[Alternatives for castration of suckling piglets, determination of catecholamines and wound healing after castration of suckling piglets at different points of time].
According to the applicable animal welfare legislation, the surgical castration of pigs is allowed up until the age of 4 weeks, without anaesthesia. According to the european guideline (2001/93/EG) it is only permitted in the first week after birth. The investigation should show, whether the castration of young piglets takes a milder course and to what extent stress reactions occur in different age groups. The healing process of castration wounds in piglets that were castrated at the age of four days progressed more rapidly and with less complications than those piglets that were castrated at 28 days of age. The catecholamine levels in younger piglets rose significantly after the operation, while these levels virtually stayed the same in piglets castrated at 28 days. As alternatives to castration without anaesthesia, several methods are in discussion: (1) Castration under general anaesthesia can only be practiced by a veterinary surgeon. The sole use of Azaperon and Ketamine has insufficient pain sedating effect. Isofluran anaesthesia is apparatively extravagant. (2) CO2-Anaesthesia in piglets leads to high strain. (3) Castration under local anaesthesia must be practiced by a veterinary surgeon. The application and the pain after the castration are not taken into consideration. (4) Jung boar fattening up until the slaughtering weight of 80 kg is not transformable, because of boar taste. (5) The breeding of slaughter pigs with little boar taint is not yet transformable. (6) Sperm sexing is not and will not, in the near future, be mature for practice. (7) Immunocastration is an active immunisation against GnRH. The immunological elimination of GnRH suppresses the development of sex hormones, such as testosterone, as well as the substance responsible for boar taint, Androstenone. To consider is the acceptance of the consumer. The preparation has the same effect in humans as it has in swine. "Self injections" have the same effect in humans as it has in swine. "Self injections" are therefore risky.


An immunohistochemical study of p53 expressions in oral submucous fibrosis.
The objective of this histopathological study was to identify the expression of tumor suppressor gene p53 and to detect the correlation between p53 expression and the degree of dysplasia in oral submucous fibrosis (OSMF). A sample size of 30 OSMF patients irrespective of sex was taken up for the study. The tissue samples obtained were subjected to immunohistochemical method to detect p53 protein. The technique used was indirect super sensitive Polymer-HRP IHC detection system. The p53 positive samples were evaluated on a 4-point scale, which ranged from 3+ to negative. Out of 30 cases 3(10%) cases were negative for p53 expression and 13(43.3%) showed + expression, and 14(46.6%) showed ++ expression. On application of Mantel-Haenszel Chi-Square test a statistically significant P <=0.05 i.e. (P=0.012) was obtained and there was Linear-by-Linear association between p53 expressions and dysplasia that showed the point probability of 0.006. Immunohistochemistry is a powerful tool to identify distinct patterns of gene expression in premalignant disorders and also Oral Squamous Cell Carcinomas (OSCC) from different populations. In the present study, a significant number of samples of OSMF were positive for p53 protein.


[Analysis on pathogen detection for 53 influenza outbreaks].
In order to provide a scientific basis for influenza prevention and control, analyzing the epidemic characteristics and laws of influenza outbreaks in Xuzhou area during 2005-2011. Using fluorescent-PCR method to detect influenza virus nucleic acid on Nasopharyngeal swab specimens collected from influenza outbreak cases during 2005-2011 and fast classifying influenza virus A1 (H1N1), A3 (H3N2), new H1N1 BV (Victoria) and BY (Yamagate) on subtypes. At the same time, isolating the influenza virus with MDCK cells, and sending them to the National Influenza Center for review, after the preliminary identification of the isolated influenza virus. During 2005-2011, there are 53 influenza outbreaks in Xuzhou area, which caused by influenza virus subtype BV accounting for 26.42% (14/53), A3 accounting for 49.1% (26/53), A3 and A1 mixture accounting for 3.77% (2/53) and the new H1N1 accounting for 20.75% (11/53). The outbreaks in 2007 and 2009 mainly caused by A3, and show that the winter spring (January) and summer autumn (September) as two popular peaks during 2005-2011; BV mainly causes the outbreaks from Feb. to Jun. In Xuzhou area, since the winter of 2005, influenza virus subtype BV, the A3, and new H1N1 has alternately as mainly predominant strain, caused local influenza outbreaks. In which BV has increased trend year by year during 2005-2011. The students in primary and secondary schools are the major crowd of influenza outbreaks. Fluorescent-PCR detection methods could be a preferred method for reliable and rapid diagnostic of epidemic influenza outbreaks.


The gap between macroeconomic and microeconomic health resources allocation decisions: The case of nurses.
The allocation of healthcare resources takes place at two distinct levels. At the macroeconomic level, policymakers decide on budgets, staffing, cost-effectiveness thresholds, clinical guidelines and insurance payments; at the microeconomic level, healthcare professionals decide on whom to treat, what the appropriate treatment is, how much time and effort should each patient receive and how urgent the need for care is. At both levels, there is a constant social need for just allocation. Policymakers are mostly guided by abstract principles of justice, thinking in terms of groups of patients, epidemiological data, impersonal statistics and economic costs. On the other hand, healthcare professionals understand the need for justice at a more personal level, as they interact with patients and, in a sense, put theory into practice. Nurses hold a unique position in healthcare systems, as, traditionally, they are closer to patients than other health professionals. This means that they have a firsthand view of the effect that their decisions have on specific patients and, therefore, nurses tend to get more influenced by their personal feelings, values and beliefs at the microeconomic level. This presentation shall examine the gap between abstract macroeconomic and concrete microeconomic health resources allocation decisions, with a particular emphasis on the role of the nurse.


High-content analysis and Kinetic Image Cytometry identify toxicity and epigenetic effects of HIV antiretrovirals on human iPSC-neurons and primary neural precursor cells.
Despite viral suppression due to combination antiretroviral therapy (cART), HIV-associated neurocognitive disorders (HAND) continue to affect half of people with HIV, suggesting that certain antiretrovirals (ARVs) may contribute to HAND. We examined the effects of nucleoside/nucleotide reverse transcriptase inhibitors tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) and the integrase inhibitors dolutegravir (DTG) and elvitegravir (EVG) on viability, structure, and function of glutamatergic neurons (a subtype of CNS neuron involved in cognition) derived from human induced pluripotent stem cells (hiPSC-neurons), and primary human neural precursor cells (hNPCs), which are responsible for neurogenesis. Using automated digital microscopy and image analysis (high content analysis, HCA), we found that DTG, EVG, and TDF decreased hiPSC-neuron viability, neurites, and synapses after 7 days of treatment. Analysis of hiPSC-neuron calcium activity using Kinetic Image Cytometry (KIC) demonstrated that DTG and EVG also decreased the frequency and magnitude of intracellular calcium transients. Longer ARV exposures and simultaneous exposure to multiple ARVs increased the magnitude of these neurotoxic effects. Using the Microscopic Imaging of Epigenetic Landscapes (MIEL) assay, we found that TDF decreased hNPC viability and changed the distribution of histone modifications that regulate chromatin packing, suggesting that TDF may reduce neuroprogenitor pools important for CNS development and maintenance of cognition in adults. This study establishes human preclinical assays that can screen potential ARVs for CNS toxicity to develop safer cART regimens and HAND therapeutics.


Effects of word-evoked object size on covert numerosity estimations.
We investigated whether the size and number of objects mentioned in digit-word expressions influenced participants' performance in covert numerosity estimations (i.e., property probability ratings). Participants read descriptions of big or small animals standing in short, medium, and long rows (e.g., There are 8 elephants/ants in a row) and subsequently estimated the probability that a health statement about them was true (e.g., All elephants/ants are healthy). Statements about large animals scored lower than statements about small animals, confirming classical findings that humans perceive groups of large objects as being more numerous than groups of small objects (Binet, 1890) and suggesting that object size effects in covert numerosity estimations are particularly robust. Also, statements about longer rows scored lower than statements about shorter rows (cf. Sears, 1983) but no interaction between factors obtained, suggesting that quantity information is not fully retrieved in digit-word expressions or that their values are processed separately.


Basic mechanisms of hyperbaric oxygen in the treatment of ischemia-reperfusion injury.
HBO treatment affects many of the components involved in I/R injury, including PMNL function, endothelial CAM expression, NO production, NOS expression, cellular energetics, lipid peroxidation, and microvascular blood flow. Given the variety of models used to study the individual components involved in I/R injury, it is difficult to determine which is the predominant factor affected by HBO and which generates the observed beneficial outcomes in most systems. Experimental differences in the types of I/R injury, the timing of HBO treatment relative to the I/R injury (before, during, after, or delayed), the duration of HBO treatment pressure and duration, and the time of outcome measurements confound our ability to compare studies and determine the key beneficial factor. Upon review, it is likely that the sum of many of these effects is responsible for the final outcome. We have been presented with many of the pieces of the puzzle with respect to the beneficial effect of HBO in ischemia-reperfusion injury states. Hopefully, future studies will unite them into a clear picture of the basic mechanism(s) responsible for the benefits of hyperbaric oxygen therapy.


Decree No. 12/1987, 29 June 1987.
This Decree sets forth unified regulations on the guardianship authorities in Hungary. It contains detailed provisions on the activities of the authorities with respect to marriage, family status, adoption, parental authority and state care, guardianship, and management of property. The Decree also contains provisions on international law with respect to guardianship and procedures.


Severe local skin reactions to interferon beta-1b in multiple sclerosis-improvement by deep subcutaneous injection.
Severe local skin reactions to subcutaneous injection of interferon beta-1b in multiple sclerosis are rare, and only 12 cases of severe skin reaction due to interferon beta-1b have been reported to date. We report two cases of severe skin reactions in multiple sclerosis patients following the injection of subcutaneous interferon beta-1b. In case 1, after five years of treatment, a painful indurated erythematous lesion appeared at the injection site on the left buttock. On histological analysis, the lesion showed septal and lobular panniculitis with lymphocytic infiltration. In case 2, cutaneous ulceration was surrounded by painful induration, which developed at the injection site on the right thigh after four years of treatment. The lesions resolved rapidly after discontinuation of interferon beta-1b treatment in both cases. Here, we review cases of similar lesions caused by interferon beta-1b reported in the literature, and discuss the characteristics, mechanism, treatment, and prevention of such lesions.


