Safety and Efficacy of Sofosbuvir with Ribavirin® in Hepatitis C, Genotype 3 Patients with Cirrhosis: A Real-world Experience.
Introduction Hepatitis C virus (HCV) is the leading cause of cirrhosis. The advent of Directly Acting Antivirals (DAAs) like Sofosbuvir (SOF) has dramatized the treatment and is the cornerstone for the treatment of HCV. Most trials have been conducted in HCV genotype 1 (GT-1) and data for Interferon-free regimen in genotype 3 (GT-3) is limited especially in cirrhotic patients. Aim To evaluate the safety and efficacy of SOF plus Ribavirin® (RIB) in patients with compensated and decompensated cirrhosis. Methods This was a quasi-experimental study in HCV patients with compensated and decompensated cirrhosis. Each group (compensated and decompensated) was further subdivided into the treatment-naïve and treatment-experienced groups. Efficacy was assessed by end treatment response (ETR) and sustained viral response (SVR) in the treatment-naïve and experienced groups. Adverse events were recorded on designed proforma on serial follow-up visits. Results The study consisted of 110 consecutive patients. Among 110 patients, 51 had compensated cirrhosis and 59 had decompensated cirrhosis. The mean age was 53.8 ± 11 years. Males were n=56 (50.9%) and females were n=54 (49.1%). All the patients in Child-Turcotte-Pugh class A were in the compensated group. CTP B class was found to be 10.5% and 89.5% in the compensated and decompensated groups, respectively, whereas all the patients in CTP class C were in the decompensated group. In the compensated cirrhosis group, ETR was achieved in 36 (87.8%) treatment-naïve and 8 (88.9%) experienced patients. In decompensated cirrhosis, treatment-naïve and experienced patients achieved ETR in 28 (82.4%) and 18 (85.7%) patients, respectively. Whereas in compensated cirrhosis treatment-naïve and experienced patients, SVR was achieved in 25 (83.3%) and five (71.4%), respectively. In decompensated cirrhosis, 21 (77.8%) treatment-naïve and 12 (75%) experienced patients achieved SVR. The most common adverse events experienced by the patients were fatigue followed by myalgia, nausea, and diarrhea. The new onset of complications found due to cirrhosis were ascites, followed by hepatoma, upper gastrointestinal bleed, portosystemic encephalopathy, acute on chronic liver failure, and death. Conclusion Sofosbuvir in combination with Ribavirin® is safe but suboptimal in treatment outcomes, particularly in treatment-experienced patients with decompensated cirrhosis than in treatment-naive patients with compensated cirrhosis due to HCV GT-3.


Multifrequency transducer for microemboli classification and sizing.
The classification of circulating microemboli as gaseous or particulate matter is essential to establish the relevance of the detected embolic signals. Until now, Doppler techniques have failed to determine unambiguously the nature of circulating microemboli. Recently, a new approach based on the analysis of radio frequency (RF) signal and using the nonlinear characteristics of gaseous bubbles to classify emboli was investigated. The main limitation of these studies was the requirement of two separate transducers for transmission and reception. This paper presents a multi-frequency transducer with two independent transmitting elements and a separate receiving part with a wide frequency band. The transmitting elements are positioned in a concentric design and cover a frequency band between 100 and 600 kHz. The receiving part consists of a polyvinylidene fluoride layer. The new transducer has been tested in vitro using gaseous emboli. It could correctly classify and size air emboli with diameters ranging from 10 microm to 105 microm.


[Addiction--a contribution from the viewpoint of adolescent psychiatry].
While a single patient's addiction arises from a pattern of individual factors there appears to be a general cultural climate fostering its genesis in many variants. In the present contribution the metamorphosis of the metaparadigm from the dialectic to the dialogue is characterized as cultural transition-time demanding from the individual to cope and live with permanent contradictions and conflicts. On the background of this anthropologic situation addiction is understood as internalized foreign determination sustaining a common though antiquated scheme of psychic and social conflict conditioned by outdated patterns of education and socialisation. Addiction is appreciated as an inadequate attempt of the individual and of society toward adaptation, based on historic evolution of culture.


The technological future of 7 T MRI hardware.
In this article we present our projections of future hardware developments on 7 T human MRI systems. These include compact cryogen-light magnets, improved gradient performance, integrated RF-receive and direct current shimming coil arrays, new RF technology with adaptive impedance matching, patient-specific specific absorption rate estimation and monitoring, and increased integration of physiological monitoring systems. Copyright © 2015 John Wiley & Sons, Ltd.


Identification of potent odourants in wine and brewed coffee using gas chromatography-olfactometry and comprehensive two-dimensional gas chromatography.
Volatile constituents in wine and brewed coffee were analyzed using a combined system incorporating both GC-olfactometry (GC-O) and comprehensive two-dimensional GC-flame ionization detection (GC×GC-FID). A column set consisting of a 15m first dimension ((1)D; DB-FFAP (free fatty acid phase)), and a 1.0m (2)D column (DB-5 phase) was applied to achieve the GC×GC separation of the volatile extracts isolated by using solid phase extraction (SPE). While 1D GC resulted in many overlapping peaks, GC×GC allowed resolution of co-eluting compounds which coincided with the odour region located using GC-O. Character-impact odourants were tentatively identified through data correlation of GC×GC contour plots across results obtained using either time-of-flight mass spectrometry (TOFMS), or with flame photometric detection (FPD) for sulfur speciation. The odourants 2-methyl-2-butenal, 2-(methoxymethyl)-furan, dimethyl trisulfide, 2-ethyl-5-methyl-pyrazine, 2-octenal, 2-furancarboxaldehyde, 3-mercapto-3-methyl-1-butanol, 2-methoxy-3-(2-methylpropyl)-pyrazine, 2-furanmethanol and isovaleric acid were suspected to be particularly responsible for coffee aroma using this approach. The presented methodology was applied to identify the potent odourants in two different Australian wine varietals. 1-Octen-3-ol, butanoic acid and 2-methylbutanoic acid were detected in both Merlot and a Sauvignon Blanc+Semillon (SV) blend with high aroma potency. Several co-eluting peaks of ethyl 4-oxo-pentanoate, 3,7-dimethyl-1,5,7-octatrien-3-ol, (Z)-2-octen-1-ol, 5-hydroxy-2-methyl-1,3-dioxane were likely contributors to the Merlot wine aroma; while (Z)-3-hexen-1-ol, β-phenylethyl acetate, hexanoic acid and co-eluting peaks of 3-ethoxy-1-propanol and hexyl formate may contribute to SV wine aroma character. The volatile sulfur compound 2-mercapto-ethyl acetate was believed to contribute a fruity, brothy, meaty, sulfur odour to Australian Merlot and SV wines.


Towards automation of single needle vascular access.
In the past, SN devices have not always fulfilled the expectations of clinicians, but adequate extracorporeal blood flows can only be expected from adequate intravascular flows, which of course applies to any SN method. In some instances, problems may have been caused by poor equipment design, but poor understanding and handling of devices may equally have at fault. Improvement of presently available SN equipment therefore seemed necessary. A fully automatic, second generation cross-over SN control device has been designed which is simple to operate and has the following advantages: Operation is restricted to the speed control setting of the blood pump in the host machine. The CO-SN system automatically responds to changes of fistula flow by modulating the stroke volumes. Recirculation can be kept below 10%. The blood pump rate can be adjusted to the maximum flow rate of the cannulated vessel. Obligatory ultrafiltration is eliminated. Blood compartment pressure is constant. The Munich prototype cross-over SN module was designed as an auxiliary SN equipment which may substitute the Unipuncture machine.


Effects of intravenous administration of human bone marrow stromal cells after intracerebral hemorrhage in rats.
The goal of this study was to investigate whether human bone marrow stromal cells (hBMSCs) administered by intravenous injection have a beneficial effect on outcome after intracerebral hemorrhage (ICH) in rats. An ICH was induced in 54 adult male Wistar rats by a stereotactically guided injection of autologous blood into the right striatum. Intravenous infusion of the hBMSCs (3, 5, or 8 million cells) was performed 1 day after ICH, and for each dose group there was a control group that received injections of vehicle. Neurological function, which was evaluated using the Neurological Severity Score (NSS) and the corner turn test, was tested before and at 1, 7, and 14 days after ICH. After 14 days of survival, the area of encephalomalacia was calculated and histochemical labeling was performed. For all three groups, there were no statistical differences in either the NSS or corner turn tests after 1 day. After 7 and 14 days, however, the three groups that received the hBMSCs showed significant improvement in functional scores compared with the control group. In addition, after 14 days there was significantly more striatal tissue loss in the placebo groups compared with each of the three treatment groups. The region of injury in the treated animals demonstrated a significantly increased presence of hBMSCs, immature neurons, neuronal migration, synaptogenesis, and newly formed DNA. Intravenous administration of hBMSCs significantly improves neurological function in rats subjected to ICH. This improvement in the treated animals is associated with reduced tissue loss and increased local presence of the hBMSCs, mitotic activity, immature neurons, synaptogenesis, and neuronal migration.


Nonreferral of possible soft tissue sarcomas in adults: a dangerous omission in policy.
Introduction. The aim of this study is to compare outcomes in three groups of STS patients treated in our specialist centre: patients referred immediately after an inadequate initial treatment, patients referred after a local recurrence, and patients referred directly, prior to any treatment. Patients and methods. We reviewed all our nonmetastatic extremity-STS patients with a minimum follow-up of 2 years. We compared three patient groups: those referred directly to our centre (group A), those referred after an inadequate initial excision (group B), and patients with local recurrence (group C). Results. The study included 174 patients. Disease-free survival was 73%, 76%, and 28% in groups A, B, and C, respectively (P < .001). Depth, size, and histologic grade influenced the outcome in groups A and B, but not in C. Conclusion. Initial wide surgical treatment is the main factor that determines local control, being even more important than the known intrinsic prognostic factors of tumour size, depth, and histologic grade. The influence on outcome of initial wide local excision (WLE), which is made possible by referral to a specialist centre, is paramount.


