Neonatal patterns of breathing after cesarean section with or without epidural fentanyl.
The pattern of breathing and lung mechanics were evaluated during the first 7 h of life in full-term healthy newborns delivered by cesarean section with bupivacaine epidural anesthesia, without (group 1) or with the addition of 100 micrograms of fentanyl (group 2). Respiration and oxyhemoglobin saturation (SpO2) were measured with calibrated inductive plethysmography and pulse oximetry, respectively, and recorded from 60-420 min following birth. Compliance of respiratory system (CRS) was measured using a multiple occlusion technique at 60 and 420 min. Pattern of breathing was compared during period I (60-240 min) and II (240-420 min) with the following results: 1) the number of apnea spells was similar in both groups during both periods; 2) in both groups, from period I to period II a significant decrease in apnea duration was observed (7.6 +/- 0.7 s-4.1 +/- 0.5 s in group 1 and 6.7 +/- 1.2 s-5.1 +/- 1.0 s in group 2, respectively (P less than 0.05); 3) respiratory rate (RR) and minute ventilation (VE) were similar in both groups during both study periods; and 4) both RR and VE significantly decreased in the two groups from period I to period II (i.e., 59 +/- 5-46 +/- 2 breath per min-1 and 313 +/- 60-248 +/- 24 ml.kg-1.min-1 in group 1, and 60 +/- 2-51 +/- 1 breath.min-1 and 318 +/- 12-290 +/- 12 ml.kg-1.min-1 in group 2, respectively; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Studies of the cell surface of Paramecium. Ciliary membrane proteins and immobilization antigens.
We have developed a procedure to isolate the ciliary membranes of Paramecium and have analysed the membrane proteins by electrophoresis on polyacrylamide gels containing either Triton X-100 or sodium dodecyl sulphate. The electrophoretic pattern on gels containing sodium dodecyl sulphate showed 12-15 minor bands of mol.wt. 25 000-150 000 and on major band of mol.wt. 200 000-300 000 that contained approximately three-quarters of the total membrane protein. 2. We present evidence that the major membrane protein is related to, but not identical with, the immobilization antigen (i-antigen), which is a large (250 000 mol.w.), soluble, surface protein of Paramecium. The similarity of the i-antigen and the major membrane protein was shown by immunodiffusion and by the electrophoretic mobilities in sodium dodecyl sulphate of these two proteins from Paramecium of serotypes A and B. The non-identity of these two proteins was shown by their different electrophoretic mobilities on Triton X-100 containing gels and their different solubilities. 3. We propose that the major membrane protein and the i-antigen have a precursor-product relationship.


Hemodynamic effects of spiral ePTFE prosthesis compared with standard arteriovenous graft in a carotid to jugular vein porcine model.
The primary patency rate of arteriovenous (AV) grafts is limited by distal venous anastomosis stenosis or occlusion due to intimal hyperplasia associated with distal graft turbulence. The normal blood flow in native arteries is spiral laminar flow. Standard vascular grafts do not produce spiral laminar flow at the distal anastomosis. Vascular grafts which induce a spiral laminar flow distally result in lower turbulence, particularly near the vessel wall. This initial study compares the hemodynamic effects of a spiral flow-inducing graft and a standard graft in a new AV carotid to jugular vein crossover graft porcine model. Four spiral flow grafts and 4 control grafts were implanted from the carotid artery to the contralateral jugular vein in 4 pigs. Two animals were terminated after 48 hours and 2 at 14 days. Graft patency was assessed by selective catheter digital angiography, and the flow pattern was assessed by intraoperative flow probe and color Doppler ultrasound (CDU) measurements. The spiral grafts were also assessed at enhanced flow rates using an external roller pump to simulate increased flow rates that may occur during dialysis using a standard dialysis needle cannulation. The method increased the flow rate through the graft by 660 ml/min. The graft distal anastomotic appearances were evaluated by explant histopathology. All grafts were patent at explantation with no complications. All anastomoses were found to be wide open and showed no significant angiographic stenosis at the distal anastomosis in both spiral and control grafts. CDU examinations showed a spiral flow pattern in the spiral graft and double helix pattern in the control graft. No gross histopathological effects were seen in either spiral or control grafts. This porcine model is robust and allows hemodynamic flow assessment up to 14 days postimplantation. The spiral flow-inducing grafts produced and maintained spiral flow at baseline and enhanced flow rates during dialysis needle cannulation, whereas control grafts did not produce spiral flow through the distal anastomosis. There was no deleterious effect of the spiral flow-inducing graft on macroscopic and histological examination. The reducing effect of spiral flow on intima hyperplasia formation will be the subject of further study using the same AV graft model at a longer period of implantation.


Efficacy of Removing Bacteria and Organic Dirt from Hands-A Study Based on Bioluminescence Measurements for Evaluation of Hand Hygiene When Cooking.
The objective of this study was to evaluate the efficacy of dirt removal (bacteria and organic matter) of several hand-cleaning procedures. The results from the hand hygiene experiment indicated that washing hands with warm water and soap for 20 s is the most effective method investigated when hands are either dirty or greasy. Even if not proper washing, rinsing under running water for 5 s is a cleaning procedure that may significantly reduce the probability of cross-contamination, as it removes 90% of the hands' dirt. Although less effective than water and soap, the usage of antibacterial wipes was significantly more effective than wet wipes, indicating that they are a better choice when water and soap are not available. The results of this study enable us to inform consumers about the effectiveness of hand-cleaning procedures applied in their homes when cooking. Moreover, it can make consumers understand why, during the COVID-19 pandemic, authorities recommended washing hands as a preventive measure of infection and using an anti-bacterial hand gel or wiping hands with an antimicrobial wipe if water and soap are not available.


Folate hydrolase-1 (FOLH1) is a novel target for antibody-based brachytherapy in Merkel cell carcinoma.
Folate Hydrolase-1 (FOLH1; PSMA) is a type II transmembrane protein, luminally expressed by solid tumour neo-vasculature. Monoclonal antibody (mAb), J591, is a vehicle for mAb-based brachytherapy in FOLH1+ cancers. Brachytherapy is a form of radiotherapy that involves placing a radioactive material a short distance from the target tissue (e.g., on the skin or internally); brachytherapy is commonly accomplished with the use of catheters, needles, metal seeds and antibody or small peptide conjugates. Herein, FOLH1 expression in primary (p) and metastatic (m) Merkel cell carcinoma (MCC) is characterized to determine its targeting potential for J591-brachytherapy. Paraffin sections from pMCC and mMCC were evaluated by immunohistochemistry for FOLH1. Monte Carlo simulation was performed using the physical properties of conjugated radioisotope lutetium-177. Kaplan-Meier survival curves were calculated based on patient outcome data and FOLH1 expression. Eighty-one MCC tumours were evaluated. 67% (54/81) of all cases, 77% (24/31) pMCC and 60% (30/50) mMCC tumours were FOLH1+. Monte Carlo simulation showed highly localized ionizing tracks of electrons emitted from the targeted neo-vessel. 42% (34/81) of patients with FOLH1+/- MCC had available survival data f or analysis. No significant differences in our limited data set were detected based on FOLH1 status (p = 0.4718; p = 0.6470), staining intensity score (p = 0.6966; p = 0.9841) or by grouping staining intensity scores (- and + vs. ++, +++, +++) (p = 0.8022; p = 0.8496) for MCC-specific survival or recurrence free survival, respectively. We report the first evidence of prevalent FOLH1 expression within MCC-associated neo-vessels, in 60-77% of patients in a large MCC cohort. Given this data, and the need for alternatives to immune therapies it is appropriate to explore the safety and efficacy o f FOLH1-targeted brachytherapy for MCC.


SNAI1-mediated epithelial-mesenchymal transition confers chemoresistance and cellular plasticity by regulating genes involved in cell death and stem cell maintenance.
Tumor cells at the tumor margin lose epithelial properties and acquire features of mesenchymal cells, a process called epithelial-to-mesenchymal transition (EMT). Recently, features of EMT were shown to be linked to cells with tumor-founding capability, so-called cancer stem cells (CSCs). Inducers of the EMT include several transcription factors, such as Snail (SNAI1) and Slug (SNAI2), as well as the secreted transforming growth factor (TGFß). In the present study, we found that EMT induction in MCF10A cells by stably expressing SNAI1 contributed to drug resistance and acquisition of stem/progenitor-like character as shown by increased cell population for surface marker CD44(+)/CD24(-) and mammosphere forming capacity. Using a microarray approach, we demonstrate that SNAI1 overexpression results in a dramatic change in signaling pathways involved in the regulation of cell death and stem cell maintenance. We showed that NF-κB/MAPK signaling pathways are highly activated in MCF10A-SNAI1 cells by IL1ß stimulation, leading to the robust induction in IL6 and IL8. Furthermore, MCF10A-SNAI1 cells showed enhanced TCF/ß-catenin activity responding to the exogenous Wnt3a treatment. However, EMT-induced stem/progenitor cell activation process is tightly regulated in non-transformed MCF10A cells, as WNT5A and TGFB2 are strongly upregulated in MCF10A-SNAI1 cells antagonizing canonical Wnt pathway. In summary, our data provide new molecular findings how EMT contributes to the enhanced chemoresistance and the acquisition of stem/progenitor-like character by regulating signaling pathways.


A conservative management is preferable in milder forms of pituitary tumor apoplexy.
Our objective was to report a single-center experience of the management of pituitary tumor apoplexy. We retrospectively analyzed a series of 44 patients hospitalized for pituitary apoplexy between January 1996 and March 2008 at the Timone Hospital, Marseille, France. Most frequent presenting symptoms were headaches (93%), visual impairment (85%) and vomiting (59%). Hypopituitarism was present at diagnosis in 88% of patients, with a high incidence of corticotroph deficiency (70%). A risk factor was found in 52% of patients, mostly hypertension. Apoplexy occurred in a previously undiagnosed pituitary adenoma in 32/44 cases (73%). The apoplectic event concerned 12 secreting, 27 non-functioning, 4 uncharacterized adenomas and one Rathke's pouch cyst. Nineteen patients underwent surgery within the first month, and one patient had conventional radiotherapy. Twenty-four patients, who had no ophthalmic or neurological signs, were conservatively treated in first intention; among them, 6 received high dose corticosteroids. After a median follow-up of 21 months, there was no significant difference in terms of endocrine or visual recovery between the operated and the conservatively treated groups, nor between patients treated with corticosteroids or not. Panhypopituitarism was observed in 52% of patients, but partial or complete visual recovery was present in the majority of patients (91%), whatever the therapeutic approach. The outcome of patients treated with or without surgery for pituitary apoplexy without severe neuro-ophthalmic deficits seems to be identical, pleading for a conservative management of pituitary apoplexy in the absence of visual emergency.


