Distinct stages of adult hippocampal neurogenesis are regulated by running and the running environment.
Hippocampal neurogenesis continues into adulthood in mammalian vertebrates, and in experimental rodent models it is powerfully stimulated by exposure to a voluntary running wheel. In this study, we demonstrate that exposure to a running wheel environment, in the absence of running, is sufficient to regulate specific aspects of hippocampal neurogenesis. Adult mice were provided with standard housing, housing enriched with a running wheel or housing enriched with a locked wheel (i.e., an environment comparable to that of running animals, without the possibility of engaging in running). We found that mice in the running wheel and locked wheel groups exhibited equivalent increases in proliferation within the neurogenic niche of the dentate gyrus; this included comparable increases in the proliferation of radial glia-like stem cells and the number of proliferating neuroblasts. However, only running animals displayed increased numbers of postmitotic neuroblasts and mature neurons. These results demonstrate that the running wheel environment itself is sufficient for promoting proliferation of early lineage hippocampal precursors, while running per se enables newly generated neuroblasts to survive and mature into functional hippocampal neurons. Thus, both running-independent and running-dependent stimuli are integral to running wheel-induced hippocampal neurogenesis.


Ketamine effect on HMGB1 and TLR4 expression in rats with acute lung injury.
Acute lung injury (ALI) is a common emergency and severe case in clinic. High mobility group protein box 1 (HMGB1) can be treated as a new anti-inflammatory treatment target. Toll-like receptor 4 (TLR4) is an important receptor of HMGB1. Ketamine is a widely used intravenous anesthetic with good anti-inflammatory and immune regulating function. Whether it can protect ALI through inhibiting HMGB1 and TLR4 expression in lung tissue still needs further investigation. Male SD rats were randomly divided into control, lipopolysaccharide (LPS) group and ketamine intervention group with 15 rats in each group. The rats were euthanatized at 24 h after modeling and the bronchoalveolar lavage fluid (BALF) was collected for HMGB1 and TLR4 level detection. Western Blot was applied to analyze HMGB1 and TLR4 protein expression in the lung tissue. HMGB1 and TLR4 concentration in BALF were 5.369 ± 1.564 ng/ml and 43.980 ± 7.524 pg/ml in the control, respectively. They were 12.358 ± 4.681 ng/ml and 102.538 ± 8.412 pg/ml in LPS group, and 7.399 ± 2.346 ng/ml and 87.208 ± 7.558 pg/ml in ketamine intervention group, respectively. Their levels increased significantly in LPS group and down-regulated after ketamine intervention. HMGB1 and TLR4 protein expression in lung tissue elevated obviously in LPS group, and decreased after ketamine treatment. HMGB1 and TLR4 protein level showed positive correlation in lung tissue (r = 0.921, P < 0.001). Ketamine can inhibit HMGB1 and TLR4 expression in ALI, and alleviate LPS induced rat lung injury.


How ethical dilemmas are resolved.
The prevalence of ethics committees in long-term care facilities has been on the rise since 1970. This study explores the nature of these committees and how ethical dilemmas are resolved where there is no committee.


The characterization of the common fragile site FRA16D and its involvement in multiple myeloma translocations.
Fragile sites appear as breaks, gaps, or decondensations on metaphase chromosomes when cells are grown under specific culture conditions. The breaks are nonrandom, appearing in defined, conserved locations throughout the mammalian genome. Common fragile sites, as their name implies, are present in virtually all individuals. With three common fragile sites cloned, their mechanism of expression and the role, if any, they play in human disease are still unclear. We have assembled a BAC contig of >1 Mb across the second most active common fragile site, FRA16D (16q23.2). We fluorescently labeled these BACs and used them as probes on metaphases from aphidicolin-induced lymphocytes and demonstrated that FRA16D decondensation/breakage occurs over a region of at least 1 Mb. Thus, this is the largest common fragile site cloned to date. Microsatellite markers that map within FRA16D show a very high loss in prostate, breast, and ovarian tumors, indicating that loss within this fragile site may be important in the development or progression of these tumors. In addition, a common t(14q32;16q23) translocation is observed in up to 25% of all multiple myelomas (MM). We localized four of four such cloned t(14;16) MM breakpoints within the FRA16D region. This work further demonstrates that the common fragile sites may play an important role in cancer development.


Learning From Morbidity and Mortality Conferences: Focus and Sustainability of Lessons for Patient Care.
It remains unclear to what extent the morbidity and mortality conference (M&M) meets the objective of improving quality and safety of patient care. It has been suggested that M&M may be too focused on individual performance, hampering system-level improvement. The aim of this study was to assess focus and sustainability of lessons for patient care that were derived from M&M. This is an observational study of routinely collected data on evaluated complications and identified lessons at surgical M&M for 8 years, assessing type and recurrence of lessons and cases from which these were drawn. Semistructured interviews with clinicians were qualitatively analyzed to explore factors contributing to lesson focus and recurrence. Three hundred eighteen lessons were drawn from 10,883 evaluated complications, primarily for those that were more severe, related to surgical or other treatment, and occurring in nonemergent, lower risk cases (all P < 0.001). Most lessons targeted intraoperative (43%) rather than preoperative or postoperative care as well as specifically technical (87%) and individual-level issues (74%). There were 43 recurring lessons (14%), mostly about postoperative care (47%) and medication management (50%). Interviewed clinicians attributed the intraoperative, technical focus primarily to greater appeal and control but identified an array of factors contributing to lesson recurrence, such as typical staff turnover in teaching hospitals. This study provided empirical evidence that learning at M&M has a tendency to focus on intraoperative, technical performance, with challenges to sustain lessons for more system-level issues. Morbidity and mortality conference formats need to anticipate these tendencies to ensure a wide focus for learning with lasting and wide impact.


Paclitaxel in patients with advanced angiosarcomas of soft tissue: a retrospective study of the EORTC soft tissue and bone sarcoma group.
Angiosarcomas of soft tissue represent a heterogenous group of rare sarcomas with specific clinical behaviour and risk factors. Paclitaxel appears to induce tumour control in a higher proportion of patients with angiosarcoma, as compared to other sarcomas. The objective of this retrospective study was to assess the anti-tumour activity of this compound in a multicentre setting. Clinical data from patients with angiosarcomas of soft tissue treated with single agent paclitaxel were collected from the centres of the soft tissue and bone sarcoma group of EORTC, using a standardised data collection form. Paclitaxel could be given every three weeks, or weekly. Statistical analysis was performed using SAS software. Data from 32 patients were collected from 10 centres. There were 17 males, 15 females, with a median age of 60.4 years (range, 25-91). Primary angiosarcomas were located in scalp and face in 8 patients (25%) and at other primary sites in 24 patients (75%). All patients had intermediate (n=13) or high grade (n=19) primary tumours. Thirteen (40%) patients had been pretreated with doxorubicin-based first-line-chemotherapy and three of them (9%) had also received second-line chemotherapy with ifosfamide. Eleven (34%) patients had been irradiated before as treatment for angiosarcoma. In 8 (25%) patients, the angiosarcoma occurred at sites of prior radiation therapy for other malignancies. The response rate was 62% (21/32) in the whole series, 75% (6/8) in scalp angiosarcomas and 58% (14/24) in other primary sites. The median time to progression was 7.6 months (range, 1-42) for the whole group. For the face/scalp group it was 9.5 months, and for patients with angiosarcomas at other sites it was 7.0 months, respectively. Paclitaxel was found to be an active agent in angiosarcoma of soft tissue in this retrospective analysis. These results need to be confirmed in a prospective randomised phase II study.


Fast network oscillations induced by potassium transients in the rat hippocampus in vitro.
Brief pressure ejection of solutions containing potassium, caesium or rubidium ions into stratum radiatum of the CA1 or CA3 regions of the hippocampal slice evoked a fast network oscillation. The activity evoked lasted approximately 3-25 s with the predominant frequency component being in the gamma frequency range (30-80 Hz), although beta frequency (15-30 Hz) and ultrafast (> 80 Hz) components could also be seen. The gamma frequency component of the oscillation remained constant, even when large changes in power occurred, and was synchronous across the CA1 region. Measurements with potassium ion-sensitive electrodes revealed that the network oscillation was accompanied by increases (0.5 to 2.0 mM) in the extracellular potassium concentration [K+]o. Bath application of the N-methyl-D-aspartate (NMDA) receptor antagonists D(-)-2-amino-5-phosphonopentanoic acid (D-AP5; 50 microM) had no significant effect but the alpha-amino-3-hydroxy-5-methyl-4-isooxazolepropionic acid (AMPA)/kainate receptor antagonist 2,3,-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulphonamide disodium (NBQX; 20 microM) caused a significant reduction (86.7 +/- 4.5 %) in the power in the gamma frequency range. Residual rhythmic activity, presumably arising in the interneuronal network, was blocked by the GABA(A) receptor antagonist bicuculline. The putative gap junction blocker octanol caused a decrease in the power of the gamma frequency component of 75.5 +/- 5.6 %, while carbenoxolone produced a reduction of only 14 +/- 42 %. These experiments demonstrate that a modest increase in exogenous [K+]o in the hippocampus in vitro is sufficient to evoke a fast network oscillation, which is an emergent property of the synaptically and electrically interconnected neuronal network.


Hepatic insig-1 or -2 overexpression reduces lipogenesis in obese Zucker diabetic fatty rats and in fasted/refed normal rats.
To determine whether the antilipogenic actions of insulin-induced gene 1 (insig-1) demonstrated in cultured preadipocytes also occur in vivo, we infected Zucker diabetic fatty (ZDF) (fa/fa) rats, with recombinant adenovirus containing insig-1 or -2 cDNA. An increase of both proteins appeared in their livers. In control ZDF (fa/fa) rats infected with adenovirus containing the beta-galactosidase (beta-gal) cDNA, triacylglycerols in the liver and plasma rose steeply whereas the insig-infected rats exhibited substantial attenuation of the increase in hepatic steatosis and hyperlipidemia. Insig overexpression was associated with a striking reduction in the elevated level of nuclear sterol regulatory element-binding protein (SREBP)-1c, the activated form of the transcription factor. The mRNA of SREBP-1c lipogenic target enzymes also fell. The mRNA of endogenous insig-1, but not -2a and -2b, was higher in the fatty livers of untreated obese ZDF (fa/fa) rats compared with controls, but the elevation was not sufficient to block the approximately 3-fold increase in SREBP-1c expression and activity. In normal animals, adenovirus-induced overexpression of the insigs reduced the increase in SREBP-1c mRNA and its target enzymes caused by refeeding. The findings demonstrated that both insigs have antilipogenic action when transgenically overexpressed in livers with increased SREBP-1c-mediated lipogenesis. However, the increase in endogenous insig-1 expression associated with augmented lipogenesis may limit it, but is insufficient to prevent it.


