Impact of diet, moisture, location, and storage on soluble phosphorus in broiler breeder manure.
Decreasing dietary phosphorus (P) has the potential to reduce P excreted in manure and therefore alleviate the environmental degradations associated with intensive animal farming. We evaluated reducing dietary P for broiler breeders as an aid to reduce manure total and water soluble phosphorus (WSP). Broiler breeders were fed diets high and low in dietary P, with and without phytase, from 22 to 64 wk of age. At the end of the 42-wk production period, manure was collected from four locations in each two-thirds slat, one-third litter breeder pen: the litter scratch area, under the drinker in the slat area, under the feeder in the slat area, and in a clean area of the slat area away from feeder or drinker. After the initial sampling, all manure was removed from pens and representative samples were stored for 6 mo with and without feed mixed in to simulate the effect of spilled feed. Total P was determined on all pen samples, and moisture and WSP determined on the pen and stored samples. The manure collected under the drinker had much greater moisture due to spilled water. This was associated with much greater WSP in this location, showing the importance of good water management. The manure from under the feeder had similar WSP as manure from the clean area, so spilled feed did not significantly affect WSP. Dietary phytase either had no effect or significantly decreased manure WSP. However, addition of dietary phytase to the feed led to slightly elevated manure moisture. Since moisture was correlated with manure WSP this may explain some of the variability in WSP results between studies. Over 6 mo of storage WSP increased and generally followed the same ranking order at 168 d as at 1 d among the dietary treatments (high>high+phytase>low>low+phytase). Combining decreased dietary P and phytase reduced both manure total P and WSP by 42%. As total P and WSP are indicators of the long and short term impacts manure applications can have on P losses from manured soils, diet modification should be seen as environmentally beneficial.


Brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism is associated with disease severity and incidence of cardiovascular events in a patient cohort.
The rs6265 (Val66Met) single-nucleotide polymorphism in the BDNF gene has been related to a number of endophenotypes that have in turn been shown to confer risk for atherosclerotic cardiovascular disease (CVD). To date, however, very few studies have examined the association of the Val66Met single-nucleotide polymorphism with CVD clinical outcomes. In a cohort of 5,510 Caucasian patients enrolled in the CATHeterization GENetics (CATHGEN) study at Duke University Hospital between 2001 and 2011, we determined the severity of coronary artery disease (CAD) and CVD event incidence through up to 11.8years of follow-up. We examined the association of Val66Met genotype with time-to-death or myocardial infarction, adjusting for age, sex, CAD risk variables, and CAD severity measures. The Val/Val genotype was associated with a higher risk than Met carriers for clinical CVD events (P=.034, hazard ratio 1.12, 95% CI 1.01-1.24). In addition, compared with Met carriers, individuals with the Val/Val genotype had a greater odds of having more diseased vessels (odds ratio 1.17, 95% CI 1.06-1.30, P=.002), and lower left ventricular ejection fraction (β=-0.72, 95% CI, -1.42 to -0.02, P=.044). The Val/Val genotype was associated with greater severity of CAD and incidence of CVD-related clinical events in a patient sample. If these findings are confirmed in further research, intervention studies in clinical groups with the Val/Val genotype could be undertaken to prevent disease and improve prognosis.


Automatic drawing of biological networks using cross cost and subcomponent data.
Automatic graph drawing function for biopathways is indispensable for biopathway databases and softwares. This paper proposes a new grid-based algorithm for biopathway layout that considers (a) edge-edge crossing, (b) node-edge crossing, (c) distance measures between nodes, as its costs, and (d) subcellular localization information from Gene Ontology, as its constraints. For this algorithm, we newly define cost functions, devise an efficient method for computing the costs (a)-(c) by employing a matrix representing the difference between two layouts, and take a steepest descent method for searching locally optimal solutions and multi-step layout method for finding better solutions. We implemented this algorithm on Cell Illustrator which is a biopathway modeling and simulation software. The algorithm is applied to a signal transduction pathway of apoptosis induced by fas ligand. We compare our layout with that of the grid-based algorithm by Li and Kurata (Bioinformatics 21 (9):2036-2042, 2005). The result shows that our algorithm reduces edge-edge crossings and node-edge crossings, and solves the ''isolated island problem'', that is, despite the intension, some groups of nodes are apart from other nodes in the layout. As a result, the biological understandability of the layout is fairly improved.


Conversion of a surfactant-based microemulsion to a surfactant-free microemulsion by CO2.
A microemulsion with a CO2 response was prepared by mixing the surfactant sodium oleate (NaOA), the co-surfactant isopropyl alcohol (IPA), oil phase oleic acid (HOA) and water. This surfactant-based microemulsion (SBME) shows a CO2 responsive behavior, and the introduction of CO2 can breakdown the microemulsion. Through the research in this paper, it is found that the content of IPA has a direct impact on the CO2 response behavior of SBME. It was found that the lower the IPA content (22.73 wt%), the more obvious the CO2 response behavior of SBME. Conversely, when the concentration of IPA is high (54.05 wt% and 63.83 wt%), the introduction of CO2 does not directly lead to the demulsification of the microemulsion. NaOA can be converted to HOA under the action of CO2, which is why SBME shows CO2 response behavior. By comparing the effects of CO2 on the (pseudo-)ternary phase diagrams of SBME and surfactant-free microemulsion (SFME), we found evidence that SBME shows different CO2 response behaviors. When CO2 was bubbled into the SBME system with a low IPA content, IPA cannot stabilize the excessive HOA and water in the system and eventually break the microemulsion. The situation is different when CO2 is applied to the SBME system with a high IPA content. IPA as an amphiphilic solvent can stabilize the HOA and water in the system to form SFME. In this process, SBME can be demulsified (low IPA content) or can be converted to SFME (high IPA content) in the presence of CO2.


Hydrophobic interactions in presence of osmolytes urea and trimethylamine-N-oxide.
Molecular dynamics simulations were carried out to study the influences of two naturally occurring osmolytes, urea, and trimethylamine-N-oxide (TMAO) on the hydrophobic interactions between neopentane molecules. In this study, we used two different models of neopentane: One is of single united site (UA) and another contains five-sites. We observe that, these two neopentane models behave differently in pure water as well as solutions containing osmolytes. Presence of urea molecules increases the stability of solvent-separated state for five-site model, whereas osmolytes have negligible effect in regard to clustering of UA model of neopentane. For both models, dehydration of neopentane and preferential solvation of it by urea and TMAO over water molecules are also observed. We also find the collapse of the second-shell of water by urea and water structure enhancement by TMAO. The orientational distributions of water molecules around different layers of neopentane were also calculated and we find that orientation of water molecules near to hydrophobic moiety is anisotropic and osmolytes have negligible effect on it. We also observe osmolyte-induced water-water hydrogen bond life time increase in the hydration shell of neopentane as well as in the subsequent water layers.


Molecular mechanism of MART-1+/A*0201+ human melanoma resistance to specific CTL-killing despite functional tumor-CTL interaction.
Durable responses in metastatic melanoma patients remain generally difficult to achieve. Adoptive cell therapy (ACT) with ex vivo engineered lymphocytes expressing high affinity T-cell receptors (TCRα/β) for the melanoma antigen MART-1₂₇₋₃₅/HLA-A*0201 [recognized by F5 cytotoxic T lymphocytes (F5 CTL)] has been found to benefit certain patients. However, many other patients are inherently unresponsive and/or relapse for unknown reasons. To analyze the basis for the acquired resistance and strategies to reverse it, we established F5 CTL-resistant (R) human melanoma clones from relatively sensitive parental lines under selective F5 CTL pressure. Surface MART-1₂₇₋₃₅/HLA-A*0201 in these clones was unaltered and F5 CTLs recognized and interacted with them similar to the parental lines. Nevertheless, the R clones were resistant to F5 CTL killing, exhibited hyperactivation of the NF-κB survival pathway, and overexpression of the antiapoptotic genes B cell lymphoma protein 2 (Bcl-2), Bcl-2 related gene (long alternatively spliced variant of Bcl-x gene; Bcl-(xL)), and myeloid cell differentiation 1 (Mcl-1). Sensitivity to F5 CTL-killing could be increased by pharmacological inhibition of the NF-κB pathway, Bcl-2 family members, or the proteasome, the latter of which reduced NF-κB activity and diminished antiapoptotic gene expression. Specific gene-silencing (by siRNA) confirmed the protective role of antiapoptotic factors by reversing R clone resistance. Together, our findings suggest that long-term immunotherapy may impose a selection for the development of resistant cells that are unresponsive to highly avid and specific melanoma-reactive CTLs, despite maintaining expression of functional peptide:MHC complexes, due to activation of antiapoptotic signaling pathways. Though unresponsive to CTL, our results argue that resistant cells can be resensitized to immunotherapy with coadministration of targeted inhibitors to antiapoptotic survival pathways.


[Sport climbing with adolescents: effect on spine stabilising muscle strength].
Indoor climbing and boulder facilities gain importance in therapy for patients with back pain or with psychic disorders. The effect of climbing on strength of the spine musculature has hardly been investigated in young men and women. To address this question 17 high school students agreed to enrol into a 10-week climbing course twice a week and 9 to serve as controls. All participants were measured before and after training on special devices for measuring the isometric strength of cervical extensors and lateral flexors as well as for thoracic/lumbal spine, the flexors, extensors, the right and left rotators and lateral flexors. The mobility was measured for the transversal and frontal plane. After the climbing course, a gain in strength was measured in all but two muscle groups, the thoracic/lumbal extensors and left lateral flexors, in the control group only for the thoracic/lumbal flexors and left lateral flexors. The gain in strength was higher in the climbing group. The ratio of maximal strength of the right to left rotators was smaller after climbing. Sport climbing in adolescence leads to increased muscle strength of the spine muscles and to an increased muscular balance; thus, for prevention of back pain climbing courses may be introduced in high schools.


OPTIMAL TRANSPORT GUIDED UNSUPERVISED LEARNING FOR ENHANCING LOW-QUALITY RETINAL IMAGES.
Real-world non-mydriatic retinal fundus photography is prone to artifacts, imperfections, and low-quality when certain ocular or systemic co-morbidities exist. Artifacts may result in inaccuracy or ambiguity in clinical diagnoses. In this paper, we proposed a simple but effective end-to-end framework for enhancing poor-quality retinal fundus images. Leveraging the optimal transport theory, we proposed an unpaired image-to-image translation scheme for transporting low-quality images to their high-quality counterparts. We theoretically proved that a Generative Adversarial Networks (GAN) model with a generator and discriminator is sufficient for this task. Furthermore, to mitigate the inconsistency of information between the low-quality images and their enhancements, an information consistency mechanism was proposed to maximally maintain structural consistency (optical discs, blood vessels, lesions) between the source and enhanced domains. Extensive experiments were conducted on the EyeQ dataset to demonstrate the superiority of our proposed method perceptually and quantitatively.


