5-Oxo-L-prolinase (L-pyroglutamate hydrolase). Purification and catalytic properties.
5-Oxo-L-prolinase, an enzyme that catalyzes the conversion of 5-oxo-L-proline (L-pyroglutamate; L-2-pyrrolidone-5-carboxylate) to L-glutamate coupled with the cleavage of ATP to ADP and Pi, has been purified about 1600-fold from rat kidney. Purification was carried out in the presence of 5-oxo-L-proline which protects the enzyme under a variety of conditions. An estimate of the molecular weight (about 325,000) was made by gel filtration on Sephadex G-200. K+ (or NH4+) and Mg2+ were required for activity. GTP, ITP, CTP, and UTP were much less active than ATP; dATP was 43% as active as ATP. ADP inhibited and addition of pyruvate kinase and phosphoenolpyruvate activated the reaction. The enzyme, which is protected during storage by dithiothreitol, is inhibited by p-hydroxymercuribenzoate, N-ethylmaleimide, and iodoacetamide. The apparent Km values for 5-oxo-L-proline and ATP are, respectively, 0.05 and 0.17 mM. The pH profile indicates a broad range of activity from about pH 5.5 to pH 11.2 with apparent maxima at about pH 7 and pH 9.7. The formation of Pi and glutamate was equimolar over a wide pH range. When the enzyme was incubated with ATP, Mg2+, K+, and L-2-imidazolidone-4-carboxylate or L-dihydroorotate, cleavage of ATP to ADP and Pi occurred, but no cleavage of the imino acid substrates was observed; when the enzyme was incubated under these conditions with 2-piperidone-6-carboxylate, 4-oxy-5-oxoproline, and 3-oxy-5-oxoproline, the corresponding dicarboxylic amino acids were formed, but the molar ratio of Pi to amino acid formation was significantly greater than unity.


High antibody responses against Plasmodium falciparum in immigrants after extended periods of interrupted exposure to malaria.
Malaria immunity is commonly believed to wane in the absence of Plasmodium falciparum exposure, based on limited epidemiological data and short-lived antibody responses in some longitudinal studies in endemic areas. A cross-sectional study was conducted among sub-Saharan African adults residing in Spain for 1 up to 38 years (immigrants) with clinical malaria (n=55) or without malaria (n=37), naïve adults (travelers) with a first clinical malaria episode (n=20) and life-long malaria exposed adults from Mozambique (semi-immune adults) without malaria (n=27) or with clinical malaria (n=50). Blood samples were collected and IgG levels against the erythrocytic antigens AMA-1 and MSP-1₄₂ (3D7 and FVO strains), EBA-175 and DBL-α were determined by Luminex. IgG levels against antigens on the surface of infected erythrocytes (IEs) were measured by flow cytometry. Immigrants without malaria had lower IgG levels than healthy semi-immune adults regardless of the antigen tested (P≤0.026), but no correlation was found between IgG levels and time since migration. Upon reinfection, immigrants with malaria had higher levels of IgG against all antigens than immigrants without malaria. However, the magnitude of the response compared to semi-immune adults with malaria depended on the antigen tested. Thus, immigrants had higher IgG levels against AMA-1 and MSP-1₄₂ (P≤0.015), similar levels against EBA-175 and DBL-α, and lower levels against IEs (P≤0.016). Immigrants had higher IgG levels against all antigens tested compared to travelers (P≤0.001), both with malaria. Upon cessation of malaria exposure, IgG responses to malaria-specific antigens were maintained to a large extent, although the conservation and the magnitude of the recall response depended on the nature of the antigen. Studies on immigrant populations can shed light on the factors that determine the duration of malaria specific antibody responses and its effect on protection, with important implications for future vaccine design and public health control measures.


DIEP flap perfusion assessment using microdialysis versus Doppler ultrasonography: A comparative study.
The increasing number of buried free-tissue transfer procedures and the need for an objective method to evaluate vascular complications of free flaps has led to the development of new technologies. Microdialysis has been used to monitor free flaps using interstitial biological markers. Previous uses mainly focused on muscular flaps. Our aim is to compare external Doppler ultrasonography (EDU) evaluation versus microdialysis in the early follow-up of adipocutaneous flaps, and propose an efficient postoperative monitoring protocol. We retrospectively assessed 68 consecutive DIEP flaps (50 patients) performed between January 2019 and March 2021. All flaps received standardized post-operative monitoring using clinical signs, EDU and microdialysis. Glucose and lactate concentrations were assessed using glucose <1 mmol/L and lactate >6 mmol/L as ischemic trend thresholds. We calculated Glucose/Lactate ratio as a new parameter for the assessment of flap viability. Among all the 68 flaps, two flaps returned to the operative theater when a combination of unsatisfactory microdialysis values and clinical/EDU signs identified vascular impairment; only one developed total flap necrosis. Reoperation rate was 2.94% with an overall flap success rate of 98.53%. External Doppler ultrasonography had 100% sensitivity and 82% specificity, while microdialysis had 100% sensitivity and 100% specificity. Microdialysis values proved flap viability sooner than external Doppler ultrasonography, making it an excellent tool for post-operative monitoring. With the appropriate thresholds for glucose and lactate concentrations, and glucose/lactate ratio used as a new parameter, it can help potentially avoiding unnecessary re-explorations, and reducing flap ischemia times.


Rituximab responsive immune thrombocytopenic purpura in an adult with underlying autoimmune lymphoproliferative syndrome due to a splice-site mutation (IVS7+2 T>C) affecting the Fas gene.
A 36 yr-old man of Israeli descent with a history of childhood splenectomy for severe thrombocytopenia and a family history of autoimmune lymphoproliferative syndrome (ALPS), presented with severe immune thrombocytopenic purpura refractory to standard therapy. He was found to possess a heterozygous mutation in the Fas gene (also termed TNFRSF6, CD95, Apo-1) affecting the donor splice site of intron 7 (IVS7+2 T>C). This frameshift mutation truncates the cytoplasmic domain of the Fas death receptor, resulting in circulating CD4/8 double negative T lymphocytes, lymphadenopathy and autoimmune complications typical of ALPS. Administration of Rituximab in this patient was associated with a durable hematologic response (currently more than 12 months). This report highlights the need to consider rare inherited causes of thrombocytopenia in adults with a family history of immune cytopenia(s) and the effective use of anti-CD20 monoclonal antibody in patients unresponsive to immunosuppression and splenectomy.


Increased platelet volume and aggregation precede the onset of preeclampsia.
To determine whether changes in platelet aggregation, numbers, or mean volume precede the onset of preeclampsia in patients given anti-platelet therapy. Changes in platelet aggregation, numbers, and volumes were followed longitudinally in 17 women who had previously lost 44 of 56 pregnancies and were thus considered to be at risk of preeclampsia. The subjects were treated with low-dose aspirin. Mean platelet volume, platelet numbers, and platelet aggregation were monitored every 2-4 weeks during pregnancy. All eight subjects who developed preeclampsia delivered growth-retarded infants before term. All showed increased platelet aggregation in vitro, accompanied by increased platelet volumes (by at least 0.8 fL) and decreased platelet numbers (by at least 60 x 10(9)/L) in five subjects, increased volumes alone in one, and decreased numbers alone in one. The increases in platelet aggregation and volumes predated the development of preeclampsia by 2-5 weeks. Nine subjects had pregnancies that progressed normally to term (beyond 37 weeks), with the delivery of eight normal and one growth-retarded infant; platelet aggregation, numbers, and volumes did not change to the same extent as in the subjects who developed preeclampsia. Increased mean platelet volume and increased platelet aggregation compared to the individual patient's first-trimester data were detected 2-5 weeks before the development of all cases of preeclampsia. In contrast, normal pregnancies did not show significant changes in mean platelet volume or platelet aggregation.


Reconciling the biomedical data commons and the GDPR: three lessons from the EUCAN ELSI collaboratory.
The coming-into-force of the EU General Data Protection Regulation (GDPR) is a watershed moment in the legal recognition of enforceable rights to informational self-determination. The rapid evolution of legal requirements applicable to data use, however, has the potential to outstrip the capabilities of networks of biomedical data users to respond to the shifting norms. It can also delegitimate established institutional bodies that are responsible for assessing and authorising the downstream use of data, including research ethics committees and institutional data custodians. These burdens are especially pronounced for clinical and research networks that are of transnational scale, because the legal compliance burden for outbound international data transfers from the EEA is especially high. Legislatures, courts, and regulators in the EU should therefore implement the following three legal changes. First, the responsibilities of particular actors in a data sharing network should be delimited through the contractual allocation of responsibilities between collaborators. Second, the use of data through secure data processing environments should not trigger the international transfer provisions of the GDPR. Third, the use of federated data analysis methodologies that do not provide analysis nodes or downstream users access to identifiable personal data as part of the outputs of those analyses should not be considered circumstances of joint controllership, nor lead to the users of non-identifiable data to be considered controllers or processors. These small clarifications of, or modifications to, the GDPR would facilitate the exchange of biomedical data amongst clinicians and researchers.


Green Synthesis of Silver Nanoparticles: Optimizing Green Tea Leaf Extraction for Enhanced Physicochemical Properties.
In this paper, we present the optimization of green tea leaf (Camellia sinensis L.) extraction, carried out using water and hydroalcoholic solvents, for the subsequent synthesis of silver nanoparticles (AgNPs). The value ranges for independent variables, including pH, time, and temperature, were selected based on single-factor experiments and used for extraction in the order presented by the Box-Behnken design. Three-dimensional response surface graphs were used to visually present the optimization results and determine the optimal extraction conditions: pH = 7, 30 min, 80 °C for water and pH = 5.5, 50 min, and 80 °C for water-ethanol. Our findings indicate that the water-ethanol mixture extracted more polyphenols. We compared the physicochemical properties of AgNPs obtained using both types of extractants via DLS and TEM analysis. We proposed a predicted mechanism for the reduction and stabilization of AgNPs based on the Fourier transform infrared data. The hydroethanolic extract leads to significant nanoparticle aggregation, which can be explained by the nucleation theory and agglomeration of nanoparticles in the presence of excess macromolecular organic substances (flocculation).


