Image-guided percutaneous bone biopsy with a simulated van sonnenberg removable hub system.
To retrospectively examine the success and complication rates associated with image-guided percutaneous bone biopsy with a simulated Van Sonnenberg removable hub system. During a 3.5-year period, 27 bone lesions at different anatomic locations with an indication for biopsy based on plain film, computed tomography (CT) and/or magnetic resonance imaging (MRI) findings were determined, and a total of 28 image-guided (fluoroscopy or CT) percutaneous biopsies were performed using a simulated Van Sonnenberg -removable hub system. This technique entailed the use of a cut-out Chiba needle hub that performed as a guide for the insertion of a larger needle. Either core and aspiration biopsy or core biopsy alone was utilized. The procedure yielded diagnostic material 89% of the cases (48% infection, 22% benign lesions, and 19% malignant lesions). Combined use of core and aspiration biopsy resulted in a higher diagnostic accuracy as compared to core biopsy alone. No false positive or false negative diagnoses were observed. No serious complications such as neurological deficits, bleeding, or organ injury were observed. The simulated Van Sonnenberg removable hub system provides a useful technique for percutaneous bone biopsies and is particulary suitable for deep seated (such as vertebral) lesions with its ability to facilitate the accessibility of the lesion with its built-in guidance needle. The procedure is safe in light of the literature data.


Excess mortality associated with the 2009 A(H1N1)v influenza pandemic in Antananarivo, Madagascar.
It is difficult to assess the mortality burden of influenza epidemics in tropical countries. Until recently, the burden of influenza was believed to be negligible in Africa. We assessed the impact of the 2009 influenza epidemic on mortality in Madagascar by conducting Poisson regression analysis on mortality data from the deaths registry, after the first wave of the 2009 A(H1N1) virus pandemic. There were 20% more human deaths than expected in Antananarivo, Madagascar in November 2009, with excess mortality in the ⩾50 years age group (relative risk 1·41). Furthermore, the number of deaths from pulmonary disease was significantly higher than the number of deaths from other causes during this pandemic period. These results suggest that the A(H1N1) 2009 virus pandemic may have been accompanied by an increase in mortality.


Morphological phylogenetic analysis of the Africana genus (Nematoda: Heterakidae).
A morphological phylogenetic hypothesis of the relationships among the species of Africana is provided. The phylogenetic analysis suggests that Squamata or Amphibia were ancestral hosts for species of Africana, with dispersal events to Testudinidae; a second transfer to amphibians is also suggested. On the basis of biological data for these parasites and the paleogeographic reconstructions, a South American origin for Africana spp. is indicated, with subsequent dispersal events to Africa. It is further proposed that Chamaleonidae acquired species of Africana after their 'out-of-Madagascar' dispersal events to Africa.


Effect of chemical composition of sunflower seed meal on its true metabolizable energy and amino acid digestibility.
The effect of chemical composition of sunflower seed meal (SFSM) on TMEn and true amino acid digestibility (TAAD) was studied. In Experiment 1, the excretion pattern of three SFSM samples force-fed (30 g) to 10 adult cockerels (Hy-Line) each was followed for 84 h to determine the time interval for complete excretion of SFSM. Type of SFSM did not affect the excretion pattern of DM and energy (P=0.438, and P=0.189, respectively). Dry matter and energy excreted every 12 h decreased linear and quadratically (P < 0.001) with collection time. No differences were found from 48 h collection time on. So, an excreta collection period of 48 h was considered adequate for determining the TMEn of SFSM. In Experiment 2, 135 adult cockerels were force-fed to determine the TMEn of 11 samples of SFSM. Type of SFSM affected TMEn (P < 0.001), which ranged from 1,558 to 2,023 kcal/kg DM for SFSM of 31 to 42% CP, respectively. The TMEn was highly correlated (P < 0.001) to hemicellulose (r=-0.90), acid detergent lignin (r=-0.84), neutral detergent fiber (r=-0.82), and CP (r=0.77). Four prediction equations are proposed, the most practical being: TMEn (kcal/kg DM)=2,816.8 - 109.5 hemicellulose (%DM), RSD=70.2. Three out of the 11 samples of SFSM were selected for determining TAAD and the effect of endogenous amino acid correction. The methodology used was that of the TMEn assay, but one more estimation of amino acid endogenous excretion was made using a N-free diet with 85% cornstarch and 15% cellulose. Endogenous amino acid excretion was greater for roosters fed the N-free diet than those deprived of feed, resulting in a higher digestibility (from 0.7 to 2.7%, P < 0.05) only for six amino acids: threonine, valine, alanine, proline, and aspartic and glutamic acids. No interaction was detected (P=0.94) between type of SFSM and method of estimation of endogenous amino acid excretion. The TAAD of SFSM increased significantly (P < 0.001) with the CP content, total TAAD being 86, 88, and 89% for SFSM of 32, 35, and 37% CP, respectively. Attention should be paid when including high fiber-low protein SFSM in poultry diets to balance its lesser digestible amino acids contribution, mainly in lysine (from 0.77 to 1.06% for SFSM of 32 and 37% CP, respectively).


Dietary inflammatory index and type 2 diabetes risk in a prospective cohort of 70,991 women followed for 20 years: the mediating role of BMI.
Diet is one of the main lifestyle-related factors that can modulate the inflammatory process. Surprisingly the dietary inflammatory index (DII) has been little investigated in relation to type 2 diabetes, and the role of BMI in this relationship is not well established. We studied this association and the role of BMI in the inflammatory process in a large population-based observational study. A total of 70,991 women from the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort study were followed for 20 years. Incident type 2 diabetes cases were identified using diabetes-specific questionnaires and drug reimbursement insurance databases, and 3292 incident cases were validated. The DII was derived from a validated food frequency questionnaire. Multivariable Cox regression models estimated HRs and 95% CIs between DII and incident type 2 diabetes. Interactions were tested between DII and BMI on incident type 2 diabetes and a mediation analysis of BMI was performed. Higher DII scores, corresponding to a higher anti-inflammatory potential of the diet, were associated with a lower risk of type 2 diabetes. Compared with the 1st quintile group, women from the 2nd quintile group (HR 0.85 [95% CI 0.77, 0.94]) up to the 5th quintile group (HR 0.77 [95% CI 0.69, 0.85]) had a lower risk of type 2 diabetes before adjustment for BMI. There was an interaction between DII and BMI on type 2 diabetes risk (pInteraction < 0.0001). The overall association was partly mediated by BMI (58%). Our findings suggest that a higher anti-inflammatory potential of the diet is associated with a lower risk of type 2 diabetes, and the association may be mediated by BMI. These results may improve our understanding of the mechanisms underlying the role of diet-related anti-inflammation in the pathogenesis of type 2 diabetes in women. Further studies are warranted to validate our results and evaluate whether the results are similar in men.


Sensitivity of winter North Atlantic-European climate to resolved atmosphere and ocean dynamics.
Northern Hemisphere western boundary currents, like the Gulf Stream, are key regions for cyclogenesis affecting large-scale atmospheric circulation. Recent observations and model simulations with high-temporal and -spatial resolution have provided evidence that the associated ocean fronts locally affect troposphere dynamics. A coherent view of how this affects the mean climate and its variability is, however, lacking. In particular the separate role of resolved ocean and atmosphere dynamics in shaping the atmospheric circulation is still largely unknown. Here we demonstrate for the first time, by using coupled seasonal forecast experiments at different resolutions, that resolving meso-scale oceanic variability in the Gulf Stream region strongly affects mid-latitude interannual atmospheric variability, including the North Atlantic Oscillation. Its impact on climatology, however, is minor. Increasing atmosphere resolution to meso-scale, on the other hand, strongly affects mean climate but moderately its variability. We also find that regional predictability relies on adequately resolving small-scale atmospheric processes, while resolving small-scale oceanic processes acts as an unpredictable source of noise, except for the North Atlantic storm-track where the forcing of the atmosphere translates into skillful predictions.


Soft lithographic patterning of spin crossover nanoparticles.
Microtransfer molding has been used to fabricate homogeneous micropatterns and nanopatterns of spin crossover nanoparticles of [Fe(NH(2)trz)](tos)(2) over a large area. We show that the use of an aprotic solvent (n-octane) may lead to successful results. Very well organized micropatterns are obtained, showing spin crossover phenomenon. Dark field optical and AFM images and Raman microspectrometry results are reported.


Ploidy of endothelium in high-grade astrocytomas.
To determine the ploidy and proliferative activity of the endothelium in high-grade astrocytomas, the nuclear DNA content of 11 high-grade astrocytomas, including two gliosarcomas, was measured by cytophotometry. This technique allowed comparison of the endothelial population with the astrocytic population. In all cases, the endothelium was diploid, with an average of 24.6% of cells in the S + G2M phases of the cell cycle. In contrast, the astrocytic population displayed marked DNA abnormalities. The two gliosarcomas had a marked difference in proliferative activity of the endothelium with 4% and 40% of cells, respectively, in the S + G2M phases. These data indicate that the vast majority of endothelial cells compromising the vascular hypercellularity observed in high-grade astrocytomas are in the normal cell cycle whereas in many cases the malignant astrocytes are not. The nuclear DNA content of gliosarcomas appears to be similar to other high-grade astrocytomas.


Design of Dyson imaging spectrometers based on the Rowland circle concept.
We aim to show that Dyson imaging spectrometers can be easily designed by applying the concept of the Rowland circle to refracting surfaces. This allows us to conceive an analytical procedure that is based on the removal of astigmatism at two wavelengths. Following this procedure, high-optical-quality spectrometers can be designed even for high speeds. Root-mean-square spot radii less than 2.5 μm are obtained for speeds as high as f/1.5, slit lengths of 15 mm, and wavelength ranges of 0.4-1.7 μm. Design examples are presented for classical Dyson spectrometers in which the detector is glued to the glass plane surface and for spectrometers with an air gap between this surface and the image plane.