Biomarker-based analysis of preclinical progression in spinal and bulbar muscular atrophy.
To identify a candidate biomarker reflecting biological changes during the preclinical progression of spinal and bulbar muscular atrophy (SBMA). We analyzed longitudinal changes in biochemical parameters obtained during health examinations before and after the diagnosis of SBMA. We estimated trajectories of clinical markers across years from the onset of weakness using linear mixed models and compared these trajectories with those estimated for male healthy controls and patients with amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD). Moreover, we examined the relationship between serum creatinine level and the onset of symptoms using Kaplan-Meier curves. Between October 2014 and October 2017, we enrolled 40 patients with genetically confirmed SBMA, 48 healthy controls, 25 patients with ALS, and 20 patients with PD. In patients with SBMA, we evaluated the patients' data for a period of 17.3 ± 7.5 years, including 11.4 ± 7.1 years of preclinical phase. Decreases in serum creatinine occurred >10 years before the onset. The mean serum creatinine concentration was 0.56 mg/dL at the onset of weakness in patients with SBMA compared to 0.88 ± 0.10 mg/dL on final evaluation in healthy controls. Serum levels of alanine transaminase and aspartate transaminase showed tendencies to increase in preclinical SBMA. These preclinical changes of biomarkers were not observed in either ALS or PD. Our findings suggest that serum creatinine begins to decrease before the onset of clinical symptoms and is a biomarker for disease progression and the efficacy of therapeutics in preclinical SBMA.


Third-year student diary.
Rosie Perrett is officially halfway through her veterinary degree and to celebrate she and her boyfriend spent a weekend in London. Here, she describes her pre-exam coping strategy.


Malignant disease after radiation treatment of benign gynaecological disorders. A study of a cohort of metropathia patients.
One hundred and seven cases of malignant tumours occurred among 788 women irradiated 1912 to 1977 for metropathia. One hundred and seventy-three women out of 1,219 referred for the same diagnosis and not irradiated developed a malignant tumour. The tumours were diagnosed between 1958 and 1982. The relative risk of malignant tumours among the irradiated women was 1.22 and among the non-irradiated 1.09 compared to cancer registry data. A statistically non-significant increase of the relative risk was found in the irradiated patients for tumours of the rectum (1.58), colon (1.46), and the nervous system (1.67). A decreased overall relative risk was seen for cancer of the breast (0.92) after irradiation, but women treated at the age of 50 or more had an increased risk (2.08). The relative cancer risk of the heavily irradiated sites was not increased during the first 20 years after irradiation, but a statistically significant increase of the risk was seen after 30 years.


Family-Centered Care in Juvenile Justice Institutions: A Mixed Methods Study Protocol.
Treatment and rehabilitation interventions in juvenile justice institutions aim to prevent criminal reoffending by adolescents and to enhance their prospects of successful social reintegration. There is evidence that these goals are best achieved when the institution adopts a family-centered approach, involving the parents of the adolescents. The Academic Workplace Forensic Care for Youth has developed two programs for family-centered care for youth detained in groups for short-term and long-term stay, respectively. The overall aim of our study is to evaluate the family-centered care program in the first two years after the first steps of its implementation in short-term stay groups of two juvenile justice institutions in the Netherlands. The current paper discusses our study design. Based on a quantitative pilot study, we opted for a study with an explanatory sequential mixed methods design. This pilot is considered the first stage of our study. The second stage of our study includes concurrent quantitative and qualitative approaches. The quantitative part of our study is a pre-post quasi-experimental comparison of family-centered care with usual care in short-term stay groups. The qualitative part of our study involves in-depth interviews with adolescents, parents, and group workers to elaborate on the preceding quantitative pilot study and to help interpret the outcomes of the quasi-experimental quantitative part of the study. We believe that our study will result in the following findings. In the quantitative comparison of usual care with family-centered care, we assume that in the latter group, parents will be more involved with their child and with the institution, and that parents and adolescents will be more motivated to take part in therapy. In addition, we expect family-centered care to improve family interactions, to decrease parenting stress, and to reduce problem behavior among the adolescents. Finally, we assume that adolescents, parents, and the staff of the institutions will be more satisfied with family-centered care than with usual care. In the qualitative part of our study, we will identify the needs and expectations in family-centered care as well as factors influencing parental participation. Insight in these factors will help to further improve our program of family-centered care and its implementation in practice. Our study results will be published over the coming years. A juvenile justice institution is a difficult setting to evaluate care programs. A combination of practice-based research methods is needed to address all major implementation issues. The study described here takes on the challenge by means of practice-based research. We expect the results of our study to contribute to the improvement of care for adolescents detained in juvenile justice institutions, and for their families.


Imaging of regional air distributions in porcine lungs using high-performance electrical impedance tomography system.
Electrical impedance tomography (EIT) allows functional imaging of regional lung ventilation for real-time bedside monitoring of mechanically ventilated patients. Images showing time-changes of regional air distributions in the lungs can provide valuable diagnostic information for lung protective mechanical ventilation. This paper reports in vivo porcine imaging experiments of regional lung ventilation using a 16-channel parallel EIT system. Real-time time-difference chest images of 10 animals were reconstructed during mechanical ventilations with a temporal resolution of 50 frame/s. Analyzing the images together with the airway volume-pressure information from the mechanical ventilator, we could successfully produce regional compliance images at PEEP (positive end expiratory pressure) titration. From in vivo animal experiments, we propose the method as a continuous monitoring means for LPV (lung protective ventilation).


Extraskeletal osteosarcoma, telangiectatic variant arising from the small bowel mesentery.
Extraskeletal osteosarcoma (EOS) is a highly aggressive and rare malignant soft tissue tumor, characterized by the production of neoplastic osseous tissue without attachment to the bone or periosteum. It rarely involves the visceral organs. Only 3 cases of mesenteric EOS have been reported in English literature. Here, we describe a male patient of 40 years, who was diagnosed to have EOS arising from small bowel mesentery. This patient presented with lower gastrointestinal (GI) bleeding. Upper GI endoscopy and colonoscopy were normal. Computed tomography scan demonstrated a well defined multi-loculated mixed density mass lesion measuring about 13x7x7 cm in lower abdomen adjacent to small bowel loops with liver metastasis. Palliative en bloc resection of tumor with adjacent small bowel was performed. The histopathology revealed a telangiectatic type osteosarcoma of mesentery. Diagnosis of EOS, its management and the outcome in context of the current literature are discussed.


Persistent Adaptations in Afferents to Ventral Tegmental Dopamine Neurons after Opiate Withdrawal.
Protracted opiate withdrawal is accompanied by altered responsiveness of midbrain dopaminergic (DA) neurons, including a loss of DA cell response to morphine, and by behavioral alterations, including affective disorders. GABAergic neurons in the tail of the ventral tegmental area (tVTA), also called the rostromedial tegmental nucleus, are important for behavioral responses to opiates. We investigated the tVTA-VTA circuit in rats after chronic morphine exposure to determine whether tVTA neurons participate in the loss of opiate-induced disinhibition of VTA DA neurons observed during protracted withdrawal. In vivo recording revealed that VTA DA neurons, but not tVTA GABAergic neurons, are tolerant to morphine after 2 weeks of withdrawal. Optogenetic stimulation of tVTA neurons inhibited VTA DA neurons similarly in opiate-naive and long-term withdrawn rats. However, tVTA inactivation increased VTA DA activity in opiate-naive rats, but not in withdrawn rats, resembling the opiate tolerance effect in DA cells. Thus, although inhibitory control of DA neurons by tVTA is maintained during protracted withdrawal, the capacity for disinhibitory control is impaired. In addition, morphine withdrawal reduced both tVTA neural activity and tonic glutamatergic input to VTA DA neurons. We propose that these changes in glutamate and GABA inputs underlie the apparent tolerance of VTA DA neurons to opiates after chronic exposure. These alterations in the tVTA-VTA DA circuit could be an important factor in opiate tolerance and addiction. Moreover, the capacity of the tVTA to inhibit, but not disinhibit, DA cells after chronic opiate exposure may contribute to long-term negative affective states during withdrawal. Dopaminergic (DA) cells of the ventral tegmental area (VTA) are the origin of a brain reward system and are critically involved in drug abuse. Morphine has long been known to affect VTA DA cells via GABAergic interneurons. Recently, GABAergic neurons caudal to the VTA were discovered and named the tail of VTA (tVTA). Here, we show that tVTA GABA neurons lose their capacity to disinhibit, but not to inhibit, VTA DA cells after chronic opiate exposure. The failure of disinhibition was associated with a loss of glutamatergic input to DA neurons after chronic morphine. These findings reveal mechanisms by which the tVTA may play a key role in long-term negative affective states during opiate withdrawal.


[Validation of the Spanish version of the Charcot-Marie-Tooth disease Pediatric Scale (CMTPedS)].
The Charcot-Marie-Tooth Pediatric Scale (CMTPedS) is a validated and change-sensitive tool for assessing the severity of neuropathy in children and adolescents between 3 and 20 years of age. The aim of this article is to translate and validate a Spanish version of the CMTPedS in order to disseminate its use in Spanish-speaking countries. The process used to translate the CMTPedS into Spanish was the reverse parallel translation method based on the principles of good practice for translation and the cultural adaptation process of the Food and Drug Administration Guidelines. A direct translation of the original source of the CMTPedS into Spanish was performed first and reviewed by experts in Charcot-Marie-Tooth (CMT) disease trained in the use of the CMTPedS tool. The Spanish version was then translated back into English by a linguist specialised in translation. The preliminary Spanish version of the CMTPedS was evaluated in 18 children with CMT aged 6-20 years (mean: 13.27). The scale was well tolerated and easy for children to understand and easy for clinicians to apply. None of the patients had any difficulty completing the scale. The Spanish version of the CMTPedS can be used for monitoring and conducting clinical trials in the Spanish population and in Spanish-speaking countries.


Identifying populations at risk: interdisciplinary environmental climate change tracking.
Climate change, experienced as extreme weather events such as heat waves can lead to poorer air quality and underscores the critical need to consider the consequences of these environmental changes on health. Changes are occurring at a rate that exceeds what the world has experienced over the last 650,000 years, yet little attention has been focused on the potentially catastrophic public health effects of climate change. This study instituted a two-phase approach. In building capacity for an Environmental Public Health Tracking Network, the District of Columbia Department of Health first examined the availability of climate change and health data. These data were then used to assess vulnerabilities and disease burden associated with heat, air quality, and hospitalizations for asthma (N = 5,921) and acute myocardial infarction (AMI) (N = 2,773) during 2007-2010. A Poisson regression analysis was applied to the time series of daily counts for hospitalizations for selected age, race, and gender groups. Although no significant associations were found for PM2.5, PM10, or ozone with asthma-related or AMI-related hospitalizations with seasonal changes, surveillance data found disparities in hospitalizations particularly in female, African American residents for both asthma and AMI. Tracking Networks are critical for assessing community environmental health vulnerabilities.