Management and outcomes of military penetrating neck injuries: An eleven-year retrospective case note review.
Penetrating Neck Injuries (PNIs) affected 3.2% of trauma patients attending US and UK deployed medical treatment facilities (MTFs) during the Iraq and Afghanistan conflicts. Injured military personnel requiring aeromedical evacuation for such injuries were managed at the Royal Centre for Defence Medicine (RCDM), Birmingham, UK. The aim of this paper was to review the management of PNI in both deployed MTFs and when evacuated back to the UK. A retrospective case note review was performed of all military patients who sustained PNI whilst on deployment overseas, and who were subsequently evacuated to RCDM between March 2003 and December 2014. Forty casualties who sustained PNI were identified, of which 28/40 (70%) sustained injury from explosive fragmentation, and 11/40 (28%) from gunshot wounds. Hard signs of PNI were present in 3/40 (7.5%) patients, soft signs in 14/40 (35%), no signs in 12/40 (30%), and unknown signs in 11/40 (28%) patients. Computed tomography angiography (CTA) was used in 39/40 (98%) patients, and was effective at ruling out significant injury, with 100% (29/29) of casualties with a negative CTA not developing vascular or aerodigestive injury. There were 9/29 (31%) patients who had surgical neck exploration despite both a negative CTA and absence of hard signs of PNI. There were 12/40 (30%) patients who required operative intervention at RCDM. UK military surgeons in Role 3 MTFs had a low threshold for surgical exploration, even in the absence of CT findings or hard signs. This was likely due to the high-energy mechanisms responsible for military PNI, in addition to the limited availability of equipment and clinical expertise in visualising the larynx.


The UWHAM and SWHAM Software Package.
We introduce the UWHAM (binless weighted histogram analysis method) and SWHAM (stochastic UWHAM) software package that can be used to estimate the density of states and free energy differences based on the data generated by multi-state simulations. The programs used to solve the UWHAM equations are written in the C++ language and operated via the command line interface. In this paper, first we review the theoretical bases of UWHAM, its stochastic solver RE-SWHAM (replica exchange-like SWHAM)and ST-SWHAM (serial tempering-like SWHAM). Then we provide a tutorial with examples that explains how to apply the UWHAM program package to analyze the data generated by different types of multi-state simulations: umbrella sampling, replica exchange, free energy perturbation simulations, etc. The tutorial examples also show that the UWHAM equations can be solved stochastically by applying the RE-SWHAM and ST-SWHAM programs when the data ensemble is large. If the simulations at some states are far from equilibrium, the Stratified RE-SWHAM program can be applied to obtain the equilibrium distribution of the state of interest. All the source codes and the tutorial examples are available from our group's web page: https://ronlevygroup.cst.temple.edu/software/UWHAM_and_SWHAM_webpage/index.html .


Gas diffusion flow injection determination of thiomersal in vaccines.
A new simple gas diffusion flow injection method has been developed for the determination of thiomersal in biological samples. The method is based on cold vapor generation of monoatomic mercury from thiomersal reaction with acidic stannous chloride solution (0.6%) acting as reducing agent. The evolved mercury partially diffuses through a Teflon membrane into an acidic permanganate (2.25 × 10(-4) mol L(-1)) acceptor stream, where it is oxidized and re-converted to Hg(II). The resulting decrease in acceptor stream absorbance is sensitively monitored at 528 nm. Flow injection variable parameters such as reagents concentrations, injected volume, reactor length, temperature and flow rate were carefully investigated and optimized. The concentration-response relationship was linear over a concentration range of 1-30 mg L(-1) with a correlation coefficient greater than 0.99 and a good reproducibility (RSD<1.42%, n=6) at 10 mg L(-1). A detection limit of 0.07 mg L(-1) (S/N=3) and a sampling frequency of 5 samples h(-1) were obtained. The method was successfully applied for the determination of thiomersal in different types of vaccines and gave results in close agreement with those found by previously established HPLC method with no significant interference from vaccines matrices.


CAR-NK cells from engineered pluripotent stem cells: Off-the-shelf therapeutics for all patients.
Clinical success of adoptive cell therapy with chimeric antigen receptor (CAR) T cells for treating hematological malignancies has revolutionized the field of cellular immunotherapy. However, due to the nature of utilizing autologous T cells, affordability and availability are major hurdles, in addition to scientific challenges relating to CAR-T therapy optimization. Natural killer (NK) cell is a specialized immune effector cell type that recognizes and kills targets without human leukocyte antigen (HLA) restriction and prior sensitization. CAR-NK cells do not cause graft vs host disease and can be obtained from unrelated donors as well as pluripotent stem cells (PSC), representing an ideal off-the-shelf therapeutics readily available for patients. Furthermore, unlike cytotoxic T cells, NK cells specifically target and eliminate cancer stem cells, which are the cells causing relapse and metastasis. PSCs can be genetically manipulated and engineered with CARs at the pluripotent stage, which allows the establishment of permanent, stable, and clonal PSC-CAR lines for the manufacture of unlimited homogenous CAR-NK cells. Multiple master PSC-CAR cell banks targeting a variety of antigens for cancer, viral infection, and autoimmune diseases provide inexhaustible cell sources for all patients. Development of a next-generation 3D bioreactor platform for PSC expansion and NK cell production overcomes major barriers related to cost and scalability for CAR-NK product.


Who Do I (Not) Ask to Play my Lottery? Effects of Perceived Positive and Negative Agency, Communion and Luck on the Illusion of Control by Proxy.
The paper investigates the illusion of control by proxy in games of chance - an attempt to exert control by assigning it to others who are perceived as more capable, communable or luckier. Following up on research by Wohl & Enzle, who showed participants' preference to ask lucky others to play a lottery instead of doing it themselves, we included proxies with positive and negative qualities in the domains of agency and communion, as well good and bad luck. In three experiments (total N = 249) we tested participants' choices between these proxies and a random number generator in a task consisting of obtaining lottery numbers. We obtained consistent preventative illusions of control (i.e. avoidance of proxies with strictly negative qualities, as well as proxies with positive communion but negative agency), however we observed indifference between proxies with positive qualities and random number generators.


Acute acalculous cholecystitis. Ultrasonic appearance.
Acute acalculos cholecystitis can be associated with severe electrical burns. Ultrasound can have a role in the evaluation of this problem.


Serious Risk of Tigecycline Resistance in Escherichia coli Isolated from Swine Manure.
The emergence of the plasmid-mediated tigecycline resistance gene tetX family in pig farms has attracted worldwide attention. The use of tetracycline antibiotics in pig farms has a facilitating effect on the prevalence of the tetX family, but the relationship among its presence, expression, and resistance phenotype in resistant bacteria is unknown. In this study, the presence and expression characteristics of tetracycline resistance genes (TRGs) in 89 strains of doxycycline-resistant E. coli (DRE) isolated from pig manure samples from 20 pig farms under low concentrations of doxycycline stress (2 μg/mL) were analyzed. The detection rate of tetO was 96.63%, which is higher than those of other TRGs, such as tetA (94.38%), tetX (76.40%), tetB (73.03%), and tet(X4) (69.66%). At least three TRG types were present in DRE strains, which thus showed extensive resistance to tetracycline antibiotics, and 37% of these strains were resistant to tigecycline. In the presence of a low concentration of doxycycline, tetA played an important role, and the expression and existence ratio of TRGs indicated low expression of TRGs. Furthermore, the doxycycline resistance of DRE was jointly determined by the total absolute abundance of TRGs, and the absolute abundance of tetX and tet(X4) was significantly positively associated with tigecycline resistance in DRE (P < 0.05). Overall, DRE isolated from swine manure is an important reservoir of the tetX family, which suggests that DRE in swine manure has a high risk of tigecycline resistance, poses a potential threat to human health, and should be of public concern.


Treatment of eyebrow hypotrichosis using bimatoprost: a randomized, double-blind, vehicle-controlled pilot study.
The Food and Drug Administration has approved bimatoprost ophthalmic solution (0.03%) for the treatment of eyelash hypotrichosis. Previous reports of its efficacy in eyebrow hypotrichosis are anecdotal. To assess the efficacy and safety of bimatoprost 0.03% ophthalmic solution applied to the eyebrows in a randomized, double-blind, vehicle-controlled study. Subjects (n = 20) with mild to moderate eyebrow hypotrichosis enrolled in the study. One group (Bim) applied bimatoprost to each eyebrow daily for 9 months, and another applied vehicle nightly to each eyebrow for 5 months. Subjects in the latter group were re-randomized to apply bimatoprost (Veh-Bim Group) or vehicle (Veh Group) daily to each eyebrow for 4 months. The primary end point was investigator-assessed eyebrow appearance; secondary end points were subject-reported outcomes. Investigator assessments showed significant improvements from baseline to 6 (p = .002) and 7 (p = .005) months for the eyebrows treated with bimatoprost. p-Values for the Veh-Bim and Veh groups were not significant at any time point. End-of-study subject satisfaction with eyebrow fullness or thickness and darkness or color was greater in the Bim group than in the Veh group. Adverse effects were not observed. Bimatoprost 0.03% ophthalmic solution applied daily for 9 months improves the appearance of eyebrows noticeably more than vehicle, without side effects.


Exploiting mutual information for the imputation of static and dynamic mixed-type clinical data with an adaptive k-nearest neighbours approach.
Clinical registers constitute an invaluable resource in the medical data-driven decision making context. Accurate machine learning and data mining approaches on these data can lead to faster diagnosis, definition of tailored interventions, and improved outcome prediction. A typical issue when implementing such approaches is the almost unavoidable presence of missing values in the collected data. In this work, we propose an imputation algorithm based on a mutual information-weighted k-nearest neighbours approach, able to handle the simultaneous presence of missing information in different types of variables. We developed and validated the method on a clinical register, constituted by the information collected over subsequent screening visits of a cohort of patients affected by amyotrophic lateral sclerosis. For each subject with missing data to be imputed, we create a feature vector constituted by the information collected over his/her first three months of visits. This vector is used as sample in a k-nearest neighbours procedure, in order to select, among the other patients, the ones with the most similar temporal evolution of the disease over time. An ad hoc similarity metric was implemented for the sample comparison, capable of handling the different nature of the data, the presence of multiple missing values and include the cross-information among features captured by the mutual information statistic. We validated the proposed imputation method on an independent test set, comparing its performance with those of three state-of-the-art competitors, resulting in better performance. We further assessed the validity of our algorithm by comparing the performance of a survival classifier built on the data imputed with our method versus the one built on the data imputed with the best-performing competitor. Imputation of missing data is a crucial -and often mandatory- step when working with real-world datasets. The algorithm proposed in this work could effectively impute an amyotrophic lateral sclerosis clinical dataset, by handling the temporal and the mixed-type nature of the data and by exploiting the cross-information among features. We also showed how the imputation quality can affect a machine learning task.