Elements affecting wound healing time: An evidence based analysis.
The purpose of this study was to identify the predominant client factors and comorbidities that affected the time taken for wounds to heal. A prospective study design used the Mobile Wound Care (MWC) database to capture and collate detailed medical histories, comorbidities, healing times and consumable costs for clients with wounds in Gippsland, Victoria. There were 3,726 wounds documented from 2,350 clients, so an average of 1.6 wounds per client. Half (49.6%) of all clients were females, indicating that there were no gender differences in terms of wound prevalence. The clients were primarily older people, with an average age of 64.3 years (ranging between 0.7 and 102.9 years). The majority of the wounds (56%) were acute and described as surgical, crush and trauma. The MWC database categorized the elements that influenced wound healing into 3 groups--factors affecting healing (FAH), comorbidities, and medications known to affect wound healing. While there were a multitude of significant associations, multiple linear regression identified the following key elements: age over 65 years, obesity, nonadherence to treatment plan, peripheral vascular disease, specific wounds associated with pressure/friction/shear, confirmed infection, and cerebrovascular accident (stroke). Wound healing is a complex process that requires a thorough understanding of influencing elements to improve healing times.© 2015 by the Wound Healing Society.


Protocol for the implementation evaluation of an integrated paediatric and primary care model: Strengthening Care for Children (SC4C).
Implementation evaluations provide insight into how interventions are delivered across varying contexts and why interventions work in some contexts and not in others. This manuscript outlines a detailed protocol of an implementation evaluation embedded in a stepped-wedge cluster randomised controlled trial of a model of care, Strengthening Care for Children (SC4C), that integrates paediatric care in general practice. The purpose of this manuscript is to describe the pragmatic methods that will be used to capture implementation evaluation process and outcome data within this trial. Our implementation evaluation will use a mixed methods design, with data collected in the intervention arm of the SC4C trial guided by a logic model developed using the Consolidated Framework for Implementation Research (CFIR) and Proctor and colleague's taxonomy of implementation outcomes. Data collection will be via questionnaires and semistructured interviews with general practitioners, paediatricians, general practice administrative staff and children and families. Each of the 21 general practices recruited into the study will be described in terms of staffing, patient throughput and location, in addition to the nuanced inner and outer contexts, use of the intervention and its acceptability. We will quantify implementation effectiveness in each general practice clinic using the CFIR validated scoring system. Importantly, we have embedded data collection post intervention to enable assessment of the sustainable adoption of the intervention. An inductive approach to the analysis of qualitative data will identify additional emerging themes that may not be covered by the formal frameworks underpinning our analysis. Ethical approval was granted by the Royal Children's Hospital Ethics Committee in August 2020 (HREC: 65955). Results will be submitted for publication in peer-reviewed journals and presented at relevant conferences. Australia New Zealand Clinical Trials Registry 12620001299998 on 1 December 2020.


Three-dimensional long-period waveguide gratings for mode-division-multiplexing applications.
We propose a three-dimensional (3D) long-period grating structure that has a controllable grating width and depth and can be formed at any chosen position on the surface of a waveguide core with a single photolithography process. The process relies on the partial etching of small structures on the surface of a polymer waveguide through a waveguide mask with narrow apertures that define the grating pattern. The 3D grating structure allows the design of mode converters for any nondegenerate guided modes of a waveguide, regardless of their symmetry properties, and thus relaxes the design constraint of conventional two-dimensional waveguide gratings. To show the flexibility of the 3D grating structure, we present several mode converters fabricated with this structure. The mode-conversion efficiencies achieved are higher than 90% at the resonance wavelengths. In addition, we demonstrate a three-mode multiplexer by integrating a grating-based mode converter with two asymmetric directional couplers. The proposed grating structure together with the fabrication process can greatly facilitate the development of grating-based devices, especially for MDM applications.


Measuring Impulsivity in Greek Adults: Psychometric Properties of the Barratt Impulsiveness Scale (BIS-11) and Impulsive Behavior Scale (Short Version of UPPS-P).
The aim of the present study was to validate the Barratt Impulsiveness Scale (BIS-11th version) scale as well as the short version of the Impulsive Behavior Scale (UPPS-P) in a population of Greek young adults. Secondly, we aimed at validating the BIS-11 in older adults. 167 (Group 1) university students completed the Greek version of the BIS-11 (BIS-11-G) and the UPPS (UPPS-P-G) scales. Additionally, BIS-11-G was also administered to 167 (Group 2) cognitively intact older adults, to identify whether it could be used to measure impulsivity in an older adult population. Both scales had satisfactory internal reliability and test-retest reliability, as well as convergent validity in the young adult population. In regard to the factor structure, a principal component analysis (PCA) extracted two factors for the BIS-11-G in the young adult population and three factors in older adults, as well as three factors for the short UPPS-P-G in young adults. The BIS-11-G and the UPPS-P-G scales can be used to measure different aspects of impulsivity in the Greek population of different ages in research and clinical practice.


Mechanism of sulfotransferase pharmacogenetics in altered xenobiotic metabolism.
Cytosolic sulfotransferases (SULTs), one of the vital enzymes of detoxication, catalyze the sulfation of native and exogenous hydrophobic molecules. Xenobiotic accumulation can induce a variety of diseases, including cancers. Sulfation facilitates the solubilization and removal of xenobiotics. However, sulfation may activate the pharmacological activities of xenobiotics. The purpose of this review was to correlate the sequence, structure and function of SULTs. We focused on understanding the sulfation mechanisms of SULT through its sequence variation. We selectively reviewed SULT drug substrates, explained the enzyme-catalyzed sulfation reaction and its kinetic mechanisms, and the effect of amino acid sequence variation, such as single-nucleotide polymorphism, on the enzyme function. A wealth of information is available in the literature for understanding the detailed mechanisms underlying xenobiotic sulfation. We reviewed information regarding the sequence, structure and reaction mechanism of SULTs and explained how SULT activities altered. In addition to revealing the SULT kinetics, the mRNA expression of specific SULTs in tissues that revealed their distribution in tissues also affects overall SULT activities. Understanding of the structure-function relationship and the reaction mechanism of SULTs is valuable for understanding, preventing and treating diseases.


Physical activity patterns and exercise performance in cardiac transplant recipients.
Cardiac transplantation (CTX) improves exercise tolerance, but CTX recipients still achieve only 50% to 70% of normal values for exercise capacity. Among the factors suggested to explain the reduced exercise tolerance in CTX recipients is deconditioning. Little is known about the relation between physical activity patterns and exercise test responses in CTX patients. Forty-seven CTX patients (mean age 47 +/- 12 years; mean 4.8 +/- 3.0 years after CTX) underwent maximal exercise testing and assessment of current and past physical activity patterns using a questionnaire. Energy expenditure from recreational and occupational activities over the last year and for adulthood were expressed in kcal/week and correlated with peak oxygen consumption (VO(2)), VO(2) at the ventilatory threshold, and the percentage of age-predicted peak VO(2) achieved. The patients reported expending a mean of approximately 1100 kcal/week in recreational activity, suggesting a moderate level of physical activity is maintained after CTX. The mean peak VO(2) achieved for the group was 17.2 +/- 5.2 mL/kg/min, corresponding to 59% +/- 14% of age-predicted exercise capacity. Significant but modest associations were observed between recreational energy expenditure during the last year and percentage of age-predicted peak VO(2) achieved (r = 0.34, P <.01), and VO(2) at the ventilatory threshold (r = 0.45, P <.01). Energy expenditure from blocks walked and stairs climbed per week was modestly associated with peak VO(2) (r = 0.36, P <.05), percentage of predicted peak VO(2) achieved (r = 0.39, P <.01), and VO(2) at the ventilatory threshold (r = 0.42, P <.01). Exercise capacity was poorly related to occupational and recreational activities when expressed as average weekly energy expended throughout adulthood. Post-CTX patients maintain a moderately active lifestyle. Measures of exercise tolerance generally are related to recent daily recreational activities in CTX patients, but these associations are modest. The many physiologic factors unique to CTX recipients likely play a more important role than deconditioning in determining exercise tolerance in these patients.


[Roentgenological symptoms of functional changes in the respiratory organs of patients with pulmonary tuberculosis].
To study typical disorders in the external respiration function of patients with pulmonary tuberculosis without concurrent bronchial obstruction and to find out an information potential of the roentgeno-pneumo-polygraphic+ (RPPG) method in detecting local obstructive disturbances, 53 subjects aged from 23 to 52 years with respiratory tuberculosis, including 38 and 15 of them with a limited or disseminated process, respectively, were examined. X-ray functional examination conducted in dynamics and with the use of physical load and bronchodilators made in possible to discover both local and disseminated occult bronchial obstruction. Application of RPPG method and administration of such bronchodilator, as berotec, revealed a functional nature of the bronchial obstruction. According to RPPG data. In a lingering tuberculous process a costal component is predominant in the course of respiration.


[Medical photography in orthopedics then and now--a historical overview].
An historical overview is given about the medical photography especially in orthopaedic surgery from the beginning until modern times. Orthopaedic surgeons early found out the advantage of this method for documentation of clinical cases. More and more photography was used from the end of the 19. century until now because of its remarkable advantages. In the last years three dimensional photographic measurement has established and is acknowledged to be useful in diagnosis and follow up of deformities, especially of scoliosis. Cinematographic methods for analysis of human movement are helpful tools for diagnosis and therapy of pathologic movement.


