NMR spectroscopy and electron microscopy identification of metabolic and ultrastructural changes to the kidney following ischemia-reperfusion injury.
Cellular, molecular, and ultrastructural nephron changes associated with ischemia-reperfusion injury-induced acute kidney injury (IRI-AKI) are not completely understood. Here, a multidisciplinary study was used to identify nephron changes in a mouse model of IRI-AKI. Histological analyses indicated distended Bowman's glomerular spaces and proximal and distal tubules. Increased filtrate volume in nephrons was caused by reduced water reabsorption by severely damaged proximal tubule brush borders and blocked flow of filtrate into collecting tubules by mucoprotein casts in distal tubules. Immunohistochemistry revealed protein AKI biomarkers in proximal tubules and glomeruli but not in distal tubules. Nuclear magnetic resonance spectroscopy revealed several metabolites that increased such as valine, alanine, and lactate. Other metabolites such as trigonelline, succinate, 2-oxoisocaproate, and 1- methyl-nicotinamide decreased or were absent in urine following IRI due to altered kidney function or metabolism. Urinary glucose increased due to reduced reabsorption by damaged proximal tubule brush borders. Scanning electron microscopy revealed flattening of podocytes and pedicals surrounding glomerular capillaries, and transmission electron microscopy (TEM) revealed effacement of podocyte pedicals, both consistent with increased hydrostatic pressure in nephrons following IRI-AKI. TEM revealed shortened proximal tubule microvilli in IRI kidneys with diminished lamina propia. TEM showed dramatic loss of mitochondria in distal tubule epithelia of IRI kidneys and emergence of multivesicular bodies of endosomes indicating ongoing cellular death. Collectively, the data define ultrastructural changes to nephrons and altered kidney metabolism associated with IRI-AKI.


Nanoscopic interactions of colloidal particles can suppress millimetre drop splashing.
The splashing of liquid drops onto a solid surface is important for a wide range of applications, including combustion and spray coating. As the drop hits the solid surface, the liquid is ejected into a thin horizontal sheet expanding radially over the substrate. Above a critical impact velocity, the liquid sheet is forced to separate from the solid surface by the ambient air, and breaks up into smaller droplets. Despite many applications involving complex fluids, their effects on splashing remain mostly unexplored. Here we show that the splashing of a nanoparticle dispersion can be suppressed at higher impact velocities by the interactions of the nanoparticles with the solid surface. Although the dispersion drop first shows the classical transition from deposition to splashing when increasing the impact velocity, no splashing is observed above a second higher critical impact velocity. This result goes against the commonly accepted understanding of splashing, that a higher impact velocity should lead to even more pronounced splashing. Our findings open new possibilities to deposit large amount of complex liquids at high speeds.


Raspberry ketone accelerates sexual maturation and improves mating performance of sterile male Queensland fruit fly, Bactrocera tryoni (Froggatt).
Tephritid fruit flies are recognized as the most economically important insect pest group, causing significant losses to horticultural crops globally. The sterile insect technique (SIT) is used to suppress or eradicate pest fruit flies in many countries. The provisioning of adult dietary or olfactory supplementation pre-release is commonly used to improve the mating performance of sterile male flies in SIT. This study on a major pest species, Queensland fruit fly, Bactrocera tryoni (Froggatt), focused on improving mating performance by providing a semiochemical, raspberry ketone (RK), in the pre-release adult diet. Survival was numerically higher for RK-supplemented males. Sexual maturity occurred 1 day earlier (from 7 to 6 days) in RK-supplemented sterile males. The mating latency period decreased with maturation age and was lower for RK-fed males. RK-supplemented sterile males increasingly mated with fertile females as they aged (10-19 days). The mating competitiveness of both RK-supplemented sterile males and RK-denied sterile males was greater than that of wild males. The early sexual maturity and increased mating performance of RK-supplemented sterile males indicate that the effectiveness of SIT programmes can be increased through dietary supplementation with RK during the pre-release period. © 2018 Society of Chemical Industry.


Joint estimation of contemporary seed and pollen dispersal rates among plant populations.
There are few statistical methods for estimating contemporary dispersal among plant populations. A maximum-likelihood procedure is introduced here that uses pre- and post-dispersal population samples of biparentally inherited genetic markers to jointly estimate contemporary seed and pollen immigration rates from a set of discrete external sources into a target population. Monte Carlo simulations indicate that accurate estimates and reliable confidence intervals can be obtained using this method for both pollen and seed migration rates at modest sample sizes (100 parents/population and 100 offspring) when population differentiation is moderate (F(ST) ≥ 0.1), or by increasing pre-dispersal samples (to about 500 parents/population) when genetic divergence is weak (F(ST) = 0.01). The method exhibited low sensitivity to the number of source populations and achieved good accuracy at affordable genetic resolution (10 loci with 10 equifrequent alleles each). Unsampled source populations introduced positive biases in migration rate estimates from sampled sources, although they were minor when the proportion of immigration from the latter was comparatively low. A practical application of the method to a metapopulation of the Australian resprouter shrub Banksia attenuata revealed comparable levels of directional seed and pollen migration among dune groups, and the estimate of seed dispersal was higher than a previous estimate based on conservative assignment tests. The method should be of interest to researchers and managers assessing broad-scale nonequilibrium seed and pollen gene flow dynamics in plants.


Nutrients influence the multi-trophic impacts of an invasive species unaffected by native competitors or predators.
Non-native species often lead to undesirable ecological and environmental impacts. Two hypotheses that predict establishment of non-native species are enemy release and biotic resistance. Support for these hypotheses in freshwater invasions is mixed. Experiments combined with field observations provide a complementary approach to understanding how interactions between native and non-native species lead to enemy release or biotic resistance. We tested experimentally whether these hypotheses provided insights into the invasion of the banded mystery snail (Viviparus georgianus), which has invaded the Great Lakes region and northeastern Unites States (US) from the southeastern US. Because freshwater systems vary widely in their nutrient concentrations due to natural and anthropogenic processes, we tested whether nutrient additions altered competitive and predatory interactions that regulate mechanisms of enemy release or biotic resistance. We evaluated the status of the mystery snail invasion in a 3-year field survey of Lake George (NY, US) to identify if field observations supported any experimental conclusions. The presence of the banded mystery snail led to a 14% and 27% reduction in biomass of a native competitor under low- and high-nutrient concentrations, respectively. The mystery snail also triggered a 29% biomass loss of a native snail predator, but only in low-nutrient concentrations. Field surveys indicated that the mystery snail dominated the snail community; of seven snail species, it comprised 77% of all snails. Results from the field surveys combined with experimental results indicate that neither competitors nor predators have likely suppressed the invasion of the banded mystery snail. This conclusion is consistent with competitive- and predatory-enemy release as we found no indication of biotic resistance via competition or predation from native species. Our results further highlight that the post-establishment impacts of invasive species are altered by the trophic state of freshwater ecosystems.


[Clonazepam in therapy of neurogenic syncopal states].
27 patients with frequent neurogenic syncopes (NS) resistant to conventional therapy were treated with clonazepam. The average age of the patients was 29.8 +/- 11.6 years. There were 1-2 syncopes in a month. Both before and after the treatment an active orthostatic test was performed with ECG registration and following analysis of variability of the cardiac rhythm. Clonazepam was administered in a dose of 2-2.5 mg/day during 8-9 weeks. Clinical improvement in the form of a lack of syncopes was observed in 20 patients (74%); 3 patients (10%) had isolated lipothymic states; 2 patients discontinued the treatment because of side-effects (dizziness). The results of the examination of 23 patients 6 months after clonazepam therapy testified the stability of the therapeutic effect.


Global Adult Tobacco Survey (GATS): a case for change in definition, analysis and interpretation of "cigarettes" and "cigarettes per day" in completed and future surveys.
The Global Adult Tobacco Survey has 15 key indicators, cigarettes smoked per day (CPD) among daily smokers being one of them. The first wave of GATS in 14 countries indicated that mean CPD use is higher in women than men in India only, which is contrary to the current understanding of tobacco use globally. This study was undertaken to understand the unusual findings for mean CPD use in the GATS-India survey. Items B06a and B06b of the GATS India survey questionnaire that collected information on daily consumption of manufactured and rolled cigarettes were analyzed using SPSS software. Exclusive users were identified from these items after excluding the concurrent users of other tobacco products. Cigarette type, exclusive use and gender stratified analyses were made. Consumption of different types of cigarettes among the mixed users of manufactured and rolled cigarettes were correlated. Higher mean number of CPD use among male daily-smokers was observed than their female counterparts in product specific analysis. Mean CPD as per GATS cigarette definition was higher in males than females for exclusive users but a reverse trend was observed in case of non-exclusive users. Use of manufactured cigarettes increased with increase in use of rolled cigarette among the mixed users and around half of these users reported equal CPD frequency for the both types of cigarettes. The anomaly in mean CPD estimate in GATS-India data was due to inclusion of two heterogeneous products to define cigarettes, variation in cigarette product specific user proportions contributing to the average and non-exclusive concurrent use of other tobacco products. The consumption pattern of cigarettes among the mixed users highlights bias in CPD reporting. Definition, analysis and interpretation of 'cigarettes per day' in the GATS India survey need to be improved by redefining cigarettes and making product specific analyses.


Development and implementation of a pharmacist-led telehealth medication management program for veterans receiving oral antineoplastic therapies through the MISSION Act.
Veterans prescribed oral antineoplastic therapies (OATs) by community providers outside the Veterans Health Administration (VA) may lack access to comprehensive medication management. To address this, our multidisciplinary team developed and implemented a pharmacist-led telehealth medication management program for veterans prescribed OATs by community providers. The program exclusively uses telehealth to connect veterans with a dedicated board-certified clinical oncology pharmacist who provides comprehensive medication management. The program is based on established pharmacy models found in the research literature. We developed a standard operating procedure, communication templates, patient education materials, and a suite of health information technology tools to help streamline pharmacy processes. The Consolidated Framework for Implementation Research was used to design implementation strategies to promote the adoption of the program. In the first year, 64 veterans from 3 VA medical centers were enrolled in the program. The oncology clinical pharmacist performed 342 encounters and 101 interventions. The program saved an estimated $200,724 in medication-related costs. The veterans we surveyed reported high levels of satisfaction with the pharmacy services provided by the program. The delivery of comprehensive medication management through telehealth is feasible from a healthcare system perspective and beneficial for patients. The board-certified oncology clinical pharmacist provided remote pharmacy services to Veterans across three sites in a large and rural service area for the VA. The program realized several benefits, including positive clinical outcomes, high levels of patient satisfaction, and cost savings on medication-related costs.


