Common causes of visual impairment in the elderly.
Aging is not a disease; rather, it is a process. As people age, visual impairment (VI) becomes more common. In 2010, the overall prevalence rate of vision impairment in all races was 25.66% in individuals aged ≥ 80 years, according to the estimate of the National Eye Institute at the National Institutes of Health. This review aimed to address the common causes of VI in the elderly. In this narrative review, an electronic search of the PubMed/MEDLINE database was conducted using "visual impairment" and "elderly" for the period between January 2010 and April 2021, to include randomized clinical trials and observational studies concerning VI in the elderly. The selected time period was chosen to provide an updated review. The search yielded 2955 articles published over the period of more than 11 years. The relevant randomized clinical trials or observational studies were included and reviewed. Cataracts, refractive errors, open-angle glaucoma, age-related macular degeneration, and diabetic retinopathy were the most common age-related ocular disorders leading to VI if untreated in the elderly. The loss of visual acuity can adversely affect quality of life in the elderly. Difficulty with activities of daily living related to VI can lead to social isolation, depression, and anxiety. Loss of vision in the elderly is linked to an increased risk of falls, hip fracture, depression, and poor quality of life. The most common causes of VI in the elderly are cataracts and refractive errors. VI in most ocular diseases is more prevalent in women than in men due to longer lifespan. The overall prevalence of the main causes of VI in the elderly is expected to increase; therefore, health policymakers should consider this when planning for the health-enhancement program of the population.


Tantala-based sol-gel coating for capillary microextraction on-line coupled to high-performance liquid chromatography.
A sol-gel organic-inorganic hybrid sorbent, consisting of chemically integrated tantalum (V) ethoxide (TaEO) and polypropylene glycol methacrylate (PPGM), was developed for capillary microextraction (CME). The sol-gel sorbent was synthesized within a fused silica capillary through hydrolytic polycondensation of TaEO and chemical incorporation of PPGM into the evolving sol-gel tantala network. A part of the organic-inorganic hybrid sol-gel network evolving in the vicinity of the capillary walls had favorable conditions to get chemically bonded to the silanol groups on the capillary surface forming a surface-bonded coating. The newly developed sol-gel sorbent was employed to isolate and enrich a variety of analytes from aqueous samples for on-line analysis by high-performance liquid chromatography (HPLC) equipped with a UV detector. CME was performed on aqueous samples containing trace concentrations of analytes representing polycyclic aromatic hydrocarbons, ketones, alcohols, amines, nucleosides, and nucleotides. This sol-gel hybrid coating provided efficient extraction with CME-HPLC detection limits ranging from 4.41pM to 28.19 pM. Due to direct chemical bonding between the sol-gel sorbent coating and the fused silica capillary inner surface, this sol-gel sorbent exhibited enhanced solvent stability. The sol-gel tantala-based sorbent also exhibited excellent pH stability over a wide pH range (pH 0-pH 14). Furthermore, it displayed great performance reproducibility in CME-HPLC providing run-to-run HPLC peak area relative standard deviation (RSD) values between 0.23% and 3.83%. The capillary-to-capillary RSD (n=3), characterizing capillary preparation method reproducibility, ranged from 0.24% to 4.11%. The results show great performance consistency and application potential for the sol-gel tantala-PPGM sorbent in various fields including biomedical, pharmaceutical, and environmental areas.


Analysis of clinical distribution and drug resistance of klebsiella pneumoniae pulmonary infection in patients with hypertensive intra cerebral hemorrhage after minimally invasive surgery.
To investigate the clinical distribution and drug resistance of Klebsiella pneumoniae pulmonary infection in patients with hypertensive intracerebral hemorrhage after minimally invasive surgery. A total of 658 patients with hypertensive intracerebral hemorrhage who underwent minimally invasive surgery admitted to the intensive care unit (ICU) and the Department of Neurology of Affiliated Hospital of Hebei University from January 2015 to January 2020 were enrolled and divided into two groups: the observation group and the control group. Three hundred and thirty-three cases with postoperative pulmonary infection were included into the observation group, and 325 cases without postoperative pulmonary infection were divided into the control group. The intubation time, neurological deficiency score and Glasgow coma scale (GCS) of the two groups were analyzed and compared. Automatic microbial identification system was utilized to isolate bacteria from patients in the observation group, identify Klebsiella pneumoniae, and analyze Klebsiella pneumoniae infection, clinical department distribution, and age distribution. The Kirby-Bauer method was adopted to carry out the drug susceptibility test of Klebsiella pneumoniae infection. The intubation time and neurological deficiency score of patients with hypertensive cerebral hemorrhage in the observation group were significantly higher than those in the control group (p<0.05), while the GCS score was significantly lower than that in the control group (p<0.05). A total of 403 strains of pathogenic bacteria were isolated from 325 patients in the observation group, of which 52 strains of Klebsiella pneumoniae were detected in 52 patients with postoperative pulmonary infection, accounting for 12.90%. The detection rates of Klebsiella pneumoniae in ICU and neurology department were 53.85% and 46.15%, respectively. Klebsiella pneumoniae had the highest detection rate (40.38%) in people aged 70 years and above. Moreover, fifty-two strains of Klebsiella pneumoniae showed low drug resistance rate (<20%) to cefoperazone/sulbactam, piperacillin/tazobactam, cefoxitin, imipenem, meropenem, amikacin, ciprofloxacin, and levofloxacin. For patients with hypertensive cerebral hemorrhage who have pulmonary infection after minimally invasive surgery, risk factors causing infection should be identified in time, their Klebsiella pneumoniae infection should be correctly monitored, and antibiotics should be taken rationally to effectively promote the elimination of brain edema in patients and protect the cranial nerve function of patients.


Perioperative Cardiometabolic Targets and Coronary Artery Bypass Surgery Mortality in Patients With Diabetes.
Background Coronary artery bypass graft (CABG) surgery represents the preferred revascularization strategy for most patients with diabetes and multivessel disease. We aimed to evaluate the role of optimized, perioperative cardiometabolic targets on long-term survival in patients who underwent CABG. Methods and Results Single-institution retrospective study was conducted in patients with diabetes who underwent CABG between January 2010 and June 2018. Demographic, surgical, and cardiometabolic determinants were identified during the perioperative period. Clinical characteristics and longitudinal survival outcomes data were obtained. A total of 1534 patients with CABG were considered for analysis and 1273 met inclusion criteria. The mean age of patients was 63.3 years (95% CI, 62.7-63.8 years), and most were men (65%) and Hispanic or Latino (47%). Comorbidities included hypertension (95%) and dyslipidemia (88%). In total, 490 patients (52%) had a low-density lipoprotein cholesterol level >70 mg/dL. Furthermore, 390 patients (31%) had uncontrolled systolic blood pressure >130 mm Hg. Last, only 386 patients (29%) had a hemoglobin A1c level between 6% and 7%. At 5 years, 121 patients (10%) died. Failure to achieve goal systolic blood pressure was associated with all-cause (hazard ratio [HR], 1.573; 95% CI, 1.048-2.362 [P=0.029]) and cardiovascular (HR, 2.023; 95% CI, 1.196-3.422 [P=0.009]) mortality at 5 years post-CABG. In contrast, prescription of a statin during the perioperative interval demonstrated a protective effect for all-cause (HR, 0.484; 95% CI, 0.286-0.819 [P=0.007]) and cardiovascular (HR, 0.459; 95% CI, 0.229-0.920 [P=0.028]) mortality. There was no association between achievement of low-density lipoprotein cholesterol, triglycerides, non-high-density lipoprotein cholesterol, or hemoglobin A1c level goals and mortality risk at 5 years. Conclusions Among patients with diabetes, blood pressure control and statin therapy were the most important perioperative cardiometabolic survival determinants 5 years after CABG.