Acute glomerulonephritis with large confluent IgA-dominant deposits associated with liver cirrhosis.
Small glomerular IgA deposits have been reported in patients with liver cirrhosis, mainly as an incidental finding in autopsy studies. We recently encountered nine cirrhotic patients who presented with acute proliferative glomerulonephritis with unusually large, exuberant glomerular immune complex deposits, in the absence of systemic lupus erythematosus (SLE) or monoclonal gammopathy-related kidney disease. Deposits were typically IgA dominant/codominant. Our aim was to further elucidate the etiology, diagnostic pitfalls, and clinical outcomes. We present clinical features and kidney biopsy findings of nine cirrhotic patients with an unusual acute immune complex glomerulonephritis. We also identified native kidney biopsies from all patients with liver cirrhosis at our institution over a 13-year period (January 2004 to December 2016) to evaluate presence of glomerular IgA deposits in them (n = 118). Six of nine cirrhotic patients with the large immune deposits had a recent/concurrent acute bacterial infection, prompting a diagnosis of infection-associated glomerulonephritis and treatment with antibiotics. In the remaining three patients, no infection was identified and corticosteroids were initiated. Three of nine patients recovered kidney function (one recovered kidney function after liver transplant); three patients developed chronic kidney disease but remained off dialysis; two patients became dialysis-dependent and one patient developed sepsis and expired shortly after biopsy. Within the total cohort of 118 patients with cirrhosis, 67 others also showed IgA deposits, albeit small; and 42 patients had no IgA deposits. These cases provide support to the theory that liver dysfunction may compromise clearance of circulating immune complexes, enabling deposition in the kidney. At least in a subset of cirrhotic patients, a superimposed bacterial infection may serve as a "second-hit" and lead to acute glomerulonephritis with exuberant immune complex deposits. Therefore, a trial of antibiotics is recommended and caution is advised before immunosuppressive treatment is offered. Unfortunately, most of these patients have advanced liver failure; therefore both diagnosis and management remain a challenge.


DNA fingerprints of chickens selected for high and low body weight for 31 generations.
Two lines of White Plymouth Rock chickens that have been divergently selected for 8-week body weight for 31 generations were compared for patterns of DNA fingerprints (DFP). Digestion of DNA with HinfI and hybridization to Jeffreys' minisatellite probe 33.6 resulted in DFPs that were relatively similar within lines (bandsharing = 0.50) and less similar between lines (bandsharing = 0.22). Analyses of scorable DFP bands produced by mixing DNA from individuals within lines indicated that 48% were line-specific. Causes for the differences in DFP patterns between lines and for occurrence of line-specific bands for the two lines divergently selected for body weight are discussed.


Diagnosis and Treatment of Nodular Fasciitis of Ear Region in Children: A Case Report and Review of Literature.
Nodular fasciitis (NF) is a benign fibroblastic and myofibroblastic proliferation of subcutaneous tissues. Rarely, it has been identified in the ear and more rarely in children. We describe a case in a four-year-old girl and the surgical management of it. The patient was referred to the otolaryngology unit of a tertiary referral center because she was affected by a painless and growing lesion in the left external auditory canal (EAC). The girl was treated by large-spectrum antibiotic therapy for one week without success. For this reason, we requested ultrasonography (US) of the left hemiface, maxillofacial and temporal bone computed tomography (CT) and magnetic resonance imaging (MRI) of the head with and without contrast. The imaging identified an irregular ovoid hypoechoic nodule with distinct margins indissociable from the cartilaginous planes and extending into the parotid loggia with local infiltration of the fascia. The lesion was surgically removed through preauricular access due its extension into the parotid area. The mass was excised in toto and sent to the pathologist for immunohistochemistry. The histopathologist based on the finding diagnosed a nodular fasciitis. In case of suspicion of malignancy, early investigations should be done to evaluate the lesion, then a traditional parotidectomy can be safely and successfully performed even in a very young child. The open technique allows the removal of NF with full control of the surgical area and facial nerve. In this article, we presented the management of a case in a 4-year-old female affected by NF of the external auditory canal (EAC), and we described clinical and surgical management of the case. We also reviewed literature of nodular fasciitis cases of ears in children.


LOD map--A visual interface for navigating multiresolution volume visualization.
In multiresolution volume visualization, a visual representation of level-of-detail (LOD) quality is important for us to examine, compare, and validate different LOD selection algorithms. While traditional methods rely on ultimate images for quality measurement, we introduce the LOD map--an alternative representation of LOD quality and a visual interface for navigating multiresolution data exploration. Our measure for LOD quality is based on the formulation of entropy from information theory. The measure takes into account the distortion and contribution of multiresolution data blocks. A LOD map is generated through the mapping of key LOD ingredients to a treemap representation. The ordered treemap layout is used for relative stable update of the LOD map when the view or LOD changes. This visual interface not only indicates the quality of LODs in an intuitive way, but also provides immediate suggestions for possible LOD improvement through visually-striking features. It also allows us to compare different views and perform rendering budget control. A set of interactive techniques is proposed to make the LOD adjustment a simple and easy task. We demonstrate the effectiveness and efficiency of our approach on large scientific and medical data sets.


Features and outcomes of renal cell carcinoma of native kidneys in renal transplant recipients.
To outline the features and outcomes of renal cell carcinoma (RCC) in native kidneys of renal transplant recipients, who are at increased risk of developing this disease. We retrospectively studied the clinicopathological features and survival of 28 surgically treated RCCs, which developed in 24 renal transplant recipients. Features and outcomes were compared with 671 patients with RCC who had no renal transplant. The median interval between renal transplantation and the occurrence of RCC was 5.6 years. Acquired cystic kidney disease was present in 83% of the transplanted patients. Compared with the patients with RCC and no renal transplant, RCCs of native kidneys in transplant recipients were more frequently incidental findings (92% vs 77%, P = 0.092), multifocal (39% vs 15%, P < 0.001), bilateral (17% vs 4%, P = 0.006), had lower T stages (P = 0.040), were smaller (P = 0.027), of lower grades (P = 0.010), were more frequently papillary (43% vs 19%, P = 0.019) and occurred at a significantly younger age (P = 0.022). After a median follow-up of 6.7 years, eight renal transplant recipients had died (33%), but only two deaths were due to RCC. Survival with metastatic RCC was only 4 months, if a full resection of all metastatic sites was not achieved. In multivariate analysis the presence of a renal transplant had no effect on survival. Most RCCs in renal transplant recipients are incidental low-stage, low-grade tumours with a favourable prognosis. The outstanding pathological findings are bilateral occurrence, papillary subtype and multifocality. Prognosis of metastatic RCC is poor but might be favourable if all metastases are resected. Screening for early detection of asymptomatic RCC is advocated.


Small scale water recycling systems--risk assessment and modelling.
This paper aims to use quantitative risk analysis, risk modelling and simulation modelling tools to assess the performance of a proprietary single house grey water recycling system. A preliminary Hazard and Operability study (HAZOP) identified the main hazards, both health related and economic, associated with installing the recycling system in a domestic environment. The health related consequences of system failure were associated with the presence of increased concentrations of micro-organisms at the point of use, due to failure of the disinfection system and/or the pump. The risk model was used to assess the increase in the probability of infection for a particular genus of micro-organism, Salmonella spp, during disinfection failure. The increase in the number of cases of infection above a base rate rose from 0.001% during normal operation, to 4% for a recycling system with no disinfection. The simulation model was used to examine the possible effects of pump failure. The model indicated that the anaerobic COD release rate in the system storage tank increases over time and dissolved oxygen decreases during this failure mode. These conditions are likely to result in odour problems.


A view of nursing epistemology through reciprocal interdependence: towards a reflexive way of knowing.
The discipline of nursing has experienced the movement from modernism to postmodernism through expressions ranging from dualistic and polarized discourse to contradicting pluralistic positions. For the purpose of this paper, these responses are described as ways of knowing and are examined for their impact on the evolution of the nursing discipline. Reciprocal interdependence is offered as an alternate way of knowing capable of incorporating differing world views into a coherent and comprehensive systemic whole. The reflexive and potentially transformational impact of reciprocal interdependence on the advancement of nursing knowledge is reviewed through a discussion of the value of polarity, as well as the contribution of complementary and dialectical perspectives to the maintenance of interactions between the whole and its constituents.


Association of menstrual blood volume and reproductive outcomes in patients with caesarean scar pregnancy managed using uterine artery embolization and curettage.
This study aimed to assess the association of menstrual blood volumes (MBV) and reproductive outcomes in patients after uterine artery embolization (UAE) combined with curettage for caesarean scar pregnancy (CSP). This retrospective observational study enrolled women who underwent UAE plus curettage for CSP at the Interventional Department of Henan Provincial People's Hospital between December 2012 and December 2017. The primary outcome was pregnancy rate and the secondary outcomes were live birth rate (LBR) and interpregnancy interval. This study finally included 37 women (16 women with normal MBV and 21 women with decreased MBV) with pregnancy intention after UAE plus curettage for CSP. The pregnancy rate in women with normal MBV was higher than those with decreased MBV (81.3% vs. 47.6%; P = 0.048). There were no differences between the two groups regarding the interpregnancy interval (18.4 ± 8.7 vs. 22.2 ± 10.0 months, P = 0.233), and LBR (63% vs. 38%, P = 0.191). In conclusion, Women with normal MBV after UAE combined with curettage for CSP management might have a higher pregnancy rate compared with patients with decreased MBV, but there were no differences in LBR between the two groups.


Implementation of Lung Cancer Screening in Primary Care and Pulmonary Clinics: Pragmatic Clinical Trial of Electronic Health Record-Integrated Everyday Shared Decision-Making Tool and Clinician-Facing Prompts.
Although low-dose CT (LDCT) scan imaging lung cancer screening (LCS) can reduce lung cancer mortality, it remains underused. Shared decision-making (SDM) is recommended to assess the balance of benefits and harms for each patient. Do clinician-facing electronic health record (EHR) prompts and an EHR-integrated everyday SDM tool designed to support routine incorporation of SDM into primary care improve LDCT scan imaging ordering and completion? A preintervention and postintervention analysis was conducted in 30 primary care and four pulmonary clinics for visits with patients who met United States Preventive Services Task Force criteria for LCS. Propensity scores were used to adjust for covariates. Subgroup analyses were conducted based on the expected benefit from screening (high benefit vs intermediate benefit), pulmonologist involvement (ie, whether the patient was seen in a pulmonary clinic in addition to a primary care clinic), sex, and race and ethnicity. In the 12-month preintervention phase among 1,090 eligible patients, 77 patients (7.1%) had LDCT scan imaging orders and 48 patients (4.4%) completed screenings. In the 9-month intervention phase among 1,026 eligible patients, 280 patients (27.3%) had LDCT scan imaging orders and 182 patients (17.7%) completed screenings. Adjusted ORs were 4.9 (95% CI, 3.4-6.9; P < .001) and 4.7 (95% CI, 3.1-7.1; P < .001) for LDCT imaging ordering and completion, respectively. Subgroup analyses showed increases in ordering and completion for all patient subgroups. In the intervention phase, the SDM tool was used by 23 of 102 ordering providers (22.5%) and for 69 of 274 patients (25.2%) for whom LDCT scan imaging was ordered and who needed SDM at the time of ordering. Clinician-facing EHR prompts and an EHR-integrated everyday SDM tool are promising approaches to improving LCS in the primary care setting. However, room for improvement remains. As such, further research is warranted. ClinicalTrials.gov; No.: NCT04498052; URL: www. gov.