Doctors and nurses in outback Australia: living with bush initiatives.
This qualitative in-depth study investigates the work and life experiences of 18 female doctors and nurses in remote Australia. The study begins to unravel some of the events and relationships in the women's lives that keep them working and living in remote areas. The study also examines social and working conditions that cause the women to leave, and concludes that action must be taken at both government and local levels to support female health professionals who work in remote locations. This may be achieved by the means of a health promotion action model to underpin such initiatives as the 1999 Commonwealth Government 'fly-in-fly-out' initiative, in which sessional female doctors provide women's health services in remote areas.


Ultrahigh precision nonlinear reflectivity measurement system for saturable absorber mirrors with self-referenced fluence characterization.
Measurement of nonlinear optical reflectivity of saturable absorber devices is discussed. A setup is described that enables absolute accuracy of reflectivity measurements better than 0.3%. A repeatability within 0.02% is shown for saturable absorbers with few-percent modulation depth. The setup incorporates an in situ knife-edge characterization of beam diameters, making absolute reflectivity estimations and determination of saturation fluences significantly more reliable. Additionally, several measures are discussed to substantially improve the reliability of the reflectivity measurements. At its core, the scheme exploits the limits of state-of-the-art digital lock-in technology but also greatly benefits from a fiber-based master-oscillator power-amplifier source, the use of an integrating sphere, and simultaneous comparison with a linear reflectivity standard.


A Comprehensive Theory of Integration.
Efforts to transform health care delivery to improve care have increasingly focused on care integration. However, variation in how integration is defined has complicated efforts to design, synthesize, and compare studies of integration in health care. Evaluations of integration initiatives would be enhanced by describing them according to clear definitions of integration and specifying which empirical relationships they seek to test-whether among types of integration or between integration and outcomes of care. Drawing on previous work, we present a comprehensive theoretical model of relationships between types of integration and propose how to measure them.


Experience of "One Stop TB Diagnostic Solution" Model in Engaging a Private Laboratory for End-to-End Diagnostic Services in the National TB Elimination Program in Hisar, India.
The complete diagnostic evaluation of tuberculosis based on its drug-resistance profile is critical for appropriate treatment decisions. The TB diagnostic landscape in India has been transformed with the scaling-up of WHO-recommended diagnostics, but challenges remain with specimen transportation, completing diagnostic assessment, turnaround time (TAT), and maintaining laboratories. Private laboratories have demonstrated efficiencies for specimen collection, transportation, and the timely testing and issue of results. A one-stop TB diagnostic model was designed to assess the feasibility of providing end-to-end diagnostic services in the Hisar district of Haryana state, India. A NTEP-certified private laboratory was engaged to provide the services, complementing the existing public sector diagnostic services. A total of 10,164 specimens were collected between May 2022 and January 2023 and these were followed for the complete diagnostic assessment of Drug-Susceptible TB (DS-TB) and Drug-Resistant TB (DR-TB) and the time taken for issuing results. A total of 2152 (21%) patients were detected with TB, 1996 (93%) Rifampicin-Sensitive and 134 (6%) with Rifampicin-Resistant TB. Nearly 99% of the patients completed the evaluation of DS-TB and DR-TB within the recommended TAT. The One-Stop TB/DR-TB Diagnostic Solution model has demonstrated that diagnostic efficiencies could be enhanced through the strategic purchase of private laboratory services.


Adjuvant hormonal treatment with radiotherapy for locally advanced prostate cancer.
Long-term results of radiotherapy in locally advanced prostate cancer are poor due to local and distant failures. Since prostate cancer is hormone dependent, tumor androgen deprivation may enhance tumor eradication. Three randomized phase III trials, RTOG and EORTC are reported: they assess androgen suppression by using a luteinizing hormone-releasing hormone analogue (LH-RHa) with or without androgen blockade before and during, or during and after external irradiation. A gain in disease-free, local relapse-free and metastasis-free survival has been obtained (p < 0.001). Only the EORTC 22863 trial has reported a significant improvement in overall survival (p = 0.001) with an LH-RHa started the first day of radiotherapy and administered every 4 weeks over 3 years. In the RTOG 85-10 trial, and LH-RHa, initiated in the last week of radiation therapy and continued until relapse, increased overall survival only in patients with poorly differentiated tumor with a Gleason score of 8-10 (p = 0.03). Androgen suppression prior to and during radiation improves disease-free survival; adjuvant hormonal therapy with an LH-RHa during and after radiation improves overall survival.


[Diabetic neuropathy and lesion of the vessels].
Data from the literature concerning the frequent lack of correlation between the clinical manifestations of diabetic neuropathy on the one hand and the morphofunctional status of the appropriate nerves, disorders in carbohydrate and lipid metabolism, and the influence of antidiabetic therapy on metabolism and the clinical picture of diabetic neuropathy on the other, are presented. In this connection, abundant evidence of frequent affection of various blood vessels, particularly small and smallest, in diabetic neuropathy is considered. But even these data attest to a non-infrequent lack in diabetic neuropathy of the involvement of the appropriate vessels, particularly the lack of basal membrane thickening which is a most common indication to the diabetic involvement of capillaries. Attention is drawn to the possible role of genetic heterogeneity of people with regard to the development of various forms of diabetic neuropathy.


Cognitive Interaction Technology in Sport-Improving Performance by Individualized Diagnostics and Error Prediction.
The interdisciplinary research area Cognitive Interaction Technology (CIT) aims to understand and support interactions between human users and other elements of socio-technical systems. Important reasons for the new interest in understanding CIT in sport psychology are the impressive development of cognitive robotics and advanced technologies such as virtual or augmented reality systems, cognitive glasses or neurotechnology settings. The present article outlines this area of research, addresses ethical issues, and presents an empirical study in the context of a new measurement and assessment system for training in karate. Recent advances in the field of cognitive assistance systems enabled largely automatized assessments of individual mental representation structures for action sequences, such as choreographed movement patterns in dance or martial arts. Empirical investigations with karate practitioners of different skill levels demonstrate that advanced software-based survey and algorithmic analysis procedures based on cognitive models generate individualized performance predictions for a movement sequence from the Kanku-dai kata (a pre-defined karate movement sequence), which correlated significantly not only with formal expertise (kyu/dan rank) but also with the actual likelihood of mistakes in action execution. This information could prospectively be used to define individual training goals for deliberate practice and incorporated into cognitive interaction technology to provide appropriate feedback. We argue that the development of cognitive interaction systems for sport should explicitly take ethical issues into consideration and present a particular developed engineering approach. The potential benefits of such an assistance system for intermediate and advanced practitioners include more effective and flexible practice, as well as supportive effects, and more flexible training schedules. Furthermore, we argue that researchers from the field of sport psychology can benefit from advances in technological systems that enhance the understanding of mental and motor control in skilled voluntary action.


Antibiotic susceptibility patterns of respiratory isolates of Staphylococcus aureus in a Turkish university hospital.
A total of 391 respiratory isolates of Staphylococcus aureus in Sivas (Turkey) were studied between January 1999-2002. The organisms were cultured from the following specimens: throat (43%), sputum (28%), transtracheal/endotracheal aspirates (27%), and bronchial lavage (2%). The isolates were tested against 11 different antibiotics by a disk diffusion method or standardized microdilution technique. Methicillin-resistant isolates constituted 76.9% of all isolates. Most of the methicillin-resistant isolates (95.1%) were isolated from inpatients. The rate of methicillin-resistant isolates in throat, sputum, and tracheal aspirates was 17.2%, 60.1%, and 68.9%, respectively. The resistance of methicillin-resistant isolates in throat to teicoplanin was 3.4%. The methicillin-sensitive isolates were susceptible to most agents tested, while most methicillin-resistant isolates were resistant to these agents. Overall resistance to erythromycin was 61.9%, tetracycline 56.6%, gentamicin 50.7%, ofloxacin 42.0%, rifampin 40.8%, clindamycin 38.9%, chloramphenicol 19.0%, co-trimoxazole 10.2%, and vancomycin 0%.


Directly observed care: can unannounced standardized patients address a gap in performance measurement?
There are three potential sources of information for evaluating a clinician's performance: documentation, patient report, and directly observed care. Current measures draw on just two of these: data recorded in the medical record and surveys of patients. Neither captures an array of performance characteristics, including clinician attention to symptoms and signs while taking a history or conducting a physical exam, accurate recording in the medical record of information obtained during the encounter, evidence based communication strategies for preventive care counseling, and effective communication behavior. Unannounced Standardized Patients (USPs) have been widely deployed as a research strategy for systematically uncovering significant performance deficits in each of these areas, but have not been adopted for quality improvement. Likely obstacles include concerns about the ethics of sending health professionals sham patients, the technical challenges of the subterfuge, and concerns about the relatively small sample sizes and substantial costs involved. However, the high frequency of significant and remediable performance deficits unmasked by USPs, and the potential to adapt registration and record keeping systems to accommodate their visits, suggest that their selective and purposeful deployment could be a cost effective and powerful strategy for addressing a gap in performance measurement.


Coordinate Representations for Interference Reduction in Motor Learning.
When opposing force fields are presented alternately or randomly across trials for identical reaching movements, subjects learn neither force field, a behavior termed 'interference'. Studies have shown that a small difference in the endpoint posture of the limb reduces this interference. However, any difference in the limb's endpoint location typically changes the hand position, joint angles and the hand orientation making it ambiguous as to which of these changes underlies the ability to learn dynamics that normally interfere. Here we examine the extent to which each of these three possible coordinate systems--Cartesian hand position, shoulder and elbow joint angles, or hand orientation--underlies the reduction in interference. Subjects performed goal-directed reaching movements in five different limb configurations designed so that different pairs of these configurations involved a change in only one coordinate system. By specifically assigning clockwise and counter-clockwise force fields to the configurations we could create three different conditions in which the direction of the force field could only be uniquely distinguished in one of the three coordinate systems. We examined the ability to learn the two fields based on each of the coordinate systems. The largest reduction of interference was observed when the field direction was linked to the hand orientation with smaller reductions in the other two conditions. This result demonstrates that the strongest reduction in interference occurred with changes in the hand orientation, suggesting that hand orientation may have a privileged role in reducing motor interference for changes in the endpoint posture of the limb.


