Reduced levels of anti-MDA LDL antibodies in patients with carbohydrate metabolism disorders.
Diabetic patients undergoing percutaneous coronary intervention (PCI) have a worse prognosis than non-diabetic patients. The anti-oxidized LDL antibodies (anti-LDLox ab) have recently been suggested to be protective against the development of diabetes. The aim of this study was to compare the levels of IgG and IgM anti-oxidized LDL antibodies with reference to the new diagnostic criteria for carbohydrate metabolism disorders after an oral glucose tolerance test (OGTT) in hospitalized patients scheduled to undergo percutaneous coronary intervention. We undertook a cross-sectional study of 110 patients undergoing PCI. The patients were classified as being normal (oral glucose test tolerance normal, OGTT-N), or having impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM) according to their glucose levels at baseline and after an OGTT. An inverse slope was found in the levels of IgG anti-oxidized LDL antibodies between the OGTT-N patients (optical density (OD) = 0.109) and the patients with IGT (OD = 0.099) or T2DM (OD = 0.084) (p = 0.019). An inverse correlation was also detected between the levels of IgG anti-oxidized LDL antibodies and baseline glycemia (r = -0.23, p = 0.018). Patients with coronary disease and carbohydrate metabolism disorders have much lower levels of IgG anti-oxidized LDL antibodies than normoglycemic patients.


Hepatitis E virus infection as a direct cause of neuralgic amyotrophy.
We describe a patient who developed neuralgic amyotrophy (NA) related to hepatitis E virus (HEV) infection. The patient underwent neurological and electrodiagnostic examinations, high-resolution analysis of serological changes, and HEV load profile, and was treated with intravenous immunoglobulin. There was evidence of bilateral, asymmetric acute inflammatory cervical polyradiculopathy and possible brachial plexopathy. Positive serum anti-HEV IgM was followed by seroconversion to anti-HEV IgG positivity. A calculated anti-HEV antibody index was compatible with intrathecal synthesis, and HEV genotype 3 RNA was found in serum and cerebrospinal fluid (CSF). Liver function tests returned to normal within 6 weeks. Bilateral involvement of cervical nerve roots and/or plexus, elevated liver function tests, and abnormal CSF are typical features of HEV-associated NA. The pathogenesis involves possible immune-mediated mechanisms. However, our findings support the hypothesis that HEV-related NA is associated with direct infection. Muscle Nerve 54: 325-327, 2016.


A time lag in the onset of ATP-Pi exchange catalyzed by purified ATP-synthase (CF0-CF1) proteoliposomes and by chloroplasts.
The time course of ATP-Pi exchange which is catalyzed by the isolated chloroplast ATP synthase in phospholipid vesicles was studied. The following observations were made. (i) The onset of 32Pi incorporation into ATP lags behind ATP hydrolysis. The lag lasts for about 2 min at 37 degrees C and is followed by a steady-state rate which is constant for more than 30 min. Under the same experimental conditions, ATP hydrolysis shows an initial burst followed by a constant, slower rate. (ii) The initial lag is independent of Mg-ATP concentration in the range 0.2-5 mM and of the presence of ADP. In contrast, the steady-state rate of ATP-Pi exchange has an apparent Km of 0.3 mM for Mg-ATP and is stimulated by ADP. (iii) Increasing the temperature from 30 to 45 degrees C decreases the lag from 6 min to zero. The steady-state rate of ATP-Pi exchange is affected to a much smaller extent by the temperature in this range. (iv) The lag is insensitive to valinomycin or tetraphenylboron, while the steady-state rate is partially inhibited. Nigericin and protonophores affect both the lag and steady-state rate. (v) ATP-induced membrane potential formation, as followed by oxonol VI, does not correlate with the lag in its kinetics and temperature dependence. ATP-induced pH gradient formation could not be detected in the proteoliposome system. (vi) Light-triggered ATP-Pi exchange in chloroplasts shows essentially the same time course as the proteoliposome system, but the lag lasts for only about 20 s at room temperature and is unaffected by a preexisting proton gradient. These results suggest that the initial lag in ATP-Pi exchange does not reflect the time required for the buildup of a protomotive force (delta - mu H+) nor the time required to produce ADP. It is suggested, therefore, that the lag reflects an internal autocatalytic conformational change in the ATP-synthase complex which is initiated by ATP hydrolysis and which converts the enzyme from an "exclusive ATPase state" to a "reversible ATP-synthase state". This slow transition is not directly coupled to a trans-membrane pH or potential gradient.


Behavioral lateralization in the T-maze and monoaminergic brain asymmetries.
Recently we have reported a marked rat lateralization in the T-maze choice. The present study examines the relationship between the ascending monoaminergic systems and the T-maze behavioral asymmetry. There were no significant differences for serotonin or norepinephrine between the T-maze preferred and non-preferred brain sides in the s. nigra, ventral tegmental area, striatum, acumbens, frontal lobe or hippocampus. Only in the hippocampus was dopamine concentration significantly greater for the brain site ipsilateral to the T-maze choice side. Previously, we reported that both apomorphine, a dopamine receptor agonist, and 6-hydroxydopamine lesion in the medial forebrain bundle of the catecholaminergic neurons affect the T-maze asymmetry; we therefore suggested that the T-maze choice could be related with the ascending dopaminergic systems. The present data strongly support this hypothesis and suggest that the DA cells involved in the spatial asymmetry in the T-maze are included in the dopaminergic mesohippocampal system.


Neurogenin2 specifies the connectivity of thalamic neurons by controlling axon responsiveness to intermediate target cues.
Many lines of evidence indicate that important traits of neuronal phenotype, such as cell body position and neurotransmitter expression, are specified through complex interactions between extrinsic and intrinsic genetic determinants. However, the molecular mechanisms specifying neuronal connectivity are less well understood at the transcriptional level. Here we demonstrate that the bHLH transcription factor Neurogenin2 cell autonomously specifies the projection of thalamic neurons to frontal cortical areas. Unexpectedly, Ngn2 determines the projection of thalamic neurons to specific cortical domains by specifying the responsiveness of their axons to cues encountered in an intermediate target, the ventral telencephalon. Our results thus demonstrate that in parallel to their well-documented proneural function, bHLH transcription factors also contribute to the specification of neuronal connectivity in the mammalian brain.


Brain-derived neurotrophic factor expression after acute administration of ethanol.
Earlier findings suggest that, in addition to its well-known neurotrophic role, brain-derived neurotrophic factor (BDNF) is also involved in the rewarding and reinforcing effects of drugs of abuse. The purpose of the present study was to examine the effects of acute administration of ethanol (1.25 or 2.5 g/kg i.p.) on the expression profile of BDNF in the rat brain by determining the BDNF mRNA expression in the frontal cortex, nucleus accumbens, amygdala, hippocampus, and ventral tegmental area. Ethanol decreased BDNF mRNA levels dose-dependently in the hippocampus, and after the higher ethanol dose in the frontal cortex, nucleus accumbens and amygdala, while increasing them in the ventral tegmental area. Furthermore, BDNF mRNA expression was found to be regulated in a temporally different manner in all investigated brain areas. These data suggest that BDNF is involved in the acute effects of ethanol, but separate brain areas may be differentially engaged in the mediation of these effects.


Autonomous activation of CaMKII exacerbates diastolic calcium leak during beta-adrenergic stimulation in cardiomyocytes of metabolic syndrome rats.
Autonomous Ca2+/calmodulin-dependent protein kinase II (CaMKII) activation induces abnormal diastolic Ca2+ leak, which leads to triggered arrhythmias in a wide range of cardiovascular diseases, including diabetic cardiomyopathy. In hyperglycemia, Ca2+ handling alterations can be aggravated under stress conditions via the β-adrenergic signaling pathway, which also involves CaMKII activation. However, little is known about intracellular Ca2+ handling disturbances under β-adrenergic stimulation in cardiomyocytes of the prediabetic metabolic syndrome (MetS) model with obesity, and the participation of CaMKII in these alterations. MetS was induced in male Wistar rats by administering 30 % sucrose in drinking water for 16 weeks. Fluo 3-loaded MetS cardiomyocytes exhibited augmented diastolic Ca2+ leak (in the form of spontaneous Ca2+ waves) under basal conditions and that Ca2+ leakage was exacerbated by isoproterenol (ISO, 100 nM). At the molecular level, [3H]-ryanodine binding and basal phosphorylation of cardiac ryanodine receptor (RyR2) at Ser2814, a CaMKII site, were increased in heart homogenates of MetS rats with no changes in RyR2 expression. These alterations were not further augmented by Isoproterenol. SERCA pump activity was augmented 48 % in MetS hearts before β-adrenergic stimuli, which is associated to augmented PLN phosphorylation at T17, a target of CaMKII. In MetS hearts. CaMKII auto-phosphorylation (T287) was increased by 80 %. The augmented diastolic Ca2+ leak was prevented by CaMKII inhibition with AIP. In conclusion, CaMKII autonomous activation in cardiomyocytes of MetS rats with central obesity significantly contributes to abnormal diastolic Ca2+ leak, increasing the propensity for β-adrenergic receptor-driven lethal arrhythmias.


Gender and food, a study of attitudes in the USA towards organic, local, U.S. grown, and GM-free foods.
Food choice is influenced by consumer attitudes towards food attributes. This U.S.-based study (n = 601) simultaneously compares attitudes towards selected food attributes of organic, locally grown, U.S. grown, and GM-free food in relation to other food attributes. Exploratory factor analysis identifies underlying constructs that determine, together and separately, female and male food choice decisions. Gendered analysis of the value of food in life and food behaviours (cooking and shopping) support the investigation of the highlighted food attributes. Respondents generally assigned greater importance to the U.S. grown, followed by GM-free, locally grown, and organically produced food attributes in deciding what to eat. Analysis of the female and male subsamples yielded similar factor results. All four main attributes were captured in a single factor, associated with respondents in both the female and male subsamples who are older, have lower incomes, and who are religiously observant. Additionally, among females, this factor was associated with higher education; and among males, living in households with children and/or with partners. Additional studies should further explore the interaction of food attributes now becoming increasingly important and prevalent in current food products.