Evaluation of projection algorithms.
A number of linear and nonlinear mapping algorithms for the projection of patterns from a high-dimensional space to two dimensions are available. These two-dimensional representations allow quick visual observation of a data set. A combination of two popular mapping algorithms-Sammon's mean-square error technique and the triangulation method-is proposed to overcome the limitations in the individual algorithms. Some factors which describe the goodness of a projection are described, and a comparison is made of six of these algorithms by running them on four data sets. The results obtained support the use of the proposed algorithm.


Heat shock protein expression independently predicts survival outcome in schistosomiasis-associated urinary bladder cancer.
Heat shock proteins (HSPs) are synthesized by cells in response to various stress conditions, including carcinogenesis. These molecules have been studied in several malignancies, among which bladder carcinoma. This is the first study attempting to clarify the significance of HSP27 and HSP70 in schistosomiasis-associated bladder carcinoma and their relation to prognosis. HSP27 and HSP70 were localized immunohistochemically in tissue sections from 75 chistosomiasis-associated bladder carcinomas. Their expression was correlated with clinical and pathological features and their impact on 5-year disease-free survival was studied with univariate and multivariate analysis. In all, 45 and 51 patients were positive for HSP27 and HSP70 expression, respectively. A significant correlation was found between expression of both HSPs and tumor grade, stage, DNA ploidy and recurrence. In univariate analysis, a statistically significant association of HSP27 and HSP70 expression with 5-year disease-free survival was found. In a multivariate Cox proportional hazards model, both HSP27 and HSP70 maintained a statistically significant impact on survival. The current results indicate that expression of HSP27 and HSP70 may have prognostic relevance in patients with schistosomiasis-associated bladder cancer. HSPs may be useful markers for patients with this type of bladder carcinoma and may be used for predicting disease progression.


Two-photon quantum interference and entanglement at 2.1 μm.
Quantum-enhanced optical systems operating within the 2- to 2.5-μm spectral region have the potential to revolutionize emerging applications in communications, sensing, and metrology. However, to date, sources of entangled photons have been realized mainly in the near-infrared 700- to 1550-nm spectral window. Here, using custom-designed lithium niobate crystals for spontaneous parametric down-conversion and tailored superconducting nanowire single-photon detectors, we demonstrate two-photon interference and polarization-entangled photon pairs at 2090 nm. These results open the 2- to 2.5-μm mid-infrared window for the development of optical quantum technologies such as quantum key distribution in next-generation mid-infrared fiber communication systems and future Earth-to-satellite communications.


University students' achievement goals and approaches to learning in mathematics.
Achievement goals (AG) and students' approaches to learning (SAL) are two research perspectives on student motivation and learning in higher education that have until now been pursued quite independently. This study sets out: (a) to explore the relationship between the most representative variables of SAL and AG; (b) to identify subgroups (clusters) of students with multiple AG; and (c) to examine the differences between these clusters with respect to various SAL and AG characteristics. The participants were 680 male and female 1st year university students studying different subjects (e.g. mathematics, physics, economics) but all enrolled on mathematics courses (e.g. algebra, calculus). Participants completed a series of questionnaires that measured their conceptions of mathematics, approaches to learning, course experience, personal 2 x 2 AG, and perceived AG. SAL and AG variables were moderately associated and related to both the way students perceived their academic environment and the way they conceived of the nature of mathematics (i.e. the perceptual-cognitive framework). Four clusters of students with distinctive multiple AG were identified and when the differences between clusters were analysed, we were able to attribute them to various constructs including perceptual-cognitive framework, learning approaches, and academic performance. This study reveals a consistent pattern of relationships between SAL and AG perspectives across different methods of analysis, supports the relevance of the 2 x 2 AG framework in a mathematics learning context and suggests that AG and SAL may be intertwined aspects of students' experience of learning mathematics at university.


Susceptibility to beta-lactam antibiotics of mutant strains of Xanthomonas maltophilia with high- and low-level constitutive expression of L1 and L2 beta-lactamases.
Xanthomonas maltophilia produces two inducible beta-lactamases, L1 and L2, and resists the antimicrobial activity of beta-lactam antibiotics, including carbapenems. L1 is a zinc-metaloenzyme with carbapenemase activity; L2 is an unusual cephalosporinase. Mutant strains with high- and low-level constitutive expression of these enzymes were derived from three reference strains of X. maltophilia. With a single exception, the mutant strains had altered expression of both enzymes, indicating that these beta-lactamases share regulatory components. The exception was a mutant strain that had low-level constitutive (basal) expression of L1 enzyme but remained inducible for L2. A parent strain with low-level beta-lactamase inducibility was more susceptible to penicillins, cephalosporins and carbapenems than were those in which higher levels of enzyme activity were inducible. Mutations that caused high-level constitutive beta-lactamase expression increased resistance to penicillins and newer cephalosporins. beta-Lactamase basal mutant strains, including the one that remained inducible for L2 enzyme, were more susceptible than inducible strains to these drugs. Organisms with inducible or high-level constitutive beta-lactamase expression were equally resistant to meropenem and imipenem but basal mutant strains, including the one that remained inducible for L2 enzyme, were more susceptible to meropenem than imipenem. Minimal inhibitory concentrations of meropenem, penicillins and cephalosporins, but not imipenem, were greater on Mueller Hinton agar than on IsoSensitest or Diagnostic Sensitivity Test agars. This behaviour was independent of beta-lactamase inducibility, and may reflect permeability differences between cells grown on different media.


Clinical Markers of Anxiety Subtypes in Parkinson Disease.
The aim of this work was to investigate marker profiles for proposed anxiety subtypes in Parkinson disease (PD). We used the persistent anxiety, episodic anxiety, and avoidance behavior subscales of the Parkinson Anxiety Scale as dependent variables in multivariable linear regression analyses using a cross-sectional data set of 311 patients with PD. Independent variables consisted of a range of demographic, psychiatric, and disease-specific markers. In the most parsimonious model of persistent anxiety, higher Hamilton Depression Rating Scale scores, a history of anxiety, fewer years of education, lower Mini-Mental State Examination scores, lower Lawton Instrumental Activities of Daily Living scores, female sex, and complications of therapy (higher Unified Parkinson Disease Rating Scale part IV scores) were all associated with more severe persistent anxiety. Markers associated with more severe episodic anxiety included PD-specific disturbances of activities of daily living, complications of therapy, higher Hamilton Depression Rating Scale scores, female sex, and a history of anxiety. Finally, higher Hamilton Depression Rating Scale scores, a history of anxiety, complications of therapy, and longer disease duration were associated with avoidance behavior. After excluding clinically depressed patients with PD, disease severity and longer disease duration were significantly associated with episodic anxiety, but not with persistent anxiety. Persistent anxiety is mainly influenced by nonspecific markers, while episodic anxiety seems to be more PD-specific compared to persistent anxiety and may be more situational or contextual. These results provide support for possible distinct underlying constructs for anxiety subtypes in PD.


Mutations of the EPHB6 receptor tyrosine kinase induce a pro-metastatic phenotype in non-small cell lung cancer.
Alterations of Eph receptor tyrosine kinases are frequent events in human cancers. Genetic variations of EPHB6 have been described but the functional outcome of these alterations is unknown. The current study was conducted to screen for the occurrence and to identify functional consequences of EPHB6 mutations in non-small cell lung cancer. Here, we sequenced the entire coding region of EPHB6 in 80 non-small cell lung cancer patients and 3 tumor cell lines. Three potentially relevant mutations were identified in primary patient samples of NSCLC patients (3.8%). Two point mutations led to instable proteins. An in frame deletion mutation (del915-917) showed enhanced migration and accelerated wound healing in vitro. Furthermore, the del915-917 mutation increased the metastatic capability of NSCLC cells in an in vivo mouse model. Our results suggest that EPHB6 mutations promote metastasis in a subset of patients with non-small cell lung cancer.


[Thymidine kinase and nucleoside phosphotransferase in blood of animals after partial hepatectomy and in patients with inflammatory diseases].
Distinct activation of thymidine kinase (exceeding 2-3-fold the control values) as well as of nucleoside phosphotransferase (about 50% higher as compared with controls) was observed in blood serum of rats within 24 hrs after partial hepatectomy. Within 48 hrs after beginning of the tissue regeneration the activities of both these enzymes were decreased 1.5-fold; the values normalized within 72 hrs. These enzymatic activities were detected in blood of the patients with impairments of liver, kidney and some other tissues.