Animal models for host-pathogen interaction studies.
There is no model of Helicobacter pylori infection that exactly mimics the human diseases. In a particular, there are no good models of ulceration or gastric adenocarcinoma. Patterns of gastritis induced in the animals tend to be lymphocytic and lack the neutrophil infiltration typical of H. pylori infection in the adult. However, the animal models are starting to provide valuable information with respect to factors involved in the colonisation of the gastric mucosa and the importance of host factors in the development of gastric atrophy, as well as making possible the screening of potential therapeutic agents and vaccine candidates. Models include gnotobiotic piglets, primates, cats, dogs, ferrets and a range of rodents. Recent advances in the mouse models mean that they will allow us to dissect bacterial host interactions in a novel manner due to the availability of a wide range of immunological reagents and numerous mutant or transgenic strains.


Cytogenetic analysis of buccal cells from shoe-workers and pathology and anatomy laboratory workers exposed to n-hexane, toluene, methyl ethyl ketone and formaldehyde.
People employed in the shoe manufacture and repair industry are at an increased risk for cancer, the strongest evidence being for nasal cancer and leukaemia. A possible causal role for formaldehyde is likely for cancer of the buccal cavity and nasopharynx. Exfoliated buccal cells are good source of tissue for monitoring human exposure to inhaled and ingested occupational and environmental genotoxicants. To assess the cytogenetic damage related to occupational exposure to airborne chemicals during shoe-making and the processes in pathology and anatomy laboratories, the micronuclei (MN) count per 3000 cells was measured in buccal smears from shoe-workers (group I, n = 22) exposed to mainly n-hexane, toluene and methyl ethyl ketone (MEK) and from anatomy and pathology staff (group II, n = 28) exposed to formaldehyde (FA). Eighteen male university staff were used as controls. The mean time-weighted average (TWA) concentrations of n-hexane, toluene and MEK in 10 small shoe workshops were 58.07 p.p.m., 26.62 p.p.m. and 11.39 p.p.m., respectively. The measured air concentrations of FA in the breathing zone of the anatomy and pathology laboratory workers were between 2 and 4 p.p.m. Levels of 2,5-hexadione (2,5-HD) and hippuric acid (HA), metabolic markers of n-hexane and toluene exposure, respectively, were significantly higher in the urine of workers in group I than in control subjects (p < 0.001 and p < 0.01, respectively). The mean (+/- SD) MN (0/00) [corrected] frequencies in buccal mucosa cells from workers in group I, group II and controls were 0.62 +/- 0.45%, 0.71 +/- 0.56% and 0.33 +/- 0.30%, respectively (p < 0.05 and p < 0.05 compared with controls for group I and group II, respectively). The effects of smoking, age and duration of exposure on the frequency of micronucleated buccal cells from workers in all three groups studied were also evaluated. Overall, the results suggest that occupational exposure to organic solvents, mainly n-hexane, toluene, MEK and FA, may cause cytogenetic damage in buccal cells and that use of exfoliated buccal cells seems to be appropriate to measure exposure to organic solvents.


The malignant "cold" nodule of the thyroid.
From 1958 to 1976, 910 patients with cold nodules of the thyroid underwent thyroid surgery (714 females, 196 males). Thyroid carcinoma was present in 202 patients (22.2 per cent) (149 females, 20.9 per cent; 53 males, 27 per cent). Rate of malignancy in an age group was greatest in patients older than seventy years (19 of 47 patients, 40.4 per cent) followed by patients twenty-one to thirty years of age (37 of 125 patients, 29.6 per cent); 90 per cent of all patients were from twenty-one to seventy years of age. Blacks had a lower rate of thyroid carcinoma than Caucasians. Data from the Cancer Surveillance Group also showed age-adjusted incidence rates in blacks in Los Angeles County to be lower than that of Caucasians.


[The journey of the vaccine against smallpox: one expedition, two oceans, three continents, and thousands of children].
Spain encouraged, during the Bourbon dynasty, the formation of scientific expeditions, among which was the Royal Philanthropic Vaccine Expedition, an example of biopolitics applied by the state in order to protect health. The expedition went all over the world, using children as a reservoir to transport the vaccine fluid. Francisco Xavier Balmis established a human chain that arm-to-arm materialized the success of the mission. The characteristics and difficulties which children had to pass through and their contribution to the spread of the smallpox vaccine are analyzed.


Influences of sex steroids on experimental carcinogenesis.
Sex steroids can apparently modify hepatic function in at least two ways (Figure 1). First, the liver contains specific receptor proteins for either androgens or oestrogens. Several studies, using effects on the monooxygenase system as an indicator of hormone action, have shown good correlations between the presence of sex-steroid receptors and hepatic response to these hormones. In general, androgens induce the activities of drug biotransformation reactions, whereas oestrogens depress them. Second, the endocrine milieu, during a critical period of early development, apparently programmes the hypothalamic-pituitary axis to release factors which cause certain aspects of liver biochemistry to undergo sex differentiation. Selected components of the cytochrome P-450 system exhibit sex differences, and these differences are imprinted by neonatal androgens and are initiated and maintained by the pituitary gland. Corresponding to sex differentiation of the hepatic monooxygenase system are significant sex differences in responses to hepatocarcinogens such as N-2-fluorenylacetamide and N-hydroxy-N-2-fluorenylacetamide. Higher incidences of hepatocellular carcinomas in males appear to result from exposure to neonatal androgens.


Sequence variability of P2-like prophage genomes carrying the cytolethal distending toxin V operon in Escherichia coli O157.
Cytolethal distending toxins (CDT) are potent cytotoxins of several Gram-negative pathogenic bacteria, including Escherichia coli, in which five types (CDT-I to CDT-V) have been identified so far. CDT-V is frequently associated with Shiga-toxigenic E. coli (STEC), enterohemorrhagic E. coli (EHEC) O157 strains, and strains not fitting any established pathotypes. In this study, we were the first to sequence and annotate a 31.2-kb-long, noninducible P2-like prophage carrying the cdt-V operon from an stx- and eae-negative E. coli O157:H43 strain of bovine origin. The cdt-V operon is integrated in the place of the tin and old phage immunity genes (termed the TO region) of the prophage, and the prophage itself is integrated into the bacterial chromosome between the housekeeping genes cpxP and fieF. The presence of P2-like genes (n = 20) was investigated in a further five CDT-V-positive bovine E. coli O157 strains of various serotypes, three EHEC O157:NM strains, four strains expressing other variants of CDT, and eight CDT-negative strains. All but one CDT-V-positive atypical O157 strain uniformly carried all the investigated genomic regions of P2-like phages, while the EHEC O157 strains missed three regions and the CDT-V-negative strains carried only a few P2-like sequences. Our results suggest that P2-like phages play a role in the dissemination of cdt-V between E. coli O157 strains and that after integration into the bacterial chromosome, they adapted to the respective hosts and became temperate.


Neonatal medical admission in a term and late-preterm cohort exposed to magnesium sulfate.
The purpose of this study was to estimate neonatal intensive care unit and special care unit (NICU) admission rates and care needs among term and late-preterm neonates who are exposed to antenatal magnesium sulfate. We conducted a retrospective cohort study of all singleton neonates of ≥35 weeks' gestation who were exposed immediately antenatally to magnesium sulfate for maternal eclampsia prophylaxis (August 2006 through July 2008). Fifty-one of 242 neonates (21.1%) who, at ≥35 weeks' gestation, had been exposed to antenatal magnesium sulfate were admitted to the NICU. NICU admission was associated in a dose-dependent fashion with total hours and mean dose of magnesium: >12 hours exposure, odds ratio, 2.81 (95% confidence interval, 1.31-6.03); >30 g exposure, odds ratio, 2.59 (95% confidence interval, 1.22-5.51). Infants in NICU who were diagnosed with hypermagnesemia required fluid or nutritional support more frequently (91.3% vs 39.3%; P < .001) than those without hypermagnesemia. Antenatal magnesium sulfate exposure is associated with NICU admission among term and late-preterm neonates in a dose-dependent fashion. Fluid and nutritional assistance commonly are needed in this cohort.


Translation, Cross-Cultural Adaptation, and Validation of the Activity Rating Scale for Disorders of the Knee.
The Activity Rating Scale (ARS) for disorders of the knee evaluates the level of activity by the frequency of participation in 4 separate activities with high demands on knee function, with a score ranging from 0 (none) to 16 (pivoting activities 4 times/wk). To translate and cross-culturally adapt the ARS into Swedish and to assess measurement properties of the Swedish version of the ARS. Cohort study (diagnosis); Level of evidence, 2. The COSMIN guidelines were followed. Participants (N = 100 [55 women]; mean age, 27 years) who were undergoing rehabilitation for a knee injury completed the ARS twice for test-retest reliability. The Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner Activity Scale (TAS), and modernized Saltin-Grimby Physical Activity Level Scale (SGPALS) were administered at baseline to validate the ARS. Construct validity and responsiveness of the ARS were evaluated by testing predefined hypotheses regarding correlations between the ARS, KOOS, TAS, and SGPALS. The Cronbach alpha, intraclass correlation coefficients, absolute reliability, standard error of measurement, smallest detectable change, and Spearman rank-order correlation coefficients were calculated. The ARS showed good internal consistency (α ≈ 0.96), good test-retest reliability (intraclass correlation coefficient >0.9), and no systematic bias between measurements. The standard error of measurement was less than 2 points, and the smallest detectable change was less than 1 point at the group level and less than 5 points at the individual level. More than 75% of the hypotheses were confirmed, indicating good construct validity and good responsiveness of the ARS. The Swedish version of the ARS is valid, reliable, and responsive for evaluating the level of activity based on the frequency of participation in high-demand knee sports activities in young adults with a knee injury.