Excitatory action of N-acetylaspartylglutamate on Purkinje cells in guinea pig cerebellar slices: an intrasomatic study.
The action of N-acetylaspartylglutamate (NAAG) on Purkinje cell somata in guinea pig cerebellar slices was intracellularly investigated in comparison with L-aspartate (Asp) and L-glutamate (Glu). A synthetic NAAG sample used was confirmed not to be contaminated with free Glu and Asp. NAAG, applied by either iontophoresis or superfusion, dose-dependently depolarized Purkinje cell somata, and iontophoretically applied NAAG decreased the membrane resistance in voltage- and Mg2+-dependent manners, like Asp or Glu. Relative depolarizing potencies seemed to be Glu greater than NAAG not equal to Asp in the presence of external Mg2+ and Asp greater than NAAG greater than or equal to Glu in the absence of Mg2+. In addition to this selective blocking effect of Mg2+, 2-amino-5-phosphonovalerate (APV) antagonized the actions of NAAG and Asp more strongly than that of Glu, while 2-amino-4-phosphonobutyrate showed rather non-selective antagonisms. The reversal potential of the NAAG action was at about 10 mV and similar to that of the action of Asp or Glu. These results suggest that NAAG itself is excitatory to guinea pig cerebellar Purkinje cells and is likely to be acting on Asp- and APV-sensitive, Mg2+-dependent receptors on cerebellar Purkinje cells.


[Persistent stapedial artery and chronic otitis: CTscan aspects, a clinical report].
The authors report a case of persistent stapedial artery in a young man who had a chronic ear infection with focus on the CT scan aspects. A review of the literature is done about this rare anomaly. Some CT scan aspects (absence of the spinosum foramina, bony canal from the hypotympanum toward the promontory, enlargement of the 2nd portion of the Fallopian canal) are very likely in favor of this diagnosis and allow a preoparative suspicion. If necessary a more complete imaging check up could be performed for searching other malformations.


Why we urgently need improved epilepsy therapies for adult patients.
Up to a third of patients with epilepsy suffer from recurrent seizures despite therapeutic advances. Current epilepsy treatments are limited by experiential data from treating different types of epilepsy. For example, we lack evidence-based approaches to efficacious multi-drug therapies or identifying potentially serious or disabling adverse events before medications are initiated. Despite advances in neuroscience and genetics, our understanding of epilepsy pathogenesis and mechanisms of treatment-resistance remains limited. For most patients with epilepsy, precision medicine for improved seizure control and reduced toxicity remains a future goal. A third of epilepsy patients suffer from ongoing seizures and even more suffer from adverse effects of treatment. There is a critical need for more effective and safer therapies for epilepsy patients with frequent comorbitidies, including depression, anxiety, migraine, and cognitive impairments, as well as special populations (e.g., women, elderly). Advances from genomic sequencing techniques may identify new genes and regulatory elements that influence both the depth of the epilepsies' roots within brain circuitry as well as ASD resistance. Improved understanding of epilepsy mechanisms, identification of potential new therapeutic targets, and their assessment in randomized controlled trials are needed to reduce the burden of refractory epilepsy. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.


The effect of gas flow on the filtration performance of breathing system filters.
When tested according to the European standard, the performance of breathing system filters is determined at a flow of 15 or 30 l.min-1 for filters intended for use with paediatric or adult patients, respectively. However, higher flows of gas may pass through a filter in some circumstances. The penetration of sodium chloride particles through seven different breathing system filters (three pleated hydrophobic and four electrostatic) was measured at five different flows ranging from 15 to 75 l.min-1. Penetration varied from 0.004% to 24.4% for the various filters at the different flows. Penetration increased by between 2 and 40 times for the different filters as the flow increased by a factor of five but this did not markedly alter the rank order of the filters in terms of performance. Testing to the standard provides a useful indication of relative performance at any flow.


Association between high serum Nogo-B and hypertension in Chinese Han.
Cellular and animal studies have shown that endoplasmic reticulum protein B (Nogo-B) is associated with hypertension, but that association has not been fully studied in humans. Therefore, the expression levels of Nogo-B were investigated in hypertensive patients. The plasma Nogo-B levels of 74 patients with hypertension and 67 non-hypertensive patients were measured by enzyme-linked immunosorbent assay. The plasma Nogo-B levels in the hypertensive group [523.43(411.41-746.79)] were higher than in the non-hypertensive group [380.29(281.57-462.13)] (P < 0.01). Pearson's correlation analysis indicated that systolic blood pressure and diastolic blood pressure were linearly and positively correlated with plasma Nogo-B levels. Multivariable logistic regression analysis was performed based on sex, age, BMI, smoking history, drinking history, and levels of TC, TG, LDL, and HDL. The results indicated that the plasma Nogo-B levels were independently associated with hypertension (OR = 1.007, 95%CI: 1.004-1.010, P < 0.01). The present study suggests that hypertensive participants exhibited higher plasma Nogo-B levels than those without hypertension. Plasma Nogo-B levels are independently associated with hypertension.


Sex estimation of the humerus: A geometric morphometric analysis in an adult sample.
Sex estimation is the keystone for positive identification when an unidentified human body is recovered in forensic contexts. However, in complex death scenes such as mass disasters, the remains are often fleshed, mutilated, burned, and/or commingled. In situations such as these where it is not possible to analyze pelvis and/or cranium data, traditional metric and qualitative morphological methods on postcranial bones can yield unsatisfactory results. In such cases, geometric morphometric techniques offer an alternative to the analysis of both shape and size components of morphological variation that can be of great utility for sex estimation in forensic investigations. The study population consisted of 72 well-preserved adult humeri (40 males and 32 females; mean age of 62 years) that were photographed in standardized positions with landmarks located in four two-dimensional views of the humerus (anterior surface of the proximal epiphysis, and anterior, posterior and inferior surface of distal epiphysis). Principal components analysis, canonical variates analysis and discriminant analysis were applied. The data indicated that males and females were classified with low levels of accuracy (54.95-77.92% for males; 56.87-71.78% for females) based on shape variables. However, when the shape variable was combined with the centroid size, the levels of accuracy increased (81.86-94.92% for males; 84.08-94.88% for females). To obtain larger differences between males and females, it is necessary the combination of centroid size with shape variables; the shape of the humerus is insufficient to discriminate sex with accuracy.


Abstracts of the 28th Annual Conference of the International Society for Environmental Epidemiology (ISEE), 1-4 September 2016, Rome, Italy.
The 28th annual conference of the International Society for Environmental Epidemiology was held 1 - 4 September 2016 in Rome, Italy. The conference theme was "Old and New Risks: Challenges for Environmental Epidemiology." The focus of this year's conference is current and future challenges in exposure assessment, study design, and data analyses.


A ball milling method for highly dispersed Ni atoms on g-C3N4 to boost CO2 photoreduction.
Atomically dispersed active sites can effectively enhance the catalytic activity, but the synthesis of highly dispersed single-atom active sites remains challenging. Herein, we report for the fabrication of single-atom Ni on g-C3N4 (CN) catalysts for photocatalytic CO2 reduction reaction (CO2RR) using a high-energy ball milling method. The uniformly loaded single-atomic Ni on the surface of the substrate suggests the improvement of synthetic methods. After optimizing the Ni loading, the photocatalyst containing 0.5 at% (0.32 wt%) single-atomic Ni (Ni/CN-0.5) exhibited the highest CO2 reduction performance (∼19.9 μmol·g-1·h-1) without any co-catalyst or sacrificial agent. As visualized by aberration-corrected high-angle annular darkfield scanning transmission electron microscopy (AC HAADF-STEM), the Ni atoms in the Ni/CN-0.5 photocatalyst are most uniformly dispersed for different loadings (0.1, 0.3, 0.5, 0.7, 1.0, 3.0 and 5.0 at%). These results suggest that the uniformity of the single-atom active sites plays a decisive role rather than the loading amount in the highly enhanced performance. This work provides insight into the design of photocatalysts with highly dispersed single-atom catalytic active sites for enhancing activity.


Evolutionary genomics of pathogenic bacteria.
Complete genome sequences are now available for multiple strains of several bacterial pathogens and comparative analysis of these sequences is providing important insights into the evolution of bacterial virulence. Recently, DNA microarray analysis of many strains of several pathogenic species has contributed to our understanding of bacterial diversity, evolution and pathogenesis. Comparative genomics has shown that pathogens such as Escherichia coli, Helicobacter pylori and Staphylococcus aureus contain extensive variation in gene content whereas Mycobacterium tuberculosis nucleotide divergence is very limited. Overall, these approaches are proving to be a powerful means of exploring bacterial diversity, and are providing an important framework for the analysis of the evolution of pathogenesis and the development of novel antimicrobial agents.


An adult case of junctional tachycardia diagnosed by premature atrial contractions and atrial overdrive pacing.
We report an adult case with JT, which could be differentiated from slow-fast AVNRT by premature atrial contractions and atrial overdrive pacing.


Effects of pipe materials on the characteristic recognition, disinfection byproduct formation, and toxicity risk of pipe wall biofilms during chlorination in water supply pipelines.
There are growing concerns over the contributions of biofilms to disinfection byproduct (DBP) formation in engineered water systems (EWSs). Three kinds of water supply pipes, ductile iron (DI), cement-lined stainless steel (SS) and polyethylene (PE) pipes, were selected for the experiment conducted in this study. Based on test results, the three pipe biofilms showed relatively obvious differences in growth, morphological characteristics, organic components and bacterial diversity. Secreted extracellular polymeric substance (EPS) accounted for more than 90% of the biofilm and had greater disinfection byproduct formation potential (DBPFP) than the cell phases. DI pipe wall biofilms had the highest DBPFP, which to a certain extent means that denser and richer organic matter can be produced as the precursor of different types of DBPs. UHPLC-Q Exactive was used to identify the types of DBPs generated from the chlorination of histidine (His), alanine (Ala) and tryptophan (Trp) shared by the three pipe materials and their formation pathways. Compared to carbonaceous disinfection by-products (C-DBPs), nitrogenous disinfection by-products (N-DBPs) had a significant advantage in toxicity generation potentials in the biofilms, especially dichloroacetonitrile (DCAN) and trichloronitromethane (TCNM). DCAN and haloacetic acids (HAAs) were the key to cytotoxicity in biofilms, while TCNM was dominant in biofilm genotoxicity.


Relation extraction: advancements through deep learning and entity-related features.
Capturing semantics and structure surrounding the target entity pair is crucial for relation extraction. The task is challenging due to the limited semantic elements and structural features of the target entity pair within a sentence. To tackle this problem, this paper introduces an approach that fuses entity-related features under convolutional neural networks and graph convolution neural networks. Our approach combines the unit features of the target entity pair to generate corresponding fusion features and applies the deep learning framework to extract high-order abstract features for relation extraction. Experimental results from three public datasets (ACE05 English, ACE05 Chinese, and SanWen) indicate that the proposed approach achieves F1-scores of 77.70%, 90.12%, and 68.84%, respectively, highlighting its effectiveness and robustness. This paper provides a comprehensive description of the approach and experimental results.


