectable HCC unsuitable for curative treatment or with no prior therapy for HCC were enrolled. The patients underwent transcatheter arterial chemoembolization with emulsion of Lipiodol and anthracycline agent, followed by embolization with gelatin sponge particles, which was repeated on an as-needed basis. The primary endpoint was 2-year survival rate, and the secondary endpoints were adverse events and response rate. The 2-year survival rate of 99 patients was 75.0% (95% confidence interval, 65.2%-82.8%). The median time-to-progression was 7.8 months, and the median overall survival period was 3.1 years. Of 99 patients, 42 (42%) achieved a complete response, and 31 (31%) had a partial response. The response rate was 73% using modified Response Evaluation Criteria in Solid Tumors. The grade 3-4 toxicities included increased alanine aminotransferase level in 36%, increased aspartate aminotransferase level in 35%, thrombocytopenia in 12%, and abdominal pain in 4% of patients. All other toxicities were generally transient. Asian transcatheter arterial chemoembolization demonstrated sufficient safety and reasonable efficacy as a standard treatment for unresectable HCC. These results could be useful as reference data for future trials of transcatheter arterial chemoembolization.


Adult Neuroplasticity: Working One Eye Gives an Advantage to the Other.
A recent study has found that viewing one image with one eye and a lower-contrast image with the other eye as briefly as a few minutes alters the subsequent balance of activity between the two eyes revealing adult neuroplasticity.


Neuroanatomical anomalies in autoimmune mice.
The cerebral cortex was examined for signs of pathology in the NZB, BXSB, and MRL autoimmune strains of mice, crosses among these strains, and control mice. Previously, we reported that 20% of NZB mice had ectopic collections of neurons in layer I of the cortex. In this study we replicated this finding in the NZB, and extended it to the BXSB strain, and BXSB/NZB and MRL/NZB hybrids. The MRL strain, however, did not have a large number of individuals with brain anomalies. Thus, a number of autoimmune mice strains and hybrids develop brain anomalies, although at least one autoimmune strain does not. We suggest that in certain autoimmune strains maternal autoantibodies cross the placenta and damage the developing fetal brain, and that these strains may be useful experimental models for studying the development of brain anomalies seen in the dyslexic human.


Nervous impulse propagation along peripheral and central fibres in patients with chronic renal failure.
In thirty-one patients with chronic renal failure we measured the conduction velocities in the proximal regions of median and peroneal nerves and concurrently evaluated the propagation properties of an afferent input along the related central (spinal and supraspinal) sensory pathways. In 26 of these patients the sensorimotor velocities of median, peroneal and sural nerves were also calculated. Lower limb peripheral conduction was more frequently abnormal than that of upper limb, the distal segment being involved to a greater degree. Since central propagation was more impaired during lower (11 out of 27 cases) than during upper limb (1 out of 27 patients) stimulation and the intracranial propagation time was rarely prolonged, a predominantly spinal defective impulse conduction was hypothesized. Neurophysiological data seem to confirm that early stages of defective neural conduction in CRF are in agreement with the model of central-peripheral distal axonopathy. However, an abnormal impulse propagation was also rarely found in proximal districts of peripheral fibres as well as along the intracranial sensory pathways. Correlations were found between some of the impulse propagation properties and the duration of CRF or dialysis. Serum parathyroid hormone, creatinine and BUN levels were correlated with some peripheral and central conduction indexes.


Odor detection in rats with 3-methylindole-induced reduction of sensory input.
Rats were tested on odor-detection tasks after treatment with 400 mg/kg of 3-methyl-indole. As revealed by anterograde transport of horseradish peroxidase from the olfactory epithelium to the olfactory bulb glomeruli, treatment produced a severe (>97%) loss in sensory input relative to untreated controls. In almost all cases, only glomeruli in a restricted ventromedial segment of the bulb contained control levels of reaction product. In Experiment 1, five of nine experimental rats were anosmic or severely hyposmic, but the remaining four rats were able to detect amyl acetate vapor. In Experiment 2, four of seven experimental rats were anosmic, but the remaining three were able to detect each of four different odors. Among all experimental rats, those that were anosmic had significantly fewer glomeruli with dense anterograde transport than did those that could smell. Among rats that could smell, performance accuracy was related to the number of glomeruli with reaction product.


Clinical electives in China: trends, experiences, barriers.
In recent decades, China has quickly transformed itself into a modern, urban, technological and economic powerhouse. China's medical education system is internationalizing and attracting a considerable number of foreign students seeking medical degrees and other clinical experience, such as observerships, in China. Although the majority of international students in China come from low- and middle income countries, China's rise towards the world's largest medical education system also offers new opportunities for stronger cooperation with European countries. Both sides maintain tight economic ties, and China's rise is also attracting more and more medial students for short-term clinical electives from the German-speaking countries. Such clinical electives are pertinent to global health education in a globalized world, and allow students to immerse in foreign healthcare systems for a short period. Notably, reasons for (and barriers to) electives in China are largely unexplored. To address this gap, we reviewed 4 popular German elective report databases and extrapolated key characteristics of electives in China undertaken by German-speaking medical student. N = 40 elective testimonies were analyzed with regard to students' elective experience, elective barriers and organizational aspects. The vast majority of students reported an elective in Shanghai (n = 29, 72.50%). More than 70% of students applied directly to an elective program for foreign students, whereas less than 25% applied through a bilateral exchange program. Frequently cited positive aspects of electives in China included the Chinese hospitality and the regular high-quality teaching in English for international students. Notably, almost half of student reported some kind of difficulties during their elective (n = 18, 45%), including language barriers (n = 6), administrative issues (n = 5) and visa problems (n = 2). Our data suggest that international electives in China were overall well-rated by German-speaking students. The combination of structured clinical elective programs with English supervision and the opportunity to learn more about the Chinese culture apparently attracted said students in the past 2 decades.


Importance of bidirectional arterial flow in dialysis fistula construction.
The normal direction of blood flow in end of cephalic vein to side of radial artery arteriovenous dialysis fistulas in the wrist was antegrade in the proximal arterial limb and retrograde through the distal arterial limb. There were no instances of arterial insufficiency in the hand due to a steal phenomenon. These findings support the surgical construction of end of vein to side of artery fistulas.


Occurrence, distribution and removal of organic micro-pollutants in a low saline water body.
A low saline backwater canal, mainly utilized for domestic and agricultural purposes, has been analyzed for the possible presence of organic micropollutants (OMP) and their potential removal was explored by multilayered microfiltration membranes. The qualitative as well as quantitative analysis were carried out for a span of one year using the technique of liquid chromatography connected with high resolution mass spectrometry (LC-Q-TOF-MS). The identification of the formally unknown compounds was initially done using non-target analysis based on the mass accuracy, isotopic pattern and MS/MS spectral interpretation. Results of the non target screening revealed the presence of 11 OMPs. Five of these OMPs were confirmed using standards; these include chlorophene (CHP), oxybenzone (OXY), N, N-diethyl-meta-toluamide (DEET), N, N-diethyl-benzamide (DEB) and dibutyl phthalate (DBP). Among the confirmed OMPs, the highest concentration was observed for DBP (244.61 ng l-1). The most frequently observed OMP in the study area was DBP while the least was DEB which is an insect repellent as well as a degradation product of DEET. The ecological risk associated with the target compounds has also been analyzed by calculating the risk quotient (RQ) and the results revealed that at the detected levels, these compounds are capable of causing low to medium risk. Low pressure (<0.3 bar) filtrations of the compounds were attempted using microfiltration (MF) and, poly(ethyleneimine)/poly(styrene sulfonate) (PEI/PSS) multi-layered MF membrane for spiked ultrapure water and also for natural water from the back-water canal. The batch mode illustrates nearly complete removal of CHP and OXY in spiked solutions and a good removal efficiency from natural water. The effect of coexisting ions and surfactants in feed is also illustrated. The high efficiency of the removal of both CHP and OXY, in such a complex medium highlights the potential application of the present method for the removal of similar OMPs in natural waters.