[Correction of hypersensitivity to strophanthin in experimental myocardial infarction by pharmacologic effects on extracardiac innervation].
Experiments on 176 cats with experimental myocardial infarction were made to study alterations in ouabain tolerance under pharmacological effects on extracardial innervation. It was shown that elimination of sympathetic innervation at different levels by benzohexonium, ornid and anapriline, as well as its relative weakening by proserine favoured the correction of hypersensitivity to ouabain in acute myocardial ischemia. Potentiation of sympatic effects by ephedrine and abolition of parasympathetic innervation by atropine increased ouabain cardiotoxicity.


New technique of kidney tissue processing for immunofluorescence microscopy: formol sucrose/gum sucrose/paraffin.
Present methods of tissue processing for immunofluorescence other than snap freezing have generally been unsatisfactory. We have developed a new kidney tissue holding and processing technique suitable for immunofluorescence, histochemical, and light microscopic analysis of the same specimen. Fifty kidney biopsies containing glomeruli in formol sucrose/gum sucrose/paraffin (FSGSP) were deparaffinized, digested with 0.1 per cent pronase, and compared both qualitatively and quantitatively with snap frozen tissue. Agreement between the two methods was very good (86 to 98 per cent), and total accuracy of FSGSP in detecting deposits ranged from 94 to 100 per cent (IgG, 94 per cent; IgM, 96 per cent; IgA, 98 per cent; fibrin, 96 per cent; Clq, 100 per cent; C3, 98 per cent). The intensity of staining based on a 0 to 4+, 11-point scale, was comparable. When both methods were positive, the intensity of staining in the same pattern was within 1 of frozen in 85 per cent of FSGSP cases and less than frozen by more than 1 in only 7.7 per cent. The overall intensity of FSGSP was slightly greater than frozen when not identical. Negative staining discrepancies were of trace amount in 73 per cent of cases with only 12 per cent differing by a quantity of 2 or greater for six stains combined. Qualitative analyses of IgE, Tamm-Horsfall protein, light chains, and alpha-2-macroglobulin were similar for the two methods. Tissue antigenicity was preserved for long periods of time in both the holding solution and paraffin. Histochemical staining for nonspecific esterase and routine light microscopic sections was comparable to regularly processed paraffin-embedded tissue. Compared with frozen methods, FSGSP was more sensitive, background was lower, few false-positives were present, resolution at high-power was better, and both linear and granular deposits were detected. This new processing method has significant advantages relative to previously described techniques and should have wide applicability to both clinical and research needs.


A developmental transition in growth control during zebrafish caudal fin development.
A long-standing question in developmental biology is how do growing and developing animals achieve form and then maintain it. We have revealed a critical transition in growth control during zebrafish caudal fin development, wherein a switch from allometric to isometric growth occurs. This morphological transition led us to hypothesize additional physiological changes in growth control pathways. To test this, we fasted juvenile and adult zebrafish. Juvenile fins continued allometric growth until development of the mature bi-lobed shape was completed. In contrast, the isometric growth of mature adult fins arrested within days of initiating a fast. We explored the biochemical basis of this difference in physiology between the two phases by assessing the sensitivity to rapamycin, a drug that blocks a nutrient-sensing pathway. We show that the nutrition-independent, allometric growth phase is resistant to rapamycin at 10-fold higher concentrations than are effective at arresting growth in the nutrition-dependent, isometric growth phase. We thus link a morphological transition in growth control between allometric and isometric growth mechanisms to different physiological responses to nutritional state of the animal and finally to different pharmacological responses to a drug (rapamycin) that affects the nutrition-sensing mechanism described from yeast to human.


[Cervical screening and surveillance of the cervix uteri before the age of 20].
The authors record a sample of 2,234 adolescents who were aged 20 years or less and who had systematic cervical screening. This was carried out in a Social Service gynaecological department and the reason for it was mainly to research in the epidemiology. The authors have analysed the results of 870 cervical smears and 62 colposcopies. They found that in this young population there were 11% dysplastic smears; 59% viral type smears (condylomata or herpes); 11% mild or moderate dysplasias and 16% flat condylomata that were proven histologically. The authors review the recent literature and their results and the risk factors for cancer of the cervix in adolescents and demonstrate the value of early screening of this population.


Optimization of Crude Oil and PAHs Degradation by Stenotrophomonas rhizophila KX082814 Strain through Response Surface Methodology Using Box-Behnken Design.
The present paper describes the process optimization study for crude oil degradation which is a continuation of our earlier work on hydrocarbon degradation study of the isolate Stenotrophomonas rhizophila (PM-1) with GenBank accession number KX082814. Response Surface Methodology with Box-Behnken Design was used to optimize the process wherein temperature, pH, salinity, and inoculum size (at three levels) were used as independent variables and Total Petroleum Hydrocarbon, Biological Oxygen Demand, and Chemical Oxygen Demand of crude oil and PAHs as dependent variables (response). The statistical analysis, via ANOVA, showed coefficient of determination R2 as 0.7678 with statistically significant P value 0.0163 fitting in second-order quadratic regression model for crude oil removal. The predicted optimum parameters, namely, temperature, pH, salinity, and inoculum size, were found to be 32.5°C, 9, 12.5, and 12.5 mL, respectively. At this optimum condition, the observed and predicted PAHs and crude oil removal were found to be 71.82% and 79.53% in validation experiments, respectively. The % TPH results correlate with GC/MS studies, BOD, COD, and TPC. The validation of numerical optimization was done through GC/MS studies and % removal of crude oil.


Comparison of multiple drug-eluting stent percutaneous coronary intervention and surgical revascularization in patients with multivessel coronary artery disease: one-year clinical results and total treatment costs.
Consecutive patients with multivessel coronary artery disease treated with multiple drug-eluting-stent (DES) percutaneous coronary intervention (PCI) (111 patients) or coronary artery bypass graft (CABG) (95 patients) on the basis of clinico-anatomical judgment were examined to investigate mediumterm clinical results and initial and total costs. Clinical and procedural characteristics, duration of hospital stay, initial and total costs and 12-month follow-up events were considered in both groups. Previous revascularization procedures and acute coronary syndromes were more frequent in the PCI group, while triple-vessel and left main disease occurred more often in the CABG group. The mean number of treated vessels in multiple DES PCI was 2.7/patient, with 2.8 DES/patient. Complete revascularization was achieved in 70% of cases. Inhospital events were postprocedural non-Q-wave acute myocardial infarction in 5.4%, and 2 retroperitoneal hemorrhages. CABG was performed with a mean of 3.9 grafts/patient; 16 patients (17%) had early complications; mean hospital stay was significantly longer than for the PCI patients (23.5 +/- 10 vs. 5.3 +/- 3 days; p < 0.001). Twelve-month total mortality and acute myocardial infarction incidents were similar, while target vessel revascularization was significantly more frequent in the PCI group (12.6% PCI vs. 2.1% CABG; p < 0.001); cumulative major adverse cardiac events were not significantly different (15.3% PCI vs. 9.5% CABG; p = 0.271). Initial and final costs were lower for multivessel PCI with DES (20,050 +/- 2,702 for CABG vs. 10,214 +/- 4,184 for PCI; p < 0.001), but not completely covered by current DRG reimbursement. Multiple DES PCI showed good earlyand medium-term results with substantially lower costs than CABG.


Pseudomonas sichuanensis sp. nov., isolated from hospital sewage.
A bacterial strain, designated WCHPs060039T, was isolated from hospital sewage in China. The strain was Gram-stain-negative, obligate aerobic, flagellum-motile and positive for oxidase and catalase. A preliminary analysis of the 16S rRNA gene sequences indicated that strain WCHPs060039T belonged to the genus Pseudomonasand was closely related to members of the Pseudomonas putida group, with the highest similarities to Pseudomonas entomophila L48T (99.5 %), Pseudomonas mosselii CIP 105259T (99.52 %), Pseudomonas taiwanensis BCRC 17751T (99.45 %) and Pseudomonas plecoglossicida NBRC 103162T (99.31 %). Whole genome sequencing of the strain was performed. Phylogenetic analysis based on a set of core gene sequences revealed that the strain was distinct from its closest Pseudomonas species. Average nucleotide identity based on blast and in silico DNA-DNA hybridizationrevealed low genome relatedness to its closest Pseudomonas species (below the recommended thresholds of 95 and 70 %, respectively, for species delineation). The major fatty acids of the strain were 16:0, 17:0 cyclo, summed feature 3 (16:1ω7c/16:1ω6c and 16:1ω6c/16:1ω7c) and summed feature 8 (18:1ω7c). The ability to utilize inositol, sorbitol and d-glucuronic acid could differentiate strain WCHPs060039T from the closely related Pseudomonas species. It is therefore evident that strain WCHPs060039T represents a novel species of the genus Pseudomonas, for which the name Pseudomonas sichuanensis sp. nov. is proposed. The type strain is WCHPs060039T (GDMCC 1.1424T=CNCTC 7662T).


A different view: sensory drive in the polarized-light realm.
Sensory drive, the concept that sensory systems primarily evolve under the influence of environmental features and that animal signals are evolutionarily shaped and tuned by these previously existing sensory systems, has been thoroughly studied regarding visual signals across many animals. Much of this work has focused on spectral aspects of vision and signals. Here, I review work on polarized-light signals of animals and relate these to what is known of polarization visual systems, polarized-light aspects of visual scenes, and polarization-related behavior (e.g., orientation, habitat-finding, contrast enhancement). Other than the broad patterns of scattered polarized light in the sky, most polarization in both terrestrial and aquatic environments results from either reflection or scattering in the horizontal plane. With overhead illumination, horizontal features such as the surfaces of many leaves or of air: water interfaces reflect horizontal polarization, and water scatters horizontally polarized light under most conditions. Several animal species have been demonstrated to use horizontally polarized light fields or features in critical aspects of their biology. Significantly, most biological signals are also horizontally polarized. Here, I present relevant polarization-related behavior and discuss the hypothesis that sensory drive has evolutionarily influenced the structure of polarization signals. The paper also considers the evolutionary origin of circular polarization vision and circularly polarized signals. It appears that this class of signals did not evolve under the influence of sensory drive. The study of signals based on polarized light is becoming a mature field of research.