Novel method for the synthesis of hydrophobic Pt-Ru nanoparticles and its application to preparing a Nafion-free anode for the direct methanol fuel cell.
Pt-Ru alloy is a bimetallic catalyst most commonly used in the direct methanol fuel cell (DMFC). In this paper, a new process to synthesize an unsupported Pt-Ru colloid has been introduced. The characteristics of synthesized nanoparticles were identified by XRD, TEM/EDX, and SEM, and it shows that Ru atoms are incorporated into the Pt fcc structure and the well-dispersed particles (diameter approximately 4 nm) possess a Pt-rich feature. This catalyst shows a hydrophobic characteristic which can adsorb very well on the hydrophobic-treated carbon paper or carbon cloth without the need of Nafion. Accordingly, this method can avoid particle agglomeration, and the synthesized catalyst demonstrates strong adsorption with carbon paper. In addition, this colloid-type Nafion-free catalyst was measured via linear sweep voltammetry (LSV) and exhibited electrochemical activity for methanol oxidation comparable to the commercial one with Nafion binding.


Cross-linked long-pitch actin dimer forms stoichiometric complexes with gelsolin segment 1 and/or deoxyribonuclease I that nonproductively interact with myosin subfragment 1.
Actin dimer cross-linked along the long pitch of the F-actin helix by N-(4-azido)-2-nitrophenyl (ANP) was purified by gel filtration. Purified dimers were found to polymerize on increasing the ionic strength, although at reduced rate and extent in comparison with native actin. Purified actin dimer interacts with the actin-binding proteins (ABPs) deoxyribonuclease I (DNase I) and gelsolin segment-1 (G1) as analyzed by gel filtration and native gel electrophoresis. Complex formation of the actin dimer with these ABPs inhibits its ability to polymerize. The interaction with rabbit skeletal muscle myosin subfragment 1 (S1) was analyzed for polymerized actin dimer and dimer complexed with gelsolin segment 1 or DNase I by measurement of the actin-stimulated myosin S1-ATPase and gel filtration. The data obtained indicate binding of subfragment 1 to actin dimer, albeit with considerably lower affinity than to F-actin. Polymerized actin dimer was able to stimulate the S1-ATPase activity to about 50% of the level of native F-actin. In contrast, the actin dimer complexed to DNase I or gelsolin segment 1 or to both proteins was unable to significantly stimulate the S1-ATPase. Similarly, G1:dimer complex at 20 microM stimulated the rate of release of subfragment 1 bound nucleotide (mant-ADP) only 1.6-fold in comparison to about 9-fold by native F-actin at a concentration of 0.5 microM. Using rapid kinetic techniques, a dissociation constant of 2.4 x 10 (-6) M for subfragment 1 binding to G1:dimer was determined in comparison to 3 x 10 (-8) M for native F-actin under identical conditions. Since the rate of association of subfragment 1 to G1:dimer was considerably lower than to native F-actin, we suspect that the ATP-hydrolysis by S1 was catalyzed before its association to the dimer. These data suggest an altered, nonproductive mode for the interaction of subfragment 1 with the isolated long-pitch actin dimer.


Dynamic alterations in the donkey fecal bacteria community and metabolome characteristics during gestation.
In donkeys, the gestation period is a dynamic and precisely coordinated process involving systemic and local alterations. Both the gut microbiota and its link with blood metabolites are thought to play significant roles in maintaining maternal health and supporting fetal development during the gestation period. This study was conducted to evaluate gut microbiota changes and the correlation with plasma metabolites in Dezhou donkeys during the gestation period. The donkeys were divided into the four following groups according to their pregnancy stages: the non-pregnant (NP), early stage of pregnancy (P1), middle stage of pregnancy (P2), and late stage of pregnancy (P3) groups. A total of 24 (n = 6 per group) samples of donkey feces and plasma were collected. The results showed that the diversity (Shannon index) of fecal bacteria significantly increased throughout the gestation period. The phyla Spirochaetota and Fibrobacterota varied significantly according to the stages of pregnancy (p < 0.05). At the genus level, the abundance of Treponema in pregnant donkeys was greater than that in non-pregnant donkeys (p < 0.05), and the genus Streptococcus reached its maximum abundance in the P2 period (p < 0.05). The abundance of Ruminococcaceae_NK4A214_group and norank_f_norank_o_WCHB1-41 linearly increased with the progression of pregnancy (p < 0.05). In addition, the host plasma metabolome was altered significantly during the gestation period. Testolic acid, estradiol-17beta 3-sulfate, equol 7'-o-glucuronide, equol 4'-o-glucuronide, estrone, estrone 3-glucuronide, and estradiol were the most significant differential enriched metabolites, and they increased gradually as gestation progressed. The altered metabolites were mainly enriched in pathways matched to bile secretion, ABC transporters, amino acid metabolism, protein digestion and absorption, mineral absorption, fatty acid degradation, glycerophospholipid metabolism, and steroid hormone biosynthesis. We also found a significant correlation between the shifts in donkey fecal bacteria and changes in the host metabolism. In summary, this study provided systematic data on the fecal bacterial changes and host plasma metabolism of donkeys throughout pregnancy. The results indicated that host-bacteria interactions during the gestation period influence the host metabolism. These interactions benefit the pregnant donkeys by providing a sufficient supply of nutrients and energy for fetal growth and maternal health.


Lactobacillus fermentum ME-3 - an antimicrobial and antioxidative probiotic.
The paper lays out the short scientific history and characteristics of the new probiotic Lactobacillus fermentum strain ME-3 DSM-14241, elaborated according to the regulations of WHO/FAO (2002). L. fermentum ME-3 is a unique strain of Lactobacillus species, having at the same time the antimicrobial and physiologically effective antioxidative properties and expressing health-promoting characteristics if consumed. Tartu University has patented this strain in Estonia (priority June 2001, patent in 2006), Russia (patent in 2006) and the USA (patent in 2007). The paper describes the process of the identification and molecular typing of this probiotic strain of human origin, its deposition in an international culture collection, and its safety assessment by laboratory tests and testing on experimental animals and volunteers. It has been established that L. fermentum strain ME-3 has double functional properties: antimicrobial activity against intestinal pathogens and high total antioxidative activity (TAA) and total antioxidative status (TAS) of intact cells and lysates, and it is characterized by a complete glutathione system: synthesis, uptake and redox turnover. The functional efficacy of the antimicrobial and antioxidative probiotic has been proven by the eradication of salmonellas and the reduction of liver and spleen granulomas in Salmonella Typhimurium-infected mice treated with the combination of ofloxacin and L. fermentum strain ME-3. Using capsules or foodstuffs enriched with L. fermentum ME-3, different clinical study designs (including double-blind, placebo-controlled, crossover studies) and different subjects (healthy volunteers, allergic patients and those recovering from a stroke), it has been shown that this probiotic increased the antioxidative activity of sera and improved the composition of the low-density lipid particles (LDL) and post-prandial lipids as well as oxidative stress status, thus demonstrating a remarkable anti-atherogenic effect. The elaboration of the probiotic L. fermentum strain ME-3 has drawn on wide international cooperative research and has taken more than 12 years altogether. The new ME-3 probiotic-containing products have been successfully marketed and sold in Baltic countries and Finland.


Functional factors associated with continuous eruption of maxillary incisors in adulthood: A 10-year prospective cohort study.
To investigate whether functional factors estimated by the masseter muscle thickness (MMT) and the maximum occlusal force (MOF), were associated with the amount of continuous eruption of maxillary incisors in adults. Dental casts were taken twice in 24 adult female patients during a 10-year prospective cohort study. At the first appointment, ultrasonographic measures of the MMT and MOF were recorded. The casts were scanned into a digital model and measurements of the eruption and clinical crown lengthening (CL) of the maxillary incisors were calculated after superimpositions on the palatal region. Univariate and multivariate mixed effect regression models were used to assess the single and joint role of functional factors, with presence or absence of occlusal contacts and CL on incisor eruption. By using the linear mixed effects regression model, we observed that both the MMT and MOF were correlated with the maxillary incisor eruption. In particular, the thicker the masseter or the stronger the occlusal force, the lower the amount of eruption. Using a backward multivariable mixed effects model, the incisor eruption was correlated with the MMT combined with presence or absence of contacts and clinical CL. The amount of tooth eruption (0.32 mm on average) was positively associated with CL (0.29 mm on average); therefore, the greater the CL (gingival recession), the greater the amount of tooth eruption. The presence of occlusion contact between the maxillary incisors and their mandibular antagonists was found as an inhibitor of eruption in the multivariate model. The functional capacity of masticatory muscles, as estimated by the MMT, plays a role in the amount of maxillary incisor eruption. The stronger the masticatory muscles, the lower the amount of eruption.


Operative nuances of an occipital artery to posterior inferior cerebellar artery bypass.
Occipital artery to posterior inferior cerebellar artery bypasses remain an important tool for cerebrovascular neurosurgeons, particularly in the management of complex aneurysms of the posterior inferior cerebellar artery requiring proximal occlusion or trapping. The procedure requires meticulous technique and attention to detail. The authors outline their technique for accomplishing this bypass emphasizing nuances for complication avoidance.


Dissipativity-Based Consensus Tracking Control of Nonlinear Multiagent Systems With Generally Uncertain Markovian Switching Topologies and Event-Triggered Strategy.
This article focuses on the dissipativity-based consensus tracking control (DBCTC) problems of time-varying delayed leader-following nonlinear multiagent systems (LFNMASs) with the event-triggered transmission strategy. The switching topologies of the LFNMASs are subject to the uncertain and partially unknown generally Markovian jumping process. The control inputs of the following agents are updated according to the proposed event-triggered transmission strategy, which could reduce the communication burden. Based on the event-triggered transmission condition and distributed consensus protocol, some dissipativity-based criteria obtained by adopting the delay-product-term Lyapunov-Krasovskii functional (DPTLKF) and higher order polynomial-based relaxed inequality (HOPRII) are proposed to guarantee the LFNMAS consensus. The validity of the main results is verified by two simulation examples.


[The RUTA project (Registro UTIC Triveneto ANMCO). An e-network for the coronary care units for acute myocardial infarction].
In the era of evidence-based medicine, the monitoring of the adherence to the guidelines is fundamental, in order to verify the diagnostic and therapeutic processes. Informatic paperless databases allow a higher data quality, lower costs and timely analysis with overall advantages over the traditional surveys. The RUTA project (acronym of Triveneto Registry of ANMCO CCUs) was designed in 1999, aiming at creating an informatic network among the coronary care units of a large Italian region, for a permanent survey of patients admitted for acute myocardial infarction. Information ranges from the pre-hospital phase to discharge, including all relevant clinical and management variables. The database uses DBMS Personal Oracle and Power-Builder as user interface, on Windows platform. Anonymous data are sent to a central server.