Positive association between ambient temperature and salmonellosis notifications in New Zealand, 1965-2006.
To investigate the temporal relationship between the monthly count of salmonellosis notifications and the monthly average temperature in New Zealand during the period 1965-2006. A negative binomial regression model was used to analyse monthly average ambient temperature and salmonellosis notifications in New Zealand between 1965 and 2006. A 1°C increase in monthly average ambient temperature was associated with a 15% increase in salmonellosis notifications within the same month (IRR 1.15; 95% CI 1.07 - 1.24). The positive association found in this study between temperature and salmonellosis notifications in New Zealand is consistent with the results of studies conducted in other countries. New Zealand is projected to experience an increase in temperature due to climate change. Therefore, all other things being equal, climate change could increase salmonellosis notifications in New Zealand. This association between temperature and salmonellosis should be considered when developing public health plans and climate change adaptation policies. Strategically, existing food safety programs to prevent salmonellosis could be intensified during warmer periods. As the association was strongest within the same month, focusing on improving food handling and storage during this time period may assist in climate change adaptation in New Zealand.


N3-methyl-mafosfamide as a chemically stable, alternative prodrug of mafosfamide.
The presence of an alkyl substituent at N3 in the oxazaphosphorine ring stabilizes N-substituted 4-(alkylthio)cyclophosphamides from spontaneous decomposition. Based on this finding, N3-methyl-mafosfamide was synthesized and examined as a chemically stable, biooxidative prodrug of mafosfamide. This prodrug was stable in aqueous buffer (pH 7.4, 37 degrees C) and underwent N-demethylation in a time dependent manner when incubated with rat hepatic microsomes. N3-Methyl-mafosfamide was 10-fold more cytotoxic in vitro than cyclophosphamide against mouse embryo Balb/c 3T3 cells (LC50 = 3.6 microM). Preliminary in vivo antitumor evaluation against L1210 leukemia in mice showed that this prodrug was active [Increase of life span (ILS) > 29%].


Suppression of canine myeloid cells by soluble factors from cultured canine tumor cells.
Cancer profoundly affects immunity and causes immunosuppression that contributes to tumor escape, metastases and resistance to therapy. The mechanisms by which cancer cells influence immune cells are not fully known but both innate and adaptive immune cells can be altered by cancer. Myeloid cells are innate immune cells that comprise the mononuclear phagocytic system (MPS) and include monocytes, macrophages, dendritic cells (DCs) and their progenitors. Myeloid cells play important roles in both the promotion and regulation of immune responses. Dysregulated myeloid cells are increasingly being recognized as contributing to cancer-related immunosuppression. This study investigated whether soluble factors produced by canine tumor cells inhibited canine myeloid cell function. These studies investigated the utility of using the canine DH82 cell line for assessment of canine myeloid responses to tumor-derived soluble factors (TDSFs). Phenotypic comparisons to canine bone marrow-derived DCs (BM-DCs) and bone marrow-derived macrophages (BM-MΦs) were performed and expression of myeloid cell markers CD11b, CD11c, CD80, and major histocompatibility complex (MHC) class II were evaluated by flow cytometry. Phenotypic and functional changes of DC populations were then determined following exposure to tumor-conditioned media (TCM) from canine osteosarcoma, melanoma and mammary carcinoma cell lines. We found that the canine BM-DCs and the DH82 cell line shared similar CD11b, CD11c and MHC II expression and morphologic characteristics that were distinct from canine BM-MΦs. Myeloid cells exposed to TDSFs showed decreased expression of MHC class II and CD80, had reduced phagocytic activity and suppressed the proliferation of responder immune cells. These results show that soluble factors secreted from canine tumor cells suppress the activation and function of canine myeloid cells. Our results suggest that, similar to humans, dysregulated myeloid cells may contribute to immunosuppression in dogs with cancer.


Detection of antibodies against pre-S1 proteins in sera of patients with hepatitis B virus (HBV) infection.
Pre-S1 (large S) proteins are components of the envelope of HBV. The presence of pre-S1 proteins is correlated with viral replication. To test sera of patients with HBV infection for the presence of antibodies against pre-S1 proteins (anti-pre-S1), an E. coli extract containing a pre-S fusion protein covering the greater part of the pre-S1 region was subjected to Western blotting and probed with sera of patients. Anti-pre-S1 was present in the sera of all 4 patients with acute self-limited HBV infection and in the sera of 3 patients with a fulminant course. The antibodies could not be detected in the sera of 6 patients with acute HBV infection entering chronicity, in the sera from 10 HBsAg carriers or in the sera of 25 patients with chronic liver disease, positive for HBsAg and antibodies to hepatitis Delta virus. In an additional study, anti-pre-S1 could not be found in 11 sera from 12 patients with previous HBV infection, positive for anti-HBs and anti-HBc. Antibodies to pre-S1 proteins appear at the early stage of acute resolving HBV infection and seem to play a role in the elimination of the virus. The antibodies are absent in the sera of patients with acute HBV infection entering a chronic course and in the sera of chronic HBsAg-carriers.


Redox regulation and pro-oxidant reactions in the physiology of circadian systems.
Rhythms of approximately 24 h are pervasive in most organisms and are known as circadian. There is a molecular circadian clock in each cell sustained by a feedback system of interconnected "clock" genes and transcription factors. In mammals, the timing system is formed by a central pacemaker, the suprachiasmatic nucleus, in coordination with a collection of peripheral oscillators. Recently, an extensive interconnection has been recognized between the molecular circadian clock and the set of biochemical pathways that underlie the bioenergetics of the cell. A principle regulator of metabolic networks is the flow of electrons between electron donors and acceptors. The concomitant reduction and oxidation (redox) reactions directly influence the balance between anabolic and catabolic processes. This review summarizes and discusses recent findings concerning the mutual and dynamic interactions between the molecular circadian clock, redox reactions, and redox signaling. The scope includes the regulatory role played by redox coenzymes (NAD(P)+/NAD(P)H, GSH/GSSG), reactive oxygen species (superoxide anion, hydrogen peroxide), antioxidants (melatonin), and physiological events that modulate the redox state (feeding condition, circadian rhythms) in determining the timing capacity of the molecular circadian clock. In addition, we discuss a purely metabolic circadian clock, which is based on the redox enzymes known as peroxiredoxins and is present in mammalian red blood cells and in other biological systems. Both the timing system and the metabolic network are key to a better understanding of widespread pathological conditions such as the metabolic syndrome, obesity, and diabetes.