Changes in the quality of flaxseed oil powder produced by incorporating with microcrystalline cellulose and thyme.
Flaxseed oil is a high nutrition oil, rich in ω-3 fatty acid, tocopherols and phenolic compounds. However, it is prone to oxidation due to its high unsaturation which needs pretreatments to be easily introduce to the market. In this study, flaxseed oil was converted to powder form by mixing with microcrystalline cellulose (MC) and thyme powder to produce flaxseed oil powder. For this purpose, 3 different levels of thyme powder (5%, 10% and 15% of oil) were mixed with oil, followed by mixing with different proportions of MC (50:50, 50:75, 50:100 (oil:MC)) and stored for 90 days at 25 °C and 4 °C. Results indicated that the total phenolic compounds (23.2-91.2 mg GAE/100 g), chlorophyll (9-63.6 mg/kg), and carotenoid (4.4-9.9 mg/kg) contents increased with the incorporation of thyme powder into the flaxseed oil on the first day in 25 °C and 4 °C. Also during 90 days storage, phenolic compound (21.8%), chlorophyll (32.5%) and carotenoid (24%) decreased in both 25 °C and 4 °C temperatures. The results confirmed that adding thyme powder to samples decreased acidity and peroxide value in compare with control. Using thyme as a natural antioxidant and also transforming the oil to powder form by MC increased the oxidative stability in compare with control. The produced high stable flaxseed oil powder has the potential to be used directly on food products like salads or to be used in different food formulations to fortify them with natural antioxidants and ω-3 essential fatty acids.


Time course of the changes in prednisolone pharmacokinetics after co-administration or discontinuation of rifampin.
We have investigated changes in the pharmacokinetics of prednisolone caused by co-administration or discontinuation of rifampin. Serial IV pharmacokinetic studies of prednisolone (1 mg/kg) in groups of 3 patients over a 1 month period of rifampin co-treatment or after its withdrawal, revealed significant changes in the area under the curve, the total clearance, the non-renal clearance and the half-life. The changes in the pharmacokinetic parameters reached a 1.5 to 2-fold plateau after 2 weeks and the half maximal effect was attained within 5 days. Neither the volume of distribution nor the protein binding of prednisolone were significantly altered.


Being an Informal Caregiver of a Person with a Pressure Ulcer in the Azores Islands.
This study aimed at both understanding the experience of informal caregivers of people with pressure ulcers (PrUs), as well as perceiving the relevant aspects of the narratives emerging from the experience of those caregivers. A qualitative, exploratory, grounded-based theory data analysis was implemented. The authors used NVivo 9 software (QSR International Inc, Burlington, Massachusetts) on semistructured interviews. The study participants were 9 informal caregivers of people with PrUs. An individual's personal characteristics, the person he or she is caring for, and social pressure are typically the primary reasons to be a caregiver. In fact, PrUs require specific care associated with an impact on caregivers at different levels, including changes in everyday life, needs and feelings emerging from the care they provide, quality of life conditioned by their professional status, and burdens induced by physical and emotional demands. Oftentimes, family members and external entities--with emphasis on the nursing team--provide support to the caregiver. Caregivers show both satisfaction and dissatisfaction with the care provided, with the evolution of the PrU and with the support of external agents. The experience of informal caregivers of people with PrUs is based on 5 dimensions: (1) reasons to be caregivers, (2) care provided to the PrU, (3) impacts on the caregiver, (4) support to the caregiver, and (5) satisfaction or dissatisfaction of the caregiver.


Preparation of α- and β-D-glucoseptanose pentaacetates.
The α- and β-D-glucoseptanose pentaacetates have been prepared by treatment of ethyl 1-thio-β-D-glucoseptanoside tetraacetate with mercury(II) acetate in acetic acid. The solid state structure of the β-isomer has been determined by X-ray diffraction.


Competition brings out the best in people, and this year's KidneyX Summit did not disappoint.
Six teams receive large-sum awards in the first round of the Artificial Kidney competition to further develop concepts that significantly improve upon existing dialysis methods.


A 250 μg/week dose of vitamin D was as effective as a 50 μg/d dose in healthy adults, but a regimen of four weekly followed by monthly doses of 1250 μg raised the risk of hypercalciuria.
The risk of vitamin D insufficiency is increased in persons having limited sunlight exposure and dietary vitamin D. Supplementation compliance might be improved with larger doses taken less often, but this may increase the potential for side effects. The objective of the present study was to determine whether a weekly or weekly/monthly regimen of vitamin D supplementation is as effective as daily supplementation without increasing the risk of side effects. Participants were forty-eight healthy adults who were randomly assigned for 3 months to placebo or one of three supplementation regimens: 50 μg/d (2000 IU/d, analysed dose 70 μg/d), 250 μg/week (10 000 IU/week, analysed dose 331 μg/week) or 1250 μg/week (50 000 IU/week, analysed dose 1544 μg/week) for 4 weeks and then 1250 μg/ month for 2 months. Daily and weekly doses were equally effective at increasing serum 25-hydroxyvitamin D, which was significantly greater than baseline in all the supplemented groups after 30 d of treatment. Subjects in the 1250 μg treatment group, who had a BMI >26 kg/m2, had a steady increase in urinary Ca in the first 3 weeks of supplementation, and, overall, the relative risk of hypercalciuria was higher in the 1250 μg group than in the placebo group (P=0·01). Although vitamin D supplementation remains a controversial issue, these data document that supplementing with ≤ 250 mg/week (≤ 10 000 IU/week) can improve or maintain vitamin D status in healthy populations without the risk of hypercalciuria, but 24 h urinary Ca excretion should be evaluated in healthy persons receiving vitamin D3 supplementation in weekly single doses of 1250 μg (50 000 IU).


[Engineering by reverse genetics and characterization of the new reassortant influenza virus strain H5N1].
Reverse genetics was applied to engineering of the reassortantvaccine candidate strain against highly pathogenic avian influenza viruses (HPAIVs) of the H5 subtype. The new strain recPR8-H5N1 contains the HA gene from the Russian HPAIV A/Kurgan/05/2005 (H5N1), the NA and internal genes from A/Puerto Rico/8/34 (H1N1). The strain recPR8-H5N1 demonstrated the antigenic specificity (H5), high proliferation rate in 12 days chicken embryos, and was lethal for the embryos in 36 hours. An inactivated emulsified vaccine based on the strain recPR8-H5N1 elicited high antibody titers and protected 6-week-old chickens from lethal challenge with the HPAIV A/Kurgan/05/2005 (H5N1) on day 21 after single immunization. Infection of non-vaccinated birds with the strain recPR8-H5N1 did not cause any pathology, and the virus was not detected using PCR in blood and cloacal swabs on day 7 p.i. Specific weak seroconversion caused by infection with the strain recPR8-H5N1 was detected on day 14 p.i. As a result, a new influenza virus strain was obtained with modified properties.


Hyaluronic acid-empowered nanotheranostics in breast and lung cancers therapy.
Nanomedicine application in cancer therapy is an urgency because of inability of current biological therapies for complete removal of tumor cells. The development of smart and novel nanoplatforms for treatment of cancer can provide new insight in tumor suppression. Hyaluronic acid is a biopolymer that can be employed for synthesis of smart nanostructures capable of selective targeting CD44-overexpressing tumor cells. The breast and lung cancers are among the most malignant and common tumors in both females and males that environmental factors, lifestyle and genomic alterations are among the risk factors for their pathogenesis and development. Since etiology of breast and lung tumors is not certain and multiple factors participate in their development, preventative measures have not been completely successful and studies have focused on developing new treatment strategies for them. The aim of current review is to provide a comprehensive discussion about application of hyaluronic acid-based nanostructures for treatment of breast and lung cancers. The main reason of using hyaluronic acid-based nanoparticles is their ability in targeting breast and lung cancers in a selective way due to upregulation of CD44 receptor on their surface. Moreover, nanocarriers developed from hyaluronic acid or functionalized with hyaluronic acid have high biocompatibility and their safety is appreciated. The drugs and genes used for treatment of breast and lung cancers lack specific accumulation at cancer site and their cytotoxicity is low, but hyaluronic acid-based nanostructures provide their targeted delivery to tumor site and by increasing internalization of drugs and genes in breast and lung tumor cells, they improve their therapeutic index. Furthermore, hyaluronic acid-based nanostructures can be used for phototherapy-mediated breast and lung cancers ablation. The stimuli-responsive and smart kinds of hyaluronic acid-based nanostructures such as pH- and light-responsive can increase selective targeting of breast and lung cancers.


Fission yeast Adf1 is necessary for reassembly of actin filaments into the contractile ring during cytokinesis.
ADF/cofilin family proteins quickly disassemble actin in vitro, and are thought to be involved in various actin dynamics in the cell. Adf1 is a member of this family proteins expressed in fission yeast, and is thought to play roles in actin patch dynamics and also contractile ring formation during cytokinesis. We aimed to understand the function of this protein in cytokinesis in detail using the temperature-sensitive mutant adf1-1. Adf1 inactivation at a restrictive temperature during late G2 phase led to a clustering of actin patches at the cell ends. It was apparent that the inactivation occurred only in a few minutes. Furthermore, we found that the actin clusters migrated to the division site during anaphase possibly by the function of both myosin 5-1 and a myosin II. The migrated actin clusters, however, were not organized into the contractile ring. When Adf1 was inactivated at mid-anaphase B before contractile ring assembly, the ring was not formed, but it was formed when Adf1 was inactivated after this point. We conclude that Adf1 functions in the interphase actin dynamics and formation of the contractile ring during mitosis.


Bayesian estimation of parameters in viral dynamics models with antiviral effect of interferons in a cell culture.
The goal of this work is to estimate the efficacy of interferon therapy in the inhibition of infection by the human immunodeficiency virus type 1 (HIV-1) in a cell culture. For this purpose, three viral dynamics models with the antiviral effect of interferons are presented; the dynamics of cell growth differ among the models, and a variant with Gompertz-type cell dynamics is proposed. A Bayesian statistics approach is used to estimate the cell dynamics parameters, viral dynamics and interferon efficacy. The models are fitted to sets of experimental data on cell growth, HIV-1 infection without interferon therapy and HIV-1 infection with interferon therapy, respectively. The Watanabe-Akaike information criterion (WAIC) is used to determine the model that best fits the experimental data. In addition to the estimated model parameters, the average lifespan of the infected cells and the basic reproductive number are calculated.


Effect of corn-steep liquor on growth and mosquito larvicidal activity of Bacillus thuringiensis var israelensis de Barjac 1978 and B. sphaericus Neide 1904.
Influence of corn steep liquor on the cell yield and toxicity of three strains of B. thuringiensis var israelensis and two strains of B. sphaericus was studied and compared with peptone-yeast extract using a laboratory fermentor. Large increase in the cell yield of all the three strains of B. thuringiensis var israelensis was observed when cornsteep liquor was used as the sole nitrogen source. Significant increase in toxicity was also observed in B. thuringiensis var israelensis strains B17 and B113. Among the two B. sphaericus strains tested, the strain 1593 showed no significant change in cell yield and toxicity, whereas the strain VCRC B42 showed increased cell yield and toxicity in this medium. The results indicate that cornsteep liquor can effectively replace both peptone and yeast extract in the media presently used for large scale multiplication of the two larvicidal bacilli.