Prevention of hydrogen sulfide (H2S)-induced mouse lethality and cytotoxicity by hydroxocobalamin (vitamin B(12a)).
Recently, H(2)S (an environmental toxin) was proposed to induce cytotoxicity not only by inhibiting cytochrome oxidase but also by generating reactive oxygen species [Truong, D., Eghbal, M., Hindmarsh, W., Roth, Sh., O'Brien, P., 2006. Molecular mechanisms of hydrogen sulfide toxicity. Drug Metab. Rev. 38, 733-744]. In the following, evidence is presented supporting the use of hydroxocobalamin (vitamin B(12a)) as an antidote against H(2)S poisoning. More than 60% of the mice administered 35 mg/kg (0.63 mmol/kg) of NaSH (LD(90)) survived (at 24 h) when hydroxocobalamin (0.25 mmol/kg) was given after NaSH administration whereas less than 15% of the mice survived without hydroxocobalamin. Hydroxocobalamin (50-100 microM) or cobalt (50-100 microM) also prevented hepatocyte cytotoxicity induced by NaSH (500 microM). Furthermore, adding hydroxocobalamin 60 min later than NaSH still showed some protective activity. Catalytic amounts of hydroxocobalamin or cobalt added to a solution containing NaSH caused the disappearance of NaSH and induced oxygen uptake, indicative of NaSH oxidation and Co reduction, respectively.


How to address the patella in revision total knee arthroplasty.
Patellar issues need to be carefully addressed during any revision TKA and the surgeon often faces the question of what to do with the patella at the time of revision. The choice of treatment is often made by balancing what is technically feasible with the risk of potential complications and takes into account the reason for the revision, the type of implant (i.e., metal-backing or all-polyethylene), the duration of implantation, the fixation, the stability, the sterilization technique, the wear, the presence of osteolysis, the compatibility with the femoral component, and most importantly the remaining bone stock. The various treatment options then include retention of the patellar component, revision of the patellar component, removal of the component with retention of the patellar bony shell (patelloplasty or resection arthroplasty), excision of the patella (partial or total patellectomy), secondary resurfacing, and reconstruction/augmentation of the patellar bone stock. Isolated patellar revision is associated with a high complication rate and recurrent failure when poor patellar tracking, incongruent designs and malalignment of the femoral and tibial components exist. Retention of a well-fixed all-PE (non-oxidized) patella is advocated where possible and revision of metal-backed patella is recommended (unless well fixed with poor bone stock). In the situation of a deficient patella, patelloplasty, augmentation procedures and very rarely patellectomy are other viable options.


Prorhombomeric subdivision of the mammalian embryonic hindbrain: is it functionally meaningful?
The technique of whole embryo culture has made significant contributions to understanding the mechanisms of morphogenesis in mammalian embryos, especially with respect to cranial neurulation and neural crest cell migration. This study traces the fate of two specifically mammalian structures, the preotic and otic sulci. Their formation at the 1/2- and 3-somite stages respectively, divides the hindbrain neuroepithelium into prorhombomeres A, B and C. The preotic sulcus is a deeply recessed structure that forms the rostral boundary of expression of both Hoxb-2 and the first domain of Krox-20. The otic sulcus is a shallow concavity in which the second Krox-20 domain is expressed. DiI labeling followed by whole embryo culture confirmed that the later fate of the preotic sulcus is the rhombomere 2/3 boundary, and the fate of the otic sulcus is the cranial part of rhombomere 5. Structurally, the preotic and otic sulci show no specialization with respect to actin, tubulin or proteoglycans, but their maintenance depends on contact with the subjacent mesenchyme. Their formation is inhibited by exposure of embryos to retinoic acid prior to the onset of somitic segmentation, indicating that the molecular events governing prorhombomeric subdivision of the hindbrain are retinoic acid-sensitive. The preotic sulcus may be essential for neuroepithelial cell movement towards and into the rapidly enlarging forebrain; the otic sulcus may simply delineate the caudal boundary of prorhombomere B, an area with a discrete neural crest cell population discontinuous with those rostral and caudal to it. Understanding the positional relationships of the preotic and otic sulci to later rhombomeric segments makes them useful landmarks for experimental purposes, but there is no evidence that prorhombomeres are functionally significant as the precursors of rhombomeric segments.


Charge Transfer Complexes of 1,3,6-Trinitro-9,10-phenanthrenequinone with Polycyclic Aromatic Compounds.
Understanding the interactions of organic donor and acceptor molecules in binary associates is crucial for design and control of their functions. Herein, we carried out a theoretical study on the properties of charge transfer complexes of 1,3,6-trinitro-9,10-phenanthrenequinone (PQ) with 23 aromatic π-electron donors. Density functional theory (DFT) was employed to obtain geometries, frontier orbital energy levels and amounts of charge transfer in the ground and first excited states. For the most effective donors, namely, dibenzotetrathiafulvalene, pentacene, tetrathiafulvalene, 5,10-dimethylphenazine, and tetramethyl-p-phenylenediamine, the amount of charge transfer in the ground state was shown to be 0.134-0.240 e-. Further, a novel charge transfer complex of PQ with anthracene was isolated in crystalline form and its molecular and crystal structure elucidated by single-crystal synchrotron X-ray diffraction.


The perceptual basis of the modality effect in multimedia learning.
Various studies have demonstrated an advantage of auditory over visual text modality when learning with texts and pictures. To explain this modality effect, two complementary assumptions are proposed by cognitive theories of multimedia learning: first, the visuospatial load hypothesis, which explains the modality effect in terms of visuospatial working memory overload in the visual text condition; and second, the temporal contiguity assumption, according to which the modality effect occurs because solely auditory texts and pictures can be attended to simultaneously. The latter explanation applies only to simultaneous presentation, the former to both simultaneous and sequential presentation. This paper introduces a third explanation, according to which parts of the modality effect are due to early, sensory processes. This account predicts that-for texts longer than one sentence-the modality effect with sequential presentation is restricted to the information presented most recently. Two multimedia experiments tested the influence of text modality across three different conditions: simultaneous presentation of texts and pictures versus sequential presentation versus presentation of text only. Text comprehension and picture recognition served as dependent variables. An advantage for auditory texts was restricted to the most recent text information and occurred under all presentation conditions. With picture recognition, the modality effect was restricted to the simultaneous condition. These findings clearly support the idea that the modality effect can be attributed to early processes in perception and sensory memory rather than to a working memory bottleneck.


The safety and adverse event profile of favipiravir in the treatment of COVID-19 patients, Turkey.
Favipiravir (FVP) is an antiviral and used to treat COVID-19. We aimed to document the safety and adverse events associated with FVP on the outcome of COVID-19 treatment. The study included 225 adult patients with moderate COVID-19 infection (World Health Organization scale-5). The adverse events (AEs) were evaluated using a grading scale supported by the Food and Drug Administration. Safety was assessed by the frequency of serious AEs. The AEs associated with FVP treatment were hepatotoxicity (87/225, 38.7%), weakness (32/225, 14.2%), nephrotoxicity (26/225, 11.6%), nausea (18/225, 8.0%), diarrhea (8/225, 3.6%), vomiting (5/225, 2.2%), and insomnia (4/225, 1.8%); rash was not detected. Hepatotoxicity was observed more frequently in patients who also developed nephrotoxicity (57.7% vs 36.2%, p = 0.03). The deceased patients were significantly older and had higher prevalence of hypertension, congestive heart failure (CHF), coronary artery disease, cancer, nephrotoxicity. and angiotensin- converting enzyme inhibitors/angiotensin receptor blocker use. While male gender (OR: 5.38 CI: 1.64-17.67) and CHF (OR: 6.8 CI: 1.92-24.74) were significantly associated with nephrotoxicity, age (OR: 1.06 CI: 1.02-1.10), cancer (OR: 3.9 CI: 1.10-14.22) and nephrotoxicity (OR: 5.5 CI: 1.74-17.74) were associated with mortality. Serious AEs were detected at very low levels that would not require discontinuation of treatment or any AE-related death. Since SARS-CoV-2 itself and drug interactions may differ, FVP-related AEs might vary in COVID-19 patients. Our study shows that FVP can be used safely with a low AE profile. More extensive evidence is required to evaluate the long-term AEs of FVP.


MicroRNA 211-5p inhibits cancer cell proliferation and migration in pancreatic cancer by targeting BMP2.
MicroRNAs (miRNAs) are essential to the tumour growth and metastasis of several cancers. However, the implied functions of miR-211-5p in pancreatic cancer (PC) remains poorly known. In the present study, we discovered that miR-211-5p was a significantly downregulated miRNA in PC tissues compared to adjacent non-tumour tissues. Moreover, we revealed that miR-211-5p overexpression suppressed the proliferation and metastasis of PC cells. Mechanistically, miR-211-5p directly bond to 3'UTR of bone morphogenetic protein-2 (BMP2) and negatively regulated its expression. Rescue experiments showed that the biological function of miR-211-5p was reversed by BMP-2 overexpression in PC cells. Clinical data indicated that BMP2 expression was negatively correlated with miR-211-5p levels in PC patients. Our study provided evidence that miR-211-5p served as a significant suppressor in PC, provided potential targets for prognosis and treatment of patients with PC.