Redox protein thioredoxin mediates neurite outgrowth in primary cultured mouse cerebral cortical neurons.
Thioredoxin system plays an important role in maintaining the cellular redox balance. Recent evidence suggests that thioredoxin (Trx) system may promote cell survival and neuroprotection. In this study, we explored the role of thioredoxin system in neuronal differentiation using a primary mouse cortical neuronal cell culture. First, Trx and Trx reductase (TrxR) protein levels were analyzed in cultured neurons from 1 to 32 days in vitro (DIV). The result showed that Trx and TrxR protein levels time-dependently increased in the neuron cell culture from 1 to 18 DIV. To establish the role of Trx in neuronal differentiation, Trx gene expression was knockdown in cultured neurons using Trx sgRNA CRISPR/Cas9 technology. Treatment with CRISPR/Cas9/Trx sgRNA decreased Trx protein levels and caused a reduction in dendritic outgrowth and branching of cultured neurons. Then, primary cortical neurons were treated with the Trx inhibitor PX12 to block Trx reducing activity. Treatment with PX12 also reduced dendritic outgrowth and branching. Furthermore, PX12 treatment reduced the ratio of phosphorylated cyclic AMP response element-binding protein (CREB)/total CREB protein levels. To investigate whether CREB phosphorylation is redox regulated, SH-SY5Y cells were treated with H2O2, which reduced phosphorylated CREB protein levels and increased CREB thiol oxidation. However, treatment with CB3, a Trx-mimetic tripeptide, rescued H2O2-decreased CREB phosphorylation. Our results suggest that Trx regulates neuronal differentiation and maturation of primary mouse cortical neurons by targeting CREB neurotrophic pathway. Trx may regulate CREB activation by maintaining the cellular redox balance.


The Tip-Localized Phosphatidylserine Established by Arabidopsis ALA3 Is Crucial for Rab GTPase-Mediated Vesicle Trafficking and Pollen Tube Growth.
RabA4 subfamily proteins, the key regulators of intracellular transport, are vital for tip growth of plant polar cells, but their unique distribution in the apical zone and role in vesicle targeting and trafficking in the tips remain poorly understood. Here, we found that loss of Arabidopsis (Arabidopsis thaliana) AMINOPHOSPHOLIPID ATPASE 3 (ALA3) function resulted in a marked decrease in YFP-RabA4b/ RFP-RabA4d- and FM4-64-labeled vesicles from the inverted-cone zone of the pollen tube tip, misdistribution of certain intramembrane compartment markers, and an obvious increase in pollen tube width. Additionally, we revealed that phosphatidylserine (PS) was abundant in the inverted-cone zone of the apical pollen tube in wild-type Arabidopsis and was mainly colocalized with the trans-Golgi network/early endosome, certain post-Golgi compartments, and the plasma membrane. Loss of ALA3 function resulted in loss of polar localization of apical PS and significantly decreased PS distribution, suggesting that ALA3 is a key regulator for establishing and maintaining the polar localization of apical PS in pollen tubes. We further demonstrated that certain Rab GTPases colocalized with PS in vivo and bound to PS in vitro. Moreover, ALA3 and RabA4d collectively regulated pollen tube growth genetically. Thus, we propose that the tip-localized PS established by ALA3 is crucial for Rab GTPase-mediated vesicle targeting/trafficking and polar growth of pollen tubes in Arabidopsis.


Spectrophotometric Assay for the Detection of 2,5-Diformylfuran and Its Validation through Laccase-Mediated Oxidation of 5-Hydroxymethylfurfural.
Modern biocatalysis requires fast, sensitive, and efficient high-throughput screening methods to screen enzyme libraries in order to seek out novel biocatalysts or enhanced variants for the production of chemicals. For instance, the synthesis of bio-based furan compounds like 2,5-diformylfuran (DFF) from 5-hydroxymethylfurfural (HMF) via aerobic oxidation is a crucial process in industrial chemistry. Laccases, known for their mild operating conditions, independence from cofactors, and versatility with various substrates, thanks to the use of chemical mediators, are appealing candidates for catalyzing HMF oxidation. Herein, Schiff-based polymers based on the coupling of DFF and 1,4-phenylenediamine (PPD) have been used in the set-up of a novel colorimetric assay for detecting the presence of DFF in different reaction mixtures. This method may be employed for the fast screening of enzymes (Z' values ranging from 0.68 to 0.72). The sensitivity of the method has been proved, and detection (8.4 μM) and quantification (25.5 μM) limits have been calculated. Notably, the assay displayed selectivity for DFF and enabled the measurement of kinetics in DFF production from HMF using three distinct laccase-mediator systems.


Comparison of supported living and traditional residential services in the state of Oregon.
Supported living has been described as an approach that contributes to higher lifestyle quality. We compared supported living and traditional residential support. Twenty supported living participants were matched with 20 participants receiving traditional support. Results indicated that participants receiving supported living services were more likely to be experiencing features of supported living and that supported living participants experienced significantly more community activity variety, did community activities more frequently, and did preferred community activities more frequently. Further, they engaged in activities with more people and did activities with these people more frequently. The costs were similar for providing supported living and traditional support.


Seprafilm(®) adhesion barrier: (2) a review of the clinical literature on intraabdominal use.
This study seeks to provide a review of the clinical data published as of July 2011 concerning the postsurgical adhesion barrier, Seprafilm (chemically modified hyaluronic acid and carboxymethylcelulose; Genzyme Corporation, Cambridge, MA). Included articles detail the application of Seprafilm for intraabdominal uses that have been approved (on-label) and those considered investigational (off-label) by the FDA. Medline and EMBASE Drugs and Pharmaceuticals databases were searched for all original clinical Seprafilm research published as of July 2011. All human Seprafilm intraabdominal clinical reports and studies, excluding those related to prosthetic mesh were included. Data extraction involved the systematic review of each article. The data synthesis is the summary of Seprafilm human intraabdominal clinical reports and studies describing safety and/or efficacy. The safety and efficacy of Seprafilm in reducing postoperative adhesions has been clearly demonstrated in abdominal and pelvic laparotomy. While reports have described the safe and successful use of Seprafilm following laparoscopy, pediatric laparotomy, and in patients with malignancy and/or infection, the safety and efficacy of Seprafilm use in these procedures has not been definitively established in randomized controlled trials.


[Mothers' perception of dental eruption syndrome and its clinical manifestation during childhood].
This study was aimed at identifying primiparous and multiparous mothers perceptions about tooth eruption and related symptoms as well as discussing such events occurrence in the light of the relevant literature. The research adopted a qualitative, descriptive design; 61 mothers who had already given birth to babies aged 3 to 12 months old were studied. Their children were outpatients at Rio Grande do Norte Federal Universitys Paediatric Hospital in Natal, RN, Brazil. A semi-structured interview was used for collecting data. ALCESTE 4.5 software was used for analysing data based on primiparous and multiparous mothers as variables; the former term referred to mothers bearing a child for the first time and multiparous to those who had born more than one child. Symptomatology was related by 75 % of the mothers interviewed here. The perception of the mothers from both groups probably pointed to a lack of knowledge regarding child development and the process leading to the presence of clinical symptoms due to tooth eruption. However, the great difference lay in how this reality was perceived; mothers having a single child clearly affirmed that knowledge was acquired by common sense, whilst mothers of more than one child reproduced such knowledge according to their experience with previous children. It was concluded that during this phase of tooth eruption, professionals must adopt a firm and defined position based on the literature providing evidence of the real relationship between tooth eruption and general symptoms, paying attention to every patient and their complaints to demystify and better understand this whole process.


On the correlation between dye coverage and photoelectrochemical performance in dye-sensitized solar cells.
Concentration depth profiles of the ruthenium based dyes Z907 and N719 adsorbed onto titania are measured directly and used for determining the adsorption isotherm of the dyes. Dye layers formed by both grow in islands on the titania which do not cover the entire titania surface even at the maximum coverage. Impedance spectroscopy in conjunction with the adsorption isotherms shows that recombination losses mainly appear between the dye and the electrolyte solution. The short circuit current and the efficiency increase linearly with the dye coverage. The open circuit voltage slightly increases with increasing dye coverage which is interpreted as most likely to be a consequence of the higher charge in the particles upon higher dye loading on the TiO2 surface.


Persistent astroglial swelling accompanies rapid reversible dendritic injury during stroke-induced spreading depolarizations.
Spreading depolarizations are a key event in the pathophysiology of stroke, resulting in rapid dendritic beading, which represents acute damage to synaptic circuitry. The impact of spreading depolarizations on the real-time injury of astrocytes during ischemia is less clear. We used simultaneous in vivo 2-photon imaging and electrophysiological recordings in adult mouse somatosensory cortex to examine spreading depolarization-induced astroglial structural changes concurrently with signs of neuronal injury in the early periods of focal and global ischemia. Astrocytes in the metabolically compromised ischemic penumbra-like area showed a long lasting swelling response to spontaneous spreading depolarizations despite rapid dendritic recovery in a photothrombotic occlusion model of focal stroke. Astroglial swelling was often facilitated by recurrent depolarizations and the magnitude of swelling strongly correlated with the total duration of depolarization. In contrast, spreading depolarization-induced astroglial swelling was transient in normoxic healthy tissue. In a model of transient global ischemia, the occurrence of a single spreading depolarization elicited by a bilateral common carotid artery occlusion coincided with astroglial swelling alongside dendritic beading. With immediate reperfusion, dendritic beading subsides. Astroglial swelling was either transient during short ischemic periods distinguished by a short-lasting spreading depolarization, or persistent during severe ischemia characterized by a long-lasting depolarization with the ultraslow negative voltage component. We propose that persistent astroglial swelling is initiated and exacerbated during spreading depolarization in brain tissue with moderate to severe energy deficits, disrupting astroglial maintenance of normal homeostatic function thus contributing to the negative outcome of ischemic stroke as astrocytes fail to provide neuronal support.