Patterns of bacterial translocation in experimental biliary obstruction.
Biliary obstruction is associated with impaired intestinal barrier function and translocation of enteric bacteria to the systemic circulation. Traditional live culture techniques may overlook translocation of dead bacterial fragments that stimulate the inflammatory response. The aim of this study was to estimate the extent and pattern of bacterial translocation in experimental biliary obstruction. Thirty 9-week-old male Wistar rats were randomized to undergo bile duct ligation (BDL, n = 20) or sham operation (n = 10). Seven days after operation, each animal received 1 ml of (111)indium-oxyquinolone-labeled Escherichia coli p.o. Samples of liver, spleen, mesenteric lymph nodes, and lung were harvested 4 h later and analyzed for live bacteria and (111)indium activity. There was significantly more live bacterial translocation detected in BDL animals than in sham-operated animals (P = 0.00008, chi(2)). Labeled bacterial fragments were detected in all locations sampled in all animals. Sham-operated animals had significantly more labeled bacterial fragments detected in the liver (P = 0.0001) and the spleen (P = 0.03) than the BDL animals. The mean total bacterial survival in the BDL group was 30 +/- 13% and 0% in the sham operated group. These results demonstrate that non-viable bacterial fragments are present in sterile extra-intestinal sites in normal animals and that translocation of live bacteria is markedly increased in experimental biliary obstruction. These results also suggest that failure of bacterial killing is an important factor facilitating bacterial translocation in the presence of established biliary obstruction.


What Are the Dry Eye Questionnaires Available in the Scientific Literature Used for? A Scoping Review.
Dry eye disease (DED) is a frequent chronic ophthalmic condition. Its diagnosis includes tests and patient reported outcomes (PRO) questionnaires. Although many PRO dry eye questionnaires (PRO-DEQs) are available, they differ greatly from each other and not all have been validated. The purpose of this study was to retrieve the PRO-DEQs present in the scientific literature by performing a descriptive analysis of them and identifying those with known validity and reliability characteristics and to perform a descriptive analysis of the geographic area, year of publication, and characteristics of the target population of the clinical studies that have used validated PRO-DEQs. Scoping review of the literature. Searches were conducted in PubMed to retrieve PRO-DEQs published up to July 2018 and written in English, French, Italian or Spanish. One thousand six hundred two records were identified and 973 were included in the final analysis. Of these, 56 provided information on the design and validation of PRO-DEQs and 49 PRO-DEQs were identified. Twenty-two PRO-DEQs were validated (17 original and 5 modified) and 27 had no associated design, validity, and reliability studies. Most of the validated PRO-DEQs were designed in English, the number of items varies from 1 to 57, the dimensions are generally not specified, and they are self-administered. The greatest use of validated PRO-DEQs in clinical studies has been in Asia since 2010, with the Ocular Surface Disease Index being the most used. These questionnaires have been used mostly in adults, retired professionals, and people with visual diseases to diagnose DED. This study aims to encourage the use of validated PRO-DEQs to guarantee the quality of the results obtained and the comparability and replicability among studies.


Dementia and use of psychotropic medication in non-'Elderly Mentally Infirm' nursing homes in South East England.
There is concern about inappropriate use of psychotropic medication in nursing homes in the UK. Older people with advanced dementia, who might need such medication, are supposed to be admitted to specialist 'Elderly Mentally Infirm' homes. To estimate the prevalence of dementia and psychotropic medication use in UK non-Elderly Mentally Infirm homes. a) Probability sample of non-elderly mentally infirm places in nursing-homes in South-East England then b) two-stage survey of a probability sample of residents in these places Non-Elderly Mentally Infirm nursing homes for older people in SE England. Residents registered non-Elderly Mentally Infirm homes. Assessment using mini mental state examination for cognitive impairment, the Behave-AD for behavioural problems and the Cornell Scale for depression. Mini mental state examination scores were validated against independent psychiatric assessment in a sub-sample of residents. We gathered medication data from prescription sheets. Of the 445 residents 74% assessed had probable clinical dementia. Of all the residents 38% had severe cognitive impairment, with a three-fold higher rate of behavioural disturbance than others. Psychotropic medication was strongly associated with cognitive impairment. Antipsychotic drugs were prescribed for only 15% of all residents. If nearly three-quarters of non-Elderly Mentally Infirm nursing home residents have dementia, many with behavioural disturbance, then dementia care is not a 'specialist' area of nursing home care. This study offers no support for the hypothesis that use of antipsychotic drugs in nursing homes is excessive. Questions are raised about policy, staffing and training in nursing homes.


Network Reconstruction as a Novel High-Level Marker of Functional Neuronal Viability.
Neuronal viability is essential for the maintenance of neuronal networks. Already slight noxious modifications, for example, the selective interruption of interneurons' function, which enhances the excitatory drive inside a network, may already be harmful for the overall network. To monitor neuronal viability on the network level, we implemented a network reconstruction approach that infers the effective connectivity of cultured neurons from live-cell fluorescence microscopy recordings. Neuronal spiking is reported by the fast calcium sensor Fluo8-AM using a relatively high sampling rate (27.33 Hz) to detect fast events such as action potential-evoked rises in intracellular calcium. Spiking records are then subjected to a machine learning-based set of algorithms that reconstruct the neuronal network. Then, the topology of the neuronal network can be analyzed via various parameters, such as the modularity, the centrality, or the characteristic path length. In summary, these parameters describe the network and how it is influenced by experimental modulations, for example, hypoxia, nutrient deficiency, co-culture models, or application of drugs and other factors.


Structural basis for CDK6 activation by a virus-encoded cyclin.
Cyclin from herpesvirus saimiri (Vcyclin) preferentially forms complexes with cyclin-dependent kinase 6 (CDK6) from primate host cells. These complexes show higher kinase activity than host cell CDKs in complex with cellular cyclins and are resistant to cyclin-dependent inhibitory proteins (CDKIs). The crystal structure of human CDK6--Vcyclin in an active state was determined to 3.1 A resolution to better understand the structural basis of CDK6 activation by viral cyclins. The unphosphorylated CDK6 in complex with Vcyclin has many features characteristic of cyclinA-activated, phosphorylated CDK2. There are, however, differences in the conformation at the tip of the T-loop and its interactions with Vcyclin. Residues in the N-terminal extension of Vcyclin wrap around the tip of the CDK6 T-loop and form a short beta-sheet with the T-loop backbone. These interactions lead to a 20% larger buried surface in the CDK6--Vcyclin interface than in the CDK2--cyclinA complex and are probably largely responsible for the specificity of Vcyclin for CDK6 and resistance of the complex to inhibition by INK-type CDKIs.


DNA polymorphisms and subpopulations in Babesia bovis.
Independent isolates of Babesia bovis differ by only a limited number of polypeptides, some of which may be important as host protective antigens. Avirulent derivatives of these parasites also differ from their virulent counterparts in only a few polypeptides. To identify genes encoding such polypeptides we have isolated cDNA clones corresponding to poly(A)+ RNAs that are expressed only in certain isolates. For this purpose a cDNA clone library was constructed from poly(A)+ RNA of the K-avirulent isolate (KA). These clones were screened by colony hybridization using [32P]cDNA complementary to poly(A)+ RNA from KA and from virulent isolates, in order to identify clones that selectively hybridize to one cDNA probe. Hybridization of DNA from three clones, designated pK4, pK5 and pK6 to poly(A)+ RNA from various isolates revealed different and complex patterns. The gene represented by clone pK5 appeared to be transcribed predominantly in avirulent parasites. Analysis of genomic DNA by the Southern procedure enabled each isolate to be distinguished and suggested that most isolates are comprised of a heterogeneous mixture of subpopulations. Analysis of genomic DNA from parasites obtained after passage of KA through the tick vector (Boophilus microplus) suggested that a subpopulation was being selected that more closely resembled KV than KA.