Calculation of narrower confidence intervals for tree mortality rates when we know nothing but the location of the death/survival events.
Many ecological applications, like the study of mortality rates, require the estimation of proportions and confidence intervals for them. The traditional way of doing this applies the binomial distribution, which describes the outcome of a series of Bernoulli trials. This distribution assumes that observations are independent and the probability of success is the same for all the individual observations. Both assumptions are obviously false in many cases.I show how to apply bootstrap and the Poisson binomial distribution (a generalization of the binomial distribution) to the estimation of proportions. Any information at the individual level would result in better (narrower) confidence intervals around the estimation of proportions. As a case study, I applied this method to the calculation of mortality rates in a forest plot of tropical trees in Lambir Hills National Park, Malaysia.I calculated central estimates and 95% confidence intervals for species-level mortality rates for 1,007 tree species. I used a very simple model of spatial dependence in survival to estimate individual-level risk of mortality. The results obtained by accounting for heterogeneity in individual-level risk of mortality were comparable to those obtained with the binomial distribution in terms of central estimates, but the precision increased in virtually all cases, with an average reduction in the width of the confidence interval of ~20%.Spatial information allows the estimation of individual-level probabilities of survival, and this increases the precision in the estimates of mortality rates. The general method described here, with modifications, could be applied to reduce uncertainty in the estimation of proportions related to any spatially structured phenomenon with two possible outcomes. More sophisticated approaches can yield better estimates of individual-level mortality and thus narrower confidence intervals.


[Conditions for the transition of premorbid states into borderline forms of pathology].
Conditions for the transformation of some premorbid states into borderline forms of pathology in the menopausal and pubertal periods are analyzed. It has been established that factors of higher risk of the transformation of a menopausal preneurosis-like condition into a neurosis-like one in women with a history of complete or partial castration are as follows: older (over 45 years) age by the time of surgical intervention, complete castration, a combination of the previous operation and attendant additional hazards (psychogenias and somatogenias) as well as the occurrence of the menopause before the operation. In the pubertal period behavioural deviations and neuropsychic disturbances usually reach a degree of obvious pathology (psychopathies, psychogenias) in cases where a long-standing psychotraumatic situation is combined with unfavourable biological factors such as minimum brain deficit, severe and prolonged debilitating somatic disease, a shain of infections, and pathological heredity.


Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions.
The Snail transcription factor has been described recently as a strong repressor of E-cadherin in epithelial cell lines, where its stable expression leads to the loss of E-cadherin expression and induces epithelial-mesenchymal transitions and an invasive phenotype. The mechanisms regulating Snail expression in development and tumor progression are not yet known. We show here that transforming growth factor beta-1 (TGFbeta1) induces Snail expression in Madin-Darby canine kidney cells and triggers epithelial-mesenchymal transitions by a mechanism dependent on the MAPK signaling pathway. Furthermore, TGFbeta1 induces the activity of Snail promoter, whereas fibroblast growth factor-2 has a milder effect but cooperates with TGFbeta1 in the induction of Snail promoter. Interestingly, TGFbeta1-mediated induction of Snail promoter is blocked by a dominant negative form of H-Ras (N17Ras), whereas oncogenic H-Ras (V12Ras) induces Snail promoter activity and synergistically cooperates with TGFbeta1. The effects of TGFbeta1 on Snail promoter are dependent of MEK1/2 activity but are apparently independent of Smad4 activity. In addition, H-Ras-mediated induction of Snail promoter, alone or in the presence of TGFbeta1, depends on both MAPK and phosphatidylinositol 3-kinase activities. These data support that MAPK and phosphatidylinositol 3-kinase signaling pathways are implicated in TGFbeta1-mediated induction of Snail promoter, probably through Ras activation and its downstream effectors.


Workplace Violence Against Iranian Nurses: A Systematic Review and Meta-Analysis.
Nurses are exposed to workplace violence more than other healthcare professionals. This study aims to examine the prevalence of different types of workplace violence against Iranian nurses. A systematic review and meta-analysis were designed according to the PRISMA statement. To avoid bias, all stages of the research were done independently by two researchers. Eligible studies were retrieved from comprehensive search of several electronic databases included Magiran, Barakat Knowledge Network System, IranDoc, Regional Information Center for Science and Technology (RICST), Scientific Information Database (SID), Iranian National Library, PubMed/Medline, Cochrane Library, Scopus, Science Direct, ISI Web of Knowledge, CINAHL, and Google Scholar until April 2017. A random effects model was applied to combine studies. Data were analyzed using Comprehensive Meta-Analysis software version 2. In 26 studies, 10,858 nurses entered the meta-analysis process. The mean age and work experience of the nurses were 33.5 ± 7.5 and 10.85 ± 10.1 years, respectively. The prevalence of workplace verbal, physical, sexist, and racist violence and threat against Iranian nurses was 80.8% (95% confidence interval [CI] [74.2, 86.0]), 24.8% (95% CI [17.4, 34.0]), 6.7% (95% CI [4.9, 9.2]), 14.6% (95% CI [10.1, 20.7]), and 44% (95% CI [30.1, 58.8]), respectively. The prevalence of verbal and physical violence against the emergency department nurses was 89.7% (95% CI [69.4, 97.1]) and 21.0% (95% CI [12.6, 32.9]), respectively. The highest prevalence of verbal, physical, sexist, and racist violence was from patient's relative (42.3%, 95% CI [30.7, 54.7]), patients (12.6%, 95% CI [5.9, 25.0]), healthcare workers (5.1%, 95% CI [2.4, 10.4]), and patients (2.3%, 95% CI [0.9, 5.4]), respectively. Given the high prevalence of violence against the nurses in Iran, it is highly necessary to take certain intervention measures and design new policies.


Linking health service utilisation and mortality data-unravelling what happens after fall-related paramedic care.
A randomised controlled trial implemented and evaluated a new model of care for non-transported older fallers to prevent future falls and unplanned health service use. This current study uses linked data to evaluate the effects of the intervention beyond the initial 12-month study period. Study data from an established cohort of 221 adults were linked to administrative data from NSW Ambulance, Emergency Department Data Collection, Admitted Patient Data Collection and Registry of Births, Deaths and Marriages evaluating health service use at 12, 24 and 36 months following randomisation including time to event (health service utilisation) and mortality. Negative binomial and Cox's proportional hazard regression were performed to capture the impact of the study between groups and adherence status. At 36 months follow-up, 89% of participants called an ambulance, 87% attended the Emergency Department and 91% were admitted to hospital. There were no significant differences in all-cause health service utilisation between the control and intervention group (IG) at 12, 24 and 36 months follow-up. Fall-related health service use was significantly higher within the IG at 12 (IRR:1.40 (95%CI:1.01-1.94) and 24 months (IRR:1.43 (95%CI:1.05-1.95)). Medication use, impaired balance and previous falls were associated with subsequent health service use. Over 40% of participants died by the follow-up period with risk of death lower in the IG at 36 months (HR:0.64, 95%CI:0.45-0.91). Non-transported fallers have a high risk of future health service use for fall and other medical-related reasons. Interventions which address this risk need to be further explored.


[T-activin in the treatment of patients with recurrent erysipelas and concomitant eczema].
Increased levels of circulating immune complexes (CIC) have been revealed in 156 patients suffering from erysipelas and chronic eczema, 109 of these with frequent recurrences of erysipelatous inflammation, during all periods of the disease. The maximal rises of CIC levels have been associated with a combination of erysipelas relapse with eczema exacerbation, with the most pathogenic medium- and low-molecular complexes, making up together 80.4 +/- 4% of CICs, predominating in the blood. T-activin therapy results in an essential decrease of CIC level and in 2.5 times reduction of the number of early recurrences of erysipelas.


[Multiple brain metastases after breast cancer and their radiotherapy management: what is the optimal treatment?].
Whole brain radiotherapy remains standard in the management of breast cancer patients with brain metastases. It allows for symptomatic improvement and good local control in most patients. However, its results remain suboptimal in terms of both efficacy and toxicity. In highly selected patients, stereotactic radiotherapy demonstrated very good local control with low toxicity. With purpose of improving the efficacy/toxicity ratio, strategies of biomodulation of tumor radiosensitivity were recently developed. First results are promising and warrant further assessment. At the same time, new technologies and new irradiation modalities demonstrated their ability in providing high dosimetric homogeneity, delivering integrated radiation boosts, and avoiding critical structures that are involved in long-term neurological toxicity. Further assessment is required and recruitment of breast cancer patients into clinical trials is encouraged.


Genotype-based association analysis using discordant pairs: a penetrance odds ratio approach.
Genotypic counts of paired relatives discordant for a complex late-onset disease are often used to test for genetic association. The power of the various statistical test options, when data on covariates are unavailable, has been the focus of recent research. Comparison of the Cochran-Armitage, Bhapkar, and McNemar tests indicates that none is superior to the others in all cases. Using an alternative approach, we found that the theoretical genotypic frequencies of the discordant pairs depend only on the penetrance odds ratios, after conditioning. These odds ratios can be estimated by maximizing a product binomial likelihood and provide insight into the mode of inheritance. We identified cases where exact maximum likelihood (ML) estimates can be explicitly obtained. This approach led us to two tests for association which depend on likelihood ratio (LR) or score statistics. We quantified the power of these tests analytically and examined their performance through simulation. We explored the utility of these tests with an example from the literature-the association between complement factor H (CFH) polymorphisms and age-related macular degeneration. The LR and Score tests serve as simple and effective ways of interpreting paired case-control data sets.


Preschool Children with and without Developmental Delay: Risk, Parenting, and Child Demandingess.
Although past literature has established relations between early child risk factors, negative parenting, and problematic child behavior, the nature of these interrelations and pathways of influence over time remains largely unknown, especially in children with developmental delays or disabilities. In the current study data were drawn from the longitudinal Collaborative Family Study and included a sample of 260 families with preschool children with and without developmental delays. Child-related risk was assessed at child age 36 months, maternal intrusiveness and negative affect at 48 months, and child demandingness at 60 months. Results indicated significant relations between early risk, negative parenting, and subsequent child demandingness. Sickliness as an infant was the most salient predictive risk factor of later child demandingness. Developmental delay was the most significant predictor of subsequent negative parenting. Results are discussed as being more indicative of additive rather than mediational processes given that early child risk and negative maternal parenting both contributed uniquely to the subsequent development of child demandingness.