Analysis of hepatocellular carcinoma associated with hepatitis B virus.
The hepatitis B virus (HBV) is considered one of the main driving forces in the development of hepatocellular carcinoma (HCC). Human HBV is a partially double-stranded DNA (dsDNA) virus consisting of approximately 3.2 kbp. HBV predominantly infects hepatocytes via the receptor sodium taurocholate cotransporting polypeptide (NTCP) and coreceptor hepatic proteoglycan. The replication of HBV in hepatocytes leads to apoptosis while simultaneously leading to cirrhosis and cancer. Although the integration of dsDNA into the hepatocyte genome seems to be the main cause of mutation, since the discovery of their function, viral proteins have been shown to regulate the P53 pathway or P13K/AKT pathway to prevent host cell apoptosis, causing uncontrolled proliferation of liver cells leading to the formation of solid tumours. The most common treatments involve nucleo(s)tide analogue (NA) and polyethylene glycol (PEG)ylated interferon-alpha (PegIFN-α). NA treatment has been found to be effective for the majority of patients and induces few side effects. Nevertheless, the rate of seroconversion is relatively low. PegIFN treatment is contraindicated during pregnancy and leads to a higher morbidity rate, but the seroconversion rate is high. Since medicines and vaccines have been developed, the incidence and mortality of HBV related to HCC have profoundly decreased compared to those in 2000. This review investigates what can be the potential mechanism that HBV can cause HBV and the treatment used in chronic and acute infection.


Naringenin more effectively inhibits inducible nitric oxide synthase and cyclooxygenase-2 expression in macrophages than in microglia.
Macrophages and microglia are thought to account for initial disease progression in acute myocardial infarction and acute ischemic stroke. Before our study, the inhibitory effects of naringenin, a flavonoid, on lipopolysaccharide (LPS)-induced inflammation in macrophages and microglia have not been fully reported and compared. We hypothesized that naringenin can effectively inhibit LPS-induced inflammation of macrophages and microglia at different concentrations, the range of which is broader, with the lowest concentration more easily achieved in macrophages. In this study, we compared the anti-inflammatory effects of naringenin on LPS-stimulated RAW 274.6 macrophages and BV2 microglia and the suppression effects of naringenin and vitamin C (a well-known anti-inflammatory agent) on LPS-induced nitrite production. The results show that macrophages could maintain cell viability at higher naringenin concentrations and were more easily activated by LPS in comparison to microglia (200 vs 100 μmol/L; 0.1 vs 1 μg/mL). Under LPS (1 μg/mL) stimulation in both cell types, naringenin (up to 200 μmol/L in macrophages and 100 μmol/L in microglia) inhibited nitrite production and inducible nitric oxide synthase and cyclooxygenase-2 expression in a dose-dependent manner. The range of naringenin concentrations for inhibition was broader, and the lowest concentration was more easily achieved in macrophages; the lowest effective concentrations of naringenin to achieve constant suppression effect were 50 μmol/L in macrophages and 100 μmol/L in microglia, respectively. Vitamin C (100 μmol/L), compared with naringenin (100 μmol/L), had less and no suppression effect on LPS (1 μg/mL)-induced nitrite production in macrophages and microglia, respectively. In conclusion, naringenin more effectively inhibits the LPS-induced inflammatory status, including nitrite production and inducible nitric oxide synthase and cyclooxygenase-2 expression, in macrophages than in microglia. The findings of the present study suggest that consumption of naringenin-containing flavonoids might be beneficial to the cardiovascular and cerebrovascular inflammatory process.


Role of Disease Progression Models in Drug Development.
The use of Disease progression models (DPMs) in Drug Development has been widely adopted across therapeutic areas as a method for integrating previously obtained disease knowledge to elucidate the impact of novel therapeutics or vaccines on disease course, thus quantifying the potential clinical benefit at different stages of drug development programs. This paper provides a brief overview of DPMs and the evolution in data types, analytic methods, and applications that have occurred in their use by Quantitive Clinical Pharmacologists. It also provides examples of how these models have informed decisions and clinical trial design across several therapeutic areas and at various stages of development. It briefly describes potential new applications of DPMs utilizing emerging data sources, and utilizing new analytic techniques, and discuss new challenges faced such as requiring description of multiple endpoints, rapid model development, application of machine learning-based analytics, and use of high dimensional and real-world data. Considerations for the continued evolution future of DPMs to serve as community-maintained expert systems are also provided.


A device to measure the cross-sectional area of soft connective tissues.
A device has been designed and fabricated to measure the cross-sectional area of soft connective tissues ex vivo. It consists of two displacement transducers; one sensing tissue thickness and the other sensing width. Outputs are recorded (via an analog to digital interface) using a personal computer. Numerical integration of a thickness versus width plot computes cross-sectional area. This plot also provides a quality check of acquired data. This device has been successfully used in biomechanical studies of rabbit patellar tendons, rat medial collateral ligaments, and dissected specimens of human fascia.


Mechanism of changes in hepatic sinusoidal and biliary glutathione efflux with age in rats.
To delineate the kinetic mechanism(s) of declining sinusoidal reduced glutathione (GSH) efflux with age, we perfused livers of male rats ages approximately 1-1.5, approximately 2-3, and approximately 3.5-6 mo old and measured sinusoidal and biliary GSH and oxidized glutathione (GSSG) effluxes. Our results showed declining GSH transport to be solely due to a falling maximum transport rate (Vmax) and not an increasing Michaelis constant (Km)(Vmax = 24.2 +/- 2.95, 15.8 +/- 1.51, and 8.61 +/- 0.75 nmol. min-1.g-1; Km = 3.0 +/- 0.42, 2.6 +/- 0.31, and 2.6 +/- 0.43 mumol/g for the three age groups, respectively). Because hepatocyte membrane potential was earlier implicated as a driving force for GSH efflux and hepatocytes of female rats were reported to be less polarized than those of males, we likewise studied the kinetics of sinusoidal GSH efflux from livers of female rats of three age groups comparable to our males. Vmax in females tended to be lower than in males. This was more pronounced in the youngest group but was diminished in the older groups. Vmax was again the only parameter declining with age in the female livers, from 19.1 +/- 2.25 to 15.0 +/- 0.95 and 7.83 +/- 0.99 nmol.min-1.g-1, whereas Km remained unchanged at 3.0 +/- 0.45, 3.1 +/- 0.35, and 3.2 +/- 0.72 mumol/g, respectively. Age-dependent changes in GSH efflux were not due to a changing membrane potential. There was no appreciable change in the paracellular permeability with age either.(ABSTRACT TRUNCATED AT 250 WORDS)


Stent-screw-assisted internal fixation: the SAIF technique to augment severe osteoporotic and neoplastic vertebral body fractures.
To describe a new technique to obtain minimally invasive but efficient vertebral body (VB) reconstruction, augmentation, and stabilization in severe osteoporotic and neoplastic fractures, combining two pre-existing procedures. The implant of vertebral body stents (VBS) is followed by insertion of percutaneous, fenestrated, cement-augmented pedicular screws that act as anchors to the posterior elements for the cement/stent complex. The screws reduce the risk of stent mobilization in a non-intact VB cortical shell and bridge middle column and pedicular fractures. This procedure results in a 360° non-fusion form of vertebral internal fixation that may empower vertebral augmentation and potentially avoid corpectomy in challenging fractures. This report provides step-by-step procedural details, rationale, and proposed indications for this procedure. The procedure is entirely percutaneous under fluoroscopic guidance. Through transpedicular trocars the VBS are inserted, balloon-expanded and implanted in the VB. Over k-wire exchange the transpedicular screws are inserted inside the lumen of the stents and cement is injected through the screws to augment the stents and fuse the screws to the stents. This technique may find appropriate applications for the most severe osteoporotic fractures with large clefts, high-degree fragmentation and collapse, middle column and pedicular involvement, and in extensive neoplastic lytic lesions. Stent-Screw-Assisted Internal Fixation (SAIF) might represent a minimally invasive option to obtain VB reconstruction and restoration of axial load capability in severe osteoporotic and neoplastic fractures, potentially obviating the need for more invasive surgical interventions in situations that would pose significant challenges to standard vertebroplasty or balloon kyphoplasty.


Vitamin D and neurocognitive dysfunction: preventing "D"ecline?
A preponderance of evidence supports a role for vitamin D beyond the classical function in mineral homeostasis. Epidemiologic investigations have revealed a beneficial role of vitamin D in muscle function, cardiovascular health, diabetes, and cancer prevention. More recently, studies have suggested a potential beneficial role of vitamin D in cognitive function. Vitamin D exhibits functional attributes that may prove neuroprotective through antioxidative mechanisms, neuronal calcium regulation, immunomodulation, enhanced nerve conduction and detoxification mechanisms. Compelling evidence supports a beneficial role for the active form of vitamin D in the developing brain as well as in adult brain function. The vitamin D receptor and biosynthetic and degradative pathways for the hydroxylation of vitamin D have been found in the rodent brain; more recently these findings have been confirmed in humans. The vitamin D receptor and catalytic enzymes are colocalized in the areas of the brain involved in complex planning, processing, and the formation of new memories. These findings potentially implicate vitamin D in neurocognitive function.


Phytochemical screening of Alstonia venenata leaf and bark extracts and their antimicrobial activities.
Alstonia venenata is a plant commonly found in South India and used in traditional medicine. The aim of this study was to characterize the phytochemicals present in A. venenata leaf and bark extracts and study their antimicrobial activities. Solvent extractions with Soxhlet apparatus of leaves and bark were obtained using hexane, benzene, isopropanol, methanol, and water. The crude extracts were concentrated and screened for qualitative phytochemical content and analyzed by thin layer chromatography. The antibacterial, antifungal and antiviral activities of crude extracts were measured by in vitro methods. Alkaloids, carbohydrates, tannins, phenolic compounds, terpenoids, cardiac glycosides and amino acids were found in the different crude extracts analyzed. Isopropanol extracts showed antifungal activity and it was more pronounced in the bark extract than the leaf extract. Moreover, the isopropanol extract exhibited antibacterial and antiviral activity. In conclusion, the leaves and bark of A. venenata have antimicrobial components which are more present in the isopropanol fraction.