Properties of the membranes containing the particulate methane monooxygenase from Methylosinus trichosporium OB3b.
The particulate methane monooxygenase (pMMO) from Methylosinus trichosporium OB3b was partially purified and characterized by measuring the effects of reducing agents and additives, and the stability of pMMO was studied. Duroquinol was a suitable reducing agent, and pMMO was stabilized by bovine serum albumin (BSA). Among the additives, the copper (II) ion stimulated pMMO at low concentration and inhibited at high concentration. The optimum conditions for pMMO activity were as follows: 45 degrees C, pH 6.5 and 55 mM 3-morpholinopropanesulfonic acid (MOPS) buffer, and the rate of propene epoxide formation was 13.6 nmol min-1 mg-1 protein. ESR spectra indicate that the copper cluster in the membrane fraction is reduced by duroquinol and oxidized by dioxygen. The result suggests that the copper cluster is contained in the active site of pMMO.


Ventral Subiculum Stimulation Promotes Persistent Hyperactivity of Dopamine Neurons and Facilitates Behavioral Effects of Cocaine.
The ventral subiculum (vSUB) plays a key role in addiction, and identifying the neuronal circuits and synaptic mechanisms by which vSUB alters the excitability of dopamine neurons is a necessary step to understand the motor changes induced by cocaine. Here, we report that high-frequency stimulation of the vSUB (HFSvSUB) over-activates ventral tegmental area (VTA) dopamine neurons in vivo and triggers long-lasting modifications of synaptic transmission measured ex vivo. This potentiation is caused by NMDA-dependent plastic changes occurring in the bed nucleus of the stria terminalis (BNST). Finally, we report that the modification of the BNST-VTA neural circuits induced by HFSvSUB potentiates locomotor activity induced by a sub-threshold dose of cocaine. Our findings unravel a neuronal circuit encoding behavioral effects of cocaine in rats and highlight the importance of adaptive modifications in the BNST, a structure that influences motivated behavior as well as maladaptive behaviors associated with addiction.


Metal-Organic Framework Templated Synthesis of Ultrasmall Catalyst Loaded ZnO/ZnCo2O4 Hollow Spheres for Enhanced Gas Sensing Properties.
To achieve the rational design of nanostructures for superior gas sensors, the ultrasmall nanoparticles (NPs) loaded on ternary metal oxide (TMO) hollow spheres (HS) were synthesized by using the polystyrene (PS) sphere template and bimetallic metal-organic framework (BM-MOFs) mold. The zinc and cobalt based zeolite imidazole frameworks (BM-ZIFs) encapsulating ultrasmall Pd NPs (2-3 nm) were assembled on PS spheres at room temperature. After calcination at 450 °C, these nanoscale Pd particles were effectively infiltrated on the surface of ZnO/ZnCo2O4 HSs. In addition, the heterojunctions of Pd-ZnO, Pd-ZnCo2O4, and ZnO-ZnCo2O4 were formed on each phase. The synthesized Pd-ZnO/ZnCo2O4 HSs exhibited extremely high selectivity toward acetone gas with notable sensitivity (S = 69% to 5 ppm at 250 °C). The results demonstrate that MOF driven ultrasmall catalyst loaded TMO HSs were highly effective platform for high performance chemical gas sensors.


Menopause Is a Determinant of Breast Aromatase Expression and Its Associations With BMI, Inflammation, and Systemic Markers.
Most estrogen-dependent breast cancers occur after menopause, despite low levels of circulating estrogens. Breast expression of the estrogen-biosynthetic enzyme, aromatase, is proposed to drive breast cancer development after menopause. However, the effects of menopause on breast aromatase expression are unknown. To determine the effect of menopause on breast aromatase expression in relation to body mass index (BMI), white adipose tissue inflammation (WATi), and systemic markers of metabolic dysfunction. Cross-sectional study of 102 premenopausal (age 27 to 56) and 59 postmenopausal (age 45 to 74) women who underwent mastectomy for breast cancer treatment/prevention. Breast tissue was assessed for the presence of crown-like structures and the expression and activity of aromatase. Systemic markers examined include interleukin (IL)-6, insulin, glucose, leptin, adiponectin, high-sensitivity C-reactive protein (hsCRP), cholesterol, and triglycerides. Multivariable analysis was performed for aromatase messenger RNA (mRNA) in relation to BMI, WATi, and blood markers. Postmenopausal women had higher BMI and more breast WATi than premenopausal women. Fasting levels of IL-6, glucose, leptin, hsCRP, and homeostatic model assessment 2 insulin resistance score were higher in the postmenopausal group. BMI was positively correlated with aromatase mRNA in both pre- and postmenopausal women. Aromatase levels were higher in breast tissue of postmenopausal women, with levels being higher in inflamed vs noninflamed, independent of BMI. Adipocyte diameter and levels of leptin, hsCRP, adiponectin, and high-density lipoprotein cholesterol were more strongly correlated with aromatase in postmenopausal than premenopausal women. Elevated aromatase in the setting of adipose dysfunction provides a possible mechanism for the higher incidence of hormone-dependent breast cancer in obese women after menopause.


o-Carboranylalkoxy-1,3,5-Triazine Derivatives: Synthesis, Characterization, X-ray Structural Studies, and Biological Activity.
Morpholine- and bis(2-methoxyethyl)amine-substituted 1,3,5-triazine derivatives containing an alkoxy-o-carborane in the 6-position of the triazine ring were successfully synthesized. The molecular structures of the methoxy- and ethoxy-o-carboranyl-1,3,5-triazines were established by X-ray crystallography. In vitro studies showed that the methylene bridged morpholine- and bis(2-methoxyethyl)amine-substituted o-carboranyl-1,3,5-triazines accumulated to high levels in B16 melanoma cells and exhibited higher cytotoxicity than p-boronophenylalanine.


[Risk communication of policy advising scientific organisations: a thematic outline using the example of the German Federal Institute for Risk Assessment].
Regulatory scientific agencies, such as the German Federal Institute for Risk Assessment (BfR), are confronted with various challenges in their science-based risk communication. On the one hand, the communication of health risks is becoming increasingly complex and, accordingly, more demanding, which is why - among other things - questions about the health literacy of consumers and target group-oriented risk communication are gaining importance. On the other hand, the outputs of regulatory scientific agencies are increasingly exposed to politicisation and public criticism, which increases the relevance of questions about the objectivity and trustworthiness of expert opinion, risk assessment, and official statements, as well as the legitimacy and reputation of such organisations. This is further intensified by the emergence of new social media actors who produce and publish their own information and communication materials. The misinformation, disinformation and malinformation consequently distributed in this context represent another challenge, which is closely related to questions of adequate communication of health risks and of stabilising legitimacy, reputation and trustworthiness.The article discusses various approaches to solving these problems, including the optimization and visual enhancement of health information, enabling social participation as well as embedding these measures in strategic stakeholder and reputation management. The article concludes with a call for a more open discussion of inherent dilemmas.