Hydrocephalus in the emergency department: descriptive nationwide data and analysis of transfer.
Hydrocephalus is a chronic, treatable, but in most cases incurable condition characterized by long periods of stability punctuated by crises. Patients in crisis usually seek care in an emergency department (ED). How patients with hydrocephalus use EDs has received almost no epidemiological study. Data were taken from the National Emergency Department Survey for 2018. Visits by patients with hydrocephalus were identified by diagnostic codes. Neurosurgical visits were identified by codes for imaging of the brain or skull or by neurosurgical procedure codes. Visits and dispositions were characterized by demographic factors for neurosurgical and unspecified visits by using methods for analysis of complex survey designs. Associations among demographic factors were assessed using latent class analysis. There were an estimated 204,785 ED visits by patients with hydrocephalus in the United States in 2018. Roughly 80% of patients with hydrocephalus who visited EDs were adults or elders. By a ratio of 2:1, patients with hydrocephalus visited EDs much more often for unspecified reasons than for neurosurgical reasons. Patients with neurosurgical complaints had more costly ED visits, and if they were admitted they had longer and more costly hospitalizations than did patients with unspecified complaints. Only 1 in 3 patients with hydrocephalus who visited an ED was sent home regardless of whether the complaint was neurosurgical. Neurosurgical visits ended in transfer to another acute care facility more than 3 times as often as unspecified visits. Odds of transfer were more strongly associated with geography and, specifically, with proximity to a teaching hospital than with personal or community wealth. Patients with hydrocephalus make heavy use of EDs, and they make more visits for reasons unrelated to their hydrocephalus than for neurosurgical reasons. Transfer to another acute care facility is an adverse clinical outcome that is much more common after neurosurgical visits. It is a system inefficiency that might be minimized by proactive case management and coordination of care.


GSK-3β inhibitor 6-bromo-indirubin-3'-oxime promotes both adhesive activity and drug resistance in colorectal cancer cells.
Multi-targets inhibitor 6-bromo-indirubin-3'-oxime (BIO) has diverse biological effects on cancer cells. The key component of the β-catenin destruction complex glycogen synthase kinase 3β (GSK-3β), one of the major target for BIO, polyubiquitination and degradation of the main oncoprotein β-catenin in colorectal cancer (CRC). In the present study, we evaluated the effect of BIO on drug resistance and biological properties of CRC cells. Whole-genome transcriptional profiling revealed that differentially expressed genes were mainly centered on well-characterized signaling pathways including stem cell, cell adhesion and cell growth in BIO-treated CRC cells. BIO treatment downregulated migration and invasion abilities of CRC cells, accompanying with MMP-9 downregulated and E-cadherin upregulated CRC cells. BIO treatment decreased apoptosis induced by 5-Fu/DDP in CRC SW480 cells. In addition, BIO treatment reversed the 5-Fu-induced CD133+ cell downregulation trend in CRC SW620 cells. After incubation with BIO, the expression levels of EpCAM, TERT and DCAMKL-1 proteins were upregulated in CRC cells. BIO treatment downregulated the activity of GSK-3β, upregulated and transported β-catenin to the nucleus in CRC cells. Our findings reveal that BIO treatment upregulated stemness, adhesive and chemoresistance of CRC cells. GSK-3β inhibition and WNT/β-catenin activation by BIO, may partly result in the biological behavior alterations in CRC cells.


Appendix sepsis tracking along the lateral cutaneous nerve of the thigh.
A patient presented with tracking of pus from a chronic appendiceal abscess along the lateral cutaneous nerve of the thigh. In the absence of such a tunnel, which is only present in a small proportion of individuals, the infection would have resulted in a subinguinal psoas abscess. Although pus may conceivably extend in any direction, the reason for this unusual complication remains poorly understood.


Lactation stage-dependent changes of lymphocyte subpopulations in mammary secretions: inversion of CD4+/CD8+ T cell ratios at parturition.
Determination of lactation stage-dependent changes in levels of lymphocyte subpopulations in milk. Flow cytometric assay was used to identify and assay lymphocyte subpopulations in bovine milk at different stages of lactation. Lymphocyte subpopulations in mammary secretions of dairy cows change during the lactation cycle. In involuting glands (dry gland), approximately 80-90% of lymphocytes were CD2+ T cells. The proportion of CD2+ T cells, however, decreased to approximately 50% at the colostral stage an fluctuated between 50 to 60% in normal (mature) milk. Throughout the lactation stages, less than 5% were B cells as identified by the monoclonal antibodies against CD21 and MHC class II antigens. Subset analysis showed, however, that the proportion of CD5+ T cells decreased from 90% in involuting gland secretions to 75% in colostrum (peripartum stage), and to approximately 40-50% in the normal (mature) milk, CD4+ T cells constituted between 45 to 55% of lymphocytes in the dry gland secretion but decreased drastically at parturition and maintained at the level below 20% throughout normal lactation. In contrast, the proportion of CD8+ T cells in the dry gland secretion was low, between 30 to 40%, but increased steadily, in an inversely-related manner with that of CD4+ T cells, to approximately 40-50% at parturition and maintained at approximately 30-40% during the normal lactation stage thereafter. Two-color immunofluorescence study revealed further that practically all of the CD8+ cells in dry gland secretions were CD2+, and approximately 40% of them were CD5-. Throughout the lactation cycle, WC1+ gamma delta T cells comprised only 2 to 5% of lymphocytes in mammary secretions. T lymphocyte subpopulations change dynamically during stages of the lactation cycle. The selective migration of T lymphocyte subpopulations to and from the mammary gland, and their functional roles in the immune competence and regulation of the dam and sucklings remain to be elucidated.


Combined measurement system for double shield tunnel boring machine guidance based on optical and visual methods.
In order to detect the position of the cutting shield at the head of a double shield tunnel boring machine (TBM) during the excavation, this paper develops a combined measurement system which is mainly composed of several optical feature points, a monocular vision sensor, a laser target sensor, and a total station. The different elements of the combined system are mounted on the TBM in suitable sequence, and the position of the cutting shield in the reference total station frame is determined by coordinate transformations. Subsequently, the structure of the feature points and matching technique for them are expounded, the position measurement method based on monocular vision is presented, and the calibration methods for the unknown relationships among different parts of the system are proposed. Finally, a set of experimental platforms to simulate the double shield TBM is established, and accuracy verification experiments are conducted. Experimental results show that the mean deviation of the system is 6.8 mm, which satisfies the requirements of double shield TBM guidance.


[Non derivated surgery indications and limits in bile duct iatrogenic injuries treatment].
Recently the incidence of iatrogenic bile duct injuries has increased proportionally to development of the laparoscopic surgery. The objective of this study is to determine the possible application of non derivated surgical repairs in iatrogenic bile duct injuries treatment of the above procedures. These surgical approaches range from simply placing a surgical drainage to liver transplantation. With reference to Strasberg's classification non derivated treatments are listed, furthermore are discussed and analysed their indications and limits. Owing to their experience and specific literature, the authors came to the following conclusions: 1) These surgical options represent an ideal reconstruction technique because they restore bile ducts continuity without altering physiological mechanisms to which these anatomical structures are appointed. 2) The indications of applying these methods are rare and usually limited to those cases in which the lesion has been recognized during operation and in the immediate post operative period.


Knowledge and decision making about future fertility and oocyte cryopreservation among young women.
The objective was to examine what young graduate student women know about preserving fertility/oocyte cryopreservation, and which reproductive resources they use. A prospective, cross-sectional design was used and the study was conducted at a University on the East Coast of the United States. The participants were 278 female graduate students. Participants completed a survey with questions about demographics, fertility knowledge, oocyte cryopreservation, and sources of fertility information. Descriptive statistics were calculated for all variables. Participants had average knowledge about fertility (64% items correct). The most used fertility information source was formal education (87.1%), information to help make fertility decisions was gynaecologists (85.3%), and oocyte cryopreservation was media (63.4%). Only 26.6% reported being well informed about fertility. Although 93.9% had heard of oocyte cryopreservation, only 7.2% had considered its use. Most (74.9%) ranked fertility as important, though 83% would consider postponing family until career (85.2%) and relationship (85.2%) were established. Half felt that there was a social stigma surrounding oocyte cryopreservation, and 70.1% believed that the media gives the impression that motherhood is viable after 40 years old. Professionally motivated women receive the most information about fertility from formal, accuracy-driven sources (i.e. education, healthcare providers), but information about fertility preservation from media. They lack knowledge about fertility planning.


Fibroblasts of rabbit kidney in culture. II. Paracrine stimulation of papillary fibroblasts by PDGF.
To examine the role of tubulointerstitial cell interaction in the regulation of fibroblast growth, fibroblasts from the rabbit renal cortex (CF) and papilla (PF) were cocultured with epithelial cells from the same tissue location. Inner medullary collecting duct epithelial cells (IMCDE) or IMCDE-conditioned medium stimulated DNA synthesis in PF, whereas proximal tubule epithelium (PTE) had no effect on the proliferation of CF. PF and CF showed a similar mitogenic response to exogenous epidermal growth factor and insulin-like growth factor 1 (IGF-I). Transforming growth factor-beta 1 inhibited growth of both cell types, and basic fibroblast growth factor (bFGF) had no effect on proliferation of either cell type. In contrast, platelet-derived growth factor (PDGF) was a potent mitogen for PF but was only weakly mitogenic for CF. Both CF and PF expressed a similar number of a single-affinity class of PDGF receptors (Kd, 2-4 x 10(-10) M). Assay for growth factor activity in conditioned medium from IMCDE and PTE showed that only IMCDE produced detectable PDGF. IMCDE-stimulated proliferation of PF was partially blocked by an antibody to PDGF, whereas antibodies to IGF-I had no neutralizing effect. The data suggest a role for PDGF in the regulation of interstitial fibroblast proliferation by IMCDE in the renal papilla. This paracrine system may be important in the pathogenesis of some forms of interstitial fibrosis of the kidney.