Periodontal disease, edentulism, and pancreatic cancer: a meta-analysis.
Periodontal disease (PD), now our commonest infectious disorder leads to tooth loss, and has been linked to various systemic diseases, including various types of cancer. The aim of this study is to provide a systematic review and a meta-analysis of the relationship between PD, edentulism, and pancreatic cancer (PC). From an initial review of 327 references we selected eight studies concerning periodontitis or edentulism with sufficient quantitative information to allow us to examine the risk of PC. We used relative risks (RRs), hazard ratios, or odds ratios to measure the association between periodontitis, edentulism, and PC. We employed random effects models to obtain summary risks, and we also provide measures of study differences and possible biases. The summary RR for periodontitis and PC was 1.74 [95% confidence interval (CI) 1.41-2.15] and 1.54 for edentulism (95% CI 1.16-2.05). There was no evidence of heterogeneity for either variable, and no evidence of publication bias. The studies included reports from three continents, suggesting that the association is generalizable. Most of the studies were adjusted for variables thought to be associated with PC, such as gender, smoking, BMI, diabetes, and alcohol. Using meta-analysis, both periodontitis and edentulism appear to be associated with PC, even after adjusting for common risk factors. As yet, the mechanisms linking oral disease and PC are uncertain, but could be related to changes in the oral microbiome-an area of current research.


Error vector magnitude based parameter estimation for digital filter back-propagation mitigating SOA distortions in 16-QAM.
We investigate the performance of digital filter back-propagation (DFBP) using coarse parameter estimation for mitigating SOA nonlinearity in coherent communication systems. We introduce a simple, low overhead method for parameter estimation for DFBP based on error vector magnitude (EVM) as a figure of merit. The bit error rate (BER) penalty achieved with this method has negligible penalty as compared to DFBP with fine parameter estimation. We examine different bias currents for two commercial SOAs used as booster amplifiers in our experiments to find optimum operating points and experimentally validate our method. The coarse parameter DFBP efficiently compensates SOA-induced nonlinearity for both SOA types in 80 km propagation of 16-QAM signal at 22 Gbaud.


Investigation into the participation of male pheromones of Rhipicephalus evertsi evertsi during infestation.
It was shown in this study that Rhipicephalus evertsi evertsi males emit pheromones in the preparasitic as well as in the parasitic phases. Conspecific unengorged male and female images exhibited a high response to water-soluble volatiles collected from unengorged males. A vigorous assembly of unfed female R. evertsi evertsi occurred on filter paper discs which had been in contact with either unfed or 5- and 9-day fed males. Progressively increasing percentages of conspecific unengorged males reacted to organic soluble volatiles obtained from 5- and 9-day fed males as well as to hexane washings of intact males which had fed for 9 days. It is concluded that R. evertsi evertsi males participate not only as pheromone receptive, but also as pheromone emitting, partners in the intraspecific communication of this tick species.


Synergism between aphidicolin and adenoviruses in the induction of breaks at fragile sites on human chromosomes.
Infection of human embryonic kidney cells with adenoviruses results in the induction of gaps and breaks in cell chromosomes. With adenovirus type 12, cytogenetic damage is known to occur primarily at fragile sites on chromosomes 1 and 17. We have mapped adenovirus type 5-induced breaks and have observed that, although they occur on all chromosomes, they are localized primarily on bands where fragile sites have been mapped. The susceptibility of fragile sites to adenovirus led us to investigate their expression upon combined treatments with virus and aphidicolin, a frequently used inducer of fragile sites. Under these experimental conditions, the frequency of damage at all sites was found to increase significantly, and the magnitude of such increases indicated a synergistic effect between drug and virus.


[Update on celiac disease].
The prevalence of Celiac disease in the general population is approximately 1% and remains undiagnosed in a significant proportion of individuals. Its clinical presentation includes the classical malabsorption syndrome, unspecific and extra-intestinal manifestations, and silent celiac disease. The serologic diagnosis has an elevated sensitivity and specificity and, at least in adult population, it must be confirmed by biopsy in every case. Diagnosis in subjects already on gluten free diet includes HLA typing and gluten challenge with posterior serologic and histologic evaluation. The core of the treatment is the gluten free diet, which must be supervised by an expert nutritionist. Monitoring must be performed with serology beginning at 3-6 months, and with histology two years after the diagnosis, unless the clinical response is poor. Poor disease control is associated with complications such as lymphoma and small bowel adenocarcinoma. In the future, it is likely that new pharmacologic therapies will be available for the management of celiac disease.


Prognostic value of decreased peripheral congestion detected by Bioelectrical Impedance Vector Analysis (BIVA) in patients hospitalized for acute heart failure: BIVA prognostic value in acute heart failure.
The objective of this study was to investigate the prognostic role of quantitative reduction of congestion during hospitalization assessed by Bioelectrical Impedance Vector Analysis (BIVA) serial evaluations in patients admitted for acute heart failure (AHF). AHF is a frequent reason for patients to be admitted. Exacerbation of chronic heart failure is linked with a progressive worsening of the disease with increased incidence of death. Fluid overload is the main mechanism underlying acute decompensation in these patients. BIVA is a validated technique able to quantify fluid overload. a prospective, multicentre, observational study in AHF and no AHF patients in three Emergency Departments centres in Italy. Clinical data and BIVA evaluations were performed at admission (t0) and discharge (tdis). A follow-up phone call was carried out at 90 days. Three hundred and thirty-six patients were enrolled (221 AHF and 115 no AHF patients). We found that clinical signs showed the most powerful prognostic relevance. In particular the presence of rales and lower limb oedema at tdis were linked with events relapse at 90 days. At t0, congestion detected by BIVA was observed only in the AHF group, and significantly decreased at tdis. An increase of resistance variation (dR/H) >11 Ω/m during hospitalization was associated with survival. BIVA showed significant results in predicting total events, both at t0 (area under the curve (AUC) 0.56, p<0.04) and at tdis (AUC 0.57, p<0.03). When combined with clinical signs, BIVA showed a very good predictive value for cardiovascular events at 90 days (AUC 0.97, p<0.0001). In AHF patients, an accurate physical examination evaluating the presence of rales and lower limbs oedema remains the cornerstone in the management of patients with AHF. A congestion reduction, obtained as a consequence of therapies and detected through BIVA analysis, with an increase of dR/H >11 Ω/m during hospitalization seems to be associated with increased 90 day survival in patients admitted for AHF.


The static balance ability on soft and hard support surfaces in older adults with mild cognitive impairment.
This study aimed to assess the static balance ability of the older adults with mild cognitive impairment (MCI) while standing on soft and hard support surfaces. Forty older adults participated in this study (21 in the MCI group and 19 in the control group). Participants were required to perform balance tests under four conditions of standing: standing on a hard support surface with eyes open, standing on a soft support surface with eyes open, standing on a hard support surface with eyes closed, and standing on a soft support surface with eyes closed. Each test was measured in three trials and each trial lasted 30 seconds. Participants were asked to take off their shoes and place their feet in a parallel position with a 20-centimeter distance for bipedal support. The trajectories of the center of pressure (COP) were measured using a Kistler force platform with a frequency of 1000 Hz to assess balance while standing in both groups, with larger COP trajectories indicating poorer static balance in older adults. With eyes open, the displacement of COP in the anterior-posterior direction(D-ap) (hard support surface: P = 0.003) and the 95% confidence ellipse area(95%AREA-CE) (soft support surface: P = 0.001, hard support surface: P < 0.001) of the COP in the MCI group standing on hard and soft support surfaces were significantly larger than the control group. The 95%AREA-CE (P < 0.001) of the COP in the MCI group on the soft support surface was significantly larger than on the hard support surface. With eyes closed, the root mean square distance(RDIST), root mean square distance-ML(RDISTml), and 95%AREA-CE of the COP were no significant between-group differences when standing on hard support surfaces. However, the RDIST (P = 0.014), RDISTml (P = 0.014), and 95%AREA-CE (P = 0.001) of the COP in the MCI group on the soft support surfaces were significantly larger than the control group. The 95%AREA-CE (P < 0.001), RDIST (P < 0.001), and RDISTml (P < 0.001) of the COP in the MCI group on the soft support surface were significantly larger than the hard support surface. With eyes open, the older adults with MCI showed poorer static balance ability compared to the older adults with normal cognition on soft and hard support surfaces. With eyes closed, the older adults with MCI showed poorer static balance on soft support surfaces, but no differences on hard support surfaces compared with the older adults with normal cognition. With eyes open and closed, the older adults with MCI showed poorer static balance on soft support surfaces as compared to hard support surfaces.


Comparison of clinical severity score indices for Clostridium difficile infection.
To compare 8 severity score indices for Clostridium difficile infection (CDI). Prospective observational study. This study was conducted from July through October 2006. All hospitalized patients in 3 university-affiliated hospitals with a positive fecal Clostridium difficile toxin assay result were evaluated. Infection was considered severe if patients had at least 1 of the following clinical events during their hospitalization: (1) death attributed to CDI within 30 days after diagnosis, (2) colectomy necessitated by CDI, or (3) intensive care unit admission for management of complications attributed to CDI. Severity was assessed on the basis of 8 severity score indices, using published criteria for severe CDI as the benchmark. The 8 severity score indices studied were Beth Israel, University of Pittsburgh Medical Center version 1, University of Pittsburgh Medical Center version 2, Hines VA, modified University of Illinois, University of Calgary version 1, University of Calgary version 2, and University of Temple. Of 184 patients with CDI evaluated, 19 had severe cases and 165 had nonsevere cases, as assessed on the basis of the defined severe CDI criteria. Sensitivities of the 8 severity score indices studied ranged from 63.2% to 84.2%, and specificities ranged from 59.4% to 93.9%. The Hines VA index had the highest kappa score (0.69 [95% confidence interval, 0.54-0.83]), followed by the University of Pittsburgh Medical Center version 1 index. Independent risk factors for severe CDI determined by multivariate analysis were abdominal distention (P = .007), fever (temperature, 38.0°C or above; P = .042), white blood cell count of at least 20,000 cells/mm(3) (P = .035), and hypoalbuminemia (serum albumin level less than 3 mg/dL; P = .029). The Hines VA CDI severity score index appeared to display the strongest correlation for predicting more severe forms of CDI.