A DFT study on the dimerization of C62, H2-C62, and F2-C62.
On the basis of calculations using the density functional theory, we show that C(62), a recently synthesized nonclassical fullerene, will presumably undergo dimerization with various isomers at elevated temperatures. This is shown by calculating the dimerization energy and the activation barrier of the dimerization. Eight possible isomers of the dimer were identified, all of which are more stable than the two isolated monomers. The relative stability of various isomers depends upon the kind of C=C bonds within the four-membered carbon ring involved in the dimerization. In addition, similar calculations were performed for the monomers and dimers of H(2)-C(62) and F(2)-C(62). Six isomers were identified for each of the dimers. Although less pronounced than the case of the C(62) dimer, all isomers of the H(2)-C(62) dimer are appreciably more stable than the individual monomers. Although a large steric repulsion due to F atoms significantly reduces the stability of F(2)-C(62) dimer, its two isomers are still more stable than separate monomers.


In search of endodontic pathogens.
Success of root canal therapy depends on the complete eradication of microflora from the root canal system. A great deal of research is needed to identify and define the role of the pathogens which are involved in the pathogenesis of the periradicular diseases. This will help the endodontist to plan the best treatment by irradiation of pathogens which, in turn predict the outcome of the treatment. This article reviews the endodontic microflora, routes of microbial entry, methods to identify endodontic microbes and markers that permit the clinician to know when to conclude the treatment.


Immunosensor for 2,4-dichlorophenoxyacetic acid in aqueous/organic solvent soil extracts.
The development of a simple electrochemical immunoassay procedure for the field-based quantification of the herbicide 2,4-D in methanolic soil extracts is presented. The sensor utilizes a competitive immunoassay format incorporating an immobilized antigen complex at the surface of a disposable screen-printed working electrode element. The extent of glucose oxidase-labeled antibody binding to the antigen--electrode is determined amperometrically and is related to sample analyte concentration. The performance of the sensor is assessed in buffer, 30% methanol, and methanolic soil extracts. The device is capable of quantifying 2,4-D in all three matrixes at the low ppm level with coefficient of variation values of 6.2-33.6%. The causes of the variation observed in the sensor response in different soil matrixes are examined and improvements proposed. The sensor, tested in parallel with a commercial 2,4-D immunoassay test kit, yields comparable quantitative data and detection limits while exhibiting greater assay simplicity.


An investigation of chemotaxis in the insect parasitic nematode Heterorhabditis bacteriophora.
We tested the chemotactic responses of dauer juvenile stages (DJs) of the insect parasitic nematode Heterorhabditis bacteriophora to a variety of compounds that are known to be highly attractive or highly repellent to Caenorhabditis elegans. While H. bacteriophora DJs respond to alcohols and some aromatic compounds as well as to host metabolites such as uric acid and CO2, the most notable difference in the responses of these two nematodes is that H. bacteriophora DJs are unresponsive to a large number of compounds which C. elegans finds highly attractive. The latter compounds are typical by-products of bacterial metabolism and include aldehydes, esters, ketones and short-chain alcohols. While C. elegans finds long-chain alcohols (e.g. 1-heptanol and 1-octanol) repellent and short-chain alcohols highly attractive, H. bacteriophora DJs are strongly attracted to 1-heptanol, 1-octanol and 1-nonanol and find short-chain alcohols to be only slightly attractive. Parasitic-stage H. bacteriophora nematodes show a very weak chemotactic response to volatile molecules that DJs find highly attractive. Our results suggest that, associated with the adoption of a parasitic mode of life by Heterorhabditis, there was an adaptive change in chemotactic behaviour of the infective stages, resulting in a decreased sensitivity to volatile by-products of bacterial metabolism and an increased sensitivity towards long-chain alcohols and other insect-specific volatiles and possibly also to herbivore-induced plant volatiles.


Receptor cluster formation during activation by bacterial products.
The recognition of bacterial products, such as lipopolysaccharide (LPS) by the innate immune system lead to a strong pro-inflammatory response that can eventually lead to fatal sepsis syndrome in humans. Although CD14 and TLR4 have been identified as the key molecules involved in LPS-induced signal transduction, accumulating evidence indicates that multiple receptors are also involved. Our group has recently identified a cluster of receptors, involving heat-shock proteins 70 and 90, chemokine receptor 4 as well as growth differentiation factor 5, that are formed following LPS stimulation. In addition, we present data demonstrating that these molecules associate with TLR4 and accumulate in membrane microdomains following LPS ligation. Our results suggest that the entire bacterial recognition is based around the recruitment of multiple signalling molecules, in addition to CD14 and TLRs, within the lipid rafts. We propose that different combinational associations of receptors within activation clusters determine the different responses to a variety of bacterial stimuli.


Glucose-induced accumulation of inositol trisphosphates in isolated pancreatic islets. Predominance of the 1,3,4-isomer.
Anion-exchange h.p.l.c. analysis of [3H]inositol phosphates derived from glucose-stimulated isolated pancreatic islets that had been prelabelled with myo-[3H]inositol revealed that the predominant inositol trisphosphate was the 1,3,4-isomer [Ins(1,3,4)P3]. The 1,4,5-isomer [Ins(1,4,5)P3] was also detectable, as was a more polar inositol phosphate with the chromatographic properties of inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4]. Glucose-induced accumulation of Ins(1,3,4)P3 was augmented by Li+ and occurred after maximal accumulation of Ins(1,4,5)P3. These findings suggest a possible role for Ins(1,3,4)P3 or its probable precursor Ins(1,3,4,5)P4 in stimulus-secretion coupling in pancreatic islets.


Functional characterization of osteoblasts and osteoclasts from alkaline phosphatase knockout mice.
Tissue nonspecific alkaline phosphatase (TNAP) knockout (ko) mice manifest defects in bone mineralization that mimic the phenotypic abnormalities of infantile hypophosphatasia. In this article, we have searched for phenotypic differences between calvarial osteoblasts and osteoclasts in wild-type (wt), heterozygous and homozygous TNAP null mice. In vitro release of 45Ca from calvarial bones, with and without stimulation with parathyroid hormone (PTH), revealed no functional difference between osteoclasts from the three TNAP genotypes. Studies of primary cultures of TNAP+/+, TNAP+/-, and TNAP-/- calvarial osteoblasts revealed no differences in the rate of protein synthesis or in the expression levels of messenger RNAs (mRNAs) for osteopontin (OP), osteocalcin (OC), collagen type I, core binding factor alpha1 (Cbfa 1), N-cadherin, Smad 5, and Smad 7. Release of interleukin-6 (IL-6) from calvarial osteoblasts under basal conditions and after stimulation with PTH, tumor necrosis factor alpha (TNF-alpha) or IL-1beta was similar in all genotypes. The amount of cyclic adenosine monophosphate (cAMP) accumulation also was comparable. However, although cultures of primary TNAP-/- osteoblasts were able to form cellular nodules as well as TNAP positive osteoblasts do, they lacked the ability to mineralize these nodules in vitro. Mineralization also was delayed in TNAP+/- osteoblast cultures compared with cultures of wt osteoblasts. Incubation with media supplemented with recombinant TNAP, but not with enzymatically inactive TNAP, restored mineralization in ko osteoblast cultures. Our data provide evidence that osteoblasts in TNAP null mice differentiate normally but are unable to initiate mineralization in vitro. The fact that even heterozygous osteoblasts show delayed mineralization provides a rationale for the presence of bone disease in carriers of hypophosphatasia.


[Secondary intrathoracic reconstruction after prosthetic repair of the brachiocephalic trunk for traumatic aneurysm of the right subclavian artery].
The article deals with a case report of successful secondary surgical treatment of a patient who endured prosthetic repair of the brachiocephalic trunk for a traumatic false aneurysm of the right subclavian artery complicated by thrombosis of the reconstruction zone. Long-term conservative treatment resulted in progression of cerebrovascular insufficiency, invalidization, increasing ischaemia of the right upper limb, which required performing secondary intrathoracic reconstruction with prosthetic repair of the common carotid artery, vertebral artery and axillary artery on the right. Presented herein are the results of check up contrast-enhanced and CT-angiography performed at 10 months after the operation.


Induced Resistance Mechanism of Novel Curcumin Analogs Bearing a Quinazoline Moiety to Plant Virus.
Plant immune activators can protect crops from plant virus pathogens by activating intrinsic immune mechanisms in plants and are widely used in agricultural production. In our previous work, we found that curcumin analogs exhibit excellent biological activity against plant viruses, especially protective activity. Inspired by these results, the active substructure of pentadienone and quinazoline were spliced to obtain curcumin analogs as potential exogenously induced resistant molecule. Bioassay results showed that compound A13 exhibited excellent protective activity for tobacco to against Tobacco mosaic virus (TMV) at 500 μg/mL, with a value of 70.4 ± 2.6% compared with control treatments, which was better than that of the plant immune activator chitosan oligosaccharide (49.0 ± 5.9%). The protective activity is due to compound A13 inducing tobacco resistance to TMV, which was related to defense-related enzymes, defense-related genes, and photosynthesis. This was confirmed by the up-regulated expression of proteins that mediate stress responses and oxidative phosphorylation.


Perioral dermatitis: etiology and treatment.
Ninety-five patients with perioral dermatitis were studied from an epidemiological aspect. Consistent clearing of the eruption was obtained with oral tetracycline in combination with a topical sodium sulfacetamide-sulfur-hydro-cortisone lotion. Comparison of the study group of patients to a group of 50 control patients revealed highly significant quantitative differences in the cosmetic preparations used by the two groups. This latter finding would suggest that lubricating and moisturizing products play some part in the etiology of perioral dermatitis.


A case-control study of antidepressants and attempted suicide during early phase treatment of major depressive episodes.
To estimate the relative risk of suicide attempts in child and adult outpatients initiating antidepressants for major depressive episodes compared to those not treated with antidepressants. A nested matched case-control study was performed with Medicaid administrative data (January 1, 1999-December 31, 2000) of out-patients treated for a major depressive episode. Beneficiaries initiating treatment for a major depressive episode were selected, excluding those who had recently received inpatient psychiatric treatment or outpatient treatment of pregnancy, major depressive episodes, bipolar disorder, schizophrenia or other psychoses, mental retardation, dementia, or delirium or recent treatment with a mood stabilizer, antidepressant, or antipsychotic. The outcome was treatment for a suicide attempt during the first 120 days after starting treatment for a major depressive episode. Controls were matched to cases on age, sex, race/ethnicity, recent treatment of substance use disorder, severity and type of major depressive episode, and other factors. Separate analyses were performed for adults (aged 19 to 64 years) and children (aged 6 to 18 years). Among children, antidepressant treatment was associated with a significant increase in suicide attempts (odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.06 to 4.10; cases, N = 51; controls, N = 239; p = .03). Among adults, antidepressant treatment was not significantly related to risk of suicide attempts (OR = 0.85, 95% CI = 0.57 to 1.28; cases, N = 185; controls, N = 893; p = .44), although among adult males, antidepressants were associated with a significant protective effect (OR = 0.32, 95% CI = 0.12 to 0.83; cases, N = 57; controls, N = 268; p = .01). In these outpatients initiating treatment for a major depressive episode, antide-pressant treatment appears to be associated with an increased risk of treated suicide attempts in children and a decreased risk in adult males.