Frequency of antibodies against E4 and E7 from human papillomavirus type 16 in Mexican soldiers.
The high prevalence of HPV in men's genitalia and the low frequency of virus-associated lesions gave rise to questions on the influence of infection-site on the HPV antibody profile. In a cross-sectional study, HPV infection in penis and urethra, and serum antibodies against HPV-16 E4 and E7 proteins were evaluated in 288 Mexican soldiers. The results showed that HPV prevalence was 31% (51% in penis, 11% in urethra and 38% in both sites), while 47% were multiple infections. Overall, seroprevalence was 13% for anti-E4 antibodies and 6% for anti-E7. However, the highest prevalence of anti-E4 antibodies was observed in men with HPV infection in urethra (30%), while for E7 antibodies, the highest prevalence (10%) was found in men who tested positive for HPV in penis. The prevalence of IgG and IgA anti-E4 was related to HPV-16 urethral infection, while detection of HPV-16 in penis was related to IgG anti-E7 prevalence. In conclusion, the high-risk sexual behavior observed in this population might be responsible for high HPV prevalence and multiple infections. However, the seroprevalence of E4 and E7 was similar to that observed in healthy Mexican women. These results suggest that the humoral immune response against HPV infection in men differs, depending on the site of infection.


Molecular regulation of muscle stem cells by 'quiescence genes'.
Skeletal muscle has great regenerative potential that depends on muscle stem cells, called satellite cells. In uninjured muscle, satellite cells reside beneath the basal lamina and are maintained in quiescent and undifferentiated state. This state is considered a requisite for sustaining the satellite cell pool, but the molecular mechanism is still unknown. In our previous study, we developed a novel monoclonal antibody that specifically recognized muscle satellite cells in skeletal muscle. Using this monoclonal antibody, we purified satellite cells and performed genome-wide transcriptome analysis. In these analyses, we found that satellite cells expressed Hesr1/Hey1 and Hesr3/HeyL genes known as down stream target of Notch signaling. Although each single knock out mice did not indicate obvious phenotype in skeletal muscle, Hesr1/Hesr3 double knock out mice showed remarkably decreased number of satellite cells. Intriguingly, dKO satellite cells were not kept in quiescent and differentiated state in adult skeletal muscle. This dysregulated state of satellite cells lead to gradually decreased number of satellite cells and age-dependent regeneration defect. These results indicate that Hesr1/3 is essential for muscle stem cell biology and will facilitate this research field.


[Monochorionic twin pregnancy and the following problems].
Monochorionic twin pregnancies have an increased risk of intrauterine and postnatal complications because of the present placental vascular anastomoses. The main problems are the development of twin-to-twin transfusion syndrome,selective intrauterine growth restriction, monoamniotic twins and single intrauterine death on the one hand and congenital abnormalities like twin reversed-arterial perfusion and conjoined twins on the other hand. Fetoscopic laser therapy with selective coagulation of placental intertwin anastomoses is the best option in the treatment of twin-to-twin transfusion syndrome. The risk of preterm delivery, cerebral injury and abnormalities of long-term neurodevelopmental outcome are increased. Perinatal management of monochorionic twin pregnancies should be performed in specialized tertiar centers.


Simultaneous, quantitative determination of opiates, amphetamines, cocaine and benzoylecgonine in oral fluid by liquid chromatography quadrupole-time-of-flight mass spectrometry.
A method using liquid chromatography coupled to tandem mass spectrometry is described for the determination of drugs of abuse in oral fluid. The method is able to simultaneously quantify amphetamines (amphetamine, methamphetamine, MDA, MDMA and MDEA), opiates (morphine and codeine), cocaine and benzoylecgonine. Only 200 micro of oral fluid is spent for analysis. The sample preparation is easy and consists of mixed mode phase solid-phase extraction. Reversed-phase chromatography is carried out on a narrow bore phenyl type column at a flow-rate of 0.2 ml/min. A gradient is applied ranging from 6 to 67.6% methanol with ammonium formate (10 mM, pH 5.0) added to the mobile phase. The column effluent was directed into a quadrupole-time-of-flight instrument by electrospray ionization, without the use of a splitter. A validation study was carried out. Recovery ranged from 52.3 to 98.8%, within-day and between-day precision expressed by relative standard deviation were less than 11.9 and 16.8%, respectively, and inaccuracy did not exceed 11.6%. The limit of quantification was 2 ng/ml (0.66 x 10(-5)-1.48 x 10(-5) M) for all compounds. Internal standards were used to generate quadratic calibration curves (r(2)>0.999). The method was applied to real samples obtained from suspected drug users. An interference was observed from the device used to sample the oral fluid, consequently this was excluded from the method which was validated on oral fluid obtained by spitting in a test-tube.


Prediction of late recurrence after radiofrequency ablation of HBV-related hepatocellular carcinoma with the age-male-albumin-bilirubin-platelets (aMAP) risk score: a multicenter study.
Long-term survivals of patients with HBV-related hepatocellular carcinoma are limited by the high incidence of tumor recurrence after radiofrequency ablation (RFA), identification of the risk factors and understanding the patterns of recurrence can help to improve the comprehensive management of patients after RFA. Therefore, the purpose of the study is to explore the prognostic value of the age-male-albumin-bilirubin-platelets (aMAP) score in patients with early-stage HBV-related hepatocellular carcinoma (HCC) receiving RFA; investigate the risk factors and patterns of late recurrence (LR); and develop a nomogram to predict recurrence-free survival (RFS). A retrospective review of HBV-related HCC patients who underwent primary RFA from March 2012 to December 2020 was conducted. The prognostic value of the aMAP score was evaluated in a primary cohort (n=302) and then further validated in an independent validation cohort (n=143). The optimal threshold of aMAP scores was calculated by X-tile 3.6.1 software. A prognostic nomogram was constructed from multivariate analysis and validated in an external validation cohort. Patients with aMAP scores ≤63.8, 63.8-67.8, and >67.8 were classified into low-, medium-, and high-recurrence risk groups, respectively. The C-index to predict LR was 0.76 (95% CI: 0.700-0.810). The high-risk group was associated with the worst RFS (HR: 5.298; 95% CI, 2.697-10.408; P<0.001) and overall survival (OS) (HR: 2.639; 95% CI, 1.097-6.344; P=0.03) compared with medium- and low-risk groups. The aMAP score, multiple tumors and preoperative HBV DNA level were independent risk factors for LR. The proposed nomogram had excellent performance in predicting LR of HBV-related HCC [C-index: 0.82 (95% CI: 0.772-0.870)]. This study demonstrated that the aMAP score can serve as an objective predictor of LR for HBV-related HCC patients after RFA. The nomogram based on preoperative HBV DNA level, aMAP score, and number of tumors can reliably help clinicians to stratify the recurrence risk of HCC patients after RFA.


Impact of an alternating first-line antibiotics strategy in febrile neutropenia.
Rising antibiotic resistance poses a challenge to the management of febrile neutropenia in patients with haematological malignancies receiving chemotherapy. We studied an alternating first-line antibiotic strategy to determine its impact on all-cause mortality and bacteremia rates in patients with febrile neutropenia. An alternating first-line antibiotic strategy was established in mid-2013. Data for 2012 (before strategy implementation) and 2014 (post-strategy implementation) were compared. Antibiotic Heterogeneity Index (AHI) for each of the two time-periods was also calculated. There were 2012 admissions (26082 patient-days) in 2012 and 1843 admissions (24331 patient-days) in 2014. There was no significant difference in the baseline characteristics of patients in the two groups. The defined daily doses (DDD) of cefepime (CEF) fell while the DDD of piperacillin-tazobactam (PTZ) rose in 2014 compared with 2012. Vancomycin DDD fell in 2014. The AHI was 0.466 in 2012 and 0.582 in 2014. The difference in all-cause mortality was not statistically significant. There was no difference in rates of bacteremia with CEF-resistant, PTZ-resistant and carbapenem-resistant gram-negative organisms in the two groups. Rates of new cases of Methicillin-resistant Staphylococcus aureus (MRSA) were 2.38/1000 and 2.59/1000 patient-days in 2012 and 2014 respectively. Rates of new cases of Vancomycin-resistant Enterococcus (VRE) were 1.84/1000 and 1.81/1000 patient-days in 2012 and 2014 respectively. There was no Carbapenem-resistant Enterobacteriaceae (CRE) bacteremia in 2012 and 1 in 2014. An alternating first-line antibiotic strategy resulted in an increase in antibiotic heterogeneity, without increasing mortality. There was also no significant increase in bacteremia rates.


Irreducible lateral dislocation of the proximal interphalangeal joint--a case report.
We present a rare case of a lateral dislocation of the proximal interphalangeal joint that required open reduction. During an operation, we found the collateral ligament and the capsule interposing into the joint space. After reducing the soft tissue and reproducing the collateral ligament with a suture anchor, sufficient joint stability and full range of motion was achieved.


Effects of cyclosporin on cholesterol 27-hydroxylation and LDL receptor activity in HepG2 cells.
The hypothesis that mitochondrial sterol 27-hydroxylase plays a role in the sterol-mediated down-regulation of LDL receptor activity was evaluated in HepG2 cells. 27-Hydroxycholesterol was found to be more potent at suppressing LDL receptor activity than cholesterol (IC50 values of 8 mu M and 142 mu M for 27-hydroxycholesterol and cholesterol, respectively) when the sterols were delivered to cells from 2-hydroxypropyl-beta-cyclodextrin (beta-CD)-solubilized solutions. Cyclosporin, an immunosuppressant which has been shown to inhibit the 27-hydroxylation of sterols, was used to assess whether the formation of endogenous 27-hydroxycholesterol was required for the cholesterol-induced suppression of LDL receptor activity. Cyclosporin dose-dependently inhibited the 27-hydroxylation of cholesterol by HepG2 mitochondria (Ki = 0.25 mu M) and HepG2 cell cultures (IC50 = 1 mu M). At 1 mu M, cyclosporin had no effect on LDL receptor activity, and did not prevent the suppression of LDL receptor activity caused by: 1) the addition of beta-CD-solubilized cholesterol, 2) the receptor-mediated uptake of beta-VLDL, or 3) the inhibition of cholesterol esterification. In contrast, 10 mu M cyclosporin was found to inhibit the esterification of cholesterol and to increase the cellular level of free cholesterol resulting in suppression of LDL receptor activity. These results suggest that if mitochondrial sterol 27-hydroxylase plays a role in the regulation of LDL receptor activity, it is not through the formation of potent regulatory oxysterols, but through its effects on the availability and/or size of the free cholesterol pool regulating LDL receptor activity.