Optimization of medium components for increased production of C-phycocyanin from Phormidium ceylanicum and its purification by single step process.
Phycocyanin is a major protein produced by cyanobacteria, but very few phycocyanin-producing strains have been reported. In the present study, response surface methodology (RSM) involving a central composite design for four factors was successfully employed to optimize medium components for increased production of phycocyanin from Phormidium ceylanicum. The production of phycocyanin and interactions between sodium nitrate, calcium chloride, trace metal mix and citric acid stock were investigated and modeled. Under optimized condition P. ceylanicum was able to give 2.3-fold increase in phycocyanin production in comparison to commonly used BG 11 medium in 32 days. We have demonstrated the extraction, purification and characterization of C-phycocyanin using novel method based on filtration and single step chromatography. The protein was extracted by repeated freeze-thaw cycles and the crude extract was filtered and concentrated in stirred ultrafiltration cell (UFC). The UFC concentrate was then subjected to a single ion exchange chromatographic step. A purity ratio of 4.15 was achieved from a starting value of 1.05. The recovery efficiency of C-phycocyanin from crude extract was 63.50%. The purity was checked by electrophoresis and UV-Vis spectroscopy.


[Effect of caffeine on the frequency of radiation-induced chromosome aberrations at different stages of the cell cycle].
The effect of caffeine on the frequency of chromosome aberrations in human lymphocytes irradiated at different stages of the cell cycle was studied. Caffeine appeared to nearly double the frequency of chromosome aberrations induced by irradiation at S and G2 stages and did not influence the effect of irradiation at G0 and G1 stages.


Can Arterial Spin Labeling Perfusion Imaging be Used to Differentiate Nasopharyngeal Carcinoma From Nasopharyngeal Lymphoma?
Differentiating nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoma (NPL) is useful for deciding the appropriate treatment. However, the diagnostic accuracy of current imaging methods is low. To explore the feasibility of arterial spin labeling (ASL) perfusion imaging in the qualitative and quantitative differentiation between NPC and NPL to improve the diagnosis of malignancies in the nasopharynx. Retrospective. Ninety seven patients: NPC (65 cases) and NPL (32 cases), histologically confirmed. 3T/3D fast spin echo pseudo-continuous ASL imaging with spiral readout scheme, 3D inverse recovery- fast spoiled gradient recalled echo brain volume (BRAVO) imaging. Cerebral blood flow (CBF) images from ASL perfusion imaging were assessed by three radiologists. Each tumor was visually scored based on CBF images. Intratumoral CBF and intramuscular CBF values were obtained from intratumoral and lateral pterygoid muscle areas, respectively. Through dividing intratumoral CBF by intramuscular CBF, normalized CBF (nCBF) was further calculated. Fleiss's kappa and intraclass correlation coefficients (ICCs) were used to assess interobserver agreement among the three readers. The Mann-Whitney U-test was used to compare visual scoring, and an unpaired t-test was performed to compare CBF value between the NPC and NPL groups. The area under the curve (AUC) value was used to quantify the diagnostic ability of each parameter. Good interobserver agreements were validated by high Fleiss's kappa and ICC values (all >0.80). NPCs showed significantly higher visual scores than NPLs (P < 0.05). Both intratumoral CBF and nCBF in NPC were significantly higher than those in NPL (both P < 0.05). Intratumoral CBF showed the highest AUC of 0.861 (P < 0.05) in differentiating NPC (n = 65) from NPL (n = 32), while the AUCs of nCBF and visual scoring were 0.847 and 0.753, respectively. For the diagnosis of distinguishing NPC from NPL, ASL perfusion imaging demonstrated high diagnostic efficiency. 3 TECHNICAL EFFICACY STAGE: 2.


A novel missense mutation of FOXC1 in an Axenfeld-Rieger syndrome patient with a congenital atrial septal defect and sublingual cyst: a case report and literature review.
Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant hereditary disease characterized primarily by maldevelopment of the anterior segment of both eyes, accompanied by developmental glaucoma, and other congenital anomalies. FOXC1 and PITX2 genes play important roles in the development of ARS. The present report describes a 7-year-old boy with iris dysplasia, displaced pupils, and congenital glaucoma in both eyes. The patient presented with a congenital atrial septal defect and sublingual cyst. The patient's family has no clinical manifestations. Next generation sequencing identified a pathogenic heterozygous missense variant in FOXC1 gene (NM_001453:c. 246C>A, p. S82R) in the patient. Sanger sequencing confirmed this result, and this mutation was not detected in the other three family members. To the best of our knowledge, the results of our study reveal a novel mutation in the FOXC1 gene associated with ARS.


Two-way coupled SPH and particle level set fluid simulation.
Grid-based methods have difficulty resolving features on or below the scale of the underlying grid. Although adaptive methods (e.g. RLE, octrees) can alleviate this to some degree, separate techniques are still required for simulating small-scale phenomena such as spray and foam, especially since these more diffuse materials typically behave quite differently than their denser counterparts. In this paper, we propose a two-way coupled simulation framework that uses the particle level set method to efficiently model dense liquid volumes and a smoothed particle hydrodynamics (SPH) method to simulate diffuse regions such as sprays. Our novel SPH method allows us to simulate both dense and diffuse water volumes, fully incorporates the particles that are automatically generated by the particle level set method in under-resolved regions, and allows for two way mixing between dense SPH volumes and grid-based liquid representations.


Influence of wheat phenolic Acids onFusarium Head Blight Resistance and Deoxynivalenol Accumulation.
Main free and bound phenolic acids were determined in ears of wheat cultivars and related to their ratings ofFusarium head blight susceptibility and DON-contents. Ferulic acid concentrations differed strongly during flowering. First results at this step of ear development show that concentrations of ferulic acid were negatively correlated with the relative ratings of cultivars with respect to FHB-susceptibility (r = -0.96) and DON-contents (r = -0.91), which suggests that this phenolic acid plays a role in the defence of fungal attacks by plants.


Combined volar and dorsal plating vs. volar plating of distal radius fractures. A single-center study of 105 cases.
Despite recent advances in the surgical management of distal radius fractures (DRFs), the optimal treatment remains controversial as different fixation methods often have similar clinical functional and radiographic outcomes. The objective of this study was to assess the differences in outcomes 1 year postoperatively between volar plating and combined plating for DRFs. In a retrospective cohort study, we evaluated 105 consecutive patients operated with either a volar locking plate or combined dorsal and volar plating. The primary outcome was wrist range of motion (ROM). Secondary outcome measures included hand grip strength, visual analog scale (VAS) pain scores, radiographic examination and patient-related outcome measures. Patients treated with combined plating had significantly inferior wrist flexion, extension and ulnar deviation. The radiographic Batra score 1 year postoperatively was similar for both groups. The PRWE (patient-rated wrist evaluation) score was 16 for the volar plating group and 14 for the combined plating group. The QuickDASH (Quick disabilities of the arm, shoulder and hand) score was 9 for the volar plating group and 16 for the combined plating group. VAS pain scores were 0 at rest and 2 during activity for both groups. Grip strength was similar between the two groups. Hardware removal was done in 18/78 patients for the combined plating group and 1/27 for the volar plate group. Two patients operated with combined plating had tendon ruptures. Our findings indicate that both methods can yield satisfactory clinical and radiographic outcomes. However, combined plating resulted in inferior wrist ROM and substantially higher frequency of hardware removal. The potential advantages of combined plating in stabilizing a comminuted DRF must be balanced by the potential drawbacks such as inferior wrist ROM and higher frequency of hardware removal.


Expression of nuclear factor kappa B components in human endometrium.
Nuclear factor kappa B (NFkappaB) is a family of transcription factors involved in signalling between IL1 and TNFalpha receptors and cytokines and adhesion molecules in a number of cell types, including those of the human endometrium. In this study, we used immunocytochemistry to investigate the in vivo expression of the p50, IkappaBalpha and IkappaBbeta NFkappaB components in endometrium obtained from normal fertile women throughout the menstrual cycle. All three components were expressed by both the stromal and epithelial cells of the endometrium and staining was predominately seen in the cytoplasm of the cells. Staining for p50 was more intense in the epithelial compartment than the stromal compartment. Staining in the stromal compartment was low to moderate throughout the cycle but, in the epithelial compartment, staining was cycle dependent and increased slightly during the mid-secretory phase. The staining patterns for IkappaBalpha and IkappaBbeta were similar. As for p50, staining for both proteins was greater in the epithelial compartment compared to the stromal compartment and stromal cell staining was low to moderate throughout the cycle. However, in contrast to p50, staining for the IkappaB proteins in epithelial cells decreased during the mid-secretory phase of the cycle. Although the immunocytochemistry technique used is only semi-quantitative, the results suggest an increased expression of the active and a decreased expression of the inhibitory NFkappaB components by the endometrium at the time of implantation. If confirmed, it would suggest that NFkappaB is involved in the control of factors important in the implantation process.


Cholesterol protects Acholeplasma laidlawii against oxidative damage caused by hydrogen peroxide.
The aim of this study was to determine whether cholesterol, added to the cell growth medium or to cell suspension buffer, could protect Acholeplasma laidlawii cells against the toxic effects of hydrogen peroxide (H(2)O(2)). Variable concentrations of cholesterol (0.05-1.0 mg/ml) were added to the A. laidlawii suspension buffer and to the growth medium. Cells were then washed carefully and incubated with 0.001% (v/v) H(2)O(2) at 37 degrees C for 30 min and the viability was determined. The results indicated that cells were more viable in the presence of cholesterol than were cells grown in the absence of cholesterol. In addition, the oxygen uptake rate resulting from the oxidation of 5.5 mmol/L glucose was 2-fold and 4-fold higher for cells grown in medium supplemented with 0.05 and 0.50 mg/ml cholesterol, respectively, compared to cells grown in a medium with no added cholesterol. These findings indicate that cholesterol might play a role in protecting Mollicutes against the oxidative damage caused by H(2)O(2).