The MPTP mouse model: cues on DA release and neural stem cell restorative role.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to cause parkinsonism in humans and this fact is a major incentive for using this toxin as an animal model to study the pathogenesis of Parkinson's disease (PD). Although the monkey MPTP model remains the best, most studies have been performed in mice. The so-called acute and sub-acute regimens are commonly used. Both induce tissue striatal dopamine (DA) depletion and nigral neuron death. Tissue striatal DA depletion does not necessarily correlate with impairment of striatal dopaminergic functioning. In freely moving mice, systemic acute or sub-acute MPTP directly induces prolonged release of striatal DA. Such DA release may be considered the first step in MPTP-induced striatal DA depletion. Reportedly, neural stem cells improve symptoms in the MPTP model of PD by interacting with the MPTP-induced pathological nigrostriatal milieu.


Uncovering Spatiotemporal Heterogeneity of High-Grade Gliomas: From Disease Biology to Therapeutic Implications.
Glioblastomas (GBM) are the most common and aggressive tumors of the central nervous system. Rapid tumor growth and diffuse infiltration into healthy brain tissue, along with high intratumoral heterogeneity, challenge therapeutic efficacy and prognosis. A better understanding of spatiotemporal tumor heterogeneity at the histological, cellular, molecular, and dynamic levels would accelerate the development of novel treatments for this devastating brain cancer. Histologically, GBM is characterized by nuclear atypia, cellular pleomorphism, necrosis, microvascular proliferation, and pseudopalisades. At the cellular level, the glioma microenvironment comprises a heterogeneous landscape of cell populations, including tumor cells, non-transformed/reactive glial and neural cells, immune cells, mesenchymal cells, and stem cells, which support tumor growth and invasion through complex network crosstalk. Genomic and transcriptomic analyses of gliomas have revealed significant inter and intratumoral heterogeneity and insights into their molecular pathogenesis. Moreover, recent evidence suggests that diverse dynamics of collective motion patterns exist in glioma tumors, which correlate with histological features. We hypothesize that glioma heterogeneity is not stochastic, but rather arises from organized and dynamic attributes, which favor glioma malignancy and influences treatment regimens. This review highlights the importance of an integrative approach of glioma histopathological features, single-cell and spatially resolved transcriptomic and cellular dynamics to understand tumor heterogeneity and maximize therapeutic effects.


Amount of rhoticity in schwar and in vowel+/r/ in American English.
We present a preliminary study of the duration of rhoticity in coda-r words in American English. We note that traditional descriptions of American English phonology divide these words into two categories: words that end in a vowel followed by a separate /r/ segment (plus possible final consonant), and words that end in an r-colored vowel (plus possible final consonant). R-colored central vowels are termed here stressed and unstressed schwar. Recordings of 15 speakers of American English producing tokens containing these types of vowels were acoustically analysed, and the durations of the rhotic parts of the tokens were measured. The results demonstrated that stressed schwars were usually completely rhotic, unstressed schwars were usually not completely rhotic, but still had on average longer rhotic portions than the vowels+/r/. These findings have implications for intervention with /r/ disorders, which are encountered commonly in child speech disorders. It is argued that if these findings are borne out in a broader study, there might be no need to teach two different types of coda-r in therapy.


Effects of low-level laser therapy on osteoblastic bone formation and relapse in an experimental rapid maxillary expansion model.
The aim of this study was to investigate the effects of low-level laser therapy (LLLT) on osteoblastic bone formation and relapse during expansion of rat palatal sutures. Thirty-two Wistar rats were randomly allocated into two groups of 16 rats each. In the first group, LLLT was applied 4 days after expansion commenced. Seven days after expansion, retainers were applied for 10 days. The second group was similarly treated, with the exception of laser therapy. All rats were sacrificed on day 7 (n = 1) (the end of the expansion period; laser group (LG) 1 [LLLT 1] and control group (CG) 1 [control 1]) and day 17 (n = 8) (the end of the retention period; LG 2 [LLLT 2] and CG 2 [control 2]) for histological assessment. The LLLT 1 group had significantly higher numbers of osteoclasts than did the control 1 group (P = 0.036). No significant between-group difference in osteoblast cell or capillary numbers was evident when day 7 and 17 data were compared. Histologically, LLLT stimulated bone formation, as revealed by analysis after the retention period. LLLT during expansion may accelerate bone healing.


The prognostic role of BRAF and WNT pathways activation in kinase inhibitors-naïve clinical stage III cutaneous melanoma.
The results of local-regional advanced melanoma (stage III) management are still not satisfactory. Particularly, there is no personalized treatment in stage III melanoma patients due to the lack of useful classical pathological markers for prognostication of indolent or aggressive course of the disease. The aim of this study was to explore melanoma genomic landscape by means of the mutational profiling of 50 genes influencing carcinogenesis pathways in the randomly selected 93 kinase inhibitor-naïve (KI-naïve) stage III patients. The genomic alterations were found in 27 out of 50 tested genes and at least one pathogenic variant was detected in 77 out of 93 cases (82.7%). Survival rate was negatively affected by the presence of the somatic mutations in AKT1, ATM, CDH1 and SMARCB1, while the BRAF+ status in KI-naïve stage III population correlated with the longer median overall survival. Genomic alterations in WNT pathway correlated with extranodal adipocyte tissue involvement (P = 0.027) and higher number of metastatic lymph nodes (P = 0.045). In terms of survival, the Cox model confirmed the worse prognosis in patients with mutation in the WNT pathway [hazard ratio (HR) = 2.9, P = 0.017], and better prognosis in cases with mutations in BRAF pathway (HR = 0.5, P = 0.004). WNT/β-catenin pathway alteration was associated with more advanced/aggressive disease. From this perspective, the concept of blocking the activity of the WNT pathway in selected cases appears promising and complementary to the BRAF inhibition therapeutic option for the future.


Population and antenatal-based HIV prevalence estimates in a high contracepting female population in rural South Africa.
To present and compare population-based and antenatal-care (ANC) sentinel surveillance HIV prevalence estimates among women in a rural South African population where both provision of ANC services and family planning is prevalent and fertility is declining. With a need, in such settings, to understand how to appropriately adjust ANC sentinel surveillance estimates to represent HIV prevalence in general populations, and with evidence of possible biases inherent to both surveillance systems, we explore differences between the two systems. There is particular emphasis on unrepresentative selection of ANC clinics and unrepresentative testing in the population. HIV sero-prevalence amongst blood samples collected from women consenting to test during the 2005 annual longitudinal population-based serological survey was compared to anonymous unlinked HIV sero-prevalence amongst women attending antenatal care (ANC) first visits in six clinics (January to May 2005). Both surveillance systems were conducted as part of the Africa Centre Demographic Information System. Population-based HIV prevalence estimates for all women (25.2%) and pregnant women (23.7%) were significantly lower than that for ANC attendees (37.7%). A large proportion of women attending urban or peri-urban clinics would be predicted to be resident within rural areas. Although overall estimates remained significantly different, presenting and standardising estimates by age and location (clinic for ANC-based estimates and individual-residence for population-based estimates) made some group-specific estimates from the two surveillance systems more predictive of one another. It is likely that where ANC coverage and contraceptive use is widespread and fertility is low, population-based surveillance under-estimates HIV prevalence due to unrepresentative testing by age, residence and also probably by HIV status, and that ANC sentinel surveillance over-estimates prevalence due to selection bias in terms of age of sexual debut and contraceptive use. The results presented highlight the importance of accounting for unrepresentative testing, particularly by individual residence and age, through system design and statistical analyses.


MP-12 virus containing the clone 13 deletion in the NSs gene prevents lethal disease when administered after Rift Valley fever virus infection in hamsters.
Rift Valley fever virus (RVFV; Bunyaviridae, Phlebovirus) causes a range of illnesses that include retinitis, fulminant hepatitis, neurologic disease, and hemorrhagic fever. In hospitalized individuals, case fatality rates can be as high as 10-20%. There are no vaccines or antivirals approved for human use to prevent or treat severe RVFV infections. We previously tested the efficacy of the MP-12 vaccine strain and related variants with NSs truncations as a post-exposure prophylaxis in mice infected with wild-type pathogenic RVFV strain ZH501. Post-exposure efficacy of the rMP12-C13type, a recombinant MP-12 vaccine virus which encodes an in-frame truncation removing 69% of the NSs protein, resulted in 30% survival when administering the virus within 30 min of subcutaneous ZH501 challenge in mice, while the parental MP-12 virus conferred no protection by post-exposure vaccination. Here, we demonstrate uniform protection of hamsters by post-exposure vaccination with rMP12-C13type administered 6 h post-ZH501 infection while no efficacy was observed with the parental MP-12 virus. Notably, both the MP-12 and rMP12-C13type viruses were highly effective (100% protection) when administered 21 days prior to challenge. In a subsequent study delaying vaccination until 8, 12, and 24 h post-RVFV exposure, we observed 80, 70, and 30% survival, respectively. Our findings indicate that the rapid protective innate immune response elicited by rMP12-C13type may be due to the truncated NSs protein, suggesting that the resulting functional inactivation of NSs plays an important role in the observed post-exposure efficacy. Taken together, the data demonstrate that post-exposure vaccination with rMP12-C13type is effective in limiting ZH501 replication and associated disease in standard pre-exposure vaccination and post-challenge treatment models of RVFV infection, and suggest an extended post-exposure prophylaxis window beyond that initially observed in mice.