Implementation of clinical guidelines using a computer charting system. Effect on the initial care of health care workers exposed to body fluids.
While clinical guidelines are considered an important mechanism to improve the quality of medical care, problems with implementation may limit their effectiveness. Few empirical data exist about the effect of computer-based systems for application of clinical guidelines on quality of care. To determine whether real-time presentation of clinical guidelines using an electronic medical record can increase compliance with guidelines. Prospective off-on-off, interrupted time series with intent-to-treat analysis. University hospital emergency department. Patients were 280 health care workers (50 in the baseline control phase, 156 in the intervention phase, and 74 in the postintervention control phase) who presented for initial treatment of occupational body fluid exposures, including 89% (248/280) who sustained punctures and 81% (208/257) who were exposed to blood. Physicians included resident physicians and attending physicians working in the emergency department during the study. Implementation of a computer charting system that provides real-time information regarding history and recommendations for laboratory testing, treatment, and disposition based on rules derived from clinical guidelines. Quality of care as determined by essential items documented in the medical record and in aftercare instructions, compliance with testing and treatment guidelines, and total charges and percentage of charges attributable to guideline-endorsed activities. Mean percent documentation of 7 essential items regarding patient history in the medical record increased from 57% during the baseline period to 98% in the intervention phase (42% increase; 95% confidence interval [CI], 34%-49%) and 11 items in aftercare instruction increased from 31 % at baseline to 93% during the intervention phase (62% increase; 95% CI, 51%-74%), but both decreased to baseline when the computer system was removed. Percent compliance with 4 laboratory testing guidelines increased from 63% at baseline to 83% during the intervention phase (20% increase; 95% CI, 9%-31 %) but decreased to 52% when the computer system was removed. Compliance with 5 treatment guidelines increased from 83% at baseline to 96% during the intervention phase (13% increase; 95% CI, 9%-17%) and decreased to 84% following the intervention. Percentage of charges incurred for indicated laboratory tests and treatment increased from 44% at baseline to 81% during the intervention phase (37% increase; 95% CI, 22%-52%) and decreased to 36% following the intervention. Average total per-patient charges were $460, $384, and $373 in each phase, respectively. Use of a computer-based system for clinical guidelines for management of patients with occupational exposure to body fluids improved documentation, compliance with guidelines, and percentage of charges spent on indicated activities, while decreasing overall charges. The parameters returned to baseline when the computer system was removed.


Neonatal androgen-dependent sex differences in lumbar spinal cord dopamine concentrations and the number of A11 diencephalospinal dopamine neurons.
A(11) diencephalospinal dopamine (DA) neurons provide the major source of DA innervation to the spinal cord. DA in the dorsal and ventral horns modulates sensory, motor, nociceptive, and sexual functions. Previous studies from our laboratory revealed a sex difference in the density of DA innervation in the lumbar spinal cord. The purpose of this study was to determine whether sex differences in spinal cord DA are androgen dependent, influenced by adult or perinatal androgens, and whether a sex difference in the number of lumbar-projecting A(11) neurons exists. Adult male mice have significantly higher DA concentrations in the lumbar spinal cord than either females or males carrying the testicular feminization mutation (tfm) in the androgen receptor (AR) gene, suggesting an AR-dependent origin. Spinal cord DA concentrations are not changed following orchidectomy in adult male mice or testosterone administration to ovariectomized adult female mice. Administration of exogenous testosterone to postnatal day 2 female mice results in DA concentrations in the adult lumbar spinal cord comparable to those of males. Male mice display significantly more lumbar-projecting A(11) DA neurons than females, particularly in the caudal portion of the A(11) cell body region, as determined by retrograde tract tracing and immunohistochemistry directed toward tyrosine hydroxylase. These results reveal an AR-dependent sex difference in both the number of lumbar-projecting A(11) DA neurons and the lumbar spinal cord DA concentrations, organized by the presence of androgens early in life. The AR-dependent sex difference suggests that this system serves a sexually dimorphic function in the lumbar spinal cord.


Elastases from inflammatory and dendritic cells mediate ultrafine carbon black induced acute lung destruction in mice.
Exposure to ultrafine particles (<100 nm in diameter) is postulated to cause chronic obstructive pulmonary disease (COPD). However, the mechanism remains to be elucidated. We aimed to evaluate whether ultrafine particle exposure causes the infiltration of inflammatory and dendritic cells (DCs) with increased elastase activity, contributing to lung parenchymal destruction. C57BL/6 male mice were intratracheally instilled with 300 µg ultrafine carbon black (ufCB; 14 nm in diameter), and sacrificed at 1, 3, 7 and 14 d post-exposure. Differential cell counts, elastase activities, and desmosine and hydroxyproline in bronchoalveolar (BAL) fluid were determined. Immunofluorescent staining and flow cytometry analysis determined the cell origin of macrophage metalloelastase (MMP-12). Anti-neutrophil antibody was applied to assess the contribution of elastase in ufCB induced lung destruction. ufCB exposure led to significant increases in neutrophils, mononuclear cells and total proteins in BAL fluid. Desmosine and hydroxyproline were significantly increased in the ufCB group. Elastase activities were found to be significantly elevated, with both neutrophil elastase and MMP-12 peaking at 3 d post-exposure. Flow cytometry analysis demonstrated that pulmonary infiltrations of MMP-12 positive DCs, including Langerhans cells-derived DCs, occurred at 3 d and 7 d, while macrophage infiltration was obvious starting at 1 d. Anti-neutrophil antibody significantly reduced neutrophil elastase activity and prevented the increases in BAL desmosine and hydroxyproline following ufCB exposure. For the first time we demonstrate the infiltration of Langerhans and myeloid dendritic cells, and show that elastase production contributes to pulmonary destruction following exposure to ultrafine particles.


The clinical significance of cytogenetic studies in 100 patients with multiple myeloma, plasma cell leukemia, or amyloidosis.
Chromosome studies were done on 82 patients with multiple myeloma, 11 with amyloidosis, 2 with multiple myeloma and amyloidosis, and 5 with plasma cell leukemia to investigate their chromosomal abnormalities and to determine the usefulness of cytogenetic studies. A chromosomally abnormal clone was found in 29 patients but was observed most often in those with active disease: in 18% of patients with newly diagnosed multiple myeloma, in 63% with aggressive disease, and in 40% with plasma cell leukemia. Survival among the newly diagnosed patients was significantly shorter (P = .0089) for those in whom an abnormal clone was identified (median survival, six months) than for those in whom only normal metaphases were observed (median survival, greater than 12 months). Among all of the patients, survival from the time of chromosome analysis was shorter for those in whom a chromosomally abnormal clone was found: the median survival was three months for patients with all abnormal metaphases and eight months for patients with normal and abnormal metaphases and has not yet been reached for patients with only normal metaphases. The most common anomalous chromosomes in patients with a plasma cell proliferative disorder were 1, 11, and 14: 11 patients had an abnormality involving chromosome 14q32 and nine patients had an anomalous chromosome 11. The single most common abnormality, a t(11;14)(q13;q32), occurred in three patients. Among the patients who developed preleukemia or acute nonlymphocytic leukemia, the most common anomaly involved chromosome 7. The results suggest that cytogenetic studies are useful for identifying patients who have a poor prognosis and can help distinguish patients with a cytopenia because of preleukemia from those with an aggressive plasma cell proliferative process.


Adaptation of Temperate Seagrass to Arctic Light Relies on Seasonal Acclimatization of Carbon Capture and Metabolism.
Due to rising global surface temperatures, Arctic habitats are becoming thermally suitable for temperate species. Whether a temperate species can immigrate into an ice-free Arctic depends on its ability to tolerate extreme seasonal fluctuations in daylength. Thus, understanding adaptations to polar light conditions can improve the realism of models predicting poleward range expansions in response to climate change. Plant adaptations to polar light have rarely been studied and remain unknown in seagrasses. If these ecosystem engineers can migrate polewards, seagrasses will enrich biodiversity, and carbon capture potential in shallow coastal regions of the Arctic. Eelgrass (Zostera marina) is the most widely distributed seagrass in the northern hemisphere. As the only seagrass species growing as far north as 70°N, it is the most likely candidate to first immigrate into an ice-free Arctic. Here, we describe seasonal (and diurnal) changes in photosynthetic characteristics, and in genome-wide gene expression patterns under strong annual fluctuations of daylength. We compared PAM measurements and RNA-seq data between two populations at the longest and shortest day of the year: (1) a Mediterranean population exposed to moderate annual fluctuations of 10-14 h daylength and (2) an Arctic population exposed to high annual fluctuations of 0-24 h daylength. Most of the gene expression specificities of the Arctic population were found in functions of the organelles (chloroplast and mitochondrion). In winter, Arctic eelgrass conserves energy by repressing respiration and reducing photosynthetic energy fluxes. Although light-reactions, and genes involved in carbon capture and carbon storage were upregulated in summer, enzymes involved in CO2 fixation and chlorophyll-synthesis were upregulated in winter, suggesting that winter metabolism relies not only on stored energy resources but also on active use of dim light conditions. Eelgrass is unable to use excessive amounts of light during summer and demonstrates a significant reduction in photosynthetic performance under long daylengths, possibly to prevent photoinhibition constrains. Our study identified key mechanisms that allow eelgrass to survive under Arctic light conditions and paves the way for experimental research to predict whether and up to which latitude eelgrass can potentially migrate polewards in response to climate change.


Miniaturized probe based on a microelectromechanical system mirror for multiphoton microscopy.
A factor that limits the use of multiphoton microscopy (MPM) in clinical and preclinical studies is the lack of a compact and flexible probe. We report on a miniaturized MPM probe employing a microelectromechanical system (MEMS) scanning mirror and a double-clad photonic crystal fiber (DCPCF). The use of a MEMS mirror and a DCPCF provides many advantages, such as size reduction, rapid and precise scanning, efficient delivery of short pulses, and high collection efficiency of fluorescent signals. The completed probe was 1 cm in outer diameter and 14 cm in length. The developed probe was integrated into an MPM system and used to image fluorescent beads, paper, and biological specimens.


Neglected dislocation in sub-axial cervical spine: Case series and a suggested treatment protocol.
Approaches suggested for treatment of neglected dislocations in the subaxial cervical spine (SACS) include only anterior approach (a), only posterior approach (b), posterior-anterior approach, posterior-anterior-posterior approach, and anterior-posterior-anterior-posterior approach. No protocol is suggested in literature to guide surgeons treating neglected dislocations. To describe a protocol for the treatment of neglected dislocation in the SACS. Retrospective case series and review of literature. Six consecutive patients of neglected dislocation (presenting to us more than 3 weeks following trauma) of the SACS were operated as per the protocol suggested in this paper. A retrospective review of the occupational therapy reports, patient records, and radiographs was performed. Only cases with time lapse of more than 3 weeks between the time of injury and initial management have been included in the review. Closed reduction (CR) was achieved in three patients following cervical traction and these were managed by anterior cervical discectomy and fusion (ACDF). Open reduction via posterior approach and soft tissue release was required to achieve reduction in two patients. Following reduction posterior instrumented fusion was done in them. One patient with preoperative neurological deficit needed a facetectomy to achieve reduction. Following short-segment fixation, ACDF was also performed in this patient. None of the patients deteriorated neurologically following surgery. Fusion was achieved in all patients. Preoperative and intraoperative traction have a role in the management of neglected dislocations in the cervical spine. If CR is achieved the patient may be managed by ACDF. If CR is not achieved, posterior soft tissue release may be done to achieve reduction and partial facetectomy must be reserved for cases in which reduction is not achieved after soft tissue release. A treatment protocol for management of neglected dislocation in the SACS has been suggested in this paper.