Molecular phylogeography and historical demography of a widespread herbaceous species from eastern North America, Podophyllum peltatum.
Glacial/interglacial cycles and topographic complexity are both considered to have shaped today's diverse phylogeographic patterns of taxa from unglaciated eastern North America (ENA). However, few studies have focused on the phylogeography and population dynamics of wide-ranging ENA herbaceous species occurring in forest understory habitat. We examined the phylogeographic pattern and evolutionary history of Podophyllum peltatum L., a widely distributed herb inhabiting deciduous forests of ENA. Using chloroplast DNA (cpDNA) sequences and nuclear microsatellite loci, we investigated the population structure and genetic diversity of the species. Molecular dating, demographic history analyses, and ecological niche modeling were also performed to illustrate the phylogeographic patterns. Our cpDNA results identified three main groups that are largely congruent with boundaries along the Appalachian Mountains and the Mississippi River, two major geographic barriers in ENA. Populations located to the east of the Appalachians and along the central Appalachians exhibited relatively higher levels of genetic diversity. Extant lineages may have diverged during the late Miocene, and range expansions of different groups may have happened during the Pleistocene glacial/interglacial cycles. Our findings indicate that geographic barriers may have started to facilitate the population divergence in P. peltatum before the Pleistocene. Persistence in multiple refugia, including areas around the central Appalachians during the Quaternary glacial period, and subsequent expansions under hospitable climatic condition, especially westward expansion, are likely responsible for the species' contemporary genetic structure and phylogeographic pattern.


Development of PD-1 blockade peptide-cell conjugates to enhance cellular therapies for T-cell acute lymphoblastic leukemia.
Blockade of the interaction of the immune checkpoint receptor programmed cell death protein (PD)-1 and its ligand PD-L1 has been found to be a promising cancer treatment. Our previous studies identified that nABPD1 competed with PD-L1 to bind PD-1. The aim of this study was to evaluate the efficacy and safety of anti-tumor immunotherapy of ICIK cells conjugated with peptides in vivo and in vitro. Here, we synthesized the nABPD1 derivatives SBP1 and SBP2 and showed that their binding efficiency to PD-1-positive improving cytokine-induced killer (ICIK) cells was 98 and 82%, respectively. The cytotoxicity of ICIK cells to T-cell acute lymphoblastic leukemia (T-ALL) cells was increased by conjugating with SBP1 or SBP2, which was 2 times higher than that of ICIK cells alone. Furthermore, mice experiments showed that the fluorescence intensity of leukemia cells in T-ALL xenograft models was reduced by more than 95%, indicating that the peptides enhanced the therapeutic effect in vivo, while morphological evaluations showed that the peptides had no toxicity to important organs. Therefore, peptide-cell conjugates (PCCs) may be a novel method to improve the efficacy of cancer immunotherapy by blocking PD-1 in T-ALL patients.


How is vaccine effectiveness scaled by the transmission dynamics of interacting pathogen strains with cross-protective immunity?
Many novel vaccines can cover only a fraction of all antigenic types of a pathogen. Vaccine effectiveness (VE) in the presence of interactions between vaccine strains and others is complicated by the interacting transmission dynamics among all strains. The present study investigated how the VE estimates measured in the field, based on estimated odds ratio or relative risks, are scaled by vaccination coverage and the transmission dynamics in the presence of cross-protective immunity between two strains, i.e. vaccine and non-vaccine strains. Two different types of epidemiological models, i.e. with and without re-infection by the same antigenic type, were investigated. We computed the relative risk of infection and the odds ratio of vaccination, the latter of which has been measured by indirect cohort method as applied to vaccine effectiveness study of Streptococcus pneumoniae. The VE based on the relative risk was less sensitive to epidemiological dynamics such as cross-protective immunity and vaccination coverage than the VE calculated from the odds ratio, and this was especially the case for the model without re-infection. Vaccine-induced (cross-protective) immunity against a non-vaccine strain appeared to yield the highest impact on the VE estimate calculated from the odds ratio of vaccination. It is essential to understand the transmission dynamics of non-vaccine strains so that epidemiological methods can appropriately measure both the direct and indirect population impact of vaccination. For pathogens with interacting antigenic types, the most valid estimates of VE, that are unlikely to be biased by the transmission dynamics, may be obtained from longitudinal prospective studies that permit estimation of the VE based on the relative risk of infection among vaccinated compared to unvaccinated individuals.


Progression of Beat-to-Beat Blood Pressure Variability Despite Best Medical Management.
Beat-to-beat variability in blood pressure (BP) is associated with recurrent stroke despite good control of hypertension. However, no study has identified rates of progression of beat-to-beat BP variability (BPV), its determinants, or which patient groups are particularly affected, limiting understanding of its potential as a treatment target. In consecutive patients one month after a transient ischaemic attack or nondisabling stroke (Oxford Vascular Study), continuous noninvasive BP was measured beat-to-beat over 5 minutes (Finometer). Arterial stiffness was measured by carotid-femoral pulse wave velocity (Sphygmocor). Repeat assessments were performed at the 5-year follow-up visit and agreement determined by intraclass correlation coefficient. Rates of progression of systolic BPV (SBPV) and diastolic BPV (DBPV) and their determinants were estimated by mixed-effect linear models, adjusted for age, sex, and cardiovascular risk factors. One hundred eighty-eight of 310 surviving, eligible patients had repeat assessments after a median of 5.8 years. Pulse wave velocity was highly reproducible but SBPV and DBPV were not (intraclass correlation coefficient: 0.71, 0.10, and 0.16, respectively), however, all 3 progressed significantly (pulse wave velocity, 2.39%, P<0.0001; SBPV, 8.36%, P<0.0001; DBPV, 9.7, P<0.0001). Rate of progression of pulse wave velocity, SBPV, and DBPV all increased significantly with age (P<0.0001), with an increasingly positive skew and were particularly associated with female sex (pulse wave velocity P=0.00035; SBPV P<0.0001; DBPV P<0.0001) and aortic mean SBP (SBPV P=0.037, DBPV P<0.0001). Beat-to-beat BP variability progresses significantly in high-risk patients, particularly in older individuals with elevated aortic systolic pressure. Beat-to-beat BPV and its progression represent potential new therapeutic targets to reduce cardiovascular risk.


Nitric oxide signaling and nitrosative stress in neurons: role for S-nitrosylation.
Nitric oxide (NO) mediates cellular signaling pathways that regulate a plethora of physiological processes. One of the signaling mechanisms mediated by NO is through S-nitrosylation of cysteine residues in target proteins, which is now regarded as an important redox-based physiological action. Deregulation of the protein S-nitrosylation upon nitrosative stress, however, has also been linked to various human diseases, such as neurodegenerative disorders. Between these physiological and pathophysiological roles, there are mechanisms whereby a milder level of nitrosative stress provides S-nitrosylation of some proteins that counteracts the pathological processes, serving as a negative feedback mechanism. In addition, NO has recently emerged as a mediator of epigenetic gene expression and chromatin changes. In this review, these molecular mechanisms, especially those in the central nervous system and neurodegenerative disorders, are described.


Religious Piety and Sexual Passion: What Is the Connection?
The association between religiosity and the construct of sexual passion was examined to see whether religiosity is associated with harmonious, inhibited, and obsessive sexual passion styles. Using multiple regression and checking for interactions between religiosity, gender, broad categories of religion (Catholic, other Christian, other religious, nonreligious), and the three sexual passion styles, the following associations were found: Religiosity had a significant curvilinear relationship to all three sexual passion styles, suggesting an overlap in levels of religiosity and the construct of sexual passion. Optimal sexual passion outcomes were found at both higher and lower levels of religiosity, whereas mid-level religiosity was associated with the less beneficial sexual passion outcomes. Religious men were significantly more obsessively passionate than religious women, and religious men and women were similarly high on levels of harmonious and low on inhibited sexual passion. There were no significant interactions between religiosity, broad categories of religion, and sexual passion styles. Understanding how religion and sexual passion are associated could be useful for applied researchers as well as those who work with religious individuals who want to help these individuals develop beneficial patterns of sexual passion.