Laparoscopic versus robotic adrenalectomy in pheochromocytoma patients.
Pheochromocytoma is a challenging tumor type requiring resection with a clear margin and an intact capsule to prevent recurrences. Our aim was to compare perioperative outcomes of laparoscopic adrenalectomy (LA) versus robotic adrenalectomy (RA) for pheochromocytoma. In an institutional review board-approved retrospective study, clinical parameters of patients who underwent LA versus RA at a single center were compared using Mann-Whitney U, χ2 , and survival analyses. Continuous data are expressed as median (interquartile range). There was a total of 157 patients (RA: n = 87, LA: n = 70) analyzed. Estimated blood loss (36.3 [35.0] vs. 99.9 [65.0] cc, p = 0.020) and hospital stay (1.3 [0.0] vs. 2.2 [1.0] days, p = 0.010) were lower in robotic versus laparoscopic group, respectively. Disease-free and overall survival was similar between groups. The rate of conversion to open for tumors ≥5 cm was less in the robotic group (0% vs. 14%, respectively, p = 0.048). In this study, long-term outcomes of LA and RA were similar, although adrenalectomies performed robotically were associated with less blood loss, shorter hospital stay, and a lower chance of conversion to open in the case of large tumors.


Patients that benefit from buprenorphine-naloxone on medically assisted treatment for opioid dependence in Malaysia.
Opioid dependence is recorded as the most common drug of abuse in Malaysia. Currently, the preferred substitution therapy for most Government treatment centres is methadone used as substitution therapy for opioid dependence. There are, however patients who may benefit from being on the combined buprenorphine-naloxone formulation as substitution therapy instead. We discuss six cases of opioid dependence of varied backgrounds that were treated with buprenorphinenaloxone therapy and their outcomes. All of the reported patients improved after the induction of buprenorphine- naloxone. Two of the cases highlighted the transfer of patients on methadone to buprenorphine-naloxone due to the adverse effect and interactions of methadone with other medications. During the transfer there were no major adverse reactions noted, and patients were safely able to continue with the maintenance therapy of buprenorphine- naloxone. Buprenorphine-naloxone is a safe and effective drug substitution therapy for opioid dependence. It has fewer interactions with other medications, and has similar efficacy to methadone. Being a partial agonist, it has a less sedating effect making patients more functional.


A fluorogenic chemically induced dimerization technology for controlling, imaging and sensing protein proximity.
Molecular tools enabling the control and observation of the proximity of proteins are essential for studying the functional role of physical distance between two proteins. Here we present CATCHFIRE (chemically assisted tethering of chimera by fluorogenic-induced recognition), a chemically induced proximity technology with intrinsic fluorescence imaging and sensing capabilities. CATCHFIRE relies on genetic fusion to small dimerizing domains that interact upon addition of fluorogenic inducers of proximity that fluoresce upon formation of the ternary assembly, allowing real-time monitoring of the chemically induced proximity. CATCHFIRE is rapid and fully reversible and allows the control and tracking of protein localization, protein trafficking, organelle transport and cellular processes, opening new avenues for studying or controlling biological processes with high spatiotemporal resolution. Its fluorogenic nature allows the design of a new class of biosensors for the study of processes such as signal transduction and apoptosis.


Results of transvenous occlusion of secundum atrial septal defects with the fourth generation buttoned device: comparison with first, second and third generation devices. International Buttoned Device Trial Group.
The purpose of this study was to assess safety and effectiveness of the fourth generation buttoned device in dosing atrial septal defects (ASDs) and to test the hypothesis that introduction of double button reduces unbuttoning rate without reducing effectiveness. Because of the high unbuttoning rate (7.2%) with first, second and third generation buttoned devices, the device was modified (fourth generation) so that there were two radiopaque spring buttons 4 mm apart on the button loop attached to the occluder. During a four-year period ending in September 1997, 423 patients, ages 1.5 to 80 years (median 16 years), underwent closure of ASD at 40 medical centers around the world. The ASD size varied between 5 and 30 mm (median 17 mm). The device size varied between 25 and 60 mm. Unbuttoning occurred in 4 (0.9%) of 423 patients. Effective occlusion, defined as no (n = 343) or trivial (n = 34) residual shunt on echo-Doppler studies performed within 24 h of the procedure, was demonstrated in 377 patients (90%). Thus, the unbuttoning rate (0.9 vs. 7.2%) decreased (p<0.01) while effective occlusion rate (90 vs. 92%) remained unchanged (p>0.1) with this device, compared with earlier generation devices. During follow-up from one month to five years (23+/-15 months), 21 (5%) of 417 patients required surgical (n = 12) or transcatheter (n = 9) reintervention, mostly to treat significant residual shunt. In the remaining patients there was gradual reduction and disappearance of the residual shunt. No wire integrity problems were observed. These data suggest that the fourth generation buttoned device is as effective as earlier generation devices, but without significant unbuttoning. Follow-up results remained good, with a reintervention-free rate of 89% at five years.


Nerve growth factor stimulates the activities of the raf-1 and the mitogen-activated protein kinases via the trk protooncogene.
Nerve growth factor (NGF) binds to two structurally unrelated transmembrane proteins on the surface of PC-12 cells, a 75-kDa glycoprotein with a short cytoplasmic sequence, and the trk protooncogene (pp140c-trk), a protein tyrosine kinase activated by NGF. Immediately after binding to cells, NGF induces changes in serine/threonine phosphorylation of several proteins. We have explored the relative roles of these two NGF binding proteins in mediating the activation of two intracellular kinases that may be responsible for some of these phosphorylations. The raf-1 protooncogene is a serine/threonine kinase activated by several growth factors and oncogenic proteins. Treatment of PC-12 cells with NGF increases the serine and threonine phosphorylation of raf-1 in an anti-raf-1 immunoprecipitate kinase assay. This increased phosphorylation observed in vitro is dose-dependent and transient and is accompanied by the NGF-dependent shift in the mobility of immunoblotted raf-1 on SDS sodium dodecyl sulfate-polyacrylamide gel electrophoresis, an effect thought to reflect phosphorylation. NGF-dependent activation of raf-1 is not dependent on protein kinase C, since prolonged exposure to phorbol esters under conditions that cause down-regulation of cellular protein kinase C activity has no effect on the NGF response. Expression of pp140c-trk in 3T3 fibroblasts (3T3-c-trk), as evidenced by cross-linking of 125I-NGF to the 140-kDa protein, permits the NGF-dependent activation of raf-1 kinase, detected in the immunoprecipitate kinase assay, anti-raf immunoblot shift on gel electrophoresis, and incorporation of [32P]orthophosphate into the raf-1 protein. The concentration dependence of raf-1 activation is identical in 3T3-c-trk and PC-12 cells, despite the absence of the 75-kDa NGF binding protein in 3T3-c-trk cells. NGF is without effect in untransfected 3T3 cells or in Chinese hamster ovary cells overexpressing p75, although raf-1 is present in these cells. Similarly, the NGF-dependent activation of mitogen-activated protein (MAP) kinase is detected in 3T3-c-trk cells, but not in untransfected 3T3 or Chinese hamster ovary cells overexpressing p75. As described for raf-1 activation, the NGF dose responses for MAP kinase activation in 3T3-c-trk and PC-12 cells are virtually superimposable. These data indicate that the activation of these two serine/threonine kinases by NGF is mediated solely by binding to and activating the pp140c-trk receptor.


Genetic variability of the postharvest pathogen Gilbertella persicaria: identification of randomly amplified polymorphic DNA (RAPD) markers correlating with (+) and (-) mating types.
Random amplified polymorphic DNA (RAPD) and isoenzyme polymorphisms among 16 isolates of the postharvest pathogen Gilbertella persicaria were examined. Six different 10-bp primers were used to determine the extent of intraspecific genetic variability. Nine composite amplification types were identified. RAPD markers were obtained which correlated with the mating types of the G. persicaria isolates. The variability of the isoenzyme patterns was very low and no correlation was found between the isoenzyme markers and the mating abilities. When 80 single carbon substrates were tested in utilization assays, most of them were utilized uniformly by the 16 G. persicaria strains. However, some compounds elicited differences between the isolates representing the two mating types. Beta-alanine (0.2%) has little effect on the germination of the sporangiospores of the (+) isolates, but inhibited the germination of (-) sporangiospores. Glycerol-1-monoacetate supported the growth of both mating types, but at concentrations higher than 4% this was accompanied with a compact (colonial) growth for plus mating type isolates only.


False-negative result of serum cryptococcal antigen lateral flow assay in an HIV-infected patient with culture-proven cryptococcaemia.
The detection of cryptococcal capsular antigen (CrAg) is very sensitive and specific, however false-negative results have been reported, mostly in cerebrospinal fluid. We report the case of an HIV-infected patient with CD4 = 42 cells/mL, asthenic, negative serum CrAg lateral flow assay (LFA) and culture-proven cryptococcaemia. Despite the high accuracy of LFA, false-negative result is possible. Careful clinical evaluation and close follow-up are relevant.


Naphthoquinone analogs as inactivators of cdc25 phosphatase.
cdc25A and cdc25B were significantly overexpressed in certain types of cancers, and they represent potential therapeutic targets for anticancer drug. In this study, naphthoquinone analogs as cdc25A phosphatase inactivators were investigated.


Immunochemical studies on the putative plasmalemmal receptor for 1, 25-dihydroxyvitamin D(3). III. Vitamin D status.
The effect of vitamin D status on levels of the putative 1, 25(OH)(2)D(3) membrane receptor (pmVDR) was studied in chick intestine, kidney, and brain. Western analyses and assays for specific [(3)H]1,25(OH)(2)D(3) binding indicated that, in intestine, pmVDR levels were greatest in -D chicks relative to +1,25D and +D animals (P < 0.05). In kidney, protein levels and specific binding followed the order +D > +1,25D, -D. In brain, vitamin D status did not affect protein levels or specific binding levels. In tissue from normal chicks, both protein and specific binding followed the order of intestine > kidney > brain membranes. Intestinal cells were further evaluated for the effect of 1,25(OH)(2)D(3) on selected "rapid responses." Extrusion of (45)Ca in response to 130 pM 1, 25(OH)(2)D(3) in vitro was greater in cells from -D chicks than from +1,25D or normal birds. Analyses of signal transduction events revealed diminished hormone-induced intracellular calcium oscillations (as assessed by fura-2 fluorescence), and lack of steroid-enhanced protein kinase (PK) A activity in intestinal epithelial cells from -D chicks relative to +D chicks. PK C activation by 130 pM 1,25(OH)(2)D(3) was approximately twofold in cells from +D or -D chicks. The combined results indicate that vitamin D status differentially affects the pmVDR in intestine, kidney, and brain. In intestine, vitamin D deficiency differentially affects (45)Ca handling, intracellular calcium oscillations, PK A and PK C activities in response to 1,25(OH)(2)D(3).


Intracellular Delivery of an Antibody-Like Molecule Capable of Inhibiting c-Myc.
A modular nanotransporter (MNT) carrying the sequence of an antibody-like molecule, anti-c-Myc nanobody, was synthesized and characterized. It was demonstrated that the created MNT is able to interact with the target protein, c-Myc oncogene, with a dissociation constant of 46 ± 14 nM, internalize into target cells, change Myc-dependent expression, and exert an antiproliferative effect.