Chemical disease in humans: problems in comparative toxicology.
Difficulties in assessment of the comparative pharmacology of drugs now apply to the effects on humans of foreign compounds from the environment (xenobiotics). Perhaps the most striking change in perspective has been the recognition that a latency of several decades may precede the development of toxic effects. Xenobiotics may persist and accumulate in tissue stores, and estimates of biologically active doses are sometimes complicated by the presence of highly toxic trace contaminants and homologues that have varying biological activity. The effects of chemical exposure on the tissues may be obscured by the absence of the pathognomonic symptoms normally associated with the structural changes of disease. Interactions between two or more xenobiotics or between xenobiotics and genetic and metabolic variables may explain the lack of coherence between carefully defined laboratory observations and the clinical effects of enzyme-inducing xenobiotics. Since we have considerable evidence that biological processes are strikingly similar in different mammalian species, the toxicological significance to humans of enzyme induction and related processes requires careful evaluation.


Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) in the early stages of Alzheimer's disease.
Alzheimer's disease (AD) is one of the most common causes of dementia in the world. Patients with AD frequently complain of vision disturbances that do not manifest as changes in routine ophthalmological examination findings. The main causes of these disturbances are neuropathological changes in the visual cortex, although abnormalities in the retina and optic nerve cannot be excluded. Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) tests are commonly used in ophthalmology to estimate bioelectrical function of the retina and optic nerve. The aim of this study was to determine whether retinal and optic nerve function, measured by PERG and PVEP tests, is changed in individuals in the early stages of AD with normal routine ophthalmological examination results. Standard PERG and PVEP tests were performed in 30 eyes of 30 patients with the early stages of AD. The results were compared to 30 eyes of 30 normal healthy controls. PERG and PVEP tests were recorded in accordance with the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Additionally, neural conduction was measured using retinocortical time (RCT)--the difference between P100-wave latency in PVEP and P50-wave implicit time in PERG. In PERG test, PVEP test, and RCT, statistically significant changes were detected. In PERG examination, increased implicit time of P50-wave (P < 0.03) and amplitudes reductions in P50- and N95-waves (P < 0.0001) were observed. In PVEP examination, increased latency of P100-wave (P < 0.0001) was found. A significant increase in RCT (P < 0.0001) was observed. The most prevalent features were amplitude reduction in N95-wave and increased latency of P100-wave which were seen in 56.7% (17/30) of the AD eyes. In patients with the early stages of AD and normal routine ophthalmological examination results, dysfunction of the retinal ganglion cells as well as of the optic nerve is present, as detected by PERG and PVEP tests. These dysfunctions, at least partially, explain the cause of visual disturbances observed in patients with the early stages of AD.


Growth inhibitory activity of extracted material and isolated compounds from the fruits of Kigelia pinnata.
A study of the components of the fruits of Kigelia pinnata was undertaken to identify compounds with potential growth inhibitory activity against human melanoma cells, since extracts from the fruits of this plant have been described in traditional medicine to have application in the treatment of skin cancer and other skin ailments. A bioactivity-guided fractionation process yielded a number of crude fractions, which demonstrated cytotoxicity in vitro against human melanoma cells. Compounds isolated and identified included the isocoumarins, demethylkigelin (1) and kigelin (2), fatty acids, oleic (3) and heneicosanoic acids (4), the furonaphthoquinone, 2-(1-hydroxyethyl)-naphtho[2,3-b]furan-4,9-dione (5), and ferulic acid (6). A number of structurally related synthetic compounds were also tested using the MTT assay. The most potent series of these compounds, the furonaphthoquinones, also demonstrated a cytotoxic effect in two human breast cancer cell lines tested.


Understanding the interaction between human serum albumin and anti-bacterial/ anti-cancer compounds.
Human serum albumin (HSA) is the most important carrier of exogenous and endogenous molecules in human plasma. Understanding and characterizing the interaction of drugs with HSA has attracted enormous research interests from decades. The nature and magnitude of these bindings have direct consequence on drug delivery, pharmacokinetics, pharmacodynamics, therapeutic efficacy and drug designing. An overview of HSA and antibacterial/ anti-cancer ligands interaction is the need of the hour as these drugs together constitute more than half of the total drug consumption in the world. In this review, the information on the number of binding sites, binding strength, the nature of binding interactions and the location of binding sites of such drugs on the HSA are summarised. The effect of such drugs on the overall conformation, stability and function of HSA is also reviewed. This review will help to gain useful insights into the significance of the binding of anti-bacterial and anti-cancer drugs with plasma protein and the effect of binding on its overall distribution and pharmacological activities.


Abnormal uterine bleeding. Diagnostic value of hysteroscopy.
To determine the specificity, sensitivity and predictive value of hysteroscopic impression versus histological diagnosis of endometrial curettings in evaluating patients with abnormal uterine bleeding. In addition, to determine whether office hysteroscopy can eliminate hospital diagnostic dilatation and curettage for patients with abnormal uterine bleeding. A retrospective study of 556 patients who underwent hysteroscopy and dilatation and curettage for abnormal uterine bleeding between January 1995 and December 1998 at the Salmaniya Medical Complex in Bahrain. A comparison was made between hysteroscopic impression and histological examination. Out of 556 patients who were included in the study, 53 were diagnosed to have endometrial polyps hysteroscopically, however only 13 patients (24.5%) were confirmed to have polyps histologically. Hysteroscopy had revealed submucous leiomyoma in 33 women but none of these were diagnosed histologically. Hysteroscopy was highly specific for diagnosis of both endometrial hyperplasia and endometrial carcinoma (specificity was 85% for endometrial hyperplasia and 99.5% for endometrial carcinoma), however the sensitivity of hysteroscopy for diagnosing endometrial cancer was 40% and 30% for endometrial hyperplasia. Hysteroscopy was more sensitive than curettage in detecting endometrial polyps and submucous fibroids, but less sensitive than curettage in detecting endometrial hyperplasia and endometrial carcinoma. Hysteroscopy should be carried out in conjunction with curettage for evaluating women with abnormal uterine bleeding. Office hysteroscopy with directed biopsies could be carried out, to reduce hospital diagnostic dilatation and curettage.


Ferrous fumarate fortification of a chocolate drink powder.
An evaluation was made into the usefulness of ferrous fumarate as an iron fortificant for an experimental chocolate drink powder targetted to children and adolescents. Organoleptically ferrous furmarate was acceptable when the chocolate drink powder was reconstituted in milk or water that was heated to less than 80 degrees. Unacceptable colour changes occurred, however, when boiling milk or water were used. In human Fe absorption studies when the Fe compounds were added to the chocolate drink immediately before consumption, ferrous fumarate was 3.31% absorbed compared with 2.82% for ferrous sulphate and 2.11% for ferric pyrophosphate. When the Fe compounds were processed during the manufacture of the chocolate drink powder, the absorption of ferrous furmarate was 5.27%, ferrous sulphate 2.62% and ferric pyrophosphate 0.55%. Ascorbic acid had little or no effect on the absorption of ferrous furmarate. It is concluded that food processing can influence the relative absorption of fortification Fe and that, if not reconstituted with boiling milk or water, ferrous fumarate could be a useful compound for the fortification of chocolate drink powders.


Is neutralizing vitreal growth factors a viable strategy to prevent proliferative vitreoretinopathy?
Proliferative vitreoretinopathy (PVR) is a blinding disorder that occurs in eyes with rhegmatogenous retinal detachment and in eyes that have recently undergone retinal detachment surgery. There are presently no treatment strategies to reduce the risk of developing PVR in eyes with retinal detachment, and surgical intervention is the only option for eyes with retinal detachment and established PVR. Given the poor visual outcome associated with the surgical treatment of PVR, considerable work has been done to identify pharmacologic agents that could antagonize the PVR process. Intensive efforts to identify molecular determinants of PVR implicate vitreal growth factors. A surprise that emerged in the course of testing the 'growth factor hypothesis' of PVR was the existence of a functional relationship amongst growth factors that engage platelet-derived growth factor (PDGF) receptor α (PDGFRα), a receptor tyrosine kinase that is key to pathogenesis of experimental PVR. Vascular endothelial cell growth factor A (VEGF), which is best known for its ability to activate VEGF receptors (VEGFRs) and induce permeability and/or angiogenesis, enables activation of PDGFRα by a wide spectrum of vitreal growth factors outside of the PDGF family (non-PDGFs) in a way that triggers signaling events that potently enhance the viability of cells displaced into vitreous. Targeting these growth factors or signaling events effectively neutralizes the bioactivity of PVR vitreous and prevents PVR in a number of preclinical models. In this review, we discuss recent conceptual advances in understanding the role of growth factors in PVR, and consider the tangible treatment strategies for clinical application.


Staphylococcus aureus bloodstream infection: a pooled analysis of five prospective, observational studies.
Staphylococcus aureus bacteraemia is a common, often fatal infection. Our aim was to describe how its clinical presentation varies between populations and to identify common determinants of outcome. We conducted a pooled analysis on 3395 consecutive adult patients with S. aureus bacteraemia. Patients were enrolled between 2006 and 2011 in five prospective studies in 20 tertiary care centres in Germany, Spain, United Kingdom, and United States. The median age of participants was 64 years (interquartile range 50-75 years) and 63.8% were male. 25.4% of infections were associated with diabetes mellitus, 40.7% were nosocomial, 20.6% were caused by methicillin-resistant S. aureus (MRSA), although these proportions varied significantly across studies. Intravenous catheters were the commonest identified infective focus (27.7%); 8.3% had endocarditis. Crude 14 and 90-day mortality was 14.6% and 29.2%, respectively. Age, MRSA bacteraemia, nosocomial acquisition, endocarditis, and pneumonia were independently associated with death, but a strong association was with an unidentified infective focus (adjusted hazard ratio for 90-day mortality 2.92; 95% confidence interval 2.33 to 3.67, p < 0.0001). The baseline demographic and clinical features of S. aureus bacteraemia vary significantly between populations. Mortality could be reduced by assiduous MRSA control and early identification of the infective focus.


