Identification of m6A-related lncRNAs-based signature for predicting the prognosis of patients with skin cutaneous melanoma.
Skin cutaneous melanoma (SKCM) is one of the fastest developing malignancies with strong aggressive ability and no proper curative treatments. Numerous studies illustrated the importance of N6-methyladenosine (m6A) RNA modification to tumorigenesis. The aim of this study was to identify novel prognostic signature by using m6A-related lncRNAs, thus to improve the survival for SKCM patients and guide SKCM therapy. We downloaded the Presentational Matrix data from The Cancer Genome Atlas (TCGA) and analyzed all the expressed lncRNAs among 468 SKCM samples. Pearson correlation analysis was performed to assess the correlations between lncRNAs and 29 m6A-related genes. Least absolute shrinkage and selection operator (LASSO), univariate and multivariate Cox regression analysis were performed to construct m6A-related lncRNAs prognostic signature (m6A-LPS). The accuracy and prognostic value of this signature were validated by using receiver operating characteristic (ROC) curves, Kaplan-Meier (K-M) survival analysis, univariate COX or multivariate COX analyses. After calculating risk scores, patients were divided into low- and high-risk subgroups by the median value of risk scores. A total of 2973 lncRNAs were found expressed among SKCM tissues. Prognostic analysis showed that 98 lncRNAs had a significant effect on the survival of SKCM patients. The m6A-LPS was validated using K-M and ROC analysis and the predictive accuracy of the risk score was also high according to the AUC of the ROC curve in training and testing sets. A nomogram based on tumor stage, gender and risk score that had a strong ability to forecast the 1-, 2-, 3-, 5-year OS of SKCM patients confirmed by calibrations. Enrichment analysis indicated that malignancy-associated biological processes and pathways were more common in the high-risk subgroup. Collectively, m6A-related lncRNAs exert as potential biomarkers for prognostic stratification of SKCM patients and may assist clinicians achieving individualized treatment for SKCM.


Graft-versus-host disease following second syngeneic stem cell transplantation for relapsed chronic myeloid leukemia.
Allogeneic bone marrow transplantation is the only curative treatment for patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML); however, recurrence of disease remains a major cause of treatment failure. A 26-year-old man with chronic myeloid leukemia who had a cytogenetic relapse 49 months after his first syngeneic bone marrow transplant (BMT) and hematologic relapse 23 months thereafter progressed to blast crisis despite treatment with IFN-alpha for 15 months. He underwent a second transplantation in early second blast crisis, 92 months after the first BMT with PBPC from his previous donor. Successful hematological reconstitution occurred. On day 50 after the second transplantation the patient developed a generalized rash, hepatomegaly, and cholestatic signs. Skin and liver biopsy revealed changes compatible with acute graft-versus-host disease (GVHD). Treatment with cyclosporin A (CSA) and prednisone was started, and the GVHD resolved. Fifteen months after PBPC transplantation he had a molecular relapse. Despite discontinuation of CSA, the patient progressed into blast crisis 7 months later. The occurrence of GVHD and disappearance of the BCR-ABL-positive clone suggest that a graft-versus-leukemia (GVL) effect may have been operative for 15 months in a patient given a second syngeneic BMT in blast crisis.


Normal tissue complication probability modeling of radiation-induced sensorineural hearing loss after head-and-neck radiation therapy.
The aim of this study was to generate the dose-response curves by six normal tissue complication probability (NTCP) models and ranking the models for prediction of radiation induced sensorineural hearing loss (SNHL) caused by head and neck radiation therapy (RT). Pure tone audiometry (PTA) was performed on 70 ears of patients for 12 months after the completion of RT. The SNHL was defined as a threshold shift ≤15 dB at two contiguous frequencies according to the common toxicity criteria for adverse events scoring system. The models evaluated were: Lyman and Logit; Mean Dose; relative seriality (RS); Individual critical volume (CV); and population CV models. Maximum likelihood analysis was used to fit the models to experimental data. The appropriateness of the fit was determined by the two-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. The dose of 50% complication rate (D50) was 51-60 Gy. Three of the examined models fitted well with clinical data in a 95% confidence interval. The RS model was ranked as the best model of prediction for radiation induced SNHL. Cochlea shows a different behavior against different NTCP models; it may be due to its small size.


Kissing aneurysms of distal anterior cerebral arteries demonstrated by magnetic resonance angiography.
BACKGROUND Multiple aneurysms, associated with distal anterior cerebral artery (ACA) aneurysm, are not rare; therefore, it is important to examine multiplicity of the aneurysms preoperatively. CASE REPORT A case of ruptured distal ACA aneurysm, associated with another one in a mirror position, is reported. A 43-year-old woman suffered subarachnoid hemorrhage. Conventional angiography demonstrated a saccular aneurysm on the bifurcation of the right or left distal ACA; however, magnetic resonance angiography (MRA) revealed two mirror-image aneurysms on both bifurcations. CONCLUSION MRA was useful for preoperative diagnosis of kissing aneurysms on distal ACAs.


Low nutritive quality as defence against herbivores: induced responses in birch.
The effects of artificial defoliation of birch trees in the previous year on the consumption and utilization of food by a geometrid larva, Epirrita autumnata, were studied in laboratory. The leaves were collected from two sites on a slope of a fell. Defoliation had a significant retarding effect on approximate digestibility, efficiency of conversion of ingested food, relative consumption rate and relative growth rate but not on efficiency of conversion of digested food. The effects were to the same direction with leaves from the two sites, but the response was stronger with leaves from the zone defoliated by Epirrita during mid-sixties. The defensive nature of the response(s) of birch to defoliation is discussed in the light of these results. It is concluded that contrary to the hypothesis of Moran and Hamilton (1980) no increase in the consumption incurred by individual trees could be shown in this system.


Postoperative medical management following pediatric epilepsy surgery.
Medical management of the post-epilepsy surgery patient depends on careful preoperative consideration of that patient's medical, social, cognitive, and emotional status. Outcome expectations should be realistic. Families should be warned that existing cognitive and psychobehavioral problems may not be following surgery, even if seizures are well controlled. As criteria for surgery and surgical techniques continue to evolve, epilepsy centers have an ongoing responsibility to provide objective assessment of outcome. Prospective multicenter studies are required to address these issues adequately.


Towards personal health record: current situation, obstacles and trends in implementation of electronic healthcare record in Europe.
In this article, we define the electronic healthcare record and present its purpose as a tool for continuity of care. We briefly describe the current situation of usage and focus on the major challenges to wide implementation in Europe and beyond. Finally, we point out trends that show stronger involvement of the patients-citizens in the health care prevention and promotion processes, and discuss the impact on the future development of the electronic healthcare record into personal health records.


Antiandrogenic effects of spironolactone: hormonal and ultrastructural studies in dogs and men.
A decrease in the level of plasma testosterone and an increase in the level of plasma progesterone were noted after spironolactone had been administered for 20 days in 5 patients with prostatic carcinoma, as well as in 8 male dogs. Electron microscopic observation disclosed myelin-like bodies in the cytoplasm of Leydig and adrenocortical cells in dogs, contributing to a resolution of the mode of antiandrogenic action of spironolactone.


Risk factors associated with the progression of COVID-19 in elderly diabetes patients.
To describe the clinical characteristics and risk factors associated with the progression of COVID-19 in elderly diabetes patients. This was a retrospective cohort study, including elderly COVID-19 patients admitted to Wuhan Huoshenshan Hospital between February 10 and 13, 2020. Demographic data, medical history, signs and symptoms, and laboratory parameters were collected and analysed. We included 131 elderly COVID-19 patients (50 patients with diabetes). COVID-19 diabetes patients experienced more severe pneumonia and abnormal organ functions than non-diabetes patients (P < 0.05 or P < 0.01). Most function indicators were significantly different between the mild to moderate and severely ill groups in diabetes patients (P < 0.05 or P < 0.01). Python analysis confirmed diabetes was the independent risk factor of COVID-19 progression in elderly patients. All blood glucose (BG) indices went into the risk factor equation. The cut-off values of COVID-19 progression were BG value on admission > 8.0 mmol/L or maximum BG value > 12.0 mmol/L in all elderly patients, and BG value on admission > 5.1 mmol/L or maximum BG value > 5.4 mmol/L in non-diabetes patients. Diabetes is an independent important risk factor, and glucose levels associate closely with COVID-19 progression in elderly patients.


N-acyl glycinates as acyl donors in serine protease-catalyzed kinetic resolution of amines. Improvement of selectivity and reaction rate.
Enzymatic kinetic resolution of aliphatic and benzylic amines leading to (S)-amides was achieved by using alkaline protease as the catalyst and N-octanoyl glycine trifluoroethyl ester as the acyl donor; enantioselectivity ranged between 4 to 244, while reaction times were dramatically shortened and ranged between 15 min to 6 h.


Thrombocytopaenia as the presenting feature of persistent generalised lymphadenopathy (PGL) in a one-year-old.
A one-year-old child who presented with thrombocytopaenia was found to be HIV positive and has now developed persistent generalised lymphadenopathy (PGL).


Dust emissions in cattle feedlots.
Dust emissions were measured at three Texas cattle feedlots on 15 occasions in 1987 to determine concentrations of total suspended particulate matter (TSP) and dust with 10 microns or less aerodynamic particle size (PM-10). Net feedlot dust concentrations (downwind minus upwind) ranged from 15.7 to 1,700.1 micrograms per m3 and averaged 412.4 +/- 271.2 micrograms per m3, which is about 37 per cent less than was determined in feedlot dust research in California approximately 17 years earlier. Upwind concentrations averaged 22 per cent of the downwind concentrations. Feedlot dust concentrations were generally highest in early evening and lowest in early morning. Using the Wedding and Andersen-321A PM-10 samplers, the PM-10 dust concentrations were 19 and 40 per cent, respectively, of mean TSP concentrations in direct comparisons. There was good correlation between PM-10 and TSP concentrations. Although dust concentrations decreased with increasing moisture, the correlation coefficients were relatively low. Odor intensity appeared to increase with decreasing net dust concentrations, perhaps due to moisture influences. Mean particle sizes of feedlot dust were 8.5 to 12.2 microns on a particle volume basis and 2.5 to 3.4 microns on a population basis. Respirable dust (below 2 microns) represented only 2.0 to 4.4 per cent of total dust on a particle volume basis. Under conditions of these experiments, the feedlots often exceeded both state and federal (U.S. Environmental Protection Agency) standards for TSP concentrations and for PM-10 concentrations measured using the Andersen-321A sampler. However, feedlots were below the new U.S. Environmental Protection Agency standards when the Wedding PM-10 sampler was used for measuring dust emissions.