Feed consumption and food passage time in mink (Mustela vison) and European ferrets (Mustela putorius furo).
The amount of feed consumed per day and the rate of food passage was measured in mink and European ferrets. Daily feed consumption averaged 40 and 42 g dry matter per kg body weight for male mink and ferrets and 53 and 49 g dry matter per kg body weight for female mink and ferrets, respectively. Using ferric oxide as a feed marker, no differences were observed in food passage time between mink and ferrets or between males and females within each species. The mean time of food passage was 187 minutes for mink and 182 minutes for European ferrets.


[Applicability of the strategic planning approach to local health organizations]
This paper presents the preliminary results from a study on the limits and possibilities of the strategic planning approach for local health organizations. A comparative analysis is developed between two experiences concerning the application of the strategic situational planning method (PES method) in the management of a health center and hospital. Questions include the following: difficulties with the use of the category actor in local health organizations; possibility of drafting a collective project based on the multiple rationalities existing in such organizations; possibility of improving communications processes with the use of the PES method; difficulties related to organizational culture; and low levels of responsibility, as well as difficulties pertaining to the method's complexity and the possibility of simplifying it, maintaining strategic situational analysis and improving organizations' managerial capacity.


The Importance of Complementary Collaboration of Researchers, Veterinarians, and Husbandry Staff in the Successful Training of Marmoset Behavioral Assays.
Interest in marmosets as research models has seen exponential growth over the last decade, especially given that the research community is eager to improve on gaps with historical animal models for behavioral and cognitive disorders. The spectrum of human disease traits that present naturally in marmosets, as well as the range of analogous human behaviors that can be assessed in marmosets, makes them ideally suited as translational models for behavioral and cognitive disorders. Regardless of the specific research aims of any project, without close collaboration between researchers, veterinarians, and animal care staff, it would be impossible to meet these goals. Behavior is inherently variable, as are marmosets that are genetically and phenotypically diverse. Thus, to ensure rigor, reliability, and reproducibility in results, it is important that in the research environment, the animal's daily husbandry and veterinary needs are being met and align with the research goals while keeping the welfare of the animal the most critical and highest priority. Much of the information described herein provides details on key components for successful behavioral testing, based on a compendium of methods from peer-reviewed publications and our own experiences. Specific areas highlighted include habituation procedures, selection of appropriate rewards, optimization of testing environments, and ways to integrate regular veterinary and husbandry procedures into the research program with minimal disruptions to the behavioral testing plan. This article aims to provide a broad foundation for researchers new to establishing behavioral and cognitive testing paradigms in marmosets and especially for the veterinary and husbandry colleagues who are indispensable collaborators of these research projects.


The Patient and Observer Scar Assessment Scale to Evaluate the Cosmetic Outcomes of the Robotic Single-Site Hysterectomy in Endometrial Cancer.
The objective of this study was to evaluate the cosmetic outcome of robotic single-site hysterectomy (RSSH) in early-stage endometrial cancer. We prospectively collected patient demographics, operative times, complications, pathologic results, and length of stay on all patients who underwent RSSH for early-stage endometrial cancer. The Patient and Observer Scar Assessment Scale (POSAS) was used for the evaluation of the cosmetic outcome. Forty-five patients were included in our study from January 2012 to October 2015. The median age of patients was 63 years (range, 35-84 years), and the median body mass index was 26.5 kg/m (range, 18-39 kg/m). No laparoscopic/laparotomic conversion was registered. The median docking time, console time, and total operative time were 7 minutes (range, 4-14 minutes), 46 minutes (range, 20-100 minutes), and 90 minutes (range, 45-150 minutes), respectively. The median blood loss was 50 mL (range, 10-150 mL). Nine patients underwent pelvic lymphadenectomy, and the median number of pelvic lymph nodes was 13 (range, 10-32). The median time to discharge was 3 days (range, 2-6 days). No intraoperative complications occurred, whereas we did observe 1 early postoperative complication. The oncological outcome was directly comparable to the literature. Patients reported low pain scores and high satisfaction in terms of postoperative scarring. The POSAS scores confirmed excellent cosmetic outcome of RSSH. Robotic single-site hysterectomy provided an efficient option for gynecologic oncologic surgery. The POSAS revealed high objective and patient-evaluated outcome, and patients were highly satisfied with the overall outcome of the appearance of their scars.


[Disease as a phenomenon of human nature: toward understanding and developing of V. Kh.Vasilenko's philosophical legacy. Part 1].
V.Kh.Vasilenko paid much attention to the development of philosophical aspects of the concept of disease and left the rich intellectual legacy and a number of advisory instructions that allow the main challenge in modern medicine (the definition of the notion of disease) to be addressed. One of his principal messages is the necessity of generalization and synthesis of facts. Following Vasilenko's instructions, Part 1 of this review is devoted to systematization of modern views of general features of pathogenesis of internal diseases for obtaining a deeper insight into the essence of the disease.


[Retracted] microRNA‑196b promotes cell migration and invasion by targeting FOXP2 in hepatocellular carcinoma.
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the images showing metastatic nodules in the mouse lung in Fig. 4 on p. 735 had apparently previously been published a few years earlier in the following paper: Jia D, Yan M, Wang X, Hao X, Liang L, Liu L, Kong H, He X, Li J and Yao M: Development of a highly metastatic model that reveals a crucial role of fibronectin in lung cancer cell migration and invasion. BMC Cancer 10: 364, 2010. Moreover, among the cell migration and invasion assay data shown in Figs. 3B and D, and 6B and 7B, there were a number of overlaps noted among the data panels such that data which were intended to show results obtained under different experimental conditions were likely to have been derived from a smaller number of original sources. Owing to the fact that the contentious data in the above article had already been publihed prior to its submission to Oncology Reports, in addition the other features of concern regarding the data, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 731‑738, 2018; DOI: 10.3892/or.2017.6130].


Molecular analysis of an aurea photosynthetic mutant (Su/Su) in tobacco: LHCP depletion leads to pleiotropic mutant phenotypes.
Su is a nuclear encoded, semi-dominant aurea mutation in Nicotiana tabacum L. The homozygous plants (Su/Su) are pale yellow and non-photosynthetic while the heterozygous (Su/+) are photosynthetically competent and have a yellow-green phenotype which is distinct from that of green wild-type plants (+/+). We have examined the RNA and protein levels for a number of nuclear and plastid encoded chloroplast proteins under high and low light plant growth conditions. Under high light conditions, the light-harvesting chlorophyll a/b binding proteins (LHCP) were undetectable in the homozygous Su/Su plants, and the large subunit (LSu) and the small subunit (SSu) of ribulose bisphosphate carboxylase (Rubisco) and cytochrome b559 were severely deficient. However, only the nuclear encoded cab and plastid encoded psbE mRNA (encoding LHCP and cytochrome b559 respectively) were reduced significantly. In heterozygous Su/+ plants, the level of LHCP was reduced to 25% of that in wild-type plants while cab and psbE mRNA, LSu, SSu and cytochrome b559 remained at normal levels, suggesting that LCHP is more immediately affected by the Su mutant gene product than the rest of the photosynthetic proteins and mRNA examined. Under low light conditions, the levels of cab and psbE mRNA, LSu, SSu and cytochrome b559 in homozygous Su/Su plants were equivalent to those in wild-type plants except LHCP which remained undetectable. Similarly, the LHCP level in low light grown Su/+ plants still remained at 25% of wild-type level. These results indicate that the decrease in LHCP is independent of light conditions and has not resulted from photooxidation, whereas the depletion of other proteins and mRNA examined under high light growth conditions is a consequence of photooxidative damage to Su/Su plastids. Furthermore, transgenic Su/Su and Su/+ plants with a cauliflower mosaic virus 35S (CaMV 35S)-cab construct constitutively maintained high levels of cab mRNA but displayed the same pattern of diminished LHCP accumulation as their non-transformed counterparts when grown under both high and low light conditions. These results indicate that the Su mutation primarily causes depletion of LHCP. The depletion of LHCP leads to photooxidative damage which results in decreased cab mRNA levels and other pleiotropic lesions in Su/Su plants.


Etiologic agent of Lyme disease, Borrelia burgdorferi, detected in ticks (Acari: Ixodidae) collected at a focus in Alabama.
The study was conducted at sites of known transmission of Borrelia burgdorferi in east central Alabama. The objectives were to determine species of ticks present at these sites, their host associations, and species of ticks and small mammals naturally infected with B. burgdorferi. A total of 451 hosts were examined for ticks, including cotton mice, Peromyscus gossypinus (Le Conte); cotton rats, Sigmodon hispidus Say & Ord; southern short-tailed shrews, Blarina carolinensis (Bachman); house mice, Mus musculus L.; golden mice, Ochrotomys nuttalli (Harlan); and white-tailed deer, Odocoileus virginianus (Zimmermann). Ticks were examined for B. burgdorferi using indirect and direct fluorescent antibody assays. Ear biopsy samples from rodents were cultured in modified Kelly's medium in attempts to isolate B. burgdorferi. A total of 859 Amblyomma americanum L., Dermacentor albipictus (Packard), D. variabilis (Say), Ixodes scapularis Say, and Rhipicephalus sanguineus (Latreille) were recovered from hosts and by dragging. A. americanum and I. scapularis accounted for 53.4% of all ticks collected. Nearly half of all ticks collected were examined for the agent. Spirochetes were detected in four nymphal and two adult A. americanum recovered from white-tailed deer and three larval I. scapularis recovered from cotton mice. No spirochetes were cultured from field-caught rodents.