Genetic parameters of resistance to pasteurellosis using novel response traits in rabbits.
Pasteurellosis (Pasteurella infection) is one of the most common bacterial infections in rabbits on commercial farms and in laboratory facilities. Curative treatments using antibiotics are only partly efficient, with frequent relapses. Breeding rabbits for improved genetic resistance to pasteurellosis is a sustainable alternative approach. In this study, we infected 964 crossbred rabbits from six sire lines experimentally with Pasteurella multocida. After post-mortem examination and bacteriological analyses, abscess, bacteria, and resistance scores were derived for each rabbit based on the extent of lesions and bacterial dissemination in the body. This is the first study to use such an experimental design and response traits to measure resistance to pasteurellosis in a rabbit population. We investigated the genetic variation of these traits in order to identify potential selection criteria. We also estimated genetic correlations of resistance to pasteurellosis in the experimental population with traits that are under selection in the breeding populations (number of kits born alive and weaning weight). Heritability estimates for the novel response traits, abscess, bacteria, and resistance scores, ranged from 0.08 (± 0.05) to 0.16 (± 0.06). The resistance score showed very strong negative genetic correlation estimates with abscess (- 0.99 ± 0.05) and bacteria scores (- 0.98 ± 0.07). A very high positive genetic correlation of 0.99 ± 0.16 was estimated between abscess and bacteria scores. Estimates of genetic correlations of the resistance score with average daily gain traits for the first and second week after inoculation were 0.98 (± 0.06) and 0.70 (± 0.14), respectively. Estimates of genetic correlations of the disease-related traits with average daily gain pre-inoculation were favorable but with high standard errors. Estimates of genetic and phenotypic correlations of the disease-related traits with commercial selection traits were not significantly different from zero. Disease response traits are heritable and are highly correlated with each other, but do not show any significant genetic correlations with commercial selection traits. Thus, the prevalence of pasteurellosis could be decreased by selecting more resistant rabbits on any one of the disease response traits with a limited impact on the selection traits, which would allow implementation of a breeding program to improve resistance to pasteurellosis in rabbits.


Two aspects of feedforward postural control: anticipatory postural adjustments and anticipatory synergy adjustments.
We used the framework of the uncontrolled manifold hypothesis to explore the relations between anticipatory synergy adjustments (ASAs) and anticipatory postural adjustments (APAs) during feedforward control of vertical posture. ASAs represent a drop in the index of a multimuscle-mode synergy stabilizing the coordinate of the center of pressure in preparation to an action. ASAs reflect early changes of an index of covariation among variables reflecting muscle activation, whereas APAs reflect early changes in muscle activation levels averaged across trials. The assumed purpose of ASAs is to modify stability of performance variables, whereas the purpose of APAs is to change magnitudes of those variables. We hypothesized that ASAs would be seen before APAs and that this finding would be consistent with regard to the muscle-mode composition defined on the basis of different tasks and phases of action. Subjects performed a voluntary body sway task and a quick, bilateral shoulder flexion task under self-paced and reaction time conditions. Surface muscle activity of 12 leg and trunk muscles was analyzed to identify sets of 4 muscle modes for each task and for different phases within the shoulder flexion task. Variance components in the muscle-mode space and indexes of multimuscle-mode synergy stabilizing shift of the center of pressure were computed. ASAs were seen ∼ 100-150 ms prior to the task initiation, before APAs. The results were consistent with respect to different sets of muscle modes defined over the two tasks and different shoulder flexion phases. We conclude that the preparation for a self-triggered postural perturbation is associated with two types of anticipatory adjustments, ASAs and APAs. They reflect different feedforward processes within the hypothetical hierarchical control scheme, resulting in changes in patterns of covariation of elemental variables and in their patterns averaged across trials, respectively. The results show that synergies quantified using dissimilar sets of muscle modes show similar feedforward changes in preparation to action.


The effects of carabid beetles (Coleoptera: Carabidae) on the arthropod fauna of wheat fields in Chile.
The role of carabid beetles in reducing populations of phytophagous insects has been an elusive subject. A field experiment was established on a commercial wheat crop (cv. Otto) with an area of 4.5 ha in Valdivia, Chile, during the spring and summer of 1996-1997. The field had been under a prairie system for two years, before wheat sowing (fertilization and a pesticide had been applied during crop development). Samples were taken at approximately monthly intervals. Carabid beetles were sampled with a grid of pitfall traps and other insects were sampled with a vacuum insect net and soil cores. The genera of the carabids found are of neotropical origin. Exclusion by polythene barriers, together with removal of carabid beetles using traps, was an effective technique for controlling carabid populations in a commercial wheat crop. A reduction in the number of carabid beetles was associated with an increase in the number of springtails and arachnids, and a decrease of agromyzid adults. Phytophagous insects, such as homopterans and lepidopterous larvae, were not affected by carabid exclusion and removal. The action of carabid beetles on the arthropod fauna can be extremely complex, due to its predatory activity at multitrophic levels.


A Roadmap for Strategic Planning in the Healthcare Practice.
The days of a practice putting up a shingle or sign and waiting for patients to come for treatment are over. The same applies to hospitals, which can't just have beds, an emergency department, an operating room, and an intensive care unit and hope to remain profitable in this tumultuous era of healthcare delivery. Now it is imperative to have a strategic plan to move forward. Practices and hospitals need a plan in order to prosper, rather than settle for mere survival. This article defines strategic planning, discusses the creation of a strategic plan, and lays out how a plan might be implemented in a medical practice or hospital.


Bone grafting for scaphoid nonunion surgery : a systematic review and meta-analysis.
The purpose of this systematic review was to determine the rates of union for vascularized versus non-vascularized grafting techniques in the operative management of scaphoid nonunion. Secondary aims were to determine the effect of the fixation techniques used, the source of grafting, as well as the influence of fracture location (proximal pole) and avascular necrosis (AVN). A search of PubMed, MEDLINE, and Embase was performed in June 2021 using the Preferred Reporting Items for Systematic Review and Meta-Analyses statement and registered using the PROSPERO International prospective register of systematic reviews. The primary outcome was union rate. There were 78 studies that met the inclusion criteria with a total of 7,671 patients (87.8% male, 12.2% female). The mean age was 27.9 years (SD 3.8) and the mean follow-up was 30.9 months (SD 25.9). The mean union rate was 88.7% (95% confidence interval (CI) 85.0 to 92.5) for non-vascularized grafts versus 87.5% (95% CI 82.8 to 92.2) for vascularized grafts (p = 0.685). Pooled analysis of trial data alone found a mean union rate of 82.4% (95% CI 66.9% to 97.9%) for non-vascularized grafts and 89.4% (95% CI 84.1% to 94.7%) for vascularized grafts (p = 0.780). No significant difference was observed in union rates between any of the fixation techniques used in the studies (p = 0.502). Distal radius and iliac crest graft source had comparable mean union rates (86.9% (95% CI 83.1 to 90.7) vs 87.6% (95% CI 82.2 to 92.9); p = 0.841). Studies that excluded patients with both proximal pole fractures and AVN (n = 14) had a mean union rate of 96.5% (95% CI 94.2 to 98.9) that was significantly greater than the mean union rate of 86.8% (95% CI 83.2 to 90.4) observed in the remaining studies (p < 0.001). Current evidence suggests vascularized bone grafting does not yield significantly superior results to non-vascularized grafting in scaphoid nonunion management. However, potential selection bias lessens the certainty of these findings. The fixation type or source of the graft used was not found to influence union rates either. Sufficiently designed and powered prospective randomized controlled trials in this area are needed. Cite this article: Bone Joint J 2022;104-B(5):549-558.


Barnase as a new therapeutic agent triggering apoptosis in human cancer cells.
RNases are currently studied as non-mutagenic alternatives to the harmful DNA-damaging anticancer drugs commonly used in clinical practice. Many mammalian RNases are not potent toxins due to the strong inhibition by ribonuclease inhibitor (RI) presented in the cytoplasm of mammalian cells. In search of new effective anticancer RNases we studied the effects of barnase, a ribonuclease from Bacillus amyloliquefaciens, on human cancer cells. We found that barnase is resistant to RI. In MTT cell viability assay, barnase was cytotoxic to human carcinoma cell lines with half-inhibitory concentrations (IC(50)) ranging from 0.2 to 13 microM and to leukemia cell lines with IC(50) values ranging from 2.4 to 82 microM. Also, we characterized the cytotoxic effects of barnase-based immunoRNase scFv 4D5-dibarnase, which consists of two barnase molecules serially fused to the single-chain variable fragment (scFv) of humanized antibody 4D5 that recognizes the extracellular domain of cancer marker HER2. The scFv 4D5-dibarnase specifically bound to HER2-positive cells and was internalized via receptor-mediated endocytosis. The intracellular localization of internalized scFv 4D5-dibarnase was determined by electronic microscopy. The cytotoxic effect of scFv 4D5-dibarnase on HER2-positive human ovarian carcinoma SKOV-3 cells (IC(50) = 1.8 nM) was three orders of magnitude greater than that of barnase alone. Both barnase and scFv 4D5-dibarnase induced apoptosis in SKOV-3 cells accompanied by internucleosomal chromatin fragmentation, membrane blebbing, the appearance of phosphatidylserine on the outer leaflet of the plasma membrane, and the activation of caspase-3. These results demonstrate that barnase is a potent toxic agent for targeting to cancer cells.


Adenosine, ketogenic diet and epilepsy: the emerging therapeutic relationship between metabolism and brain activity.
For many years the neuromodulator adenosine has been recognized as an endogenous anticonvulsant molecule and termed a "retaliatory metabolite." As the core molecule of ATP, adenosine forms a unique link between cell energy and neuronal excitability. In parallel, a ketogenic (high-fat, low-carbohydrate) diet is a metabolic therapy that influences neuronal activity significantly, and ketogenic diets have been used successfully to treat medically-refractory epilepsy, particularly in children, for decades. To date the key neural mechanisms underlying the success of dietary therapy are unclear, hindering development of analogous pharmacological solutions. Similarly, adenosine receptor-based therapies for epilepsy and myriad other disorders remain elusive. In this review we explore the physiological regulation of adenosine as an anticonvulsant strategy and suggest a critical role for adenosine in the success of ketogenic diet therapy for epilepsy. While the current focus is on the regulation of adenosine, ketogenic metabolism and epilepsy, the therapeutic implications extend to acute and chronic neurological disorders as diverse as brain injury, inflammatory and neuropathic pain, autism and hyperdopaminergic disorders. Emerging evidence for broad clinical relevance of the metabolic regulation of adenosine will be discussed.