Linc01232 promotes the metastasis of pancreatic cancer by suppressing the ubiquitin-mediated degradation of HNRNPA2B1 and activating the A-Raf-induced MAPK/ERK signaling pathway.
Pancreatic cancer (PC) is a malignant cancer with high mortality and poor prognosis. In this study, we found that Linc01232 was significantly upregulated in PC tissues and cells and higher Linc01232 expression was associated with poorer prognosis. Linc01232 overexpression promoted and Linc01232 knockdown inhibited the migration and invasion of PC cells. The results of RNA pull-down, RNA Binding Protein Immunoprecipitation (RIP) assays revealed that Linc01232 physically interacted with Heterogeneous Nuclear Ribonucleoprotein A2/B1 (HNRNPA2B1) (680-890 nt fragment with the RNA recognition motif 2 domain) to inhibit its ubiquitin-mediated degradation in PC cells. RNA sequencing was performed to obtain the transcriptional profiles regulated by Linc01232 and we further demonstrated that Linc01232 participated in the alternative splicing of A-Raf by stabilizing HNRNPA2B1 and subsequently regulated the MAPK/ERK signaling pathway. Collected, our study showed that Linc01232/HNRNPA2B1/A-Raf/MAPK axis participated in the progression of PC and provided a potential therapeutic target for PC.


Relation of improvement in left ventricular ejection fraction versus improvement in heart failure symptoms after coronary revascularization in patients with ischemic cardiomyopathy.
In the present study, the relation between improvement in the left ventricular ejection fraction (LVEF) and heart failure symptoms was evaluated in 100 patients with ischemic cardiomyopathy undergoing coronary revascularization. In patients with viable myocardium, the improvement in the LVEF after revascularization was accompanied by improvement in heart failure symptoms in most patients (80%); most viable patients (75%) without improvement in LVEF also showed an improvement in New York Heart Association functional class. Conversely, most nonviable patients failed to improve in LVEF or New York Heart Association class.


Interference KRT17 reverses doxorubicin resistance in triple-negative breast cancer cells by Wnt/β-catenin signaling pathway.
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with the highest degree of malignancy and is easily resistant to drugs due to the lack of hormone receptors. Research on the resistance mechanisms in TNBC is particularly important. Keratin 17 (KRT17) is highly expressed in TNBC. Anthracycline doxorubicin (Dox) is a commonly used chemotherapeutic drug for early stage triple-negative breast cancer. This study investigated the role of KRT17 in TNBC-Dox resistance. Immuno-histochemical staining, qPCR, western blotting (WB), and immunofluorescence were used to detect the expression of KRT17 in TNBC-Dox-resistant patients and in TNBC-Dox-resistant MDA-MB-468 and MDA-MB-231. the effect of KRT17 on the proliferation and migration in KRT17 knockdown of TNBC-Dox-resistant cells was determined by the CCK8, clone formation, transwell invasion and wound healing assays were used to determine. KRT17 was highly expressed in the TNBC-Dox-resistant cells. Knockdown of KRT17 significantly reduced the IC50s of TNBC-Dox-resistant and parental strains and also reduced the proliferation and invasion abilities of TNBC-Dox-resistant cell lines. KRT17 regulated the Wnt/β-catenin signaling pathway. The inhibitory effect of KRT17 knockdown on the proliferation and migration of TNBC-Dox-resistant cells was reversed by an activator of the Wnt signaling pathway. KRT17 can inhibit the Wnt/β-catenin signaling pathway, thereby reducing the proliferation and invasion ability of TNBC-Dox-resistant cells.


[Electroacupuncture at "Zusanli"(ST 36) can inhibit frequencies of transient lower esophageal sphincter relaxation induced by gastric distention in cats].
To observe the influence of electroacupuncture (EA) of "Zusanli" (ST 36) and ST 36 + "Neiguan" (PC 6) on gastric distention induced transient lower esophageal sphincter relaxation (TLESR) in cats. Forty cats were randomly divided into model (gastric distension) group, EA-ST 36 group, EA-PC 6 group, EA-ST 36 + PC 6 group, EA-non-acupoint group, EA-ST 36 + saline (2 mL i.v.) group, EA-ST 36 + L-arginine (precusor of nitric oxide, 200 mg/kg i.v.) group, and EA-ST 36+Tacrine (cholinesterase inhibitor, 5.6 mg/kg i. p.) group, with 5 cats being in each group. TLESR model was established by extending the stomach with an air balloon. EA (2 Hz/100 Hz, 3-4 mA) was applied to bilateral ST 36, PC 6 and ST 36 + PC 6 and non-acupoint (exterior-superior site of the hip) while gastric distension. L-Arginine was given 10 min before EA, and Tacrine was given 30 min before EA. The frequency of TLESR and lower esophageal sphincter pressure (LESP) were recorded by using a perfused sleeve assembly. Compared with the model group, the frequency of TLESR in 60 min as well as the percentage of common cavity during TLESR were significantly decreased in the EA-ST 36, EA-PC 6, EA-ST 36 + PC 6, EA-ST 36 + saline groups (P < 0.05). Compared with the EA-ST 36 + saline group, the frequency of TLESR in 60 min was up-regulated significantly in the EA-ST 36 + Tacrine group (P < 0.01) rather than in the EA-ST 36 + L-Arginine group, suggesting a reduction of the efficacy of EA-ST 36 by cholinergic suppression (not by nitric oxide). No significant differences were found among the EA-ST 36, EA-PC 6 and EA-ST 36 + PC 6 groups in the frequency of TLESR and the percentage of common cavity (P > 0.05). In comparison with the baseline level, LESP was increased significantly only in the EA-ST 36 group (P < 0.05). EA at ST 36 can reduce both the frequency of TLESR and the percentage of common cavity during TLESR in gastric distension cats, which may be mediated by cholinergic pathway.


ACUTE RETINAL PIGMENT EPITHELIITIS: ASSOCIATION WITH ACUTE COXSACKIE A VIRUS INFECTION.
The purpose of this study was to describe the occurrence of acute retinal pigment epitheliitis in association with serologic evidence of acute Coxsackie A virus infection. This study is a case report. A 37-year-old man noted an acute onset of paracentral scotomas in his right eye correlating with stippled retinal pigment epithelial pigment alterations with whitish halos surrounding the fovea. Spectral domain optical coherence tomography revealed scattered distinct retinal pigment epithelial elevations in the paracentral macular region arranged in an annular fashion, with associated alterations in the interdigitation and ellipsoid zone layers anterior to the retinal pigment epithelial, characteristic of acute retinal pigment E. Suspicion of acute Coxsackie A virus in the patient because of the presence of simultaneous viral exanthematous illness in the patient's 1-year-old son prompted serologic testing for Coxsackie virus. Titers showed strongly positive IgM ("early") antibody for several Coxsackievirus A serotypes, including A16 (most commonly associated with hand-foot-mouth disease). Spontaneous regression of the anatomical and clinical findings occurred over the next month, with complete resolution noted 16 months later. This is the first documented case of acute retinal pigment epitheliitis associated with evidence of acute Coxsackie A virus infection. Corroboration with serology in future cases would add to evidence that acute retinal pigment epitheliitis is part of the apparently expanding spectrum of recognized "Coxsackie retinopathies."


The origin of the PB1 segment of swine influenza A virus subtype H1N2 determines viral pathogenicity in mice.
Swine appear to be a key species in the generation of novel human influenza pandemics. Previous pandemic viruses are postulated to have evolved in swine by reassortment of avian, human, and swine influenza viruses. The human pandemic influenza viruses that emerged in 1957 and 1968 as well as swine viruses circulating since 1998 encode PB1 segments derived from avian influenza viruses. Here we investigate the possible role in viral replication and virulence of the PB1 gene segments present in two swine H1N2 influenza A viruses, A/swine/Sweden/1021/2009(H1N2) (sw 1021) and A/swine/Sweden/9706/2010(H1N2) (sw 9706), where the sw 1021 virus has shown to be more pathogenic in mice. By using reverse genetics, we swapped the PB1 genes of these two viruses. Similar to the sw 9706 virus, chimeric sw 1021 virus carrying the sw 9706 PB1 gene was not virulent in mice. In contrast, replacement of the PB1 gene of the sw 9706 virus by that from sw 1021 virus resulted in increased pathogenicity. Our study demonstrated that differences in virulence of swine influenza virus subtype H1N2 are attributed at least in part to the PB1 segment.


Dual polarization interferometric and capillary electrophoretic analysis of supported lipid bilayer constructed on silica-based surface: evaluation of its anti-protein adsorption effect.
Supported lipid bilayer (SLB) has been demonstrated as a model of cell membranes with prospective bioanalytical or biotechnological applications. In this study, the formation of SLB and their potential biofunctionality against protein adsorption were investigated by Dual Polarization Interferometry (DPI) and Capillary Electrophoresis (CE). DPI studies on different formulations of double-chained, zwitterionic phospholipidlipids, allow the process of bilayer formation to be followed in situ and in real time. Furthermore the anti-protein adsorption effect provided by the various formulated SLBs was examined by DPI. In addition, the SLB coatings of the same lipid formulations were subsequently employed in CE experiments as a pseudo-stationary phase for demonstrating more efficient separation of alkaline protein standard mixtures. SLB-assisted CE was found to be capable of separating 4 alkaline proteins (protonated at neutral pH). This study demonstrates the applicability of DPI to monitor the process of SLB formation; and our findings, obtained by both DPI and CE, confirm that the presence of the SLB reduced drastically the problematic interactions between cationic, alkaline proteins and the negatively charged silica capillary wall, leading to better recovery and efficient separation of the proteins under investigation.