Results after elective open repair of pararenal abdominal aortic aneurysms.
This study presents a retrospective analysis of long-term outcomes and factors influencing early and late results of a 20-year experience with open repair of atherosclerotic pararenal abdominal aortic aneurysms (PAAAs). Records of consecutive patients who underwent open repair of PAAA between 1990 and 2010 at a tertiary referral care center were analyzed for demographics, comorbidities, operative variables, complications, and 30-day mortality. Long-term results were also assessed through a local electronic medical database and direct follow-up. Variables influencing early and late results were evaluated by univariate and multivariate logistic regression analyses, stepwise backward elimination, and Cox proportional hazard regression. The study included 200 patients (94% men; mean age, 69.5 years) who were monitored for a mean of 107.3 months. The aneurysm was juxtarenal in 78% of patients, suprarenal in 19.5%, and type IV thoracoabdominal in 2.5%. Mortality at 30 days was 2.5%. At least one major complication occurred in 51.5%. Postoperative acute renal failure (pARF) occurred in 11% of the patients, 3% had temporary hemodialysis, but only 0.5% required chronic hemodialysis. pARF was significantly related to preoperative renal function (P = .009), visceral ischemia >30 minutes (P = .05), and supraceliac or supramesenteric clamp site (P = .005). Respiratory complications (13.8%) were associated with an increasing stage of chronic obstructive pulmonary disease (P = .020), proximal clamp site (P = .047), and intraoperatively infused crystalloids (P = .014). Cardiac complications (12.8%) were related to previous myocardial infarction (P = .031) and proximal clamp site (P = .003). Late deaths were observed in 21.5%. Mean survival was 50 months, with Kaplan-Meier survival estimates of 78% at 5 years and 60.5% at 10 years. Variables influencing long-term survival included age (hazard ratio [HR], 2.67; P = .01), chronic obstructive pulmonary disease stage 2 (HR, 5.14; P = .01) and stage 3 (HR, 4.54; P = .03), postoperative cardiac complication (HR, 3.93; P ≤ .00), previous myocardial infarction (HR, 1.47; P = .02), peripheral artery disease (HR, 1.97; P = .03), and smoking (HR, 1.17; P = .02). Survival and late-onset renal insufficiency were unaffected by preoperative renal function. Late renal failure was observed in 6.2% of the patients but did not predict mortality. Conventional surgical repair of PAAAs can be performed with acceptable short-term and long-term mortality. Although pARF is frequent, chronic hemodialysis at discharge is rare. Cardiac and respiratory complications are also common and associated with worse survival. Our data represent a potentially useful benchmark for complex endovascular repairs of this type of aneurysm.


Three years' follow-up of bone density in adult coeliac disease: significance of secondary hyperparathyroidism.
The mechanisms of disturbances in bone mineral density (BMD) in coeliac disease are not completely understood. The aim of this prospective study was to investigate the possible significance of secondary hyperparathyroidism (SHPT) with regard to BMD in patients with untreated coeliac disease. One hundred and five adult patients with untreated coeliac disease were examined for BMD and serum parathyroid hormone (PTH) concentration. BMD in the hip, lumbar spine, and forearm were examined up to 3 years after the introduction of a gluten-free diet. SHPT was found in 27% (28 of 105) of the patients. In patients with SHPT serum levels of 25-hydroxy-vitamin D were lower and those of alkaline phosphatase higher than in patients with normal PTH, but ionized serum calcium did not differ between the two groups. BMD was more severely reduced in patients with SHPT. Although the BMD increment was more rapid in patients with than in those without SPTH, only in the latter group did mean BMD became normal after 1-3 years on a gluten-free diet (GFD). After 3 years on a GFD more than half of the patients with initial SHPT still had low BMD in both the hip and the forearm. Furthermore, in patients with SHPT the intestinal mucosa more often remained atrophic at the 1-year follow-up, despite good compliance with the diet. Low BMD in patients with untreated coeliac disease is often associated with SHPT. After 3 years on a GFD the BMD remains low only in patients with initial SHPT. We therefore suggest that PTH should be measured when the diagnosis of coeliac disease is made, as an indicator of more serious intestinal disorder and complicating bone disease.


Natural size variation among embryos leads to the corresponding scaling in gene expression.
Xenopus laevis frogs from laboratory stocks normally lay eggs exhibiting extensive size variability. We find that these initial size differences subsequently affect the size of the embryos prior to the onset of growth, and the size of tadpoles during the growth period. Even though these tadpoles differ in size, their tissues, organs, and structures always seem to be properly proportioned, i.e. they display static allometry. Initial axial patterning events in Xenopus occur in a spherical embryo, allowing easy documentation of their size-dependent features. We examined the size distribution of early Xenopus laevis embryos and measured diameters that differed by about 38% with a median of about 1.43 mm. This range of embryo sizes corresponds to about a 1.9-fold difference in surface area and a 2.6-fold difference in volume. We examined the relationship between embryo size and gene expression and observed a significant correlation between diameter and RNA content during gastrula stages. In addition, we investigated the expression levels of genes that pattern the mesoderm, induce the nervous system and mediate the progression of ectodermal cells to neural precursors in large and small embryos. We found that most of these factors were expressed at levels that scaled with the different embryo sizes and total embryo RNA content. In agreement with the changes in transcript levels, the expression domains in larger embryos increased proportionally with the increase in surface area, maintaining their relative expression domain size in relation to the total size of the embryo. Thus, our study identified a mechanism for adapting gene expression domains to embryo size by adjusting the transcript levels of the genes regulating mesoderm induction and patterning. In the neural plate, besides the scaling of the expression domains, we observed similar cell sizes and cell densities in small and large embryos suggesting that additional cell divisions took place in large embryos to compensate for the increased size. Our results show in detail the size variability among Xenopus laevis embryos and the transcriptional adaptation to scale gene expression with size. The observations further support the involvement of BMP/ADMP signaling in the scaling process.


Upper girdle imaging in facioscapulohumeral muscular dystrophy.
In Facioscapulohumeral muscular dystrophy (FSHD), the upper girdle is early involved and often difficult to assess only relying on physical examination. Our aim was to evaluate the pattern and degree of involvement of upper girdle muscles in FSHD compared with other muscle diseases with scapular girdle impairment. We propose an MRI protocol evaluating neck and upper girdle muscles. One hundred-eight consecutive symptomatic FSHD patients and 45 patients affected by muscular dystrophies and myopathies with prominent upper girdle involvement underwent this protocol. Acquired scans were retrospectively analyzed. The trapezius (100% of the patients) and serratus anterior (85% of the patients) were the most and earliest affected muscles in FSHD, followed by the latissimus dorsi and pectoralis major, whilst spinati and subscapularis (involved in less than 4% of the patients) were consistently spared even in late disease stages. Asymmetry and hyperintensities on short-tau inversion recovery (STIR) sequences were common features, and STIR hyperintensities could also be found in muscles not showing signs of fatty replacement. The overall involvement appears to be disease-specific in FSHD as it significantly differed from that encountered in the other myopathies. The detailed knowledge of single muscle involvement provides useful information for correctly evaluating patients' motor function and to set a baseline for natural history studies. Upper girdle imaging can also be used as an additional tool helpful in supporting the diagnosis of FSHD in unclear situations, and may contribute with hints on the currently largely unknown molecular pathogenesis of this disease.


Microvascular Free Tissue Transfer for Reconstruction of Complex Abdominal Wall Defects.
Patients with significant loss of abdominal wall soft tissue represent a reconstructive challenge. The purpose of this study was to describe the authors' experience using microvascular free tissue transfer to repair complex abdominal wall defects with insufficient overlying soft tissue. In this report, the authors highlight their techniques and experiences in performing microvascular free tissue transfer to the abdominal wall for these massive, complex defects. In total, 14 patients who underwent 16 free-flap reconstructions were included in the series. The patients' mean age was 50 ± 14 years, and mean body mass index was 27 ± 5 kg/m2. The mean hernia defect size was 412 ± 149 cm2. Ten flaps were fasciocutaneous anterolateral thigh flaps, one myocutaneous anterolateral thigh flap, two subtotal thigh flaps, one myocutaneous latissimus dorsi flap, one parascapular/latissimus dorsi flap, and one free filet of the lower leg. Five cases (36 percent) developed hernia recurrence, and seven developed surgical site complications. All flaps survived, with no total flap loss. This report highlights that microsurgical free tissue transfer in combination with mesh repair is a safe and reliable method for restoring complex, large, full-thickness abdominal wall defects. This case series illustrates a number of techniques and considerations that are of importance to achieve a favorable outcome when faced with these complex defects. Therapeutic, IV.


Gender and Authorship in Pediatric Critical Care Randomized Control Trials.
To examine the gender distribution of authorship of pediatric critical care randomized control trials. The 415 randomized control trials in pediatric critical care published before 2019. We included all randomized control trials enrolling children in a PICU. We used PICUtrials.net, which uses comprehensive search strategies of multiple databases, to identify published randomized control trials. We manually extracted the name and profession of each listed author from each publication and classified each author as male or female based on their name. We included 2,146 authors and were able to classify 1,888 (88%) as men or women. Overall, 38% of authors were women, this varied with the authorship position: 37% of first, 38% of middle, and 25% of last authors were women (p < 0.001). The three most common professions were physician (63%), nonclinician (11%), and nurse (6%)-of which 30%, 45%, and 97%, respectively, were women. The percentage of female authorship overall has increased from 28% in 1985-1989 to 39% in 2015-2018 (p for trend = 0.004). There were no significant differences in the characteristics of randomized control trials published with a female first or last author versus those with both male first and last authors with respect to the median number of children randomized (60 vs. 50; p = 0.41), multicentred trials (17% vs. 24%; p = 0.12), trials at low risk of bias (50% vs. 66%; p = 0.26), reporting any funding (55% vs. 51%; p = 0.66), or median number of citations per year (1.5 vs. 2.4; p = 0.09). Although increasing over time, the percentage of researchers publishing pediatric critical care randomized control trials who are women still lags behind the percentage clinicians who are women. Trials that female researchers publish are similar in characteristics and impact as male researchers. Further work should identify barriers to gender diversity and potential solutions in pediatric critical care research.