A randomised placebo-controlled trial of vaginal misoprostol for cervical priming before hysteroscopy in postmenopausal women.
To investigate the effectiveness of misoprostol given vaginally for cervical priming before hysteroscopy in postmenopausal women. Double-blind randomised controlled study. Regional hospital, Hong Kong. One hundred women with postmenopausal bleeding scheduled for hysteroscopy from October 1998 to September 2001 were randomly assigned to receive either misoprostol or placebo vaginally before the operation. The number of women requiring cervical dilatation, outcome of hysteroscopy and side effects of the medication were assessed. Forty-eight women receiving misoprostol and 48 women receiving placebo were compared. The mean degree of endocervical diameter estimated by Hegar's dilator was similar between the treatment group and the control group. A similar number of women in the treatment group and the control group required cervical dilatation. The operative times for both groups were similar. The incidence of side effects was comparable in both groups. The most common side effects for misoprostol were febrile episodes and diarrhoea. There was no cervical tear nor uterine perforation encountered in both groups. The mean duration of hospital stay in both groups were similar. Subanalysis of results were similar in women receiving vaginal medication at least five hours before the operation. Vaginal misoprostol was not shown to reduce the need for cervical dilatation in postmenopausal women. It cannot convert diagnostic hysteroscopy from a hospital procedure into an office one in postmenopausal women with tight cervical os.


Hemobilia complicating elective laparoscopic cholecystectomy: a case report.
Iatrogenic injury to the hepatic or cystic arteries can occur during laparoscopic cholecystectomy and can be seen in isolation or in association with bile-duct injury. The most common manifestation of arterial injury is intraoperative hemorrhage; also, interruption of the right hepatic artery can occur without hemorrhage, and this can be clinically insignificant or associated with hepatic ischemia. A less common manifestation of arterial injury during laparoscopic cholecystectomy is presented. A 48-year-old woman had a pseudoaneurysm of the major anterior branch of the right hepatic artery in association with an injury to the common hepatic duct. This complication presented as massive hemobilia after she had been discharged from the hospital. Definitive repair of the pseudoaneurysm was carried out at the time of Roux-en-Y hepaticojejunostomy for correction of the associated duct injury. This unusual vascular complication should be considered in patients after laparoscopic cholecystectomy who demonstrate evidence of late occult or obvious hemorrhage.


Adenovirus-mediated gene transfer of human lipoprotein lipase ameliorates the hyperlipidemias associated with apolipoprotein E and LDL receptor deficiencies in mice.
Lipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of triglyceride-rich lipoproteins. We tested the efficacy of adenovirus-mediated gene transfer of LPL as treatment of experimental hyperlipidemias associated with apolipoprotein (apoE) deficiency (apoE-/-) and low-density lipoprotein receptor (LDLr) deficiency (LDLr-/-) in mice. Replication-defective adenovirus containing the human LPL cDNA driven by a cytomegalovirus promoter (Ad.hLPL) efficiently transduced CHO-ldlA7 cells in vitro, inducing in these cells the production of bioactive LPL (73 mU/ml). Intravenous injection of Ad.hLPL (2 x 10(9) pfu) led to high-level expression of hLPL mRNA and LPL activity in the liver (88.3 mU/ml) and in post-heparin plasma (116.1 mU/ml). Overexpression of LPL resulted in marked reductions in total plasma cholesterol (TC; 48%, 43%, 25%) and triglycerides (TTg; 63%, 40%, 70%, p < 0.01) in apoE-/-, LDLr-/-, and wild-type (WT) mice, respectively. Fast protein liquid chromatography (FPLC) fractionation of plasma lipoproteins showed a marked decrease in very-low-density lipoprotein (VLDL)/chylomicron remnant cholesterol (V/CR-C) in apoE-/- (83%), LDLr-/- (84%), and WT mice (58%, p < 0.01). VLDL/chylomicron remnant triglycerides (V/CR-Tg) were virtually eliminated in apoE-/- (92%), LDLr-/- (86%), and WT mice (84%, p < 0.05). No significant changes were detected in LPL activities, plasma lipids, or lipoproteins of mice injected with a control virus, Ad.Luc, containing the luciferase instead of the LPL cDNA. In summary, infusion of Ad.hLPL leads to increased liver and post-heparin plasma LPL activities, significantly reduced TC, TTg, V/CR-C, and V/CR-Tg in WT mice, as well as in mice with apoE and LDLr deficiencies. Adenovirus-mediated LPL gene transfer to the liver is an effective means of reversing many of the lipoprotein abnormalities in apoE- and LDLr-deficient mice.


Adiponectin-impaired adipocyte differentiation negatively regulates fat deposition in chicken.
Adiponectin is a protein hormone secreted exclusively by adipocytes that plays an important role in the modulation of glucose and lipid metabolism. To investigate the effect of adiponectin on lipid metabolism in chicken, rosiglitazone (agonist of adiponectin) and dexamethasone (inhibitor of adiponectin) were used to treat 23-day-old broilers in vivo. To verify the functionality of adiponectin on fat deposition, chicken pre-adipocytes were cultured in the medium containing 10 μg/ml adiponectin. Serum adiponectin and lipids and fat distribution were analysed. Oil Red O staining was used to determine lipid deposition in adipocytes. The expression levels of adiponectin, adiponectin receptors (AdipoR) and lipid metabolism-related genes in different tissues and pre-adipocytes were measured using real-time PCR, and the abundance of lipid metabolism-related proteins was measured by Western blot. Rosiglitazone increased serum adiponectin concentration and the expression levels of adiponectin and adiponectin receptor 1 (AdipoR1) in tissues and significantly decreased levels of serum lipids and fat deposition. Rosiglitazone significantly increased the expression levels of adipose triglyceride lipase (ATGL) and AdipoR1 and decreased the expression levels of fatty acid synthase (FAS). Dexamethasone had the converse effects compared with rosiglitazone. Oil red O staining results showed a marked decrease in fat deposition in cells treated with adiponectin. In adipocytes, adiponectin could decrease the expression levels of CCAAT/enhancer-binding protein α (C/EBPα) and FAS and increased the expression levels of ATGL and AdipoR1. These results indicate that adiponectin has a remarkable effect on impairment of adipocyte differentiation, which contributes to the negative regulation of fat deposition in chicken.


Estimation of physical activity and prevalence of excessive body mass in rural and urban Polish adolescents.
Excessive body mass and sedentary lifestyle are well-known factors for cardiovascular risk, which when present in the young population may have significant health consequences, both in the short- and long-term. The aim of the study was to evaluate the prevalence of overweight, obesity, and sedentary lifestyle in two teenage populations living in an urban or rural area. An additional aim was to compare their physical activity. The study was designed and conducted in 2009. The study population consisted of 116 students aged 15-17 years - 61 males (52.7%) and 55 females (47.3%), randomly selected from public junior grammar schools and secondary schools in the Poznań Region. There were 61 respondents from a rural area - 32 males (52.5%) and 29 females (47.5%), whereas 55 teenagers lived in an urban area - 29 males (47.5%) and 26 females (47.3%). Students were asked to complete a questionnaire, which was especially prepared for the study and contained questions concerning health and lifestyle. A basic physical examination was carried out in all 116 students, including measurements of the anthropometric features. Calculations were performed using the statistical package STATISTICA (data analysis software system), Version. 8.0. When comparing these two populations, no statistically significant differences were detected in the ratio of weight-growth, with the exception of the fact that the urban youths had a larger hip circumference (97.1 v. 94.3 cm, p<0.05). In the group of urban students there were also significantly more subjects with excessive body weight (27.3% v. 24.6%, p<0.05), with a predominant proportion of obese students (60%). There were significantly more male obese individuals (66.7%). In the population of rural teenagers, obesity rate did not differ statistically significantly from the percentage of overweight (11.5% v. 13.1%, p>0.05), the problem of excessive weight affected both sexes in a similar proportion (25% boys and 24.1% girls, p>0.05). In this paper it is shown that there were differences concerning physical activity of teenagers living in urban and rural areas. Urban students much more often declared an active lifestyle (72.7% v.42.6%, p<0.05), used a variety of additional forms of activity (not counting compulsory physical education classes).


Asymptomatic pancreatic adenocarcinoma presenting as an orbital metastatic tumor.
Although rare, orbital metastatic tumors may be the initial presentation of an asymptomatic primary carcinoma. We report a rare case, with clinicopathological correlation, of metastatic pancreatic adenocarcinoma, presenting first in the orbit with symptoms of diplopia, blurring of vision and supraorbital ache. Computed tomography and magnetic resonance imaging of the orbit showed a left solid intraconal tumor with peripheral rim enhancement. The tumor demonstrated hypointensity on both T1- and T2-weighted sequences. Excisional biopsy was performed and histopathology confirmed a metastatic adenocarcinoma. Subsequent gastrointestinal imaging and tumor markers revealed an asymptomatic pancreatic adenocarcinoma, with multiple liver metastases. Our patient developed hepatobiliary sepsis and passed away 44 days after diagnosis. This case highlights the role of early biopsy of atypical orbital tumors in the localization of an asymptomatic primary carcinoma.


Remarks on feedforward circuits, adaptation, and pulse memory.
This note studies feedforward circuits as models for perfect adaptation to step signals in biological systems. A global convergence theorem is proved in a general framework, which includes examples from the literature as particular cases. A notable aspect of these circuits is that they do not adapt to pulse signals, because they display a memory phenomenon. Estimates are given of the magnitude of this effect.


Evaluation of communicative and functional abilities in Wolf-Hirshhorn syndrome.
Wolf-Hirschhorn syndrome (WHS) is a genetic condition characterized by many clinical disorders, learning difficulties, dysphagia, neuromotor deficits and communicative deficits. Up until now, no studies in the literature have described the development of communicative and functional abilities in subjects with WHS. In the present study of 11 patients with WHS, a descriptive analysis was made of several abilities and three groups of patients were identified on the basis of the severity of their functional deficit. A non-homogeneous picture of impairment emerged in various areas of development. Overall, the neuromotor abilities of these patients were more adequate than their abilities related to autonomy in personal life, alimentary function, and cognitive and communicative-linguistic aspects. Based on the identification of specific patterns of communicative and functional impairment in subjects with WHS, rehabilitative intervention strategies can be planned to increase their communicative opportunities, and possibilities for active and autonomous participation in various life contexts (e.g. home, school and the social environment).