Amplified inhibition of atherosclerotic plaque-induced platelet activation by glenzocimab with dual antiplatelet therapy.
Aspirin and platelet P2Y12 inhibitors, such as ticagrelor, suboptimally inhibit microvascular thrombosis during ST-elevation myocardial infarction. Glycoprotein (GP) IIb/IIIa inhibitors may further inhibit this but cause excessive bleeding. We investigated whether combination of glenzocimab, a GPVI inhibitor, with aspirin and ticagrelor provides additional antithrombotic effects, as GPVI has a critical role in atherothrombosis but minimal involvement in hemostasis. We investigated the effects of glenzocimab (monoclonal antibody Fab fragment) using blood from healthy donors and patients with acute coronary syndrome treated with aspirin and ticagrelor. Platelets were stimulated with multiple agonists, including atherosclerotic plaque, from patients undergoing carotid endarterectomy. Aspirin and ticagrelor partially inhibited atherosclerotic plaque-induced platelet aggregation by 48% compared with control (34 ± 3 vs 65 ± 4 U; P < .001). Plaque-induced platelet aggregation, adhesion, secretion, and activation were critically dependent on GPVI activation. Glenzocimab alone reduced plaque-induced aggregation by 75% compared with control (16 ± 4 vs 65 ± 4 U; P < .001) and by >95% when combined with aspirin and ticagrelor (3 ± 1 vs 65 ± 4 U; P < .001). Glenzocimab reduced platelet aggregation, adhesion, and thrombin generation when added to blood of aspirin- and ticagrelor-treated patients with acute coronary syndrome. Glenzocimab shared several antithrombotic effects with the GPIIb/IIIa inhibitor eptifibatide with less effect on general hemostasis assessed by rotational thromboelastometry. In a murine intravital model of ST-elevation myocardial infarction, genetic depletion of GPVI reduced microvascular thrombosis. Addition of glenzocimab to aspirin and ticagrelor enhances platelet inhibition via multiple mechanisms of atherothrombosis. Compared with a GPIIb/IIIa inhibitor, glenzocimab shares multiple antithrombotic effects, with less inhibition of mechanisms involved in general hemostasis.


LS-MolGen: Ligand-and-Structure Dual-Driven Deep Reinforcement Learning for Target-Specific Molecular Generation Improves Binding Affinity and Novelty.
Deep learning-based molecular generative models have garnered considerable interest in the field of de novo drug design. However, most extant models focus on either ligand-based or structure-based strategies, thereby failing to effectively harness the combined knowledge derived from both ligands and the structure of the binding target. In this article, we introduce LS-MolGen, a novel ligand and structure-integrated molecular generative model. This model synergistically combines representation learning, transfer learning, and reinforcement learning. The targeted knowledge assimilation from transfer learning, coupled with an advanced exploration strategy in reinforcement learning, empowers LS-MolGen to efficiently generate novel and high-affinity molecules efficiently. The comparable performance of our model is affirmed through multiple evaluations, including EGFR, DRD3, CDK2, AA2AR, ADRB2, and a dedicated case study of inhibitor design for SARS-CoV-2 Mpro. The results indicate that LS-MolGen performs better than other ligand-based or structure-based generative models in de novo designing promising compounds with novel scaffolds and high binding affinity. This proof-of-concept study signifies the potential of our ligand- and structure-based generative model, LS-MolGen, as a promising new tool for target-specific molecular generation and drug design.


Is there a correlation between membrane phospholipid metabolism and cell division?
The specificity of lipid/protein interactions in bacterial membranes is based on the diversity and variability of whole phospholipid molecules and of their polar and non-polar moieties. Of particular interest is the synthesis and turnover of anionic phospholipids facilitating variations in the phosphatidylglycerol (PG)/diphosphatidylglycerol (DPG) ratio in correlation with cell growth and division. Accumulation of DPG increases the anionic character of the cell membrane which is known to hinder the septation process. Consequently, the decrease in PG/DPG observed in stationary and in penicillin- or UV-inhibited non-dividing bacteria can be explained in this manner. On the other hand, the presence of lysophosphatidylethanolamine observed in the chain-forming mutant envC PM61 of Escherichia coli, and resulting from an anomaly in the deacylation-reacylation cycle, appears to be an indirect consequence rather than the cause of septation deficiency. Variations in the ratio of saturated/unsaturated fatty acids in phospholipids are also correlated with the physiological state of the cell. Hence, the levels of fluid and non-fluid phospholipids, their polymorphism and interaction with membrane proteins appear to be implicated in cell wall modelling. Future work will show how all these correlations function on the genetic and molecular levels.


Web and computer telephone-based diabetes education: lessons learnt from the development and use of a call center.
Diabetes is a chronic disease that causes a great deal of morbidity and mortality and poor quality of life for millions of people. Continuing care and patient education help maintain a good control of the disease and prevent complications. Since current available resources are limited to providing such an education during clinic or physician visits only, alternative ways to educate people about diabetes need to be identified. In this article we discuss the implementation of an automated diabetes education call center, we define the evaluation procedures we adopted, we summarize general guidelines for the implementation of the entire system based on our experience, and we present preliminary results about the use of the call center. We believe our system is providing "active health" since we deliver educational messages to patients at regular intervals and at the time of their choice without waiting for their actions.


Incorporating soil structure and root distribution into plant uptake models for radionuclides: toward a more physically based transfer model.
Most biosphere and contamination assessment models are based on uniform soil conditions, since single coefficients are used to describe the transfer of contaminants to the plant. Indeed, physical and chemical characteristics and root distribution are highly variable in the soil profile. These parameters have to be considered in the formulation of a more realistic soil-plant transfer model for naturally structured soils. The impact of monolith soil structure (repacked and structured) on Zn and Mn uptake by wheat was studied in a controlled tracer application (dye and radioactive) experiment. We used Brilliant Blue and Sulforhodamine B to dye flow lines and 65Zn and 54Mn to trace soil distribution and plant uptake of surface-applied particle-reactive contaminants. Spatial variation of the soil water content during irrigation and plant growth informs indirectly about tracer and root location in the soil profile. In the structured monolith, a till pan at a depth of 30 cm limited vertical water flow and root penetration into deeper soil layers and restricted tracers to the upper third of the monolith. In the repacked monolith, roots were observed at all depths and fingering flow allowed for the fast appearance of all tracers in the outflow. These differences between the two monoliths are reflected by significantly higher 54Mn and 65Zn uptake in wheat grown on the structured monolith. The higher uptake of Mn can be modelled on the basis of radionuclide and root distribution as a function of depth and using a combination of preferential flow and rooting. The considerably higher uptake of Zn requires transfer factors which account for variable biochemical uptake as a function of location.


On-site mercury-contaminated soils remediation by using thermal desorption technology.
In this study, the thermal desorption process was used to treat a mercury-contaminated soils in Taipei. A series of bench or pilot plant experiments were also performed the optimized operation condition. The results showed that the concentrations of residual mercury in all treated soils were below 2 mg/kg, some even lower than 0.05 mg/kg. The supernatant and exhaust gas stream of the condensed desorbed mercury vapor in the remediation site were also met with the effluent standard. The total fee was estimated to be US 3,557,000 dollars, when treating contaminated soil leading to a unit treatment cost of US 834 dollars/m3 of soil.


Hydrogen sulfide alleviates oxidative stress injury and reduces apoptosis induced by MPP+ in Parkinson's disease cell model.
Hydrogen sulfide (H2S), an endogenously produced gas, is a cardioprotective agent against neurotoxin-induced neurodegeneration in Parkinson's disease (PD). However, the roles of H2S in 1-methyl-4-phenylpyridinium ion (MPP+)-treated SH-SY5Y cells with the involvement of reactive oxygen species-nitric oxide (ROS-NO) signaling pathway in PD remain unclear. For this study, a MPP+-treated SH-SY5Y cell model was established to explore the regulatory role of H2S in oxidative stress injury and cell apoptosis. With the cell viability, apoptosis, cytotoxicity, levels of reactive oxygen species (ROS) and nitric oxide (NO), mitochondrial transmembrane potential (Δψm), contents of oxidative stress injury-related markers (glutathione, superoxide dismutase, malondialdehyde), levels of apoptosis-related proteins (Caspase 3, Bax, Bcl-2) and inducible nitric oxide synthase (iNOS) determined, this study demonstrated that NaHS (an H2S donor) treatment could alleviated the reduction of cell viability and cytotoxicity, cell apoptosis, Δψm loss, contents of ROS and NO, and oxidative stress injury induced by MPP+. The present study showed that H2S may protect SH-SY5Y cells from MPP+-induced injury in PD cell model via the inhibition of ROS-NO signaling pathway and provide insight into the potential of H2S for PD therapy.