Artificial light at night alters trophic interactions of intertidal invertebrates.
Despite being globally widespread in coastal regions, the impacts of light pollution on intertidal ecosystems has received little attention. Intertidal species exhibit many night-time-dependent ecological strategies, including feeding, reproduction, orientation and predator avoidance, which are likely negatively affected by shifting light regimes, as has been observed in terrestrial and aquatic taxa. Coastal lighting may shape intertidal communities through its influence on the nocturnal foraging activity of dogwhelks (Nucella lapillus), a widespread predatory mollusc that structures biodiversity in temperate rocky shores. In the laboratory, we investigated whether the basal and foraging activity of this predator was affected by exposure to night-time lighting both in the presence and absence of olfactory predator cues (Carcinus maenas, common shore crab). Assessments of dogwhelks' behavioural responses to night-time white LED lighting were performed on individuals that had been acclimated to night-time white LED lighting conditions for 16 days and individuals that had not previously been exposed to artificial light at night. Dogwhelks acclimated to night-time lighting exhibited natural refuge-seeking behaviour less often compared to control animals, but were more likely to respond to and handle prey irrespective of whether olfactory predator cues were present. These responses suggest night-time lighting likely increased the energetic demand of dogwhelks through stress, encouraging foraging whenever food was available, regardless of potential danger. Contrastingly, whelks not acclimated under night-time lighting were more likely to respond to the presence of prey under artificial light at night when olfactory predator cues were present, indicating an opportunistic shift towards the use of visual instead of olfactory cues in risk evaluation. These results demonstrate that artificial night-time lighting influences the behaviour of intertidal fauna such that the balance of interspecific interactions involved in community structuring may be affected.


LINEs, SINEs and repetitive DNA: non-LTR retrotransposons in plant genomes.
Retroelements and remnants thereof constitute a large fraction of the repetitive DNA of plant genomes. They include LTR (long terminal repeat) retrotransposons such as Ty1-copia and Ty3-gypsy retrotransposons, which are widespread in plant genomes and show structural similarity to retroviruses. Recently, non-LTR retrotransposons, lacking the long terminal repeats and subdivided into LINEs (long interspersed nuclear elements) and SINEs (short interspersed nuclear elements), have been discovered as ubiquitous components of nuclear genomes in many species across the plant kingdom. LINEs are probably the most ancient class of retrotransposons in plant genomes, but the evolutionary borders between non-LTR retrotransposons, LTR retrotransposons and retroviruses are indistinct as shown by the detection of intermediate forms in other eukaryotic taxa. Transposition of non-LTR retrotransposons is only rarely observed in plants indicating that the majority of these retroelements are inactive and/or under regulation of the host genome. Transposition is poorly understood, but experimental evidence from other genetic systems, in particular from insect and mammalian species, shows that LINEs are able to transpose autonomously, while non-autonomous SINEs depend on the reverse transcription machinery of other retrotransposons. Fluorescence in situ hybridization demonstrated that different classes of retrotransposons differ largely in their chromosomal organization and are often excluded from blocks of rapidly homogenizing tandem repeats. In particular, LINEs contribute considerably to the repetitive DNA of nuclear plant genomes.


Optimisation in a natural system: Argentine ants solve the Towers of Hanoi.
Natural systems are a source of inspiration for computer algorithms designed to solve optimisation problems. Yet most 'nature-inspired' algorithms take only superficial inspiration from biology, and little is known about how real biological systems solve difficult problems. Moreover, ant algorithms, neural networks and similar methods are usually applied to static problems, whereas most biological systems have evolved to perform under dynamically changing conditions. We used the Towers of Hanoi puzzle to test whether Argentine ants can solve a potentially difficult optimisation problem. We also tested whether the ants can adapt to dynamic changes in the problem. We mapped all possible solutions to the Towers of Hanoi on a single graph and converted this into a maze for the ants to solve. We show that the ants are capable of solving the Towers of Hanoi, and are able to adapt when sections of the maze are blocked off and new sections installed. The presence of exploration pheromone increased the efficiency of the resulting network and increased the ants' ability to adapt to changing conditions. Contrary to previous studies, our study shows that mass-recruiting ant species such as the Argentine ant can forage effectively in a dynamic environment. Our results also suggest that novel optimisation algorithms can benefit from stronger biological mimicry.


A novel translation initiation region from Mycoplasma genitalium that functions in Escherichia coli.
The tuf gene of Mycoplasma genitalium uses a signal other than a Shine-Dalgarno sequence to promote translation initiation. We have inserted the translation initiation region of this gene in front of the Escherichia coli lacZ gene and shown that it is recognized by the translational machinery of E. coli; the signal operates in vivo at roughly the same efficiency as a synthetic Shine-Dalgarno sequence. The M. genitalium sequence was also used to replace the native translation initiation region of the cat gene. When assayed in E. coli, the M. genitalium sequence is equivalent to a Shine-Dalgarno sequence in stimulating translation of this mRNA also. Site-directed mutagenesis enabled us to identify some of the bases that comprise the functional sequence. We propose that the sequence UUAACAACAU functions as a ribosome binding site by annealing to nucleotides 1082-1093 of the E. coli 16S rRNA. The activity of this sequence is enhanced when it is present in the loop of a stem-and-loop structure. Additional sequences both upstream and downstream of the initiation codon are also involved, but their role has not been elucidated.


The Soil Microbiome of GLORIA Mountain Summits in the Swiss Alps.
While vegetation has intensively been surveyed on mountain summits, limited knowledge exists about the diversity and community structure of soil biota. Here, we study how climatic variables, vegetation, parent material, soil properties, and slope aspect affect the soil microbiome on 10 GLORIA (Global Observation Research Initiative in Alpine environments) mountain summits ranging from the lower alpine to the nival zone in Switzerland. At these summits we sampled soils from all four aspects and examined how the bacterial and fungal communities vary by using Illumina MiSeq sequencing. We found that mountain summit soils contain highly diverse microbial communities with a total of 10,406 bacterial and 6,291 fungal taxa. Bacterial α-diversity increased with increasing soil pH and decreased with increasing elevation, whereas fungal α-diversity did not change significantly. Soil pH was the strongest predictor for microbial β-diversity. Bacterial and fungal community structures exhibited a significant positive relationship with plant communities, indicating that summits with a more distinct plant composition also revealed more distinct microbial communities. The influence of elevation was stronger than aspect on the soil microbiome. Several microbial taxa responded to elevation and soil pH. Chloroflexi and Mucoromycota were significantly more abundant on summits at higher elevations, whereas the relative abundance of Basidiomycota and Agaricomycetes decreased with elevation. Most bacterial OTUs belonging to the phylum Acidobacteria were indicators for siliceous parent material and several OTUs belonging to the phylum Planctomycetes were associated with calcareous soils. The trends for fungi were less clear. Indicator OTUs belonging to the genera Mortierella and Naganishia showed a mixed response to parent material, demonstrating their ubiquitous and opportunistic behaviour in soils. Overall, fungal communities responded weakly to abiotic and biotic factors. In contrast, bacterial communities were strongly influenced by environmental changes suggesting they will be strongly affected by future climate change and associated temperature increase and an upward migration of vegetation. Our results provide the first insights into the soil microbiome of mountain summits in the European Alps that are shaped as a result of highly variable local environmental conditions and may help to predict responses of the soil biota to global climate change.


Barium sulfate as contrast medium for evaluation of postoperative anastomotic leaks.
To assess the value of barium swallow as a method for immediate re-examination after the failure of an aqueous iodinated agent in detection of clinically suspected postoperative esophageal leakage, and as the initial study in asymptomatic postoperative patients. Prospective examinations were performed in 114 postoperative patients, 95 males and 19 females (mean age 60 years). Initial esophagography with an aqueous contrast agent was performed in all cases. The patients who had no evidence of leakage underwent immediate re-examination with barium sulfate. Leakage volume was calculated in cm3. Clinical presentations of leakage before the examinations and the complications after the study were recorded. Leakage was shown with the initial study, using aqueous medium, in 23 patients (20%). The volume of leakage was between 0.05 and 36 cm3 (mean 3.95 cm3). Clinical signs and symptoms presented in 13 cases (56%). Fourteen of 91 patients (15%), who had negative results with the initial study, had evidence of leakage at barium swallow. The leakage volume ranged between 0.06 and 0.53 cm3 (mean 0.18 cm3). Clinical evidence of leakage was shown in 3/14 (21%) cases. No complications were detected over a 6-month period following the study. A barium swallow should follow a negative study using an aqueous agent in clinically suspected postoperative leakage, and could be considered as a safe initial study in postoperative patients where a leak is not suspected on clinical grounds.


A wireless implantable passive microdosimeter for radiation oncology.
Wireless measurement of ionizing radiation in close proximity or/and within an irradiated solid tumor is extremely valuable for dose verification and quality control in radiation oncology. For such applications, it is preferable to manufacture such sensors using passive components since high levels of ionizing radiation can damage active electronics. In addition, passive implementation can reduce the cost associated with fabrication and assembly. This paper reports on the development of an implantable micro-machined passive LC transponder for in situ radiation measurement. Dose measurement is performed by monitoring the resonance frequency change associated with the decay of surface change of an electret upon exposure to radiation. This is achieved through a micromachned capacitor with a movable plate that is partially filled with a Teflon electret and connected in parallel with an inductor, thus forming a passive LC tank circuit. For an implantable prototype encapsulated in a glass capsule (2.5 mm in diameter, 2.8 cm in length), test results show that a dose of 30 Gy (from a Co60 source) can produce 1.46 MHz frequency shift resulting in a sensitivity of 49 kHz/Gy.


Relationship between virgin olive oil phenolic compounds and acrylamide formation in fried crisps.
In this paper the relationship between virgin olive oil (VOO) phenol compounds and the formation of acrylamide in potato crisps was investigated. The phenol compositions of 20 VOO samples were screened by LC-MS, and 4 oils, characterized by different phenol compound patterns, were selected for frying experiments. Slices of potatoes were fried at 180 degrees C for 5, 10, and 15 min, and acrylamide content was determined by LC-MS. Results demonstrated that VOO phenolic compounds are not degraded during frying, and crisp color was not significantly different among the four VOOs. Acrylamide concentration in crisps increased during frying time, but the formation was faster in the oil having the lowest concentration of phenolic compounds. Moreover, the VOO having the highest concentration of ortho-diphenolic compounds is able to efficiently inhibit acrylamide formation in crisps from mild to moderate frying conditions. It was concluded that the use of ortho-diphenolic-rich VOOs can be proposed as a reliable mitigation strategy to reduce acrylamide formation in domestic deep-frying.


An artificial gastrocnemius for a transtibial prosthesis.
A transtibial amputee does not have a functional gastrocnemius muscle, which affects the knee as well as the ankle joint. In this investigation, we developed a transtibial prosthesis comprising an artificial gastrocnemius mechanism as well as a powered ankle-foot device. A pilot study was conducted with a bilateral transtibial amputee walking at a self-selected speed. The trial compared muscle electromyography and metabolic cost data for the amputee while using the active gastrocnemius prosthesis and a conventional Flex-Foot prosthesis. The experimental data showed that the compensation for ankle-foot and gastrocnemius function offered by the active device resulted in a reduced metabolic cost for the amputee participant.