Health care utilization and attitudes toward health insurance. A comparison of privately insured and medical assistance or uninsured patients.
A questionnaire was distributed to 108 patients to find if there were differences in health care resource usage and attitudes towards health insurance between patients seen in the hand clinic, designed for patients with medical assistance or without insurance (57 patients), and those seen in the private offices of staff hand surgeons (51 patients). Clinic patients reported a mean of 18 visits to their physician in the past year as compared with 7 for private patients (P < 0.0005) and attended 52% of their scheduled appointments as compared to an 83% attendance rate for private patients (P < 0.001). Patients enrolled in a medical assistance program were less willing to pay for their health care than were private patients. Sixty-two percent of clinic patients responded that they would not be willing to pay anything at all for their health care coverage. These data suggest that health care and health insurance is a lower priority for the clinic patient. Any new health care system that includes the uninsured and underinsured must be prepared to handle different attitudes toward health care and an increase in utilization of resources.


Monitoring of the mercury mining site Almadén implementing remote sensing technologies.
The Almadén area in Spain has a long history of mercury mining with prolonged human-induced activities that are related to mineral extraction and metallurgical processes before the closure of the mines and a more recent post period dominated by projects that reclaim the mine dumps and tailings and recuperating the entire mining area. Furthermore, socio-economic alternatives such as crop cultivation, livestock breeding and tourism are increasing in the area. Up till now, only scattered information on these activities is available from specific studies. However, improved acquisition systems using satellite borne data in the last decades opens up new possibilities to periodically study an area of interest. Therefore, comparing the influence of these activities on the environment and monitoring their impact on the ecosystem vastly improves decision making for the public policy makers to implement appropriate land management measures and control environmental degradation. The objective of this work is to monitor environmental changes affected by human-induced activities within the Almadén area occurring before, during and after the mine closure over a period of nearly three decades. To achieve this, data from numerous sources at different spatial scales and time periods are implemented into a methodology based on advanced remote sensing techniques. This includes field spectroradiometry measurements, laboratory analyses and satellite borne data of different surface covers to detect land cover and use changes throughout the mining area. Finally, monitoring results show that the distribution of areas affected by mercury mining is rapidly diminishing since activities ceased and that rehabilitated mining areas form a new landscape. This refers to mine tailings that have been sealed and revegetated as well as an open pit mine that has been converted to an "artificial" lake surface. Implementing a methodology based on remote sensing techniques that integrate data from several sources at different scales greatly improves the regional characterization and monitoring of an area dominated by mercury mining activities.


First metatarsophalangeal joint arthrodesis - Do joint configuration and preparation technique matter?
The purpose of this study was to investigate the influence of joint configuration and preparation on first metatarsophalangeal (MTPJ) union rates. We performed a retrospective analysis of first MTPJ arthrodeses undertaken in our institution. Clinical notes, radiographs and postal questionnaires were used to determine outcome. Two hundred first MTPJ arthrodeses (172 patients) were included in the analysis (34 male: 138 female; mean age 62 yr). The overall union rate was 93.5%. Union was achieved in 109/118 MTPJs (92.4%) prepared in the flat-on-flat configuration and in 78/82 (95%) prepared in the ball-and-socket configuration (p=0.438). Higher union rates favoured low-velocity joint preparation [using rongeur only 21/21 (100%), rongeur and burr 26/27 (96.3%) and conical reamer 31/34 (91.2%)] but this did not reach statistical significance (p=0.317). There was a 95% satisfaction rate with surgery but male patients were less satisfied (p=0.031). Union rates were not influenced by joint configuration or preparation techniques.


[Transplantation of human embryonal tissues in athymic mice].
Various tissues of 8-10-week-old human embryos and 5-8-month-old fetuses were transplanted to nude mice. Liver, stomach, colon and musculocutaneous tissues were used for transplantation. Embryonal tissue transplants showed much more rapid growth than tissues of human fetuses.


A one-pot route to thioamides discovered by gas-phase studies: palladium-mediated CO2 extrusion followed by insertion of isothiocyanates.
A new palladium mediated "one pot" synthesis of thioamides from aromatic carboxylic acids (ArCO2H + RNCS → ArC(S)NHR + CO2) was discovered by gas-phase experiments and theoretical studies. Palladium-mediated decarboxylation of aromatic carboxylic acids followed by addition of substituted isothiocyanates leads to the corresponding thioamide derivatives.


Remotely programmed sacral neuromodulation for the treatment of patients with refractory overactive bladder: a prospective randomized controlled trial evaluating the safety and efficacy of a novel sacral neuromodulation device.
The efficacy and safety of a novel remotely programmed BetterStim sacral neuromodulation (SNM) system was evaluated in patients with refractory overactive bladder (OAB) in a prospective, controlled, multicenter trial. A total of 84 patients referred for SNM therapy from October 2015 to January 2018 were studied. Of the patients who qualified for implantation, 37 and 33 were randomly assigned to treatment and control groups, respectively. Patients in the treatment group underwent stimulation upon implantation, while stimulation was delayed in the control group for 3 months. Follow-up visits, consisting of voiding diary outcome, questionnaires regarding overactive bladder symptom score (OABSS) and quality of life were conducted at 1, 3, and 6-month post-implantation. Compared with the control group, subjects in the treatment group exhibited statistically significant improvement in OAB symptoms at 3 months. The overall success rate was achieved in 72% of the treatment group, compared with 12% of the control group at 3 months. At 6 months, there were no significant differences in key voiding diary variables between the two groups. Further, this study demonstrated sustained improvement in urinary symptom interference in OAB patients. In addition, nearly all patients expressed great satisfaction with the remote-programming methods. No serious adverse events occurred, and device-related adverse events rate was 12.86%. This clinical study demonstrates subjective and objective success of the BetterStim SNM system. Importantly, our data suggest that remote programming can be safely used as a viable option for the conventional programming with a high degree of patient satisfaction.


Serum pentraxin 3 as a biomarker for prognosis of acute minor stroke due to large artery atherosclerosis.
Pentraxin 3 (PTX3) may reflect local inflammatory status in tissues and thus serve as a potential biomarker of inflammation. Here, we investigated the utility of serum PTX3 as an index for assessing the 90-day prognosis of acute minor stroke patients. Acute minor stroke patients (N = 241) and matched healthy control subjects (N = 241) were prospectively recruited. Clinical, laboratory, and imaging data were assessed. Blood samples were collected within 48h after acute minor stroke onset and serum PTX3 levels were determined. Significant increases in stroke patients versus controls were obtained for serum PTX3 (3.14 ± 1.23 vs. 2.44 ± 0.74 ng/ml; p < .001) and C-reactive protein (CRP - 1.53 ± 0.38 vs. 1.35 ± 0.35 μg/ml; p < .05). Among the four stroke subtypes, as defined by modified Trial of Org 10172 in Acute Stroke Treatment classification, there were no statistically significant differences in serum PTX3 levels (p > .05). Multivariate logistic regression analysis revealed that serum PTX3 and LDL cholesterol could predict unfavorable outcomes at day 90 in Large Artery Atherosclerosis (LAA) patients. Serum Pentraxin 3 may serve as an independent predictor for an unfavorable outcome in the LAA subtype of acute minor stroke and may possess a superior prognostic value as compared to CRP in this LAA subgroup.


Chronic Kidney Disease Impairs Bone Defect Healing in Rats.
Chronic kidney disease (CKD) has been regarded as a risk for bone health. The aim of this study was to evaluate the effect of CKD on bone defect repair in rats. Uremia was induced by subtotal renal ablation, and serum levels of BUN and PTH were significantly elevated four weeks after the second renal surgery. Calvarial defects of 5-mm diameter were created and implanted with or without deproteinized bovine bone mineral (DBBM). Micro-CT and histological analyses consistently revealed a decreased newly regenerated bone volume for CKD rats after 4 and 8 weeks. In addition, 1.4-mm-diameter cortical bone defects were established in the distal end of femora and filled with gelatin sponge. CKD rats exhibited significantly lower values of regenerated bone and bone mineral density (BMD) within the cortical gap after 2 and 4 weeks. Moreover, histomorphometric analysis showed an increase in both osteoblast number (N.Ob/B.Pm) and osteoclast number (N.Oc/B.Pm) in CKD groups due to hyperparathyroidism. Notably, collagen maturation was delayed in CKD rats as verified by Masson's Trichrome staining. These data indicate that declined renal function negatively affects bone regeneration in both calvarial and femoral defects.


Guillain Barré syndrome (GBS): new insights in the molecular mimicry between C. jejuni and human peripheral nerve (HPN) proteins.
Profile and immunoreactivity of proteins from HPN tissue, and from Campylobacter jejuni (O:19) were investigated. Proteins were extracted, separated by SDS-PAGE, their cross reactivity monitored by Western blotting, and identified by nHPLC-nESI-HRMS analysis. Proteins from C. jejuni, at Mw ~70 KDa were chaperone/co-chaperone proteins (GroEL, DnaK and HtpG). In the corresponding HPN band were serum albumin, neurofilament light peptide, cytoskeletal keratins and one HSP 70 and one HSP60. These chaperones reciprocally share high primary sequence homology and conservation of their known epitopes. These findings suggest that HSP chaperones may be suitable candidates involved in the molecular mimicry triggering GBS.


Efficient retrograde transport of pseudorabies virus within neurons requires local protein synthesis in axons.
After replicating in epithelial cells, alphaherpesviruses such as pseudorabies virus (PRV) invade axons of peripheral nervous system neurons and undergo retrograde transport toward the distant cell bodies. Although several viral proteins engage molecular motors to facilitate transport, the initial steps and neuronal responses to infection are poorly understood. Using compartmented neuron cultures to physically separate axon infection from cell bodies, we found that PRV infection induces local protein synthesis in axons, including proteins involved in cytoskeletal remodeling, intracellular trafficking, signaling, and metabolism. This rapid translation of axonal mRNAs is required for efficient PRV retrograde transport and infection of cell bodies. Furthermore, induction of axonal damage, which also induces local protein synthesis, prior to infection reduces virion trafficking, suggesting that host damage signals and virus particles compete for retrograde transport. Thus, similar to axonal damage, virus infection induces local protein translation in axons, and viruses likely exploit this response for invasion.