Optimization of immunomagnetic separation for cord blood-derived hematopoietic stem cells.
There is a growing interest in cord blood as a source of primitive stem cells with the capacity for multilineage differentiation. Pure cell fractions are needed for the characterization and in vitro expansion of stem cells as well as for their use in preclinical research. However, enrichment of stem cells is challenging due to the lack of stem cell-specific markers and gentle protocols for the isolation of highly pure stem cell fractions. Protocols developed for the enrichment of peripheral blood-derived stem cells have been found to be suboptimal for cord blood. In this study, immunomagnetic cell sorting protocols to purify CD34+, CD133+ and Lin- cells from fresh and cryopreserved cord blood were optimized. Reproducible purities of up to 97% were reached. The selected cells were highly viable having substantial colony-forming potential. The optimized protocols enable rapid enrichment of highly pure hematopoietic stem cells from both fresh and cryopreserved cord blood.


A biomarker based severity progression indicator for COVID-19: the Kuwait prognosis indicator score.
COVID-19 is a worldwide pandemic that is mild in most patients but can result in a pneumonia like illness with progression to acute respiratory distress syndrome and death. Predicting the disease severity at time of diagnosis can be helpful in prioritizing hospital admission and resources. We prospectively recruited 1096 consecutive patients of whom 643 met the inclusion criterion with COVID-19 from Jaber Hospital, a COVID-19 facility in Kuwait, between 24 February and 20 April 2020. The primary endpoint of interest was disease severity defined algorithmically. Predefined risk variables were collected at the time of PCR based diagnosis of the infection. Prognostic model development used 5-fold cross-validated regularized logit regression. The model was externally validated against data from Wuhan, China. There were 643 patients with clinical course data of whom 94 developed severe COVID-19. In the final model, age, CRP, procalcitonin, lymphocyte percentage, monocyte percentages and serum albumin were independent predictors of a more severe illness course. The final prognostic model demonstrated good discrimination, and both discrimination and calibration were confirmed with an external dataset. We developed and validated a simple score calculated at time of diagnosis that can predict patients with severe COVID-19 disease reliably and that has been validated externally. The KPI score calculator is now available online at covidkscore.com.


Isolation, sequence, and developmental expression of rat UGT2B2: the gene encoding a constitutive UDP glucuronosyltransferase that metabolizes etiocholanolone and androsterone.
The UDP glucuronosyltransferase gene UGT2B2 is constitutively expressed in rat liver, and the enzyme has been shown to conjugate glucuronic acid with various endogenous steroids, especially etiocholanolone and androsterone. We have cloned and sequenced much of the UGT2B2 gene and 5'-flanking (247 bp) and 3'-flanking (734 bp) regions. The gene contains six exons spanning about 15.3 kb. Translation begins at nucleotide 36 of exon 1 and terminates with 280 coding nucleotides into exon 6, encoding a protein of 530 amino acids (calculated Mr of the unmodified chain = 60,913). We have determined that the UGT2B2 full-length cDNA is 1,974 bp. Northern hybridization revealed that the hepatic UGT2B2 transcript is detectable 4 days before birth, becomes markedly elevated in the neonate, and is even further increased at 3 and 12 weeks of age in the liver of both male and female rats.


Comparative Analyses on the Bioactive Compounds and in Vitro Antioxidant Capacity of Tea Infusions Prepared from Selected Medicinal Fruits.
This study was conducted to analyze the bioactive compounds and in vitro antioxidant capacity of tea infusions prepared from whole and ground medicinal fruits, including gardenia, jujube, magnolia, quince, and wolfberries. The dried medicinal fruit samples were ground, and then passed through a 60-mesh sieve (pore size, 250 μm). Hot water (80 °C) infusions of whole and ground fruits were examined. In average of both whole and ground tea infusions, the maximum bioactive compounds were found in gardenia (β-carotene, lycopene, and vitamin C), magnolia (total chlorophyll and anthocyanin), quince (flavonoid), and wolfberries (phenolic), and the maximum antioxidant capacity was found in quince (ABTS and DPPH) and wolfberries (NSA). Whole fruit tea infusions showed a higher brightness than the ground fruit tea infusions. The total chlorophyll, anthocyanin, β-carotene, lycopene, phenolic, flavonoid, and vitamin C contents were found to be significantly (p≤0.001) higher in the ground fruit tea infusions than in the whole fruit tea infusions; additionally, the ground fruit tea infusions had a higher antioxidant capacity especially ABTS, DPPH and NSA. Therefore, the ground fruit tea infusions appeared to be more powerful with regard to the contents of bioactive compounds and antioxidant capacities than the whole fruit tea infusions.


The association between body mass index and mortality among Asian peritoneal dialysis patients: A meta-analysis.
Previous studies have revealed that increased body mass index (BMI) is associated with decreased mortality among hemodialysis patients. However, few studies have dealt with the association between BMI and mortality among patients undergoing peritoneal dialysis (PD) and even fewer studies have focused on the Asian PD patients. The reported studies were often non-conclusive and some even yielded contradictory results. This paper, to our best knowledge, registers the first attempt to systematically review the current literature and summarize new results on the association between BMI and mortality among the Asian PD population. A systematic literature review was performed in Medline and EMBASE to identify relevant cohort studies on all-cause and cardiovascular disease (CVD) mortality stratified by BMI categories tailored to Asians among the Asian PD population. We meta-analyzed individual results based on a random effect model, strictly complying with Preferred Reporting Items for Systematic Reviews and Meta-analysis. The paper reviews seven cohort studies with a total of 3,610 Asian PD patients. Obese group (BMI = 25-29.9 kg/m2) was associated with higher risk of all-cause mortality (HR = 1.46, 95%CI [1.07-1.98]; p = 0.02) and CVD mortality (HR = 2.01, 95%CI [1.14-3.54]; p = 0.02), compared to the normal group (BMI = 18.5-22.9 kg/m2). The underweight group (BMI<18.5kg/m2) was also associated with an elevated risk of all-cause mortality (HR = 2.11, 95%CI [1.46-3.07]; p<0.001). No significant associations between BMI with all-cause mortality were found among the overweight group (23-24.9 kg/m2) (HR = 1.00, 95%CI [0.76-1.32]; p = 0.9). The association between BMI and CVD mortality risk among the underweight and overweight groups was found nonsignificant (p = 0.5 and 0.6 respectively). Obesity is associated with increased mortality in Asian PD patients. The study indicates a "V-shaped" trend in the association between BMI and mortality in these patients.


[Neurologic changes following proton irradiation of the hypophysis in patients with generalized breast cancer].
Proton irradiation was applied to suppress the hypophyseal functions in patients with breast cancer metastases previously treated with other conventional methods. The procedure proved to increase the patients' lifetime and not to elicit any of the irreversible neurologic disorders, despite the severity of the underlying disease itself.


Synthesis of diastereomerically and enantiomerically pure 2,3-disubstituted tetrahydrofurans using a sulfoxonium ylide.
Nucleophilic substitution reactions of 2,3-epoxy alcohols, easily prepared via Sharpless asymmetric epoxidation chemistry, offer access to a wide variety of enantiomerically pure compounds. In this communication, we describe the use of a Payne rearrangement to control regioselectivity in the ring-opening of a series of 2,3-epoxy alcohols with dimethylsulfoxonium methylide to yield diastereomerically and/or enantiomerically pure disubstituted tetrahydrofuran rings. The factors influencing the success and substitution pattern of the THF ring products are discussed, including steric, electronic, and solvent effects.


The coagulation barrier in xenotransplantation: incompatibilities and strategies to overcome them.
Dysregulated coagulation is now recognized as a major contributor to graft loss in xenotransplantation. This review summarizes recent data on putative mechanisms of pathogenic coagulation in xenotransplantation and discusses progress on strategies to overcome them. Evidence continues to grow that the primary cause of failure of pig cardiac and renal xenografts is probably antibody-mediated injury to the endothelium, leading to development of microvascular thrombosis. Several factors that may exacerbate the problem will remain, even in the absence of a humoral response. These include molecular incompatibilities that affect the control of coagulation - in particular the failure of pig thrombomodulin to activate the primate protein C pathway - and platelet reactivity. Expression of anticoagulant and antiplatelet molecules within the graft is a potential solution that has been successfully tested in rodent models and will soon be applied to the pig-to-primate model. This strategy, in parallel with physical methods such as encasing islets in a protective layer, also holds promise for reducing the thrombogenicity of pig islet xenografts. Thrombosis is a barrier to long-term survival and function of porcine xenografts, which may eventually be overcome by various combinations of genetic and physical manipulation.


Early experiential effects on laterality: research on chicks has relevance to other species.
The influence of early experience on the development of lateralisation of hemispheric function was further investigated, using the chick as a model. A range of functions are lateralised in the chick and these correlate with asymmetry in the organisation of the visual projections. Chicks using the right eye and, therefore, primarily the left hemisphere are able to switch from pecking randomly at grain and pebbles to pecking mainly at grain, whereas those using the left eye and primarily the right hemisphere continue to peck at random. Exposure to light during the last days of incubation establishes this lateralisation in males, as a consequence of the embryo being oriented in the egg so that the left eye only is occluded. Males incubated in the dark peck at random when using either the right or left eye. Irrespective of light experience, females perform the same as dark-incubated males: they are not influenced by light exposure. Monocular performance of the pebble-grain task is compared to binocular performance, and the sensitive period for the influence of light is delineated. The interactive effects of sex hormone levels on the differentiation of lateralisation are discussed and also the relevance of the results to other species, including humans.


Circadian rhythms of feeding activity in sea bass, Dicentrarchus labrax L.: dual phasing capacity of diel demand-feeding pattern.
The nocturnal versus diurnal feeding patterns of sea bass under controlled experimental conditions were studied in order to investigate the existence of such a dualistic feeding behavior. The animals (six groups of 4 animals and 8 single fish) were held in tanks filled with recirculating salt water and installed in a "chronolab" under constant conditions (23.5 degrees C and 2.4% salinity). The fish were given access to self-demand feeders and first exposed to a photoperiod regime of 12:12 (12 h light, 70 lx, and 12 h dark, complete darkness) and then to light:dark (LD) pulses (40 min light, 40 min dark). The LD 12:12 cycle was reversed by doubling the light period in day 16, and reversed again in day 27 by doubling the dark period. The circadian rhythm of food demand was strongly synchronized with the LD cycle, and fish exhibited both diurnal and nocturnal patterns. In most fish, the shift of the feeding rhythm to the new LD cycle was very fast for each reversal (bringing forward or delaying their feeds 12 h), indicating a weak participation of an endogenous circadian rhythm. However, when submitted to LD pulses, fish began to free-run with a periodicity of about 23 h and kept feeding in the light or dark phase according to their prior behavior. The existence of a dualism in the diel feeding pattern in sea bass was thus clearly demonstrated and it appeared that the diurnal and nocturnal behavior did not depend exclusively on a circadian phase inversion of the feeding rhythms as this pattern of behavior was enhanced under ultradian LD pulses. The ecological implications of such dual capacity and the switch from one type of phasing to another are hitherto unknown and need further field and laboratory investigation.