Structural and functional analysis of the human mitotic-specific ubiquitin-conjugating enzyme, UbcH10.
Cell cycle progression is controlled at several different junctures by the targeted destruction of cell cycle regulatory proteins. These carefully orchestrated events include the destruction of the securin protein to permit entry into anaphase, and the destruction of cyclin B to permit exit from mitosis. These destruction events are mediated by the ubiquitin/proteasome system. The human ubiquitin-conjugating enzyme, UbcH10, is an essential mediator of the mitotic destruction events. We report here the 1.95-A crystal structure of a mutant UbcH10, in which the active site cysteine has been replaced with a serine. Functional analysis indicates that the mutant is active in accepting ubiquitin, although not as efficiently as wild-type. Examination of the crystal structure reveals that the NH2-terminal extension in UbcH10 is disordered and that a conserved 3(10)-helix places a lysine residue near the active site. Analysis of relevant mutants demonstrates that for ubiquitin-adduct formation the presence or absence of the NH2-terminal extension has little effect, whereas the lysine residue near the active site has significant effect. The structure provides additional insight into UbcH10 function including possible sites of interaction with the anaphase promoting complex/cyclosome and the disposition of a putative destruction box motif in the structure.


Is there any role for antithymocyte induction in renal transplantation?
The use of an antibody induction agent in kidney transplantation lowers the risk of an acute rejection episode and may improve graft outcomes. Antithymocyte globulin (ATG) is the most commonly used antibody induction agent for kidney transplantation in the United States, despite its significant side effect profile and cost compared to the interleukin-2 receptor antagonists (IL2-RA). Our review suggests the IL2-RA are safe and well tolerated, and provide equal clinical benefit to ATG at a lower cost. We propose that there is insufficient evidence to justify the use of ATG induction in kidney transplantation.


Metabolically Healthy Obesity and the Risk of Cardiovascular Disease in the Elderly Population.
Whether being metabolically healthy obese (MHO)-defined by the presence of obesity in the absence of metabolic syndrome-is associated with subsequent cardiovascular disease (CVD) remains unclear and may depend on the participants' age. We examined the association of being MHO with CVD risk in the elderly. This study included 5,314 individuals (mean age 68 years) from the prospective population-based Rotterdam Study. We categorized our population in groups according to body mass index (BMI) and presence and absence of metabolic syndrome, and estimated the hazard ratio (HR) and 95% confidence interval (95%CI) for every group by using Cox proportional hazard models. Among 1048 (19.7%) obese individuals we identified 260 (24.8%) MHO subjects. Over 14 years of follow-up there were 861 incident CVD cases. In the multivariable adjusted analysis, we did not observe an increased CVD risk in MHO individuals (HR 1.07, 95%CI 0.75-1.53), compared to normal weight individuals without metabolic syndrome. CVD risk was increased by the presence of metabolic syndrome in normal weight (HR 1.35, 95%CI 1.02-1.80), overweight (HR 1.32, 95%CI 1.09-1.60) and obese (HR 1.33, 95%CI 1.07-1.66) individuals, compared to those with normal weight without metabolic syndrome. In a mediation analysis, 71.3% of the association between BMI and CVD was explained by the presence of metabolic syndrome. In our elderly population, we found that the presence of obesity without metabolic syndrome did not confer a higher CVD risk. However, metabolic syndrome was strongly associated with CVD risk, and was associated with an increased risk in all BMI categories. Therefore, preventive interventions targeting cardiometabolic risk factors could be considered in elderly, regardless of weight status.


Role of the Transforming Growth Factor-β in regulating hepatocellular carcinoma oxidative metabolism.
Transforming Growth Factor beta (TGF-β) induces tumor cell migration and invasion. However, its role in inducing metabolic reprogramming is poorly understood. Here we analyzed the metabolic profile of hepatocellular carcinoma (HCC) cells that show differences in TGF-β expression. Oxygen consumption rate (OCR), extracellular acidification rate (ECAR), metabolomics and transcriptomics were performed. Results indicated that the switch from an epithelial to a mesenchymal/migratory phenotype in HCC cells is characterized by reduced mitochondrial respiration, without significant differences in glycolytic activity. Concomitantly, enhanced glutamine anaplerosis and biosynthetic use of TCA metabolites were proved through analysis of metabolite levels, as well as metabolic fluxes from U-13C6-Glucose and U-13C5-Glutamine. This correlated with increase in glutaminase 1 (GLS1) expression, whose inhibition reduced cell migration. Experiments where TGF-β function was activated with extracellular TGF-β1 or inhibited through TGF-β receptor I silencing showed that TGF-β induces a switch from oxidative metabolism, coincident with a decrease in OCR and the upregulation of glutamine transporter Solute Carrier Family 7 Member 5 (SLC7A5) and GLS1. TGF-β also regulated the expression of key genes involved in the flux of glycolytic intermediates and fatty acid metabolism. Together, these results indicate that autocrine activation of the TGF-β pathway regulates oxidative metabolism in HCC cells.


BRCA1 exon 11 alternative splicing, multiple functions and the association with cancer.
BRCA1 (breast cancer early-onset 1) alternative splicing levels are regulated in a cell-cycle- and cell-type-specific manner, with splice variants being present in different proportions in tumour cell lines as well as in normal mammary epithelial cells. The importance of this difference in the pathogenesis of breast cancer has yet to be determined. Developing an understanding of the impact of BRCA1 isoform ratio changes on cell phenotype will be of value in breast cancer and may offer therapeutic options. In the present paper, we describe the splicing isoforms of BRCA1 exon 11, their possible role in cancer biology and the importance of maintaining a balanced ratio.


Functional dissociation of ventral frontal and dorsomedial default mode network components during resting state and emotional autobiographical recall.
Humans spend a substantial share of their lives mind-wandering. This spontaneous thinking activity usually comprises autobiographical recall, emotional, and self-referential components. While neuroimaging studies have demonstrated that a specific brain "default mode network" (DMN) is consistently engaged by the "resting state" of the mind, the relative contribution of key cognitive components to DMN activity is still poorly understood. Here we used fMRI to investigate whether activity in neural components of the DMN can be differentially explained by active recall of relevant emotional autobiographical memories as compared with the resting state. Our study design combined emotional autobiographical memory, neutral memory and resting state conditions, separated by a serial subtraction control task. Shared patterns of activation in the DMN were observed in both emotional autobiographical and resting conditions, when compared with serial subtraction. Directly contrasting autobiographical and resting conditions demonstrated a striking dissociation within the DMN in that emotional autobiographical retrieval led to stronger activation of the dorsomedial core regions (medial prefrontal cortex, posterior cingulate cortex), whereas the resting state condition engaged a ventral frontal network (ventral striatum, subgenual and ventral anterior cingulate cortices) in addition to the IPL. Our results reveal an as yet unreported dissociation within the DMN. Whereas the dorsomedial component can be explained by emotional autobiographical memory, the ventral frontal one is predominantly associated with the resting state proper, possibly underlying fundamental motivational mechanisms engaged during spontaneous unconstrained ideation.


Current rates of purchasing of antibiotics without a prescription across sub-Saharan Africa; rationale and potential programmes to reduce inappropriate dispensing and resistance.
Antimicrobial resistance (AMR) is a global concern. Currently, the greatest mortality due to AMR is in Africa. A key driver continues to be high levels of dispensing of antibiotics without a prescription. A need to document current rates of dispensing, their rationale and potential ways forward including antimicrobial stewardship programmes (ASPs). A narrative review was undertaken. The highest rates of antibiotic purchasing were in Eritrea (up to 89.2% of antibiotics dispensed), Ethiopia (up to 87.9%), Nigeria (up to 86.5%), Tanzania (up to 92.3%) and Zambia (up to 100% of pharmacies dispensing antibiotics without a prescription). However, considerable variation was seen with no dispensing in a minority of countries and situations. Key drivers of self-purchasing included high co-payment levels for physician consultations and antibiotic costs, travel costs, convenience of pharmacies, patient requests, limited knowledge of antibiotics and AMR and weak enforcement. ASPs have been introduced in some African countries along with quality targets to reduce inappropriate dispensing, centering on educating pharmacists and patients. ASP activities need accelerating among community pharmacies alongside quality targets, with greater monitoring of pharmacists' activities to reduce inappropriate dispensing. Such activities, alongside educating patients and healthcare professionals, should enhance appropriate dispensing of antibiotics and reduce AMR.


Application of partial least-squares regression to near-infrared reflectance spectroscopic determination of shive content in flax.
Shive, the nonfiberous core portion of the stem, in flax fiber after retting is related to fiber quality. The objective of this study is to develop a standard calibration model for determining shive content in retted flax by using near-infrared reflectance spectroscopy. Calibration samples were prepared by manually mixing pure, ground shive and pure, ground fiber from flax retted by three different methods (water, dew, and enzyme retting) to provide a wide range of shive content from 0 to 100%. Partial least-squares (PLS) regression was used to generate a calibration model, and spectral data were processed using various pretreatments such as a multiplicative scatter correction (MSC), normalization, derivatives, and Martens' Uncertainty option to improve the calibration model. The calibration model developed with a single sample set resulted in a standard error of 1.8% with one factor. The best algorithm was produced from first-derivative processing of the spectral data. MSC was not effective processing for this model. However, a big bias was observed when independent sample sets were applied to this calibration model to predict shive content in flax fiber. The calibration model developed using a combination sample set showed a slightly higher standard error and number of factors compared to the model for a single sample set, but this model was sufficiently accurate to apply to each sample set. The best algorithm for the combination sample set was generated from second derivatives followed by MSC processing of spectral data and from Martens' Uncertainty option; it resulted in a standard error of 2.3% with 2 factors. The value of the digital second derivative centered at 1674 nm for these spectral data was highly correlated to shive content of flax and could form the basis for a simple, low-cost sensor for the shive or fiber content in retted flax.


Iridopathy in eyes with proliferative diabetic retinopathy: detection of early stage of rubeosis iridis.
Forty-two eyes of 31 proliferative diabetic retinopathy patients with laser flare intensity > or = 20 photon counts/ms underwent fluorescein iris angiography to evaluate any changes in the blood-iris barrier and iris biomicroscopy to detect rubeosis iridis. Fluorescein iris angiography revealed abnormal dye leakage in all eyes. Laser flare intensity significantly correlated with the degree of dye leakage. Eyes with dye leakage from only the pupillary border had no rubeosis. In 11 out of 18 (61%) eyes with moderate dye leakage, proliferative diabetic iridopathy with early rubeosis was present in 8 and advanced iridopathy in 3 eyes. In all eyes with excessive leakage, rubeosis iridis was detected under slitlamp examination. High laser flare intensity has a close relationship with advanced blood-ocular barrier disruption. High flare intensity may be a helpful indicator in detecting incipient rubeosis or advanced diabetic iridopathy.