Blood lactate accumulation in intermittent supramaximal exercise.
Blood lactate accumulation rate and oxygen consumption have been studied in six trained male runners, aged 20 to 30 years. Subjects ran on a treadmill at a rate representing 172 +/- 5% VO2max for four 45 s sessions, separated by 9 min rest periods. Oxygen consumption was measured throughout. Blood lactate was determined in samples taken from the ear and VO2 was measured at the end of each exercise session, and two, five and nine minutes later. After the fourth exercise session, the same measurements were made every five min for 30 min. 4 subjects repeated a single exercise of the same type, duration and intensity and the same measurements were taken. With repetitive intermittent exercise, gradual increases in blood lactate concentration [( LA]b) occurred, whereas its rate of accumulation (delta[LA]b) decreased. The amount of oxygen consumed during each 45 s exercise session remained unchanged for a given subject. After cessation of intermittent exercise, the half-time of blood lactate was 26 min, whereas it was only 15 min after a single exercise session. VO2 values, on the other hand, returned to normal after 15 to 20 min. All other conditions being equal, the gradual decrease in delta[LA]b during intermittent exercise could be explained if the lactate produced during the first exercise session is used during the second period, and/or if the diffusion space of lactate increases. The diffusion space seems to be multi-compartmental on the basis of half-time values noted for [LA]b after intermittent exercise, compared with those noted after a single exercise session.(ABSTRACT TRUNCATED AT 250 WORDS)


What Do We Know About the Pathophysiology of Chronic Pain? Implications for Treatment Considerations.
We discuss the complex features of the pathophysiology of chronic pain and the implications for treatment and provide an overview of nociceptive processes, neuropathic pain, cold hyperalgesia, peripheral nerve injury, wind-up pain, central sensitization, and common clinical presentation and diagnostic criteria. Advanced medicine has proven that chronic pain need not involve any structural pathology as pain is a complex biopsychosocial experience. Treatment of the specific mechanisms responsible for pain should be aimed at preventing and or reducing dysfunctional neuro-plasticity resulting from poorly controlled chronic pain. Further study is needed to reduce the probability and of persistent changes that cause chronic pain.


Nanobioanalytical luminescence: Förster-type energy transfer methods.
Förster resonance energy transfer-based analytical techniques represent a unique tool for bioanalysis because they allow one to detect protein-protein interactions and conformational changes of biomolecules at the nanometer scale, both "in vitro" and "in vivo" in cells, tissues and organisms. These techniques are applied in diverse fields, from the detection and quantification of ligands able to bind to proteins or receptors to the development of RET-based whole-cell biosensors, microscope imaging techniques and "in vivo" whole-body imaging for the monitoring of physiological and pathological processes. However, their quantitative performances need further improvements and, even though RET measurement principles and procedures have been continuously improved, in some cases only qualitative or semiquantitative information can be obtained. In this review we report recent applications of RET-based analytical techniques and discuss their advantages and limitations.


Estimation of heat transfer and temperature rise in partial-body regions during MR procedures: an analytical approach with respect to safety considerations.
In order to assess thermal response to RF exposure during MR procedures at the tissue level, simple analytical solutions to the non-stationary Pennes' bio-heat equation were obtained using the Green's function approach. Two thermal models appropriate for partial-body exposure were analyzed: In the first model, the temperature field at the periphery of an idealized volume RF resonator was modeled. The analytical solution reveals that tissue response to RF heating is characterized by an equilibration time and length. Both parameters are inversely related to tissue perfusion and vary for the soft-tissues considered between 0.27-25 min and 1.5-12 mm, respectively. None of the tissues investigated increase in temperature more than 0.5 degrees C for each W/kg of power dissipated. Secondly, a homogeneous tissue solution was derived that predicts the temperature-time course to an MR examination with time-varying specific absorption rates (SAR). Since SAR limits indicated in current MR safety standards relate to running SAR averages computed over an appropriate period of time, an expression was formulated that gives an upper limit for the temperature rise averaged over the same period of time, as a function of both the upper limit of running SAR averages and the duration of the MR examination. The analysis revealed that the partial-body SAR limits indicated in the IEC standard may not guarantee under all circumstances compliance with the basic restrictions concerning temperature rise.


Pentoxifylline potentiates nitric oxide production in interleukin-1beta-stimulated vascular smooth muscle cells through cyclic AMP-dependent protein kinase A pathway.
In the present study, we observed that pentoxifylline (PTX) significantly augmented the nitric oxide (NO) production and the iNOS gene expression by interleukin-1beta (IL-1beta)-stimulated vascular smooth muscle cells (VSMCs). The enhancing effects of PTX on the IL-1beta-induced NO production was associated with an increased intracellular cyclic AMP (cAMP) levels, and the synergistic effects of PTX on the IL-1beta-induced NO production was blocked by cAMP-dependent protein kinase A (PKA) inhibitors. PKA inhibitors, KT5720 and H89, markedly decreased the augmented expression of iNOS gene whereas ODQ, a soluble guanylate cyclase inhibitor, did not affect the enhancing effect. In addition, the pretreatment with KT5720 or H89 abolished the increased translocation of the p65 subunit of NF-kappaB into the nucleus by PTX in the IL-1beta-stimulated VSMCs. These results suggest that enhancing effects of PTX on the iNOS gene expression in the IL-1beta-stimulated VSMCs is mediated predominantly through the activation of NF-kappaB via cAMP-dependent PKA pathway.


Clinical reasoning and patient-centred care in musculoskeletal physiotherapy in Portugal--a qualitative study.
Clinical reasoning has been described as a common process that underpins the myriad of tasks in the clinicians' practice. To date clinical reasoning models have emerged from research developed in specific and well-developed health care and professional cultures, such as those in Australia and the United States, but there has been little discussion of their relevance and applicability to other cultural settings. The aim of this investigation was to explore clinical reasoning processes in a sample of experienced Portuguese musculoskeletal physiotherapists. The study focused on clinicians' interaction with their patients in order to define and manage clinical problems. Data were collected through non-participant observation, semi-structured interviews, memos and field notes, and analysed thematically to explore and interpret clinical practice and reasoning. Findings highlighted that the clinicians were more likely to carry out their reasoning approach as a purely cognitive and clinician centred process. Perspectives of clinical reasoning therefore differ between cultures and contexts of practice and this has potential implications in the way physiotherapists interpret health and illness, their role as clinicians, as well as the patient-physiotherapist relationship.


Neurogenesis: premature mitotic entry lets cleavage planes take off!
Mutations in the gene microcephalin/MCPH1 result in the neurodevelopmental disease microcephaly. A recent report provides evidence that MCPH1 controls neuroprogenitor entry into mitosis via the Chk1-Cdc25b centrosome maturation pathway.


Partial duplication of the lower limb with agenesis of ipsilateral kidney--a new syndrome: report of a case and review of the literature.
A detailed account is given of a 19-month-old female infant with partial duplication of the left lower limb and aplasia of the ipsilateral kidney, plus other congenital malformations. Although the etiology is unknown, we believe this constellation of findings, which has been reported previously, represents a new congenital malformation syndrome.


Solid-state fermentation of cornmeal with the basidiomycete Ganoderma lucidum for degrading starch and upgrading nutritional value.
The objective of this research was to study the ability of the basidiomycete Ganoderma lucidum to degrade starch and upgrade nutritional value of cornmeal during solid-state fermentation (SSF). On the basal medium that consisted of cornmeal and salt solution, alpha-amylase activity of G. lucidum reached its maximum value of 267 U g(-1) of culture on day 20 after inoculation. Prolongation of fermentation time from 10 to 25 days increased significantly the degradation rate of starch and ergosterol yield (a kind of physiologically active substances of G. lucidum, also as an indicator of mycelial biomass) (P < 0.01). Supplementation of glucose, sucrose or maltose to the basal medium also caused a significant increase in either the degradation rate of starch or the ergosterol yield as compared with control (P < 0.01). Among five kinds of nitrogen sources supplemented, yeast extract, casamino acid and peptone were more effective than (NH4)2SO4 and NH4NO3, and yeast extract gave the highest degradation rate of starch and ergosterol yield, followed by peptone. Through orthogonal experiments, the theoretical optimum culture medium for SSF of this fungus was the following: 100 g cornmeal, ground to 30-mesh powder, moistened with 67 ml of nutrient salt solution supplemented with 3 g yeast extract and 7.5 g glucose per litre. Under the optimum culture condition, the degradation rate of starch reached its maximum values of 70.4%; the starch content of the fermented product decreased from 64.5 to 25.3%, while the reducing sugar content increased from 4.2 to 20.6%. SSF also produced a significant increase (P < 0.01) from 11.0 to 16.5% in protein content. After SSF by G. lucidum, the digesting and absorbing ratio of cornmeal was strikingly increased and some active substances originated from G. lucidum remained in the fermented product. This implied that cornmeal could be processed into many kinds of special functional foods by SSF of G. lucidum.


Use of MR Urography in Pediatric Patients.
In this article, we describe the basics of how magnetic resonance urography (MRU) is performed in the pediatric population as well as the common indications and relative performance compared to standard imaging modalities. Although MRU is still largely performed in major academic or specialty imaging centers, more and more applications in the pediatric setting have been described in the literature. MRU is a comprehensive imaging modality for evaluating multiple pediatric urologic conditions combining excellent anatomic detail with functional information previously only available via renal scintigraphy. While generally still reserved for problem solving, MRU should be considered for some conditions as an early imaging technique.


Perineal ultrasound in the study of urethral mobility: proposal of a normal physiological range.
The aim of the study was to determine, using perineal ultrasound, the physiological range for urethral mobility in normal women. Sixty healthy women were enrolled. The ultrasound parameters obtained with a perineal "static" and "dynamic" evaluation method were: pubic-urethral distance and inclination angle of the urethral axis. We propose a physiological range of pubic-urethral distance under stress in young women between 10 and 15 mm, the inclination angle of the urethral axis is between 60 and 100 degrees . In peri-post-menopause women we establish a non-rigid range of mobility in relation to age and parity: between 15 and 18 mm for the pubis-urethra distance and 80 degrees and 120 degrees for the angle of the urethral axis. Defining a range of normality for urethral mobility through ultrasound is useful for further studying therapeutic choices and help to identify the surgical correction and post-operative follow-up.


Impact of cash incentives for low-income individuals to seek a primary care visit on mental health outcomes: Evidence from a randomized controlled trial.
We explore whether a cash incentive to see a primary care provider (PCP) improves self-reported depression, anxiety, and pain among low-income patients in a randomized trial. Secondary outcomes of a randomized controlled trial, enrolling low-income uninsured adults to receive cash incentives ($0, $25, $50) to see a PCP. Interview data was collected at enrollment and 12 months later. Health outcomes were measured with the PROMIS depression, anxiety, and pain interference scales. We estimated adjusted logistic regressions to determine whether self-reported improvements occurred in depression, anxiety, or pain. 981 subjects completed surveys 12 months following study enrollment (80% retention). Subjects who were incentivized were 5.7 percentage points more likely to see a PCP in the initial six months (p<0.05). Incentivized subjects were 6 percentage points more likely to experience an improvement in depression and pain at 12 months. Among those who reported high levels of depression and pain at baseline, they were 10.6 and 8 percentage points, respectively, to experience an improvement relative to those who were not incentivized. Meaningful improvements were observed for depression and pain PROMIS domains for subjects randomized to the incentive groups, presumably through their interaction with a PCP and the health care system. This finding was robust for the full sample and a group that reported more severe symptoms at baseline.