Activation-Induced Conformational Changes of Dopamine D3 Receptor Promote the Formation of the Internal Water Channel.
The atomic-level dopamine activation mechanism for transmitting extracellular ligand binding events through transmembrane helices to the cytoplasmic G protein remains unclear. In the present study, the complete dopamine D3 receptor (D3R), with a homology-modeled N-terminus, was constructed to dock different ligands to simulate conformational alterations in the receptor's active and inactive forms during microsecond-timescale molecular dynamic simulations. In agonist-bound systems, the D3R N-terminus formed a "lid-like" structure and lay flat on the binding site opening, whereas in antagonist and inverse agonist-bound systems, the N-terminus exposed the binding cavity. Receptor activation was characterized using the different molecular switch residue distances, and G protein-binding site volumes. A continuous water pathway was observed only in the dopamine-Gαi-bound system. In the inactive D3Rs, water entry was hindered by the hydrophobic layers. Finally, a complete activation mechanism of D3R was proposed. Upon agonist binding, the "lid-like" conformation of the N-terminus induces a series of molecular switches to increase the volume of the D3R cytoplasmic binding part for G protein association. Meanwhile, water enters the transmembrane region inducing molecular switches to assist in opening the hydrophobic layers to form a continuous water channel, which is crucial for maintaining a fully active conformation for signal transduction.


Up-regulation of human leukocyte antigen G expression in primary cutaneous malignant melanoma associated with host-vs-tumor immune response.
Human leukocyte antigen G (HLA-G) is one of the molecules implicated in immunotolerance. To investigate the role of HLA-G in primary cutaneous malignant melanoma (CMM), a series of 47 skin melanocytic lesions were immunohistochemically evaluated. The correlation between HLA-G expression and CMM clinicohistopathological data and Bcl-2 expression was also analyzed. HLA-G expression was detected in a variety of cell types. No significant difference in HLA-G expression was observed between malignant and non-malignant melanocytic lesions. HLA-G expression was significantly correlated with the inflammatory infiltration and Bcl-2 expression, whereas no significant correlation with ulceration, tumor thickness, clinical stage, histopathological subtypes were observed. HLA-G expression may be the result of host immune reaction in tumor microenvironment rather than a malignant feature of CMM.


Fertilization and early pregnancy loss in healthy women attempting conception.
The rosette inhibition test was used to monitor the activity of an early pregnancy factor (EPF) in sera collected from 18 healthy women who were attempting to conceive. Serial blood samples collected during the luteal phase of 21 menstrual cycles demonstrated the appearance of EPF in 14 of the cycles, of which six showed only transient EPF activity over a 5-10 day period following ovulation. These results indicate a 67% rate of fertilization and a 36% rate of early conceptus losses.


MicroRNAs Derived from Extracellular Vesicles: Keys to Understanding SARS-CoV-2 Vaccination Response in Cancer Patients?
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provoked a global pandemic identified as coronavirus disease (COVID-19), with millions of deaths worldwide. However, several important questions regarding its impact on public health remain unanswered, such as the impact of vaccination on vulnerable subpopulations such as cancer patients. Cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion, being manifested in most immunocompromised individuals. This strong immunosuppression can lead to a dysfunctional antiviral response to natural viral infection and compromised vaccination response. Extracellular vesicles (EVs) are membrane-bound vesicles released from cells that are involved in intercellular communication. EVs carry various molecules including microRNAs that play a crucial role in COVID-19 pathophysiology, influencing cellular responses. This review summarizes the state of the art concerning the role of EV-derived miRNAs in COVID-19 infection and their potential use as prognosis biomarkers for vaccination response in cancer patients.


Imipenem: a new carbapenem antibiotic.
Imipenem is a new carbapenem antibiotic that has an extremely broad spectrum of antibacterial activity. It has been used to treat a variety of serious infections and an increasing volume of literature documents its value in infections due to multiresistant bacteria. This article reviews the antibacterial activity, pharmacology, and clinical uses of imipenem.


Effects of seasonal changes in the Midwest on Crassulacean Acid Metabolism (CAM) in Opuntia humifusa Raf.
Seasonal changes in the Crassulacean Acid Metabolism (CAM) activity and growth characteristics of Opuntia humifusa Raf. were examined under midwest climatic conditions. Twenty-four hour studies were done at monthly intervals for two years, with diurnal changes in transpiration, gas exchange, and titratable acidity monitored under natural conditions. CAM activity was observed only from April to September, but occurred regardless of changes in temperature or precipitation. The maximum rate of dark CO2 uptake occurred in May, while greatest acid fluctuations coincided with flowering, new growth, and high tissue water content in June. In spite of conditions favorable for CAM, acidification and rate of dark CO2 assimilation decreased progressively through September as stem water content dropped and shoot production ceased. No CAM was evident during sub-zero winter months and tissue water content decreased to only 65% (Ψ<-20 bars). Winter survival of plants in test plots was found to be affected by the amount of water received the preceding growing season; the driest group showing the lowest mortality rate.Although spring and autumn were considered periods likely to exhibit CAM, it was not observed during those months just prior to or immediately following winter (Oct. and March). Acid fluctuations were minimal with CO2 being taken up during the day and released at night, indicating some degree of flexibility in the CAM activity of Opuntia humifusa.


The effect of etretinate compared with different regimens of PUVA in the treatment of persistent palmoplantar pustulosis.
Eighty-four patients with persistent palmoplantar pustulosis (PPP) of long duration were treated with either etretinate or one of three PUVA regimens. PUVA was given either with oral methoxsalen (thirteen cases), with a 1% methoxsalen cream (thirty-three cases) or with trioxsalen baths (eighteen cases). Twenty patients were treated with etretinate. Patients were assessed every fourth week. A mean score for each group was calculated at each visit based on erythema, desquamation, induration and pustulation. In addition, the number of pustules was calculated at each visit. After 12 weeks four of twenty-eight patients treated with local methoxsalen and fourteen of seventeen patients treated with etretinate had completely cleared. At this stage no patient treated with local trioxsalen or oral methoxsalen showed complete clearance.


Initial experience with bendamustine in patients with recurrent primary central nervous system lymphoma: a case report.
Novel therapeutic options for patients with recurrent primary central nervous system lymphoma (RPCNSL) are needed. Bendamustine, a bifunctional purine analog/alkylating agent, is approved for use in patients with progressive systemic indolent non-Hodgkin's B-cell lymphomas. Limited data suggests that bendamustine may partition into the brain in the setting of a disrupted blood-brain barrier. This report describes the first known experience of patients with RPCNSL treated with bendamustine. Therapy was well-tolerated and best response was noted as stable disease after eight cycles of bendamustine followed by a subsequent local systemic recurrence found at five months follow-up. CNS involvement in this patient remained stable 20 + months post-bendamustine treatment. Based on our observations, further neuropharmacokinetic and efficacy studies with bendamustine may be warranted in this patient population.


PD-1+ T-Cells Correlate with Nerve Fiber Density as a Prognostic Biomarker in Patients with Resected Perihilar Cholangiocarcinoma.
Perihilar cholangiocarcinoma (pCCA) is a hepatobiliary malignancy, with a dismal prognosis. Nerve fiber density (NFD)-a novel prognostic biomarker-describes the density of small nerve fibers without cancer invasion and is categorized into high numbers and low numbers of small nerve fibers (high vs low NFD). NFD is different than perineural invasion (PNI), defined as nerve fiber trunks invaded by cancer cells. Here, we aim to explore differences in immune cell populations and survival between high and low NFD patients. We applied multiplex immunofluorescence (mIF) on 47 pCCA patients and investigated immune cell composition in the tumor microenvironment (TME) of high and low NFD. Group comparison and oncological outcome analysis was performed. CD8+PD-1 expression was higher in the high NFD than in the low NFD group (12.24 × 10-6 vs. 1.38 × 10-6 positive cells by overall cell count, p = 0.017). High CD8+PD-1 expression was further identified as an independent predictor of overall (OS; Hazard ratio (HR) = 0.41; p = 0.031) and recurrence-free survival (RFS; HR = 0.40; p = 0.039). Correspondingly, the median OS was 83 months (95% confidence interval (CI): 18-48) in patients with high CD8+PD-1+ expression compared to 19 months (95% CI: 5-93) in patients with low CD8+PD-1+ expression (p = 0.018 log rank). Furthermore, RFS was significantly lower in patients with low CD8+PD-1+ expression (14 months (95% CI: 6-22)) compared to patients with high CD8+PD-1+ expression (83 months (95% CI: 17-149), p = 0.018 log rank). PD-1+ T-cells correlate with high NFD as a prognostic biomarker and predict good survival; the biological pathway needs to be investigated.


Effect of methylene blue and cobaltous chloride on the alloxan-induced changes in collagen characteristics in the skin of garden lizard Calotes versicolor.
In the present study the effect of two chemicals such as methylene blue and CoCl2 on the accelerated ageing of collagen in alloxan-diabetic lizards has been tested. Both methylene blue and CoCl2 have been found to accelerate the ageing of collagen in normal lizards. While methylene blue enhanced the effects of alloxan in alloxanized lizards, CoCl2 tended to reverse it. It appears that methylene blue acts as a potentiator of alloxan; CoCl2, on the contrary, showed clear anti-ageing effects.


Qualitative analysis of a reaction-diffusion SIRS epidemic model with nonlinear incidence rate and partial immunity.
In this paper, a reaction-diffusion SIRS epidemic model with nonlinear incidence rate and partial immunity in a spatially heterogeneous environment is proposed. The well-posedness of the solution is firstly established. Then the basic reproduction number R0 is defined and a threshold dynamics is obtained. That is, when R0 < 1, the disease-free steady state is locally stable, which implies that the disease is extinct, when R0 > 1, the disease is permanent, and there exists at least one positive steady state solution. Finally, the asymptotic profiles of the positive steady state solution as individuals disperse at small and large rates are investigated. Furthermore, as an application of theoretical analysis, a numerical example involving the spread of influenza is discussed. Based on the numerical simulations, we find that the increase of transmission rate and spatial heterogeneity can enhance the risk of influenza propagation, and the increase of diffusion rate, saturation incidence for susceptible and recovery rate can reduce the risk of influenza propagation. Therefore, we propose to reduce the flow of people to lower the effect of spatial heterogeneity, increase the transfer of infected individuals to hospitals in surrounding areas to increase the diffusion rate, and increase the construction of public medical resources to increase the recovery rate for controlling influenza propagation.