Influence of lactic acid fermentation on the microbiological, biogenic amines and volatile compounds of bovine colostrum.
In this study we hypothesized that the relations between the bovine colostrum (BC) microbiota, biogenic amine (BA) as well as volatile compound (VC) profiles can lead to new deeper insights concerning the BC changes during the biological preservation. To implement such an aim, BC samples were collected from 5 farms located in Lithuania and fermented with Lactiplantibacillus plantarum and Lacticaseibacillus paracasei strains. Non-fermented and fermented BC were subjected to microbiological [lactic acid bacteria (LAB), Escherichia coli, and total bacteria (TBC), total Enterobacteriaceae (TEC) and total mold/yeast (M/Y) viable counts] and physicochemical (pH, color coordinates, BA content and VC profile) parameters evaluation, and the relationship between the tested parameters were also further analyzed. In comparison pH and dry-matter (DM) of non-fermented samples, significant differences were not found, and pH of BC was, on average, 6.30, and DM, on average, 27.5%. The pH of fermented samples decreased, on average, until 4.40 in Lp. plantarum fermented group, and, on average, until 4.37 in Lc. paracasei fermented group. Comparing color characteristics among non-fermented BC groups, significant differences between lightness (L*) and yellowness (b*) were not detected, however, the origin (i.e. agricultural company), LAB strain used for fermentation and the interaction between these factors were statistically significant on bovine colostrum redness (a*) coordinate. The microbial contamination among all the tested BC groups was similar. However, different LAB strains used for BC fermentation showed different effects toward the microbial contamination reduction, and specifically Lc. paracasei was more effective than Lp. plantarum strain. Predominant BA in BC were putrescine and cadaverine. The main VC in non-fermented and fermented BC were decane, 2-ethyl-1-hexanol, dodecane, 1,3-di-tert-butylbenzene, 3,6-dimethyldecane and tetradecane. Moreover, this study showed worrying trends with respect to the frozen colostrum storage, because most of the dominant VC in BC were contaminants from the packaging material. Additionally, significant correlations between separate VC and microbial contamination were obtained. Finally, these experimental results showed that the separate VCs in BC can be an important marker for biological as well as chemical contamination of BC. Also, it should be pointed out that despite the fermentation with LAB is usually described as a safe and natural process with many advantages, control of BA in the end product is necessary.


Anti-CNS antibodies in neurological and psychiatric disorders.
To investigate the possibility that anti-CNS antibodies may play a pathogenic role in a number of neurological and psychiatric disorders, a population study was undertaken. Serum samples were obtained from a total of 257 adults and were screened against sodium dodecyl sulphate polyacrylamide gel electrophoretic blots of various normal, necropsy-derived adult human brain regions. The incidence of IgG immunoreactive banding in the total sample was 30%. Within the diagnostic groups the incidence of banding was: controls 32%, schizophrenia 28%, mental retardation 27%, cerebellar ataxia 33%, Parkinson's disease 22%, myasthenia gravis 45% and epilepsy 31%. The differences are not statistically significant. There was no significant difference in the numbers and locations of bands between the various diagnostic groups and the controls. The overall incidence of immunoreactivity corresponding to the high molecular weight subunit of neurofilaments was only 6%, thus not confirming a previously reported incidence of 95%. The similarity between the diagnostic and the control sera suggests that caution should be exerted in interpreting the pathogenic significance of anti-CNS immunoreactive banding on Western blots.


["Initial results of the first ambulatory program for in vitro fertilization in Mexico"].
Infertile couples treated with in vitro fertilization and embryo transfer (IVF-ET) seeking highest standards of case. The new programmes of IVF-ET are under pressure to generate as quickly as possible acceptable pregnancy rates. We report our experiences at a new IVF clinic, performing conventional IVF-ET and oocyte donation. Patients were treated in groups, their menstrual cycles were previously synchronized with luteal phase noretisterone. Both variants of IVF produced clinical pregnancies since the start of activity. In this paper the logistic and methodology are discussed. Today the aim of the programme is increasing the efficiency and efficacy of same.


FSH and testosterone effects in seminiferous tubules of immature hypophysectomized rats.
The effects of follicle-stimulating hormone (FSH) and testosterone on the development of the cytosolic germ cell adenylate cyclase and germ cell morphology in rats hypophysectomized at 29 days of age were studied. Following hypophysectomy, the adenylate cyclase content fell to marginal levels and germ cell development ceased at the late pachytene stage. Testosterone treatment led to a moderate increase in the cytosolic enzyme content and to progression of spermatid cell development to stages 8-12. FSH treatment with doses of 80-100 micrograms/day restored enzyme content to levels seen in control rats, as well as progression of germ cell development up to stages 15-16, i.e., to the same stages present in age-matched control (sham-operated) rats. The results indicate that in immature rats FSH is essential for spermatid cell maturation as is evidenced by its ability to stimulate the formation of cytosolic germ cell adenylate cyclase to quantitatively normal levels, as well as to stimulate the development of spermatid cells.


Reproductive suppression in subordinate, non-breeding female Damaraland mole-rats: two components to a lifetime of socially induced infertility.
The Damaraland mole-rat Cryptomys damarensis exhibits an extreme reproductive division of labour. Reproduction in the colony is restricted to a single breeding pair, resulting from a two-fold control: (i) a reduced pituitary synthesis and/or secretion of luteinizing hormone leading to a block to ovulation in non-reproductive females; and (ii) a strong inhibition to breeding with familiar kin. Circulating basal concentrations of luteinizing hormone as well as luteinizing hormone levels measured in response to a single exogenous gonadotrophin releasing hormone challenge, were significantly lower in non-reproductive females in the presence of the reproductive female than those in colonies lacking a reproductive female. Urinary progesterone concentrations before the removal of the reproductive female were significantly higher in non-reproductives than the post removal values. Behavioural studies from sib-sib and non-sib pairings provide evidence for a strong incest avoidance, probably resulting from an inhibition of breeding with familiar colony members. A total of four pairings of non-sibs resulted in copulatory activity and eventual conception. In contrast, four couples of sib-sib combinations failed to produce any sexual activity or offspring. Thus, suppression of reproduction in these non-reproductive, subterranean bathyergids is complicated by the masking effect of familiarity that prevents incest, in addition to the physiological inhibition of fertility in the presence of the reproductive female.


A Conjoint Analysis of the Acceptability of Targeted Long-Acting Injectable Antiretroviral Therapy Among Persons Living with HIV in the U.S.
With long-acting injectable antiretroviral therapy likely to be a treatment option for people living with HIV (PLWH), it is critical to assess its acceptability among potential end-users. Based on formative qualitative work and our own ongoing development of targeted long-acting products in nanosuspension formulations, we created eight hypothetical medication scenarios varying along six dichotomous attributes: administration location (home versus [vs.] clinic), dosing frequency (every 2 weeks vs. 1 week), injections per dose (one vs. two), injection pain (mild vs. moderate), injection site reaction (mild vs. moderate), and effectiveness (better vs. same as pills). PLWH from three outpatient care clinics in Seattle, WA and Riverside, CA rated acceptability (i.e., willingness to try each hypothetical medication) from 0 (very unlikely) to 100 (very likely). In conjoint analyses, we examined level and correlates of acceptability, the impact of each attribute on overall acceptability, and moderators of this effect. Participants (median age 52 years; 71% male, 34% White, 36% Black/African American, 20% Hispanic) rated acceptability of the 8 scenarios from 47.8 (standard deviation [SD] = 37.0) to 68.8 (SD = 34.1), with effectiveness (impact score = 7.3, SD = 18.7, p = 0.005) and dosing frequency (impact score = 5.7, SD = 19.6, p = 0.034) the only attributes with a significant impact on acceptability. There were no statistically significant differences in overall acceptability according to any participant socio-demographic or other characteristic; however, gender, education, employment status, and experience with and hatred/avoidance of injections moderated some effects. Overall acceptability for targeted long-acting antiretroviral treatment as proposed was modest, with superior effectiveness and lower dosing frequency most impactful on acceptability. Future acceptability research should continue to evaluate specific products in development with a full range of conjoint analytic and other techniques.


Functional positioning principles for image-based robotic-assisted TKA achieved a higher Forgotten Joint Score at 1 year compared to conventional TKA with restricted kinematic alignment.
Few comparative studies assessed the current concept of individualised alignment for total knee arthroplasty (TKA) and their outcomes at mid-term. This study aimed to evaluate the functional outcomes at 1 year of primary TKA performed with a functional positioning technique based on an image-based robotic-assisted system, compared to conventional TKA performed with a restricted kinematic alignment technique. This retrospective comparative study included 100 primary TKAs performed with functional positioning principles using an image-based robotic-assisted system. A control group included 100 primary TKAs with the same posterior-stabilised implant as the robotic group but performed with manual instrumentation and restricted kinematic alignment technique. In the robotic group, the mean age was 69.2 years old ± 7.9; the mean body mass index was 29.7 kg/m2 ± 4.6. The demographic characteristics were similar between both groups. Kujala score, Forgotten Joint Score (FJS), Knee Society Score (KSS) knee and KSS function were collected 12 months postoperatively. Normally distributed continuous variables were compared using the Student t test. For non-normally distributed continuous variables, the Mann-Whitney test was used. FJS was significantly higher in the robotic group (76.3 ± 13 vs. 68.6 ± 16.9 in the conventional group; p = 0.026). At a 1-year follow-up, there was no significant difference in the KSS knee and KSS function scores and the Kujala score between both groups. The mean KSS knee score was 90.8 ± 11.4 in the robotic group versus 89.4 ± 9.6 in the conventional group (p = 0.082). The mean KSS function score was 91.4 ± 12.3 versus 91.3 ± 12.6, respectively (p = 0.778). Functional positioning principles using an image-based robotic-assisted system achieved a higher Forgotten Joint Score 1 year after TKA compared to restricted kinematic alignment. Personalised alignment and implant positioning are interesting paths to improve the functional outcomes after TKA. III.