Closure of abdominal wounds with continuous nonabsorbable sutures: experience in 1697 cases.
From September 1976 to September 1989, the author routinely used continuous nonabsorbable sutures for closing abdominal incisions in 1697 consecutive laparotomy patients, including 696 men and 1001 women. These cases did not involve any type of hernia repair. In addition to being quick and cost-efficient, the continuous technique allowed tension to be distributed evenly along the suture line. During a follow-up period of up to 13 years, six patients presented suture granulomas, and two had late incisional hernias (greater than six months postoperatively). No hematoma formation, infection, or suture-line disruption was encountered. The author concludes that continuous nonabsorbable sutures are preferable to interrupted nonabsorbable sutures for closing a wide range of abdominal incisions.


Understanding an Aboriginal and Torres Strait Islander child's journey through paediatric care in Western Australia.
To explore caregiver perspectives of their children's journey through the specialist paediatric service, the Aboriginal Ambulatory Care Coordination Program (AACC), and non-AACC services at the Perth Children's Hospital. Eighteen semi-structured interviews with families of Aboriginal children were completed. Indigenous research methodology and a phenomenological approach guided data collection and analysis. Four key themes were identified from interviews: hospital admissions, discharge and follow-up outpatient appointments; communication; financial burden; and cultural issues. Our findings suggest Aboriginal children and their caregivers using the AACC program had more positive and culturally secure experiences than those using non-AACC services. However, barriers relating to health providers' understanding of Aboriginal cultural issues and lived experience were commonly discussed, regardless of which service families received. Australian Aboriginal children have an increased use of tertiary hospital care compared to non-Indigenous children. Healthcare programs specifically designed for Aboriginal children and their families can improve their experience of care in hospital. However, improvements in cultural awareness for other hospital staff is still needed. Implications for public health: Dedicated Aboriginal programs in mainstream services can successfully improve cultural care to their clients, which is fundamental to improving service delivery for families.


A study of the compaction process and the properties of tablets made of a new co-processed starch excipient.
This article deals with the study of the energetic relationships during compaction and the properties of tablets produced from a co-processed excipient based on starch and called StarCap 1500®. This article compares it with the substance Starch1500®. The study also includes the mixtures of StarCap 1500® and the granulated directly compressible lactose Pharmatose DCL®15. The tablet properties tested included tensile strength and disintegration time, examined in dependence on compression force, and also a 0.4% addition of magnesium stearate. The results show a better compressibility of StarCap 1500 in comparison with Starch 1500 and a lower elastic component of energy. The tablets were stronger and disintegrated more rapidly, but the substance possessed a higher sensitivity to an addition of a lubricant than Starch 1500. Increasing portions of StarCap 1500 in the mixtures with Pharmatose DCL 15 increased the tensile strength of tablets, disintegration period as well as the sensitivity to an addition of a lubricant. From the energetic viewpoint, energy for friction was decreasing, while the energy accumulated by the tablet during compaction and the elastic component of energy were increased.


Early pregnancy interruption by 15 (S) 15 methyl prostaglandin F2alpha methyl ester.
Suppositories of 15-methyl PGF2alpha methyl ester in triglyceride were administered vaginally to 75 women in whom 31 to 49 days had elapsed since their last menstrual period. Three or four suppositories of 0.5, 1.0, or 1.5 mg were given at intervals of 3 hours. Pregnancy was later confirmed in 63 of the women. In the pregnant women vaginal bleeding usually started 3 to 6 hours after the initiation of therapy and continued for 10 to 14 days. Patients were followed for 2 to 4 weeks with serial measurement of serum progesterone and hCG. There were no failures in the trial, but in 2 cases the treatment resulted in incomplete abortion. In 2 other patients curettage was performed due to prolonged bleeding, but histologic examination revealed no remaining signs of pregnancy. Gastrointestinal side effects were well within acceptable limits, and no serious complications occurred. Clinical signs of pelvic inflammatory disease were not found. The vaginal use of 15-methyl PGF2alpha methyl ester seems promising as a reliable outpatient nonsurgical self-administered procedure for termination of early pregnancy.


Ribonucleotide reductase M1 subunit in cellular proliferation, quiescence, and differentiation.
Ribonucleotide reductase catalyzes the first unique, rate-limiting step in DNA synthesis; both its large (M1) and small (M2) subunits are necessary for activity. While direct studies of M2 expression have previously shown a tight correlation with S phase, the kinetic features of M1-expressing cells have remained ill defined. Therefore we have, using immunofluorescence flow cytometry, analyzed changes in whole cell M1 levels and DNA content during various cell cycle and differentiation events. In asynchronous cultures M1 levels are sustained throughout the cell cycle, including G1 phase when M2 levels and ribonucleotide reductase catalytic activity are known to be very low. In contrast M1 is virtually absent from quiescent lymphocytes but is expressed following mitogen stimulation, shortly before S phase cells appear. M1 declines to low levels in "plateau phase" cultures, the major reduction occurring in cells with 2n (G0/G1) DNA content. HL-60 promyelocytic leukemia cells, induced into either myeloid or monocyte-macrophage differentiation, show a similar marked decrease in M1 levels concomitant with the cessation of cell division. We conclude that the M1 subunit of ribonucleotide reductase is constitutively expressed by cycling cells. It is acquired during stimulated transition from G0 to G1 and is lost during exit to G0 or terminal differentiation. This pattern of expression suggests that determination of cellular M1 content may be useful in distinguishing proliferating (including G1) and quiescent (including G0) cells in vivo.


Hit the right spots: cell cycle control by phosphorylated guanosines in alphaproteobacteria.
The class Alphaproteobacteria includes Gram-negative free-living, symbiotic and obligate intracellular bacteria, as well as important plant, animal and human pathogens. Recent work has established the key antagonistic roles that phosphorylated guanosines, cyclic-di-GMP (c-di-GMP) and the alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively referred to as (p)ppGpp), have in the regulation of the cell cycle in these bacteria. In this Review, we discuss the insights that have been gained into the regulation of the initiation of DNA replication and cytokinesis by these second messengers, with a particular focus on the cell cycle of Caulobacter crescentus. We explore how the fluctuating levels of c-di-GMP and (p)ppGpp during the progression of the cell cycle and under conditions of stress control the synthesis and proteolysis of key regulators of the cell cycle. As these signals also promote bacterial interactions with host cells, the enzymes that control (p)ppGpp and c-di-GMP are attractive antibacterial targets.


The effects of loading conditions and specimen environment on the nanomechanical response of canine cortical bone.
Bone is a viscoelastic connective tissue composed primarily of mineral and type I collagen, which interacts with water, affecting its mechanical properties. Therefore, both the level of hydration and the loading rate are expected to influence the measured nanomechanical response of bone. In this study, we investigated the influence of three distinct hydration conditions, peak loads and loading/unloading rates on the elastic modulus and hardness of canine femoral cortical bone via nanoindentation. Sections from three canine femurs from multiple regions of the diaphysis were tested for a total of 670 indentations. All three hydration conditions (dry, moist and fully hydrated tissue) were tested at three different loading profiles (a triangular loading profile with peak loads of 600, 800 and 1000 μN at loading/unloading rate of 60, 80 and 100 μN/s, respectively; each test was 20s in duration). Significant differences were found for both the elastic modulus and hardness between the dry, moist and fully hydrated conditions (p≤0.02). For dry bone, elastic modulus and hardness values were not found to be significantly different between the different loading profiles (p>0.05). However, in both the moist and fully hydrated conditions, the elastic modulus and hardness were significantly different under all loading profiles (with the exception of the moist condition at the 600- and 800-μN peak load). Given these findings, it is critical to perform nanoindentation of bone under fully hydrated conditions to ensure physiologically relevant results. Furthermore, this work found that a 20-s triangular loading/unloading profile was sufficient to capture the viscoelastic behavior of bone in the 600- to 1000-μN peak load range. Lastly, specific peak load values and loading rates need to be selected based on the structural region for which the mechanical properties are to be measured.


EFFECT OF MECHANICAL STIMULI ON REMODELING AND MINERAL DENSITY OF THE SPINE.
The aim: The aim of our study was to determine effect of whole body vibration on the bone tissue remodeling, determine the correlation between bone mineral density, markers of bone metabolism and level of vibration stimulus. Materials and methods: Four experimental groups Wistar rats were exposed to vertical whole body vibration during 28 days. Blood intake and QCT-scanning of the lumbar spine was performed on the 28th and 56th day of study. Results: The largest loss of trabecular bone was observed in experimental groups III (0.51g) and IV (1.15g), which was decreasing to 12% (p<0.05) and 14% (p<0.05), respectively, in comparison with the control group. After 56th day of the experiment, bone loss dynamics was the following: in the 1st group ≤ 10% (p <0.05), in the 2nd ≤ 12% (p <0.05), in the 3rd ≤ 17 % (p <0.05), and 4th ≤ 22% (p <0.05) compared with the control group. Changes in the level of hydroxyproline in the first experimental group were not statistically significant (p>0.05), in the second group - increased by 19.3% compared with the control rates, in the third - by 65.3%, and in the fourth - the level doubled (p<0.05). Increase of free hydroxyproline indicates violations in the balance between destruction and compensatory acceleration of collagen biosynthesis, which gradually decreases up to the 56th day. It has been determined that with the increase in vibration frequency, elevation of osteocalcin level in rats' blood is observed. Conclusions: Acceleration 0.51g increases the rate of bone metabolism, causes collagen metabolism disorders, loss of bone mineral mass, which further leads to osteoporosis.