High-performance liquid chromatographic assay of erythromycin from biological matrix using electrochemical or ultraviolet detection.
Two chromatographic methods were developed for the determination of erythromycin A (EA) residues in animal tissues (muscle, liver, kidney and fat of cattle, pigs and poultry) and cow's milk. In addition to a more traditional method using electrochemical detection, we developed an original alternative method based on UV detection at 236 nm, by pretreating to create a chromophore in the molecule. An internal standard was used with both methods to check the variability of the analytical system. Analysis times and performance were compared. The recovery of EA from various matrices was greater than 95%. For both methods the quantification limit for EA was 0.25 microgram ml-1 for plasma, 0.025 microgram g-1 for milk and 0.125 microgram g-1 for the other biological matrices. The methods can be used to check for EA residues in these matrices; in fact, the statutory maximum residue limits (MRLs) of EA are 0.4 microgram g-1 in muscle, kidney, liver and fat of beef cattle, sheep, pigs and poultry, and 0.04 microgram g-1 in cow's and sheep's milk.


W value measurements for protons in tissue-equivalent gas and its constituent gases.
Values of W (the mean energy required to create an ion pair when a charged particle is stopped in a gas) are needed in radiation dosimetry to convert ionisation chamber current readings to absorbed dose. For neutron dosimetry the most important W values are those for protons, and this paper describes absolute measurements for protons with energies between 1.2 and 3.5 MeV for methane-based tissue-equivalent gas and its constituent gases, i.e. methane, carbon dioxide and nitrogen. An ionisation chamber with a parallel-plate arrangement was used to determine the integrated charge created by a measured number of protons, and W values were determined with an estimated uncertainty of about +/- 0.5%. The results are presented and compared with previous measurements. In general the present data tend to be somewhat lower than previously reported values. Finally the accuracy of a formula for predicting W values for gas mixtures from the values for the individual constituents is investigated.


Preproduction quality assurance: quality intrinsic to design.
The Safe Medical Devices Act of 1990 made important changes to the Federal Food, Drug, and Cosmetic Act's provisions governing medical devices and in vitro diagnostics. Not the least of these changes is the addition of preproduction design validation "including a process to assess the performance of a device but not including an evaluation of the safety or effectiveness of a device," under the good manufacturing practice (GMP) regulation. Combining this new law with the existing GMP regulation on manufacturing operations yields the beginning of total quality management (TQM).


Borderline personality disorder in adolescents: prevalence, diagnosis, and treatment strategies.
Using the same Diagnostic and Statistical Manual of Mental Disorders, fifth version (DSM-V) criteria as in adults, borderline personality disorder (BPD) in adolescents is defined as a 1-year pattern of immature personality development with disturbances in at least five of the following domains: efforts to avoid abandonment, unstable interpersonal relationships, identity disturbance, impulsivity, suicidal and self-mutilating behaviors, affective instability, chronic feelings of emptiness, inappropriate intense anger, and stress-related paranoid ideation. BPD can be reliably diagnosed in adolescents as young as 11 years. The available epidemiological studies suggest that the prevalence of BPD in the general population of adolescents is around 3%. The clinical prevalence of BPD ranges from 11% in adolescents consulting at an outpatient clinic to 78% in suicidal adolescents attending an emergency department. The diagnostic procedure is based on a clinical assessment with respect to developmental milestones and the interpersonal context. The key diagnostic criterion is the 1-year duration of symptoms. Standardized, clinician-rated instruments are available for guiding this assessment (eg, the Diagnostic Interview for Borderlines-Revised and the Childhood Interview for DSM-IV-TR BPD). The assessment should include an evaluation of the suicidal risk. Differential diagnosis is a particular challenge, given the high frequency of mixed presentations and comorbidities. With respect to clinical and epidemiological studies, externalizing disorders in childhood constitute a risk factor for developing BPD in early adolescence, whereas adolescent depressive disorders are predictive of BPD in adulthood. The treatment of adolescents with BPD requires commitment from the parents, a cohesive medical team, and a coherent treatment schedule. With regard to evidence-based medicine, psychopharmacological treatment is not recommended and, if ultimately required, should be limited to second-generation antipsychotics. Supportive psychotherapy is the most commonly available first-line treatment. Randomized controlled trials have provided evidence in favor of the use of specific, manualized psychotherapies (dialectic-behavioral therapy, cognitive analytic therapy, and mentalization-based therapy).


Physical Exercise and Health, 3: The Health Care Professional and Patient's Guide to Understanding What to Do, How, and Why-Part 1.
Physical activity and exercise are associated with important short- and long-term health benefits. It does not take much effort to reap these benefits; every little bit of activity counts, including activities that are performed as part of daily life. Everybody can exercise, even those with existing medical conditions, and even those with existing cardiac or orthopedic conditions; all that is necessary is to tailor the exercise to individual capacity with appropriate dos and don'ts. This article, addressed to health care professionals, their patients, and the general public, provides practical guidance on exercise, mostly in the form of points and short paragraphs, so that the reader can easily understand and assimilate what to do, how, and why. The article explains what the health benefits of exercise are; how much exercise one ideally needs to perform for optimal health outcomes; what targets to set for exercise; what effects exercise has on muscles, bones, and the heart; and how these effects are beneficial. The article offers suggestions on how to create time and opportunity for exercise, how to motivate oneself for exercise, and how to avoid boredom and discouragement. Most important of all, this article provides a detailed discussion on exercise-related risks, especially orthopedic risks, and how to avoid these risks. Protecting the knee joint from injury receives particular attention. Practical guidance on what to actually do appears in the next article in the series.


The Use of Indocyanin Green for Peroperative Diagnostic of Chylous Ascites and Autologous Tissue Glue (Vivostat) for the Treatment.
Chylous ascites or chyloperitoneum can be caused by peroperative injury of the lymphatic pathways; the lymph is accumulated in the abdominal cavity. The incidence of chylous ascites varies according to the type of surgery and the extent of the lymphadenectomy. The first choice of treatment is a conservative procedure - total parenteral nutrition or a strict low-fat diet. If this fails, a surgical revision is indicated. However, this is often difficult due to postoperatively altered terrain and the chronic presence of pathological secretion in the abdominal cavity. The application of a fat emulsion or indocyanine green (ICG) to the lymphatic drainage area may help identify the lymph source. Nowadays, ICG is used in various clinical indications, e.g. evaluation of liver function, angiography in ophthalmology, assessment of blood supply to the tissues, search for lymph nodes in oncological surgeries. The advantage of ICG lymphography is the possibility of observing the source of the leak in real time directly during surgical revision. A polymorbid 66-year-old patient after radical oncogynaecological surgery with aortopelvic lymphadenectomy was postoperatively complicated by persistent, high-volume chylous ascites, not responding to conservative treatment. Therefore, we performed surgical revision of the abdominal cavity and successful treatment of the leak source using ICG peroperative lymphography and subsequent application of Vivostat autologous tissue glue to this area. High-volume consistent chylous ascites is not a frequent postoperative complication but it has a significant impact on the quality of life, nutritional status of the patient and further patient prognosis. The treatment is strictly individual. The first choice should be a conservative approach. Where that fails, a difficult surgical revision is indicated. Today, however, the surgeon can be helped by modern technologies such as fluorescent navigated surgery or treatment of the source with autologous tissue adhesives. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedice papers.


[New type of mitochondrial mutation in yeasts--temperature-dependent mitochondrial mutations resistant to antibiotics].
Mitochondrial mutants of yeast Saccharomyces cerevisiae XII race resistant to erythromycin, neomycin and monomycin were used in the experiments. It is found that there are mitochondrial mutants resistant to antibiotics at 30 degrees C, but sensitive at 37 degrees C. In most cases the sensitivity to antibiotics was accompanied by a loss of the ability to growth on non-fermental carbon sources at the elevated temperature (37 degrees C). The genetic analysis revealed the extra-chromosomal inheritance of the markers. Probable interpretation of this phenomenon is discussed.


Fibrinogen-to-Albumin Ratio and Clinical Outcomes in Patients With Large Artery Atherosclerosis Stroke.
A high fibrinogen-to-albumin ratio (FAR), a novel inflammatory marker, is considered to be a prognostic marker in vascular diseases. However, the association of FAR with large artery atherosclerosis (LAA) stroke is still unknown. This study was conducted to evaluate the association between FAR levels and clinical outcomes in patients with acute LAA stroke. A total of 809 patients within 72 hours of LAA stroke were included and followed up to 1 year. FAR was calculated as fibrinogen (g/L)/albumin (g/L). The associations of FAR with clinical outcomes were assessed by multivariate Cox regression or logistic regression analysis. Clinical outcomes included stroke recurrence, all-cause death, poor functional outcome (modified Rankin Scale score 3-6), and dependence (modified Rankin Scale score 3-5). Among the 809 patients with acute LAA stroke, the median FAR was 0.075 (interquartile range, 0.064-0.087). At 1 year, 103 (12.7%) patients had stroke recurrence, 105 (13.0%) had poor functional outcome, 76 (9.8%) had dependence, and 29 (3.6%) had died. After adjusting for all confounding risk factors, a high FAR level was associated with stroke recurrence (hazard ratio, 2.57 [95% CI, 1.32-5.02]), poor functional outcome (odds ratio, 3.30 [95% CI, 1.57-6.94]), and dependence (odds ratio, 3.49 [95% CI, 1.49-8.19]). A high FAR level was associated with an increased risk of stroke recurrence, poor functional outcome, and dependence in patients with acute LAA stroke.


Effect of the type of emulsifying salt on microstructure and rheological properties of "requeijão cremoso" processed cheese spreads.
The role of different types of emulsifying salts-sodium citrate (TSC), sodium hexametaphosphate (SHMP), sodium tripolyphosphate (STPP) and tetrasodium pyrophosphate (TSPP)-on microstructure and rheology of "requeijão cremoso" processed cheese was determined. The cheeses manufactured with TSC, TSPP, and STPP behaved like concentrated solutions, while the cheese manufactured with SHMP exhibited weak gel behavior and the lowest values for the phase angle (G"/G'). This means that SHMP cheese had the protein network with the largest amount of molecular interactions, which can be explained by its highest degree of fat emulsification. Rotational viscometry indicated that all the spreadable cheeses behaved like pseudoplastic fluids. The cheeses made with SHMP and TSPP presented low values for the flow behavior index, meaning that viscosity was more dependent on shear rate. Regarding the consistency index, TSPP cheese showed the highest value, which could be attributed to the combined effect of its high pH and homogeneous fat particle size distribution.