An unusual transposon encoding heat shock inducible and developmentally regulated transcripts in Dictyostelium.
We have isolated and characterized a transposable element from Dictyostelium discoideum denoted Tdd-1. There are approximately 50 complete copies of the element per haploid genome and approximately 100-150 partial elements. Southern blots of DNA from different Dictyostelium discoideum strains show that Tdd-1 is a mobile element. Tdd-1 is 4.9 kb long, with 313 bp inverted repeats. These repeats lie near the termini, but unlike other transposable elements one end of Tdd-1 extends 36 bp past the repeat and the other extends 1 bp. Tdd-1 encodes a series of developmentally regulated transcripts, all with the same polarity, that increase dramatically in abundance after approximately 10 hr of development. We have also identified a heat shock inducible transcript of the opposite polarity.


Volumetric bone mineral density is an important tool when interpreting bone mineralization in healthy children.
In adults, it is well known that gender influences bone mass, but studies in children have shown contradictory results. Also, conflicting results have been reported regarding bone mineral density in obese children. To investigate bone parameters in healthy 8-year-old children and relate them to anthropometry and self-reported physical activity (PA). Bone measurements were performed with dual X-ray absorptiometry in 96 children, and questionnaires were used to assess self-reported PA. Bone mineral content and density differed by gender. Eighteen percent of the children were overweight/obese and they had higher bone mineral content and density than children with normal weight. Bone mineral apparent density (g/cm(3)) of the lumbar spine did not differ, since the vertebral size differed, as was also the case between genders. Self-reported weight-bearing PA influenced bone mass in the hip. PA influenced bone mineralization at this age. The differences in bone mineral content and density in healthy children would mainly be explained by the differences in bone size, reflected in body height and the width of the vertebrae. This indicates the importance of determining volumetric bone mineralization in children.


Hippocampal-cortical functional connectivity during memory encoding and retrieval.
Memory encoding and retrieval are critical sub-processes of episodic memory. While the hippocampus is involved in both, less is known about its connectivity with the neocortex during memory processing in humans. This is partially due to variations in demands in common memory tasks, which inevitably recruit cognitive processes other than episodic memory. Conjunctive analysis of data from different tasks with the same core elements of encoding and retrieval can reduce the intrusion of patterns related to subsidiary perceptual and cognitive processing. Leveraging data from two large-scale functional resonance imaging studies with different episodic memory tasks (514 and 237 participants), we identified hippocampal-cortical networks active during memory tasks. Whole-brain functional connectivity maps were similar during resting state, encoding, and retrieval. Anterior and posterior hippocampus had distinct connectivity profiles, which were also stable across resting state and memory tasks. When contrasting encoding and retrieval connectivity, conjunctive encoding-related connectivity was sparse. During retrieval hippocampal connectivity was increased with areas known to be active during recollection, including medial prefrontal, inferior parietal, and parahippocampal cortices. This indicates that the stable functional connectivity of the hippocampus along its longitudinal axis is superposed by increased functional connectivity with the recollection network during retrieval, while auxiliary encoding connectivity likely reflects contextual factors.


Ploidy, ascus formation and recombination in Torulaspora (Debaryomyces) hansenii.
X-ray inactivation studies on the type strain of Torulaspora hansenii carried out to determine ploidy, provided proof that the species has a haplontic life cycle, a fact which hitherto has only been presumed. Observations on the genesis of the ascus by light microscopy and transmission electron microscopy provide no evidence for, what some earlier workers in this field have presumed to be, heterogamous conjugation between a mother cell and its bud. They do, however, show that asci, bearing obliquely-attached, vestigal, bud-like appendages, arise from some cells to form single, non-abstricting, and frequently, recurving protuberances which enlarge. These could, conceivably, be responsible for the impression that abstricted buds are connected to the mother-cells by bent copulatory tubes. The formation during sporulation of elongated protuberances and the presence of a medial, electron-dense line within the electron-translucent layer of the walls of ascospores fixed with OsO4 preclude the possibility of using these features to differentiate between the genera Torulaspora and Debaryomyces. Furthermore, recombinant studies, which involved the use of auxotrophic mutants, indicated that during sporulation the fusion of independent cells accounted for only 0.03-0.6% of the asci formed. The conclusion was reached that somatogamous autogamy must be the main agency of diploidization and that the species is largely inbreeding.


Universal Health Insurance and its association with long term outcomes in Pediatric Trauma Patients.
Racial disparities in mortality exist among pediatric trauma patients; however, little is known about disparities in outcomes following discharge. We conducted a longitudinal cohort study of children admitted for moderate to severe trauma, covered by TRICARE from 2006 to 2014. Patients were followed up to 90days after discharge. All children <18 years with a primary trauma diagnosis, an Injury Severity Score >9 and 90days of follow-up after discharge were included. Complications, readmissions and utilization of healthcare services up to 90days after discharge were compared between Black and White patients. Of the 5192 children included, majority were White (74.6%, n=3871), with 15.4% Black (n=800) and 10.0% Other (n=521). Most common injuries involved the extremities or the pelvic girdle followed by the head or neck. Complication and readmission rates were 3.6% and 8.9% within 30days of discharge respectively and 4.4% and 9.3% within 90days of discharge. 99.0% of children had at least one outpatient visit by 90days. After adjusting for patient and injury characteristics no significant differences were detected between Black and White children in outcomes after discharge. Universal insurance may help mitigate disparities in post discharge care in pediatric trauma populations by increasing access to outpatient services overall and within each racial group. Further studies are required to determine the appropriate timing and frequency of follow up care in order to achieve maximum reduction in use of acute care services after discharge.


Alterations in gastric acid secretion following hepatic vagotomy at a stage of development in rats.
The relation of gastric acid secretion to the hepatic vagal section was examined in consideration of developmental stages of a rat. Acid outputs in rats deprived of food for 22 hr before the experiment were estimated with or without insulin. The animals were classified into five groups according to their body weights at the experiments (50, 100, 200, 300 and 400 g). Hepatic vagotomy was effective in decreasing acid output in all of the groups treated with food deprivation and insulin, and it was found that there was a close relationship between the output and glucose concentration in the portal blood. In rats treated only with food deprivation, hepatic vagotomy produced different effects for the five groups; the vagotomy failed to cause acid response when the rats weighed about 300 and 400 g, while in the animals weighing about 50, 100 and 200 g acid outputs were reduced following the vagotomy. It was noted that the sensitivity to hypoglycemia in the acid output was greater in the young rats than the older ones. Results suggest that function of the hepatic vagal nerve may be prominent in modulating acid secretion in an earlier stage of development when the animals are most sensitive to hypoglycemia.


Type III and type IV endoleak: toward a complete definition of blood flow in the sac after endoluminal AAA repair.
In this document the authors continue to refine their seminal categorization of endoleak, a major complication of endovascular aneurysm repair. In addition to type I (related to the graft device itself) and type II (retrograde flow from collateral branches) endoleak, they propose two new categories: endoleak due to fabric tears, graft disconnection, or disintegration would be classified type III, and flow through the graft presumed to be associated with graft wall "porosity" would be categorized as type IV endoleak.


Four deaths due to intravenous injection of cocaine.
Cocaine is a potent psychotropic drug that alters mood and behavior by stimulating the central nervous system. Deaths from abuse of cocaine are relatively rare. Most such deaths appear to be related to the intravenous injection of the drug. Acute fatal cocaine intoxication is characterized by headache, cold sweats, rapid pulse, tremors and nausea, followed by convulsions, unconsciousness and death. The prime mode of death appears to be respiratory paralysis, secondary to the effects of cocaine on the medullary portion of the brain. This paper presents four deaths due to acute cocaine intoxication following intravenous injection. Blood concentrations of cocaine were 0.11, 0.37, 0.36 and 0.75 mg/dl.


Impact of smelter re-development on spatial and temporal airborne Pb concentrations.
Total suspended particulate (TSP) and PM10 filters collected from two ambient air monitoring stations in Port Pirie were analysed to determine the impact of a lead (Pb) smelter redevelopment on air quality parameters including total elemental concentration, Pb isotopic ratio, Pb bioaccessibility and Pb speciation. Filters from 2009 to 2020 were analysed with a focus on samples from 2017 (immediately prior to smelter redevelopment) and 2020 (post-smelter redevelopment). Lead concentration in 2009-2020 TSP was variable ranging up to 6.94 μg m-3 (mean = 0.57 μg m-3), however, no significant decrease in Pb concentration was observed at either Port Pirie West (p = 0.56, n = 34) or Oliver Street (p = 0.32, n = 28) monitoring stations when 2017 and 2020 TSP values were compared. Similarly, no significant difference (p = 0.42) in PM10 Pb concentration was observed in 2017 (mean = 0.80 μg m-3) and 2020 (0.60 μg m-3) Oliver Street filters. Although no change in percentage Pb bioaccessibility was observed when 2017 and 2020 Port Pirie West TSP samples were compared (mean of 88.7% versus 88.0%), Pb bioaccessibility was lower (p < 0.005) in both 2020 TSP (mean of 83.9% versus 62.9%) and PM10 (mean of 70.8% versus 58.3%) Oliver Street filters compared to 2017. While scanning electron microscopy, energy dispersive x-ray spectroscopy identified a number of Pb phases within filters (galena, anglesite, cerussite, conglomerates), differences in Pb speciation between 2017 and 2020 filters could not be identified although it was presumed that this influenced Pb bioaccessibility outcomes at Oliver Street. Data from this study suggests that recent smelter redevelopments have not significantly decreased the concentrations of airborne Pb in Port Pirie although re-entrainment of soil-Pb from historical impact may also be a contributing Pb source.


Vitamin D receptor FokI, BsmI, and TaqI polymorphisms and susceptibility to rheumatoid arthritis : A meta-analysis.
The aim of this study was to explore whether vitamin D receptor (VDR) polymorphisms are associated with susceptibility to rheumatoid arthritis (RA). Meta-analyses were conducted on the associations between the VDR FokI, BsmI, and TaqI polymorphisms and RA. A total of seven studies were considered in the meta-analysis, involving a total of 923 patients and 912 controls. Meta-analysis of the VDR FokI polymorphism showed no association between RA and the F allele in the entire studied cohort (odds ratio, OR = 1.1740, 95 % confidence interval, CI = 0.994-1.387, p = 0.059). However, stratification by ethnicity revealed a significant association between the F allele and RA in Europeans (OR = 1.402, 95 % CI = 1.126-1.746, p = 0.003). Furthermore, an association was found between RA and the VDR FokI polymorphism using both the dominant model and homozygote contrast. Meta-analysis revealed no association between RA and the VDR BsmI B and TaqI T polymorphisms in Europeans (OR for the B allele = 1.065, 95 % CI = 0.911-1.245, p = 0.427; OR for the T allele = 1.065, 95 % CI = 0.834-1.361, p = 0.613). This meta-analysis suggests that the VDR FokI polymorphism is associated with susceptibility to RA in European populations.