MRI of the knee in asymptomatic adolescent swimmers: a controlled study.
Swimming is a widespread sporting activity generally regarded as an ideal form of exercise, which has little or no impact on the knees. However, overuse or repetitive microtrauma injuries may often affect the knee joint of young competitive swimmers. These early lesions are frequently asymptomatic for a considerable period of time before causing discomfort or joint pain. The aim of the present study is to use MRI to evaluate the knee joints of asymptomatic young elite swimmers and to compare them with age- and sex-matched controls who do not practice any impact sports regularly. Cross-sectional case-control study. The authors performed a cross-sectional controlled study to evaluate 54 knees of 27 asymptomatic male adolescents aged 14-15 years, paired by age and weight. Participants were divided in two groups: 13 elite swimmers and 14 control adolescents. The authors performed all the exams using a 0.35-T open-field MRI unit and evaluated by two experienced radiologists blinded to study groups. The images were evaluated to detect the presence or absence of abnormalities. One or more imaging abnormalities were detected in 18 knees in the group of swimmers (69.2%; p=0.013). The most prevalent findings in the athletes were infrapatellar fat pad edema (53.8%; p=0.049), followed by bone marrow edema (26.9%; p=0.022), edema of prefemoral fat pad (19%; p=0.022) and joint effusion (15.3%; p=0.047). Significantly more MRI abnormalities were found in the knee joints of asymptomatic adolescent elite swimmers. This high prevalence of positive imaging findings in swimmers may correspond to benign changes or preclinical lesions, which should be evaluated in a follow-up study.


GRAPPA Treatment Recommendations: Updates and Methods.
The development and updating of treatment recommendations for optimal treatment approaches for patients with psoriatic arthritis (PsA) has been an important mission of the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) since its inception. Even though the most recent iteration of the GRAPPA PsA recommendations was completed only a few years ago, there have been many significant advances related to therapies and treatment approaches for PsA since their publication. Because of these advances, the process to update the recommendations again has begun. The standard approaches to guideline (or treatment recommendation) development have also evolved in recent years. Herein, the basis for the approach that will be taken for the next version of the GRAPPA PsA treatment recommendations is reviewed.


The role of tyrosine phosphorylation in lipopolysaccharide- and zymosan-induced procoagulant activity and tissue factor expression in macrophages.
The expression of surface procoagulants by exudative macrophages represents an important mechanism underlying local fibrin deposition at sites of extravascular inflammation. The present studies investigated the contribution of tyrosine phosphorylation to the generation of macrophage procoagulant activity (PCA) and tissue factor expression in response to proinflammatory stimuli. Both lipopolysaccharide (LPS) and zymosan rapidly stimulated tyrosine phosphorylation in elicited murine peritoneal macrophages. This effect was prevented by the tyrosine kinase inhibitors genistein and herbimycin and augmented by the addition of the phosphotyrosine phosphatase inhibitor vanadate. The vanadate-mediated rise in phosphotyrosine accumulation was abrogated by the use of diphenylene iodonium, an inhibitor of the respiratory burst oxidase, suggesting a role for peroxides of vanadate as contributors to the tyrosine phosphorylation. This notion was supported by the finding that vanadyl hydroperoxide markedly increased the accumulation of phosphotyrosine residues. To define the role of tyrosine phosphorylation in the induction of macrophage PCA by LPS, the effects of tyrosine kinase inhibition by genistein and herbimycin were investigated. Both agents inhibited the expression of macrophage PCA. Further, Northern blot analysis with the cDNA probe for murine tissue factor indicated that the inhibition occurred at the mRNA level or earlier. Since vanadate augmented phosphotyrosine accumulation, it was hypothesized that it might enhance generation of macrophage products. However, vanadate reduced induction of PCA in response to LPS. By contrast, vanadate augmented basal prostaglandin E2 (PGE2) release and stimulated PGE2 release by macrophages. Indomethacin prevented the increase in PGE2 but only partially restored normal levels of PCA. The effect of vanadate on tissue factor expression appeared to be posttranscriptional. These studies thus demonstrate, by functional Western blotting and Northern blotting techniques, that tyrosine phosphorylation plays a role in the regulation of macrophage PCA and tissue factor expression in response to proinflammatory stimuli.


Looking back and moving forward: 50 years of soil and soil fertility management research in sub-Saharan Africa.
Low and declining soil fertility has been recognized for a long time as a major impediment to intensifying agriculture in sub-Saharan Africa (SSA). Consequently, from the inception of international agricultural research, centres operating in SSA have had a research programme focusing on soil and soil fertility management, including the International Institute of Tropical Agriculture (IITA). The scope, content, and approaches of soil and soil fertility management research have changed over the past decades in response to lessons learnt and internal and external drivers and this paper uses IITA as a case study to document and analyse the consequences of strategic decisions taken on technology development, validation, and ultimately uptake by smallholder farmers in SSA. After an initial section describing the external environment within which soil and soil fertility management research is operating, various dimensions of this research area are covered: (i) 'strategic research', 'Research for Development', partnerships, and balancing acts, (ii) changing role of characterization due to the expansion in geographical scope and shift from soils to farms and livelihoods, (iii) technology development: changes in vision, content, and scale of intervention, (iv) technology validation and delivery to farming communities, and (v) impact and feedback to the technology development and validation process. Each of the above sections follows a chronological approach, covering the last five decades (from the late 1960s till today). The paper ends with a number of lessons learnt which could be considered for future initiatives aiming at developing and delivering improved soil and soil fertility management practices to smallholder farming communities in SSA.


Statistics of gastro-enteritis mortality in Venezuela.
Gastro-enteritis constituted the chief cause of death in Venezuela during the period 1950-54 in both urban and rural areas, being responsible for an annual death-rate of 166 per 100 000 inhabitants, but was a particularly acute problem in localities with under 5000 inhabitants, where only one in every three fatal cases received medical care before death. Although the disease is not a very important cause of neo-natal mortality, nearly 90% of gastro-enteritis deaths occur among children between 4 weeks and 5 years of age. There is some seasonal variation, with relatively low mortality values in the first and last four months of the year and an appreciable rise in the intermediary period.An analysis is made of all death certificates in 1953 on which death was attributed to a cause interpreted as being gastro-enteritis (totalling over 7000), and it is thought that, despite the variable terminology used, the same disease is in fact referred to in the great majority of certificates. The authors suggest measures for ensuring the comparability of gastro-enteritis statistics in the circumstances prevailing in Venezuela.


[A sudden-death in a case of Arnold-Chiari malformation (type I) with sleep apnea].
We presented a sudden-death case of Arnold-Chiari malformation (type 1) accompanied with spina bifida and closed meningomyelocele. Polysomnography revealed the increase of both central and mixed type apneas to compare with the findings of typical Pickwikian syndrome. 30-year-old female without obese or obstruction of upper air way. Spina bifida and closed meningomyelocele at sacral portion were found at her birth. She had no treatment and had not been able to walk because of paralysis at low extremities. Since she was 25-year-old, she had had insomnia which accompanied by choked feelings, palpitations, clumsiness of hands and anxiety. Snoring was light, and she had neither respiratory disturbances nor hypersomnia during awake. She was admitted to our hospital for treatment of decubitus. 2nd June, 1977, she was found acrocyanosis during sleep and immediately she was resurrected. Physical examinations revealed there was no accounting for sudden respiratory arrest: the cardio-pulmonary system was normal during awake and laboratory findings also failed to disclose the episode. But she had slight dysfunctions of lower cranial nerves: fine nystagmus according to the head-position, decreased gag reflex, and paresis in the recurrence nerve of N.XII and etc. Angiography showed communicating hydrocephalus. Though ventriculoperitoneal shunt operation was performed at 8th June, sleep apnea could not be improved. Therefore we examined in order to clarify her sleep apnea. She was not obese, we could not find any obstructions of upper air way. Nocturnal polygraphy was performed at 8th July. The results were summarized as follows: (1) Total sleep time was 293 minutes and numbers of sleep apnea were 134 times.(ABSTRACT TRUNCATED AT 250 WORDS)


Bowtie-shaped nanoaperture: a modal study.
Using the N-order finite-difference time-domain (FDTD) method, we show that optical resonances of the bowtie nanoaperture (BNA) are due to the combination of a guided mode inside the aperture and Fabry-Perot modes along the metal thickness. The resonance of lower energy, which leads to the well-known light confinement in the gap zone, occurs at the cutoff wavelength of the fundamental guided mode. No plasmon resonance is directly involved in the generation of the light hot spot. We also define a straightforward relationship between the resonance wavelengths of the BNA and its geometrical parameters. This brings a simple tool for the optimization of the BNA design.


Immunoregulation by low density lipoproteins in man. Inhibition of mitogen-induced T lymphocyte proliferation by interference with transferrin metabolism.
Human low density lipoprotein (LDL, d = 1.020-1.050 g/ml) inhibits mitogen-stimulated T lymphocyte DNA synthesis. Because both LDL and transferrin bind to specific cell surface receptors and enter cells by the similar means of receptor-mediated endocytosis, and because transferrin is necessary for lymphocyte DNA synthesis, we investigated the possibility that LDL may inhibit mitogen-stimulated lymphocyte responses by interfering with transferrin metabolism. LDL inhibited mitogen-stimulated lymphocyte [3H]thymidine incorporation in a concentration-dependent manner. The degree of inhibition was most marked in serum-free cultures, but was also observed in serum-containing cultures. The addition of transferrin not only augmented mitogen-induced lymphocyte [3H]thymidine incorporation in serum-free medium but also completely reversed the inhibitory effect of LDL in both serum-free and serum-containing media. Similar results were obtained when lymphocyte proliferation was assayed by counting the number of cells in culture. Transferrin also reversed the inhibition of lymphocyte responses caused by very low density lipoproteins and by cholesterol. The ability of transferrin to reverse the inhibitory effect of lipoproteins was specific, in that native but not denatured transferrin was effective whereas a variety of other proteins were ineffective. These results indicate that LDL inhibits mitogen-stimulated lymphocyte responses by interfering with transferrin metabolism. LDL only inhibited lymphocyte responses after a 48-h incubation if present from the initiation of the culture. By contrast, transferrin reversed inhibition when added after 24 h of the 48-h incubation. LDL did not inhibit lymphocyte responses by nonspecifically associating with transferrin. In addition, the acquisition of specific lymphocyte transferrin receptors was not blocked by LDL. Moreover, transferrin did not prevent the binding and uptake of fluorescent-labeled LDL by activated lymphocytes. Furthermore, LDL did not prevent the binding of transferrin to its receptor. Finally, LDL inhibition did not require specific high affinity cell surface receptors for cholesterol transport by LDL because similar inhibition and reversal by transferrin were observed with lymphocytes from a patient with homozygous familial hypercholesterolemia. Thus, LDL alters lymphocyte responses in a non-LDL receptor-mediated way by interfering with transferrin metabolism after specific binding of transferrin to receptors on activated lymphocytes.