Proteomics and phylogenetic analysis of the cathepsin L protease family of the helminth pathogen Fasciola hepatica: expansion of a repertoire of virulence-associated factors.
Cathepsin L proteases secreted by the helminth pathogen Fasciola hepatica have functions in parasite virulence including tissue invasion and suppression of host immune responses. Using proteomics methods alongside phylogenetic studies we characterized the profile of cathepsin L proteases secreted by adult F. hepatica and hence identified those involved in host-pathogen interaction. Phylogenetic analyses showed that the Fasciola cathepsin L gene family expanded by a series of gene duplications followed by divergence that gave rise to three clades associated with mature adult worms (Clades 1, 2, and 5) and two clades specific to infective juvenile stages (Clades 3 and 4). Consistent with these observations our proteomics studies identified representatives from Clades 1, 2, and 5 but not from Clades 3 and 4 in adult F. hepatica secretory products. Clades 1 and 2 account for 67.39 and 27.63% of total secreted cathepsin Ls, respectively, suggesting that their expansion was positively driven and that these proteases are most critical for parasite survival and adaptation. Sequence comparison studies revealed that the expansion of cathepsin Ls by gene duplication was followed by residue changes in the S2 pocket of the active site. Our biochemical studies showed that these changes result in alterations in substrate binding and suggested that the divergence of the cathepsin L family produced a repertoire of enzymes with overlapping and complementary substrate specificities that could cleave host macromolecules more efficiently. Although the cathepsin Ls are produced as zymogens containing a prosegment and mature domain, all secreted enzymes identified by MS were processed to mature active enzymes. The prosegment region was highly conserved between the clades except at the boundary of prosegment and mature enzyme. Despite the lack of conservation at this section, sites for exogenous cleavage by asparaginyl endopeptidases and a Leu-Ser[downward arrow]His motif for autocatalytic cleavage by cathepsin Ls were preserved.


Dopamine autoreceptor regulation of the kinetic state of striatal tyrosine hydroxylase.
Tyrosine hydroxylase isolated from striatal synaptosomes exhibits biphasic Lineweaver-Burk kinetics for its tetrahydrobiopterin cofactor, consistent with multiple Km forms of the enzyme. Incubation of striatal synaptosomes with forskolin (EC50 0.45 microM) or dibutyryl cyclic AMP (EC50 1.2 mM), results in activation of tyrosine hydroxylase, isolated from these synaptosomes via conversion of the enzyme to a single low Km form (Km 40 microM). The activation of synaptosomal tyrosine hydroxylase by forskolin or dibutyryl cyclic AMP is not additive and is similar to activation seen with cyclic AMP-dependent protein kinase phosphorylation of purified tyrosine hydroxylase. The addition of dopamine (IC50 1.0 microM) (with nomifensine and pargyline) or apomorphine (IC50 30 nM) to the synaptosomal incubation medium blocks the activation of tyrosine hydroxylase by forskolin. This effect of dopamine and apomorphine can in turn be blocked by preincubation of the synaptosomes with the dopamine receptor antagonist haloperidol (IC50 30 nM and 4.5 nM, respectively) or chlorpromazine (IC50 50 nM versus apomorphine). In contrast to the forskolin data above, dopamine failed to block the activation of tyrosine hydroxylase by dibutyryl cyclic AMP. Addition of dopamine to the tyrosine hydroxylase assay, in amounts equivalent to that carried over from the synaptosomal incubation with the tyrosine hydroxylase, had no effect on forskolin-activated enzyme. The observations that dopamine and apomorphine can block forskolin activation of tyrosine hydroxylase, that this blockade can in turn be prevented by preincubation with haloperidol or chlorpromazine, and that the amount of dopamine required for blockade of forskolin activation in synaptosomes has no effect on tyrosine hydroxylase when added to the enzyme assay constitute the first clear evidence of a presynaptic dopamine receptor (autoreceptor). This autoreceptor regulates the activity of tyrosine hydroxylase by preventing or reversing cyclic AMP-dependent activation of the enzyme, probably through a decrease in the phosphorylation state of tyrosine hydroxylase. Failure of dopamine to block dibutyryl cyclic AMP activation of tyrosine hydroxylase suggests that, if forskolin and dibutyryl cyclic AMP activate tyrosine hydroxylase through identical changes in phosphorylation state, then autoreceptor regulation of tyrosine hydroxylase must occur through a decrease in cyclic AMP levels.


T-cell receptor and immunoglobulin genes are rearranged together in Abelson virus-transformed pre-B and pre-T cells.
We have assessed the state of rearrangement and expression of B- and T-cell antigen receptor genes in cells of Abelson murine leukemia virus-transformed thymomas and other tumors. We found that unrearranged TcR gamma genes are expressed, as are unrearranged C mu genes, in pre-T, pre-B, and myeloid cells. We also found TcR gamma genes rearranged and expressed in putative pre-T cells and in cells apparently committed to the B-cell lineage. This is in contrast to the data from more mature T- and B-cell tumors. We conclude that in immature lymphoid cells both immunoglobulin and TcR gamma genes are accessible for rearrangement. We discuss the implications of these observations for an understanding of the B-T lymphoid differentiation event.


Human access impacts biodiversity of microscopic animals in sandy beaches.
Whereas most work to understand impacts of humans on biodiversity on coastal areas has focused on large, conspicuous organisms, we highlight effects of tourist access on the diversity of microscopic marine animals (meiofauna). We used a DNA metabarcoding approach with an iterative and phylogeny-based approach for the taxonomic assignment of meiofauna and relate diversity patterns to the numbers of tourists accessing sandy beaches on an otherwise un-impacted island National Park. Tourist frequentation, independently of differences in sediment granulometry, beach length, and other potential confounding factors, affected meiofaunal diversity in the shallow "swash" zone right at the mean water mark; the impacts declined with water depth (up to 2 m). The indicated negative effect on meiofauna may have a consequence on all the biota including the higher trophic levels. Thus, we claim that it is important to consider restricting access to beaches in touristic areas, in order to preserve biodiversity.


Contractile dysfunction of atrial myocardium from endotoxin-shocked guinea pigs.
Atrial muscle isolated from guinea pigs subjected to Escherichia coli endotoxin shock was used to study the myocardial changes associated with this experimental disease state. Isometric contractile tension and its first derivative (dT/dt) consistently were depressed by about 45% in muscle from the shock group (P less than 0.001), but contraction time intervals of the shock tissues were not significantly altered. The inotropic deficit of shock was completely antagonized by high concentrations of Ca2+ (greater than 4.5 mM). However, the maximal positive inotropic response to increased frequency of stimulation (0.1-2.2 Hz) only partially antagonized shock-induced cardiac depression. Heart muscle from shocked animals exhibited increased sensitivity to the negative inotropic effects of Mn2+, low Ca2+, and gentamicin; recovery from the depressant actions of these agents was prolonged 3.6- to 4.8-fold in shock. However, the negative inotropic potency of slow Ca2+ channel blockers, D 600 and nifedipine, was unaffected by shock. Similarly, studies with an isoproterenol-activated slow Ca2+ channel technique demonstrated equivalent inotropic responses of shock and control heart muscle. Present data provide evidence for a disruption of myocardial Ca2+ metabolism associated with endotoxin-induced inotropic depression of the heart but suggest that slow Ca2+ channels of the sarcolemma remain functional in this disease state.


Athletic pubalgia and "sports hernia": optimal MR imaging technique and findings.
Groin injuries are common in athletes who participate in sports that require twisting at the waist, sudden and sharp changes in direction, and side-to-side ambulation. Such injuries frequently lead to debilitating pain and lost playing time, and they may be difficult to diagnose. Diagnostic confusion often arises from the complex anatomy and biomechanics of the pubic symphysis region, the large number of potential sources of groin pain, and the similarity of symptoms in athletes with different types or sites of injury. Many athletes with a diagnosis of "sports hernia" or "athletic pubalgia" have a spectrum of related pathologic conditions resulting from musculotendinous injuries and subsequent instability of the pubic symphysis without any finding of inguinal hernia at physical examination. The actual causal mechanisms of athletic pubalgia are poorly understood, and imaging studies have been deemed inadequate or unhelpful for clarification. However, a large-field-of-view magnetic resonance (MR) imaging survey of the pelvis, combined with high-resolution MR imaging of the pubic symphysis, is an excellent means of assessing various causes of athletic pubalgia, providing information about the location of injury, and delineating the severity of disease. Familiarity with the pubic anatomy and with MR imaging findings in athletic pubalgia and in other confounding causes of groin pain allows accurate imaging-based diagnoses and helps in planning treatment that targets specific pathologic conditions.


The MAPK pathway is a predominant regulator of HLA-A expression in esophageal and gastric cancer.
Downregulation of HLA class I expression may contribute to a poor prognosis in cancer patients. There is limited information about epigenetic and oncogenic regulation of HLA class I, and multiple mechanisms may be involved. In the current study, we examined the relationship between the HER2-signaling pathway (MAPK and PI3K-Akt) and the expression of HLA class I and Ag-processing machinery (APM) components. A panel of gastric and esophageal cancer cell lines was treated with wortmannin as an Akt-signal inhibitor; the MAPK signal inhibitor PD98059; lapatinib, which inhibits both the epidermal growth factor receptor and HER2 tyrosine kinase; or siRNA for MAPK. The levels of HER2-signaling molecules, APM components, and HLA class I were evaluated by Western blot, quantitative PCR, and flow cytometry. Resected gastric tumor tissues (n = 102) were analyzed for p-Erk and HLA class I expression by immunohistochemistry. As a result, inhibition of the MAPK pathway induced upregulation of HLA-A02 and HLA-A24 expression in parallel with an increase in APM components and enhanced target sensitivity to tumor Ag-specific CTL lysis. HLA-A expression was predominantly regulated by the MAPK pathway, but it was also influenced, in part, by the Akt pathway. There was a strong inverse correlation between p-Erk expression and HLA class I expression in clinical tumor samples. In conclusion, HLA-A expression is predominantly regulated by the MAPK pathway in gastric and esophageal cancer.


Hypotensive Transfusion Reaction Treated With Vasopressin in a Patient Taking an Angiotensin-Converting Enzyme Inhibitor: A Case Report.
Hypotensive transfusion reactions, which account for almost 3% of all transfusion reactions, are associated with patients treated with angiotensin-converting enzyme inhibitors. The current hypothesis suggests that they are caused by bradykinin-induced vasodilation in the absence of allergic, hemolytic, or septic mechanisms. The hypotension observed frequently is unresponsive to conventional therapy with catecholamines. The suggested intraoperative management includes cessation of transfusion and washing red blood cells before blood replacement. We present a patient experiencing a severe intraoperative hypotensive transfusion reaction, unresponsive to epinephrine and norepinephrine, in whom we were able to restore blood pressure and continue the transfusion of blood and plasma by infusing vasopressin.