In Vivo Immunological Effects of CD73 Deficiency.
The extracellular ecto-5'-nucleotidase (CD73) is involved in the production of immunosuppressive adenosin (Ado), which can influence different immune cells through the specific adenosine receptors. The main aim of this work was to characterize immune cell populations as well as serum cytokine level in healthy CD73-deficient mice compared to healthy wild-type animals. Profound immnophenotyping of splenocytes from healthy CD73-deficient and wild-type mice was done using flow cytometry (FACS analysis). Cytokine measurement in the serum of the animals was carried out with a Bio-Plex assay. The CD73-deficience leads to an increase in a percentage of NK cells and pDC, as well as influences expression of the costimulatory molecules CD80 and CD86. The knockout mice in opposite to wild-type animals show high amount of effector CD4+ T-cells in the spleens. No changes have been found in the subpopulations of CD8+ T-cells. Besides, CD73-deficience leads to a decrease in the percentage of regulatory T cells. Compared with the wild-type animals we found that CD73 knockout mice possess low serum concentration of IL-6. This in vivo study clear demonstrated certain immunological changes in the CD73-deficient mice and thus immunoregulatory potential of CD73 molecule. This makes this extracellular enzyme to a real immune check point molecule, attractive for further investigations and clinical studies.


What do adolescents want? An exploratory study regarding end-of-life decision-making.
To explore whether differences exist between chronically ill and healthy adolescents with regard to their attitudes about end-of-life (EOL) issues. A convenience sample of 25 adolescents without and 25 with a chronic illness, aged 13 to 21 years, were surveyed in hospital clinics, using a 25-item instrument; 60% were female and 76% were African-American. Items were developed based on previous research, interviews with health care providers, and a focus group with patients. Data were analyzed using the Fisher's exact test for 2-tailed p values. Ninety-six percent of chronically ill and 88% of healthy teens want to share decision-making if they are very ill; 76% prefer to discuss their wishes earlier in the course of a life-threatening illness. There was a trend for chronically ill adolescents to prefer to wait until later in the course of their illness (32% at diagnosis, 32% when first ill, 20% first hospitalization, or 16% if dying), when compared with their healthy peers (68% at diagnosis, 20% first ill, 4% first hospitalization, 8% if dying) (p = .074). Chronically ill adolescents were significantly more likely to prefer to wait to have these discussions, if the data were collapsed for time (first hospitalized and/or dying) (Fisher's p = .037). Half of all adolescents believed that they would be allowed to change their minds once they had made a decision. Eighty percent of chronically ill and 68% of healthy teens believed that their doctor would respect their wishes, while many were uncertain. Even teenagers without chronic illness have thoughts about end-of-life issues and have opinions remarkably similar to those of chronically ill teens. Those who are chronically ill are less likely to wish to discuss EOL issues early in their illness.


Sexual dimorphism in territorial scent marking by adult Eurasian beavers (Castor fiber).
Mammalian scent marking is often associated with territorial defense. However, males and females may demonstrate different activity patterns and play different roles. Female mammals nurture the young during lactation, while males purportedly perform other tasks more frequently, such as territorial maintenance and defense. This paper investigates the contribution made by mated pairs of adult males and females to territorial scent-marking in the obligate monogamous Eurasian beavers (Castor fiber). We hypothesized that both sexes should show territorial behavior, and predicted that they deposit a higher proportion of scent marks at borders. We also hypothesized that a sexual dimorphism exists due to reproductive constraints on the females, and predicted that males should invest significantly more in scent-marking behavior than females during summer. We obtained behavioral data by radio tracking six mated pairs of Eurasian beavers during spring and summer 2000-2001 on two rivers in southeastern Norway. Our results showed that both males and females clustered their scent marks near territorial borders, but males deposited a larger number of scent marks than females and spent more time at borders. Males were also found to have a higher scent marking rate and scent marks per night than females during summer, but not during spring. Overall, scent marks per night were higher in males than females. We conclude that both males and females Eurasian beavers carry out territorial behavior by scent marking, but males carry a larger part of the territorial defense during summer when females lactate. Our results are discussed in the light of the codefense hypothesis.


The intricate role of mast cell proteases and the annexin A1-FPR1 system in abdominal wall endometriosis.
Endometriosis is a continuous and progressive disease with a poorly understood aetiology, pathophysiology and natural history. This study evaluated the histological differences between eutopic and ectopic endometria (abdominal wall endometriosis) and the expression of mast cell proteases (tryptase and chymase), annexin A1 (ANXA1) and formyl peptide receptor 1 (FPR1). Ectopic endometrium from 18 women with abdominal wall endometriosis and eutopic endometrium from 10 women without endometriosis were obtained. The endometrial samples were analysed by histopathology, immunohistochemistry and ultrastructural immunogold labeling to determine mast cell heterogeneity (tryptase and chymase positive cells) and the expression levels of ANXA1 and FPR1. Histopathological analysis of the endometriotic lesions showed a glandular pattern of mixed differentiation and an undifferentiated morphology with a significant influx of inflammatory cells and a change in mast cell heterogeneity, as evidenced by a significant increase in the number of chymase-positive cells and endogenous chymase expression. The undifferentiated glandular pattern of endometriotic lesions was positively associated with a marked increase and co-localization of ANXA1 and FPR1 in the epithelial cells. In conclusion, the co-upregulated expression of mast cell chymase and ANXA1-FPR1 system in ectopic endometrium suggests their involvement in the development of endometriotic lesions.


Rationale and design of the multicentre randomized trial investigating the efficacy and safety of pulsed infusions of levosimendan in outpatients with advanced heart failure (LevoRep study).
Advanced chronic heart failure (CHF) is a clinical syndrome with high morbidity and mortality that often requires inotropic support for the alleviation of symptoms and congestion. There are no definite evidence-based data on the safety and efficacy of intermittent infusions of inotropic agents in this severe clinical condition. The purpose of the LevoRep study is to clarify whether pulsed infusions of the new inotropic agent levosimendan administered in an outpatient setting can safely improve exercise capacity, quality-of-life (QoL), and outcome in advanced CHF patients. The LevoRep study is a prospective, randomized, double-blind, placebo-controlled, two-armed, parallel-group, multicentre trial. The study is designed to investigate the effects of pulsed infusions of levosimendan (6 h administration at 0.2 microg/kg/min every 2 weeks) on the composite endpoint (primary endpoint) comprising changes in functional capacity and QoL (20% or greater improvement in the 6 min walk test and 15% or higher score on the Kansas City Cardiomyopathy Questionnaire) at the end of the 24 week study period. In addition, short-term (8 weeks from randomization) and long-term (24 weeks from randomization) event-free survival (secondary endpoint) will be assessed. The LevoRep study aims to include 120 outpatients with advanced CHF. LevoRep is the first prospective randomized trial to assess the effects of pulsed infusions of an inotrope on hard endpoints as well as on the safety in patients with advanced CHF on an outpatient basis. The results are expected to promote the development of evidence-based recommendations for the ambulatory management of patients with end-stage heart failure.


Effects of insulin, cortisol and prolactin on lipid, protein and casein syntheses in goat mammary tissue in organ culture.
The actions of insulin, prolactin and cortisol on protein, lipid and casein syntheses were examined in goat mammary explants in culture. The synthesis of the three products was stimulated by insulin and prolactin associated or not with cortisol. Casein synthesis was stimulated only when prolactin was present in the culture medium. Prolactin alone was able to significantly support the induction of casein synthesis. After preculture in the presence of insulin alone, the tissue lost part of its capacity to respond to the prolactin stimulus but, when precultured in the presence of insulin + cortisol, it retained its total sensitivity. These data suggest that insulin, prolactin and cortisol are involved in the maintenance of goat mammary tissue in culture but that prolactin essentially stimulates milk synthesis.


Reactivity for boryl(phosphino)carbenyl carbene analogues with group 14 elements (C, Si, Ge, Sb, and Pb) as a heteroatom: a theoretical study.
The potential energy surfaces for the chemical reactions of group 14 carbenes have been studied using density functional theory (B3LYP/LANL2DZ). Five boryl(phosphino)-based carbene (B-Ë-P) species, where Ë = C, Si, Ge, Sn, and Pb, have been chosen as model reactants in this work. Also, four kinds of chemical reactions; intramolecular 1,2-migration, water insertion, alkene cycloaddition, and intermolecular dimerization, have been used to study the chemical reactivities of these group 14 carbenes. The present theoretical investigations suggest that the relative carbenic reactivity decreases in the order C > Si > Ge > Sn > Pb. That is, the heavier the group 14 atom (E), the more stable is the boryl(phosphino)-based B-Ë-P species towards chemical reactions. Our theoretical findings thus demonstrate that all boryl(phosphino)-based carbenes are isolable at room temperature because they are quite inert to chemical reactions, except that they are also moisture-sensitive molecules. Furthermore, the singlet-triplet energy splitting of the B-Ë-P, as described in the configuration mixing model attributed to the work of Pross and Shaik, can serve as a diagnostic tool for a better understanding and predicting of their chemical reactivities, kinetically and thermodynamically. The results obtained allow a number of predictions to be made.


Reduction in All-Cause Acute Otitis Media in Children <3 Years of Age in Primary Care Following Vaccination With 10-Valent Pneumococcal Haemophilus influenzae Protein-D Conjugate Vaccine: A Whole-Population Study.
The 10-valent pneumococcal conjugate vaccine (PHiD-CV10) was introduced in Iceland in 2011, without catch-up. The aim of this study was to estimate vaccine impact (VI) on acute otitis media (AOM). In this whole-population study, all primary care visits due to AOM from 2005 to 2015 in children <3 years of age were included. Birth cohorts were grouped as vaccine noneligible (VNEC) or vaccine eligible (VEC). Crude incidence rates (IRs) were compared between the VNEC and VEC. A Cox regression model for repeated events was used to model the individual-level data. VI was calculated as (hazard ratio [HR] - 1) × 100%. Included were 53150 children, with 140912 person-years of follow-up and 58794 AOM episodes. Both IR and the mean number of episodes differed significantly between VNEC and VEC; 43 compared to 38 episodes per 100 person-years and 1.61 episodes per child compared to 1.37. IR was significantly reduced in all age brackets, with the largest reduction in children <4 months of age (40% [95% confidence interval {CI}, 31%-49%). The VI on all-cause AOM was 22% (95% CI, 12%-31%). The impact was mediated through its effect on the first (HR, 0.84 [95% CI, .82-.86]) and second (HR, 0.95 [95% CI, .93-.98]) episodes. The impact of PHiD-CV10 on all-cause AOM was considerable, mediated mainly by preventing the first two episodes of AOM. A decrease in the IR of AOM in children too young to receive direct vaccine protection was demonstrated, suggesting herd effect.