[Prophylaxis of blood loss and allogenic blood transfusion with fibrinolysis inhibitors produced in Russian Federation in patients undergoing cardiac surgery].
Significant bleeding during cardiac surgery, enough to cause re-exploration and/or blood transfusion, increases morbidity and mortality. Bleeding after cardiopulmonary bypass is related to multiple factors: endothelial dysfunction, thrombocytopenia, dilution coagulopathy. Hyperfibrinolysis is one of the important contributors to increased bleeding. To compare the effect of aprotinin with the effect of lysine analogues (aminomethylbenzoic acid and epsilon aminocaproic acid) examined 63 patients were divided into three equal groups depending on the product used for the prevention of activation of fibrinolysis. Data from rotational thromboelastometry measurements (Rotem Gamma Pentapharm, Germany), blood loss and transfusion were collected. The results confirm that used in the study antifibrinolytics: the lysine analogues aminomethylbenzoic acid and epsilon aminocaproic acid prevent hyperfibrinolysis after cardiopulmonary bypass as well as aprotinin.


Endocytosis function of a ligand-gated ion channel homolog in Caenorhabditis elegans.
Ligand-gated ion channels are transmembrane proteins that respond to a variety of transmitters, including acetylcholine, gamma-aminobutyric acid (GABA), glycine, and glutamate [1 and 2]. These proteins play key roles in neurotransmission and are typically found in the nervous system and at neuromuscular junctions [3]. Recently, acetylcholine receptor family members also have been found in nonneuronal cells, including macrophages [4], keratinocytes [5], bronchial epithelial cells [5], and endothelial cells of arteries [6]. The function of these channels in nonneuronal cells in mammals remains to be elucidated, though it has been shown that the acetylcholine receptor alpha7 subunit is required for acetylcholine-mediated inhibition of tumor necrosis factor release by activated macrophages [4]. We show that cup-4, a gene required for efficient endocytosis of fluids by C. elegans coelomocytes, encodes a protein that is homologous to ligand-gated ion channels, with the highest degree of similarity to nicotinic acetylcholine receptors. Worms lacking CUP-4 have reduced phosphatidylinositol 4,5-bisphosphate levels at the plasma membrane, suggesting that CUP-4 regulates endocytosis through modulation of phospholipase C activity.


Antimicrobial resistance and stewardship in long-term care settings.
Infections and antimicrobial resistance (AMR) in long-term care facilities (LTCFs) are a public health challenge and a future infectious disease threat. More and more data show the dimension and impact of AMR and of inappropriate use of antimicrobials in this setting. Recently, the spread of carbapenemase-producing Enterobacteriaceae has provided new insights into the dangerous role the long-term care sector may play in the AMR problem in a community. Implementation of effective infection and surveillance control programs in LTCFs is challenging, due to scarce resources (personnel, expertise, diagnostic and supportive services), and no or poor coordination of medical care. However, interventions in LTCFs have been proven to be effective: inappropriate use of antibiotics for asymptomatic bacteriuria may be reduced; hand hygiene compliance may be improved; and the transmission of multidrug-resistant organisms may be halted. This paper reviews the most recent epidemiological information on this issue, providing references to valuable intervention programs.


Eosinophil peroxidase increases membrane permeability in mammalian urinary bladder epithelium.
Eosinophil peroxidase (EPO), a cationic protein found in eosinophils, has been reported to be cytotoxic independent of its peroxidase activity. This study investigated with electrophysiological methods whether EPO is toxic to mammalian urinary bladder epithelium. Results indicate that EPO, when added to the mucosal solution, increases apical membrane conductance of urinary bladder epithelium only when the apical membrane potential is cell interior negative. The EPO-induced conductance was concentration dependent, with a maximum conductance of 411 microseconds/cm2 and a Michaelis-Menten constant of 113 nM. The EPO-induced conductance was nonselective for K+ and Cl-. The conductance was partially reversed using voltage but not by removal of EPO from the bulk solution. Mucosal Ca2+ reversed the EPO-induced conductance by a mechanism involving reversible block of the conductance. Prolonged exposure (up to 1 h) to EPO was toxic to the urinary bladder epithelium, as indicated by an irreversible increase in transepithelial conductance. These results suggest that EPO is indeed toxic to urinary bladder epithelium via a mechanism that involves an increase in membrane permeability.


PEG-liposomal oxaliplatin combined with nuclear factor-κB inhibitor (PDTC) induces apoptosis in human colorectal cancer cells.
To achieve sufficient antitumor activity for colorectal carcinoma, optimization of the therapeutic regimen is of great importance. The aim of the present study was to investigate the effects of polyethylene glycol (PEG)-liposomal oxaliplatin (L-OHP) on the induction of apoptosis in human colorectal cancer SW480 cells and how the nuclear factor-κB (NF-κB) pathway may contribute to mediating PEG-liposomal L-OHP-induced apoptosis. PEG-liposomal L-OHP was prepared and used to treat colorectal cancer SW480 cells. SW480 cell uptake of liposomes was observed by laser focus or SEM. Apoptosis was measured by flow cytometry (FCM) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay. Expression of NF-κB, Bcl-2, Bax and activated caspase-3 (P17) was examined by western blot analyses. The results indicated that PEG-liposomal L-OHP induced apoptosis. When pretreated with pyrrolidine dithiocarbamate (PDTC), PEG-liposomal L-OHP induced a significant apoptotic response. Moreover, apoptosis was associated with concentration of PDTC. Expression of protein p-P65, Bcl-2 was downregulated, but Bax and P17 were upregulated. These findings indicate that PEG-liposomal L-OHP enhances the anticancer potency of the chemotherapeutic agent. Moreover, NF-κB signaling pathways may contribute to mediating PEG-liposomal L-OHP-induced apoptosis.


LAMP-1 gene is overexpressed in high grade glioma.
High-grade gliomas (HGG) are the most frequent brain tumors in adults. Glioblastoma multiforme (GBM) is their most aggressive form resistant to therapy. It was shown that inhibition of autophagy reduced GBM development and autophagy interfering agents are regarded as a new strategy to fight glioma cells. The lysosome-associated membrane proteins (LAMPs) display differential expression particularly in cancer. There are few data on their expression and especially on their molecular profile. The aim of the present study is to investigate the expression of LAMP-1 and LAMP-2 genes and proteins in HGG. Newly diagnosed patients with HGG and healthy controls were examined by immunohistochemistry and qPCR for both protein and mRNA levels of LAMP-1 and LAMP-2. The transcriptional activity of LAMP-1 in HGG was significantly higher compared to normal brain and to LAMP-2. The two glycoproteins were detected in the cytosol of tumor cells with varying intensity, LAMP-1 showing again enhanced expression. In conclusion, novel data on LAMP-1 overexpression in HGG are presented suggesting involvement of this gene and protein in cell adhesion and tumor progression. These findings might help the elucidation of the complex biological role of the multifunctional LAMPs proteins and to predict novel therapeutic targets in lysosomes.