[Application of the new serum markers in the research and development of innovative hepatitis B drugs].
Chronic hepatitis B (CHB) poses a serious threat to the health of the Chinese people. Viral markers are of great significance during antiviral therapy and research and development of innovative drugs. However, traditional serovirological markers such as HBV DNA and hepatitis B surface antigen (HBsAg) have certain limitations in assessing the efficacy of antiviral treatment and accurately reflecting the transcriptional activity of covalently closed circular DNA (cccDNA). In recent years, the role of new viral markers such as HBV RNA, hepatitis B core-related antigen (HBcrAg) and quantitative anti-hepatitis B core protein (qAnti-HBc) have attracted more and more attention because of accurately reflecting the transcription activity of cccDNA, determining the therapeutic effect and predicting the risk of recurrence after drug discontinuation. This article briefly introduces the application of new and old markers in various stages of antiviral therapy in CHB patients, and combines the application of new viral markers in the evaluation of drug efficacy, and expounds its possible role in the research and development of new antiviral therapy.


[General muscular rigidity syndrome (stiff man syndrome) in multiple sclerosis].
In a 57-year-old woman with a long history of multiple sclerosis a syndrome corresponding to the stiff-man syndrome was observed.


Preparation of nanocomposite based on chitosan-PDCOEMA containing biosynthesized ZnO: Biological and thermal characterization.
In this study, poly(2-(3,5-dichloroanilino)-2-oxoethyl 2-methylprop-2-enoate) (PDCOEMA), a new synthetic polymer based on methacrylate, was synthesized and characterized. The blend of PDCOEMA with chitosan (CS) was prepared by the hydrothermal method and the DSC technique confirmed its formation. It was observed that PDCOEMA increased the thermal stability and glass transition temperature (Tg) of CS. The Tg value of the PDCOEMA-CS blend was increased at about 7 °C with the highest ZnO NPs contribution rate. PDCOEMA-CS/ZnO nanocomposites were prepared by adding ZnO NPs produced by biosynthesis at different weight ratios to the PDCOEMA-CS blend by hydrothermal method. When the thermal stability of nanocomposites determined by TGA was examined, it was observed that it increased significantly compared to CS. While the initial decomposition temperature of CS was 270 °C, this value increased to 293 °C after blending with DCOEMA, and to 317 °C with the addition of 7 % ZnO NPs. Antimicrobial, anticancer, cytotoxic, antioxidant, and wound healing properties of PDCOEMA, CS, PDCOEMA-CS blend, and nanocomposites were determined. According to the obtained results, it was observed that nanocomposites containing 5 % and 7 % ZnO NPs showed good anticancer activity against A549 cells at a dose of 10 μg/mL. The results show that the produced nanocomposites can contribute to developing CS-based materials.


Synaptic migration and reorganization after noise exposure suggests regeneration in a mature mammalian cochlea.
Overexposure to intense noise can destroy the synapses between auditory nerve fibers and their hair cell targets without destroying the hair cells themselves. In adult mice, this synaptopathy is immediate and largely irreversible, whereas, in guinea pigs, counts of immunostained synaptic puncta can recover with increasing post-exposure survival. Here, we asked whether this recovery simply reflects changes in synaptic immunostaining, or whether there is actual retraction and extension of neurites and/or synaptogenesis. Analysis of the numbers, sizes and spatial distribution of pre- and post-synaptic markers on cochlear inner hair cells, in guinea pigs surviving from 1 day to 6 months after a synaptopathic exposure, shows dramatic synaptic re-organization during the recovery period in which synapse counts recover from 16 to 91% of normal in the most affected regions. Synaptic puncta move all over the hair cell membrane during recovery, translocating far from their normal positions at the basolateral pole, and auditory-nerve terminals extend towards the hair cell's apical end to re-establish contact with them. These observations provide stronger evidence for spontaneous neural regeneration in a mature mammalian cochlea than can be inferred from synaptic counts alone.


Comparison of a 1.0 molar and a 0.5 molar formulation of gadobutrol in dynamic MR imaging of the liver in rats with hepatocellular carcinoma.
The efficacy of a 1.0 molar formulation of gadobutrol was compared with that of a 0.5 molar formulation in dynamic magnetic resonance (MR) imaging of the liver in rats with hepatocellular carcinoma (HCC). Seven nodules histologically identified as moderately differentiated HCC underwent dynamic study. In the normal parenchyma surrounding these tumors, the 0.5 molar and 1.0 molar formulations yielded similar enhancement patterns, with maximum enhancement value of approximately 35% at 20 to 40 s after injection. In the tumors, the 0.5 molar formulation induced approximately 65% enhancement, whereas the 1.0 molar formulation, used at the same dose as the 0.5 molar formulation, induced significantly higher enhancement until 10 min after injection with maximum enhancement of approximately 90%. These findings indicate that the 1.0 molar formulation could be more efficacious than the 0.5 molar formulation in dynamic MR studies of moderately differentiated HCC even when injected at the same dose.


Molecular modeling study of cyclic pentapeptide CXCR4 antagonists: new insight into CXCR4-FC131 interactions.
CXCR4 is a G-protein coupled receptor that is associated with many diseases such as breast cancer metastasis, HIV infection, leukemic disease and rheumatoid arthritis, and is thus considered an attractive drug target. Previously, we identified a cyclic pentapeptide, FC131, that is a potent antagonist for CXCR4. In this study, we constructed a three dimensional model of the CXCR4-FC131 complex. To investigate the backbone flexibility of FC131, we performed molecular dynamics simulations of FC131 based on the NMR structure of FC131, and obtained snapshot structures from the trajectories which were used to model the docking pose of FC131 into CXCR4. Our final model of the CXCR4-FC131 complex is partially different from the X-ray crystal structure of CXCR4-CVX15 and suggests water-mediated interactions. Nevertheless, this docking pose is consistent with the experimental data. We believe our model will aid in the discovery and development of small-molecule antagonists for CXCR4.


Mental Health in Inuit Youth from Nunavik: Clinical Considerations on a Transcultural, Interdisciplinary, Community-oriented Approach.
This paper discusses the organization of mental health care for youth in Nunavik and considers how best to adapt care to the sociocultural and geographical specificities of this region. Services are described and discussed by a general practitioner and a community worker in Nunavik. Current social and medical care delivery in Nunavik is provided by professionals who are largely non-Inuit and who are supported by Inuit community workers and interpreters. Community workers are key players in the provision of social and mental health care for youth. Efforts are made to adapt care to the sociocultural specificities of Inuit youth, and to locally-based multidisciplinary care addressing the multiple determinants of mental health. While efforts to adapt care are ongoing, the ideal model of care integrating transcultural, multidisciplinary and community-oriented approaches are yet to become a reality. Increased communication among care providers is suggested as a way to strengthen the current collaborative model of care. Future goals include having a majority of care being provided locally and building community ownership and governance of care institutions.


Color preference of Sergentomyia minuta (Diptera: Phlebotominae) determined using Flebocollect Do It Yourself light traps based on LED technology.
Whether phlebotomine sand flies show a preference for different light colors remains controversial. As light-capture methods are widely used to study sand flies, knowing the visual stimuli they respond to could help the design of novel control tools to prevent their attraction to hosts. We have detected a significant preference of male Sergentomyia minuta for green and red light sources. Accordingly, male S. minuta were 2.16 and 2.01 times more likely to be lured by Flebocollect model traps with green and red diode-lights, respectively, than the commercial CDC traps. Flebocollect traps are homemade light traps developed through citizen science. Dipterans are widely considered unable to distinguish the color red so this finding was unexpected. To our knowledge, this is the first description of a color preference in a species of the genus Sergentomyia. Our research also confirms the great potential of Flebocollect light traps for use in medical entomology studies.