Organocatalytic Asymmetric Biginelli-like Reaction Involving Isatin.
The first asymmetric, Brønsted acid catalyzed Biginelli-like reaction of a ketone has been developed, employing N-substituted isatins as carbonyl substrates, and urea and alkyl acetoacetates as further components. BINOL-derived phosphoric acid catalysts have been used to achieve the synthesis of a small library of chiral, enantioenriched spiro(indoline-pyrimidine)-diones derivatives. The absolute configuration of the new spiro stereocenter was assessed on diastereoisomeric derivatives through computer-assisted NMR spectroscopy. X-ray diffractometry allowed the disclosure of the overall molecular conformation in the solid state and the characterization of the crystal packing of a Br-substituted Biginelli-like derivative, while computational studies on the reaction transition state allowed us to rationalize the stereochemical outcome.


Transference-focused psychotherapy for borderline personality disorder: change in reflective function.
Borderline personality disorder is associated with deficits in personality functioning and mentalisation. In a randomised controlled trial 104 people with borderline personality disorder received either transference-focused psychotherapy (TFP) or treatment by experienced community therapists. Among other outcome variables, mentalisation was assessed by means of the Reflective Functioning Scale (RF Scale). Findings revealed only significant improvements in reflective function in the TFP group within 1 year of treatment. The between-group effect was of medium size (d = 0.45). Improvements in reflective function were significantly correlated with improvements in personality organisation.


Successful Treatment of a Locally Recurrent and Metastatic Malignant Phyllodes Tumor with Accelerated Radiotherapy and Nab-Paclitaxel, Cisplatin, and Liposomal Doxorubicin Chemotherapy.
Phyllodes tumors are rare breast lesions of fibroepithelial origin. Malignant transformation with metastases is linked with poor prognosis. We present a case of a 62-year-old woman with a recurrent malignant phyllodes tumor of the breast and lung metastases. The patient was originally presented with a borderline phyllodes tumor (7.4 cm) of the left breast, treated with wide local excision. A year later, the patient returned with palpable left breast masses. On PET-CT, increased uptake of 18F-FDG by large breast tumors was evident. A right lung lesion of metastatic origin was also present. A simple left breast mastectomy was performed. Histopathological report described 2 malignant phyllodes tumors (7 cm and 6.5 cm). One month later, during the CT simulation for radiotherapy planning, encysted fluid in the chest wall and 2 additional pulmonary lesions of the right lung were identified, confirming progressive lung metastatic disease. Both the chest wall and the regional lymph node area were irradiated with hypofractionated and accelerated radiotherapy. Biweekly chemotherapy with albumin-bound paclitaxel, cisplatin, and liposomal doxorubicin was also prescribed at the start of radiotherapy for 12 cycles. At the end of chemotherapy, complete regression of lung metastases was achieved, and there was no evidence of local recurrence. Within 2 years of follow-up, the patient is free of disease and treatment-related toxicities. Accelerated hypofractionated radiotherapy is effective in the locoregional control of malignant phyllodes tumors. The combination of cisplatin with nab-paclitaxel and liposomal doxorubicin chemotherapy has acceptable toxicity and is highly effective in eradicating metastatic lesions.


Multicenter closed-loop/hybrid meal bolus insulin delivery with type 1 diabetes.
This study evaluated meal bolus insulin delivery strategies and associated postprandial glucose control while using an artificial pancreas (AP) system. This study was a multicenter trial in 53 patients, 12-65 years of age, with type 1 diabetes for at least 1 year and use of continuous subcutaneous insulin infusion for at least 6 months. Four different insulin bolus strategies were assessed: standard bolus delivered with meal (n=51), standard bolus delivered 15 min prior to meal (n=40), over-bolus of 30% delivered with meal (n=40), and bolus purposely omitted (n=46). Meal carbohydrate (CHO) intake was 1 g of CHO/kg of body weight up to a maximum of 100 g for the first three strategies or up to a maximum of 50 g for strategy 4. Only three of 177 meals (two with over-bolus and one with standard bolus 15 min prior to meal) had postprandial blood glucose values of <60 mg/dL. Postprandial hyperglycemia (blood glucose level >180 mg/dL) was prolonged for all four bolus strategies but was shorter for the over-bolus (41% of the 4-h period) than the two standard bolus strategies (73% for each). Mean postprandial blood glucose level was 15.9 mg/dL higher for the standard bolus with meal compared with the prebolus (baseline-adjusted, P=0.07 for treatment effect over the 4-h period). The AP handled the four bolus situations safely, but at the expense of having elevated postprandial glucose levels in most subjects. This was most likely secondary to suboptimal performance of the algorithm.


[Gel derived bioactive ceramic as bone substitute--an in vivo study].
The paper presents the histopathological and radiological study performed on a series of male, mixed-race rabbits. All rabbits had a 20 x 4 x 4 mm-bone fragment extracted from the radial bone according to a modified technique by Scmitt and Weller. In the right radius bone the bone defect was filled with approximately 0.5 cm3 bioglass S2. In the left rius, which served as control, allogenic bone graft (the size of the defect) collected from the tibia and femur was implanted. Rabbits were sacrificed 3, 6 and 12 weeks after the procedure and histopathological and radiological studies were performed. These studies revealed a heterogeneous increase of new bone regeneration in all three phases of the study. The S2 biomaterial both stimulated and accelerated bone regeneration in the rabbits.


The relationship between expected engagement and talking therapy outcome.
The aim of the study was to investigate whether client-reported expected engagement with therapy predicted therapy outcome. It was hypothesized that higher expected engagement with cognitive behavioural therapy (CBT) or person-centred experiential therapy (PCET) would predict more symptomatic improvement following therapy and higher likelihood of therapy completion. The Sheffield Expected Engagement with Therapy Scale was administered to 96 clients at pre-therapy assessment with all meeting a diagnosis of moderate or severe depression with 53 receiving CBT and 43 receiving PCET. Higher expected engagement predicted more symptomatic improvement in CBT but not PCET. Expected engagement only predicted improvement in CBT when clients rated the credibility of CBT as low or moderate. Expected engagement did not predict therapy completion in either therapy. Assessment of expected engagement could be a useful tool in prediction of symptomatic improvement in CBT.


[Effect of phenol ring polymers on the release of plasminogen activators].
The effects of synthetic and natural phenol polymers on the release of plasminogen activator were examined on an isolated vascular preparation of the pig ear. Of the synthetic phenol polymers, the products of caffeine acid and 3,4-dihydroxyphenylacetic acid were found to raise the activity of plasminogen activator. As far as the natural polymers of phenol are concerned, only sodium humate was found to produce an action similar to that of the products of caffeinic acid and 3,4-dihydroxyphenylacetic acid.


Global Strain Measured by Three-Dimensional Speckle Tracking Echocardiography Is a Useful Predictor for 10-Year Prognosis After a First ST-Elevation Acute Myocardial Infarction.
Three-dimensional (3D) speckle tracking echocardiography (STE) after ST-elevation acute myocardial infarction (STEMI) is associated with left ventricular (LV) remodeling and 1-year prognosis. This study investigated the clinical significance of 3D-STE in predicting the long-term prognosis of patients with STEMI.Methods and Results:A total of 270 patients (mean age 64.6 years) with first-time STEMI treated with reperfusion therapy were enrolled. At 24 h after admission, standard 2D echocardiography and 3D full-volume imaging were performed, and 2D-STE and 3D-STE were calculated. Patients were followed up for a median of 119 months (interquartile range: 96-129 months). The primary endpoint was occurrence of a major adverse cardiac event (MACE: cardiac death, heart failure with hospitalization), and 64 patients experienced MACEs. Receiver operating characteristic curves and Cox hazard multivariate analysis showed that the 3D-STE indices were stronger predictors of MACE compared with those of 2D-STE. Additionally, 3D-global longitudinal strain (GLS) was the strongest predictor for MACE followed by 3D-global circumferential strain (GCS). The Kaplan-Meier curve demonstrated that 3D-GLS >-11.0 was an independent predictor for MACE (log-rank χ2=132.2, P<0.0001). When combined with 3D-GCS >-18.3, patients with higher values of 3D-GLS and 3D-GCS were found to be at extremely high risk for MACE. Global strain measured by 3D-STE immediately after the onset of STEMI is a clinically significant predictor of 10-year prognosis.


[Water exposure modes and times of different populations in mountainous schistosomiasis endemic areas near Qionghai lake].
To investigate water exposure modes and times of different populations in mountainous schistosomiasis endemic areas and to inform about the control strategies. All 1054 residents from populations around Qionghai Lake were randomly sampled according to occupation for a retrospective questionnaire survey in November 2001. Each individual was interviewed for his/her mode, frequency, and duration of water exposure occurring between April and October 2001. The average exposure times and intensity were higher in farmers (median: 16 - 18 min/day and 2.41 - 2.5, respectively) who grow rice, tobacco, and vegetables than others (median: 3.74 - 7.39 min/day and 0.81 - 1.52, respectively); exposure frequency was found highest in farmers (median: 2.04 times/day) in all occupations; schoolchildren had low exposure frequency and times, but very high exposure intensity (median 2.34). Between April and June it is an agriculturally busy season, that is also a peak season of water exposure of adults. Schoolchildren's water exposure peaks on July and August, mainly due to playing water and swimming. Exposure times and intensities were higher in females than in males. Water exposure modes, times, and intensities of different populations were different in mountainous schistosomiasis endemic areas of Xichang. Between April and June should be the peak infection season of adults who are engaging in agricultural activities, while July to August should be the peak infection season for schoolchildren with non-agricultural activities.


Review of antimicrobial resistance control strategies: low impact of prospective audit with feedback on bacterial antibiotic resistance within hospital settings.
Antimicrobial stewardship constitutes an essential element of any concerted effort to tackle bacterial resistance, a rising public health threat both in community as well as hospital settings. The term comprises variable strategies which aim to optimise prescribing practices through either antibiotic restrictions or prospective audits of prescriptions with subsequent feedback to clinicians. Although highly debated, the actual effects of the latter on the antimicrobial susceptibility patterns of hospital flora are uncertain. The present study aims to review and evaluate the literature concerning the impact of persuasive stewardship strategies on antimicrobial resistance within hospitals. A literature review covering the period to 1st April 2020 was conducted using the PubMed/Medline, Embase, Global Health and CINAHL Plus databases. Fifteen studies were retrieved, including twelve simple before-and-after, and three interrupted time-series studies. Audit frequency and compliance rates varied broadly. The rationale of treatment optimisation is not clear in most cases. Overall, surveillance of sentinel microorganisms through antibiograms indicates ambiguous results, with uncertainty as to whether the few successes are due to a causal effect, random incidence fluctuations, or confounding. The most informative approach targeted solely fluoroquinolones, reporting improvements in relevant Pseudomonas susceptibilities and MRSA, but without sufficient data on other effects of the strategy to assess its overall utility in clinical practice. Higher standard research is needed to address the actual effects of persuasive stewardship strategies on antimicrobial susceptibility patterns. At present, they seem inadequate to play a decisive role in bacterial resistance control within hospitals.