Serum concentrations of high-molecular weight adiponectin and their association with sex steroids in premenopausal women.
At present, the association between adiponectin and sex hormones in women is controversial. Recent studies suggest that it is high-molecular weight (HMW) adiponectin and the HMW to total adiponectin ratio rather than total adiponectin that are associated with antiatherogenic activities, insulin sensitivity, metabolic syndrome, and prediction of cardiovascular events. The present study aimed to investigate whether measuring HMW adiponectin and the HMW to total adiponectin ratio rather than total adiponectin might be more useful to detect an association between circulating female sex steroids and adipocytokines. In a clinical trial, we investigated the associations of total adiponectin, HMW adiponectin, and the HMW to adiponectin ratio with several androgens and estradiol in 36 healthy premenopausal women with regular cycles. No association between the investigated sex hormones and adiponectin was observed. The HMW adiponectin was negatively correlated with estradiol after adjustment for age and body mass index. The HMW to total adiponectin ratio was significantly negatively associated with testosterone, free testosterone, and androstenedione. The testosterone to estradiol ratio, as a parameter for the estrogen-androgen balance, was not associated with adiponectin or the HMW isoform. In conclusion, there is a negative association between estradiol and HMW adiponectin, and between testosterone, free testosterone, and androstenedione and the HMW to adiponectin ratio. Thus, one mechanism whereby female sex steroids may influence the cardiovascular risk of women could be alteration of the relationship between HMW and total adiponectin concentrations in plasma.


Revision of the classical dopamine D2 agonist pharmacophore based on an integrated medicinal chemistry, homology modelling and computational docking approach.
The scientific advances during the 1970ies and 1980ies within the field of dopaminergic neurotransmission enabled the development of a pharmacophore that became the template for design and synthesis of dopamine D2 agonists during the following four decades. A major drawback, however, is that this model fails to accommodate certain classes of restrained dopamine D2 agonists including ergoline structures. To accommodate these, a revision of the original model was required. The present study has addressed this by an extension of the original model without compromising its obvious qualities. The revised pharmacophore contains an additional hydrogen bond donor feature, which is required for it to accommodate ergoline structures in a low energy conformation and in accordance with the steric restrictions dictated by the original model. The additional pharmacophore feature suggests ambiguity in the binding mode for certain compounds, including a series of ergoline analogues, which was reported recently. The ambiguity was confirmed by docking to a homology model of the D2 receptor as well as by pharmacological characterization of individual enantiomers of one of the analogues. The present research also addresses the potential of designing ligands that interact with the receptor in a large, distal cavity of the dopamine D2 receptor that has not previously been studied systematically. The pharmacological data indicate that this area may be a major determinant for both the dopamine D2 affinity and efficacy, which remains to be explored in future studies.


Metaanalysis of the effect of antenatal indomethacin on neonatal outcomes.
The objective of the study was to determine whether indomethacin used as a tocolytic agent is associated with adverse neonatal outcomes. We used published guidelines of the Metaanalysis of Observational Studies in Epidemiology Group (MOOSE) to perform the metaanalysis. The search strategy used included computerized bibliographic searches of MEDLINE (1966-2005), PubMed (1966-2005), abstracts published in Obstetrics and Gynecology (1991-2005), abstracts published in Pediatric Research (1991-2005), and references of published manuscripts. Study inclusion criteria were publication in English, more than 30 deliveries less than 37 weeks' gestation, and meeting diagnostic criteria for individual neonatal outcomes. Exclusion criteria included case reports, case series, and multiple publications from the same author. Metaanalysis was performed using random effects model if there were more than 2 observational studies for a specific outcome. Eggers test was performed to exclude publication bias. Sensitivity analysis was performed to evaluate the effect of antenatal steroid exposure, gestation, and recent antenatal indomethacin exposure (duration of 48 hours or more between the last dose and delivery). Fifteen retrospective cohort studies and 6 case-controlled studies met inclusion criteria. Antenatal indomethacin was associated with an increased risk of periventricular leukomalacia (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.3-3.1). Recent exposure to antenatal indomethacin was associated with necrotizing enterocolitis (OR, 2.2; 95% CI; 1.1-4.2). Antenatal indomethacin was not associated with intraventricular hemorrhage, patent ductus arteriosus, respiratory distress syndrome, bronchopulmonary dysplasia, and mortality. Antenatal indomethacin may be associated with an increased risk of periventricular leukomalacia and necrotizing enterocolitis in premature infants and therefore should be used judiciously for tocolysis.


NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia.
Parkinson's disease is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra. We have previously reported that lipopolysaccharide (LPS)-induced degeneration of dopaminergic neurons is mediated by the release of proinflammatory factors from activated microglia. Here, we report the pivotal role of NADPH oxidase in inflammation-mediated neurotoxicity, where the LPS-induced loss of nigral dopaminergic neurons in vivo was significantly less pronounced in NADPH oxidase-deficient (PHOX-/-) mice when compared with control (PHOX+/+) mice. Dopaminergic neurons in primary mensencephalic neuron-glia cultures from PHOX+/+ mice were significantly more sensitive to LPS-induced neurotoxicity in vitro when compared with PHOX-/- mice. Further, PHOX+/+ neuron-glia cultures chemically depleted of microglia failed to show dopaminergic neurotoxicity with the addition of LPS. Neuron-enriched cultures from both PHOX+/+ mice and PHOX-/- mice also failed to show any direct LPS-induced dopaminergic neurotoxicity. However, the addition of PHOX+/+ microglia to neuron-enriched cultures from either strain resulted in reinstatement of LPS-induced dopaminergic neurotoxicity, supporting the role of microglia as the primary source of NADPH oxidase-generated insult and neurotoxicity. Immunostaining for F4/80 in mensencephalic neuron-glia cultures revealed that PHOX-/- microglia failed to show activated morphology at 10 h, suggesting an important role of reactive oxygen species (ROS) generated from NADPH oxidase in the early activation of microglia. LPS also failed to elicit extracellular superoxide and produced low levels of intracellular ROS in microglia-enriched cultures from PHOX-/- mice. Gene expression and release of tumor necrosis factor alpha was much lower in PHOX-/- mice than in control PHOX+/+ mice. Together, these results demonstrate the dual neurotoxic functions of microglial NADPH oxidase: 1) the production of extracellular ROS that is toxic to dopamine neurons and 2) the amplification of proinflammatory gene expression and associated neurotoxicity.


Theoretical study of alpha/beta-alanine and their protonated/alkali metal cationized complexes.
Density functional theory has been employed to model the structure and the relative stabilities of alpha/beta-alanine conformers and their protonated and alkali metal cationized complexes. In general, we find that the behavior of the beta-alanine (beta-Ala) system is quite similar to that of alpha-alanine (alpha-Ala). However, the presence of the methylene group (-CH2-) at the beta position in beta-Ala leads to a few key differences. First, the intramolecular hydrogen bonding patterns are different between free alpha- and beta-Ala. Second, the stability of zwitterionic species (in either the free ligand or alkali metal cationized complexes) is often enhanced in beta-Ala. Third, the preferred mode of alkali metal cation (M+) binding may also differ in alpha- and beta-Ala. Natural energy decomposition analysis has been applied here to gain further insight into the effects of the ligand, cation size, and mode of binding on the nature of interaction in these M+-Ala complexes.


Adjuvant phytotherapy in the treatment of cervical cancer: a systematic review and meta-analysis.
Clinical trials have investigated phytotherapy (PT) in the treatment of cervical cancer. This study aimed to assess the quality and data of current available trials, to compare the efficacy and safety of conventional therapies (CT) including surgical therapy, radiotherapy, and chemotherapy with that of CT plus PT (CT-PT), and to identify herbs used commonly in clinical trials. Forty-three (43) electronic databases were searched. The quality of eligible trials was assessed by Jadad's scale, and Revman 5.0 software was used for data syntheses and analyses. (1) Of the 48 potential trials retrieved, 18 trials involving 1657 patients met the inclusion criteria, and two trials were graded as high-quality trials; (2) CT-PT achieved a higher 1-year survival rate (SR, p = 0.0002) and tumor remission rate (TRR, p < 0.0001) than CT alone; (3) PT showed therapeutic effects comparable to those of Western medications in diminishing vesical complications (VC, p < 0.0001) and rectal complications (RC, p = 0.08) caused by CT; (4) top 15 herbs used frequently to improve SR or TRR and to treat VC or RC in the retrieved trials were identified. Adjuvant PT may improve the efficacy and safety of CT in clinical treatments of cervical cancer, although this result needs to be further verified by more high-quality trials.