[Health costs in times of pandemic].
The 2008 financial crisis provides some useful lessons for understanding future challenges in relation to the Covid-19 pandemic. Knowledge of the share of gross domestic product contributing to health expenditure sheds light on the efficiency of health policies in the major countries of the Organisation for Economic Co-operation and Development.


Differential effects of GTP on the coupling of beta-adrenergic receptors to adenylate cyclase from frog and turkey erythrocytes. Application of new methods for the analysis of receptor-effector coupling.
A detailed comparison of the interaction of beta-adrenergic receptors with adenylate cyclase stimulation and modification of this interaction by guanine nucleotides has been made in two model systems, the frog and turkey erythrocyte. Objective analysis of the data was facilitated by the development of new graphical methods which involve the use of logit-logit transformations of percent receptor occupancy versus percent enzyme stimulation plots (coupling curves). Receptor-cyclase coupling in turkey erythrocyte membranes demonstrates a proportional relationship between receptor occupancy and adenylate cyclase activation and is unaffected by exogenous guanine nucleotides. By comparison, the proportional relationship of receptor occupancy and adenylate cyclase activation observed in frog erythrocyte membranes in the absence of guanine nucleotides is modified by the addition of exogenous guanine nucleotides such that a greater fractional enzyme stimulation is elicited by low receptor occupancy. Methodological criteria crucial for valid comparison of receptor occupancy and adenylate cyclase activity are delineated. In addition, the possible molecular mechanisms of receptor-cyclase coupling which might give rise to the coupling curves observed are discussed.


Microinjection of a glutamate antagonist into the nucleus accumbens reduces psychostimulant locomotion in rats.
In order to study a possible modulatory effect of glutamatergic afferents to the nucleus accumbens (NAC) on psychostimulant-induced locomotion, L-glutamic acid diethyl ester (GDEE), a glutamate antagonist, was injected in the NAC of rats acutely treated with cocaine, amphetamine or caffeine. GDEE at the doses of 5, 10, and 20 micrograms/side significantly reduced locomotion induced by cocaine (20 mg/kg, i.p.). Amphetamine-induced hyperactivity was also reduced by GDEE, whereas caffeine-induced hyperactivity was not significantly decreased by GDEE. This suggests that glutamatergic afferents to the NAC modulate the effects of psychostimulants and also dopamine function in the mesolimbic system.


Meta-analysis of the Association between Alzheimer Disease and Variants in GAB2, PICALM, and SORL1.
The genetic variants play a crucial role in the pathogenesis of Alzheimer's disease (AD), while the relationships of specific single nucleotide polymorphisms (SNPs) with AD are still controversial. We performed the meta-analysis to obtain a more precise estimation of whether growth factor receptor-bound protein-associated binding protein 2 (GAB2), phosphatidylinositol binding clathrin assembly protein (PICALM), and sortilin-related receptor (SORL1) variants are associated with AD. Databases including PubMed, Embase, and Cochrane Library were searched to find relevant studies. Cochran's Q-statistic and I 2 were used to assess the heterogeneity among the included studies. Odds ratios (OR) and 95 % confidence intervals (95 % CIs) were conducted to evaluate the association between the SNP and the susceptibility to AD. Publication bias was estimated by funnel plots. All of the statistical analyses were implemented using R Version 3.2.1 software. A total of 35 case-control studies involving 15 SNPs were included. There was no significant association between SNPs of GAB2 rs2373115 (G > T) and PICALM rs541458 (C > T) and AD. The allele T of rs3851179 in PICALM was associated with a 13 % increase in the risk of AD. Seven SNPs on SORL1 were significantly associated with AD. Four SNPs, including rs1010159*T, rs641120*A, rs668387*T, and rs689021*A, were associated with a decreased risk of AD, while the other three SNPs, including rs12285364*T, rs2070045*G, and rs2282649*T, were all associated with an increased risk of AD. The results of the present study suggested that multiple gene variants were associated with AD. The SNP of rs3851179 (PICALM), rs12285364 (SORL1), rs2070045 (SORL1), and rs2282649 (SORL1) was associated with an increased risk of AD, whereas SORL1 rs1010159, rs641120, rs668387, and rs689021 were associated with a decreased risk of AD.


Deep Learning Utilizing Suboptimal Spirometry Data to Improve Lung Function and Mortality Prediction in the UK Biobank.
Spirometry measures lung function by selecting the best of multiple efforts meeting pre-specified quality control (QC), and reporting two key metrics: forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). We hypothesize that discarded submaximal and QC-failing data meaningfully contribute to the prediction of airflow obstruction and all-cause mortality. We evaluated volume-time spirometry data from the UK Biobank. We identified "best" spirometry efforts as those passing QC with the maximum FVC. "Discarded" efforts were either submaximal or failed QC. To create a combined representation of lung function we implemented a contrastive learning approach, Spirogram-based Contrastive Learning Framework (Spiro-CLF), which utilized all recorded volume-time curves per participant and applied different transformations (e.g. flow-volume, flow-time). In a held-out 20% testing subset we applied the Spiro-CLF representation of a participant's overall lung function to 1) binary predictions of FEV1/FVC < 0.7 and FEV1 Percent Predicted (FEV1PP) < 80%, indicative of airflow obstruction, and 2) Cox regression for all-cause mortality. We included 940,705 volume-time curves from 352,684 UK Biobank participants with 2-3 spirometry efforts per individual (66.7% with 3 efforts) and at least one QC-passing spirometry effort. Of all spirometry efforts, 24.1% failed QC and 37.5% were submaximal. Spiro-CLF prediction of FEV1/FVC < 0.7 utilizing discarded spirometry efforts had an Area under the Receiver Operating Characteristics (AUROC) of 0.981 (0.863 for FEV1PP prediction). Incorporating discarded spirometry efforts in all-cause mortality prediction was associated with a concordance index (c-index) of 0.654, which exceeded the c-indices from FEV1 (0.590), FVC (0.559), or FEV1/FVC (0.599) from each participant's single best effort. A contrastive learning model using raw spirometry curves can accurately predict lung function using submaximal and QC-failing efforts. This model also has superior prediction of all-cause mortality compared to standard lung function measurements. MHC is supported by NIH R01HL137927, R01HL135142, HL147148, and HL089856.BDH is supported by NIH K08HL136928, U01 HL089856, and an Alpha-1 Foundation Research Grant.DH is supported by NIH 2T32HL007427-41EKS is supported by NIH R01 HL152728, R01 HL147148, U01 HL089856, R01 HL133135, P01 HL132825, and P01 HL114501.PJC is supported by NIH R01HL124233 and R01HL147326.SPB is supported by NIH R01HL151421 and UH3HL155806.TY, FH, and CYM are employees of Google LLC.