Predicting Tacit Coordination Success Using Electroencephalogram Trajectories: The Impact of Task Difficulty.
In this study, we aim to develop a machine learning model to predict the level of coordination between two players in tacit coordination games by analyzing the similarity of their spatial EEG features. We present an analysis, demonstrating the model's sensitivity, which was assessed through three conventional measures (precision, recall, and f1 score) based on the EEG patterns. These measures are evaluated in relation to the coordination task difficulty, as determined by the coordination index (CI). Tacit coordination games are games in which two individuals are requested to select the same option out of a closed set without the ability to communicate. This study aims to examine the effect of the difficulty of a semantic coordination task on the ability to predict a successful coordination between two players based on the compatibility between their EEG signals. The difficulty of each of the coordination tasks was estimated based on the degree of dispersion of the different answers given by the players reflected by the CI. The classification of the spatial distance between each pair of individual brain patterns, analyzed using the random walk algorithm, was used to predict whether successful coordination occurred or not. The classification performance was obtained for each game individually, i.e., for each different complexity level, via recall and precision indices. The results showed that the classifier performance depended on the CI, that is, on the level of coordination difficulty. These results, along with possibilities for future research, are discussed.


Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men.
Hypogonadism or Testosterone Deficiency (TD) in adult men as defined by low levels of serum testosterone accompanied by characteristic symptoms and/or signs as detailed further on can be found in long-recognized clinical entities such as Klinefelter syndrome, Kallmann syndrome, pituitary or testicular disorders, as well as in men with idiopathic, metabolic or iatrogenic conditions that result in testosterone deficiency. These recommendations do not encompass the full range of pathologies leading to hypogonadism (testosterone deficiency), but instead focus on the clinical spectrum of hypogonadism related to metabolic and idiopathic disorders that contribute to the majority of cases that occur in adult men.


Dynamics of wet granular hexagons.
The collective behavior of vibrated hexagonal disks confined in a monolayer is investigated experimentally. Due to the broken circular symmetry, hexagons prefer to rotate upon sufficiently strong driving. Due to the formation of liquid bridges, short-ranged cohesive interactions are introduced upon wetting. Consequently, a nonequilibrium stationary state with the rotating disks self-organized in a hexagonal structure arises. The bond length of the hexagonal structure is slightly smaller than the circumdiameter of a hexagon, indicating geometric frustration. This investigation provides an example where the collective behavior of granular matter is tuned by the shape of individual particles.


Multiple primary epidermoid carcinomas of the upper aerodigestive tract.
In a series of 405 patients with epidermoid carcinoma of the head and neck, 52 patients (13%) developed multiple epidermoid carcinomas of the upper aerodigestive tract. Subsequent primary tumors developed with nearly equal frequency in the head and neck, lung, and esophagus. Forty of the patients developed a subsequent primary carcinoma within five years of the first. Thirty-eight (73%) of the patients who developed a subsequent primary carcinoma survived less than two years from its diagnosis. The majority (34/50) of the patients died from the subsequent primary carcinoma. We recommend that panendoscopy and an esophagogram be performed on initial evaluation of patients with head and neck cancer. A thorough reexamination is warranted if new symptoms or signs develop.


[Schizophrenia: neurodevelopmental disorder or degenerative brain process?].
In the last two decades schizophrenia is viewed increasingly as a neurodevelopmental (ND) disorder; as indicators are discussed f.e. premorbid personality, behaviour anomalies, premorbid somatic signs, deviations shown by brain imaging methods, neuropathological findings or neuropsychological deficits. Premorbid personality and behaviour anomalies have to be distinguished from precursor syndromes (prodromes and outpost syndromes), preceding the first psychotic episode many years. Moreover, only a minority of patients, later developing schizophrenia, reveal abnormal premorbid personality traits. Explanations why clinical expression of the disorder is delayed until adult life or at least adolescence, remain speculative. Findings of neocortical and limbic maldevelopment, e.g. in parahippocampal cortex, are hitherto not yet conclusive. As an argument for the ND hypothesis is claimed that ventricular enlargement already is present at the onset of positive symptoms and does not progress on follow-ups. But, if a ND disorder would have caused the ventricular enlargement, cranial volume and head size must be decreased, what is not the case in schizophrenia. Furtheron, there are findings of progressive increase in ventricular size and also of gliosis, especially in subcortical and periventricular areas. Anomalies of cerebral asymmetry; also distinct ND brain anomalies such as cavum septi pellucidi or dysgenesis of corpus callosum do not occur more frequently than expected in schizophrenia. As to the rate of obstetric complications (OCs) and viral infections sufficiently reliable data are missing; the great majority of schizophrenics have no OCs. Altogether, attempts to correlate brain findings, regarded as expression of an aberrant brain development with clinical subgroups of schizophrenia, were not very successful. This is also valid for ND concepts confined to male, early onset or sporadic schizophrenias. Only a distinct psychopathological remission type with the component of an irreversible pure dynamic-cognitive deficiency can be correlated with distinct brain imaging changes. There are associations between brain imaging and psychopathological findings and also between the progression of neuroradiological and psychopathological changes. The investigation of the long-term course of schizophrenia with progression to different residual syndromes has shown some hints that schizophrenia certainly is not a neurodegenerative process in the usual sense, but may be a special neuroregressive illness in the majority of cases. Data, relevant for this assumption are, that the disorder in 78% shows no full remitting courses; that the progression concerns only 5 until 10 years after onset; that chronic defect psychoses can remit still after decades of course to non-psychotic pure deficiency syndromes; that some cases (15%) can progress even after years and decades of remitting course and, finally, that altogether no correlation exists between the duration of course and outcome. The data prove that schizophrenia is not an illness progressing continuously over the whole lifelong course in the sense of a primary neurodegenerative process, but rather a disorder, progressing transiently in brief stages and afterwards coming to a standstill. That schizophrenia is not neurodegenerative in the traditional sense, does not mean that it is a ND disorder. This applies only to a small subgroup, while the assumption of a non-ND subgroup with an only transitory, in short periods advancing special regressive brain process seems to be plausible. There are analogies to organic brain disorders . Hence ensues the interpretation of the brain findings in a subgroup of schizophrenia as "premature, locally accentuated involution of advanced age". The argument that at time of the first psychotic episode the brain changes already have developed without progressing in the further course, can be refuted by neuropsychiatric observations in brain atrophic processes and the knowledge of the true onset of schizophrenia with prodromes and outpost syndromes several years before the first psychotic manifestation with positive symptoms.


A Cluster-Randomized Trial on Small Incentives to Promote Physical Activity.
There has been limited research investigating whether small financial incentives can promote participation, behavior change, and engagement in physical activity promotion programs. This study evaluates the effects of two types of small financial incentives within a physical activity promotion program of a Swiss health insurance company. Three-arm cluster-randomized trial comparing small personal financial incentives and charity financial incentives (10 Swiss Francs, equal to US$10.40) for each month with an average step count of >10,000 steps per day to control. Insureds' federal state of residence was the unit of randomization. Data were collected in 2015 and analyses were completed in 2018. German-speaking insureds of a large health insurer in Switzerland were invited. Invited insureds were aged ≥18 years, enrolled in complementary insurance plans and registered on the insurer's online platform. Primary outcome was the participation rate. Secondary outcomes were steps per day, the proportion of participant days in which >10,000 steps were achieved and non-usage attrition over the first 3 months of the program. Participation rate was 5.94% in the personal financial incentive group (OR=1.96, 95% CI=1.55, 2.49) and 4.98% in the charity financial incentive group (OR=1.59, 95% CI=1.25, 2.01) compared with 3.23% in the control group. At the start of the program, the charity financial group had a 12% higher chance of walking 10,000 steps per day than the control group (OR=1.68, 95% CI=1.23, 2.30), but this effect dissipated after 3 months. Steps per day and non-usage attrition did not differ significantly between the groups. Small personal and charity financial incentives can increase participation in physical activity promotion programs. Incentives may need to be modified in order to prevent attrition and promote behavior change over a longer period of time. This study is registered at www.isrctn.com ISRCTN24436134.


Involvement of amfC in physiological and morphological development in Streptomyces coelicolor A3(2).
amfC plays a regulatory role in aerial mycelium formation in Streptomyces griseus and is distributed widely among Streptomyces species. Disruption of the chromosomal amfC gene in Streptomyces coelicolor A3(2) severely reduced formation of aerial hyphae, indicating that amfC is important in morphological development. In addition, the disruption caused S. coelicolor A3(2) M130 to produce much less actinorhodin, and to produce undecylprodigiosin at a later stage of growth, indicating that amfC also regulates secondary metabolism. S1 nuclease mapping showed that transcription of actII-ORF4, the pathway-specific transcriptional activator in the act gene cluster, was greatly reduced in the amfC disruptants. The defect in secondary metabolite formation was suppressed or overcome by a mutation in sre-1. Consequently, an amfC-disrupted strain derived from S. coelicolor A3(2) M145, an actinorhodin-overproducing strain due to the sre-1 mutation, still produced a large amount of actinorhodin. Extra copies of amfC in strains M130 and M145 did not change spore-chain morphology or secondary metabolite formation. However, the spores in these strains remained white even after prolonged incubation. Since only spore pigmentation was affected, all known whi genes, except whiE, responsible for the polyketide spore pigment formation, were assumed to function normally. S1 nuclease mapping showed that transcription of whiEP1, one of the promoters in the whiE locus, was reduced in S. coelicolor A3(2) containing extra copies of amfC. Introducing amfC into several other Streptomyces species, such as Streptomyces lividans, Streptomyces lavendulae and Streptomyces lipmanii, also abolished spore pigment formation. An increase in the amount of AmfC appeared to disturb the maturation of spores.