Conceptual adequacy of the neuropathic pain symptom inventory in six countries.
Neuropathic pain results from a nerve lesion or nerve damage. Because it is a subjective experience, patient-reported outcomes may measure both the symptoms and impact on the patient's life. The purpose of this study was to determine whether the Neuropathic Pain Symptom Inventory (NPSI) adequately assesses neuropathic pain symptoms in patients with diabetic peripheral neuropathy, post-herpetic neuralgia, trigeminal neuralgia, and sciatica across multiple cultures. From data collected from 132 subjects in 6 countries, qualitative research methods identified their most important symptoms (and verbal descriptions) associated with neuropathic pain. A core set of commonly described symptoms spanning multiple cultures was also described. Moderators using a semi-structured discussion guide conducted focus groups consisting of patients in the U.S., Brazil, Japan, China, Finland, and Spain to elicit concepts that were most important and relevant (concept elicitation phase). Study subjects ranked the importance of each neuropathic pain symptom, completed the NPSI, and commented on its ability to capture key symptoms (face and content validation phase). Descriptive terms for sensations of neuropathic pain were similar in all countries; burning, electric shocks, and pins and needles were among the most-common sensations. Individuals with neuropathic pain experienced all sensations that were included in the NPSI. They also tended to describe pins and needles and numbness interchangeably, perhaps reflecting the relative number of DPN subjects on study. Based on data from these focus groups, the NPSI is an acceptable instrument for assessing neuropathic pain.


The degree of difficulty of embryo transfer is an independent factor for predicting pregnancy.
The role of embryo transfer as regards the success of IVF/ICSI treatments is recognized but has not been comprehensively evaluated. In order to determine its importance, the degree of difficulty of 4807 embryo transfers after IVF/ICSI was analysed retrospectively. Logistic regression analysis identified the age of the subject, type of treatment (IVF versus ICSI), number of embryos transferred and degree of difficulty of embryo transfer as independent factors predicting pregnancy. The main focus of the study was to evaluate the importance of the difficulty of embryo transfer after taking into account the other confounding variables. Embryo transfer was classified as easy (2821), intermediate (1644) or difficult (342). The transfer was considered difficult if it was time consuming, the catheter met great resistance, there was a need to change the catheter, if sounding or cervical dilatation was needed or if blood was found in any part of the catheter. Easy or intermediate transfers resulted in a 1.7-fold higher pregnancy rate than difficult transfers (P < 0.0001; 95% confidence interval: 1.3-2.2). This study demonstrates that the degree of difficulty of embryo transfer is an independent factor as regards achieving pregnancy after IVF/ICSI. All efforts should be made to avoid difficult embryo transfers. Physicians should be alert to the factors associated with embryo transfer and should be instructed to use a stepwise approach in difficult transfers.


Immunohistochemical Characterization of a Renal Nephroblastoma in a Trp53-mutant and Prolyl Isomerase 1-deficient Mouse.
A nephroblastoma is a tumor arising from metanephric blastema occurring in childhood. Among laboratory rodents, nephroblastoma has been frequently reported in rats, but it remains exceedingly rare in mice. The present work describes a nephroblastoma in a young mouse homozygous for the specific Trp53 R172H point mutation coupled with targeted deletion of the Pin1 gene. The affected kidney was effaced by a biphasic tumor with an epithelial component arranged in tubules surrounded by nests of blastemal cells. Immunohistochemically, the neoplasm was diffusely positive for Wilms' tumor antigen. The epithelial component expressed markers of renal tubular differentiation including wide-spectrum cytokeratin, E-cadherin and folate-binding protein. Furthermore, the neoplasm exhibited a high proliferative index and diffuse nucleocytoplasmic β-catenin expression. Based on histological and immunohistochemical features, a diagnosis of nephroblastoma potentially associated with Trp53 loss and oncogenic β-catenin activation has been proposed.


Folding energy landscape of the thiamine pyrophosphate riboswitch aptamer.
Riboswitches are motifs in the untranslated regions (UTRs) of RNA transcripts that sense metabolite levels and modulate the expression of the corresponding genes for metabolite import, export, synthesis, or degradation. All riboswitches contain an aptamer: an RNA structure that, upon binding ligand, folds to expose or sequester regulatory elements in the adjacent sequence through alternative nucleotide pairing. The coupling between ligand binding and aptamer folding is central to the regulatory mechanisms of thiamine pyrophosphate (TPP) riboswitches and has not been fully characterized. Here, we show that TPP aptamer folding can be decomposed into ligand-independent and -dependent steps that correspond to the formation of secondary and tertiary structures, respectively. We reconstructed the full energy landscape for folding of the wild-type (WT) aptamer and measured perturbations of this landscape arising from mutations or ligand binding. We show that TPP binding proceeds in two steps, from a weakly to a strongly bound state. Our data imply a hierarchical folding sequence, and provide a framework for understanding molecular mechanism throughout the TPP riboswitch family.


A novel missense mutation in human TTF-2 (FKHL15) gene associated with congenital hypothyroidism but not athyreosis.
Thyroid dysgenesis is the most frequent cause of congenital hypothyroidism (CH), and its genetic basis is largely unknown. Hitherto, two mutations in the human thyroid transcription factor 2 (TTF-2) gene have been described in unrelated cases of CH with cleft palate, spiky hair, variable choanal atresia, and complete thyroid agenesis. Here, we describe a novel TTF-2 mutation in a female child resulting in syndromic CH in the absence of thyroid agenesis. The index case is homozygous for an arginine to cysteine mutation (R102C) of a highly conserved residue within the forkhead, DNA binding domain of TTF-2. Her consanguineous, heterozygous parents are unaffected, and the mutation was not detected in 100 control chromosomes. Consonant with its location, the R102C mutant TTF-2 protein showed loss of DNA binding and was transcriptionally inactive. CH in the proposita was associated with cleft palate, spiky hair, and bilateral choanal atresia. However, radiological studies showed the presence of thyroid tissue in a eutopic location. Our findings indicate that human thyroid development can occur despite loss of TTF-2 function and suggest that TTF-2 gene defects should also be considered in cases of syndromic CH without total athyreosis.


MINOES: a new approach to select a representative ensemble of structures in NMR studies of (partially) unfolded states. Application to Delta25-PYP.
In nature, some proteins partially unfold under specific environmental conditions. These unfolded states typically consist of a large ensemble of conformations; their proper description is therefore a challenging problem. NMR spectroscopy is particularly well suited for this task: information on conformational preferences can be derived, for example, from chemical shifts or residual dipolar couplings. This information, which is measured as a time- and ensemble-average, can be used to model these states by generating large ensembles of conformations. The challenge is then to select a minimum representative set of conformations out of a large ensemble to represent the unfolded state. We have developed for this purpose an algorithm called MINOES (MINimum Optimal Ensemble Selection), which is based on an iterative procedure based on a driven expansion/contraction selection process. MINOES aims at selecting an optimal and minimal ensemble of conformations that, on average, maximizes the agreement between back-calculated and experimental (NMR) data, without any a-priori assumption about the required ensemble size. This approach is demonstrated by modeling the partially unfolded state of a deletion mutant of the Photoactive Yellow Protein, Delta25-PYP, which has been previously characterized by NMR (Bernard et al., Structure 2005;13:953-962).


Molecular screening of cat and dog ectoparasites for the presence of Bartonella spp. in Attica, Greece.
The purpose of this study was the molecular detection of Bartonella spp. in fleas and ticks parasitizing cats and dogs from 39 locations in Attica, Greece. One hundred and forty five ectoparasites (104 fleas and 41 ticks) from 92 cats and 53 dogs were investigated individually using PCRs targeting the 16S-23S ribosomal RNA intergenic spacer (ITS) and the citrate synthase (gltA) genetic loci. Bartonella spp. were detected in 14 out of 104 fleas (13.5%) and in none of the ticks examined. Consequent sequence analysis of the amplicons from the two loci identified 3 strains as Bartonella henselae, and 11 as Bartonella clarridgeiae. Οur study demonstrates the presence of B. henselae and B. clarridgeiae in Ctenocephalides felis fleas from cat and dog in Greece. We also report a novel ITS sequence for B. clarridgeiae. Considering that fleas could pose a risk for human bartonellosis from their infected hosts, further studies on the public health risk of Bartonella presence in animal ectoparasites are warranted.


[Effect of some nonsteroid antiinflammatory drugs on Fenton-reaction initiated degradation of 2-deoxy-D-ribose].
The authors examined the possible interactions of some nonsteroidal anti-inflammatory drugs with hydroxyl radicals by means of the test based on degradation of 2-deoxy-D-ribose initiated by hydroxyl radicals. The method is based on spectrophotometric measurement of thiobarbituric acid (TBA)-reactive carbonyl compounds that are formed in the degradation reaction of 2-deoxy-D-ribose by hydroxyl radicals (HO*) generated in the Fenton-reaction between iron(II)-ions and hydrogen peroxide (H2O2). The authors studied the degradation-inhibitory effect of phenacetin, paracetamol (acetaminophen), indomethacin, ibuprofen, diclofenac sodium, salicylic acid and salicylamide used in 100 microM and 200 microM concentrations, in the present or without addition of EDTA. In the short term (10 minute) studies paracetamol and salicylic acid proved to show the most effective degradation inhibitory effect. In the longer-time (120 minute) studies after the early inhibitory effect of paracetamol, indometacine and salicylic acid, an increase of the TBA-reactive compounds could be observed.


Palliation of malignant esophageal strictures with self-expanding nitinol stents: drawbacks and complications.
To evaluate the usefulness of self-expanding nitinol stents in the palliative treatment of malignant dysphagia. Eighty self-expanding nitinol stents were placed in 59 patients (43 men, 16 women; mean age, 55 years; age range, 23-75 years) with inoperable malignant stenosis due to squamous cell carcinoma of the esophagus (n = 36), adenocarcinoma (n = 19), invasion of the esophagus due to carcinoma of the lung (n = 2), and recurrent anastomotic carcinoma (n = 2). Dysphagia was graded on a scale of 0 to 3. Follow-up esophagograms were obtained to evaluate stent patency. Stent placement was successful in all patients. The severity of dysphagia decreased at least one grade in all but one patient. Tumor ingrowth and overgrowth were seen in 21 (36%) patients 2 days to 7 months after stent placement and caused recurrent dysphagia. These 21 patients underwent balloon dilation and additional stent placement. A mediastinal fistula was seen in three patients (5%), ulceration in four (7%), stent torsion in three (5%), and incomplete expansion of the stent in two (2%). Repeat intervention was necessary in 51% of the patients. There is a substantial range of drawbacks and complications associated with the use of self-expanding nitinol stents for palliation of malignant esophageal strictures. A covering would be necessary to prevent tumor ingrowth.