Overexpression of integrin α11 induces cardiac fibrosis in mice.
To understand the role of the collagen-binding integrin α11 in vivo, we have used a classical approach of creating a mouse strain overexpressing integrin α11. A transgenic mouse strain overexpressing α11 in muscle tissues was analysed in the current study with special reference to the heart tissue. We generated and phenotyped integrin α11 transgenic (TG) mice by echocardiography, magnetic resonance imaging and histology. Wild-type (WT) mice were subjected to aortic banding (AB) and the expression of integrin α11 was measured in flow cytometry-sorted cardiomyocytes and non-myocytes. TG mice developed left ventricular concentric hypertrophy by 6 months, with increased collagen deposition and reactivation of mRNA encoding foetal genes associated with cardiovascular pathological remodelling compared to WT mice. Masson's trichrome staining revealed interstitial fibrosis, confirmed additionally by magnetic resonance imaging and was found to be most prominent in the cardiac septum of TG but not WT mice. TG hearts expressed increased levels of transforming growth factor-β2 and transforming growth factor-β3 and upregulated smooth muscle actin. Macrophage infiltration coincided with increased NF-κB signalling in TG but not WT hearts. Integrin α11 expression was increased in both cardiomyocytes and non-myocyte cells from WT AB hearts compared to sham-operated animals. We report for the first time that overexpression of integrin α11 induces cardiac fibrosis and left ventricular hypertrophy. This is a result of changes in intracellular hypertrophic signalling and secretion of soluble factors that increase collagen production in the heart.


[Research on endemic diseases and Japanese colonial rule: focusing on the emetine poisoning accident in Yeongheung and Haenam counties in 1927].
This paper aims to examine the spread of paragonimiasis and the Japanese colonial government's response to it. To consolidate colonial rule, the Japanese colonial government needed medications to cure paragonimiasis. When Dr. Ikeda Masakata invented acid emetine to cure paragonimiasis in Manchuria in 1915, emetine treatment carried the risk of emetine poisoning such as fatigue, inappetence, heart failure, and death. Nonetheless, Japanese authorities forced clinical trials on human patients in colonial Korea during the 1910s and 1920s. The emetine poisoning accident in Yeongheung and Haenam counties in 1927 occurred in this context. The Japanese government concentrated on terminating an intermediary host instead of injecting emetine to repress endemic disease in Japan. However, the Japanese colonial government pushed ahead with emetine injections for healthy men through the Preliminary Bureau of Land Research in colonial Korea in 1917. This clinical trial simultaneously presented the effects and the side effects of emetine injection. Because of the danger emetine injections posed, the colonial government investigated only the actual condition of paragonimiasis, delaying the use of emetine injection. Kobayashi Harujiro(1884-1969), a leading zoologist and researcher of endemic disease for three decades in the Government General Hospital and Keijo Imperial University in colonial Korea, had used emetine while researching paragonimiasis, but he did not play a leading role in clinical trials with emetine injections, perhaps because he mainly researched the intermediary host. Government General Hospital and Keijo Imperial University therefore faced limitations that kept them from leading the research on endemic disease. As the health administration shifted the central colonial government to local colonial government, the local colonial government pressed ahead with emetine injections for Korean patients. Emetine poisoning had something to do with medical power's localization. Nevertheless, the central colonial government still supported emetine injections with funds from the national treasury. The emetine poisoning accident that occurred simultaneously in two different regions resulted from the Japanese colonial government's support. This accident represented the Japanese colonial rule's atrocity, its suppression of hygiene policies, and its disdain for colonial inhabitants. The colonial government sought to accumulate medical knowledge not to cure endemic disease, but to expand the Japanese Empire.


Levels of p21(WAF1/CIP1) do not affect radiation-induced cell death in human breast epithelial cells.
Loss of the wild-type p53 activity and/or overexpression of the proto-oncogene bcl-2 are frequently detected in breast cancer and suggested to be related to chemotherapy and radiation therapy resistance. To identify the downstream signaling molecules for anti-proliferative and apoptotic activities of p53 and to investigate the interaction of bcl-2 with p53 in human breast epithelial cells, we have used the MCF10A cell line. We previously showed that overexpression of bcl-2 downregulates expression of p21(WAF1/CIP1) (a cyclin dependent kinase inhibitor which mediates p53 dependent G(1) arrest) and suppresses DNA damage-induced apoptosis in MCF10A cells. In the present study, we constitutively overexpressed p21(WAF1/CIP1) in bcl-2 overexpressing MCF10A cells to determine whether downregulation of p21(WAF1/CIP1) is necessary for the anti apoptotic activity of bcl-2, and to investigate the roles of p21(WAF1/CIP1) in p53-mediated cell death upon irradiation. Overexpression of p21(WAF1/CIP1) resulted in growth inhibition, but had no effect on bcl-2 inhibition of apoptosis following irradiation. Also, overexpression of p21(WAF1/CIP1) did not affect the dose-dependent radiation-induced cell lethality as determined by a clonogenic survival assay. These results suggest that bcl-2 downregulation of p21(WAF1/CIP1) is independent of the anti-apoptotic activity of bcl-2, and that p21(WAF/CIP1) is not involved in the p53-mediated cell death pathway.


Human pericytes adopt myofibroblast properties in the microenvironment of the IPF lung.
Idiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown etiology characterized by a compositionally and mechanically altered extracellular matrix. Poor understanding of the origin of α-smooth muscle actin (α-SMA) expressing myofibroblasts has hindered curative therapies. Though proposed as a source of myofibroblasts in mammalian tissues, identification of microvascular pericytes (PC) as contributors to α-SMA-expressing populations in human IPF and the mechanisms driving this accumulation remain unexplored. Here, we demonstrate enhanced detection of α-SMA+ cells coexpressing the PC marker neural/glial antigen 2 in the human IPF lung. Isolated human PC cultured on decellularized IPF lung matrices adopt expression of α-SMA, demonstrating that these cells undergo phenotypic transition in response to direct contact with the extracellular matrix (ECM) of the fibrotic human lung. Using potentially novel human lung-conjugated hydrogels with tunable mechanical properties, we decoupled PC responses to matrix composition and stiffness to show that α-SMA+ PC accumulate in a mechanosensitive manner independent of matrix composition. PC activated with TGF-β1 remodel the normal lung matrix, increasing tissue stiffness to facilitate the emergence of α-SMA+ PC via MKL-1/MTRFA mechanotranduction. Nintedanib, a tyrosine-kinase inhibitor approved for IPF treatment, restores the elastic modulus of fibrotic lung matrices to reverse the α-SMA+ phenotype. This work furthers our understanding of the role that microvascular PC play in the evolution of IPF, describes the creation of an ex vivo platform that advances the study of fibrosis, and presents a potentially novel mode of action for a commonly used antifibrotic therapy that has great relevance for human disease.


Towards Visual-Tactile Integration of Shoulder and Hand Using Immersive Virtual Reality.
Shoulder-controlled hand neuroprostheses are wearable devices designed to assist hand function in people with cervical spinal cord injury (SCI). They use preserved shoulder movements to control artificial actuators. Due to the concurrent afferent (i.e., shoulder proprioception) and visual (i.e., hand response) feedback, these wearables may affect the user's body somatosensory representation. To investigate this effect, we propose an experimental paradigm that uses immersive virtual reality (VR) environment to emulate the use of a shoulder-controlled hand neuroprostheses and an adapted version of a visual-tactile integration task (i.e., Crossmodal Congruency Task) as an assessment tool. Data from seven non-disabled participants validates the experimental setup, with preliminary statistical analysis revealing no significant difference across the means of VR and visual-tactile integration tasks. The results serve as a proof-of-concept for the proposed paradigm, paving the way for further research with improvements in the experimental design and a larger sample size.