Polymeric micellar delivery reduces kidney distribution and nephrotoxic effects of Cyclosporine A after multiple dosing.
The aim of this study was to test the ability of poly(ethylene oxide)-b-poly (epsilon-caprolactone) (PEO-b-PCL) micelles to reduce the renal uptake and nephrotoxicity of Cyclosporine A (CyA) after multiple dose administration. Sprague-Dawley rats received CyA i.v. at a dose of 20 mg/kg/day delivered as the commercial formulation (Sandimmune) or polymeric micellar formulation (PM-CyA). Cremophor EL (the solubilizing agent in Sandimmune), unloaded PEO-b-PCL micelles, or normal saline were also administered i.v. to control rats. After 7 days, kidney function was assessed through measurement of creatinine (CLcr) and urea clearances, as well as electrolyte concentrations in plasma. Blood and kidney were collected and assayed for CyA. Sandimmune administration led to decreased CLcr, and increased urea and potassium levels in plasma. In contrast, functional nephrotoxicity with the PM-CyA was not apparent, as the CLcr did not change significantly. The rate of increase in body weight in control rats was 3.1-3.4% per day. Weight gains (1.8% per day) were also noted in the rats given PM-CyA, although the body weight of animals receiving Sandimmune remained constant. Compared to Sandimmune, polymeric micelles reduced kidney uptake of CyA by 2.6-fold, and increased CyA levels in blood by 2.1-fold. The results show a potential for PEO-b-PCL micelles in restricting the nephrotoxicity of CyA.


Mammary ovarian metastases with stroma cell hyperplasia and postmenopausal virilization.
The case of a 57-year-old woman with a history of breast cancer is reported. She presented 10 years later with virilization. Stroma cell hyperplasia was present in the metastatic ovaries. The authors describe hormonal data and discuss the pathogenesis of the stromal activity. Mammary ovarian metastases associated with stroma cell hyperplasia, in the absence of pregnancy, that cause virilization are rare.


A novel benzamide derivative protects ligature-induced alveolar bone erosion by inhibiting NFATc1-mediated osteoclastogenesis.
Since elevated osteoclast formation and/or activity by inhibitory responses against pathogens leads to diverse osteolytic bone diseases including periodontitis, inhibition of osteoclast differentiation and bone resorption has been a primary therapeutic strategy. In this study, we investigated the therapeutic potential of a novel benzamide-linked molecule, OCLI-070, for preventing alveolar bone loss in mice with ligature-induced experimental periodontitis. OCLI-070 inhibited osteoclast formation by acting on both early and late stages of differentiation, and attenuated the induction of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and the expression of osteoclast-specific genes. In addition, OCLI-070 significantly suppressed the formation of actin rings and resorption pits. Analysis of the inhibitory action of OCLI-070 showed that it markedly suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced extracellular signal-regulated kinase (ERK) and NF-κB signaling cascades. Moreover, OCLI-070 prevented ligature-induced alveolar bone erosion in mice by suppressing osteoclast formation. These findings demonstrate that OCLI-070 attenuated osteoclast differentiation and function as well as ligature-induced bone erosion by inhibiting RANKL-mediated ERK and NF-κB signaling pathways.


Multimodal Management of a Ruptured Right Medial Parietal Arteriovenous Malformation: 2-Dimensional Operative Video.
Arteriovenous malformations (AVM) of the medial surface of the cerebral hemispheres are challenging because of the limited access to the interhemispheric fissure, the presence of the bridging veins, and the difficult control of arterial feeders and deep venous drainage. We present a 20-yr-old patient with a grade 3 Spetzler Martin ruptured right medial parietal AVM revealed by headaches, left hemiparesis, and ataxia. We highlight the importance of a detailed and selective study of AVM angioarchitecture with new sequences as XperCT (Philips Medical) viewing which permits a better understanding of the anatomy and pathology and a better therapeutical planning. Selective embolization of arterial feeders with Glubran2 (GEM) allows a better control of selected sectors of the AVM which may be difficult to access at surgery. This type of planning is especially important when the AVM is in close relationship with an important sulcus, as was the case of this patient whose AVM was adherent to the postcentral sulcus. We present the surgical nuances concerning patient positioning, craniotomy, AVM dissection, and resection. Early identification and interruption of the main arterial feeders facilitate further dissection. We discuss the timing of deep venous drainage interruption in AVMs with mixed superficial and deep venous drainage. The postoperative course was favorable and the postoperative angiogram showed complete resection of the AVM. At the last follow-up, the patient had only slight left ataxia. Multimodal management with planned selective embolization may facilitate microsurgical resection of AVMs. Given the retrospective nature of this report, informed consent was not required.


[The effect of intrapleural pingyangmycin administration on activity of fibrinolytic system and transforming growth factor-beta1 in malignant pleural effusion].
To observe the changes of the concentrations of plasminogen activator inhibitor-1(PAI-1), tissue-type plasminogen activator(t-PA), transforming growth factor-beta(1)(TGF-beta(1)) in peripheral blood and pleural effusion before and after intrapleural pingyangmycin administration, and therefore to investigate the mechanism by which pingyangmycin produces pleurodesis. Since February to September 2008, a total of 26 patients with malignant pleural effusion (MPE) underwent intrapleural pingyangmycin administration. The concentrations of PAI-1, t-PA, TGF-beta(1) and the number of leucocytes in peripheral blood and pleural effusion before and after treatment were detected. The pleurodesis efficacy according to WHO standard was evaluated 1 month later. Patients who showed complete disappearance of pleural effusion lasting more than 1 month and reduction of pleural effusion more than 50% were classified as the effective group, while the others were classified as the failure group. One month after intrapleural pingyangmycin administration, the total response rate of MPE control was 57.7% (effective group = 15 cases). The number of leucocytes and neutrophils in peripheral blood were significantly higher after intrapleural pingyangmycin administration [the number of leucocytes: effective group (9.2 +/- 2.0) x 10(9)/L, failure group (9.4 +/- 3.8) x 10(9)/L; neutrophil count: effective group (7.9 +/- 2.1) x 10(9)/L, failure group (8.1 +/- 3.3) x 10(9)/L] than in those before[the number of leucocytes: effective group (6.6 +/- 1.4) x 10(9)/L, failure group (5.6 +/- 0.9) x 10(9)/L; neutrophil count: effective group (4.5 +/- 1.3) x 10(9)/L, failure group (4.2 +/- 1.0) x 10(9)/L. F = 30.80, 46.08 respectively, all P < 0.01]. However, the concentrations of PAI-1, t-PA and TGF-beta(1) in the peripheral blood showed no significant difference before and after treatment(P > 0.05). The concentrations of PAI-1 were significantly lower in the pleural effusion before treatment [effective group (1054 +/- 1039) microg/L, failure group (1027 +/- 955) microg/L] than after treatment [24 h after intrapleural pingyangmycin administration: effective group (2195 +/- 861) microg/L, failure group (1099 +/- 568) microg/L]; 72 h after treatment: effective group (1688 +/- 703) microg/L, failure group (1383 +/- 797) microg/L(F = 6.29, P = 0.01). The levels of t-PA were significantly higher in the pleural effusion before treatment [the effective group (42 +/- 33) microg/L, failure group (54 +/- 25) microg/L] than after treatment[24 h after intrapleural pingyangmycin administration: the effective group (49 +/- 49) microg/L, failure group (53 +/- 40) microg/L; 72 h after treatment: the effective group (17 +/- 20) microg/L, failure group (28 +/- 22) microg/L (F = 19.85, P < 0.01). The levels of TGF-beta(1) in the pleural effusion showed no significant difference before and after treatment (P > 0.05). The number of leucocytes in pleural effusion was significantly higher after intrapleural pingyangmycin administration [the effective group (4.7 +/- 4.7) x 10(9)/L, failure group (2.1 +/- 1.4) x 10(9)/L] than before [the effective group (2.3 +/- 1.9) x 10(9)/L, failure group (1.0 +/- 0.9) x 10(9)/L. F = 8.05, P < 0.01]. The number of leucocytes, neutrophils and the concentrations of PAI-1, t-PA, TGF-beta(1) in the peripheral blood showed no significant difference between the effective group and the failure group before and after treatment (P > 0.05). However, the concentrations of PAI-1 in pleural effusion after treatment were higher in the effective group than in the failure group (F = 8.51, P < 0.01). Intrapleural pingyangmycin administration is a safe and effective treatment for MPE. The mechanism of pleurodesis is related to inhibiting the activity of plasminogen in the pleural cavity.


Preventing Violent Extremism and Social Work: Recent US History and Prospects.
Anti-immigrant, anti-Semitic, and anti-Muslim violent extremism is on the rise in Western nations while jihadist terrorism continues throughout the Middle East and Africa. Despite significant efforts by governmental, non-governmental, and civic society organizations to address violent extremism, little progress has been made to prevent it. White supremacist organizations are now organizing globally through a variety of next generation communication networks using techniques developed by ISIS and Al-Qaeda. Throughout, relatively few social work academics have engaged in preventing violent extremism (PVE) scholarship. Though the profession is referenced frequently in the PVE literature, it is dominated by those in psychology and political science. Few articles in major social work journals have discussed social work's role or advanced PVE research. What has been published has mainly been critical of social work in this arena for legitimate fears of securitization, lack of resources/training, and the potential to discriminate against particular groups. The profession has a long history of impactful work in violence prevention in a myriad of practice areas. Given this wealth of experience and focus on social justice, social work should be a leader in this field. Areas of potential engagement in practice and research are discussed.