[Evaluation of the efficiency of aspheric eximer laser keratoablation (a preliminary communication)].
The authors have evaluated the efficiency of aspheric customized keratoablation (ORK-CAM) versus LASIK operation by the routine technology. The studies were conducted in 2 groups: 1) 11 patients (22 eyes) who had undergone aspheric individualized keratoablation (a study group); 2) 13 patients (24 eyes) who had LASIK operation by the routine technology (a control group). After aspheric individualized correction, the clinical and functional results were comparable in visual acuity and correction accuracy with those after routine laser operations. After optimized ablation, there was a statistically significantly less increase in spheric aberration, cumulative high-grade aberrations than after routine LASIK operation. Questioning about visual comfort revealed that aspheric individualized keratoablation was effective in solving characteristic optical problems. The studies have yielded encouraging preliminary results. Further complex studies are required for comprehensive evaluation of the efficiency of aspheric keratoablation.


Genetically engineered mesenchymal stromal cells produce IL-3 and TPO to further improve human scaffold-based xenograft models.
Recently, NOD-SCID IL2Rγ-/- (NSG) mice were implanted with human mesenchymal stromal cells (MSCs) in the presence of ceramic scaffolds or Matrigel to mimic the human bone marrow (BM) microenvironment. This approach allowed the engraftment of leukemic samples that failed to engraft in NSG mice without humanized niches and resulted in a better preservation of leukemic stem cell self-renewal properties. To further improve our humanized niche scaffold model, we genetically engineered human MSCs to secrete human interleukin-3 (IL-3) and thrombopoietin (TPO). In vitro, these IL-3- and TPO-producing MSCs were superior in expanding human cord blood (CB) CD34+ hematopoietic stem/progenitor cells. MLL-AF9-transduced CB CD34+ cells could be transformed efficiently along myeloid or lymphoid lineages on IL-3- and TPO-producing MSCs. In vivo, these genetically engineered MSCs maintained their ability to differentiate into bone, adipocytes, and other stromal components. Upon transplantation of MLL-AF9-transduced CB CD34+ cells, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) developed in engineered scaffolds, in which a significantly higher percentage of myeloid clones was observed in the mouse compartments compared with previous models. Engraftment of primary AML, B-cell ALL, and biphenotypic acute leukemia (BAL) patient samples was also evaluated, and all patient samples could engraft efficiently; the myeloid compartment of the BAL samples was better preserved in the human cytokine scaffold model. In conclusion, we show that we can genetically engineer the ectopic human BM microenvironment in a humanized scaffold xenograft model. This approach will be useful for functional study of the importance of niche factors in normal and malignant human hematopoiesis.


Antemortem identification by fusion of MR and CT of the paranasal sinuses.
Radiologic forensic identification is usually performed by comparing antemortem and postmortem radiographs. While computed tomography (CT) has become a valuable addition to radiologic identification, magnetic resonance (MR) imaging has only rarely been used for this purpose. In our case, identification was accomplished using fused MR- and CT images in a survivor of a gunshot injury to the head. This case supports and highlights the possibility to perform intermodality radiologic identification comparing preexisting MR imaging to subsequently aquired CT data in living (or deceased) humans as long as manual modifications of windowing, color and contrast enable differentiation of the two modalities in the fused image.


Evaluation of isotopic enrichment factors for the biodegradation of chlorinated ethenes using a parameter estimation model: toward an improved quantification of biodegradation.
A model was developed to predict the concentrations of chlorinated ethenes and ethene during sequential reductive dechlorination of tetrachloroethene (PCE) from stable carbon isotope values using Rayleigh model principles and specified isotopic enrichment factors for each step of dechlorination. The model was tested using three separate datasets of concentration and isotope values measured during three experiments involving the degradation of PCE to vinyl chloride (VC), trichloroethene (TCE) to ethene, and cis-1,2-dichloroethene (cDCE) to ethene. The model was then coupled to a parameter estimation method to estimate values for the isotopic enrichment factors of TCE, cDCE, and VC when they are intermediates in the dechlorination to ethene. The enrichment factors estimated for TCE and cDCE when they were intermediates in biodegradation experiments were close to or within the published range of enrichment factors determined from experiments where TCE or cDCE were the initial substrates. In contrast, the enrichment factors determined by parameter estimation for experiments in which VC was an intermediate in biodegradation experiments were consistently more negative (by approximately 10 per thousandth) than the most negative published enrichment factor determined from experiments where VC was the initial substrate. This finding suggests that the range of enrichment factors for VC dechlorination may not be as narrow as previously suggested (-21.5 per thousandth to -26.6 per thousandth) and that fractionation during VC dechlorination when VC is an intermediate compound may be significantly larger than when VC is the initial substrate. These findings have important implications both for the current practice of extrapolating laboratory-derived isotopic enrichment factors to quantify biodegradation of chlorinated ethenes in the field and for understanding the details of enzymatic reductive dechlorination.


Turning dilemmas into opportunities: a UNU/SCN capacity development network in public nutrition in Central and Eastern Europe.
Capacity development in nutrition is a process whereby individuals, groups, institutions, organizations and societies enhance their abilities to identify and meet challenges in a sustainable manner. To address these issues, in 2001 the UN System Standing Committee on Nutrition (SCN) established a Working Group on Capacity Development under the joint coordination of the United Nations University (UNU) and the International Union of Nutritional Sciences. Several regional professional networks have developed under this working group, the latest for the Central and Eastern Europe (CEE) countries. Ten CEE countries formed a network in 2006 and identified major nutritional challenges in the region, which included: irregular meal patterns; low consumption of fruits/vegetables, milk products and fish; low intake of some micronutrients; and high intakes of fat, sugar and salt. Public policies in nutrition were either weak or absent. Some countries had recently developed nutrition plans. Higher education in nutrition was seen as very important for public nutrition work by professionals in the region, who considered it a prerequisite for reversing the negative trend of the nutrition transition. The network will continue to work on issues that are still not covered adequately. Its activities to date and prospects for the future are assessed against ten principles for good capacity development suggested by the United Nations Development Programme.


Long non-coding RNA PVT1 regulates the migration of hepatocellular carcinoma HepG2 cells via miR-3619-5p/MKL1 axis.
Hepatocellular carcinoma (HCC) is the third most common malignant tumor of the digestive system. Plasma cell tumor heterotopic gene 1 (PVT1) is an intergenic long non-coding RNA that is aberrantly expressed in different cancers. Myocardin-related transcription factor A or megakaryoblastic leukemia 1 (MKL1) is a transcriptional coactivator of serum response factor that has been shown to promote cancer cell migration and invasion. In this study, we investigated the relationship between PVT1 and MKL1 as a novel regulatory mechanism underlying HCC progression. We used HepG2 and Cos‑7 cell lines. Transfection experiments with miR-3619-5p mimics/inhibitor, PVT1, siRNA-PVT1, MKL1, or siRNA-MKL1 were performed. RNA and protein levels were analyzed by quantitative reverse transcription PCR and Western blot, respectively. Cell migration was assessed by transwell assay. Luciferase assays, RNA-FISH, RNA immunoprecipitation, and chromatin immunoprecipitation assays were performed to confirm the interaction between PVT1, miR-3619-5p, and MKL1 in HCC cells. Overexpression of PVT1 was positively correlated with MKL1 upregulation, which promoted HepG2 cell migration. miR-3619-5p inhibited MKL1 expression in HCC cells by acting on its 3'-UTR. Furthermore, PVT1 promoted MKL1 expression and migration in HCC cells by directly binding to miR-3619-5p. In a positive feedback loop, MKL1 could activate PVT1 transcription by binding to the CArG box in the promoter region. Our findings may provide a basis for the development of novel targeted therapies in HCC.


Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones.
The importance of estrogens in homeostatic regulation of many cellular and biochemical events is well illustrated by the pathophysiologic changes that occur with estrogen deficiency. Many of the major diseases of Western populations are hormone dependent and epidemiologic data have shown a strong association between their incidence and diet. In particular, the importance of a plant-based diet is evident from the current dietary recommendations that emphasize an increase in the proportion and amount of fruit and vegetables that should be consumed. Although interpretation of the role of individual components of the diet is difficult from epidemiologic and dietary studies, it is recognized that there are many plant-derived bioactive nonnutrients that can confer significant health benefits. Among these phytochemicals is the broad class of nonsteroidal estrogens called phytoestrogens, and in the past decade there has been considerable interest in the role of isoflavones because of their relatively high concentrations in soy protein. The isoflavones in modest amounts of ingested soy protein are biotransformed by intestinal microflora, are absorbed, undergo enterohepatic recycling, and reach circulating concentrations that exceed by several orders of magnitude the amounts of endogenous estrogens. These phytoestrogens and their metabolites have many potent hormonal and nonhormonal activities that may explain some of the biological effects of diets rich in phytoestrogens.


Mannitol metabolism in brown algae involves a new phosphatase family.
Brown algae belong to a phylogenetic lineage distantly related to green plants and animals, and are found predominantly in the intertidal zone, a harsh and frequently changing environment. Because of their unique evolutionary history and of their habitat, brown algae feature several peculiarities in their metabolism. One of these is the mannitol cycle, which plays a central role in their physiology, as mannitol acts as carbon storage, osmoprotectant, and antioxidant. This polyol is derived directly from the photoassimilate fructose-6-phosphate via the action of a mannitol-1-phosphate dehydrogenase and a mannitol-1-phosphatase (M1Pase). Genome analysis of the brown algal model Ectocarpus siliculosus allowed identification of genes potentially involved in the mannitol cycle. Among these, two genes coding for haloacid dehalogenase (HAD)-like enzymes were suggested to correspond to M1Pase activity, and thus were named EsM1Pase1 and EsM1Pase2, respectively. To test this hypothesis, both genes were expressed in Escherichia coli. Recombinant EsM1Pase2 was shown to hydrolyse the phosphate group from mannitol-1-phosphate to produce mannitol but was not active on the hexose monophosphates tested. Gene expression analysis showed that transcription of both E. siliculosus genes was under the influence of the diurnal cycle. Sequence analysis and three-dimensional homology modelling indicated that EsM1Pases, and their orthologues in Prasinophytes, should be seen as founding members of a new family of phosphatase with original substrate specificity within the HAD superfamily of proteins. This is the first report describing the characterization of a gene encoding M1Pase activity in photosynthetic organisms.