Use of peritoneal ultrafiltration in the elderly refractory congestive heart failure patients.
Refractory congestive heart failure (RCHF), due to its high mortality and hospitalization rates, is a growing health problem. In this study, as an alternative and/or supportive treatment to conventional medical therapies, we have evaluated the clinical value of peritoneal ultrafiltration, performed as a single daily exchange with icodextrin or conventional dextrose-based peritoneal dialysis solutions, in elderly patients with RCHF. This was an observational study of 6 elderly patients with RCHF and non-terminal chronic kidney disease (CKD). Their mean age was 72.8 ± 4.9 years. Four of the six patients had NYHA class 4 and two had NYHA class 3 RCHF and a medical history of 18.6 ± 14.9 days/year hospitalization on average, due to decompensated congestive heart failure (CHF). Their baseline glomerular filtration rate, as calculated by the MDRD formula was 49.4 ± 14.6 mL/min/1.73 m(2). During hospitalization, patients were initially treated with several sessions of continuous veno-venous hemofiltration and, following the achievement of hemodynamic stabilization, peritoneal ultrafiltration was initiated as the maintenance ultrafiltration modality. Patients were followed up monthly in terms of their clinical status, hospitalization rates, weight changes, serum sodium levels, and renal function. Echocardiographic changes were also evaluated every 3 months. All patients tolerated peritoneal ultrafiltration well, their functional status improved by 1 or 2 NYHA classes to reach a mean of NYHA class 2 CHF status. During the follow-up period, with a mean daily ultrafiltration rate of 850 ± 176 mL, no hospitalization for decompensated CHF or acute renal failure was required. The patients' renal function was well preserved, with a mean GFR of 49 ± 14.6 mL/min/1.73 m(2) at baseline and 51.6 ± 22.9 mL/min/1.73 m(2) at the 6th month of the study. Additionally, their mean serum sodium levels increased from 128 ± 5.7 mEq/L to 138 ± 5 mEq/L. Echocardiographic evaluation did not show any significant changes during the observation period. No peritonitis or other non-infectious complication of chronic peritoneal dialysis was seen in any of the patients. Peritoneal ultrafiltration seems to be an efficient and safe procedure and a treatment of choice in elderly patients with RCHF without non-terminal CKD. Peritoneal ultrafiltration improves the quality of life and the effort capacity, and reduces hospitalization rates due to decompensated heart failure and acute renal failure.


Preoperative irradiation therapy and radical hysterectomy: prognostic value of tumor regression after initial irradiation of squamous cell carcinoma of the cervix.
To investigate the role of tumor persistence in patients submitted to irradiation therapy and radical hysterectomy. A retrospective analysis of prognostic factors. Hospital A.C. Camargo, São Paulo, Brazil, a private non-profitmaking foundation and tertiary referral centre. A total of 629 cases of invasive squamous cell carcinoma of the cervix were studied. Criteria for inclusion in the study were: confirmed histological diagnosis of squamous cell carcinoma and no previous treatment (except for preoperative radiotherapy carried out at the Hospital A.C. Camargo itself). At the end of the follow-up period, 410 patients (65%) had no evidence of disease and 219 (34.8%) had died because of the tumor. The patients were submitted to radical surgery and radiation therapy, separately or in combination between 1953 and 1982. Multivariate analysis of the different variables was performed according to the Cox regression method. The variables of prognostic value were, in decreasing order of importance: the decade of patient admission (p = 0.0001), the modality of therapy employed (p = 0.0005), the presence of residual tumor in the surgical specimens (p = 0.0055) and the clinical stage of the disease (p = 0.0575). Radiation therapy controlled a considerable number of local tumors and pelvic lymph nodes but not all of them in every patient. There is a specific group of patients for whom radical surgery is necessary to achieve control of the disease.


Reduction in HTLV-I proviral load and spontaneous lymphoproliferation in HTLV-I-associated myelopathy/tropical spastic paraparesis patients treated with humanized anti-Tac.
Human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurological disease that results from an interaction of retroviral infection and immune activation. In this study, five doses (1 mg/kg) of humanized anti-Tac antibody were administered to 9 HAM/TSP patients at weeks 0, 2, 6, 10, and 14. Preliminary immunological studies on HAM/TSP patients treated with humanized anti-Tac indicate that there is a selective down-regulation of activated T cells and a decrease in the HTLV-I viral load in peripheral blood lymphocytes, most likely through the selective removal of HTLV-I-infected, activated CD4+ lymphocytes.


In vitro synthesis of type IV procollagen.
Total RNA was isolated from parietal endoderm cells of 131/2-day mouse embryos that synthesize large amounts of type IV procollagen. In vitro translation of this RNA in the reticulocyte lysate supplemented with a ribonuclease inhibitor yielded two equally prominent polypeptides of Mr = 165,000 and 168,000, immunoprecipitable with anti-mouse type IV collagen serum. The Mr = 165,000 polypeptide was shown by one-dimensional peptide mapping to represent an unmodified chain of type IV procollagen. The Mr = 168,000 polypeptide, the in vitro synthesis of which was barely detectable in the absence of a ribonuclease inhibitor, most likely represents the other genetically distinct chain of type IV procollagen. Similar results to those described were also obtained using poly(A) + RNA prepared from murine F9 embryonal carcinoma cells induced to differentiate in vitro into parietal endoderm.


The effect of nitrogen nutrition on growth and biomass partitioning of annual plants originating from habitats of different nitrogen availability.
The hypothesis was tested that faster growth of nitrophilic plants at high nitrogen (N) nutrition is counterbalanced by faster growth of non-nitrophilic plants at low N-nutrition. Ten annual plant species were used which originated from habitats of different N-availability. The species' preference for N was quantified by the "N-number" of Ellenberg (1979), a relative measure of nitrophily. The plants were cultivated in a growth cabinet at five levels of ammonium-nitrate supply. At low N-supply, the relative growth rate (RGR) was independent of nitrophily. At high N-supply, RGR tended to be higher in nitrophilic than in non-nitrophilic species. However, the response of RGR to N-supply was strongly and positively correlated with the nitrophily of species. Increasing N-supply enhanced partitioning to leaf weight per total biomass (LWR) and increased plant leaf area per total biomass (LAR). Specific leaf weight (SLW) and LWR were both higher in non-nitrophilic than in nitrophilic species at all levels of N-nutrition. NAR (growth per leaf area or net assimilation rate) increased with nitrophily only under conditions of high N-supply. RGR correlated positively with LAR, irrespective of N-nutrition. Under conditions of high N-supply RGR correlated with SLW negatively and with NAR positively.


Evaluation of recombinant BgSA3 protein based indirect-ELISA for sero-diagnosis and sero-surveillance of Babesia gibsoni in dogs.
Canine babesiosis, a tick-borne haemoprotozoan disease of dogs, is of significance globally due to its rapid spread. A precise confirmatory diagnosis is required to curtail the rapid spread of infection. Our study described the evaluation of recombinant BgSA3 protein based indirect ELISA for sero-diagnosis and sero-surveillance of Babesia gibsoni infection in dogs. A partial BgSA3 gene segment (1921 bp) of B. gibsoni, encoding for recombinant truncated BgSA3 (75 kDa) protein devoid of predicted signal peptide (23 aa) at N-terminus and transmembrane region (20 aa) at C-terminus, was expressed in E. coli using a pET28a(+) vector. The rBgSA3 protein purified under native conditions using Ni-NTA superflow cartridge was confirmed by SDS-PAGE and Western blotting using sera from dogs infected/uninfected with B. gibsoni, and erythrocyte lysate/ plasma from infected/uninfected dogs. The rBgSA3 protein was specific only to B. gibsoni antibodies but did not react with uninfected sera. Further, rBgSA3 protein was evaluated for sero-diagnosis/sero-surveillance using Indirect-ELISA format. There was no cross reactivity to B. vogeli, E. canis, H. canis and D. repens infected dogs serum samples. The diagnostic sensitivity and specificity of rBgSA3 based I-ELISA was found to be 86.4 and 93.1 % respectively, in comparison with cytb based PCR assay. Additionally, rBgSA3-ELISA evaluated using survey serum samples (n = 287), detected 11.85 % samples as positive. In conclusion, B. gibsoni infection, an emerging disease is prevalent in the present study area and the standardized rBgSA3 protein based indirect-ELISA was found to be a specific and sensitive test for large scale sero-diagnosis and sero-surveillance of B. gibsoni infection in dogs.


Aminothiazole-derived N,S,Fe-doped graphene nanosheets as high performance electrocatalysts for oxygen reduction.
N,S,Fe-doped graphene nanosheets were directly synthesized from aminothiazole, a precursor molecule that contains N and S atoms, through Fe catalysis under heat treatment. The graphene nanosheets exhibited high electrocatalytic activity toward oxygen reduction reaction in both acidic and alkaline media during rotating disk electrode half-cell and fuel cell tests.


[Clinical results of endovascular stent graft repair for fifty cases of thoracic aortic aneurysms].
Between February 1995 and December 1997, 50 cases (55 lesions) of thoracic aortic aneurysms including 20 cases of aortic dissections were treated with an endovascular technique using the stent grafts. All patients were treated in the operating room under general anesthesia and the stent grafts were implanted through 18 Fr. or 20 Fr. sheaths via femoral arteries under fluoroscopic guidance. The stent graft was composed of several units of self-expanding stainless-steel Z stents covered with an ultra-thin polyester fabric. Stent graft deployment was technically successful in 53 of 55 lesions (delivery success rate: 96.4%). Exclusion of the aneurysms and entry closing without endoleak were achieved within two weeks after the operation in 43 of 53 lesions (initial success rate: 81.1%). Endoleak was found in 10 lesions (minor endoleak: 8 and major endoleak: 2 lesions). Two patients died in the periopertive period of delivery failures as injury to external iliac artery and damage to the delivery sheath caused by tortuous and narrow access routes. Endovascular stent graft repair of thoracic aortic aneurysms is minimally invasive operation in comparison with conventional surgical graft replacement with extracorporeal circulation. These early results suggest that the stent graft repair is possibly safe and useful treatment for the patients of thoracic aortic aneurysms especially in high risk patients. However, careful long-term follow-up is necessary to prove the value and the effects of this endovascular treatment and improvement of the stent graft system and technical training of endovascular surgery for operators are required to reduce the delivery failure and to determine the stent graft repair is reliable treatment.