Blood acid-base changes during experimental emersion and reimmersion of the intertidal crab Carcinus maenas (L.).
The time course of blood acid-base changes was studied in Carcinus maenas during experimental emersion and reimmersion at 15 degrees C by measuring pH and PCO2 and calculating bicarbonate concentration. During the first 4 hr of the emersion period, a marked rise of PCO2 entails a respiratory acidosis which is progressively compensated by a slow increase of the bicarbonate concentration; this compensation is completed after about 100 hr and the steady state mean pH value approximates that found for the immersed controls. Return to aquatic conditions is characterized by a rapid decrease of both PCO2 and blood bicarbonate concentration. During the first 2 hr of the reimmersion period, the decrease of blood bicarbonate concentration is accompanied by excretion of a significant amount of base in water, thus suggesting that readjustments of acid-base balance take place at least in part by ionic exchanges between the blood and the external milieu. Initial status was restored after 9 hr. These finding agree with the general views concerning the blood acid-base changes which must occur at transition from water-to air-breathing.


The French paradox: possible involvement of ethanol in the protective effect against cardiovascular diseases.
This review surveyed the literature on the cardioprotective effects of moderate alcohol consumption. The putative cardioprotective effects of alcohol and other substances in alcoholic beverages are discussed by taking "the French paradox" as a starting point. A survey of the literature highlighted various hypotheses explaining the protective effects of moderate alcohol consumption. The positive effects of moderate quantities of alcohol have been attributed in part to increased plasma levels of high-density lipoprotein, an inhibition of platelet aggregation, and improved endothelial function. Many investigators have claimed that wine is the significant factor explaining the French paradox. Red wine has been shown ex vivo to inhibit low-density lipoprotein oxidation, increase antioxidant capacity in humans, and reduce susceptibility of human plasma to lipid peroxidation. The non-alcoholic fraction of wine, represented mainly by phenolic compounds, may be the primary factor responsible for this protective effect. However, the protective effects are not restricted to a particular type of alcoholic drink, suggesting that alcohol per se rather than compounds specific to certain beverages reduces mortality risk. It is difficult to explain the effect of alcohol on risk factors associated with cardiovascular diseases by a uniform biochemical mechanism. Moreover, its protective effects are counterbalanced by its addictive properties.


Application of positron emission tomography in the heart. Council on Scientific Affairs. Report of the Positron Emission Tomography Panel.
This report discusses experimental and clinical applications of positron emission tomography to the heart, including measurements of blood flow to the myocardium and studies of metabolism and experimental injury. Most initial clinical studies have concentrated on ischemic heart disease, but the technique also has potential for investigation of cardiomyopathies, studying the neural control of the heart, and evaluating the effects of drugs on cardiac tissues.


Birth weight, birth type and pre-weaning survivability of West African Dwarf goats raised in the Dangme West District of the Greater Accra Region of Ghana.
A study was conducted on 441 West African Dwarf goat (WADG) kids born from September 1999 to August 2002 at three locations in the Dangme West District of the Greater Accra Region in Ghana to determine the effect of environmental factors on birth weight, birth type and pre-weaning survivability. The overall mean birth weight was 1.32 +/- 0.01 kg. Birth weights were similar (p > 0.05) between single births (1.43 +/- 0.04 kg) and twins (1.34 +/- 0.03 kg), but singles were significantly heavier (p < 0.05) than triplets (1.24 +/- 0.05 kg). Kids born in the major wet season recorded the best mean birth weight (1.37 +/- 0.04 kg). Sex, parity of does, and year of birth of kids had no significant (p > 0.05) effect on birth weight. Mean litter size was 1.93 +/- 0.03. Does that kidded in the dry season had a significantly (p < 0.05) higher litter size (2.05 +/- 0.06) than those that kidded in the minor wet season (1.80 +/- 0.10). Litter size of first-parity kids was significantly smaller (p < 0.05) than in subsequent parities. Litter size dropped significantly (p < 0.05) from year 2 (2.03 +/- 0.07) to year 3 (1.83 +/- 0.07). Pre-weaning survivability was 79.1% and season of kidding had a significant (p < 0.05) effect on survivability. Survivability of quadruplets (61.8%) was significantly (p < 0.05) lower than in the other birth types.


Oxygen binding characteristics of the hemocyanins of two deep-sea hydrothermal vent crustaceans.
Effects of pH and temperature on hemocyanin oxygen binding were examined using dialyzed blood from the hydrothermal vent crustaceans Bythograea thermydron (Brachyura) and Alvinocaris lusca (Caridea); blood samples were dialyzed against physiological salines having the same inorganic ion concentration as the blood. Hemocyanin of dialyzed B. thermydron blood demonstrated the highest O2 affinity at 10 degrees C (P50 = 1.8, 3.4 and 4.5 Torr at pH = 8.01, 7.7 and 7.4, respectively), with lower affinities at both higher and lower temperatures for all experimental pH values. A moderate Bohr effect (delta logP50/delta pH = -0.34 to -0.67) was found at all experimental temperatures (2-20 degrees C, pH 7.4-8.01), and a CO2 effect, independent of the pH Bohr effect, was measured at 5 degrees C. Hill coefficients varied widely (n50 = 0.95-3.95) and did not appear to vary with temperature or pH. The hemocyanin oxygen binding properties of B. thermydron blood are not affected by dialysis against salines having the same inorganic ion composition as the blood. Hemocyanin of dialyzed blood from A. lusca demonstrated a reverse temperature effect and a large Bohr effect (delta logP50/delta pH = -0.77 at 5 degrees C, pH 7.4-7.7). Functional aspects of oxygen binding are discussed in relation to the hydrothermal vent environment, and in the context of recent work on crustacean hemocyanins.


Effects of opium addiction on bleeding after coronary artery bypass graft surgery: report from Iran.
Opium abuse is a major type of drug abuse in Iran. This study was designed to find the possible relation between opium addiction and excessive bleeding after coronary artery bypass graft (CABG) surgery. In a historical cohort study during a 1.5-year period, consecutive patients scheduled for elective CABG surgery were assigned to two group on the basis of having or not having the criteria for inhalational opium addiction. Before and after operations, the complete blood count, bleeding time, prothrombin time, partial thromboplastin time, and platelet count were checked for all patients. The volumes of infused red blood cells during and after the operation were recorded. After operations, the volumes of bleeding through the patients' chest tubes were recorded. The recorded data were analyzed using SPSS software version 11.5. Independent t, chi-square and repeated measure tests were used; and P < 0.05 was considered statistically significant. In total, 84 nonaddicted patients were assigned in group 1, and 110 patients who fulfilled the addiction criteria were assigned in group 2. Total bleeding from the three chest tubes was significantly different between the two groups (P = 0.001). The mean hemoglobin level, prothrombin time, partial thromboplastin time, and platelet counts before and after the operations were similar in the two groups. Opium-addicted patients received more packed red blood cells during and after the operations. Inhalational opium addiction might lead to more hemorrhage after CABG surgery. It is recommended that cardiac surgeons consider these patients at high risk for major complications after surgery.


Association of preoperative sensory monofixation with surgical failure in adult-onset divergence insufficiency-type esotropia.
We investigated the frequency of sensory monofixation in patients with adult-onset divergence insufficiency esotropia and whether preoperative sensory monofixation was associated with surgical failure. Twenty-five patients with esotropia greater at distance than near who underwent bilateral medial rectus recessions were included. Near stereoacuity was measured preoperatively and 8 weeks postoperatively using the Randot Preschool test. Patients with best-corrected visual acuity worse than 0.3 logMAR in either eye or preoperative diplopia "rarely" or "never" in straight-ahead gaze at distance were excluded to minimize the inclusion of decompensated childhood strabismus. Sensory monofixation was defined as stereoacuity of 200 arcsec or worse and bifixation as 40 or 60 arcsec. Surgical failure was defined as esodeviation of >4Δ or exodeviation of >10Δ at distance or near, assessed 8 weeks (range, 6-17 weeks) postoperatively. We calculated the frequency of monofixation and surgical failure rates among patients with preoperative monofixation and those with preoperative bifixation. Preoperatively, sensory monofixation was common in divergence insufficiency-type esotropia (16 of 25 [64%]; 95% CI, 45%-83%). None of those with preoperative sensory monofixation had surgical failure, which does not support an association of surgical failure with preoperative monofixation.


Comparative Distribution, Correlation, and Chemometric Analyses of Selected Metals in Scalp Hair of Angina Patients and Healthy Subjects.
Numerous epidemiological studies are preponderance of evidences intimating development of coronary artery disease caused by metal imbalance. The present study was aimed to analyze Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Pb, Sr, and Zn in the scalp hair of angina patients and healthy subjects/controls employing HNO3-HCLO4-based wet digestion followed by quantification with atomic absorption spectrophotometry. The average concentrations of Cd, Cu, Cr, Fe, Mn, Pb, and Sr revealed significantly higher levels in scalp hair of patients than controls; however, Na and Zn were appreciably higher in healthy subjects. Dissimilarity in the trace metal distribution was also observed with gender, residence, dietary habits, and smoking habits of both donor groups. The correlation study and multivariate analyses revealed diverse mutual relationships and apportionment of the trace metals in the scalp hair of patients and controls.


True congenital aneurysm of the septum primum not associated with obstructive right- or left-sided lesions: identified by two-dimensional echocardiography and angiography in a newborn.
Aneurysms of the interatrial septum are unusual anomalies that have been demonstrated by (M-mode and 2-dimensional) echocardiography in patients with complex congenital heart defects. They have also been found at autopsy in adults without heart defects. Complications have resulted from these aneurysms in adults. A true aneurysm of the septum primum was an incidental finding identified by 2-dimensional echocardiography and angiography in a newborn with an atrial septal defect.


Cl transport across the basolateral membrane in frog skin epithelium.
Cellular Cl concentrations were determined by electron microprobe analysis to obtain further insight into the Cl transport across the basolateral membrane of the frog skin epithelium. Cl-free media on the serosal side led in all epithelial layers within 1 h to a decrease in cellular Cl concentration from about 40 to 15 mmol/kg wet wt, whereas the application of Cl-free solutions or amiloride to the apical side had no effect. Na-free media, furosemide or bumetanide on the serosal side had little effect on cellular Cl but abolished the Cl-reuptake into Cl-depleted cells. It is concluded that cellular Cl concentration is maintained above electrochemical equilibrium by a co-transport system, which is relatively silent under control conditions.