Effects of heparin and epsilon-aminocaproic acid in dogs on plasmin-125-I generation in response to urokinase injections and venous injury.
The isotopic method described previously for quantification of plasmin- (125)I by disc gel electrophoresis was modified by inclusion of euglobulin precipitation to expand its applicability to plasmas containing low radioactivity of plasmin- (125)I and plasminogen- (125)I. It was found that the euglobulin precipitation method precipitates 72.4+/-2.1 (sd)% of both plasmin- (125)I and plasminogen- (125)I. Using this method and plasminogen- (125)I as a tracer, studies were first made of the effects of heparin and epsilon-aminocaproic acid in dogs on plasmin- (125)I generation in responese to a single injection of urokinase and to venous injury; second, of the effects of venous occlusion and thrombosis on plasmin- (125)I generation; and third, in vitro studies of plasminogen- (125)I affinity to fibrin and its activation in blood clots. The venous injury was produced by the damage of venous endothelium by an injection of 90% phenol and the thrombosis by a thrombin injection into an occluded vein. Heparin and epsilon-aminocaproic acid under the present experimental conditions inhibited about 78 and 100%, respectively of plasmin- (125)I generation by the urokinase injection. Similar inhibitory effects of heparin and epsilon-aminocaproic acid were observed on plasmin- (125)I generation in response to venous injury. The venous occlusion caused a small degree of plasmin- (125)I generation, but thrombin thrombosis did not seem to stimulate the generation of plasmin- (125)I. The in vitro studies showed that plasminogen- (125)I does not have a specific affinity to fibrin and is incorporated into blood clots in approximately equal concentrations as those in serum during clotting processes, and that blood clots per se do not stimulate plasmin- (125)I generation. These results suggest that injured veins release considerable amounts of vascular plasminogen activators into circulation and that these play an important role in thrombus dissolution in vivo.


A correlated light and electron microscopic study of identified cholinergic basal forebrain neurons that project to the cortex in the rat.
Cholinergic neurons in the basal forebrain which project to the frontal cortex were studied by combining the retrograde transport of a conjugate of horseradish peroxidase and wheat germ agglutinin with choline acetyltransferase immunohistochemistry. Neurons that were both retrogradely labelled and immunoreactive were found on the medial, lateral, and ventral borders of the globus pallidus, within the globus pallidus, as well as in the substantia innominata and ventral pallidum region. The cell bodies averaged 31 by 19 micron in size and had sparsely branching dendrites. Cells which were labelled by both techniques were first characterised in the light microscope and then studied in the electron microscope. The perikarya had large amounts of cytoplasm with abundant organelles. The nuclei were indented, were usually eccentrically placed, and contained prominent nucleoli. The synaptic input onto the cell bodies and their dendrites was studied in serial sections. The synaptic input onto the perikarya and proximal dendrites was sparse but the density increased on more distal regions of the dendrites. Subjunctional bodies were associated with the postsynaptic membrane in 20-30% of the synaptic contacts and these were classified as asymmetrical; the remaining contacts could not be classified because of an association of the immunoreaction product with the postsynaptic membrane. The synaptic input to these cells was distinctly different from that onto typical globus pallidus cells, the perikarya and dendrites of which were characteristically ensheathed in synaptic boutons.


Lung cryobiopsies: a paradigm shift in diagnostic bronchoscopy?
In 1963, the first bronchoscopic lung biopsy was performed. Less than 10 years later, the technique of transbronchial lung biopsy using a flexible bronchoscope was introduced into clinical practice, significantly reducing the rate of major complications and the rate of surgical lung biopsies in patients with diffuse parenchymal lung diseases. The diagnostic yield of transbronchial lung biopsy varies among various parenchymal lung diseases. In pulmonary sarcoidosis and lymphangitis carcinomatosa, a diagnosis can be obtained in up to 80% of patients. This method is considered inadequate, however, in identifying more complex histological patterns such as usual interstitial pneumonitis or nonspecific interstitial pneumonitis. Introduction of the 'jumbo forceps' and of a more 'surgically oriented' procedural setting (patients deeply sedated and intubated) allowed larger and more numerous lung specimens to be obtained without a significant increase of complications such as pneumothorax or bronchial bleeding. However, the possibility to obtain enough parenchymal tissue for a morphological diagnosis of complex patterns remained unmet. Recently, the use of cryoprobes has achieved a significant impact on this issue allowing to obtain large quantity of tissue. Recent studies document that with transbronchial cryobiopsies the diagnosis of usual interstitial pneumonitis can be made confidently by pathologists with a good inter-observer agreement. Pneumothorax is the main complication (reported in up to one fourth of cases in some series); bronchial bleeding is easily controlled using Fogarty balloon. Transbronchial cryobiopsy is a promising new technique that may become a valid alternative to surgical lung biopsy in the near feature.


PIMiner: a web tool for extraction of protein interactions from biomedical literature.
Information on Protein Interactions (Pls) is valuable for biomedical research, but often lies buried in the scientific literature and cannot be readily retrieved. While much progress has been made over the years in extracting Pls from the literature using computational methods, there is a lack of free, public, user-friendly tools for the discovery of Pls. We developed an online tool for the extraction of PI relationships from PubMed-abstracts, which we name PIMiner. Protein pairs and the words that describe their interactions are reported by PIMiner so that new interactions can be easily detected within text. The interaction likelihood levels are reported too. The option to extract only specific types of interactions is also provided. The PIMiner server can be accessed through a web browser or remotely through a client's command line. PIMiner can process 50,000 PubMed abstracts in approximately 7 min and thus appears suitable for large-scale processing of biological/biomedical literature.


[Discussion of Application Status and Key Attentions on Registration for Ossicular Replacement Prosthesis].
The ossicular replacement prosthesis should have good biocompatibility, stability, easy to install, and excellent sound transmission capacity. In this study, the characteristics of ideal materials for the ossicular replacement prosthesis were analyzed by searching the types of materials used in clinical practice and comparing the advantages and disadvantages of various materials and structures. At the same time, in combination with the current evaluation requirements and evaluation experience, the focus of the performance research project of ossicular replacement prosthesis in the process of registration is discussed to clarify the performance evaluation requirements of these products, so as to provide reference for the future work of manufacturers and regulators. The performance evaluation of ossicular replacement prosthesis focuses on its mechanical properties, fixation stability, sound transmission characteristics, biological characteristics, and magnetic resonance compatibility.


Posttraumatic stress in women after the September 11 terrorist attacks in New York City.
Women have been shown to be at higher risk than men of developing posttraumatic stress disorder (PTSD) after traumatic events. Women in New York City were more likely than men to have probable PTSD 5-8 weeks after the September 11, 2001, terrorist attacks on the World Trade Center. We explored the factors that could explain the higher prevalence of probable PTSD among women in the aftermath of the attacks. Data from a telephone survey of a randomly selected group of residents of Manhattan living south of 110th street, conducted 5-8 weeks after September 11, were used in these analyses. The survey assessed demographic information, lifetime experience of traumatic events, life stressors, social support, event exposure variables, perievent panic attacks, postevent concerns, and probable PTSD related to the attacks. We determined the contribution of key covariates that could explain the gender-probable PTSD relation through stratified analyses and manual stepwise logistic regression model building. Among 988 respondents, women were two times more likely than men to report symptoms consistent with probable PTSD after the September 11 attacks. When adjusted for potential confounders, the association between gender and probable PTSD diminished from OR = 2.2 (95% confidence interval [CI] 1.3-3.6) to OR = 1.2 (95% CI 0.7-2.2). These results suggest that specific behavioral and biographic factors (including previous traumatic experiences and psychological disorders, social responsibilities, and perievent emotional reactions) explained most of the excess burden of probable PTSD among women after a disaster. Isolating the characteristics that place women at greater risk for probable PTSD after disasters can inform public health prevention strategies and spur further research.


Insulin secretion, insulin content and glucose phosphorylation in RINm5F insulinoma cells after transfection with human GLUT2 glucose-transporter cDNA.
The insulin-secretory response to glucose is defective in the RINm5F insulin-producing tumour cell line. Stable transfection with human low-affinity GLUT2 glucose-transporter cDNA revealed a significant improvement in stimulus-secretion coupling in these insulinoma cells. 3-O-Methylglucose uptake increased 10-fold in the concentration range 10-20 mM, whereas non-transfected control cells were unresponsive. Northern-blot analysis revealed a 7-fold increase in expression of the insulin gene in the GLUT2-transfected RINm5F cell clone T1. In contrast, glucokinase and GLUT1 glucose-transporter mRNA gene expression were not affected by transfection with GLUT2 glucose-transporter cDNA. The insulin content of transfected RINm5F cells was 7-fold higher after tissue culture at high glucose concentrations than in non-transfected controls. GLUT2-transfected RINm5F cells also regained insulin-secretory responsiveness toward high glucose concentrations. Tissue culture for 72 h in 20 mM glucose induced glucokinase activity in the GLUT2-transfected RINm5F clone T1, raising the glucokinase/hexokinase phosphorylation ratio from 0.2 to 0.6. The experiments demonstrate that an increased glucose uptake via a low-affinity glucose transporter and an increased metabolic flux rate are important factors in the induction of insulin-gene expression and glucokinase activity and thus improved glucose-induced biosynthesis and secretion of insulin in RINm5F insulinoma cells.


Drug induced parkinsonism: a common cause of parkinsonism in older people.
Drug induced parkinsonism is the second most common cause of parkinsonism in older people after idiopathic Parkinson's disease (PD). Risk factors for developing drug induced parkinsonism include: older age; female gender; dose and duration of treatment; type of agent used; cognitive impairment; acquired immunodeficiency syndrome (AIDS); tardive dyskinesia; and pre-existing extrapyramidal disorder. In most patients parkinsonism is reversible upon stopping the offending drug, though it may take several months to resolve fully and in some patients it may even persist. In this case, one needs to consider the possibility of PD which has been unmasked by the offending drug, and treatment with dopaminergic agents may be warranted. Drug induced parkinsonism adversely affects the quality of life in older patients and is potentially reversible, highlighting the importance of early recognition of this condition. This article discusses the drugs implicated, as well as the epidemiology, pathophysiology, clinical features, and management of drug induced parkinsonism.