Evaluation of the Nutritive Value and Digestibility of Sprouted Barley as Feed for Growing Lambs: In Vivo and In Vitro Studies.
The main objective of this study was to investigate the effects of freshly sprouted barley on the growth of lambs, in addition to its nutritional value and digestibility. In addition, sprouted barley digestibility and rumen fermentation were studied in vitro on a dry matter (DM) basis. A total of 45 three-month-old Awassi lambs were randomly assigned to five treatments of sprouted barley (0, 25, 50, 75, 100%) diets. Bodyweight, weight gain, feed intake and feed efficiency were recorded every two weeks. Nutrient analyses were performed on feed, faecal, and urine samples. DM and non-fibrous carbohydrates were measured. Digestibility of DM, organic matter (OM), and neutral detergent fiber (NDF), as well as gas production, pH value, ammonia-N, and volatile fatty acids (VFAs), were determined in vitro using continuous culture. The results showed that final bodyweight was lower (p < 0.05), while feed intake and the feed-to-gain ratio were increased (p < 0.05) in sprouted barley treatments. Nutrient analysis indicators of sprouted barley treatments (25 to100%) were lower (p < 0.05) for DM, crude protein, acid detergent fiber, lignin and ash, and higher for total digestible nutrients, NDF, fat, phosphorus, zinc, copper, and net energy than the traditional diet. In the in vivo study, the digestibility of nutrients in sprouted barley treatments was improved (p < 0.05), while the diet (sprouted barley 100%) had the lowest digestibility of DM, OM, and NDF compared with the other treatments in the in vitro study. In conclusion, the addition of sprouted barley improved digestibility, and fermentation characteristics, while having a negative effect on growth. Further studies are recommended for optimal growth performance.


Respiration in heat stressed camels.
Respiration and heat exchange in relation to brain temperature (Th) and body temperature (Tb) were investigated in four heat stressed camels subjected daily to high temperature (47 degrees C) in a climate chamber while resting when hydrated and dehydrated by approximately 10%, 15% and 20% of initial weight. Diurnally Tb followed patterns described previously. Th was usually 0.2-0.5 degrees C greater than Tb: occasional reversals with brain cooling were observed. Minute ventilation increased with Tb: above 37.5 degrees C it was approximately half as much in dehydrated as in hydrated animals. Respiratory frequency increased with Tb up to 60/min. Tidal volume fell with increasing frequency; above 25 breaths/min, tidal volume approximated dead space volume. Exhaled air was almost always unsaturated with no systematic effect of dehydration. Metabolic rate fell on dehydration reducing ventilatory demand. Th and Tb were measured in two of the animals walking outdoors: then Th fell below Tb if exercise exceeded 30 min. The data indicate that heat stressed camels pant, but turbinate vasoconstriction in a hot environment prevents cooling of the brain by carotid rete heat exchange.


Smoking policy in the workplace and other public places.
In may 1989, the Council of Health Ministers of the European Community adopted a joint resolution which urges the 12 member states to adopt legislation restricting smoking in public places. European citizens support this action. A survey in March-April 1987 using a sample of 12,000 Europeans in the 12 member states concluded that 77% of European citizens want measures to ban smoking in public places. The conditions that are necessary to make a smoking policy successful in the workplace and other public places will be discussed. We want to stress that an information and awareness campaign before the enforcement of the smoking ban is the most important condition.


Apolipoprotein E is required for brain iron homeostasis in mice.
Apolipoprotein E deficiency (ApoE-/-) increases progressively iron in the liver, spleen and aortic tissues with age in mice. However, it is unknown whether ApoE affects brain iron. We investigated iron contents, expression of transferrin receptor 1 (TfR1), ferroportin 1 (Fpn1), iron regulatory proteins (IRPs), aconitase, hepcidin, Aβ42, MAP2, reactive oxygen species (ROS), cytokines and glutathione peroxidase 4 (Gpx4) in the brain of ApoE-/- mice. We demonstrated that ApoE-/- induced a significant increase in iron, TfR1 and IRPs and a reduction in Fpn1, aconitase and hepcidin in the hippocampus and basal ganglia. We also showed that replenishment of ApoE absent partly reversed the iron-related phenotype in ApoE-/- mice at 24-months old. In addition, ApoE-/- induced a significant increase in Aβ42, MDA, 8-isoprostane, IL-1β, IL-6, and TNFα and a reduction in MAP2 and Gpx4 in hippocampus, basal ganglia and/or cortex of mice at 24-months old. Our findings implied that ApoE is required for brain iron homeostasis and ApoE-/--induced increase in brain iron is due to the increased IRP/TfR1-mediated cell-iron uptake as well as the reduced IRP/Fpn1 associated cell-iron export and suggested that ApoE-/- induced neuronal injury resulted mainly from the increased iron and subsequently ROS, inflammation and ferroptosis.


Comparison of the microbiological characteristics and virulence factors of ST131 and non-ST131 clones among extended-spectrum β-lactamase-producing Escherichia coli causing bacteremia.
We evaluated the molecular epidemiology and microbiological characteristics of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) isolates that cause bacteremia in Korean hospitals, focusing especially on ST131. Our data suggest that ST131 isolates possessed more virulence traits and showed more multidrug resistance patterns than non-ST131 isolates. Among CTX-M-15 producers, the frequency of serum resistance was significantly higher in ST131 than in non-ST131. As in other parts of the world, the ESBL-EC ST131 clone has emerged and disseminated in both community and hospital settings in Korea, including in blood isolates in patients with bacteremia.


Correction to: Comparison of the effects of weight loss from a high-protein versus standard-protein energy-restricted diet on strength and aerobic capacity in overweight and obese men.
The original version of this article unfortunately contained a mistake.


The ginsenoside metabolite compound K stimulates glucagon-like peptide-1 secretion in NCI-H716 cells by regulating the RhoA/ROCKs/YAP signaling pathway and cytoskeleton formation.
Ginsenoside Rb1 has been shown to have antidiabetic and anti-inflammatory effects. Its major metabolite, compound K (CK), can stimulate the secretion of glucagon-like peptide-1 (GLP1), a gastrointestinal hormone that plays a vital role in regulating glucose metabolism. However, the mechanism underlying the regulation of GLP1 secretion by compound K has not been fully explored. This study was designed to investigate whether CK ameliorates incretin impairment by regulating the RhoA/ROCKs/YAP signaling pathway and cytoskeleton formation in NCI-H716 cells. Using NCI-H716 cells as a model cell line for GLP1 secretion, we analyzed the effect of CK on the expression of RhoA/ROCK/YAP pathway components. Our results suggest that the effect of CK on GLP1 secretion depends on the anti-inflammatory effect of CK. We also demonstrated that CK can affect the RhoA/ROCK/YAP pathway, which is downstream of transforming growth factor β1 (TGFβ1), by maintaining the capacity of intestinal differentiation. In addition, this effect was mediated by regulating F/G-actin dynamics. These results provide not only the mechanistic insight for the effect of CK on intestinal L cells but also the molecular basis for the further development of CK as a potential therapeutic agent to treat type 2 diabetes mellitus (T2D).


Extraction of flavanones from immature Citrus unshiu pomace: process optimization and antioxidant evaluation.
Dietary guidelines recommend the consumption of flavonoid-rich extracts for several health benefits. Although immature Citrus unshiu pomace (ICUP) contains high levels of flavanone glycosides, many studies have concentrated on the optimization of flavonoid extraction from mature citrus peels. Therefore, we developed an optimized extraction method for hesperidin and narirutin from ICUP, and evaluated their antioxidant activities using ten different assay methods. The extraction conditions for the highest flavonoid yields based on a response surface methodology were 80.3 °C, 58.4% (ethanol concentration), 40 mL/g (solvent/feed), and 30 min, where the hesperidin and narirutin yields were 66.6% and 82.3%, respectively. The number of extractions was also optimized as two extraction steps, where the hesperidin and narirutin yields were 92.1% and 97.2%, respectively. Ethanol was more effective than methanol and acetone. The ethanol extract showed high scavenging activities against reactive oxygen species but relatively low scavenging activities for nitrogen radicals and reactive nitrogen species. The antioxidant activities showed a higher correlation with hesperidin content than narirutin content in the extracts. This study confirms the potential of an optimized method for producing antioxidant-rich extracts for the functional food and nutraceutical industries.


Troponin--past, present, and future.
Cardiac troponin is the analyte of choice for the diagnosis of cardiac injury. It is highly specific for the heart and much more sensitive than prior biomarkers. Because of this increased sensitivity, clinicians have had to struggle with elevations in novel clinical situations. We have developed new understandings about coronary artery disease but also have begun to appreciate that many other entities as well can result in cardiac injury. As assays have increased in sensitivity over time, this trend has, if anything, accelerated. This review attempts to put the past, the present, and the future into a clinical perspective that will help clinicians.


Augmented osteosynthesis in fragility fracture.
Due to poor bone quality and complexity, some fractures are difficult to treat, with high risk of failure. Moreover, general health is often poor in elderly patients with multiple comorbidity and poor compliance, necessitating perfect first-line management to avoid re-operation. The armamentarium comprises specific internal fixation implants and also complementary methods such as autologous, homologous or heterologous bone graft or bone substitutes with varying mechanical and biological characteristics. Associating these options is what is mean by "augmented fixation". The present review of augmented osteosynthesis addresses the following questions: What are the characteristics of fragility fractures? Fragility fracture is caused by low-energy trauma on bone with poor structural quality and low mineral density. Treatment aims to enable early mobilization and weight-bearing while avoiding mechanical failure of fixation. Prolonged bedrest, loss of mobility and surgical revision are aggravating and sometimes fatal factors in these fragile patients. What are the biological techniques of fixation augmentation in fragility fracture? Autologous or homologous bone graft are the most widely used biological augmentation techniques. They fill spaces and promote osteoconduction and consolidation. Some bone-like phosphocalcic structures are opening up promising lines of research. What are the non-biological techniques of fixation augmentation in fragility fracture? Hydroxyapatite, phosphocalcic cement and acrylic cement are the most widely used synthetic materials. Biological and mechanical effects are variable according to composition, requiring specific implementation. What are the mechanical techniques of fixation augmentation in fragility fracture? There is at present no consensus as to the augmentation techniques to be applied in fragility fracture. Cerclage or complementary plating, or external fixation associated to internal fixation are possibilities. However, the literature consists only of small series reporting surgical techniques specific to a given surgeon or team. When and how should osteosynthesis for fragility fracture be augmented? The choice of augmentation depends on fracture location, comminution, available material and local experience. The more severe the fracture, the more complex the fixation. The approach needs to be adapted to the preoperative planning and the associated mechanical means (plate, complementary cerclage) and prosthetic replacement should be considered in certain joint fractures or fractures close to load-bearing surfaces. LEVEL OF EVIDENCE: V; expert opinion.