Molecular mapping of a quantitative trait locus for aluminum tolerance in wheat cultivar Atlas 66.
Genetic improvement of aluminum (Al) tolerance is one of the cost-effective solutions to improve wheat (Triticum aestivum) productivity in acidic soils. The objectives of the present study were to identify quantitative trait loci (QTL) for Al-tolerance and associated PCR-based markers for marker-assisted breeding utilizing cultivar Atlas 66. A population of recombinant inbred lines (RILs) from the cross Atlas 66/Century was screened for Al-tolerance by measuring root-growth rate during Al treatment in hydroponics and root response to hematoxylin stain of Al treatment. After 797 pairs of SSR primers were screened for polymorphisms between the parents, 131 pairs were selected for bulk segregant analysis (BSA). A QTL analysis based on SSR markers revealed one QTL on the distal region of chromosome arm 4DL where a malate transporter gene was mapped. This major QTL accounted for nearly 50% of the phenotypic variation for Al-tolerance. The SSR markers Xgdm125 and Xwmc331 were the flanking markers for the QTL and have the potential to be used for high-throughput, marker-assisted selection in wheat-breeding programs.


The relationship of catatonia symptoms to symptoms of schizophrenia.
To evaluate the relationships of symptoms of catatonic schizophrenia to 77 symptoms relevant for diagnosing schizophrenia and to socioanamnestic variables. Data from a sample of 112 Canadian patients diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) were evaluated via phi correlation coefficients. Forty-five (40.2%) of our 112 patients had catatonic symptoms, either at the time of this study or in the past. However, only weak correlations (phi < 0.31) to other symptoms relevant for diagnosing schizophrenia were found, and no significant correlations to socioanamnestic variables were found. Symptoms of catatonia appear to be independent of the key symptoms of schizophrenia.


Laparoscopic blood-saving liver resection using a new radiofrequency-assisted device: preliminary report of an in vivo study with pig liver.
The aim of any device designed for liver resection is to allow blood saving and quick resections. This may be optimized using a minimally invasive approach. A radiofrequency-assisted device is described that combines a cooled blunt-tip electrode with a sharp blade on one side in an in vivo preliminary study using hand-assisted laparoscopy to perform partial hepatectomies. Eight partial hepatectomies were performed on pigs with hand-assisted laparoscopy using the radiofrequency-assisted device as the only method for transection and hemostasis. The main outcome measures were transection time, blood loss, transection area, transection speed, blood loss per transection area, and tissue coagulation depth. The risk for biliary leak also was assessed using the methylene blue test. The transection time was 13 +/- 7 min for a mean transected area of 34 +/- 11 cm(2). The mean total blood loss was 26 +/- 34 ml. The mean transection speed was 3 +/- 1 cm(2)/min, and the blood loss per transection area was 1 +/- 1 ml/cm(2). Abdominal examination showed no complications in nearby organs. One biliary leak was identified in one case using the methylene blue test. The transection surface was 34 +/- 11 cm(2), and the mean tissue coagulation depth was 9 +/- 2 mm. The inviability of the coagulated surface was assessed by adenine dinucleotide (NADH) staining. The radiofrequency-assisted device has shown with a laparoscopic approach that it can perform liver resections faster and with less blood loss using a single device in a minimally invasive manner without vascular control than other commercial devices. The results show no significant differences with the same device used in an open procedure.


Primary liposarcoma of the mediastinum. Report of a case and review of the literature.
Primary liposarcomas of the mediastinum are very rare tumors. We record herein the fiftieth documented case, and the sixth in which there was evidence of superior vena caval obstruction. All previously reported cases have been studied; their salient clinical and pathological features have been tabulated. Review of these case reports reveals that the majority of patients have complaints of respiratory distress or chest pain. Other common presenting complaints include cough and weight loss. These tumors grow to an enormous size, and symptoms are referable to compression of contiguous intrathoracic structures. Radiotherapy or chemotherapy or both are ineffective theraputic modalities. The treatment of choice is surgical in all cases. Such an approach serves to establish a tissue diagnosis, to relieve the patient's symptoms, and may at times result in a cure.


Hyperglycemia in the hamster anesthetized with Inactin [5-ethyl-5-(-methyl propyl)-2-thiobarbiturate].
Adult, male hamsters anesthetized with lnactin [5-ethyl-5-(1-methyl propyl)-2-thiobarbiturate] were found to be hyperglycemic. Blood glucose concentrations in anesthetized hamsters (300.1+/-15.6 mg/dl) were more than twice those of control animals (144.8+/-7.7 mg/dl). Neither the length of time under anesthesia nor the performance of surgery influenced the blood glucose concentration.


Serum plasminogen as a potential biomarker for the effects of low-dose benzene exposure.
Exposure to low-dose benzene may lead to hematotoxicity and cause health problems. Though peripheral blood cell count is widely used in benzene exposure assessment and health risk assessment, the reports regarding the effects of low-dose benzene exposure on blood cell count remain inconsistent. To uncover more sensitive biomarkers for low-dose benzene exposure, our previous study screened out three potential serum proteins-plasminogen (PLG), platelet basic protein (PBP) and apolipoprotein B100 (ApoB100)-as biomarkers from chronic benzene poisoning patients by using proteomic analysis. In the present study, we verify the three serum proteins as biomarkers for the effects of low-dose benzene exposure in a large low-dose benzene exposure population. The study showed that serum PLG increased in benzene exposed workers and was positively correlated with benzene exposure levels. However, no significant changes in serum PBP or ApoB100 were found in the benzene exposed workers. To explore whether the candidate serum proteins are associated with hematotoxicity, the study population was regrouped into two groups, based on their WBC counts. Our results showed that the workers with high serum PLG levels suffered higher risk of WBC abnormalities than did workers with low serum PLG levels. Taken together, these findings indicate that the increase in serum PLG might be associated with low-dose benzene exposure and benzene-induced hematotoxicity. Thus, we suggest serum PLG could be used as a potential biomarker for the effects of low-dose benzene exposure.


[Light, laser and PDT therapy for acne].
In recent years, a number of studies have evaluated the treatment of acne using electromagnetic waves, such as lasers, photodynamic therapy, visible light or radio waves. While the efficacy of laser treatment is still uncertain, photodynamic therapy shows promising results, but with marked side-effects, as destruction of sebaceous glands. Treatment with blue light (405-420 nm wavelength) also appears effective and can be regarded as an treatment option for inflammatory acne.


Immobilization of a hexaphyrin(184.108.40.206.0.0) derivative onto a tentagel-amino resin and its use in uranyl cation detection.
The synthesis of an isoamethyrin derivative containing two CH(2)CH(2)CO(2)CH(3) moieties in the beta-pyrrolic positions and its use in the colorimetric detection of the uranyl cation after immobilization onto a solid support is reported.


Convolutional neural network framework for the automated analysis of transition metal X-ray photoelectron spectra.
X-ray photoelectron spectroscopy is an indispensable technique for the quantitative determination of sample composition and electronic structure in diverse research fields. Quantitative analysis of the phases present in XP spectra is usually conducted manually by means of empirical peak fitting performed by trained spectroscopists. However, with recent advancements in the usability and reliability of XPS instruments, ever more (inexperienced) users are creating increasingly large data sets that are harder to analyze by hand. In order to aid users with the analysis of large XPS data sets, more automated, easy-to-use analysis techniques are needed. Here, we propose a supervised machine learning framework based on artificial convolutional neural networks. By training such networks on large numbers of artificially created XP spectra with known quantifications (i.e., for each spectrum, the concentration of each chemical species is known), we created universally applicable models for auto-quantification of transition-metal XPS data that are able to predict the sample composition from spectra within seconds. Upon evaluation against more traditional peak fitting methods, we showed that these neural networks achieve competitive quantification accuracy. The proposed framework is shown to be flexible enough to accommodate spectra containing multiple chemical elements and measured with different experimental parameters. The use of dropout variational inference for the determination of quantification uncertainty is illustrated.


Reproductive factors and the risk of breast cancer in old age: a Norwegian cohort study.
Reproductive factors, including early age at menarche, late age at first birth, low parity, and late age at menopause, are associated with increased risk of breast cancer, but it is not clear to which degree the associations persist into old age. Altogether 58,426 Norwegian women born between 1886 and 1928 were followed up for breast cancer incidence from 1961 to 2008. Associations of reproductive factors with breast cancer risk were analyzed separately for the age intervals 55-69 and 70 years and older, using Cox regression. The associations were of similar strength in the two age strata. At 70 years and later, hazard ratios (HR) for the following comparisons were found: late (≥17 years) versus early (<13 years) age at menarche [HR 0.79, 95 % confidence interval (CI): 0.62, 1.01, P for trend <0.001]; late (≥35 years) versus early (<20 years) age at first birth (HR 1.54, 95 % CI: 1.13, 2.11, P for trend <0.001); high (≥5) versus low (1) parity (HR 0.68, 95 % CI: 0.54, 0.86, P for trend = 0.001) and late (50-54 years) versus early (<45 years) age at menopause (HR 1.44, 95 % CI: 1.10, 1.90, P for trend = 0.002). These findings suggest that reproductive events may have life-long effects on breast cancer risk.


LncRNA FAF attenuates hypoxia/ischaemia-induced pyroptosis via the miR-185-5p/PAK2 axis in cardiomyocytes.
Pyroptosis is associated with various cardiovascular diseases. Increasing evidence suggests that long noncoding RNAs (lncRNAs) have been implicated in gene regulation, but how lncRNAs participate in the regulation of pyroptosis in the heart remains largely unknown. In this study, we aimed to explore the antipyroptotic effects of lncRNA FGF9-associated factor (FAF) in acute myocardial infarction (AMI). The expression patterns of lncRNA FAF, miR-185-5p and P21 activated kinase 2 (PAK2) were detected in hypoxia/ischaemia-induced cardiomyocytes. Hoechst 33342/PI staining, lactate dehydrogenase (LDH) release assay, immunofluorescence and Western blotting were conducted to assay cell pyroptosis. The interaction between lncRNA FAF, miR-185-5p and PAK2 was verified by bioinformatics analysis, small RNA sequencing luciferase reporter assay and qRT-PCR. The expression of LncRNA FAF was downregulated in hypoxic cardiomyocytes and myocardial tissues. Overexpression of lncRNA FAF could attenuate cardiomyocyte pyroptosis, improve cell viability and reduce infarct size during the procession of AMI. Moreover, lncRNA FAF was confirmed as a sponge of miR-185-5p and promoted PAK2 expression in cardiomyocytes. Collectively, our findings reveal a novel lncRNA FAF/miR-185-5p/PAK2 axis as a crucial regulator in cardiomyocyte pyroptosis, which might be a potential therapeutic target of AMI.