Collagen deposition around polypropylene tapes implanted in the rectus fascia of female rats.
Implantation of the mesh induces a foreign-body reaction followed by the development of connective tissue that may alter tape property. The aim of our study was to evaluate the deposition of collagen in the vicinity of monofilament tension-free vaginal tape (TVT; Ethicon Inc., Johnson & Johnson) and multifilament intravaginal slingplasty (IVS; Tyco Healthcare) polypropylene tapes implanted in female rats. The samples of the meshes (10 mg each) were implanted in the rectus fascia of 14 Wistar female rats and removed after 42 days. Collagen was extracted with 0.5 M acetic acid and subsequently with pepsin (1 mg/ml in 0.5 M acetic acid). Collagen concentration was measured using Sircol Collagen Assay (Biocolor Ltd.) and normalised for milligrams of tape weight. For histological examination, tape samples were stained with haematoxylin and eosin or with silver for type III collagen. The total amount of collagen extracted did not differ significantly between TVT and IVS samples. For both tapes, extraction with acetic acid yielded a higher amount of collagen (about 70%) than extraction with pepsin. On histological examination, less densely packed bundles of collagen fibres and a slightly more intense inflammatory reaction were observed with TVT compared with IVS mesh. The total amount of collagen deposited around the polypropylene mesh implanted in female rats was similar for TVT and IVS meshes, but differences were noted in the arrangement of the collagen fibres and the intensity of the inflammatory reaction.


Telephone assistance for smoking cessation: one year cost effectiveness estimations.
A randomised trial evaluated the American Cancer Society's telephone counselling service to assist smoking cessation. Counselling nearly doubles a smokers' odds of quitting and maintaining cessation for one year. The estimated cost for each case of maintained smoking cessation attributable to counselling availability is approximately 1300 dollars.


MRI measurements of the dependence on T1 of the echo amplitudes using a multiple spin-echo scheme.
Analytical calculations using the Bloch formalism were performed to assess the dependence on T1 of the echo amplitudes for the Phase-Alternating Phase-Shift (PHAPS) multiple spin-echo protocol. Measurements in a 0.5 T MR imaging unit were performed to ratify the analytical results. Especially for low T2 values, the echo amplitudes were erroneous, with an increasing contribution from stimulated echo components with increasing T1. Apart from affecting T2 estimates, stimulated echoes generated a non-monoexponential signal decay of the echo trains. The results confirmed previous simulation studies as regards the dependence on T1 of T2 estimates from PHAPS.


The vasculature of the rat embryo: an electron microscope study.
The ultrastructure of portions of the arterial and venous systems of the 11.5 day old Wistar rat embryos has been studied by scanning and transmission electron microscopy. The vessels at this stage of development are in the form of capillaries, and the arterial and venous types can be distinguished by the morphology of the endothelial cells by SEM. The endothelial cells of the arterial vessels gave prominent nuclear bulges and numerous microvilli apart from their spindle shape, whilst those of the veins appear flattened, are polygonal in shape, and have few microvilli. Transmission electron microscopy shows that the endothelial cells of the arteries and veins are identical in structure. The ultrastructure of these cells resembles that of endothelial cells at later stages of development including the adult type in that mature forms of cytoplasmic organelles are obtained. In studies on the intercellular junctions and fenestrations with lanthanum nitrate, the impression is formed that the vessels at this stage are impermeable to small molecular size particles, compared with adult capillaries. This suggests that cytoplasmic vesicles must play a major role in the transport of macromolecules in the 11.5 day embryonic vessels.


Weight estimation in Paediatrics: how accurate is the Broselow-tape weight estimation in the Nigerian child.
Determination of weight in children is an important aspect of their assessment. It has a wide range of usefulness including assessing their nutritional status and drug dose calculation. Despite its usefulness, weight estimation in children in certain conditions can be challenging particularly in emergency situations or in children who are severely ill or cannot stand on standard scales. The Broselow Tape which is a validated tape that is used to estimate weight based on length was developed using height/weight correlations from Western data. However, considering the variations in anthropometric measurements of children from different geographic locations, there is need to ascertain how accurate it is to estimate weight using the Broselow tape among children in Nigeria. The study was carried out to determine the accuracy in the use of the Broselow Tape in weight estimation among Nigerian children. A total 1456 children aged 1-12 years who satisfied the inclusion criteria were enrolled over a 2½ year period from two tertiary health facilities in Enugu state Nigeria. Weight was taken using standard weighing scale and Broselow tape. Data collected was analysed using SPSS. Of the 1456 children studied, majority (84.2%) had normal Body-Mass-Index (BMI) while about 4.6% had a low BMI percentile for age. The mean weight difference between the two methods was not significantly different between the 1 to 6 years old category. Significant differences were observed from 7 up to 12 years. The Broselow Tape overestimated weights in 1 year old by 3.88%, 2 years 1.58%, 3 years by 2.13%, 4 years (1.94%) and 5 year (0.07%). After 5 years, the degree of overestimation rises sharply to 4.25% in 6, 9.25% in 7, 7.29% in 8 and 9.29%. 9.18, 11.61% & 6.75% in 9, 10, 11 and 12 years old respectively. The proportion of estimated weights that was within 10- 20% of the actual weight was higher in the 1-6 years age categories compared to weight estimates in older age categories. Weight estimates obtained using the Broselow tape correlated better in children that are 6 years or younger compared to those in the older age categories. There is need for re-validation and/or adjustments of the Broselow tape especially in children over 6 years old.


Quantitative evaluation of hyperbaric oxygen efficacy in experimental traumatic brain injury: an MRI study.
To use DCE-magnetic resonance imaging (MRI) and diffusion-weighted imaging to evaluate the hyperbaric oxygen efficacy (HBO) in experimental traumatic brain injury (TBI). Forty-two rabbits were randomly divided into four groups: TBI, TBI + HBO, sham group, sham + HBO. The TBI + HBO and sham + HBO received a total of 10 HBO treatments within 7 days following TBI, and MRI was performed within a month after TBI. Functional assessments were performed pre-TBI, and at 1 and 30 days. In focal lesion area, K(trans) in TBI + HBO group was lower than TBI group at both acute and subacute phase (p < 0.05). ADC was higher in TBI + HBO group than TBI group at acute phase (p < 0.01), but lower at subacute phase (p < 0.05). In perifocal area, K(trans) were lower in TBI + HBO group than TBI group at acute phase (p < 0.01) after TBI. ADC was lower in the TBI + HBO group than in the TBI group at both acute and subacute phase (p < 0.01).The VCS was higher in TBI + HBO group than TBI group at 30 days (p < 0.05). HBO could improve the impaired BBB and cytotoxic edema after TBI and promote the recovery of neurofunction.


Expression of a sonic hedgehog signal transducer, hedgehog-interacting protein, by human basal cell carcinoma.
Aberrant activation of the hedgehog pathway has been identified in various human tumours, including familial and sporadic basal cell carcinomas (BCCs). It has been postulated that binding of sonic hedgehog protein (SHH) to its receptor, patched protein (PTC), releases the inhibitory effect of PTC against smoothened protein (SMO), another protein of the SHH signalling pathway. The positive SMO signalling is not downregulated in BCCs because of the mutational inactivation of PTC. Recently, hedgehog-interacting protein (HIP) was found to bind to SHH directly and attenuate SHH signalling like PTC, while its expression was induced by SHH signals. To examine the expression patterns of HIP, SHH and PTC gene mRNA by human BCCs, in comparison with those by normal human skin and various skin tumours. We performed quantitative reverse transcriptase-polymerase chain reaction analyses with a series of samples from BCCs, other skin tumours and normal skin. We found that the mRNA expression of both HIP and PTC genes was enhanced in all samples of BCCs, whereas none of the other skin tumours tested exhibited an increased level of such mRNAs as compared with normal skin. The transcription of the SHH gene, however, was at a baseline level in most BCCs. These results indicate that both HIP and PTC gene expression are specifically involved in the development of BCCs, and that the production of HIP is linked with the expression of the PTC gene but not the SHH gene.