Imaging Interactions between Alzheimer's disease and cerebrovascular disease.
There is a growing body of evidence suggesting that Alzheimer's disease (AD) and cerebrovascular disease (CVD), two common disorders of aging, are related in ways that extend beyond their coincident co-occurrence. Thus, there is a need to understand how the two pathological processes interact to contribute to dementia. In this article, we review two recent studies from our laboratory that use MRI and PET to begin to reveal the nature and mechanisms of the relationship between AD, CVD, and dementia.


P53 overexpression in colorectal metastases confined to the liver and outcome of liver resection.
The results of hepatic surgery for colorectal metastases are distorted by the high incidence of recurrence, despite an apparently radical resection. Selection of high-risk patients is a mandatory step towards effective application of neo-adjuvant chemotherapy. In this study, expression of the tumor suppresser gene p53 in colorectal liver metastases was correlated with recurrence after resection. In a retrospective case-series p53 expression was assessed using standard immunohistochemical methods in the paraffin-embedded specimens of 45 liver resections for colorectal metastases, performed in 43 patients in a single institution between '86 and '96. Hospital and office charts were reviewed and follow-up was completed with a General Physicians' questionnaire in October '97. Relapse-free and cancer-specific survival from diagnosis of hepatic metastases were assessed and compared for p53+ and p53- groups. Median survival was 36 months with an estimated 5-year cancer-specific survival of 43% (95% confidence interval 35%-51%). Relapse-free and cancer-specific survival were not significantly different between p53+ (n = 24, 53%) and p53- (n = 21) groups (P = 0.86 and P = 0.91 respectively). P53 expression was not associated with other potential predictors, which were not of predictive value either. Patients at risk for recurrent disease following partial hepatectomy for colorectal metastases cannot be identified by p53 expression.


Duration and quality of the peer review process: the author's perspective.
To gain insight into the duration and quality of the scientific peer review process, we analyzed data from 3500 review experiences submitted by authors to the SciRev.sc website. Aspects studied are duration of the first review round, total review duration, immediate rejection time, the number, quality, and difficulty of referee reports, the time it takes authors to revise and resubmit their manuscript, and overall quality of the experience. We find clear differences in these aspects between scientific fields, with Medicine, Public health, and Natural sciences showing the shortest durations and Mathematics and Computer sciences, Social sciences, Economics and Business, and Humanities the longest. One-third of journals take more than 2 weeks for an immediate (desk) rejection and one sixth even more than 4 weeks. This suggests that besides the time reviewers take, inefficient editorial processes also play an important role. As might be expected, shorter peer review processes and those of accepted papers are rated more positively by authors. More surprising is that peer review processes in the fields linked to long processes are rated highest and those in the fields linked to short processes lowest. Hence authors' satisfaction is apparently influenced by their expectations regarding what is common in their field. Qualitative information provided by the authors indicates that editors can enhance author satisfaction by taking an independent position vis-à-vis reviewers and by communicating well with authors.


DNA adducts: effects of low exposure to ethylene oxide, vinyl chloride and butadiene.
Dose-response relationships of genotoxic agents differ greatly depending on the agent and the endpoint being evaluated. Simple conclusions that genotoxic effects are linear cannot be applied universally. The shape of the molecular dose of DNA adducts varies from linear, to supralinear, to sublinear depending on metabolic activation and detoxication, and repair of individual types of DNA adducts. For mutagenesis and other genotoxicity endpoints, the dose-response reflects the molecular dose of each type of DNA adduct, cell proliferation, as well as endogenous factors that lead to mutagenesis such as the formation and repair of endogenous DNA adducts. These same factors are important when interpreting the shape of dose-response data for carcinogenesis of genotoxic agents, however, tumor background variability adds additional complexity. Endogenously formed DNA adducts may be identical to those formed by chemicals, as in the case of vinyl chloride and ethylene oxide, or they may be those associated with oxidative stress. Data presented in this paper demonstrate that the exogenous number of adducts induced by 5 days of exposure to 10 ppm vinyl chloride is only 2. 2-fold greater than that present as a steady-state amount in unexposed control rats. Similar data are shown for ethylene oxide. Extremely sensitive methods have been developed for measuring the molecular dose of genotoxins. These methods can detect DNA adducts as low as 1 per 10(9) to 10(10). However, in view of the high number of endogenous DNA adducts that are present in all cells, it is unlikely that causal relationships can be attributed to very low numbers of such DNA adducts. Effects of both exogenous and endogenous DNA adducts need to be factored into the interpretation of chemical exposures.


Structure, stability, and spectra of C9H3, C11H3, and C13H3 radicals.
Density functional theory has been used to investigate the geometries, vibrational frequencies, rotational constants, and dipole moments of the C(9)H(3), C(11)H(3), and C(13)H(3) radicals. Vertical electronic transition energies of C(9)H(3), C(11)H(3), and C(13)H(3) are calculated by the time-dependent density functional theory. Present results show that the most stable arrangements of C(9)H(3), C(11)H(3), and C(13)H(3) are H(2)C(9)H, H(2)C(11)H, and H(2)C(13)H with a C(2v) symmetry, respectively. Such lowest-energy isomers have an obvious single and triple bond alternation carbon chain. Their isomers HC(4)(HC)C(4)H, HC(4)[C(C(2)H)]C(4)H, and C(C(4)H)(3) are predicted to have vibrational frequencies and vertical excitation energies in good agreement with experimental observations. HC(4)(HC)C(4)H, HC(4)[C(C(2)H)]C(4)H, and C(C(4)H)(3) have similar trigonal structure, which gives rise to the remarkably similar spectroscopic features as obtained experimentally. On the basis of present calculations, the isomers HC(4)(HC)C(4)H, HC(4)[C(C(2)H)]C(4)H, and C(C(4)H)(3) of C(9)H(3), C(11)H(3), and C(13)H(3) radicals are most likely the carriers of the observed spectra.


Roscovitine in B-chronic lymphocytic leukemia cells: high apoptosis-inducing efficacy and synergism with alemtuzumab independent of the patients' pretreatment status.
Roscovitine induced apoptosis in isolated B-chronic lymphocytic leukemia cells of 25 patients of whom nine with relapsed and seven with fludarabine-refractory disease. It was synergistic with alemtuzumab and restored sensitivity to alemtuzumab in initially alemtuzumab-resistant samples. Observed roscovitine-induced up-regulation of CD52 surface expression may be one of the underlying mechanisms for this synergism.


EndoLive UK 2015: introducing the best of UK endoscopy to the world.
The inaugural EndoLive UK held in the International Convention Centre (ICC) Birmingham on the 12-13 March 2015 was a watershed moment for UK endoscopy and for the British Society of Gastroenterology (BSG). The event provided the perfect platform to demonstrate how the UK is delivering some of the highest quality endoscopic practice, training and research in the world. Organised by UK endoscopy experts and supported by internationally renowned endoscopists such as Professors Paul Fockens, Douglas Rex and Peter Siersema, EndoLive UK pushed back the boundaries of innovation and interaction during a 'Live Endoscopy' event. Frontline Gastroenterology supported the event with a special edition of this journal dedicated to Endoscopic Practice in April 2015. With over 500 people from around the globe attending this first event, the aim of highlighting the very best of UK endoscopy on a national and international stage was achieved. Furthermore, the educational content of the course was developed to be accessible and appropriate to a variety of clinicians with different levels of experience-endoscopy trainees, nurses, General practitioner (GP) endoscopists, gastroenterologists and surgeons. This article reviews this event and its many highlights and successes.


Nonmonotonic d(x(2)-y(2)) superconducting order parameter in Nd2-xCexCuO4.
Low energy polarized electronic Raman scattering of the electron-doped superconductor Nd2-x Ce x CuO4 ( x = 0.15, T(c) = 22 K) has revealed a nonmonotonic d(x(2)-y(2)) superconducting order parameter. It has a maximum gap of 4.4k(B)T(c) at Fermi surface intersections with an antiferromagnetic Brillouin zone (the "hot spots") and a smaller gap of 3.3k(B)T(c) at fermionic Brillouin zone boundaries. The gap enhancement in the vicinity of the hot spots emphasizes the role of antiferromagnetic fluctuations and the similarity in the origin of superconductivity for electron- and hole-doped cuprates.


[The physician scientist, problems and hope].
The dawn of the third millenium views a shift of focus from society to the individual. Personal accomplishments, comfort and well being have priority over such issues as contribution to society and general good. Physicians, among other professionals, have shifted their priorities to personal and economic status rather than an academic position. Despite this trend, the number of researchers among hospital physicians has not declined and the quality of research by clinicians seems to improve. There is, however, some retardation in our progress, relative to other industrial countries mainly due to major shrinkage of public financial resources. Physicians-scientists are those who generate the ideas for research in medicine and those who best apply new data to clinical practice. Indeed they constitute the backbone of the medical system. In order to ensure future preservation of the quality of medical care, clinical and basic research in medical schools and in hospitals must receive better support.


Breath-hold gadolinium-enhanced MR angiography of the abdominal aorta and its major branches.
To develop and evaluate a sequence for breath-hold three-dimensional gadolinium-enhanced magnetic resonance (MR) angiography of the abdominal aorta. In 63 patients, the abdominal aorta and its branches were imaged for 29, 43, or 58 seconds with breath holding. A fast spoiled gradient-echo sequence was used at 1.5 T during infusion of 42 mL of a gadolinium chelate. Correlation with conventional angiography was performed in 19 patients. MR image quality (signal-to-"total" noise ratio [S/N*]) with breath holding was compared with that with free breathing (104 patients). With breath-hold gadolinium-enhanced MR angiography, renal, celiac, and superior mesenteric artery occlusive disease was graded appropriately in 15 of 19 patients, and 10 of 11 accessory renal arteries were depicted correctly. Renal artery branches were visualized in 86 of 95 kidneys on breath-hold images compared with only 84 of 236 kidneys with free breathing (P < .001). Distal renal artery S/N* was 3.1 with breath holding and 2.1 with free breathing (P < .001). Breath holding statistically significantly improves three-dimensional gadolinium-enhanced MR angiography of the renal, celiac, and superior mesenteric arteries.