Male circumcision and human papillomavirus infection in men: a systematic review and meta-analysis.
We systematically reviewed the evidence for an association between male circumcision and Human Papillomavirus (HPV) infection and genital warts in men. PubMed and Embase were searched to 15 September 2010. The measure of effect was the adjusted odds ratio (OR) or rate ratio (RR) when present and the crude estimate otherwise. Random effects meta-analyses were used to calculate summary measures of effect. We identified 23 papers about the association between circumcision and HPV DNA. Circumcised men were less likely to have prevalent genital HPV infection than uncircumcised men (summary OR, 0.57, 95% confidence interval [CI], 0.45-0.71) with between-study heterogeneity (P-heterogeneity = 0.006; I(2) = 50.5%; 19 studies). Similar summary associations were seen in clinical and methodological subgroups. The effect of circumcision was stronger at the glans/corona (OR, 0.47; 95% CI, 0.37-0.60) and urethra (OR, 0.35; 95% CI, 0.12-1.05) compared with sites more distal to the foreskin. There was weak evidence that circumcision was associated with decreased HPV incidence (summary RR, 0.75, 95% CI, 0.57-0.99; 3 studies) and increased HPV clearance (summary RR, 1.33; 95% CI, 0.89-1.98; 3 studies) but no evidence of an association with prevalent genital warts (OR, 0.93, 95% CI, 0.65-1.33; 15 studies). Several countries are expanding access to voluntary medical male circumcision to reduce HIV prevalence. This could provide additional benefit in reducing HPV prevalence.


Drug concentration monitoring with tolerability and efficacy assessments during open-label, long-term sertraline treatment of children and adolescents.
The aim of this study was to evaluate the long-term pharmacokinetics, safety, and efficacy of sertraline in children and adolescents with obsessive-compulsive disorder (OCD) or major depressive disorder (MDD). After 42-day initial treatment and 9-day withdrawal phases, children (6-12 years, n = 16) and adolescents (13-18 years, n = 27) entered a 24-week open-label phase, with sertraline titrated to 200 mg/day. Blood samples for plasma sertraline and N-desmethylsertraline levels were taken at the beginning of the 24-week phase and at weeks 1, 4, 8, 12, and 24. Efficacy and safety data were also collected. Mean maximum daily dose at endpoint was 157 +/- 49 mg. For female and male children, mean sertraline/N-desmethylsertraline concentrations normalized to a 200-mg dose were 85.0/160 ng/mL (n = 8) and 79.3/134 ng/mL (n = 8), respectively, and for female and male adolescents, 70.5/109 ng/mL (n = 16) and 76.3/120 ng/mL (n = 8). No significant age or gender effects or age-by-gender interactions were observed in sertraline values. Mean sertraline plasma concentrations normalized for dose and body weight did not differ significantly by age or gender. Three (3) patients (7%) discontinued owing to adverse events. In patients with OCD (n = 10), improvements were observed in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) (p = 0.029) and National Institute of Mental Health (NIMH) Global Obsessive Compulsive Scale (OCS) (p = 0.01). In MDD patients (n = 32), Clinical Global Impression (CGI) Severity (p = 0.002) and Improvement (p = 0.011) improved. Long-term treatment of MDD and OCD with sertraline up to 200 mg/day in children and adolescents results in dose-normalized plasma concentrations comparable to those seen in adults. Sertraline was generally well tolerated, and patients demonstrated clinical improvement over 24 weeks of treatment.


Concomitant acute sinusitis and acute lung rejection.
Two lung transplant recipients had concomitant acute sinusitis and acute lung rejection. Antibiotics and decongestants alleviated the sinusitis, but the symptoms of cough and dyspnea as well as spirometric defects necessitated treatment of acute lung rejection. In patients with clinical evidence of acute sinusitis after lung transplantation, concomitant acute lung rejection should be suspected if dyspnea or pulmonary dysfunction is also present. This appears to be the first report of concomitant acute sinusitis and acute lung rejection.


Do food web models reproduce the structure of mutualistic networks?
Simple models inspired by processes shaping consumer-resource interactions have helped to establish the primary processes underlying the organization of food webs, networks of trophic interactions among species. Because other ecological interactions such as mutualisms between plants and their pollinators and seed dispersers are inherently based in consumer-resource relationships we hypothesize that processes shaping food webs should organize mutualistic relationships as well. We used a likelihood-based model selection approach to compare the performance of food web models and that of a model designed for mutualisms, in reproducing the structure of networks depicting mutualistic relationships. Our results show that these food web models are able to reproduce the structure of most of the mutualistic networks and even the simplest among the food web models, the cascade model, often reproduce overall structural properties of real mutualistic networks. Based on our results we hypothesize that processes leading to feeding hierarchy, which is a characteristic shared by all food web models, might be a fundamental aspect in the assembly of mutualisms. These findings suggest that similar underlying ecological processes might be important in organizing different types of interactions.


Ramachandran plot on the web.
A graphics package has been developed to display the main chain torsion angles phi, psi (phi, Psi); (Ramachandran angles) in a protein of known structure. In addition, the package calculates the Ramachandran angles at the central residue in the stretch of three amino acids having specified the flanking residue types. The package displays the Ramachandran angles along with a detailed analysis output. This software is incorporated with all the protein structures available in the Protein Databank.


Nanowire piezo-phototronic photodetector: theory and experimental design.
The piezo-phototronic effect is about the use of the inner crystal piezoelectric potential to tune/control charge carrier generation, separation, transport and/or recombination in optoelectronic devices. In this paper, a theoretical model for describing the characteristics of a metal-nanowire-metal structured piezo-phototronic photodetector is constructed. Numerical simulations fit well to the experimental results of a CdS and ZnO nanowire based visible and UV detector, respectively.


Stem cell-coated titanium implants for the partial joint resurfacing of the knee.
The goal of the present study was to evaluate the partial surface replacement of the knee with stem cell-coated titanium implants and to provide a basis for a successful treatment of large osteochondral defects. Mesenchymal stem cells (MSCs) were isolated from bone marrow aspirates of adult sheep. Round titanium implants with a diameter of 2 x 7.3 mm were seeded with autologous MSC and inserted into an osteochondral defect in the medial femoral condyle. As controls, defects received either an uncoated implant or were left untreated. Nine animals with 18 defects were sacrificed after 6 months. Histological evaluation was performed by intravital polychrome fluorescent labelling, intravital perfusion with Indian ink, microradiographs and differential staining with toluidine blue. The quality of regenerated cartilage was assessed by in situ hybridization of collagen type II and immunohistochemistry of collagen types I and II. In 50% of the cases, defects treated with MSC-coated implants showed a complete regeneration of the subchondral bone layer. In these cases collagen type II and only traces of collagen type I were detected. A high level of collagen type II mRNA expression compared to articular cartilage indicates regenerating hyaline-like cartilage. A total of 50% of MSC-coated and uncoated implants failed to osseointegrate and formation of fibrocartilage was observed. Untreated defects as well as defects treated with uncoated implants demonstrated incomplete healing of subchondral bone and formation of fibrous cartilage. A modified histological score according to Wakitani significantly demonstrated better results for cell-coated implants (8.8+/-6.4) than for uncoated implants (5.5+/-3.9) and for untreated defects (2.8+/-2.5). Our results demonstrate that, in a significant number of cases, a partial joint resurfacing of the knee with stem cell-coated titanium implants occur. A slow bone and cartilage regeneration and an incomplete healing in half of the MSC-coated implants are limitations of the presented method. To improve our approach and optimize the experimental parameters, further investigations are needed prior to clinical application.


Hepatitis C virus core protein stimulates fibrogenesis in hepatic stellate cells involving the obese receptor.
Hepatitis C virus core protein (HCVcp), which is secreted by infected cells, is reported as an immunomodulator in immune cells. However, the effects of HCVcp on hepatic stellate cells (HSCs), the key cells in liver fibrosis, still remain unclear. In this study, we investigated the effects of HCVcp on obese receptor (ObR) related downstream signaling pathways and fibrogenic gene expression in HSCs. LX-2, a human HSC line, was incubated with HCVcp. Inhibitors and short interfering RNAs were used to interrogate the mechanisms of HCVcp action on HSCs. HCVcp (20-100 ng/ml) concentration-dependently stimulated α-smooth muscle actin (α-SMA) protein expression and mRNA expression of α-SMA, procollagen α2(I) and TGF-β1 genes, with a plateau of 220% of controls at 100 ng/ml. HCVcp induced mRNA and protein expression of ObR. Blocking of Ob-Rb with a neutralizing antibody inhibited phosphorylation of signal transducer and activator of transcription 3 (STAT3) and AMPKα stimulated by HCVcp. Furthermore, knockdown of Ob-Rb down-regulated HCVcp-induced STAT3, AKT, and AMPKα phosphorylation, and reversed HCVcp-suppressed mRNA expression of matrix metalloproteinase (MMP)-1, peroxisome proliferator-activated receptor (PPAR)γ and sterol regulatory element binding protein-1c (SREBP-1c) genes. AMPKα signaling blockade reversed HCVcp-suppressed SREBP-1c mRNA expression. HCVcp stimulated reactive oxygen species formation and gp91(phox) (a component of NADPH oxidase) protein expression, together with AKT phosphorylation, leading to suppression of PPARγ and SREBP-1c genes. Our results provide a new finding that HCVcp induced ObR-dependent Janus Kinase (JAK) 2-STAT3, AMPKα, and AKT signaling pathways and modulated downstream fibrogenetic gene expression in HSCs.


Nonparametric meta-analysis for single-case research: Confidence intervals for combined effect sizes.
In this article we present a nonparametric technique for meta-analyzing randomized single-case experiments by using inverted randomization tests to calculate nonparametric confidence intervals for combined effect sizes (CICES). Over the years, several proposals for single-case meta-analysis have been made, but most of these proposals assume either specific population characteristics (e.g., heterogeneity of variances or normality) or independent observations. However, such assumptions are seldom plausible in single-case research. The CICES technique does not require such assumptions, but only assumes that the combined effect size of multiple randomized single-case experiments can be modeled as a constant difference in the phase means. CICES can be used to synthesize the results from various single-case alternation designs, single-case phase designs, or a combination of the two. Furthermore, the technique can be used with different standardized or unstandardized effect size measures. In this article, we explain the rationale behind the CICES technique and provide illustrations with empirical as well as hypothetical datasets. In addition, we discuss the strengths and weaknesses of this technique and offer some possibilities for future research. We have implemented the CICES technique for single-case meta-analysis in a freely available R function.


A protease-resistant prion protein isoform is present in urine of animals and humans affected with prion diseases.
Prion protein (PrP)(Sc), the only known component of the prion, is present mostly in the brains of animals and humans affected with prion diseases. We now show that a protease-resistant PrP isoform can also be detected in the urine of hamsters, cattle, and humans suffering from transmissible spongiform encephalopathies. Most important, this PrP isoform (UPrP(Sc)) was also found in the urine of hamsters inoculated with prions long before the appearance of clinical signs. Interestingly, intracerebrally inoculation of hamsters with UPrP(Sc) did not cause clinical signs of prion disease even after 270 days, suggesting it differs in its pathogenic properties from brain PrP(Sc). We propose that the detection of UPrP(Sc) can be used to diagnose humans and animals incubating prion diseases, as well as to increase our understanding on the metabolism of PrP(Sc) in vivo.