Arsenate removal from aqueous solutions by cuttlebone/copper oxide nanobiocomposite.
This study aims to illustrate the preparation of a new nanobiocomposite by incorporating copper oxide nanoparticles into cuttlebone matrix (CB/CuO NPs), and it was tested to define how effective it was to adsorb and remove arsenate from aqueous systems. CB is the bone tissue of cuttlefish with high porosity, permeability, and low cost. CuO NPs have been introduced as an effective arsenate adsorbent. Producing nanocomposite by introducing of CuO NPs in the structure of CB enhanced their stability and facilitated their separation from solution. Incorporation of CuO NPs in the structure of CB enhanced the adsorption capacity of CB. The adsorption data were fitted with both Langmuir and Freundlich isotherms, but Langmuir isotherm exhibited better matching rather than Freundlich isotherm. The maximum adsorption capacity (qmax) was calculated from Langmuir adsorption isotherm which was around 25.13 mg g-1. Kinetic data fitted well to the pseudo-second-order reaction model. The results indicate that the possible mechanism of arsenate adsorption on CB/CuO is through development of inner sphere complex. Simple preparation and abundant and good adsorption capacity in the presence of calcium ions indicate that the CB/CuO is suitable for removal of arsenate from contaminated drinking water.


Dual AV nodal pathways--vagal influences on AV nodal conduction.
This 52-year-old male presented with syncope and demonstrated two distinct PR intervals on the electrocardiogram. Electrophysiologic studies showed dual AV nodal pathways. Right-sided carotid sinus massage induced prolonged periods of sinus arrest with no change in AH interval. Left-sided carotid sinus massage produced long AH intervals (slow pathway conduction) with some slowing of sinus rate. Whenever sinus rhythm with slow pathway conduction was observed (long AH) a 20-30 mmHg drop systolic pressure was seen. Following implantation of an AV sequential pacemaker, the patient has been asymptomatic.


International Turbulence and Russia.
Using a multidisciplinary approach, this report analyzes the current transformation of the world-order architecture. It is noted that the speed and depth of this transformation is unprecedented for peacetime over the past 200 years. One of the most important indicators of turbulence is a certain deglobalization of the world economy. A study of the technological, social, economic, and political variables of social change has revealed that the traditional (for developed countries) social contract between government, business, and civil society has come to a crisis. This social contract has been in effect for more than half a century, since the times before globalization, the times of an industrial and bipolar world. Its inconsistency with modern realities, coupled with the inability of the old political center to offer convincing approaches to its modernization, has polarized societies and weakened social cohesion in the developed part of the world. As a result, populist and isolationist political forces have come to power. It is these forces that have started the dismantling of the existing system of global governance and its norms and institutions. The main contradiction of the current transformation in the world order is an attempt to bring back the polycentric world to a unipolar architecture with the dominance of the United States. The most likely scenario for resolving this contradiction is to create a new bipolarity. The author of the report expresses his views on the possible outlines of Russia's foreign policy, which would enable the country to adapt to the bipolarity of the 21st century and to a new role as a balance-keeper. A new design of global architecture is proposed, which is based on multilateral responsible leadership.


Variables associated with asthma control among adult patients.
Objective: Asthma is one of the most prevalent chronic diseases with a substantial impact on the health status of affected patients. Further research is necessary to identify factors contributing to poor asthma control. The current study aimed to investigate the factors associated with poor asthma control among adult asthmatic patients.Methods: In this case-control study, the Asthma Control Test (ACT) was translated into Arabic and distributed to adults with asthma attending two hospitals in Jordan to evaluate the degree of asthma control. The following variables were collected for each patient: sociodemographic information, comorbidities, appropriate use of inhaler technique, spirometric measurements, and medications use. Binary regression was used to evaluate factors associated with asthma control.Results: A total of 314 participants with a mean age of 51.47 years (±16.37) completed the study. ACT score had a mean of 16.68 (±4.86). The majority of asthmatic patients had insufficiently controlled asthma (64.6%). Binary regression results showed that previous respiratory infection history (p = 0.014, OR = 0.473 (95%CI 0.261-0.857)), higher exposure to irritants (p = 0.010, OR = 0.747 (95%CI 0.598-0.933)) decreased the odds of being in the controlled asthma group. Patients receiving inhaled corticosteroids (ICS) had higher odds of being in the controlled asthma group (p = 0.039, OR = 2.372 (95%CI 1.043-5.392)).Conclusions: The majority of asthma patients had insufficiently managed disease. The main factors that contributed to poor asthma control were respiratory infection history, increased exposure to asthma symptoms triggers, and ICS nonuse.


Sustained Complete Remission in Multi-Relapsed Primary CNS Lymphoma Treated with Ibrutinib Monotherapy: A Case Report.
Primary CNS lymphoma (PCNSL) is a highly aggressive malignant disease with a high recurrence rate and a poor prognosis. We present the case of a 71-year-old woman diagnosed with PCNSL in June 2010. After 3 relapses and intensive treatment with multiple chemotherapy regimens and whole-brain radiotherapy, she received off-label treatment with the Bruton tyrosine kinase inhibitor ibrutinib, responded well, achieved a complete remission, and is progression-free for now >3 years.


Use of chlorite to improve HPLC detection of pyridoxal 5'-phosphate.
The sensitivity of fluorescent detection of the biologically active form of Vitamin B-6, pyridoxal 5'-phosphate (PLP), in biological samples has been improved approximately four-fold by adopting chlorite as a post-column derivatization reagent (instead of bisulfite) in high-performance liquid chromatography (HPLC) separation. Chlorite oxidizes PLP to the more fluorescent 4-pyridoxic acid 5'-phosphate, and avoids the toxicity and heating of the cyanide procedure. Detection of another major metabolite, 4-pyridoxic acid (4-PA), is not effected. Detection of pyridoxal (PL) is slightly lowered due to eluting at a lower pH.


The insufficiency of a simple stress question in assessing stress for chronic daily headache in clinical practice.
In managing chronic daily headaches (CDH), a comprehensive approach is necessary to evaluate stress, a closely linked factor. However, limited time and costs often lead to the use of a simple stress question in clinical settings. This study aims to assess the validity of using a simple stress question for CDH patients and explore its implications for clinical practice. We recruited 103 patients with CDH who completed structured self-administered questionnaires, including a simple stress question ("Have you had any stress or concerns in the last 4 weeks?") and validated Korean versions of questionnaires for depression, anxiety, insomnia, and the Brief Encounter Psychosocial Instrument (BEPSI). A headache specialist conducted clinical interviews. The stress group consisted of patients who acknowledged overt stress (answering "yes" to the simple question) and covert stress (initially answering "no" but later admitting during the interview). Results showed no statistical difference between the subgroups, so they were combined as the "acknowledged stress" group. Out of 103 patients, 54.4% had chronic migraine, 45.6% had chronic tension-type headache, and 66 patients (64.1%) acknowledged experiencing stress. No significant differences were found in demographic and clinical characteristics, BEPSI stress assessment, or depression, anxiety, and insomnia profiles between patients with overt stress (n = 51) and covert stress (n = 15). The average BEPSI score was 2.3 ± 0.9, with 45.6% of patients exceeding the criteria (>2.4). Two (5.4%) patients in denial of stress had scores above the BEPSI criteria. Among patients below the criteria of BEPSI, 21 acknowledged stress, while 35 denied stress, with no significant differences observed. This study suggests the limitations of relying solely on a simple stress question for assessing stress in patients with CDH in clinical practice. It is possible to encounter covert stress, include individuals who do not exhibit noticeable stress, and misclassify stress levels. To overcome these limitations, it is necessary to foster a supportive environment for open communication on stress and implement a comprehensive assessment strategy when needed.


Nascent very low density lipoproteins from rat hepatocytic Golgi fractions are enriched in phosphatidylethanolamine.
The phospholipid composition of nascent very low density lipoproteins (VLDL) of rat hepatocytic Golgi fractions differs greatly from that of plasma VLDL. The phospholipids of nascent VLDL contain about four times more phosphatidylethanolamine (PE) than plasma VLDL, whereas plasma VLDL contain considerably more sphingomyelin. Thus, the ratio of PE to sphingomyelin differs by a factor of about 12 between nascent Golgi VLDL and circulating plasma VLDL. It is evident from these data that the PE/sphingomyelin ratio of VLDL can be used to estimate endosomal contamination of hepatocytic Golgi fractions.


Green tea extract attenuates CCl4-induced hepatic injury in male hamsters via inhibition of lipid peroxidation and p53-mediated apoptosis.
Keeping in mind the beneficial effects of GTE administration on liver damage, the present study was undertaken to evaluate the hepatoprotective effect of green tea extract (GTE) against carbon tetrachloride (CCl4)-induced liver injuries in male hamsters for 8 weeks. Twenty hamsters were equally divided into 4 groups, the control ones (group I) received only dis. water. Hamsters of group II had free access to 10% of GTE, while hamsters of group III received 1 ml/kg of 50% CCl4 in corn oil via gavage daily. Hamsters of group IV (GTE + CCl4) received a free access to GTE supplementation in combination with 1 ml/kg of 50% CCl4 in corn oil via gavage daily. Lipid profile, hepatic enzyme levels and apoptosis molecular marker (p53) were investigated in hamsters. GTE + CCl4 treated hamsters showed lower levels of hepatic malondialdehyde (MDA) than CCl4 exposed hamsters. Hepatic activity levels of GSH, ALD and cytochrome 450 reductase were declined after CCl4 administration while they were remarkably improved with GTE administration. Serum lipid profiles as T-cholesterol (TC), triglyceride (TG) and low density lipoproteins (LDL) were improved in GTE and CCl4 treated hamsters than CCl4 group. Moreover, hepatic tissue damage and p53 expression induced with CCl4 were improved with the treatment of GTE. These results suggested that GTE possesses hepatoprotective properties against the effect of CCl4.


Prevalence of selective immunoglobulin A deficiency in Greek children and adolescents with type 1 diabetes.
The association of selective immunoglobulin A (IgA) deficiency with type 1 diabetes (T1D) remains unclear. This study was to evaluate serum IgA concentrations in Greek children and adolescents with T1D. In two hundred individuals with T1D, serum IgA concentrations were quantitatively determined using nephelometry. Immunoglobulin A deficiency was detected in 6 (3.0%) of 200 patients who were subjected to immunological evaluation. Recurrent infections were not recorded, but human papilloma virus infection was clinically suspected and confirmed by laboratory examination in a 5-year-old girl. In regard to coincidence of selective IgA deficiency with autoimmune diseases, celiac disease was detected in a girl and juvenile idiopathic arthritis in a boy. Serum IgA concentrations differed significantly when patients were grouped according to age at the beginning of the study (P<0.001), age at diagnosis of T1D (P=0.015) and coincidence of celiac disease (CD) (P=0.038). However, when the age of the patients was adjusted, difference in serum IgA concentrations was not statistically significant despite CD was present or not. Moreover, serum IgA concentrations were positively correlated with serum IgG (P<0.001) and IgE (P=0.001) concentrations and negatively correlated with serum antigliadin antibody IgG (P=0.035) concentrations. There was no association or correlation of serum IgA concentrations with glycemic control. The prevalence of selective IgA deficiency in Greek children and adolescents with T1D is high (3.0%). The correlation of serum IgA concentrations with serum IgG, IgE and anti-gliadin antibody IgG concentrations needs further investigation.