Evaluation of protection conferred by a vaccination program based on the H120 and CR88 commercial vaccines against a field variant of avian infectious bronchitis virus.
Due to serotype variations among different avian infectious bronchitis viruses isolated in Tunisia since 2000, protection of chicks, especially broiler flocks, with Mass H120 vaccine often fails. Therefore, association of CR88 (793B type) with H120 vaccines was used for better response. Challenge experiments were then conducted to evaluate tracheal and renal cross-protection in chickens immunized via nasal and eye drops. Conferred protection was measured by clinical signs and macroscopic lesions observed, based on scores attributed according to their severities. The results showed a low protection conferred by H120 alone, as vaccination did not reduce tracheal and kidney lesions (70% scored as 3) after TN20/00 virus challenge, which also led to 10% mortality. Conversely, the challenge results indicated that the combination of the 2 strains (H120/CR88) allow high protection. Based on the results of the challenge experiments, a vaccination protocol coupling CR88 to H120 was applied for industrial broiler flocks. Clinical observations and serological results confirmed that association of heterologous serotypes (H120 and CR88 vaccines) increased the levels of protection against infectious bronchitis viruses compared with the H120 vaccine given alone.


An automated dosimetry system for testing whole-body ultraviolet phototherapy cabinets.
A new technique is described for automated ultraviolet dosimetry within whole-body phototherapy cabinets. A dual-head detector system has been designed, permitting simultaneous assessment of irradiance levels and radiant intensities from individual lamps. One detector is used in combination with a diffuser/filter system for the measurement of irradiance and the other is mounted at the end of a slit collimator to provide a measurement which can be related to the radiant intensities of the individual lamps. These quantities are derived from 800 separate measurements made during rotation of the detector head around a 360 degrees circle at a fixed height and position within the cabinet under remote computer software control. The device has advantages compared with standard techniques, enabling measurements to be made without the need for a person to be present in the cabinet. A full set of measurements is made with minimal switching of the power supply to the lamps. This simplifies the assessment and reduces the uncertainty from variation in output after the lamps are switched on. Variations in irradiance with orientation for the smaller phototherapy cabinets are clearly demonstrated. Plots of data from the collimated detector show peaks corresponding to the lamps and the surrounding reflectors. The plots enable failed lamps to be detected and peak values can be related to radiant intensities of individual lamps.


Addition of olive oil to diet of rats with mild pre-gestational diabetes impacts offspring β-cell development.
Maternal diabetes impairs fetal development and increases the risk of metabolic diseases in the offspring. Previously, we demonstrated that maternal dietary supplementation with 6% of olive oil prevents diabetes-induced embryo and fetal defects, in part, through the activation of peroxisome proliferator-activated receptors (PPARs). In this study, we examined the effects of this diet on neonatal and adult pancreatic development in male and female offspring of mothers affected with pre-gestational diabetes. A mild diabetic model was developed by injecting neonatal rats with streptozotocin (90 mg/kg). During pregnancy, these dams were fed a chow diet supplemented or not with 6% olive oil. Offspring pancreata was examined at day 2 and 5 months of age by immunohistochemistry followed by morphometric analysis to determine number of islets, α and β cell clusters and β-cell mass. At 5 months, male offspring of diabetic mothers had reduced β-cell mass that was prevented by maternal supplementation with olive oil. PPARα and PPARγ were localized mainly in α cells and PPARβ/δ in both α and β cells. Although Pparβ/δ and Pparγ RNA expression showed reduction in 5-month-old male offspring of diabetic rats, Pparβ/δ expression returned to control levels after olive-oil supplementation. Interestingly, in vitro exposure to oleic acid (major component of olive oil) and natural PPAR agonists such as LTB4, CPC and 15dPGJ2 also significantly increased expression of all Ppars in αTC1-6 cells. However, only oleic acid and 15dPGJ2 increased insulin and Pdx-1 expression in INS-1E cells suggesting a protective role in β-cells. Olive oil may be considered a dietary supplement to improve islet function in offspring of affected mothers with pre-gestational diabetes.


Unsupervised segmentation of heel-strike IMU data using rapid cluster estimation of wavelet features.
When undertaking gait-analysis, one of the most important factors to consider is heel-strike (HS). Signals from a waist worn Inertial Measurement Unit (IMU) provides sufficient accelerometric and gyroscopic information for estimating gait parameter and identifying HS events. In this paper we propose a novel adaptive, unsupervised, and parameter-free identification method for detection of HS events during gait episodes. Our proposed method allows the device to learn and adapt to the profile of the user without the need of supervision. The algorithm is completely parameter-free and requires no prior fine tuning. Autocorrelation features (ACF) of both antero-posterior acceleration (aAP) and medio-lateral acceleration (aML) are used to determine cadence episodes. The Discrete Wavelet Transform (DWT) features of signal peaks during cadence are extracted and clustered using Swarm Rapid Centroid Estimation (Swarm RCE). Left HS (LHS), Right HS (RHS), and movement artifacts are clustered based on intra-cluster correlation. Initial pilot testing of the system on 8 subjects show promising results up to 84.3%±9.2% and 86.7%±6.9% average accuracy with 86.8%±9.2% and 88.9%±7.1% average precision for the segmentation of LHS and RHS respectively.


High-resolution mapping of a novel rat blood pressure locus on chromosome 9 to a region containing the Spp2 gene and colocalization of a QTL for bone mass.
Through linkage analysis of the Dahl salt-sensitive (S) rat and the spontaneously hypertensive rat (SHR), a blood pressure (BP) quantitative trait locus (QTL) was previously located on rat chromosome 9. Subsequent substitution mapping studies of this QTL revealed multiple BP QTLs within the originally identified logarithm of odds plot by linkage analysis. The focus of this study was on a 14.39 Mb region, the distal portion of which remained unmapped in our previous studies. High-resolution substitution mapping for a BP QTL in the setting of a high-salt diet indicated that an SHR-derived congenic segment of 787.9 kb containing the gene secreted phosphoprotein-2 (Spp2) lowered BP and urinary protein excretion. A nonsynonymous G/T polymorphism in the Spp2 gene was detected between the S and S.SHR congenic rats. A survey of 45 strains showed that the T allele was rare, being detected only in some substrains of SHR and WKY. Protein modeling prediction through SWISSPROT indicated that the predicted protein product of this variant was significantly altered. Importantly, in addition to improved cardiovascular and renal function, high salt-fed congenic animals carrying the SHR T variant of Spp2 had significantly lower bone mass and altered bone microarchitecture. Total bone volume and volume of trabecular bone, cortical thickness, and degree of mineralization of cortical bone were all significantly reduced in congenic rats. Our study points to opposing effects of a congenic segment containing the prioritized candidate gene Spp2 on BP and bone mass.


Marfan syndrome affecting four generations of a family without ocular involvement.
Thirty eight relatives of a patient with Marfan syndrome were screened for the presence of this disorder. Marfan syndrome was newly diagnosed in living members of 4 generations in this family without evidence of ocular abnormality in any. After screening, 10 relatives were newly diagnosed as having definite, and 5 relatives as having possible, Marfan syndrome. Family screening has drawbacks as well as benefits for the patients. The main benefit is the identification and treatment of previously undiagnosed patients at risk of cardiac complications which are the major cause of mortality. The drawbacks include employment problems created for patients with Marfan syndrome as a direct consequence of our screening programme and the anxiety induced in previously asymptomatic family members who did not realize that they could be at risk. Also, the 4 adult patients with possible Marfan syndrome found it difficult to accept that a definite diagnosis could not be reached after they had been invited to attend a screening programme for a serious genetic disorder. This report illustrates the importance of screening all the relatives of a patient with Marfan syndrome to identify previously undiagnosed cases. However, before screening a family, the physician should be aware that a clear diagnosis may not be reached in all patients, and financial, psychological or social problems may arise as a result of the screening programme.


Different kinds of information affect word learning in the preschool years: the case of part-term learning.
Two studies investigated how preschool children's interpretations of novel words as names for parts of objects were affected by 3 kinds of information: (a) whole object familiarity, (b) whole part juxtaposition, and (c) syntactic information indicating possession. Study 1 tested 3- to 4-year-olds and found that although there was evidence that all information affected children's part-term interpretations to some extent, they were most systematic when provided with 2 or more kinds of information. Study 2 adapted the procedure for use with 2.5-year-olds and found the same general pattern of results. Variations across studies were found that may reflect changes in how different kinds of information affect word learning with development.


Geometrically customizable alginate hydrogel nanofibers for cell culture platforms.
The extracellular matrix (ECM) is composed of a hydrogel derived from natural polymers with an anisotropic structure that plays an important role in cell proliferation and differentiation. Alginates-algae-derived polysaccharides-form into the hydrogel, and can be potentially used for the synthesis of cell scaffold materials following the addition of calcium ions. However, to date, the synthesis of anisotropic alginate hydrogels has not been reported. Fibrillization by electrospinning is a simple method used to prepare anisotropic materials. However, it is difficult to fabricate pure alginate nanofibers by electrospinning without adding other polymers. In this study, we exploited the electrospinning method to prepare core-shell fibers in which alginate was encapsulated in the shell of a water-soluble polymer. Anisotropically aligned fibers were obtained with the use of a collector at a high-rotational speed. The gelation of alginate with calcium ions and the following washing process of the shell polymer were carried out and successfully formed pure and aligned alginate fibers. By immobilizing fibronectin on the fabricated alginate fibers and by culturing the cells, it was possible to control cell elongation in the fiber direction. We also successfully prepared a fibrous hydrogel on a wire that was used to construct a conduit-like structure after cells were cultured on it. This material provides a biomimetic cellular microenvironment that can be applied as a three-dimensional platform for cell culture.


Markarian 348: a tidally disturbed seyfert galaxy.
Combined optical and radio images of galaxies can provide new insights into the sizes, masses, and possible evolution of these objects. Deep optical and neutral hydrogen images of Markarian 348, a type 2 Seyfert galaxy, show that it is a gigantic spiral (perhaps the largest known non-cluster galaxy). Measurements of the neutral hydrogen velocity field and spiral structure, and detection of an optical "tidal plume," all provide evidence that it has been subject to tidal disruption. The measured velocities yield a mass-to-light ratio for this object (within a radius of 130 kiloparsecs from its nucleus) that is similar to the ratio found for the inner regions of most galaxies of similar type. This is one of the few cases where detailed velocity measurements have demonstrated that a galaxy with an active nucleus has been subject to extensive tidal perturbation.