[Current problems in mutual relations of cerebral vascular and cardiovascular diseases in elderly and senile age].
The authors have been taking up the problems of the cardiovascular pathology caused by atherosclerosis for many years, and are supporters of universality of the specified pathology. The article demonstrates the results of the researches executed by authors, and other leaders of this direction in a medical science. Questions of mutual relations of various diseases of cardiovascular system on clinical, pathogenetic, pathomorphological, biochemical levels are considered. Aging of a human body, and also brain and heart vessels as leading "targets" of the atherosclerosis are supposed to be a pathogenetic basis of formation and development of universal atherosclerotic defeat processes. Therefore the gerontology plays a prior role in studying the strategic aspects of this field of a medical science, and tactical questions of diagnostics and treatment of cardiovascular diseases should be a prerogative of clinical disciplines, namely cardiology, neurology, cardiovascular surgery, etc.


Efficacy of Tranexamic Acid in Reducing Seroma and Hematoma Formation Following Reduction Mammaplasty.
Tranexamic acid (TXA) has gained increasing recognition as a valuable pharmacologic agent within plastic surgery. The aim of this study was to investigate the value and safety profile of both intravenous and topically administered TXA in the setting of bilateral reduction mammaplasty. A retrospective review was performed to identify consecutive patients who underwent bilateral reduction mammaplasty for symptomatic macromastia (January 2016-July 2021). Pertinent preoperative, intraoperative, and postoperative details were collected/reviewed. Primary outcome measures included hematoma requiring surgical evacuation and clinically significant/symptomatic seroma formation mandating percutaneous aspiration. Patients taking anticoagulation/antiplatelet medication or those with a history of thromboembolic diseases were excluded. Patients who had received TXA were compared to a historical control group who did not receive TXA within the same consecutive cohort. A total of 385 consecutive patients (770 breasts) were included. TXA was used in 514 (66.8%) cases (topical, 318 [61.9%]; intravenous, 170 [33.1%]; intravenous and topical, 26 [5.1%]). Neither seroma nor hematoma were impacted/reduced with TXA (P > 0.05). Increased age (hazards ratio, 1.06 per 1-year increase; 95% CI, 1.004-1.118) significantly increased the risk of hematoma (P = 0.032). The use of drains significantly decreased the risk of seroma (P < 0.0001). Increased BMI increased the risk of seroma (hazards ratio, 1.16 per 1-kg/m2 increase; 95% CI, 1.06-1.26; P = 0.0013). The use of TXA did not impact drain duration. This study, the largest to date on the use of IV and topical TXA, did not find any reduction in risk when using TXA in breast reduction surgery.


Preferences in the management of osteoarthritis of the hip and knee: results of a survey of community-based rheumatologists in the United States.
To determine rheumatologists' preferences in the medical management of osteoarthritis (OA) of the hip and knee, and examine possible variations in these preferences. A stratified random sample of 1,001 rheumatologists in community-based practice in the United States was surveyed by mail. Responses were obtained form 594 subjects (529 white, 499 male, mean +/- SD age 47.4 +/- 8.1 years). Over 80% used acetaminophen or nonaspirin, nonsteroidal antiinflammatory drugs (NSAIDs) either always or frequently for the management of OA of the hip and knee. A majority used the following nonpharmacologic methods either always or frequently: weight loss, cane or crutch, physical and/or occupational therapy referral, and exercise. Variation in practice preferences was noted by age (< 47 versus > or = 47 years), sex, board certification in rheumatology, and number of patients seen per month. Respondents felt that severe pain and limitation of function were the most important factors in recommending total join arthroplasty for patients. These data demonstrate that practicing rheumatologists most often use either acetaminophen and/or NSAIDs in combination with nonpharmacologic methods in the medical management of OA of the hip and knee. The existence of variation in practice preferences has policy implications.


Multivalent & multifunctional ligands to beta-amyloid.
Ligands selectively targeting beta-amyloid in the living brain are promising candidates of therapeutics and early diagnosis tools for Alzheimer's disease. Among the major stages of beta-amyloid aggregation, monomers and oligomers are excellent targets to reduce neurotoxic brain damages for prevention of the disease progression, while oligomers and fibrils, abundant in the late stage of the disease, are pathological objectives to develop reliable imaging probes. So far, there have been many efforts to develop a wide variety of monovalent beta-amyloid ligands such as thioflavin T, PIB, FDDNP, curcumin, and tramiprosate. However, pathology of Alzheimer's disease is not fully understood yet so that there is currently no cure and further investigations on Alzheimer's disease are needed. For past several years, multivalent beta-amyloid ligands have offered an alternative route by enhancing binding affinity of drug candidates. In addition, it has been revealed that not only neurotoxicity due to the protein misfolding but also other factors are involved in the beta-amyloid cascade such as oxidative stress, inflammation, metal chelation, and several types of neurotransmitters. Thus, there have been numerous studies to improve binding affinities of single beta-amyloid ligands via adopting multivalent effects or to develop drug candidates targeting multiple stages of the pathological cascade. In this review, multivalent and multifunctional beta-amyloid ligands and their promising aspects as an alternative approach to Alzheimer's disease are discussed.


The isolation of glycoproteins from bovine achilles tendon and their interaction with collagen.
Two glycoprotein fractions, A and B, were isolated from bovine achilles tendon. Glycoprotein A was prepared from a 0.2m-sodium chloride extract and glycoprotein B was isolated from a 3m-magnesium chloride extract. They were free from serum proteins. Glycoprotein A was essentially free of collagen, but glycoprotein B contained about 8% collagen. Both glycoproteins gave several bands on isoelectric focusing. This technique was also used to demonstrate that both glycoprotein fractions interacted strongly with acid-soluble calf skin tropocollagen. It is concluded that these fractions are true components of tendon, and that they may have some function in the macromolecular organization of the tissue.


Synovectomy of the hip in juvenile rheumatoid arthritis.
Review of the results of subtotal and complete synovectomy of 9 hips in 5 female patients with subluxation or progressive joint destruction (roentgenographically) than any 2 years showed improvement or retention of joint motion in 4 patients. Complete synovectomy, performed in 7 hips, necessitated surgical dislocation of the joint, but there was no evidence that this surgical dislocation comprised the proximal femoral blood supply. The mildest synovial and cartilagenous changes were present in the patient who has bilateral partial synovectomies. At follow-up these hips showed more severe destruction evaluated during a minimum of the hips treated by total synovectomy. No postoperative dislocations occurred. Synovectomy of the hip may be useful for progressive hip involvement in younger patients whose skeletal immaturity contraindicates major reconstructive procedures.


Context effects on probability estimation.
Many decisions rely on how we evaluate potential outcomes and estimate their corresponding probabilities of occurrence. Outcome evaluation is subjective because it requires consulting internal preferences and is sensitive to context. In contrast, probability estimation requires extracting statistics from the environment and therefore imposes unique challenges to the decision maker. Here, we show that probability estimation, like outcome evaluation, is subject to context effects that bias probability estimates away from other events present in the same context. However, unlike valuation, these context effects appeared to be scaled by estimated uncertainty, which is largest at intermediate probabilities. Blood-oxygen-level-dependent (BOLD) imaging showed that patterns of multivoxel activity in the dorsal anterior cingulate cortex (dACC), ventromedial prefrontal cortex (VMPFC), and intraparietal sulcus (IPS) predicted individual differences in context effects on probability estimates. These results establish VMPFC as the neurocomputational substrate shared between valuation and probability estimation and highlight the additional involvement of dACC and IPS that can be uniquely attributed to probability estimation. Because probability estimation is a required component of computational accounts from sensory inference to higher cognition, the context effects found here may affect a wide array of cognitive computations.


Development and validation of a test for environmental estrogens: Checking xeno-estrogen activity by CXCL12 secretion in BREAST CANCER CELL LINES (CXCL-test).
Several methods have been developed to evaluate and quantify the effects of Endocrine disruptor chemicals (EDC). Nevertheless, most of these methods are time-consuming or not enough sensitive to detect EDC at the environmental range. To link the biological effect of tested EDC to natural protein secretion, we have developed a new screening method based on the secretion of the cytokine CXCL12 (or SDF-1, Stroma-cell Derived Factor 1), which plays a capital role in cell survival and migration. We have demonstrated that CXCL12 secretion is regulated by estrogenic compounds in a dose-dependent way in ER-positive breast cancer cell lines (MCF-7 and T47D). By combining cell culture and ELISA test, we used this up-regulation of CXCL12 secretion to test several major environmental contaminants. Our results showed that 17β-estradiol (from 10(-11) M), 17α-ethynylestradiol (from 10(-12) M), genistein (from 10(-8) M) and bisphenol A (from 10(-6) M) dose-regulate CXCL12 secretion in T47D. In contrast, antiestrogens, raloxifen and 4-hydroxytamoxifen, had no effect on the CXCL12 secretion, but were able to inhibit E2 effect. Moreover, we used cell proliferation assays to evaluate the effect of these different compounds on the growth of T47D cells. We found strong correlation (P = 0.7) between proliferation and CXCL12 secretion. However CXCL12 secretion was as sensitive as cell proliferation assays but appeared more rapid. Thus, this bioassay named CXCL-test (for Checking Xeno-estrogen activity by CXCL12 secretion in breast cancer cell Lines) constitutes a fast and sensitive method for the detection of estrogenic compounds allowing in 14 h to achieve a detection limit of 10(-11) M of E2 (2.7 ng/L).


Multiview spectral embedding.
In computer vision and multimedia search, it is common to use multiple features from different views to represent an object. For example, to well characterize a natural scene image, it is essential to find a set of visual features to represent its color, texture, and shape information and encode each feature into a vector. Therefore, we have a set of vectors in different spaces to represent the image. Conventional spectral-embedding algorithms cannot deal with such datum directly, so we have to concatenate these vectors together as a new vector. This concatenation is not physically meaningful because each feature has a specific statistical property. Therefore, we develop a new spectral-embedding algorithm, namely, multiview spectral embedding (MSE), which can encode different features in different ways, to achieve a physically meaningful embedding. In particular, MSE finds a low-dimensional embedding wherein the distribution of each view is sufficiently smooth, and MSE explores the complementary property of different views. Because there is no closed-form solution for MSE, we derive an alternating optimization-based iterative algorithm to obtain the low-dimensional embedding. Empirical evaluations based on the applications of image retrieval, video annotation, and document clustering demonstrate the effectiveness of the proposed approach.