Prognostic significance of plasminogen activator inhibitor-1 in breast cancer, with special emphasis on locoregional recurrence-free survival.
The independent prognostic value of protease uPA and its inhibitor PAI-1 for survival in breast cancer patients is firmly established. However, there is very little data on the prognostic value of serine proteases and their inhibitors for locoregional recurrence in breast cancer. The prognostic value of PAI-1 for local control in a group of 766 patients treated at our institute with either breast conserving treatment or modified radical mastectomy was evaluated. The locoregional recurrence-free survival (LRFS) of patients with PAI-1 values above the median value was significantly worse than that of patients with PAI-1 values below the median value (log-rank; p=0.0078). In multivariate analysis PAI-1 levels proved to be of independent statistical significance for LRFS (p=0.0401, relative risk 2.28, 95% confidence interval 1.04-5.02). The independent prognostic value of PAI-1 for metastasis-free survival and overall survival was also confirmed. In addition, our data suggest that PAI-1 antigen levels in tumor tissue might be of prognostic value for survival after locoregional recurrence (log-rank; p=0.0618). According to our findings, PAI-1 levels could be used as a biological marker that could facilitate the identifation of patients with a higher risk of local relapse already at the time of primary treatment. These patients should then be offered more aggressive treatment.


Two-dimensional and three-dimensional ultrasound of fetal anasarca: the glass baby.
Fetal edema was recognized in the past as a complication of alloimmune disease. More recently, fetal edema is frequently seen in conditions that cause non-immune fetal hydrops with increased soft tissue thickness. Classically there is a halo pattern around fetal head, neck, thorax, and abdomen. Fetal edema is associated with karyotype abnormalities, with multiple congenital anomalies, and with certain fetal infections like parvovirus B19 that cause severe fetal anemia. In the present case there was no evidence of infection or karyotype abnormality, but there was hypoplasia of umbilical cord vessels, pulmonary hypoplasia, and pericardial effusion. The etiology of fetal hydrops may remain unknown in up to 30% of cases.


Incremental diagnostic value of regional left ventricular function over coronary assessment by cardiac computed tomography for the detection of acute coronary syndrome in patients with acute chest pain: from the ROMICAT trial.
The incremental value of regional left ventricular function (LVF) over coronary assessment to detect acute coronary syndrome (ACS) is uncertain. We analyzed 356 patients (mean age, 53+/-12 years; 62% men) with acute chest pain and inconclusive initial emergency department evaluation. Patients underwent 64-slice contrast-enhanced cardiac computed tomography before hospital admission. Caregivers and patients remained blinded to the results. Regional LVF and presence of coronary atherosclerotic plaque and significant stenosis (>50%) were separately assessed by 2 independent readers. Incremental value of regional LVF to predict ACS was determined in the entire cohort and in subgroups of patients with nonobstructive coronary artery disease, inconclusive assessment for stenosis (defined as inability to exclude significant stenosis due to calcium or motion), and significant stenosis. During their index hospitalization, 31 patients were ultimately diagnosed with ACS (8 myocardial infarction, 22 unstable angina), of which 74% (23 patients) had regional LV dysfunction. Adding regional LVF resulted in a 10% increase in sensitivity to detect ACS by cardiac computed tomography (87%; 95% confidence interval, 70% to 96%) and significantly improved the overall accuracy (c-statistic: 0.88 versus 0.94 and 0.79 versus 0.88, for extent of plaque and presence of stenosis, respectively; both P<0.03). The diagnostic accuracy of regional LVF for detection of ACS has 89% sensitivity and 86% specificity in patients with significant stenosis (n=33) and 60% sensitivity and 86% specificity in patients with inconclusive coronary computed tomographic angiography (n=33). Regional LVF assessment at rest improves diagnostic accuracy for ACS in patients with acute chest pain, especially in those with coronary artery disease and thus may be helpful to guide further management in patients at intermediate risk for ACS.


The protective effects of beta-mangostin against sodium iodate-induced retinal ROS-mediated apoptosis through MEK/ERK and p53 signaling pathways.
Previous studies have indicated that NaIO3 induces intracellular reactive oxygen species (ROS) production and has been used as a model for age-related macular degeneration (AMD) due to the selective retinal pigment epithelium (RPE) cell damage it induces. Beta-mangostin (BM) is a xanthone-type natural compound isolated from Cratoxylum arborescens. The influence of BM on NaIO3-induced oxidative stress damage in ARPE-19 cells has not yet been elucidated. In this study, we investigated how BM protects ARPE-19 cells from NaIO3-induced ROS-mediated apoptosis. Our results revealed that BM notably improved cell viability and prevented ARPE-19 cell mitochondrial dysfunction mediated-apoptosis induced by NaIO3; it was mediated by significantly reduced NaIO3-upregulated ROS, cellular H2O2 production and improved downregulated glutathione and catalase activities. Furthermore, we found that BM could suppress the expression of Bax, cleaved PARP, and cleaved caspase-3 by decreasing phosphorylation of MEK/ERK and p53 expression in NaIO3-induced ARPE-19 cells. At the same time, we also used MEK inhibitors (PD98059) to confirm the above phenomenon. Moreover, our animal experiments revealed that BM prevented NaIO3 from causing retinal deformation; it led to thicker outer and inner nuclear layers and downregulated cleaved caspase-3 expression compared to the group receiving NaIO3 only. Collectively, these results suggest that BM can protect the RPE and retina from NaIO3-induced apoptosis through ROS-mediated mitochondrial dysfunction involving the MEK/ERK and p53 signaling pathways.


Young children can extend motion verbs to point-light displays.
In the first study using point-light displays (lights corresponding to the joints of the human body) to examine children's understanding of verbs, 3-year-olds were tested to see if they could perceive familiar actions that corresponded to motion verbs (e.g., walking). Experiment 1 showed that children could extend familiar motion verbs (e.g., walking and dancing) to videotaped point-light actions shown in the intermodal preferential looking paradigm. Children watched the action that matched the requested verb significantly more than they watched the action that did not match the verb. In Experiment 2, the findings of Experiment 1 were validated by having children spontaneously produce verbs for these actions. The use of point-light displays may illuminate the factors that contribute to verb learning.


A Multi-Atlas Label Fusion Tool for Neonatal Brain MRI Parcellation and Quantification.
Structure-by-structure analysis, in which the brain magnetic resonance imaging (MRI) is parcellated based on its anatomical units, is widely used to investigate chronological changes in morphology or signal intensity during normal development, as well as to identify the alterations seen in various diseases or conditions. The multi-atlas label fusion (MALF) method is considered a highly accurate parcellation approach, and anticipated for clinical application to quantitatively evaluate early developmental processes. However, the current MALF methods, which are designed for neonatal brain segmentations, are not widely available. In this study, we developed a T1-weighted, neonatal, multi-atlas repository and integrated it into the MALF-based brain segmentation tools in the cloud-based platform, MRICloud. The cloud platform ensures users instant access to the advanced MALF tool for neonatal brains, with no software or installation requirements for the client. The Web platform by braingps.mricloud.org will eliminate the dependence on a particular operating system (eg, Windows, Macintosh, or Linux) and the requirement for high computational performance of the user's computers. The MALF-based, fully automated, image parcellation could achieve excellent agreement with manual parcellation, and the whole and regional brain volumes quantified through this method demonstrated developmental trajectories comparable to those from a previous publication. This solution will make the latest MALF tools readily available to users, with minimum barriers, and will expedite and accelerate advancements in developmental neuroscience research, neonatology, and pediatric neuroradiology.


Characterization of PetM cytochrome b6f subunit 7 domain-containing protein in tomato.
In recent years, multiple advances have been made in understanding the photosynthetic machinery in model organisms. Knowledge transfer to horticultural important fruit crops is challenging and time-consuming due to restrictions in gene editing tools and prolonged life cycles. Here, we characterize a gene encoding a PetM domain-containing protein in tomato. The CRISPR/Cas9 knockout lines of the PetM showed impairment in the chloroplastic electron transport rate (ETR), reduced CO2 assimilation, and reduction of carotenoids and chlorophylls (Chl) under several light conditions. Further, growth-condition-dependent elevation or repression of Chl a/b ratios and de-epoxidation states were identified, underlining possible impairment compensation mechanisms. However, under low light and glasshouse conditions, there were basal levels in CO2 assimilation and ETR, indicating a potential role of the PetM domain in stabilizing the cytochrome b6f complex (Cb6f) under higher light irradiance and increasing its quantum efficiency. This suggests a potential evolutionary role in which this domain might stabilize the site of the Cb6f regulating ratios of cyclic and linear electron transport and its potential importance during the conquest of terrestrial ecosystems during which plants were exposed to higher irradiance. Finally, the results are discussed with regard to metabolism and their implication to photosynthesis from an agronomic perspective.


Epidemiological aspects of cutaneous malignant melanoma (review).
There is an increasing interest in the etiology of cutaneous malignant melanoma (CMM). Once considered a rare tumour, CMM is now the fourth commonest cancer in Australia and New Zeland, the tenth in the Usa, Canada and Scandinavia and the eighteenth in Great Britain. The growing scientific concern on the urgent need to highlight the cause/s of CMM is well documented by the large number of well-designed and well-conducted epidemiological studies reported in the last two decades. Such studies facilitated testing of many etiological hypotheses derived from earlier descriptive investigations and contributed to significant progress in understanding the etiology of such disease. The quantification of the extent to which the increases in CMM incidence and mortality rates are related to new lifestyles and to new patterns of exposure to potential carcinogenetic agents is essential in order to establish an appropriate preventive strategy. In population of mainly European origin a substantial proportion of the increased incidence of CMM is attributable to steady change from predominantly occupational to predominantly recreational exposure to solar radiation. Therefore the present review puts particular emphasis on exposure to sunlight as well as to artificial ultraviolet light, as modifiable causes of CMM. Incidence and mortality data and other potential risk factors for the development of CMM will also be briefly reviewed.