Testing quality improvement interventions.
The quality of health care is in drastic need of improvement. Surgeons are key players in the health care delivery system, and as such, they should be involved by leading or participating in the improvements that should take place. This article posits some suggestions as to how surgeons can participate in the efforts to make the health care provided to patients better and make the system a better place to work for surgeons and for other health professionals. Participation in quality improvement (QI) initiatives has the potential to bring much personal satisfaction for surgeons who help the process to move forward, even though it takes some effort and even forces them to learn some new skills and attitudes to what can be accomplished by QI teams. This article provides a methodologic guide to conducting and evaluating QI research.


Prevalence and gender patterns of mental health problems in German youth with experience of violence: the KiGGS study.
Research examining mental health in violence-affected youth in representative samples is rare. Using data from the nationally representative German Health Interview and Examination Survey for Children and Adolescents (KiGGS) this study reports on gender-specific prevalence rates and associations of a broad range of internalizing and externalizing mental health problems: emotional problems, conduct problems, ADHD, disordered eating, somatic pain and substance use in youth variously affected by violence. While internalizing is generally more common in girls and externalizing in boys, observations of prior non-normative studies suggest reverse associations once an individual is affected by violence. The occurrence of such "gender cross-over effects" is therefore examined in a representative sample. The sample consisted of 6,813 adolescents aged 11 to 17 from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS): Applying multivariate logistic regression analyses, associations between each type of violence history and mental health indicator were determined for perpetrators, victims, and perpetrating victims of youth violence. Moderating effects of gender were examined by using product term interaction. Victim status was associated primarily with internalizing problems, while perpetrators were more prone to externalizing problems. Perpetrating victims stood out with respect to the number and strength of risk associations with all investigated mental health indicators. However, the risk profiles of all violence-affected youth included both internalizing and externalizing mental health problems. Gender cross-over effects were found for girls and boys: despite lower overall prevalence, girls affected by violence were at far higher risk for conduct problems and illicit drug use; by contrast, somatic pain, although generally lower in males, was positively associated with perpetrator status and perpetrating victim status in boys. All violence-affected youth exhibited significantly higher rates of cumulative mental health problems. The results highlight the importance of violence for the mental health of youth. They reveal a particular vulnerability as a function of gender. Implications for policy making, clinical practice and research are discussed.


The mere perception of elaboration creates attitude certainty: exploring the thoughtfulness heuristic.
Attitude theory has long proposed a mechanism through which antecedents of message elaboration produce attitude strength consequences. However, little direct evidence exists for the intervening process. The proposed thoughtfulness heuristic holds that perceiving that more thought has taken place leads to greater attitude certainty. Two roles were established for this heuristic: first as a mediator of the impact of antecedents of elaboration on attitude certainty and second as a way to influence attitude certainty independent of actual elaboration. In Studies 1 and 2, antecedents of elaboration (need for cognition, distraction) impacted attitude certainty because they impacted the actual amount of processing, which in turn affected perceptions of the amount of processing. In Studies 3 and 4, a manipulation of perceived thought impacted certainty independent of actual thought (i.e., after thinking had already occurred). Furthermore, the thoughtfulness heuristic was shown to influence behavioral intentions, establishing perceived amount of processing as both a mediator and an independent cause of attitude strength consequences.


Proteasome modulates mitochondrial function during cellular senescence.
Proteasome plays fundamental roles in the removal of oxidized proteins and in the normal degradation of short-lived proteins. Previously we have provided evidence that the impairment in proteasome observed during the replicative senescence of human fibroblasts has significant effects on MAPK signaling, proliferation, life span, senescent phenotype, and protein oxidative status. These studies have demonstrated that proteasome inhibition and replicative senescence caused accumulation of intracellular protein carbonyl content. In this study, we have investigated the mechanisms by which proteasome dysfunction modulates protein oxidation during cellular senescence. The results indicate that proteasome inhibition during replicative senescence has significant effects on intra- and extracellular ROS production in vitro. The data also show that ROS impaired the proteasome function, which is partially reversible by antioxidants. Increases in ROS after proteasome inhibition correlated with a significant negative effect on the activity of most mitochondrial electron transporters. We propose that failures in proteasome during cellular senescence lead to mitochondrial dysfunction, ROS production, and oxidative stress. Furthermore, it is likely that changes in proteasome dynamics could generate a prooxidative condition at the immediate extracellular microenvironment that could cause tissue injury during aging, in vivo.


Physical and sensory characterizations of oral coatings of oil/water emulsions.
The physical and sensory properties of oil coatings on the tongue formed by five oil/water emulsions varying in oil content were investigated. A total of 20 subjects processed orally each emulsion for 30 s in triplicate. In vivo fluorescence measurements at the front and back of the anterior tongue were made to quantify the oil fraction deposited at different time points. Calibration lines relating fluorescence intensity to oil fraction were determined using pig tongues at 37.5 °C to mimic oral conditions. The oil fraction on the tongue increased linearly with an increasing oil content of the emulsions. The oil fraction deposited at the back of the anterior tongue was 1.5-2.0× larger than at the front. The intensity of sensory attributes describing after-feel perception was related to the oil fraction by Weber-Fechner's law. This study uses in vivo fluorescence to study food behavior in the mouth and unravel new insights in after-feel perception of emulsions.


IgE peptide-specific CTL inhibit IgE production: a transient IgE suppression model in wild-type and HLA-A2.1 transgenic mice.
Effect of IgE peptide-specific CTL on IgE antibody production was studied in mouse models. CTL elicited in B6.A2Kb tg mice against a human IgE peptide nonamer, pWV, lysed human IgE-secreting U266 myeloma cells and inhibit IgE production by these cells. U266 transfected with mouse A2Kb transgene (U266-A2Kb) were optimally lysed by these CTL, because the alpha3 domain of A2Kb interacts well with the CD8 co-receptors. The CTL generated were more effective in inhibiting IgE production by U266-A2Kb cells than lysing these cells. IgE production by and progression of U266 myeloma were suppressed in B6.A2Kb tg mice rendered tolerant to these cells and vaccinated with pWV along with CpG. We also studied the CTL response elicited in wild-type mice by a mouse nonameric IgE peptide, PI-1, along with CpG. This treatment caused a transient suppression of the IgE response in mice previously sensitized to an antigen. In mice treated with this regimen repeatedly, the IgE response was fully recovered 20 days after each treatment. Notably, while IgE peptide/CpG-treated mice remained unresponsive to antigen challenge in vivo, antigen-specific IgE production can be elicited by antigen in cultured splenocytes from these mice. Moreover, IgE peptide/CpG also inhibited an on-going IgE response, including IgE production by bone marrow cells. Taken together, these observations indicate that a CTL-based IgE peptide vaccine targeting IgE-secreting B/plasma cells may be safely employed as a therapeutic approach for suppressing IgE production.


Reflectance Confocal Microscopy Features of Plaque Psoriasis Overlap With Horizontal Histopathological Sections: A Case Series.
Reflectance confocal microscopy (RCM) displays horizontal, en face tissue sections of the epidermis and upper dermis, and interpretation of its features is classically based on the comparison with vertical conventional histopathological sections that, as known, do not reflect the same plane of observation. In 10 patients affected by psoriasis, we correlated RCM images with horizontal histopathological sections from skin biopsies, observing in all cases marked overlaps between the 2 techniques. Although vertical section examination remains the gold standard for the diagnosis of psoriasis, this novel comparative approach may contribute to a more precise definition of RCM findings and could represent the drive for further research as well as an innovative tool for educational purposes.


[The meaning of the alcoholic relapse].
The author is concerned with the difficulty for physicians to treat alcoholic patients who relapse. The systemic model is the only approach which allows an insight in the meaning of this recurring disease. The author reports on several studies undertaken in France and relates the various circumstances of relapses. Paradoxically, the relapse may be a positive phenomenon leading to an awareness of the patient regarding his weakness toward alcohol. From that moment on, the alcoholic patient will be able to engage in the direction of a lasting abstinence.