Platelet-derived nanovesicles for hemostasis without release of pro-inflammatory cytokines.
Natural platelet-derived nanovesicles with a vacant core were prepared by hypotonic sonication. The nanovesicles efficiently formed platelet-like aggregates using membrane protein in the presence of thrombin and calcium chloride without a notable release of pro-inflammatory cytokines. These natural and biocompatible platelet-derived nanovesicles have great potential as biomaterials for inflammation-free injectable hemostasis.


Density of fat-free body mass: relationship with race, age, and level of body fatness.
The two-compartment body composition method assumes that fat-free body mass (FFM) has a density of 1.100 kg/l. This study tested the hypothesis that FFM density is independent of race, age, and body fatness. Subjects were 703 black and white subjects, ages 20-94 yr, with body mass index (BMI) 17-35 kg/m2. Body composition was assessed using a four-compartment model based on tritium dilution volume, body density by underwater weighing, bone mineral by dual-energy X-ray absorptiometry, and body weight. No relationship was observed between FFM density and race or BMI. A tendency was observed for a lower FFM density only in older white women. The difference in percent body fat (delta fat) between the four-compartment model and underwater weighing was < 2% for all groups. Race, age, and BMI explained only 2.3 (women) and 1.4% (men) of the variance in delta fat, whereas the total body water fraction of FFM explained 77%. In contrast to current thinking, these results show that the assumption of constant FFM density is valid in black, elderly, and obese subjects.


On-line sample preparation using restricted-access media in the analysis of the soy isoflavones, genistein and daidzein, in rat serum using liquid chromatography electrospray mass spectrometry.
Soy isoflavones are the subject of many investigations in experimental animals and humans regarding possible modulation of endocrine activity and chemoprevention of carcinogenesis. Genistein and daidzein, the principal biologically active isoflavones in soy, were measured using on-line solid-phase extraction (SPE) and liquid chromatography electrospray mass spectrometry (LC/ES-MS) detection in serum of rats consuming a common open-formula (NIH 31) chow that contained approximately 30 microg each of genistein and daidzein per gram of feed and a specially designed 'soy-free' chow that contained approximately 60-fold lower isoflavones. The use of a restricted-access/reverse phase trap cartridge and automated column switching permitted rapid and robust analytical performance with many injections of plasma onto a reverse phase LC column. Enzymatic deconjugation and a single centrifugation step were the only sample preparation steps required. The limit of detection for the isoflavones, based on the MS responses observed in serum from male and female rats consuming the soy-free chow, was 0.020 microM. The method, which uses deuterated isoflavones as internal standards, was determined to be accurate using spiked control serum (102-110% of added amounts) and precise using spiked control serum and incurred serum (<6% relative standard deviation). The average genistein and daidzein levels were determined in female (0.62 and 0.25 microM, respectively) and male rats (0.35 and 0.20 microM, respectively) consuming the standard diet. The sex difference observed for serum genistein concentrations was statistically significant (p < 0.0001). These results underscore the potential impact of standard open-formula diets on the results from rodent bioassays of biological activity.


Quality of life in automated and continuous ambulatory peritoneal dialysis.
Despite a lack of strong evidence, automated peritoneal dialysis (APD) is often prescribed on account of an expected better quality of life (QoL) than that expected with continuous ambulatory peritoneal dialysis (CAPD). Our aim was to analyze differences in QoL in patients starting dialysis on APD or on CAPD with a follow-up of 3 years. Adult patients in the prospective NECOSAD cohort who started dialysis on APD or CAPD were included 3 months after the start of dialysis. The Medical Outcomes Survey Short Form 36 [SF-36 (Medical Outcomes Trust and QualityMetric, Lincoln, RI, USA)] and Kidney Disease and Quality of Life Short Form [KDQOL-SF (KDQOL Working Group, Santa Monica, CA, USA)] questionnaires were used to measure QoL. Differences in QoL over time were calculated using linear mixed models. Patients were followed until transplantation, death, or a first switch to any other dialysis modality. The clinical and social characteristics of the 64 APD and 486 CAPD patients were slightly different at baseline. In the crude analysis, the pattern of the mental summary score differed between the modalities (p = 0.03, adjusted p = 0.06), because of a different pattern for role function emotional (p = 0.03, adjusted p = 0.05). The pattern of the physical summary score was not different between the groups. Scores on dialysis staff encouragement had a different pattern over time (p = 0.01), because of an inequality in scores 3 months after the start of dialysis, which disappeared after 18 months on dialysis. Over time, patients on APD scored higher on sexual function. After adjustment for age, sex, glomerular filtration rate, comorbidity, and primary kidney disease, that difference disappeared. This study showed no major differences in QoL on the KDQOL-SF and the SF-36 between the two modalities.


Evolutionary patterns and coevolutionary consequences of MIRNA genes and microRNA targets triggered by multiple mechanisms of genomic duplications in soybean.
The evolutionary dynamics of duplicated protein-encoding genes (PEGs) is well documented. However, the evolutionary patterns and consequences of duplicated MIRNAs and the potential influence on the evolution of their PEG targets are poorly understood. Here, we demonstrate the evolution of plant MIRNAs subsequent to a recent whole-genome duplication. Overall, the retention of MIRNA duplicates was correlated to the retention of adjacent PEG duplicates, and the retained MIRNA duplicates exhibited a higher level of interspecific preservation of orthologs than singletons, suggesting that the retention of MIRNA duplicates is related to their functional constraints and local genomic stability. Nevertheless, duplication status, rather than local genic collinearity, was the primary determinant of levels of nucleotide divergence of MIRNAs. In addition, the retention of duplicated MIRNAs appears to be associated with the retention of their corresponding duplicated PEG targets. Furthermore, we characterized the evolutionary novelty of a legume-specific microRNA (miRNA) family, which resulted from rounds of genomic duplication, and consequent dynamic evolution of its NB-LRR targets, an important gene family with primary roles in plant-pathogen interactions. Together, these observations depict evolutionary patterns and novelty of MIRNAs in the context of genomic duplication and evolutionary interplay between MIRNAs and their PEG targets mediated by miRNAs.


Systematic Review of Platelet-Rich Plasma Use in Androgenetic Alopecia Compared with Minoxidil®, Finasteride®, and Adult Stem Cell-Based Therapy.
The number of articles evaluating platelet-rich plasma (PRP) efficacy in androgenic alopecia (AGA) have exponentially increased during the last decade. A systematic review on this field was performed by assessing in the selected studies the local injections of PRP compared to any control for AGA. The protocol was developed in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases was performed to identify studies on hair loss treatment with platelet-rich plasma. Of the 163 articles initially identified, 123 articles focusing on AGA were selected and, consequently, only 12 clinical trials were analyzed. The studies included had to match predetermined criteria according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach. In total, 84% of the studies reported a positive effect of PRP for AGA treatment. Among them, 50% of the studies demonstrated a statistically significant improvement using objective measures and 34% of the studies showed hair density and hair thickness improvement, although no p values or statistical analysis was described. In total, 17% of the studies reported greater improvement in lower-grade AGA, while 8% noted increased improvement in higher-grade AGA. Only 17% of the studies reported that PRP was not effective in treating AGA. The information analyzed highlights the positive effects of PRP on AGA, without major side effects and thus it be may considered as a safe and effective alternative procedure to treat hair loss compared with Minoxidil® and Finasteride®.


Increasing Incidence of Primary Aldosteronism in Western Sweden During 3 Decades - Yet An Underdiagnosed Disorder.
Primary aldosteronism (PA) is the most common cause of secondary hypertension. Yet, the incidence of PA in the general population has not been studied. To estimate the incidence of PA in the general population. Patients who had received a diagnostic code for PA between 1987 and 2016 were identified in the Swedish National Patient Registry. Assessment of clinical and biochemical data was used to validate the diagnosis. The annual incidence of PA was calculated by using the number of inhabitants in the Västra Götaland County as a reference. Of 570 identified patients, 473 (83%) had confirmed PA. Eligible for the incidence analysis were 416 patients, 248 (60%) men and 168 (40%) women, diagnosed with PA between 1987 and 2016. The mean (± standard deviation) age at diagnosis was 56 ± 12 years. The median (interquartile range) annual incidence was 2 (1-2) cases per million between 1987 and 1996, 6 (4-9) cases per million between 1997 and 2006 and 17 (12-24) cases per million between 2007 and 2016. At the end of the study (December 31, 2016), 386 patients with confirmed PA were alive and living in the Västra Götaland County, giving a prevalence of 231 cases per million (0.022%). Despite increasing incidence, the proportion of patients identified with PA is lower than expected. Given the serious consequences of untreated PA, the noticeably low prevalence at the end of the study stresses the need to increase the awareness of PA among health care providers.


Posterior cerebral artery infarction from middle cerebral artery infarction.
While it is known that posterior cerebral artery (PCA) infarction may simulate middle cerebral artery (MCA) infarction, the frequency and localization of this occurrence are unknown. To determine the frequency of PCA infarction mimicking MCA infarction and the territory of the PCA most commonly involved in this simulation. We studied 202 patients with isolated infarction in the PCA admitted to our stroke center to determine the frequency of PCA infarction simulating MCA infarction, the involved PCA territory, and the patterns of clinical presentation. We found 36 patients (17.8%) with PCA ischemic stroke who had clinical features suggesting MCA stroke. The PCA territory most commonly involved was the superficial PCA territory (66.7%), followed by the proximal PCA territory (16.7%) and both the proximal and the superficial PCA territories (16.7%). The principal stroke mechanism was cardioembolic (54.1%) in the superficial PCA territory, lacunar (46.2%) in the proximal PCA territory, and undetermined (40.2%) in both the proximal and the superficial territories. Among the 36 patients, the most common clinical associations were aphasia (13 patients), visuospatial neglect (13 patients), and severe hemiparesis (7 patients). Posterior cerebral artery infarction simulating MCA infarction is more common than previously thought. Early recognition of the different stroke subtypes in these 2 arteries may allow specific management.