Lichens biomonitoring as feasible methodology to assess air pollution in natural ecosystems: combined study of quantitative PAHs analyses and lichen biodiversity in the Pyrenees Mountains.
The air quality in the Aragón valley, in the central Pyrenees, has been assessed by evaluation of lichen biodiversity and mapped by elaboration of the Index of Air Purity (IAP) based on observations of the presence and abundance of eight kinds of lichen with different sensitivity to air pollution. The IAP values obtained have been compared with quantitative analytical measures of 16 PAHs in the lichen Evernia prunastri, because this species was associated with a wide range of traffic exposure and levels of urbanization. Analyses of PAHs were carried out by the DSASE method followed by an SPE clean-up step and GC-MS analysis. The concentration of total PAHs found in lichen samples from the Aragón valley ranged from 692 to 6420 ng g(-1) and the PAHs profile showed predominance of compounds with three aromatic rings. The influence of the road traffic in the area has been shown because values over the median concentration of PAHs (>1092 ng g(-1)), percentage of combustion PAHs (>50%), and equivalent toxicity (>169) were found in lichens collected at places exposed to the influence of traffic. The combination of both methods suggests IAP as a general method for evaluating the air pollution referenced to PAHs because it can be correlated with the content of combustion PAHs and poor lichen biodiversity can be partly explained by the air pollution caused by specific PAHs.


Time-resolved fluorescence study of the neuron-specific phosphoprotein synapsin I. Evidence for phosphorylation-dependent conformational changes.
Synapsin I is a major nerve terminal-specific phosphoprotein. It consists of a hydrophobic head region containing one phosphorylation site for either cAMP-dependent protein kinase or Ca2+/calmodulin-dependent protein kinase I and of a basic and elongated tail region containing two phosphorylation sites for Ca2+/calmodulin-dependent protein kinase II. The steady-state emission spectrum of synapsin I was centered at 330 nm and was markedly red shifted upon denaturation, as expected for tryptophan residues segregated from the external aqueous environment in native conditions. Quenching studies showed a low accessibility of synapsin I tryptophans at low ionic strength which was further decreased by exposure to 200 mM NaCl but not significantly affected by phosphorylation. The intrinsic fluorescence of synapsin I was resolved into three major decay components with lifetimes of about 0.2, 3, and 7 ns. Upon phosphorylation of synapsin I on the tail sites, the spectra associated with the intermediate and long lifetimes were shifted to the red region, while the spectrum associated with the short lifetime was shifted to the blue region, in the absence of significant changes of the lifetimes. Phosphorylation of synapsin I on the head site was less effective. The anisotropy decay of synapsin I labeled with the long-living chromophore pyrene on Cys-223 was also analyzed. A shorter rotational correlation time was found for the tail phosphorylated form (corresponding to a Stokes radius of 41-42 A) than for the dephosphorylated or for the head phosphorylated form (corresponding to a Stokes radius of 60-63 A). The data suggest that phosphorylation of the tail sites induces changes in the conformation and hydrodynamic properties of synapsin I which may play a role in the regulation of the molecular interactions of synapsin I within the nerve terminal.


Two novel multiple mutations in chinese patients with adrenoleukodystrophy.
X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder caused by mutations in the ABCD1 gene. Up to now, more than 1 050 mutations have been reported in the ABCD1 gene, of which only 10 are multiple mutations in one allele of the gene. In this study, we report 2 novel multiple mutations in 2 patients with X-ALD from 2 unrelated Chinese families. Total RNA and genomic DNA were isolated from peripheral blood of the 2 patients, and the ABCD1 gene was analyzed by direct sequencing and denaturing high-performance liquid chromatography. We detected [p.Ser108X+p.Arg259Trp] in patient 1, [p.Lys217Glu+p.Val489Val] in patient 2 in one allele of the ABCD1 gene. Both novel multiple mutations have not previously been reported and this is the first report of multiple mutations identified in Chinese patients with X-ALD.


[Auricular fibrillation as a risk factor of cerebrovascular events in the over-65s. Is clinical practice in anticoagulant prophylaxis adequate?].
To describe the clinical practice in antithrombotic therapy to prevent stroke in older patients with atrial fibrillation (AF). Cross-sectional study. Ourense's area with 95,840 inhabitants over 65 years. Patients over 65 with non rheumatic AF, chronic or paroxistic; 411 cases, 69.6% older than 75 year. Demographic characteristics, personal history, stroke risk, diagnostic characteristics of AF, antithrombotic treatment, and its adequacy. Only 33% high risk patients received oral anticoagulation (OCA) with warfarin at diagnosis. Some features were found to be significant independent risk factors for OCA: age (older than 75 vs 65-74 years; odds ratio =0.32; 95% confidence interval, 0.18-0.59), and prior stroke (odds ratio =2.02; 95% confidence interval, 1.16-3.55). Warfarin prophylactic is insufficiently prescribed, especially in older than 75 years (with high baseline risk of stroke and no counter-indications). There was inadequate prescription in 73.4% cases.


Cystatin C and apoe polymorphisms in Italian Alzheimer's disease.
Recent studies have reported a genetic association between the 73 G/A polymorphism within exon 1 of the cystatin C gene and Alzheimer's disease (AD) with conflicting results. To further investigate the proposed association and to clarify the role of CST3 as risk factor for AD, we analyzed the genotype and allele frequency distribution of CST3 G73A and apolipoprotein (ApoE) gene polymorphisms in 243 Italian patients with AD and 186 controls. Patients with AD were consecutively collected among the outpatients from the Neurology Department at the University of Florence. All 429 subjects were genotyped for CST3 and ApoE polymorphisms. After stratification according to age, the GG frequency resulted slightly higher in younger (<65 years) cases, but far from statistically significant. There was also no evidence of a statistical interaction between CST3 and ApoE polymorphisms. In conclusion, our data suggest that the CST3 genetic variant is not a susceptibility factor in AD, nor mitigate the effect of the ApoE varepsilon4 allele in the risk of developing AD.


Aflagellar Epimastigote of Trypanosoma caninum: Biological and Ultrastructural Study of this Atypical Evolutionary Form.
Trypanosoma caninum exhibits atypical epimastigote forms under axenic conditions. This study aimed to analyze this evolutionary form under different cultivation conditions and provide more information about this evolutionary form. We selected a T. caninum isolate with a high percentage of aflagellar epimastigote forms in axenic cultures. Two separate growth curves were generated for T. caninum cultured in Schneider axenic medium and co-cultured with the DH82 cell line, followed by analysis and quantification of evolutionary forms using bright field microscopy. In addition, ultrastructural analysis of T. caninum was performed under both cultivation conditions. The growth curves of T. caninum under axenic and co-cultivation conditions exhibited similar profiles. However, in the axenic culture, the number of parasites was three times higher at the peak of the exponential phase than in the co-culture. In contrast to that in the axenic culture, in which only the epimastigote forms were observed along the entire curve, during co-cultivation with the DH82 cell line, differentiation was observed for the trypomastigote and spheromastigote forms in low proportions. These results demonstrated that when cultured alone, the T. caninum isolate preserved the aflagellar epimastigote form, but in the presence of DH82 canine macrophages, they differentiated into evolutionary forms, particularly trypomastigote forms. Moreover, this study is the first to describe the presence of lipid bodies, structure described as the parasite's nutritional reserve, throughout the body of T. caninum. These findings describe biological and ultrastructural aspects of epimastigote aflagellar and suggest that this evolutionary form may be involved in the biological cycle of T. caninum, still unknown.


China's value-added tax policy and intertemporal optimal assets allocation of enterprises--Based on the dual perspectives of VAT input refund and VAT rate.
The article sought to detect the impact of the value-added tax (VAT) policy on the enterprises' asset allocation from the dual perspectives of the VAT input refund and the VAT rate. Based on the influenced mechanism of the VAT input refund and the tax burden effect (and the price effect) caused by the VAT rate, enterprises' intertemporal optimal asset allocation models are constructed under the states of adopting the VAT input refund and maintaining the theoretical tax (non-)neutrality of VAT. When VAT rates of the general taxpayers are predicted to be reduced, we also use China's manufacturing and economic data to simulate specific cases to verify propositions under different states. The results show that: (1) When the VAT output tax rate decreases: if returns to scale are diminishing, enterprises will increase the number of productive material assets and labor and reduce financial assets. (2) When the VAT input tax rate reduces: under the state of adopting the VAT input refund and maintaining the theoretical tax (non-)neutrality of VAT, if returns to scale are decreasing, enterprises will reduce the number of productive material assets and labor and increase financial assets. Under the state of adopting the VAT input refund and maintaining the theoretical tax neutrality of VAT, if returns to scale are increasing and the expected rate of return of financial assets is lower than the additional tax rate, or the enterprise has diminishing returns to scale and the expected rate of return of financial assets is higher than the additional tax rate, enterprises will increase the number of productive material assets and labor. (3) When VAT output and input tax rates reduce simultaneously: under the state of adopting the VAT input refund and maintaining the theoretical tax neutrality of VAT, if returns to scale are increasing and the expected return rate of financial assets is higher than the additional tax rate, the enterprise will reduce the number of productive material assets and labor and increase financial assets. Under the diminishing returns to scale in China's national economy, the research conclusions endorse the rational necessity of the VAT policy change-VAT rate reduction to develop the entity economy and provide a reference for enterprises to make asset allocation decisions. The conclusions also provide possible changes in VAT policy for different countries according to their actual economic conditions.


Isolation and structural characterization of alkali-labile oligosaccharides from bovine milk-fat-globule membrane.
Treatment of sialoglycopeptides derived from bovine milk-fat-globule membrane with alkaline borohydride released a reduced oligosaccharide fraction from which a tetrasaccharide and two trisaccharides were isolated. Periodate-oxidation studies coupled with methylation analysis and g.l.c.-mass spectrometry established their structures as: N-acetylneuraminyl-(2 leads to 3)-beta-D-galactopyranosyl-(1 leads to 3)-[N-acetylneuraminyl-(2 leads to 6)]-N-acetyl-D-galactosaminitol, N-acetylneuraminyl-(2 leads to 3)-D-glactopyranosyl-(1 leads to 3)-N-acetyl-D-galactosaminitol and beta-D-galactopyranosyl-(1 leads to 3)-[N-acteylneuraminyl-(2 leads to 6)]-N-acetyl-D-galactosaminitol respectively.