A retrospective long-term comparison of early RME-facemask versus late Hybrid-Hyrax, alt-RAMEC and miniscrew-supported intraoral elastics in growing Class III patients.
To compare the long-term dentoskeletal effects of early treatment with banded or bonded RME (Rapid Maxillary Expansion)-Face Mask (RME-FM) versus late treatment with bonded Hybrid-Hyrax, alt-RAMEC (Alternate Rapid Maxillary Expansion and Contraction) and intraoral Class III elastics anchored to miniscrew-reinforced-Lower-lingual-Arch (alt-RAMEC-HH-LLA) in growing, maxillary retrognathic patients. Two groups were matched at long-term follow-up retrospectively. Patients received either early RME-FM (n=16, 5 males, 11 females, age T1: 6.5±0.9 years, age T2: 15.8±2.5 years) or late alt-RAMEC-HH-LLA (n=15, 7 males, 8 females, age T1: 12.52±0.94 years, age T2: 16.8±0.9 years). Total follow-up was 9.2±2.3 years and 4.2±0.2 years respectively, including fixed appliances to compete treatment. Both treatments resulted in Class III correction except one unsuccessful case of alt-RAMEC-HH-LLA. Active maxillary protraction was 1.6±0.5years with RME-FM and 0.5 years with alt-RAMEC-HH-LLA being significantly shorter (P<0.001). Values at T2 estimation with multivariate linear regression for correlated multiple outcomes, conditional on baseline estimates, age and sex showed alt-RAMEC-HH-LLA inducing significantly more retroclined lower incisors (mean: -6.11°; 95%CI: -10.66, -1.57; P=0.01), less overbite (mean: -1.28mm; 95%CI: -1.79, -0.761; P<0.001), less maxillo (Co-A)- (mean: -4.54mm; 95%CI: -7.91, -1.16; P=0.01) mandibular (Co-Gn) (mean: -10.5mm; 95%CI: -17.45, -3.55; P=0.003) projections/size, more open gonial angle (mean: 4.93°; 95%CI: 2.27, 7.59; P<0.001), and less S-N length (mean: -5.04mm; 95%CI: -6.57, -3.51; P<0.001). Patients treated with either early RME-FM or late Alt-RAMEC-HH-LLA had comparable overall post-pubertal skeletal and overjet corrections. However, the late Alt-RAMEC-HH-LLA showed less correction of dentoalveolar compensations and in particular of the mandibular incisors. The overbite, maxillary and mandibular projection and size were lower and the gonial angle was more open.


Mussel-inspired silver-releasing antibacterial hydrogels.
A silver-releasing antibacterial hydrogel was developed that simultaneously allowed for silver nanoparticle formation and gel curing. Water-soluble polyethylene glycol (PEG) polymers were synthesized that contain reactive catechol moieties, inspired by mussel adhesive proteins, where the catechol containing amino acid 3,4-dihydroxyphenylalanine (DOPA) plays an important role in the ability of the mussel to adhere to almost any surface in an aqueous environment. We utilized silver nitrate to oxidize polymer catechols, leading to covalent cross-linking and hydrogel formation with simultaneous reduction of Ag(I). Silver release was sustained for periods of at least two weeks in PBS solution. Hydrogels were found to inhibit bacterial growth, consistent with the well-known antibacterial properties of silver, while not significantly affecting mammalian cell viability. In addition, thin hydrogel films were found to resist bacterial and mammalian cell attachment, consistent with the antifouling properties of PEG. We believe these materials have a strong potential for antibacterial biomaterial coatings and tissue adhesives, due to the material-independent adhesive properties of catechols.


Age, symptoms, and functional outcome after mild traumatic brain injury.
Previous older adult studies have examined outcome from moderate-to-severe traumatic brain injury (TBI), but fewer have focused on the effects of milder brain injuries. This study examined age-related differences in symptom reporting and whether symptoms are differentially related to functional outcome based on age. Patients presenting with a head injury at the Tampere University Hospital emergency department (N = 325, aged 18-100) were evaluated at 1 week post injury on the Modified Rankin Scale and Rivermead Post Concussion Symptoms Questionnaire (RPQ). A quarter of participants had missing RPQ data, with missingness associated with greater age and strongly associated with pre-existing functional impairment, dementia, and/or neurological conditions. Among participants with complete data, participants <65 years old endorsed headaches, noise/light sensitivity, irritability, and frustration/impatience at a greater frequency than participants ≥65 years old. However, no differences were found in the number of symptoms endorsed or the total symptom severity score. The correlations between the severity of symptoms and change in function were similar between the two age groups. Older adults tended to report fewer symptoms, but symptoms had a roughly equivalent relationship with declines in functioning across age groups. A large percentage of older adults in this study had pre-injury dementia or neurological disease that contributed to missing data on the 1-week outcome measures. The results provide insight into the impact of mild spectrum TBI on older adults compared to younger patients.


"Burning tongue" sensation during routine coronary angiography--a phenomenon related to a rare coronary anomaly.
We present the case of rare coronary circulation anomaly discovered during the routine coronary angiography that was associated with unusual "burning" sensation reported by the patient.


[HIV infection in the intensive care unit].
Around 88,000 people in Germany live with an HIV (human immunodeficiency virus) infection. The proportion of those over 50 is around 30% and it has now become more likely that an older HIV-positive patient with other pre-existing illnesses will have to be treated in an intensive care unit (ICU) for a reason not directly associated with HIV than a person with a new HIV diagnosis for acquired immune deficiency syndrome (AIDS). Nevertheless, one third of patients with a new HIV diagnosis already have an advanced immune deficiency. Neurological or respiratory symptoms that require intensive medical care must be expected in these patients. The present article aims to raise awareness of these clinical pictures and the necessary differential diagnostics, and to provide the reader with an overview of the most important opportunistic infections and their treatment. In addition, the main focus of this article is on the possibilities of antiretroviral therapy in intensive care patients and provides the clinician with an overview of the start of treatment, the selection of suitable substances, and their dosage in the ICU.


Interactions between NEEP21, GRIP1 and GluR2 regulate sorting and recycling of the glutamate receptor subunit GluR2.
Trafficking of AMPA-type glutamate receptors (AMPAR) between endosomes and the postsynaptic plasma membrane of neurons plays a central role in the control of synaptic strength associated with learning and memory. The molecular mechanisms of its regulation remain poorly understood, however. Here we show by biochemical and atomic force microscopy analyses that NEEP21, a neuronal endosomal protein necessary for receptor recycling including AMPAR, is associated with the scaffolding protein GRIP1 and the AMPAR subunit GluR2. Moreover, the interaction between NEEP21 and GRIP1 is regulated by neuronal activity. Expression of a NEEP21 fragment containing the GRIP1-binding site decreases surface GluR2 levels and delays recycling of internalized GluR2, which accumulates in early endosomes and lysosomes. Infusion of this fragment into pyramidal neurons of hippocampal slices induces inward rectification of AMPAR-mediated synaptic responses, suggesting decreased GluR2 expression at synapses. These results indicate that NEEP21-GRIP1 binding is crucial for GluR2-AMPAR sorting through endosomes and their recruitment to the plasma membrane, providing a first molecular mechanism to differentially regulate AMPAR subunit cycling in internal compartments.


Di-μ-chlorido-bis-(chlorido-{8-[2-(di-methyl-amino)-ethyl-amino]-quinoline}-cadmium) ethanol monosolvate.
The title solvated bimetallic complex, [Cd2Cl4(C13H17N3)2]·C2H5OH, comprises two Cd2+ metal ions linked by a pair of μ2 Cl- ions. The coordination sphere around each Cd2+ ion is completed by three N atoms of a tridentate 8-[2-(di-methyl-amino)-ethyl-amino]quinoline ligand and another chloride ion to form a distorted fac-CdN3Cl3 octa-hedron. The ethanol mol-ecule is both an acceptor of an N-H⋯O and a donor of an O-H⋯Cl hydrogen bonds to its adjacent complex unit. In the crystal, weak aromatic π-π stacking is observed.


High BANCR expression is associated with worse prognosis in human malignant carcinomas: an updated systematic review and meta-analysis.
BRAF-activated noncoding RNA (BANCR) is aberrantly expressed in various tumor tissues and has been confirmed to function as a tumor suppressor or oncogene in many types of cancers. Considering the conflicting results and insufficient sampling, a meta-analysis was performed to explore the prognostic value of BANCR in various carcinomas. A comprehensive literature search of PubMed, Web of Science, EMBASE, Cochrane Library and the China National Knowledge Infrastructure (CNKI) was conducted to collect relevant articles. The pooled results showed a strong relationship between high BANCR expression and poor overall survival (OS) (HR (hazard ratio) =1.60, 95% confidence interval (CI): 1.19-2.15, P = 0.002) and recurrence-free survival (RFS) (HR = 1.53, 95% CI: 1.27-1.85, P < 0.00001). In addition, high BANCR expression predicted advanced tumor stage (OR (odds ratio) =2.39, 95% CI: 1.26-4.53, P = 0.008), presence of lymph node metastasis (OR = 2.03, 95% CI: 1.08-3.83, P = 0.03), positive distant metastasis (OR = 3.08, 95% CI: 1.92-4.96, P < 0.00001) and larger tumor sizes (OR = 1.63, 95% CI: 1.09-2.46, P = 0.02). However, no associations were found for smoking status (OR = 1.01, 95% CI: 0.65-1.56, P = 0.98), age (OR = 0.88, 95% CI: 0.71-1.09, P = 0.236) and sex (OR = 0.91, 95% CI: 0.72-1.16, P = 0.469). The sensitivity analysis of OS showed that the results of each publication were almost consistent with the combined results, and the merged results have high robustness and reliability. The results showed that elevated BANCR expression was associated with unfavorable prognosis for most cancer patients, and BANCR could serve as a promising therapeutic target and independent prognostic predictor in most of cancer types.


One-step enzyme immunochromatographic assay for theophylline.
The convenience of the previously described enzyme immunochromatography method for visually quantifying theophylline in whole blood has been improved with the development of a one-step protocol. The capillary migration and color generation in the two-step enzyme immunochromatographic assay have been combined into a single step. Ascorbic acid is used as a signal inhibitor to delay enzymatic color product formation until the inhibitor itself is consumed. The concept of internal delay reaction is presented and the mechanism of ascorbate's action as an inhibitor to temporarily delay color generation is described. The internal delay reaction has been applied to a practical one-step quantitative visual enzyme immunochromatographic assay for theophylline in whole blood.