Epidemiology of distal radius fracture in Akershus, Norway, in 2010-2011.
Several studies published over the last decade indicate an increased incidence of distal radius fractures (DRF). With Norway having one of the highest reported incidence of DRFs, we conducted a study to assess the epidemiology of DRFs and its treatment in the catchment area of Akershus University Hospital (AHUS). Patients 16 years or older who presented to AHUS with an acute DRF during the years 2010 and 2011 were prospectively recorded and classified according to the AO fracture classification system. The mechanism of injury and treatment modality were noted. Overall, 1565 patients with an acute DRF presented to the institution in 2010-2011, of which 1134 (72%) were women. The overall annual incidence was 19.7 per 10,000 inhabitants 16 years or older. Women had an exponential increase in incidence after the age of 50, though the incidence for both genders peaked after the age of 80 years. There was an even distribution between extra- and intra-articular fractures. Falling while walking outside was the most common mechanism of injury. Of the 1565 registered, 418 (26.7%) patients underwent surgery, with a volar locking plate being the preferred surgical option in 77% of the cases. The overall incidence of distal radius fractures was lower in our study than earlier reports from Norway. Postmenopausal women had a higher risk of fracture than the other groups, and low-energy injuries were most dominant. 26.7% were treated operatively, which is higher than earlier reports, and might reflect an increasing preference for surgical treatment.


Hepatoprotective effect of three herbal extracts on aflatoxin B1-intoxicated rat liver.
Roots of Ixora coccinea (Rubiaceae), and Rhinacanthus nasuta (Acanthaceae) and whole plants of Spilanthes ciliata (Asteraceae) are extensively used by tribal communities in South India to treat liver diseases. However, the veracity of these tribal claims has not been investigated scientifically using the liver toxin, aflatoxin. This study reports on the protective effects of these three herbal ethanolic extracts on the aflatoxin B1 (AFB1)-intoxicated livers of albino male Wistar rats. Biochemical parameters, including serum hepatic enzymes (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase), were studied. Hepatic tissues were processed for assay of reduced glutathione (GSH) and histological alterations. Pre-treatment of the rats with oral administration of the plant ethanolic extracts, Ixora coccinea (IC), Rhinacanthus nasuta (RN), Spilanthes ciliata (SC), prior to AFB1 was found to provide significant protection against toxin-induced liver damage, determined 72 hours after the AFB1 challenge (1.5 mg/kg, intraperitoneally) as evidenced by a significant lowering of the activity of the serum enzymes and enhanced hepatic reduced GSH status. Pathological examination of the liver tissues supported the biochemical findings. The three plant extracts, IC, RN and SC, showed significant antilipid peroxidant effects in vitro. It was concluded that the hepatoprotective effects of the three plant extracts observed in this study might result from their potent antioxidative properties.


Tizanidine-induced depression of polysynaptic cutaneous reflexes in nonanesthetized monkeys is mediated by an alpha 2-adrenergic mechanism.
Previous studies in anesthetized or reduced preparations of nonprimate animals revealed that the alpha 2-adrenergic agonist tizanidine, clinically used as an antispastic drug, effectively reduces polysynaptic flexor reflexes. To further clarify the invoked adrenergic mechanism for physiological motor functions, and in view of the clinical relevance of tizanidine, the effect of this substance was reinvestigated in awake, nonanesthetized monkeys. Systemic applications of tizanidine dose-dependently reduced the magnitude of the electromyographic response of the flexor reflex that was induced by nonnoxious stimulation of cutaneous afferents. Whereas the effects on the flexor response were consistent, the changes of the background electromyogram were much more variable, often not paralleling those of the reflex. The reflex depression produced by tizanidine could be prevented by pretreatment with the alpha 2-antagonist yohimbine. It is concluded that the action of tizanidine on spinal reflexes, and therefore probably also on hyperactive reflexes of spastic patients, is mediated via the alpha 2-adrenergic properties of the drug. On the basis of the present results, taken together with previous observations that tizanidine transiently inactivates neurons of the nucleus locus coeruleus, it is proposed that the reflex depression may be caused by a removal of a descending noradrenergic facilitation exerted on spinal reflex transmission. This interpretation leaves open further possible actions of tizanidine exerted directly on spinal interneurons.


A Dual-Scale Convolutional Neural Network for Sleep Apnea Detection with Time-Delayed SpO2 Signals.
Sleep apnea (SA) is a common breathing disease, with clinical manifestations of sleep snoring at night with apnea and daytime sleepiness. It could lead to ischemic heart disease, stroke, or even sudden death. SpO2 signal is highly related to SA, and many automatic SA detection methods have been proposed. However, extant work focuses on small datasets with relatively few subjects (less than 100) and is unaware of SA syndromes occurring about 5 seconds prior to the SpO2 change. This study proposes an automatic SA detector called DSCNN using a single-lead SpO2 signal with a dual-scale convolutional neural network. To solve the time-delayed problem of SpO2 changes, we enlarge the target SpO2 segment information by combining its subsequent segment information. To utilize neighbouring segments information and further facilitate the SA detection performance, a dual-scale neural network with the fusing information of the prolonged target segment and its two surrounding segments is proposed. Three datasets from multiple centres are employed to verify the generic performance of DSCNN. Here, we must point out that we use two datasets as external datasets, and one of them is collected from the First Affiliated Hospital of Sun Yat-sen University with a large sample size (450 subjects). Extensive experiment results show that DSCNN can achieve promising results which are superior to the existing state-of-the-art methods.


A dopamine-precursor-based nanoprodrug for in-situ drug release and treatment of acute liver failure by inhibiting NLRP3 inflammasome and facilitating liver regeneration.
Acute liver failure (ALF) is a severe liver disease with high mortality rate. Inflammasome is a newly-found and promising target for effective treatment of immunity-associated diseases including liver disease, and dopamine has recently been proved as an inhibitor for NLRP3 inflammasome. This work demonstrates a diselenide-based nanodrug for ALF treatment through inhibiting NLRP3 inflammasome activation and enhancing liver regeneration. A diselenide-containing molecule (DSeSeD) has been synthesized via covalently linking two l-Dopa molecules to a diselenide linker, and the resultant molecules form stable nanoparticles in aqueous media and encapsulate SW033291 (an inhibitor of prostaglandin-degrading enzyme that hampers liver regeneration) to produce the nanodrug (SW@DSeSeD). As a nanoscale prodrug, SW@DSeSeD protects its payloads from decomposition in bloodstream upon administration, accumulates in liver of ALF mice, then responds to the overexpressed ROS and thereby releases SW033291 as well as a stable dopamine precursor that can transform into dopamine in hepatic cells, thus achieving significant therapeutic efficacy against ALF through inhibiting NLRP3 inflammasome activation and enhancing hepatic regeneration. Moreover, multiple contrast agents have been loaded onto the nanodrug to achieve fluorescence, optoacoustic and magnetic resonance imaging for nanodrug location and disease evaluation.


Induction of apoptosis by ursolic acid through activation of caspases and down-regulation of c-IAPs in human prostate epithelial cells.
Previous results indicate that ursolic acid (UA), a pentacyclic triterpene acid, has strong cytotoxic activity and effectively induces growth arrest in a variety of systems. However, the molecular mechanisms underlying anti-tumorigenic or chemopreventive activities of UA are poorly understood. To further determine the mechanism of UA, we investigated the effects of UA on the growth of human prostate epithelial cells. Upon treatment with UA, a concentration-dependent inhibition of cell viability was observed and cells developed many of the hallmark features of apoptosis, including condensation of chromatin and DNA fragmentation. These apoptotic effects of UA were accompanied by proteolytic cleavage of specific target proteins such as PARP, beta-catenin and Rad51 proteins suggesting the possible involvement of caspases. Western blotting and in vitro assay demonstrated that processing/activation of at least four caspases (caspase-1, -3, -8 and -9) accompanies the generation of UA-mediating apoptotic cell death. In addition to activation of caspases, the down-regulation of c-IAPs family proteins, which suppress the apoptotic death signaling by the direct inhibition of activated caspases, was also observed. However, UA did not affect both the level of p53 expression and the alteration of the balance between Bcl-2 and Bax expression. These data suggest that apoptotic signals evoked by UA treatment may converge caspases activation through down-regulation of c-IAPs family and without mitochondrial dysfunction.


Use of Internet Search Data to Monitor Rotavirus Vaccine Impact in the United States, United Kingdom, and Mexico.
Previous studies have found a strong correlation between internet search and public health surveillance data. Less is known about how search data respond to public health interventions, such as vaccination, and the consistency of responses in different countries. In this study, we aimed to study the correlation between internet searches for "rotavirus" and rotavirus disease activity in the United States, United Kingdom, and Mexico before and after introduction of rotavirus vaccine. We compared time series of internet searches for "rotavirus" from Google Trends with rotavirus laboratory reports from the United States and United Kingdom and with hospitalizations for acute gastroenteritis in the United States and Mexico. Using time and location parameters, Google quantifies an internet query share (IQS) to measure the relative search volume for specific terms. We analyzed the correlation between IQS and laboratory and hospitalization data before and after national vaccine introductions. There was a strong positive correlation between the rotavirus IQS and laboratory reports in the United States (R2 = 0.79) and United Kingdom (R2 = 0.60) and between the rotavirus IQS and acute gastroenteritis hospitalizations in the United States (R2 = 0.87) and Mexico (R2 = 0.69) (P < .0001 for all correlations). The correlations were stronger in the prevaccine period than in the postvaccine period. After vaccine introduction, the mean rotavirus IQS decreased by 40% (95% confidence interval [CI], 25%-55%) in the United States and by 70% (95% CI, 55%-86%) in Mexico. In the United Kingdom, there was a loss of seasonal variation after vaccine introduction. Rotavirus internet search data trends mirrored national rotavirus laboratory trends in the United States and United Kingdom and gastroenteritis-hospitalization data in the United States and Mexico; lower correlations were found after rotavirus vaccine introduction.


The new thinking on lipids and coronary artery disease.
Detection and treatment of high blood cholesterol has significantly reduced cardiovascular events. However, most individuals with coronary artery disease do not have hypercholesterolemia. Atherosclerosis is a complex interaction of inherited susceptibility and environmental issues that combine to create an atherogenic milieu. Appropriate diagnosis and treatment of patients with coronary artery disease can be of significant benefit, but if treatment is not individualized to the patient's individual metabolic abnormality, many patients will receive little to no benefit despite improved lipid profiles.