Strategies to manage cognitive dissonance when experiencing resistiveness to care in people living with dementia: A qualitative study.
To explore the experiences of healthcare personnel when they face resistiveness to care in people living with dementia in nursing homes. The study has a qualitative explorative design. Three focus group interviews were conducted in June 2019. A total of 16 nurses and other healthcare personnel employed in three different nursing homes participated. A semi-structured interview guide was used during the focus group interviews. Data were transcribed verbatim and analysed using an inductive qualitative content analysis. The analysis generated one overarching category-'Tension when facing resistiveness to care', which describes the discomfort healthcare personnel experienced when confronted with resistiveness to care in people with dementia-and two other categories: 'Attitude change' and 'Changing behaviour', which describes their strategies to reduce and/or manage the discomfort. Four subcategories-'Changing the mindset', Conceptual shift', Stepping back' and 'Not giving up'-described the actions taken by healthcare personnel to manage or reduce their cognitive dissonance. The strategies used to manage or reduce cognitive dissonance provide a new understanding of how healthcare personnel choose to approach resistiveness to care in people living with dementia. This study addresses cognitive dissonance, a discomfort experienced by healthcare personnel when facing resistiveness to care from people living with dementia. To reduce their dissonance, the participants employed several strategies, including coercive measures, when providing care. The theory of cognitive dissonance may help explain why healthcare personnel sometimes choose to employ coercive measures while providing care.


Controlled trial of antituberculous chemotherapy in Crohn's disease: a five year follow up study.
It has been suggested that Mycobacterium paratuberculosis is the cause of Crohn's disease. In a previous report the immediate effect of two years treatment with antituberculous chemotherapy showed no clinical benefit. To assess both the immediate and longer term effect of treatment on the disease. Patients were followed for five years from their date of entry to the study. One hundred and thirty patients entered the initial study, and of these 111 (81%) were followed regularly. Overall, there was no evidence of consistent benefit or disadvantage from antituberculous chemotherapy in any of the assessments made, including the number of acute relapses, surgical episodes, hospital admissions, disease activity, blood tests, or medication required for Crohn's disease during the follow up period. The absence of any benefit at the end of the initial two year trial period, and during the three year subsequent follow up, fails to support the hypothesis that mycobacteria play an important part in the pathogenesis of Crohn's disease, or that antituberculous chemotherapy may be of benefit.


Genetic Liability for Depression, Social Factors and Their Interaction Effect in Depressive Symptoms and Depression Over Time in Older Adults.
The objectives of this study were to investigate the effect of genetic and social factors on depressive symptoms and depression over time and to test whether social factors moderate the relationship between depressive symptoms and its underlying genetics in later life. The study included 2,279 participants with a mean follow-up of 15 years from the Longitudinal Aging Study Amsterdam with genotyping data. The personal genetic loading for depression was estimated for each participant by calculating a polygenic risk scores (PRS-D), based on 23,032 single nucleotide polymorphisms associated with major depression in a large genome-wide association study. Partner status, network size, received and given emotional support were assessed via questionnaires and depressive symptoms were assessed using the CES-D Scale. A CES-D Scale of 16 and higher was considered as clinically relevant depression. Higher PRS-D was associated with more depressive symptoms whereas having a partner and having a larger network size were independently associated with less depressive symptoms. After extra adjustment for education, cognitive function and functional limitations, giving more emotional support was also associated with less depressive symptoms. No evidence for gene-environment interaction between PRS-D and social factors was found. Similar results were found for clinically relevant depression. Genetic and social factors are independently associated with depressive symptoms over time in older adults. Strategies that boost social functioning should be encouraged in the general population of older adults regardless of the genetic liability for depression.


Lectin receptors of rods and cones. Visualization by fluorescent label.
The binding of eight fluorescence-labeled lectins to visual cells was investigated. Concanavalin A (Con A) (specific for oligosaccharides containing mannose) bound evenly to the surfaces of rod outer segments (ROSs) from frog, cattle, goldfish, and turtle (Pseudemys). In frog, binding was observed on the inner segment, with intensifications at the inner/outer segment junction and in the region of the nucleus. No binding occurred on the surfaces of ROS discs. In 0.1% Triton X-100, rods formed convoluted tubular structures that bound Con A to their surfaces. Isolated cone outer segments (COSs) showed uniform fluorescence as compared with the inner segments, which displayed only surface labeling. Only lectins with an affinity for fucose (UeA, LTA) failed to bind to the ROSs and COS. Lectins with an affinity for oligosaccharides containing galactose (RCA-120, RCA-60, and PNA) bound hardly at all to the rod inner segments. Both WGA (N-acetyl glucosamine) and SBA (N-acetyl galactosamine and galactose) bound indiscriminately to all ROSs, whereas PNA bound preferentially to the accessory cones.


Behavioral changes associated with fever in transition dairy cows.
Dairy cows are often diagnosed with fever without showing clinical symptoms of disease. The aim of this study was to investigate changes in feeding, social, and lying behaviors of cows with fever but without clinical disease, as compared with healthy cows. After parturition, dairy cows of mixed parities were housed in a dynamic group of 20. In the freestall pen, cows had access to 12 electronic feed bins, 2 electronic water bins, and 24 lying stalls. Feeding and social behaviors were recorded using the electronic feed bins, and lying behaviors were measured using electronic data loggers attached to the cow. Rectal body temperature was assessed on a daily basis, and fever defined as a body temperature >39.5°C. All cows were examined for metritis every third day after calving, and all other diseases (e.g., mastitis, ketosis) were diagnosed as per farm protocol. Cows with multiple days of fever (n = 8) and cows with 1 d of fever (n = 18) that were not diagnosed with a clinical disease were compared with a matched sample of healthy cows (i.e., cows that were not clinically ill and never had a fever recorded) of the same parity (categorized as primiparous vs. multiparous). Feeding, social, and lying behaviors were compared for the first 2 d of fever in cows with multiple days of fever, and the day of fever in cows with 1 d of fever. Cows of both fever groups spent less time feeding compared with controls (135 vs. 181 ± 7.6 min/d for multiple fever days, and 158 vs. 185 ± 9.7 min/d for 1 d of fever). Cows with 1 d of fever ate at a faster rate (109 vs. 91 ± 5 g/min) and had a lower number of replacements at the feed bunk (actor replacements: 9.7 vs. 14.6 ± 1.7 no./d; reactor replacements: 11.1 vs. 15.9 ± 1.6 no./d) compared with healthy controls. Overall, cows with fever showed behavioral changes such as decreased feeding time that are consistent with sickness responses described in other species.


Effect of phorbol myristate acetate on the recovery of spontaneous and ultraviolet light-induced 6-thioguanine and ouabain-resistant Chinese hamster cells.
12-0-Tetradecanoyl-phorbol-13-acetate (TPA) and phorbol were tested in Chinese hamster cells for their effects on mutagenesis (resistance to 6-thioguanine and to ouabain), DNA repair, and survival after ultraviolet (UV) irradiation. Recovery of 6-thioguanine- and ouabain-resistant colonies was significantly increased by TPA treatment and, to a lesser extent, by phorbol in UV-irradiated cells. Moreover, maximum enhancement of recoverable UV-induced 6-thioguanine- and ouabain-resistant mutants occurred when TPA was present after the mutation "expression" time and after the completion of DNA repair. This eenhancement effect, while persisting up to 18 days in the 6-thioguanine mutation system, was maximal when TPA was applied about 2 days after UV irradiation for the ouabain resistance mutation system. No significant decrease in cell survival was noted after post-UV treatment with TPA or phorbol, under conditions where there was a slight but nonspecific inhibition of unscheduled DNA repair synthesis. These results do not support the hypothesis that the tumor-promoting activity of TPA is due to its ability to inhibit "error-free" excision repair. The results are, however, consistent with a "two-stage" hypothesis of carcinogenesis which includes mutational and epigenetic mechanisms to explain the initiation and promotion phases.


Prognostic value of Doppler-derived mitral deceleration time in postinfarction patients with left ventricular ejection fractions of 35% or more.
Short Doppler-derived mitral deceleration time of early filling has been proved to be an independent predictor of poor prognosis in patients with left ventricular dysfunction. However, the prognostic value of Doppler-derived mitral deceleration time in postinfarction patients without overt left ventricular dysfunction is poorly understood. A total of 27 survivors of acute myocardial infarction with left ventricular ejection fractions of 35% or more, as determined by radionuclide ventriculography, were prospectively studied. Doppler study was performed 5 to 7 days after the index infarction. The patients were divided into two groups. Group A included 10 patients whose mitral deceleration time was 125 msec or less and group B consisted of 17 patients whose mitral deceleration time was 125 msec or more. The two groups were similar in terms of age and gender distribution and there were no statistically significant differences in coronary risk factors, peak creatine kinase concentration, location of infarction, Killip classification, thrombolytic therapy, left ventricular ejection fraction, or medications. After a mean follow-up period of 30 months, the rate of congestive heart failure (New York Heart Association, NYHA, class II or above) was significantly higher in group A (5/10) than in group B (1/17) (p < 0.01). These results suggest that a short mitral deceleration time could be a useful early predictor of the potential development of future congestive heart failure in postinfarction patients with left ventricular ejection fractions of 35% or more.


Nonredundant function of soluble LTα3 produced by innate lymphoid cells in intestinal homeostasis.
Immunoglobulin A (IgA) production at mucosal surfaces contributes to protection against pathogens and controls intestinal microbiota composition. However, mechanisms regulating IgA induction are not completely defined. We show that soluble lymphotoxin α (sLTα3) produced by RORγt(+) innate lymphoid cells (ILCs) controls T cell-dependent IgA induction in the lamina propria via regulation of T cell homing to the gut. By contrast, membrane-bound lymphotoxin β (LTα1β2) produced by RORγt(+) ILCs is critical for T cell-independent IgA induction in the lamina propria via control of dendritic cell functions. Ablation of LTα in RORγt(+) cells abrogated IgA production in the gut and altered microbiota composition. Thus, soluble and membrane-bound lymphotoxins produced by ILCs distinctly organize adaptive immune responses in the gut and control commensal microbiota composition.