Clinical, Cellular, and Molecular Effects of Corticosteroids on the Response to Intradermal Lipopolysaccharide Administration in Healthy Volunteers.
The intradermal lipopolysaccharide (LPS) challenge in healthy volunteers has proven to be a valuable tool to study local inflammation in vivo. In the current study the inhibitory effects of oral and topical corticosteroid treatment on intradermal LPS responses were evaluated to benchmark the challenge for future investigational drugs. Twenty-four healthy male volunteers received a two-and-a-half-day twice daily (b.i.d.) pretreatment with topical clobetasol propionate 0.05% and six healthy volunteers received a two-and-a-half-day b.i.d. pretreatment with oral prednisolone at 0.25 mg/kg body weight per administration. Participants received one injection regimen of either 0, 2, or 4 intradermal LPS injections (5 ng LPS in 50 µL 0.9% sodium chloride solution). The LPS response was evaluated by noninvasive (perfusion, skin temperature, and erythema) and invasive assessments (cellular and cytokine responses) in suction blister exudate. Both corticosteroids significantly suppressed the clinical inflammatory response (erythema P = 0.0001 for clobetasol and P = 0.0016 for prednisolone; heat P = 0.0245 for clobetasol, perfusion P < 0.0001 for clobetasol and P = 0.0036 for prednisolone). Clobetasol also significantly reduced the number of monocytes subsets, dendritic cells, natural killer cells, and T cells in blister exudate. A similar effect was observed for prednisolone. No relevant corticosteroid effects were observed on the cytokine response to LPS. We successfully demonstrated that the anti-inflammatory effects of corticosteroids can be detected using our intradermal LPS challenge model, validating it for evaluation of future investigational drugs, as an initial assessment of the anti-inflammatory effects of such compounds in a minimally invasive manner.


Guidelines for Risk-Based Changeover of Biopharma Multi-Product Facilities.
In multi-product biopharma facilities, the protection from product contamination due to the manufacture of multiple products simultaneously is paramount to assure product quality. To that end, the use of traditional changeover methods (elastomer change-out, full sampling, etc.) have been widely used within the industry and have been accepted by regulatory agencies. However, with the endorsement of Quality Risk Management (1), the use of risk-based approaches may be applied to assess and continuously improve established changeover processes. All processes, including changeover, can be improved with investment (money/resources), parallel activities, equipment design improvements, and standardization. However, processes can also be improved by eliminating waste. For product changeover, waste is any activity not needed for the new process or that does not provide added assurance of the quality of the subsequent product. The application of a risk-based approach to changeover aligns with the principles of Quality Risk Management. Through the use of risk assessments, the appropriate changeover controls can be identified and controlled to assure product quality is maintained. Likewise, the use of risk assessments and risk-based approaches may be used to improve operational efficiency, reduce waste, and permit concurrent manufacturing of products.


Pig castration: will the EU manage to ban pig castration by 2018?
In 2010, the 'European Declaration on alternatives to surgical castration of pigs' was agreed. The Declaration stipulates that from January 1, 2012, surgical castration of pigs shall only be performed with prolonged analgesia and/or anaesthesia and from 2018 surgical castration of pigs should be phased out altogether. The Federation of Veterinarians of Europe together with the European Commission carried out an online survey via SurveyMonkey© to investigate the progress made in different European countries. This study provides descriptive information on the practice of piglet castration across 24 European countries. It gives also an overview on published literature regarding the practicability and effectiveness of the alternatives to surgical castration without anaesthesia/analgesia. Forty usable survey responses from 24 countries were received. Besides Ireland, Portugal, Spain and United Kingdom, who have of history in producing entire males, 18 countries surgically castrate 80% or more of their male pig population. Overall, in 5% of the male pigs surgically castrated across the 24 European countries surveyed, castration is performed with anaesthesia and analgesia and 41% with analgesia (alone). Meloxicam, ketoprofen and flunixin were the most frequently used drugs for analgesia. Procaine was the most frequent local anaesthetic. The sedative azaperone was frequently mentioned even though it does not have analgesic properties. Half of the countries surveyed believed that the method of anaesthesia/analgesia applied is not practicable and effective. However, countries that have experience in using both anaesthesia and post-operative analgesics, such as Norway, Sweden, Switzerland and The Netherlands, found this method practical and effective. The estimated average percentage of immunocastrated pigs in the countries surveyed was 2.7% (median = 0.2%), where Belgium presented the highest estimated percentage of immunocastrated pigs (18%). The deadlines of January 1, 2012, and of 2018 are far from being met. The opinions on the animal-welfare-conformity and the practicability of the alternatives to surgical castration without analgesia/anaesthesia and the alternatives to surgical castration are widely dispersed. Although countries using analgesia/anaesthesia routinely found this method practical and effective, only few countries seem to aim at meeting the deadline to phase out surgical castration completely.


Effectiveness of static weight-bearing exercises in children with cerebral palsy.
Physiotherapists commonly use static weight-bearing exercises in children with cerebral palsy, which are believed to stimulate antigravity muscle strength, prevent hip dislocation, improve bone mineral density, improve self-esteem, improve feeding, assist bowel and urinary functions, reduce spasticity, and improve hand function. The effectiveness of these exercises has not been thoroughly investigated. This systematic review aimed to examine the research evidence of the effectiveness of static weight-bearing exercises in children with cerebral palsy. Ten studies met the inclusion criteria for this review. The evidence supporting the effectiveness of static weight-bearing exercises in children with cerebral palsy, except the findings of increased bone density and temporary reduction in spasticity, remains limited because of an inadequate number of studies undertaken, inadequate rigor of the research designs and the small number of subjects involved. Clinicians should carefully consider all available evidence before making a decision regarding the potential effectiveness of static weight-bearing for the targeted outcomes.


Effect of thermal processing on the degradation, isomerization, and bioaccessibility of lycopene in tomato pulp.
Thermal processing affects the nutritional value of food products. The nutritional value is not only determined by the content but also by the bioaccessibility of nutrients. The present study was performed to gain detailed insight into the influence of thermal processing on the degradation, isomerization, and bioaccessibility of lycopene isomers in tomato pulp, without adding any other ingredient. The bioaccessibility, which is defined as the fraction of the nutrient that can be released from the food matrix, was measured using an in vitro method. The results demonstrated the rather high thermal stability of lycopene. Although a treatment at 140 °C induced isomerization, the contribution of cis-lycopene to the total lycopene content remained small. Results also confirmed that thermal processing as such can improve the in vitro bioaccessibility of lycopene in tomato pulp, but the improvement was only significant upon treatments at temperatures of 130 and 140 °C. At such intense process conditions, one should be aware of the negative effect on other quality and nutrient parameters. Possibilities of thermal processing as such to improve the nutritional value of tomato pulp (without the addition of other ingredients) thus looks rather limited.


Comparison of the performance of the NucliSENS EasyQ HPV E6/E7 mRNA assay and HPV DNA chip for testing squamous cell lesions of the uterine cervix.
This study aims to evaluate the clinical performance of the NucliSENS EasyQ assay and compare it with HPV DNA genotyping for the detection of high-grade squamous intraepithelial lesions (HSIL) and cancer in a Korean population. In 188 total thin prep samples, the remaining fluid after cytology slide preparation was tested with Goodgene HPV DNA chips and the NucliSENS EasyQ HPV E6/E7 messenger RNA (mRNA) assay. The sensitivity and specificity of each test were calculated with HSIL and squamous cell carcinoma (SCC) as the disease endpoint. Out of the 188 samples, 139 (74%) were positive for DNA of 14 HPV types, while 57 (30%) cases were positive for E6/E7 mRNA. The DNA test was positive in cytology cases of SCC, HSIL, and atypical squamous cell. The mRNA test yielded results of 75%, 74%, 60%, 56%, and 29% positivity in abnormal cytology cases of SCC, HSIL, atypical squamous cells - cannot exclude HSIL, atypical squamous cells of undetermined significance, and low-grade squamous intraepithelial lesion, respectively. In normal cytology cases, the positivity rates were 9% and 53% for the mRNA and DNA tests, respectively. For detection of HSIL and SCC, the sensitivity of the mRNA test was 74.36% and that of the DNA test was 100%, while the specificities of the tests were 85% and 40.83%, respectively. These findings suggest that the HPV E6/E7 mRNA assay can overcome the shortcoming of low specificity of DNA assays for clinical detection of high-grade cervical lesions and malignancies.


Characterization of the diffuse mucosal associated lymphoid tissue of feline small intestine.
Characterization of the feline intestinal mucosal associated lymphoid tissue (MALT) will facilitate investigation of intestinal disease in the cat and promote the cat as an animal model for a range of human diseases which involve the intestinal lymphoid tissue. This includes inflammatory bowel disease, viral and non-viral associated intestinal lymphomas and immunodeficiency associated syndromes. Morphologic and phenotypic characterization of the normal small intestinal diffuse MALT in 22 SPF cats was performed using flow cytometry and cytology on isolated intestinal leukocytes from the intra-epithelial and lamina proprial compartments, as well as immunohistology on tissues from the feline duodenum, jejunum and ileum. The intra-epithelial compartment (IEC) was dominated by lymphocytes (>85%) which frequently contained intracytoplasmic granules. The most striking findings in the IEC were the elevated percentages of CD8 alpha+ lymphocytes (40%), presumed to express CD8 alpha alpha chains, and CD4-/CD8- (double negative) lymphocytes (44%), and the consistent presence of a minor subpopulation of CD3+/CD11d+ IELs (6%). Small percentages of CD4+ lymphocytes (10%) were observed such that the IEL CD4:CD8 ratio (0.25) was low. The LPC also contained a majority of T cells and few plasma cells. However, this compartment had reduced percentages of CD8 alpha+ lymphocytes (28%) and increased percentages of CD4+ lymphocytes (27%) relative to the IEC. However, the LPL CD4:CD8 ratio (1.0) remained low compared with the ratio in peripheral blood. In feline MALT, MHC class II expression was lower than in other peripheral lymphoid compartments. The results of this study provide important reference values for future investigations involving feline intestinal lymphocytes and demonstrates that the leukocyte distribution and phenotypic characteristics of the feline diffuse MALT appear largely similar to the murine, rat and human counterparts.