Different methods of assessing udder temperature through thermography and their relation with rectal temperature.
Infrared thermography of the lateral side portion of the udder was taken from 38 lactating cows in a 6-day experiment. Thermograms were analyzed using specific software with the use of eight different methods. The experiment was aimed at correlating the different methods with each other and with rectal temperature (RT), in order to suggest a method to assess udder side temperature, and also at creating regression equations to enable RT calculation through the use of thermographic data. All methods of analyzing thermograms were highly correlated; correlations between thermograms and RT were significant (P < 0.01) and above 0.840. The highest correlation was between RT and the maximum temperature obtained using a horizontal rectangle placed within the lateral (side) portion of the udder (maximum temperature in a horizontal rectangle (MHR), 0.897). With the exception of the average temperature of a horizontal rectangle, linear regression coefficients were significant (P < 0.05) and coefficients of determination were higher than 75.51%. We suggest the use of MHR to evaluate udder side temperature. The ease of accessing the side of the udder, the welfare advantages of non-invasive observations, and the high correlation with RT suggest the use of thermograms in the lateral portion of the udder to assess animals' temperature.


Frontotemporal dementia.
Frontotemporal dementia (FTD) is the second commonest cause of young onset dementia. Our understanding of FTD and its related syndromes has advanced significantly in recent years. Among the most prominent areas of progress is the overlap between FTD, MND, and other neurodegenerative conditions at a clinicopathologic and genetic level. In parallel major advances in neuroimaging techniques, the discovery of new genetic mutations as well as the development of potential biomarkers may serve to further expand knowledge of the biologic processes at play in FTD and may in turn propel research toward identifying curative and preventative pharmacologic therapies. The aim of this chapter is to discuss the clinical, pathologic, and genetic complexities of FTD and related disorders.


French adaptation of the "Frenchay Dysarthria Assessment 2" speech intelligibility test.
Speech intelligibility can be defined as "the degree to which a speaker's intended message is recovered by a listener". Loss of intelligibility is one of the most frequent complaints in patients suffering from speech disorder, impairing communication. Measurement of intelligibility is therefore an important parameter in follow-up. We developed a French version of the "Frenchay Dysarthria Assessment, 2nd edition" (FDA-2), an intelligibility test recognized internationally in its English version. The present study details the construction of the test and its preliminary validation. We first compiled a set of words and phrases in French, based on the criteria defined in FDA-2. In a second step, we validated the test in healthy subjects in normal and noisy conditions, to check sensitivity to speech signal degradation. The test proved valid and sensitive, as scores were significantly lower for noise-degraded stimuli. This French-language intelligibility test can be used to evaluate speech disorder: for example, in dysarthria, head and neck cancer or after cochlear implantation.


Vitrectomy for diabetic traction retinal detachment involving the macula.
We analyzed the surgical results for 197 eyes that underwent vitrectomy for diabetic traction detachment of the macula. The retina was successfully reattached in 130 of the 197 cases (66%), although the final level of vision depended on the amount of permanent macular damage from the previous detachment and on the effects of the retinal vascular disease. At the final examinations, 112 eyes (57%) had improved visual acuities, 68 eyes (35%) were worse, and 17 eyes (9%) were unchanged. Thirteen eyes (7%) had final visual acuities of 20/40 or better, 103 eyes (52%) had final visual acuities of 20/50 to 20/800, and 81 eyes (41%) had final visual acuities worse than 20/800. Two preoperative factors were associated with a worse prognosis for achieving a final visual acuity of 20/800 or better: preoperative vitreous hemorrhage (P less than .01) and the absence of preoperative scatter retinal photocoagulation (P less than .01). Additionally, two surgical factors, lens removal and the creation of iatrogenic retinal breaks, were associated with a poorer visual prognosis (P less than .002 and P less than .01, respectively). The group of eyes that underwent lens removal during vitrectomy also had a significantly higher incidence of postoperative iris neovascularization compared to eyes in which the lenses were not removed (P less than .05).


[Valid liability law in surgery. Principles of legal requirements and clinical benchmarks exemplified by visceral surgery].
The spectacular increase in liability processes in the field of surgery and in particular in visceral surgery, necessitates an objectification of the conflict between surgical medical professionals and medico-legal institutions, firms of solicitors and courts. Out of court settlements assisted by expert opinion commissions of the Medical Council can avoid many legal conflicts. For improvement of the legal standpoint of a defendant medical professional an unambiguous, extensive and detailed documentation of medical examination findings, the indications for the planned operative intervention, extensive and detailed documentation on disclosure and informed consent of the patient for the planned operative intervention, an extensive, detailed careful and responsibly guided report of the operation as well as a systematic, orderly well-planned postoperative complication management are necessary to counter the accusation of an organizational failure of medical professionals and the accused hospital. The mutual building of confidence between surgical medical professionals and legal institutions is safeguarded by a comprehensive documentation and an unambiguous description and formulation of the medical discharge report on termination of inpatient treatment.


MAP Kinase Inhibition Promotes T Cell and Anti-tumor Activity in Combination with PD-L1 Checkpoint Blockade.
Targeted inhibition of mitogen-activated protein kinase (MAPK) kinase (MEK) can induce regression of tumors bearing activating mutations in the Ras pathway but rarely leads to tumor eradication. Although combining MEK inhibition with T-cell-directed immunotherapy might lead to more durable efficacy, T cell responses are themselves at least partially dependent on MEK activity. We show here that MEK inhibition did profoundly block naive CD8(+) T cell priming in tumor-bearing mice, but actually increased the number of effector-phenotype antigen-specific CD8(+) T cells within the tumor. MEK inhibition protected tumor-infiltrating CD8(+) T cells from death driven by chronic TCR stimulation while sparing cytotoxic activity. Combining MEK inhibition with anti-programmed death-ligand 1 (PD-L1) resulted in synergistic and durable tumor regression even where either agent alone was only modestly effective. Thus, despite the central importance of the MAP kinase pathway in some aspects of T cell function, MEK-targeted agents can be compatible with T-cell-dependent immunotherapy.


A simple parasitological technique to increase detection of Strongyloides stercoralis in Bolivian primary health care system.
Strongyloides stercoralis is widespread; however, there is limited information on its prevalence owing to laboratory underestimation and low clinical manifestations. The Baermann method and agar culture stand out among the parasitological techniques. Strongyloides stercoralis is present in Bolivia, but its prevalence in children remains unknown. The objective of this study was to estimate the applicability of simple parasitological techniques to increase the detection of this parasite in children living in the tropics. This cross-sectional study was conducted in a tropical village in Cochabamba, Bolivia. Participants were 304 children aged 5 - 12 years who provided stool samples for different parasitological analyses (direct examination, Ritchie, Baermann, and Dancescu techniques), and their parents provided informed consent. Up to 64.8% of pathogenic parasites were detected using the modified Ritchie method. The Baermann technique identified 17.8% of Strongyloides stercoralis cases, and a high sensitivity with respect to the Baermann technique was only for the Dancescu technique (75.9%) that is also specific for Strongyloides stercoralis, followed by 66.7% for the modified Ritchie technique, which is used in second-line care. The Baermann technique is the best parasitological option for improving Strongyloides stercoralis diagnosis in the first-line care of the Primary Health Care System. A particular cycle of reinfection, combined with the environment and some other risk factors are related with persistence. Control is difficult without a proper diagnosis, and the Baermann technique is an approach to the solution. We conclude that with a high suspicion of the presence of Strongyloides stercoralis, the use of the Baermann technique is strongly recommended as support for direct examination in primary health care systems especially in tropical areas.


Decreased serum voriconazole levels caused by hepatic enzyme induction after rifapentine discontinuation: a case report and literature review.
Rifapentine is a rifamycin with unique bactericidal activity against Mycobacterium tuberculosis. It is also a potent inducer of CYP3A activity. However, the duration of rifapentine-induced hepatic enzyme activity after withdrawal is unclear. We report a case of a patient with Aspergillus meningitis treated with voriconazole after discontinuing rifapentine. Within ten days of rifapentine discontinuation, serum levels of voriconazole failed to reach the effective treatment range. Rifapentine is a potent inducer of hepatic microsomal enzymes. The induction of hepatic enzymes may exceed ten days after rifapentine discontinuation. Clinicians should be reminded of residual enzyme induction by rifapentine, especially when treating critically ill patients.


Sutureless mesh-plug femoral hernioplasty.
Prosthetic mesh groin hernioplasty is well established. We aimed to determine whether a sutureless mesh-plug repair of femoral hernias was a reliable proposition. A prospective study of 42 patients undergoing femoral hernioplasty with a preformed three-dimensional mesh plug placed in the preperitoneal plane. There were no complications, and no recurrences were detected at a median follow-up of 2 years (range 2 to 44). Preperitoneal mesh plug femoral hernioplasty appears to be universally applicable and deserves further evaluation.


Glare disability secondary to YAG laser intraocular lens damage.
Neodymium:YAG laser intraocular lens damage results in opacities in the pseudophakos. When located in the visual axis, these opacities may cause glare and image degradation. In this paper, we report a patient who experienced disabling glare sufficient to require the explanation of the YAG-damaged intraocular lens. The patient, her management and clinical course, and the pathology of the explanted lens are discussed.


Functional classification of secondary lymphedema.
The epidemiological classifications of primary lymphedema based on age at emergence and the severity of the edema are fundamental to the transmission of information about this condition. In the secondary type, the lymphatic system is intact at birth but is injured during the course of life, causing a deficiency that leads to lymphedema. However, years of clinical experience and progress in treatment suggest new classifications to assist in the therapeutic planning of each patient. In clinical practice, we have observed inappropriate treatments that can cause more harm than good. Such observations are important and suggest the need for a proper diagnosis that considers all physiopathological processes involved for the establishment of the best form of treatment.


Swallowing dynamics status post caustic ingestion in a pediatric patient: A multidisciplinary case report.
A case report of a 10 year old male illustrates the effect of damage to the tongue base, hypopharynx, cricopharyngeus, and esophagus on the sensory and motor components of the swallowing mechanism. The characteristics of the dysphagia were manifested clinically, radiographically, and endoscopically. A myectomy was required to restore functional swallowing as scar tissue formation in the cricopharyngeus severely interfered with the dynamic components of swallowing. A collaborative approach facilitated communication and effective treatment planning; the multidisciplinary components in the management of this case are discussed.