Nulling the motion aftereffect with dynamic random-dot stimuli: limitations and implications.
We used biased random-dot dynamic test stimuli to measure the strength of the motion aftereffect (MAE) to evaluate the usefulness of this technique as a measure of motion adaptation strength. The stimuli consisted of noise dots whose individual directions were random and of signal dots moving in a unique direction. All dots moved at the same speed. For each condition, the nulling percentage (percentage of signal dots needed to perceptually null the MAE) was scaled with respect to the coherence threshold (percentage needed to perceive the coherent motion of signal dots without prior adaptation). The increase of these scaled values with the density of dots in the test stimulus suggests that MAE strength is underestimated when measured with low densities. We show that previous reports of high nulling percentages at slow speeds do not reflect strong MAEs, but are actually due to spatio-temporal aliasing, which dramatically increases coherence thresholds. We further show that MAE strength at slow speed increases with eccentricity. These findings are consistent with the idea that using this dynamic test stimulus preferentially reveals the adaptation of a population of high-speed motion units whose activity is independent of adapted low-speed motion units.


Selective accumulation of the endoplasmic reticulum-Golgi intermediate compartment induced by the antitumor drug KRN5500.
KRN5500 is a semisynthetic spicamycin analogue consisting of a seven-carbon amino sugar linked to a C(14) unsaturated fatty acid through glycine and to the amino group of adenine. The drug inhibits cell growth potently and has antitumor activity in in vivo models. The mechanism of the antiproliferative effect of KRN5500 remains to be elucidated. We have found that acute exposure of drug-sensitive HT-29 colon adenocarcinoma cells to the drug results initially in swelling of the Golgi apparatus. Continuous exposure to the drug resulted in the emergence of a resistant population of cells characterized by numerous intracellular vacuoles. These KRN5500-resistant tumor cells exhibited increased staining with the Golgi stain NBD C(6)-ceramide and the ER-Golgi fluorescent dye BODIPY-brefeldin A, which, unlike the parental drug-sensitive cells, was dispersed throughout the cytoplasm. Marker enzymes associated with the ER (glucose 6-phosphatase) and cis-Golgi (GalNAc transferase) were elevated >2-fold and nearly 4-fold, respectively, in drug-resistant cell lines while the trans-Golgi marker enzyme, galactosyltransferase, was not. The additional findings that the KRN5500-resistant cells have a >2-fold elevation in ERGIC-53, a cis-Golgi marker protein of the ER-Golgi intermediate compartment (ERGIC), as well as increased 58K, a 58-kDa microtubule-binding protein with formiminotransferase cyclodeaminase activity, and tubulin indicate that the cellular secretory pathway is a primary determinant of sensitivity to KRN5500, as resistance to this agent corresponds with accumulation of several components relatable to ER and cis-Golgi function. Further support for this conclusion is provided by studies which demonstrate that KRN5500 alters the distribution of newly synthesized carcinoembryonic antigen within the secretory pathway, including arrest of this N-glycosylated protein in the Golgi of LS-174T colon carcinoma cells.


[Cancer of the jejunum and Fraumeni syndrome].
An observation of multiple primary tumors of various histogenesis and a rare combination (uterine body carcinoma, mammary fibroadenoma, bronchial carcinoid, jejunum carcinoma) developing in a female patient at various periods of her life is described. The autosome-dominant type of the transfer proves the possibility of a genetic predisposition of the tumor development (the patient's mother and brother also had tumors). This observation demonstrates the variety of tumor combinations and tumor topography in cases of genetically predetermined blastomogenic process. This may represent a basis for distinguishing separate variants of Fraumeni syndrome.


Single Layered Versus Double Layered Intestinal Anastomosis: A Randomized Controlled Trial.
Gastrointestinal anastomosis is one of the most common procedures being performed in oesophagogastric, hepatobiliary, bariatric, small bowel and colorectal surgery; however, the safety and efficacy of single layer or double layer anastomotic technique is still unclear. To assess and compare the efficacy, safety and cost effectiveness of single layered versus double layered intestinal anastomosis. This prospective, double-blind, randomized controlled comparative study comprised of patients who underwent intestinal resection and anastomosis. They were randomly assigned to undergo either single layered extra-mucosal anastomosis (Group-A) or double layered intestinal anastomosis (Group-B). Primary outcome measures included average time taken for anastomosis, postoperative complications, mean duration of hospital stay and cost of suture material used; secondary outcome measures assessed the postoperative return of bowel function. Statistical analysis was done by Chi-square test and student t-test. A total of 97 participants were randomized. Fifty patients were allocated to single layered extramucosal continuous anastomosis (Group-A) and 47 patients to double layered anastomosis (Group-B). The patients in each group were well matched for age, sex and diagnosis. The mean time taken for anastomosis (15.12±2.27 minutes in Group-A versus 24.38±2.26 minutes in Group-B) and the length of hospital stay (5.90±1.43 days in Group-A versus 7.29±1.89 days in Group-B) was significantly shorter in Group-A {p-value <0.001}. The postoperative return of bowel function was quicker in the single layer group (2.42±1.11 days) as compared to the double layer group (3.1±1.34 days). The cost of suture material used was relatively more in the single layered group (564 INR vs. 480 INR) which might be the only factor favoring a double layered anastomosis. However, there was no significant difference in the complication rates between the two groups. It can be concluded that single layered extramucosal continuous intestinal anastomosis is equally safe and perhaps more cost effective than the conventional double layered method and may represent the optimal choice for routine surgical practice.


The Effect of ACTN3 and VDR Polymorphisms on Skeletal Muscle Performance in Axial Spondyloarthropathies.
Spondyloarthritis (SpA) are the most common group of chronic inflammatory rheumatic diseases affecting about 1.5% of the adult Caucasian population. Low back pain is the most common symptom. The aetiopathogenesis of SpA is multifactorial, with well-known genetic and environmental contributions. Furthermore, muscle properties might also be involved in the pathophysiological process and these could be modulated by the genetic background. Alpha-actinin-3 (ACTN3) and Vitamin D receptor (VDR) genes are well-known genes related with muscle performance. Our aim was to analyze four SNPs of these genes and to evaluate their influence in axial SpA (axSpA) susceptibility, phenotype and muscle properties. We performed a pilot study based on case-control approach involving 56 participants: 28 axSpA patients and 28 healthy controls matched by age, gender and levels of physical activity. Clinical, epidemiological and muscle characterization data-muscle physical properties (stiffness, tone, and elasticity), strength, mass, and performance, were collected. Two different muscles were considered for analysis, the Multifidus and Gastrocnemius. Four SNPs of ACTN3 (rs1815739) and VDR (rs2228570, rs731236, and rs7975232), were selected, analyzed and correlated with clinical, epidemiological and muscle characterization data. In total, 51 individuals (27 axSpA patients and 24 matched controls) were eligible for further genetic analysis, 66.7% being male and with a mean age of 36 years. Muscle physical properties, muscle strength and muscle mass were similar in both groups; however, axSpA patients showed a decrease in muscle performance. None of the studied SNPs were associated with disease susceptibility/phenotype, muscle physical properties, muscle strength or muscle mass. However, ACTN3 rs1815739 and VDR rs2228570 were shown to be associated with muscle performance. Our results suggest an association between ACTN3 and VDR polymorphisms and muscle performance in axSpA.


Uncovering the temporal dynamics and regulatory networks of thermal stress response in a hyperthermophile using transcriptomics and proteomics.
Facing rapid fluctuations in their natural environment, extremophiles, like the hyperthermophilic archaeon Pyrococcus furiosus, exhibit remarkable adaptability to extreme conditions. However, our understanding of their dynamic cellular responses remains limited. This study integrates RNA-sequencing and mass spectrometry data, thereby elucidating transcriptomic and proteomic responses to heat and cold shock stress in P. furiosus. Our results reveal rapid and dynamic changes in gene and protein expression following these stress responses. Heat shock triggers extensive transcriptome reprogramming, orchestrated by the transcriptional regulator Phr, targeting a broader gene repertoire than previously demonstrated. For heat shock signature genes, RNA levels swiftly return to baseline upon recovery, while protein levels remain persistently upregulated, reflecting a rapid but sustained response. Intriguingly, cold shock at 4°C elicits distinct short- and long-term responses at both RNA and protein levels. Cluster analysis identified gene sets with either congruent or contrasting trends in RNA and protein changes, representing well-separated arCOG groups tailored to their individual cellular responses. Particularly, upregulation of ribosomal proteins and significant enrichment of 5'-leadered sequences in cold-shock responsive genes suggest that translation regulation is important during cold shock adaption. Further investigating transcriptomic features, we reveal that thermal stress genes are equipped with basal sequence elements, such as strong promoter and poly(U)-terminators, facilitating a regulated response of the respective transcription units. Our study provides a comprehensive overview of the cellular response to temperature stress, advancing our understanding of stress response mechanisms in hyperthermophilic archaea and providing valuable insights into the molecular adaptations that facilitate life in extreme environments.IMPORTANCEExtreme environments provide unique challenges for life, and the study of extremophiles can shed light on the mechanisms of adaptation to such conditions. Pyrococcus furiosus, a hyperthermophilic archaeon, is a model organism for studying thermal stress response mechanisms. In this study, we used an integrated analysis of RNA-sequencing and mass spectrometry data to investigate the transcriptomic and proteomic responses of P. furiosus to heat and cold shock stress and recovery. Our results reveal the rapid and dynamic changes in gene and protein expression patterns associated with these stress responses, as well as the coordinated regulation of different gene sets in response to different stressors. These findings provide valuable insights into the molecular adaptations that facilitate life in extreme environments and advance our understanding of stress response mechanisms in hyperthermophilic archaea.


Amino acid profile of bovine bone during growth.
The amino acid profile of bovine bones at 2, 25 and 130 months of age was examined and the data were expressed as amino acid residues per 1000 total amino acid residues recovered. As age advance proline and hydroxyproline significantly increased in whole bone (P less than .01), while valine, tyrosine, methionine and histidine decreased (P less than .01). To a lesser extent phenylalanine and glutamic acid decreased with increasing age (P greater than .05). A substantial increase (P less than .05) in glycine and arginine, and a considerable decrease (P less than .05) in valine, tyrosine, methionine and histidine occurred between young (2 months) and intermediate (25 months) age bovine bone. The largest differences in amino acid distribution during growth were observed in bones from the young and intermediate age groups. Lower amounts of glycine were present in lumbar vertebra (P less than .05), whereas the highest amount of glycine was found in sacral vertebra when vertebra, ribs and femurs were compared. Proline and hydroxyproline residues were highest in the rib and femur. Vertebrae often contained higher levels of threonine, arginine, histidine, lysine and aspartic acid than either the rib or femur.