Composition and Antimicrobial Activity of Euphrasia rostkoviana Hayne Essential Oil.
Eyebright, Euphrasia rostkoviana Hayne (Scrophulariaceae), is a medicinal plant traditionally used in Europe for the treatment of various health disorders, especially as eyewash to treat eye ailments such as conjunctivitis and blepharitis that can be associated with bacterial infections. Some Euphrasia species have been previously reported to contain essential oil. However, the composition and bioactivity of E. rostkoviana oil are unknown. Therefore, in this study, we investigated the chemical composition and antimicrobial activity of the eyebright essential oil against some organisms associated with eye infections: Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, and Candida albicans. GC-MS analysis revealed more than 70 constituents, with n-hexadecanoic acid (18.47%) as the main constituent followed by thymol (7.97%), myristic acid (4.71%), linalool (4.65%), and anethole (4.09%). The essential oil showed antimicrobial effect against all organisms tested with the exception of P. aeruginosa. The best activity was observed against all Gram-positive bacteria tested with the minimum inhibitory concentrations of 512 µg/mL. This is the first report on the chemical composition of E. rostkoviana essential oil and its antimicrobial activity.


A measure of engagement for children with intellectual disabilities in early childhood settings: a preliminary study.
The purpose of this study was to develop a measure of engagement that could be used in practice with children with disabilities, including children with severe intellectual disabilities. The Individual Child Engagement Record (ICER) was designed to observe and record the engagement of individual children in order to identify optimal programs for them. Using the measure, 5 children with mild to severe disabilities were observed in an inclusive childcare setting across 4 types of ongoing activities: routine, one-to-one instruction, planned, and child-initiated. Generally, the children were better engaged in routine activities. The lowest level of engagement was found for planned activities. There were, however, differences across children with regard to the relative value of the different types of activities in promoting engagement. The measure allowed for the identification of activities that would provide better learning opportunities for children with significant disabilities.


[Quantitative analysis of resveratrol from grape seeds and grape skins by high performance liquid chromatography method].
In order to perform a quantitative analysis of resveratrol from grape seeds, grape skins and waste residue of grape winery, acetonitrile-water (26:74) was applied as the fluxion phase. The detective wave-length (lambda) was 303 nm. Colume temperature was 35 degrees C. The type of chrimato pattern colume was SupelcosiLTMLC-18 (250 mm x 4.6 mm, 5 microns). Results showed that the contents of resveratrol from grape skins were higher than those of grape seeds. Among different kinds of grape skins, resveratrol contents varied. The reserveratrol content of Suo Suo grape skin was the lowest (0.9850 microgram/g). Among the same kinds of grape skins from the same production area, the resveratrol content was highest in the skin of waste residue of grape winery followed by the fresh grape skin and the old grape skin ranked thirdly, and the differences of resveratrol contents were statistically significant.


Single tertiary cancer center experience on the management of pT3b prostate cancer after robotic-assisted laparoscopic prostatectomy.
Pathological involvement of the seminal vesicle poses a treatment dilemma following robotic prostatectomy. Margin status plays an important role in deciding further management. A wide range of treatment options are available, including active monitoring, adjuvant radiotherapy, salvage radiotherapy, and occasionally androgen deprivation therapy. Patients undergoing postoperative radiotherapy tend to have higher risk of urinary and bowel morbidities. The recent RADICALS-RT concluded that adjuvant radiotherapy did not have any benefit compared with salvage radiotherapy. We aim to audit the incidence, margin status, and management of T3b cancer cases at our center. A retrospective analysis was conducted of all patients diagnosed with pathological T3b (pT3b) prostate cancer following robotic-assisted laparoscopic prostatectomy from January 2012 to July 2020. Preoperative parameters analyzed included prostate-specific antigen (PSA), T stage, and age. A chi-square test and 2-tailed t test were used to determine the relationship between categorical and continuous variables, respectively. Kaplan-Meier survival curves were generated to assess overall survival in patients with pT3b prostate cancer and used to compare unadjusted progression-free survival among those who underwent adjuvant and salvage radiotherapy. A total of 83 (5%) of 1665 patients who underwent robotic prostatectomy were diagnosed with pT3b prostate cancer between January 2012 and July 2020. Among these, 36 patients (44%) did not receive any radiotherapy during follow-up, compared with 26 patients (31%) who received adjuvant radiotherapy and 21 (25%) who received salvage radiotherapy. The median age of our cohort was 64 (SD, 6.4) years. Mean PSA at presentation was 12.7 μg/L. Positive margins were seen in 36 patients (43%); however, there was no statistically significant difference between treatment groups (p = 0.49). The median overall survival was 96%. There was no significant difference between the adjuvant and salvage groups in terms of biochemical progression-free survival (p = 0.66). Five-year biochemical progression-free survival was 94% for those in the adjuvant radiotherapy group and 97% for those in the salvage radiotherapy group. Our audit corroborates with the recently concluded RADICALS-RT study, although we had fewer patients with positive margins. Radiotherapy can be avoided in patients with T3b prostate cancer, even if margin is positive, until there is definitive evidence of PSA recurrence. In keeping with the conclusion of RADICALS-RT, salvage radiotherapy may be preferable to adjuvant radiotherapy.


[The effect of the delta-sleep peptide on the adrenaline level in rat tissues under normal conditions and during cold stress].
Adrenalin content in the brain, liver and adrenal glands under the effect of cold stress grows by 314, 500 and 56% as compared to the control. A single administration of the delta-sleep inducing peptide (DSIP) in a dose of 12 microgram/100 g to intact animals makes the adrenalin content in the brain higher 1, 3, 6 and 24h after administration; two and three days later the adrenalin content in the brain does not change. The amount of adrenalin in the liver of the same animals increases 1, 3, 6 h and 1, 2, 3 days after DSIP administration. Intraperitoneal administration of DSIP induces an increase of the adrenalin level in the adrenal glands of rats an hour and a day after administration. Two days later the level of adrenaline decreases by 41%; 3, 6 h and 3 days after DSIP administration the content of adrenaline remains unchanged. As a result of the DSIP administration in a dose of 12 micrograms/100 g to the animals in the state of cold stress, the content of adrenalin increases in the rat brain by 129, in the liver--by 300, adrenal glands--by 44% as compared with the control.


Hybrid Fo complexes of the ATP synthases of spinach chloroplasts and Escherichia coli. Immunoprecipitation and mutant analyses.
Hybrid Fo complexes of the ATP synthases of spinach chloroplast (CFo) and Escherichia coli (EFo) were investigated. Immunoprecipitations with polyclonal antibodies against the different Fo subunits clearly revealed that hybrid Fo complexes derived from CFo subunit III and EFo subunits a and b were formed in vivo. In addition, the ATPase activities of the hybrid ATP synthase, measured in everted cytoplasmic membranes of an atpE mutant strain transformed with the atpH gene coding for CFo III, were comparable to activities obtained for the same mutant strain complemented with the atpE gene (EFo c). Nevertheless, CFo III was not able to replace EFo c functionally, since the strain containing the hybrid ATP synthase was not able to grow on succinate. In order to investigate the reason for this lack of function, hybrid proteolipids of CFo III and EFo c were constructed. Only a chimaeric protein comprising the seven N-terminal amino acid residues from CFo III and the remaining part of EFo c was able to replace wild-type EFo c, whereas hybrid proteins with 13 and 33 N-terminal amino acids of CFo III were not functional. The results suggested that a network of interactions between the subunits essential for proton translocation and/or coupling of the F1 part exists, which was optimized for each species during evolution, although the overall structure of FoF1 complexes has been conserved.


High-resolution spatial analysis of slow wave initiation and conduction in porcine gastric dysrhythmia.
The significance of gastric dysrhythmias remains uncertain. Progress requires a better understanding of dysrhythmic behaviors, including the slow wave patterns that accompany or promote them. The aim of this study was to use high-resolution spatiotemporal mapping to characterize and quantify the initiation and conduction of porcine gastric dysrhythmias. High-resolution mapping was performed on healthy fasted weaner pigs under general anesthesia. Recordings were made from the gastric serosa using flexible arrays (160-192 electrodes; 7.6mm spacing). Dysrhythmias were observed to occur in 14 of 97 individual recordings (from 8 of 16 pigs), and these events were characterized, quantified and classified using isochronal mapping and animation. All observed dysrhythmias originated in the corpus and fundus. The range of dysrhythmias included incomplete conduction block (n=3 pigs; 3.9±0.5cpm; normal range: 3.2±0.2cpm) complete conduction block (n=3; 3.7±0.4cpm), escape rhythm (n=5; 2.0±0.3cpm), competing ectopic pacemakers (n=5, 3.7±0.1cpm) and functional re-entry (n=3, 4.1±0.4cpm). Incomplete conduction block was observed to self-perpetuate due to retrograde propagation of wave fragments. Functional re-entry occurred in the corpus around a line of unidirectional block. 'Double potentials' were observed in electrograms at sites of re-entry and at wave collisions. Intraoperative multi-electrode mapping of fasted weaner healthy pigs detected dysrhythmias in 15% of recordings (from 50% of animals), including patterns not previously reported. The techniques and findings described here offer new opportunities to understand the nature of human gastric dysrhythmias.


Inverted gull-wing hinge decompressive craniotomy for infantile acute subdural hematoma: A case report.
Infantile severe acute subdural hematomas (ASDHs) usually require a decompressive craniotomy. However, these infantile patients often suffer surgical site infection and aseptic bone-flap resorption after external decompression. In this report, we showed a case of a simplified hinge decompressive craniotomy in an infant with severe ASDH. A 2-month-old girl suffered from status epilepticus, impaired consciousness, multiple rib fractures, bilateral fundus hemorrhage, and a right ASDH. We performed a simplified hinge decompressive craniotomy, making a vascularized bone flap with a hinge using the partial temporal bone and temporal muscle and not fixing the bone flap like an inverted gull wing. Cranioplasty was performed 4 weeks after the decompression craniotomy with replaced resorbable substitute dura. Six months after the transfer, her development was generally in line with her age. The decompressive craniotomy with an inverted gull-wing hinge has shown a good outcome.