Correction to: The application of "upper-body yoga" in elderly patients with acute hip fracture: a prospective, randomized, and single-blind study.
In the original publication of this article [1], there are several errors that need to be corrected as below.


Oestrogen-receptor-mediated transcription and the influence of co-factors and chromatin state.
Oestrogen receptor-alpha (ERalpha)-regulated transcription in breast cancer cells involves protein co-factors that contribute to the regulation of chromatin structure. These include co-factors with the potential to regulate histone modifications such as acetylation or methylation, and therefore the transcriptional state of target genes. Although much of the information regarding the interaction of specific co-factors with ER has been generated by studying specific promoter regions, we now have an improved understanding of the nature of these interactions and are better placed to relate these with ER activity and potentially with the activity of breast cancer drugs, including tamoxifen.


Preoperative hydronephrosis: independent predictor for changes in renal function following nephroureterectomy.
Partial or complete urinary obstruction caused by a tumor itself may affect renal function and the eligibility for perioperative cisplatin-based chemotherapy in patients with upper tract urothelial carcinoma. We investigated whether the status of preoperative hydronephrosis provides additional predictive information concerning changes in perioperative renal function. A total of 155 patients who underwent nephroureterectomy for upper tract urothelial carcinoma from 1997 to 2010 were identified. The association between preoperative parameters including the grade of hydronephrosis and perioperative renal function was analyzed. Hydronephrosis was observed in 104 patients. The grade of hydronephrosis was 1, 2, 3 and 4 in 6 (3.9%), 25 (16.1%), 42 (27.1%) and 31 (20.0%) cases. Using a defined cut-off creatinine clearance value of ≥50 ml/min indicating eligibility for cisplatin-based chemotherapy, only 94 patients (60.6%) were eligible in the neoadjuvant setting. Of these 94 patients, 30 (31.9%) were judged to be ineligible in the adjuvant setting. Multivariate analysis demonstrated that patient age ≥70 years [P < 0.001, hazard ratio (HR) 27.9] and the absence of a higher grade hydronephrosis (P = 0.013, HR 7.40) were independent risk factors for predicting patients ineligible to receive adjuvant cisplatin-based chemotherapy. The proportion of patients ineligible to receive cisplatin-based chemotherapy changed from 40.9 to 88.6% following nephroureterectomy in patients aged ≥70 years and those with no or a lower grade hydronephrosis. The status of hydronephrosis is an independent predictor of eligibility to receive adjuvant cisplatin-based chemotherapy. The information on preoperative hydronephrosis and patient age may assist in part of the decision-making when considering neoadjuvant cisplatin-based chemotherapy.


Rare case of acral calcified angioleiomyoma with macroscopic calcium extrusion.
Acral calcified angioleiomyoma is an uncommon tumor that presents as a non-descript papule or subcutaneous nodule, classically on the foot. Biopsy or excision is typically the diagnostic method of choice as well as the treatment for these sometimes painful tumors. We report an uncommon clinical presentation of acral calcified angioleiomyoma with considerable extrusion of calcium perforating through the skin.


Effects of electroimmobilisation on blood gas and pH status in sheep.
Arterial blood gases, pH and haemoglobin concentrations were monitored for 20 minutes before, during and for 120 minutes after 60 seconds of electroimmobilisation (E-IM) at current strengths of 0 mA (control), 40 mA and 60 mA in 17 Merino ewes (36.3 +/- 1.0 kg) previously prepared with unilateral carotid artery loops. E-IM elicited whole body rigidity. During E-IM, breathing was stopped for 50 +/- 3 seconds (40 mA) and 56 +/- 2 seconds (60 mA). Arterial PO2 decreased to 43.2 +/- 2.4 mmHg (5.68 +/- 0.32 kPa) (40 mA) and 36.4 +/- 1.8 mmHg (60 mA) while arterial PCO2 rose to 59.7 +/- 1.9 mmHg (40 mA) and 69.8 +/- 2.0 mmHg (60 mA). There was a significant fall in arterial pH to 7.272 +/- 0.014 (40 mA) and 7.233 +/- 0.011 (60 mA) during E-IM and arterial haemoglobin increased by 34 +/- 3 per cent and 35 +/- 3 per cent at 40 mA and 60 mA, respectively. All the arterial blood gas and pH changes were significantly greater (P less than 0.05) during E-IM at 60 mA than at 40 mA. Multiple regression analysis indicated that the decrease in arterial PO2 during E-IM was directly related to the latency to breathe while the changes in arterial PCO2 and pH during E-IM were not.2+off


Advances in long-wavelength native phasing at X-ray free-electron lasers.
Long-wavelength pulses from the Swiss X-ray free-electron laser (XFEL) have been used for de novo protein structure determination by native single-wavelength anomalous diffraction (native-SAD) phasing of serial femtosecond crystallography (SFX) data. In this work, sensitive anomalous data-quality indicators and model proteins were used to quantify improvements in native-SAD at XFELs such as utilization of longer wavelengths, careful experimental geometry optimization, and better post-refinement and partiality correction. Compared with studies using shorter wavelengths at other XFELs and older software versions, up to one order of magnitude reduction in the required number of indexed images for native-SAD was achieved, hence lowering sample consumption and beam-time requirements significantly. Improved data quality and higher anomalous signal facilitate so-far underutilized de novo structure determination of challenging proteins at XFELs. Improvements presented in this work can be used in other types of SFX experiments that require accurate measurements of weak signals, for example time-resolved studies.


Automated analysis of 2,3-diamino-2,3-dideoxy-D-glucuronic acid by cation exchange chromatography with fluorometric postcolumn derivatization.
2,3-Diamino-2,3-dideoxy-D-glucuronic acid (diaminoglucuronic acid) occurs as its di-N-acetyl derivative as a unique constituent of some bacterial cell walls. A sensitive chromatographic method for its determination is described. Diaminoglucuronic acid was well separated from glucosamine and galactosamine in about 80 min on a Dionex DC-6A cation exchange column (0.9 x 18 cm, 50 degrees C) with a sodium citrate buffer (pH 5.28) containing boric acid (0.2 M). The amino sugars in the eluate were monitored fluorometrically by postcolumn derivatization with orthophthalaldehyde detection reagent. This method allowed the automated determination of 50-100 pmol of glucosamine, galactosamine, and diaminoglucuronic acid and was applied successfully to the analysis of diaminoglucuronic acid in Propionibacterium acnes cells.


The role of vaginal immunoglobulin A in girls with recurrent urinary tract infections.
Vaginal immunoglobulin A in girls with recurrent urinary tract infections was significantly lower when compared to an age-matched group of controls who had never experienced bacteriuria. The possible role of deficiencies in vaginal secretory immunoglobulin A leading to recurrent urinary tract infection in this age group is discussed.


New species of Nothybus Rondani, 1875 (Diptera: Nothybidae) from Vietnam with a key to Vietnamese species of the genus.
This study is part of an ongoing series of studies on the Vietnamese cyclorrhaphous fauna. One new species from Vietnam, Nothybus kuznetsovorum sp.nov., is described and figured. A key to species of Nothybus is provided. Genital structures are described and figured.


Synthesis and farnesylation of a-factor fusion proteins in Saccharomyces cerevisiae.
We have generated in-frame fusions between the mouse dihydrofolate reductase (DHFR) and parts of the a-factor MFA1 gene to explore the potential of a-factor as a secretion signal for larger polypeptides. We demonstrated that the fusion proteins are farnesylated by comparing the mobility of fusion proteins prepared from a wild-type strain and a farnesyltransferase mutant (ste16/ram1) on SDS-gels and by an in vitro farneyslation assay. In contrast to unmodified DHFR, the fusion proteins could be sedimented from cell extracts by centrifugation. Solubilization experiments indicated that the highly hydrophobic a-factor moiety renders the fusion proteins insoluble, explaining why the fusions are not secreted into the culture medium.


Isolation of a collagen fraction from the body-wall glycoproteins of the leech (Hirudo medicinalis), and characterization of its carbohydrate--amino acid portion.
Fractionation of the leech (Hirudo medicinalis) body-wall glycoproteins yielded a collagen fraction containing only D-glucose and D-galactose as its carbohydrate constituents. Digestion of the collagen with trypsin and pronase, and alkaline degradation of the resulting glycopeptides, gave a product that contained a disaccharide linked to hydroxylysine. Mild, acid hydrolysis of the N-acetylated glycopeptides yielded a disaccharide consisting of a D-glucose and a D-galactose residue. Various chemical and enzymic reactions of the disaccharide, the glycosyloxylysine, and the glycopeptide fraction indicated that the disaccharide is 2-O-alpha-D-glucopyranosyl-D-galactose, and that this is beta-glycosidically linked to O-5 of the hydroxylysine residue in the collagen.


Corrigendum to "Patient Delay in Initiating Tuberculosis Treatment and Associated Factors in Oromia Special Zone, Amhara Region".
[This corrects the article DOI: 10.1155/2020/6726798.].


Glucocorticoids and the renal Na-H antiporter: role in respiratory acidosis.
We examined the role of glucocorticoids in the activity of the renal brush border Na-H antiporter under baseline conditions (5% CO2 gassing) and during respiratory acidosis (10% CO2 gassing) in cultured monolayers of a proximal tubule suspension (primary cultures of the proximal tubule). Primary cultures of the proximal tubule showed an adaptive increase in renal brush border Na-H antiporter activity in response to respiratory acidosis in presence but not in the absence of physiologic concentrations of hydrocortisone in the medium. The effect of hydrocortisone to increase the activity of the renal brush border Na-H antiporter in respiratory acidosis could also be elicited by dexamethasone. Deletion of hydrocortisone from the medium also impaired the baseline activity of the Na-H antiporter. The effect of hydrocortisone to increase the activity of the Na-H antiporter under baseline conditions and during respiratory acidosis was elicited by physiologic concentrations of the hormone and 100-fold increase in concentration did not further increase the activity of the Na-H antiporter. These results demonstrate that the presence of physiologic concentrations of glucocorticoids are necessary for the baseline activity of the renal brush border Na-H antiporter and its adaptive increase in response to respiratory acidosis.