Two new species of Ophrynopus Konow, 1897 (Hymenoptera: Orussidae), with a new definition of the genus.
Two species of Orussidae are described: Ophrynopus rufocephalus new species and Ophrynopus savinai new species. The new taxa are analyzed with an existing data set for the Orussidae of the world. The results of the analyses indicate that the generic classification within the ophrynopine clade needs to be adjusted. Argentophrynopus Vilhelmsen D.R. Smith, 2002 new synonym and Ophrella Middlekauff, 1985 new synonym are treated as junior synonyms of Ophrynopus Konow, 1897. This results in the following additional taxonomic changes: Ophrynopus amazonicus (Westwood, 1874) combination reestablished, Ophrynopus eldorado (Vilhelmsen, 2013) new combination, Ophrynopus enigmus (Vilhelmsen D.R. Smith, 2002) new combination, Ophrynopus gauldi (Vilhelmsen D.R. Smith, 2002) new combination, Ophrynopus seagi (Vilhelmsen, 2016) new combination. Furthermore, Ophrynopus andrei Konow, 1897 new synonym is regarded as a junior synonym of Ophrynopus fulvostigma (Westwood, 1874). A revised key to Ophrynopus spp. is presented.


[Assessment of VEGF and VEGF receptor concentrations in patients with benign and malignant thyroid tumors].
Neoangiogenesis is a significant event in a cascade of growth and progression of solid tumors. Assessment of the tissue expression and measurement of the concentrations of angiogenic and antiangiogenic factors, contributing to this process, in body fluids, can be used not only for an early diagnosis of tumors and their staging but also as an important parameter of treatment efficiency evaluation. The aim of this study is to evaluate the concentrations of crucial angiogenic cytokine VEGF and its soluble receptors in peripheral blood of patients with benign and malignant thyroid tumors. The study comprised 35 patients with thyroid cancer and 10 patients with follicular neoplasm, both diagnosed by means of ultrasound-guided fine-needle aspiration biopsy. For these patients surgical treatment was instituted. The examined angiogenic factors were determined preoperatively and 4 weeks after the surgical procedures. The results were compared with the control group which comprised 10 healthy individuals. Analysing obtained results, we demonstrated high VEGF concentrations and low soluble VEGF receptor concentrations in patients with benign and malignant thyroid tumors. This fact confirms a vital role of VEGF in angiogenesis of thyroid tumors and a hypothetical antiangiogenic activity of its soluble receptors. Disequilibrium of the above-mentioned angiogenic factor concentrations is probably essential for the growth and progression of benign and malignant thyroid tumors.


Acoustic Emissions in 3D Printed Parts under Mode I Delamination Test.
This paper applies an innovative approach based on the acoustic emission technique to monitor the delamination process of 3D parts. Fused deposition modelling (FDM) is currently one of the most widespread techniques for additive manufacturing of a solid object from a computer model. Fundamentally, this process is based on a layer-by-layer deposition of a fused filament. The FDM technique has evolved to the point where it can now be proposed, not only as a prototyping technique, but also as one applicable to direct manufacturing. Nonetheless, a deeper comprehension of mechanical behavior and its dependence on process parameters must include the determination of material properties as a function of the service load. In this work, the effects of extrusion temperature on inter-layer cohesion are studied using a method employing a double cantilever beam (DCB). The ASTM D5528 standard was used to determine the delamination energy, GI. In addition, the acoustic emission technique was employed to follow the delamination process during testing. Finally, a Charge-Coupled Device (CCD) camera and a calibrated grid was employed to evaluate crack propagation during testing.


Amiodarone pulmonary toxicity: CT findings in symptomatic patients.
The computed tomographic (CT) chest scans of 11 patients who developed respiratory or constitutional symptoms while receiving amiodarone therapy were reviewed. CT findings indicative of significant amiodarone exposure included (a) high-attenuation parenchymal-pleural lesions in eight of the 11 patients (73%), and (b) increased liver and/or spleen attenuation in 10 of the 11 patients (91%). Nonspecific pulmonary infiltrates were identified in nine of the 11 patients (82%). Four patients had interstitial infiltrates, four had mixed alveolar and interstitial disease, and one had a conglomerate mass. CT findings of high-attenuation parenchymal-pleural abnormalities are thought to be related to the iodinated chemistry of the drug and its prolonged half-life within the lung. These unique properties of the drug and the use of CT to discriminate attenuation levels provide a means of identifying patients with significant pulmonary accumulation of amiodarone.


[Study on spatial clustering characteristics of tuberculosis in China, 2013-2018].
Objective: To explore the tuberculosis (TB) clustering areas and changing tendency in China from 2013 to 2018, so as to provide evidence for improving the control and prevention programs on TB. Methods: Spatial distribution of TB in China from 2013 to 2018 was studied using data from TB information management system of Chinese disease prevention and control information system. The SaTScan 9.6 software was used to detect and analyze the TB clusters and relative risks. Likelihood ratio and P value under the scan windows were used as the main index to define the clusters. Results: The TB registration rate declined in China from 2013 to 2018. High-risk clusters were mainly located in western regions of Xinjiang, Tibet, Shaanxi, Sichuan, Chongqing, Yunnan, Guizhou, Guangxi provinces and central and eastern regions of Inner Mongolia, Hubei, Hunan, Jiangxi, Guangdong and Hainan provinces. The number of counties with TB clusters declined slowly, from 1 112 in 2013 to 806 in 2018. In comparison with areas other than the clusters, the RR of TB in the clusters remained at high levels in southern Xinjiang and western Tibet from 2013 to 2018 (RR>3.0). Conclusions: The number of the counties with TB clustering declined slowly from 2013 to 2018, and most of them were located in western and central China. Early detection and health education should be focused on TB patients to prevent the spread of TB. Management programs set for TB patients should be strengthened, especially in the western parts of the country where TB clusters and high relative risks existed.


Early childhood externalising behaviour problems: child, parenting, and family-related predictors over time.
This study examined the dynamic relationships between child, parenting, and family-related predictor variables and early childhood externalising behaviour problems. A community sample of 395 Australian children was followed longitudinally, and assessed at 4 and 6 years with the Child Behavior Checklist, Teacher Report Form, and standard measures of parenting, temperament, and familial adversity. Variables based on the average scores across the two assessments and the change in scores between assessments were utilised as predictors of parent-reported and teacher-reported externalising behaviour problems at age 6. It was hypothesised that both higher average scores and more detrimental changes in scores, would independently predict externalising problems at age 6. Multivariable analyses found that the presence of parent-reported child externalising problems in six-year-olds were predicted by: (i) the presence of parent-reported child externalising problems at age 4, (ii) higher average "teacher-reported child externalising behaviour," "inflexible temperament," "non-persistent temperament," and "over-reactive parenting," and (iii) an increased "inflexible temperament" score between age 4 and age 6. The presence of teacher-reported child externalising problems at age 6 was predicted by higher average "parent-reported child externalising behaviour," and "over-reactive parenting." The results provide further evidence of the adverse impact of continuing high levels of temperament difficulties and over-reactive parenting on externalising behaviour in early childhood. However, contrary to expectations, the contribution of including the dynamic change scores was limited.


Triptolide induces adverse effect on reproductive parameters of female Sprague-Dawley rats.
The aim of this study was to investigate the adverse effects of triptolide, a diterpenoid triepoxid and a major active component isolated from Triptergium wilfordii Hook.f (TWHF), on various reproductive parameters of female Sprague-Dawley (SD) rats. Female SD rats were treated with triptolide by oral administration (gastric infusion; 0, 100, 200, and 400 μg/kg) once-daily for 90 days. During the experimental period, vaginal smears were taken to monitor the estrous phase for the last 30 days. Relative ovary and uterus weights to body and histopathologically changes were determined on the last day. Serum levels of estradiol (E(2)), progesterone (P), follicle-stimulating hormone (FSH), and luteotropic hormone (LH) were assessed by enzyme immunoassay. ERα expression in the uterus and ovaries were analyzed from using immunohistochemical detection. The results showed that treatment with 200 and 400 ug/kg of triptolide significantly reduced serum levels of E(2) and P and increased levels of FSH and LH. At these dose levels, relative weights of ovary and uterus were significantly reduced. Qualitative histological analysis of the ovaries revealed a reduction in developing follicles and increase in atretic follicles in treated animals. Further, estrous cycles were prolonged significantly. The expression of ERα in ovaries and the uterus decreased in treated animals. These data suggest that triptolide had a direct effect on the ovaries, and the decrease in steroids elicited feedback on FSH and LH. Thus, reduced levels of E(2) and P may affect follicular development, estrous cycle, and expression of ERα.


[Cavernovenous leakage, a surgically treatable cause of erectile impotence].
In 17 of 33 patients with proven organic erectile impotence, caverno-venous leakage was determined by dynamic cavernosography in conjunction with high flow rates to induce and maintain artificial erection. The normal values of dynamic cavernosography in 12 healthy males are presented as well. Of these 17 patients 12 (aged 26-51 yr) underwent surgical ligation or resection of the deep dorsal vein of the penis and ligation of ectopic veins if present. Potency was restored immediately postoperatively in 8 of these 12 patients. In 2 of the other 4 operated patients cohabitation was possible again only with auto-injections of papaverine. The short-term results are presented.


Recovery from run training: efficacy of a carbohydrate-protein beverage?
Post-exercise nutrition is critical to facilitate recovery from training. To determine if added protein (P) or increased carbohydrate (CHO) differentially improves recovery, eight runners ingested: 6% CHO (CHO6), 8% CHO + 2% protein (CHO-P), and isocaloric 10% CHO (CHO10) following a 21-km run plus treadmill run to fatigue (RTF) at 90% VO2max. RTF was repeated after 2 h recovery. After 24 h, a 5 km time trial was performed. Insulin and blood glucose were higher (P < 0.05) following CHO10 compared to CHO-P and CHO6, but did not affect improvement from the first to second RTF (29.6% +/- 6, 40.5% +/- 8.8, 40.5% +/- 14.5) or 5 km time (1100 +/- 36.3, 1110 +/- 37.3, 1118 +/- 36.5 s). CK was not different, but perceived soreness with CHO-P (2.1 +/- 0.5) was lower than CHO10 (5.2 +/- 0.7). Additional calories from CHO or P above that provided in sports drinks does not improve subsequent performance after recovery; but less soreness suggests benefits with CHO-P.


The phenomenon of reversal of reticulum action potentials recorded from the body surface of sheep.
The experiments were carried out on sheep with reticulum fistula. The biopotentials and transformed mechanogram of the reticulum were recorded simultaneously on the body surface with an electrocardiograph. Lactic acid solution 1.6 mol/l was administered through the fistula into the reticulum in an amount of 15 mmol/kg of body weight. It was found that administration of this acid caused reversal of the biopotentials of the reticulum. This phenomenon lasted from 10 to several scores of hours and occurred with pH of reticulum contents below the normal range as well as after return of normal pH.