Towards an operational system for oil-spill forecast over Spanish waters: initial developments and implementation test.
The ESEOO Project, launched after the Prestige crisis, has boosted operational oceanography capacities in Spain, creating new operational oceanographic services and increasing synergies between these new operational tools and already existing systems. In consequence, the present preparedness to face an oil-spill crisis is enhanced, significantly improving the operational response regarding ocean, meteorological and oil-spill monitoring and forecasting. A key aspect of this progress has been the agreement between the scientific community and the Spanish Search and Rescue Institution (SASEMAR), significantly favoured within the ESEOO framework. Important achievements of this collaboration are: (1) the design of protocols that at the crisis time provide operational state-of-the-art information, derived from both forecasting and observing systems; (2) the establishment, in case of oil-spill crisis, of a new specialized unit, named USyP, to monitor and forecast the marine oceanographic situation, providing the required met-ocean and oil-spill information for the crisis managers. The oil-spill crisis scenario simulated during the international search and rescue Exercise "Gijón-2006", organized by SASEMAR, represented an excellent opportunity to test the capabilities and the effectiveness of this USyP unit, as well as the protocols established to analyze and transfer information. The results presented in this work illustrate the effectiveness of the operational approach, and constitute an encouraging and improved base to face oil-spill crisis.


Contribution of high risk groups' unmet needs may be underestimated in epidemic models without risk turnover: A mechanistic modelling analysis.
Epidemic models of sexually transmitted infections (STIs) are often used to characterize the contribution of risk groups to overall transmission by projecting the transmission population attributable fraction (tPAF) of unmet prevention and treatment needs within risk groups. However, evidence suggests that STI risk is dynamic over an individual's sexual life course, which manifests as turnover between risk groups. We sought to examine the mechanisms by which turnover influences modelled projections of the tPAF of high risk groups. We developed a unifying, data-guided framework to simulate risk group turnover in deterministic, compartmental transmission models. We applied the framework to an illustrative model of an STI and examined the mechanisms by which risk group turnover influenced equilibrium prevalence across risk groups. We then fit a model with and without turnover to the same risk-stratified STI prevalence targets and compared the inferred level of risk heterogeneity and tPAF of the highest risk group projected by the two models. The influence of turnover on group-specific prevalence was mediated by three main phenomena: movement of previously high risk individuals with the infection into lower risk groups; changes to herd effect in the highest risk group; and changes in the number of partnerships where transmission can occur. Faster turnover led to a smaller ratio of STI prevalence between the highest and lowest risk groups. Compared to the fitted model without turnover, the fitted model with turnover inferred greater risk heterogeneity and consistently projected a larger tPAF of the highest risk group over time. If turnover is not captured in epidemic models, the projected contribution of high risk groups, and thus, the potential impact of prioritizing interventions to address their needs, could be underestimated. To aid the next generation of tPAF models, data collection efforts to parameterize risk group turnover should be prioritized.


Anorectal physiology measurement: report of a working party.
A 2-day meeting was held in Bristol on 5 and 6 July 1988 immediately before the Tripartite meeting of the Surgical Research Society in order to discuss methods and identify areas of agreement with regard to measurement of indices of anorectal physiology. The following report highlights our findings.


Characterization of the hydroperoxide-reducing activity of human plasma.
A peroxidase was identified in human plasma using a novel peroxidase assay. In this assay both the substrate 5-phenyl-4-pentenyl hydroperoxide (PPHP) and its reduction product, 5-phenyl-4-pentenyl alcohol (PPA) are quantitated by HPLC. Substrate specificity studies indicated that the peroxidase requires glutathione as reducing substrate. No reduction was detected using the classical heme peroxidase reducing substrates, phenol and hydroquinone. Peroxidase activity was not due to glutathione transferases. Failure to saturate the peroxidase activity with reduced glutathione and inhibition by Cd+2 indicated that it is probably selenium dependent. The enzyme appears to be different from erythrocyte glutathione peroxidase based on kinetic and immunological experiments. The apparent Km values for PPHP are 25 microM for erythrocyte peroxidase and 54 microM for plasma peroxidase at 0.5 mM reduced glutathione. Anti-peroxidase prepared against bovine erythrocyte glutathione peroxidase partially inhibited human erythrocyte peroxidase but did not inhibit human plasma peroxidase.


TIL 2.0: More effective and predictive T-cell products by enrichment for defined antigen specificities.
Adoptive transfer of in vitro-expanded T cells derived from tumor-infiltrating lymphocytes (TILs) in melanoma patients started the era of tumor immunotherapy three decades ago. The approach has demonstrated remarkable clinical responses in several studies since. Reinfusion of TIL-derived T cells represents a highly personalized form of immunotherapy, taking into account the enormous interindividual tumor heterogeneity. However, despite its successes, TIL therapy does not lead to objective clinical responses in all cases. It is thus crucial to find out which tumor antigens are particularly valuable targets and to develop strategies to enhance the reactivity of T-cell products toward them. In this issue of the European Journal of Immunology, Kelderman et al. [Eur. J. Immunol. 2016. 46: 1351-1360] present a platform for the generation of antigen-specific TIL therapy. Combining recently developed technologies for clinical identification and enrichment of antigen-specific CD8(+) T cells, such as MHC Streptamers and UV-mediated peptide exchange, the authors could enrich T-cell populations with defined antigen specificities from melanoma-derived TILs. This T-cell product showed higher reactivity against autologous tumor cell lines than bulk TIL-derived T cells. The novel platform might enable the generation of more effective and predictable TIL-derived T-cell products for future clinical applications.


Clinical presentation and short-term outcome of endoscopic therapy of patients with symptomatic incomplete pancreas divisum.
The clinical significance of incomplete pancreas divisum (IPD) has not been fully described. In this study we report the clinical presentation and results of endoscopic treatment of the 32 (0.6%) patients with IPD seen at our center over a 10-year period. The study population consisted of 24 women and 8 men (mean age 42 years, range 13 to 82 years). Ten (31%) patients presented with acute recurrent pancreatitis, 5 (16%) with chronic pancreatitis, and 3 (9%) with pancreatic type pain. Detailed history, laboratory tests, US, CT, and ERCP excluded other etiologies for their symptoms. The remaining 14 (44%) presented with biliary problems. The 18 symptomatic patients with IPD were treated as follows: 8 received dorsal duct stents, 3 underwent minor papilla endoscopic sphincterotomy and dorsal duct stent placement, 4 had minor papilla dilatation only, and 3 had ventral duct stents placed. Patients were then followed for recurrence of pancreatitis and pancreatic-type pain. Mean follow-up was 15.5 months (range 3 to 30 months). Six (60%) of the patients with acute recurrent pancreatitis and 4 (80%) with chronic pancreatitis benefitted from the endoscopic therapy. However, only 1 (33%) of the patients with pancreatic-type pain benefitted. The clinical presentation and response to endoscopic therapy of patients with ICP appeared to be similar to that of patients with complete pancreas divisum.


Mothers' ability to determine and measure paracetamol doses for children-a contrived observational study.
Caregivers are primarily responsible for the administration of Over The Counter (OTC) medications in children. This study examines the mothers' ability to determine and measure paracetamol doses for children aged between 1 and 5 years. A contrived observational study was conducted for mothers of preschool aged children at two Public Health Midwifery (PHM) areas in Southern province, Sri Lanka. Stratified random sampling was used. Only 26.9% (n = 95, 95% CI = 22.5%-31.7%) of the 353 participants correctly determined and measured the doses of paracetamol. Errors were frequently made in both determining and measuring dose together (n = 113, 32.0%, 95% CI = 27.3%-37.1%), determining only (n = 94, 26.6%, 95% CI = 22.2%-31.5%) and measurement only (n = 51, 14.4%, 95% CI = 11.1%-18.5%). Dose determined errors were not significantly associated with maternal education, number of children in the family, total monthly income and age of the index child. Similarly measuring errors were not significantly associated with mothers' education, income of the family and number of children in the family. However, there was a weak positive correlation between measuring errors and age of the index child. The study suggests that mothers made errors when determining doses and measuring doses of paracetamol. Results emphasize importance of clear, concise guardian information leaflet and healthcare professionals' guidance to minimize dosing errors of child medication.


A longitudinal study of humoral immune responses induced by a 3-dose inactivated COVID-19 vaccine in an observational, prospective cohort.
To determine the dynamic SARS-CoV-2 specific antibody levels induced by 3 doses of an inactivated COVID-19 vaccine, CoronaVac. An observational, prospective cohort study was performed with 93 healthy healthcare workers from a tertiary hospital in Nanjing, China. Serum SARS-CoV-2 specific IgM, IgG, and neutralizing antibodies (NAb) were measured at different time points among participants who received 3 doses of inactivated COVID-19 vaccine. 91.3% (85/93) and 100% (72/72) participants showed positive both for SARS-CoV-2 specific IgG and NAb after 2-dose CoronaVac and after 3-dose CoronaVac, respectively. Anti-SARS-CoV-2 IgG responses reached 91.21 (55.66-152.06) AU/mL, and surrogate NAb was 47.60 (25.96-100.81) IU/mL on day 14 after the second dose. Anti-SARS-CoV-2 IgG responses reached 218.29 (167.53-292.16) AU/mL and surrogate NAb was 445.54 (171.54-810.90) IU/mL on day 14 after the third dose. Additionally, SARS-CoV-2 specific surrogate neutralizing antibody titers were highly correlated with serum neutralization activities against Ancestral, Omicron, and Delta strains. Moreover, significantly higher SARS-CoV-2 IgG responses, but not NAb responses, were found in individuals with breakthrough infection when compared to that of 3-dose CoronaVac recipients. CoronaVac elicited robust SARS-CoV-2 specific humoral responses. Surrogate NAb assay might substitute for pseudovirus neutralization assay. Monitoring SARS-CoV-2 antibody responses induced by vaccination would provide important guidance for the optimization of COVID-19 vaccines.


Isolation of bovine cardiodilatin by fast protein liquid chromatography and reversed-phase high-performance liquid chromatography.
Cardiodilatin (CDD), a polypeptide exhibiting vasorelaxant and diuretic natriuretic bioactivity, was isolated from bovine atria. The isolation procedure reported here is different from that originally used for the purification of porcine and bovine CDD. Instead of cation-exchange chromatography on Fractogel TSK-CM 650 S and several purification steps on different high-performance liquid chromatographic (HPLC) columns, it is now possible to obtain CDD-88 by an automated fast-protein liquid chromatography system for repeated injections and a motor valve as fraction collector and only one final step of reversed-phase HPLC on a TSK-ODS-120T column.


Perinatal malnutrition programs gene expression of leptin receptors isoforms in testis and prostate of adult rats.
The aim of this paper was to evaluate if maternal malnutrition during lactation programs the expression of leptin receptor isoforms in the testes and prostate ventral lobe of adult rats. At delivery, Wistar rats were separated into 3 groups: control group (C) with free access to a standard laboratory diet containing 22% protein; protein-energy restricted group (PER) with free access to an isoenergy and protein-restricted diet containing 8% protein; and energy-restricted group (ER) receiving standard laboratory diet in restricted quantities, which were calculated according to the mean ingestion of the PER group. All animals were sacrificed at 90 days of age. Both PER and ER groups presented low body weight from the first days after birth, however, while the ER group reached the control weight around day 80, the body weight of PER group was significantly lower compared to controls until the day the animals were killed. In relation to tissue weight, only the relative testis weight of the ER group presented an alteration compared to the control group (p<0.03). There was also no alteration in the leptin serum levels among the groups. The main leptin receptors isoforms, OBRa and OBRb were significantly increased in the testis (OBRa: C=0.71±0.10; PER=1.14±0.17; ER=1.92±0.70, p<0.0007, OBRb: C=0.87±0.04; PER=1.20±0.05; ER=1.44±0.17, p<0.001) and prostate (OBRa: C=0.70±0.18; PER=1.30±0.14; ER=1.65±0.22, p<0.014, OBRb: C=0.77±0.14; PER=1.16±0.04; ER=1.30±0.13, p<0.027) of both malnourished groups. However, the testis OBRc (C=1.52±0.06; PER=1.35±0.23; ER=3.50±0.72, p<0.023) and OBRf (C=1.31±0.12; PER=1.66±0.27; ER=3.47±0.55, p<0.009) and prostate OBRc (C=0.48±0.13; ER=1.18±0.34, p<0.01) and OBRf (C=0.73±0.15; PER=0.99±0.11; ER=1.83±0.30, p<0.016) isoforms were significantly increased only in the ER group. The results presented here show for the first time that both testis and prostate leptin receptor isoforms gene expression are programmed by perinatal malnutrition. These data further stress the importance of monitoring maternal and neonatal status, as well as other pathophysiological situations, to combat the appearance of long-term diseases.


An experimental study on perceptions of energy drink ads among youth and young adults in Canada.
Current regulations in Canada prohibit the marketing of caffeinated energy drinks (CEDs) for use during sports, with alcohol, and by children. The study examined perceptions of CED ads in association with sports and alcohol use, as well as target age groups. An online survey was conducted in 2015 with youth and young adults aged 12-24 years (n = 2010). Participants completed three experiments in which they were randomized to view CED advertisements: 1) sports/party-themed ads, 2) sports-themed ad, and 3) party-themed ad, vs. control 'product information' ads. For each ad, participants were asked about perceived target age group, and if the ad promoted using CEDs during sports and with alcohol. Logistic regression models were fitted to test differences in outcomes between conditions. The majority of respondents reported that the ads, across all themes, targeted people their age. In experiment 1, both sports/party-themed ads were more likely to be perceived as promoting use of CEDs during sports (AOR = 13.32; 95% CI 9.90, 17.91, and AOR = 9.73; 95% CI 7.38, 12.81, respectively), and with alcohol (AOR = 8.55; 95% CI 6.37, 11.48, and AOR = 2.81; 95% CI 2.08, 3.78, respectively), compared to the control ad. In experiment 2, the sports-themed ad was more likely to be perceived as promoting use of CEDs during sports (AOR = 15.02; 95% CI 11.83, 19.08), but not with alcohol, compared to the control ad. In experiment 3, the party-themed ad was more likely to be perceived as promoting use of CEDs with alcohol (AOR = 13.79; 95% CI 10.69, 17.78), but not during sports, compared to the control ad. Ads from leading energy drink brands are perceived as targeting young people and encouraging energy drink use during sports and with alcohol, despite Canadian regulations prohibiting these marketing practices.


Growth physiology and dimorphism of Mucor circinelloides (syn. racemosus) during submerged batch cultivation.
Mucor circinelloides is being investigated as a possible host for the production of heterologous proteins. Thus, the environmental conditions defining the physiology and morphology of this dimorphic fungus have been investigated in submerged batch cultivation. The optimal conditions for growth of each form have been defined. Pure cultures of the multi-polar budding yeast form could be obtained under anaerobic conditions (with 70% N2/30% CO2 or 100% N2 as the sparge gas and without aeration). The highest maximum specific growth rate (0.30 h(-1)) was obtained in anaerobic cultivation, the yield of biomass on glucose (Y(SX)) was 0.12 (c-mole basis). A high maximum specific growth rate was obtained when the organism grew as the filamentous form under aerobic conditions (0.25 h(-1)), with a Y(SX) of 0.24 (c-mole basis). The maximum specific growth rates achieved are comparable to most industrial filamentous fungi under similar growth conditions. High levels of ethanol were observed with all growth conditions. The overriding effector of morphological development was found to be oxygen. In batch cultures it was therefore possible to induce the dimorphic shift by controlling the influent gas atmosphere. A specific growth rate of 0.19 h(-1) was maintained during the shift from the yeast to the filamentous form.


Every family: a population approach to reducing behavioral and emotional problems in children making the transition to school.
A large-scale population trial using the Triple P-Positive Parenting Program (TPS) was evaluated. The target population was all parents of 4- to 7-year-old children residing in ten geographical catchment areas in Brisbane (intervention communities) and ten sociodemographically matched catchment areas from Sydney (5) and Melbourne (5), care as usual (CAU) comparison communities. All five levels of the Triple P multilevel system of intervention were employed; including a local mass media strategy, a primary care strategy, and three more intensive levels of parenting intervention delivered by a range of service providers (e.g., health, education, and welfare sectors). Program outcomes were assessed through a computer-assisted telephone interview of a random sample of households (N = 3000) in each community at pre-intervention and again at two years post-intervention. At post-intervention there were significantly greater reductions in the TPS communities in the number of children with clinically elevated and borderline behavioral and emotional problems compared to the CAU communities. Similarly parents reported a greater reduction in the prevalence of depression, stress and coercive parenting. Findings show the feasibility of targeting dysfunctional parenting practices in a cost-effective manner and the public acceptance of an approach that blends universal and targeted program elements. Editors' Strategic Implications: This is the first positive parenting program to demonstrate longitudinal, population-level effects for parents and children. The authors provide an excellent example of multilevel prevention planning, coordination, execution, and evaluation.


Effects of centrally administered neuropeptides on discriminative stimulus properties of cocaine in the rat.
The present study was designed to investigate the effects of centrally administered neuropeptides on the discriminative stimulus properties of cocaine in the rat. Rats were trained to discriminate 10.0 mg/kg of cocaine from vehicle in a shock avoidance paradigm. The mu-selective opioid agonist [D-Ala2,NMePhe4,Gly-ol]enkephalin (DAMGO) (0.03-0.3 microgram, ICV) or the kappa-selective opioid agonist dynorphin A-(1-13) (1.0-10.0 micrograms, ICV) did not generalize to cocaine cue, although the delta-selective opioid agonist [D-Pen2,L-Pen5]enkephalin (DPLPE) (10.0 micrograms, ICV) reportedly generalizes to it through the mediation of delta-opioid receptors. Thyrotropin-releasing hormone (10.0-56.0 micrograms, ICV), somatostatin (0.3-3.0 micrograms, ICV), substance P (3.0-17.5 micrograms, ICV), or neurotensin (3.0-17.5 micrograms, ICV) did not produce any stimulus effects in common with cocaine. It appears that neuropeptides other than the delta-selective opioid do not play a major role in the discriminative stimulus properties of cocaine.


Leukocyte mitochondrial DNA copy number and built environment in Mexican Americans: a cross-sectional study.
Mitochondrial DNA (mtDNA) copy number in leukocytes has been regarded as a biomarker for various environmental exposures and chronic diseases. Our previous study showed that certain demographic factors (e.g. age, gender, BMI, etc.) significantly affect levels of leukocyte mtDNA copy number in Mexican Americans. However, the effect of the built environment on leukocyte mtDNA copy number has not been studied previously. In this cross-sectional study, we examined the association between multiple components of the built environment with leukocyte mtDNA copy number among 5,502 Mexican American adults enrolled in Mano-A-Mano, the Mexican American Cohort Study (MACS). Based on the median levels of mtDNA copy number, the study population was stratified into low mtDNA copy number group (< median) and high mtDNA copy number group (≥ median). Among all built environment exposure variables, household density and road/intersection ratio were found to be statistically significant between groups with low and high mtDNA copy number (P < 0.001 and 0.002, respectively). In the multivariate logistic regression analysis, individuals living in areas with elevated levels of household density had 1.24-fold increased odds of having high levels of mtDNA copy number [Odds ratio (OR) = 1.24, 95% confidence interval (CIs) 1.08, 1.36]. Similarly, those living in areas with elevated levels of road/intersection ratio had 1.12-fold increased odds of having high levels of mtDNA copy number (OR = 1.12, 95% CI 1.01, 1.27). In further analysis, when both variables were analyzed together in a multivariate logistic regression model, the significant associations remained. In summary, our results suggest that selected built environment variables (e.g. population density and road/intersection ratio) may influence levels of mtDNA copy number in leukocytes in Mexican Americans.


Wolbachia-infected Trichogramma dendrolimi is outcompeted by its uninfected counterpart in superparasitism but does not have developmental delay.
Wolbachia infection increases the superparasitism frequency of Trichogramma females and provides an opportunity for horizontal intraspecific transmission. However, superparasitism may lead to interstrain competition between Wolbachia-infected Trichogramma offspring and their uninfected counterparts. This study investigated the outcome of interstrain intrinsic competition between Wolbachia-infected thelytokous strain (W) and uninfected bisexual strain (B) of Trichogramma dendrolimi. To determine the developmental rate of both strains, the sizes of immature stages of T. dendrolimi offspring at different times after parasitisation were measured in single parasitism and superparasitism conditions. The results reflect increased superparasitism by Wolbachia-infected females compared with uninfected females. Trichogramma females did not discriminate between host eggs previously parasitised by either B or W females. When the first oviposition was performed by B females, the B offspring outcompeted W offspring deposited later. Although when W offspring was deposited 8 h earlier than the B offspring, it gained no advantage over B offspring. Regardless of parasitism conditions, differences in the development rate between W and B offspring were not significant. The results reconfirmed that W females presented a higher tendency for superparasitism than B females, and showed that B offspring outcompeted W offspring even when the latter was deposited 8 h earlier. The inferiority of Wolbachia-infected Trichogramma compared with their uninfected counterparts is not due to the developmental delay. This study provides insights into the effects of intrinsic competition on the control efficacy of Wolbachia-infected Trichogramma against pests in biological control programs. © 2022 Society of Chemical Industry.