Recent clinically relevant highlights from the Diabetic Retinopathy Clinical Research Network.
To present some recent clinically relevant results from Diabetic Retinopathy Clinical Research (DRCR) Network trials that may guide management of diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR). Among eyes with DME and visual acuity 20/50 or worse, aflibercept, on average, had greater improvement in visual acuity over 2 years compared with bevacizumab or ranibizumab. Aflibercept is associated with higher rates of improvements in diabetic retinopathy severity among eyes with PDR and vision-impairing DME at baseline compared with bevacizumab or ranibizumab. Among eyes with persistent central-involved DME after at least six antivascular endothelial growth factor (anti-VEGF) injections, no difference in mean visual acuity improvement was observed between eyes that received continued ranibizumab and sham injections versus ranibizumab and intravitreous sustained dexamethasone drug-delivery system, especially for phakic eyes. For eyes with PDR, ranibizumab was associated with lower rates of developing PDR-worsening events compared with panretinal photocoagulation, especially among eyes that did not receive ranibizumab for central-involved DME at baseline. Ranibizumab is cost-effective for PDR for eyes with, not without, vision-impairing central-involved DME, highlighting challenges when safety and efficacy results are at odds with cost-effectiveness results. Aflibercept for DME, in certain circumstances, is more likely to have superior visual acuity and anatomical outcomes compared with bevacizumab or ranibizumab. No vision benefits are apparent, especially for phakic eyes, by adding intravitreous corticosteroids for persistent DME following anti-VEGF injections.


Social contacts and loneliness in people with psychotic and mood disorders.
Social relations can be measured through: a) objective indicators, i.e. the number of social contacts in a given time interval or b) subjective indicators, i.e. feelings of loneliness. Comparing subjective and objective indicators in patients with psychotic and mood disorders may help to understand whether diagnosis-specific interventions should be designed for increasing their social relations. In this study we assessed social contacts outside home, work environments and mental health services, which may be increased by these interventions. We also explored feelings of loneliness which could influence readiness of patients to participate in interventions. 100 patients in outpatient mental health care were asked to: a) list their social contacts; b) report their feelings of loneliness on a validated five point Likert scale. Multiple logistic regression models were used to test associations of diagnostic categories with: a) having more than one social contact in the previous week; b) reporting at least moderate feelings of loneliness. Patients had on average 1.7 (SD=1.7) social contacts in the previous week (median=1.0); 77 patients reported at least moderate feelings of loneliness. Patients with psychotic disorders (n=30) showed a statistical trend towards having just one or no contacts in the week before the assessment (Odds ratio, OR=2.246, p=.087). Patients with mood disorders were more likely to report at least moderate feelings of loneliness (OR=2.798; p<.05). Patients with psychotic disorders, compared to those with mood disorders, may be less likely to report feeling lonely although they tend to have less social contacts. Strategies to enhance social relations of people with psychotic disorders may include approaches to increase patients' drive to establish new social contacts and to emotionally support them in this process.


Coconut oil ameliorates behavioral and biochemical alterations induced by D-GAL/AlCl3 in rats.
Alzheimer's disease (AD) is a chronic, progressive neurodegenerative condition marked by cognitive impairment. Although coconut oil has been shown to be potentially beneficial in reducing AD-related cognitive deficits, information on its mechanism of action is limited. Thus, we investigated the effects of coconut oil on spatial cognitive ability and non-cognitive functions in a rat model of AD induced by G-galactose (D-GAL) and aluminum chloride (AlCl3), and examined the changes in synaptic transmission, cholinergic activity, neurotrophic factors and oxidative stress in this process. The AD model was established by administering D-GAL and AlCl3 for 90 days, while also supplementing with coconut oil during this time. Cognitive and non-cognitive abilities of the rats were evaluated at the end of the 90-day supplementation period. In addition, biochemical markers related to the pathogenesis of the AD were measures in the hippocampus tissue. Exposure to D-GAL/AlCl3 resulted in a reduction in locomotor activity, an elevation in anxiety-like behavior, and an impairment of spatial learning and memory (P < 0.05). The aforementioned behavioral disturbances were observed to coincide with increased oxidative stress and cholinergic impairment, as well as reduced synaptic transmission and levels of neurotrophins in the hippocampus (P < 0.05). Interestingly, treatment with coconut oil attenuated all the neuropathological changes mentioned above (P < 0.05). These findings suggest that coconut oil shows protective effects against cognitive and non-cognitive impairment, AD pathology markers, oxidative stress, synaptic transmission, and cholinergic function in a D-GAL/AlCl3-induced AD rat model.


In vitro antiplasmodial and cytotoxic properties of some medicinal plants from western Burkina Faso.
Resistance of malaria parasites to existing drugs complicates treatment, but an antimalarial vaccine that could protect against this disease is not yet available. It is therefore necessary to find new effective and affordable medicines. Medicinal plants could be a potential source of antimalarial agents. Some medicinal plants from Burkina Faso were evaluated for their antiplasmodial and cytotoxic properties in vitro. Crude dichloromethane, methanol, water-methanol, aqueous and alkaloids extracts were prepared for 12 parts of 10 plants. Chloroquine-resistant malaria strain K1 was used for the in vitro sensibility assay. The Plasmodium lactacte dehydrogenase technique was used to determine the 50% inhibitory concentration of parasites activity (IC50). The cytotoxic effects were determined with HepG2 cells, using the tetrazolium-based colorimetric technique, and the selectivity index (SI) was calculated. Sixty crude extracts were prepared. Seven extracts from Terminalia avicenoides showed IC50 < 5 µg/mL. The IC50 of dichloromethane, methanol, aqueous and alkaloids extracts ranged between 1.6 µg/mL and 4.5 µg/mL. Three crude extracts from Combretum collinum and three from Ficus capraefolia had an IC50 ranging between 0.2 µg/mL and 2.5 µg/mL. Crude extracts from these three plants had no cytotoxic effect, with SI > 1. The other plants have mostly moderate or no antimalarial effects. Some extracts from Cordia myxa, Ficus capraefolia and Opilia celtidifolia showed cytotoxicity, with an SI ranging between 0.4 and 0.9. Our study showed a good antiplasmodial in vitro activity of Terminalia avicenoides, Combretum collinum and Ficus capraefolia. These three plants may contain antiplasmodial molecules that could be isolated by bio-guided phytochemical studies.


The influence of resting period length on jumping performance.
The purpose of this study was to determine a resting interval between countermovement jumps (i.e., volleyball spikes) that allows the maintenance of maximal jumping performance. Ten male volleyball players (1.85 +/- 0.05 m, 77.2 +/- 10.6 kg, 21.6 +/- 5.3 years) performed 6 experimental jumping sessions. In the first and sixth sessions, maximal countermovement jump height was measured, followed by submaximal countermovement jumps to the point of volitional fatigue. The number of countermovement jumps was used as a reference to test the effect of rest period between volleyball spikes. From the second to fifth experimental sessions, 30 maximal volleyball spikes were performed with different resting periods (i.e., 8, 14, 17, and 20 seconds) followed by countermovement jumps. Between the 15th and 30th spikes, the blood lactate concentration and heart rate were measured. Because the performance on the first and sixth sessions was the same, no training effects were noticed. During the 8-second resting interval set, the lactate concentration increased significantly between the 15th and 30th spikes (i.e., from 3.37 +/- 1.16 mmol to 4.94 +/- 1.49 mmol); the number of countermovement jumps decreased significantly after spikes compared to those performed without a previous effort (i.e., from 23 +/- 7 jumps to 17 +/- 9 jumps); and these variables were significantly correlated (r = -0.7). On the other hand, the lactate concentration and number of countermovement jumps were stable across the other resting intervals, without a heart rate steady state. The results indicate that an adequate resting period between spikes allowed participants to achieve a lactate steady state in which the performance was maintained during the exercise. These findings show that resting intervals between 14 and 17 seconds, typical during volleyball matches, are indicated to use in volleyball spike drills due to their capacity to maintain maximal jumping performance.


Effects of an aqueous-ethanolic extract of ginger on cytochrome P450 enzyme-mediated drug metabolism.
Ginger has been extensively used as a herbal medicine for thousands of years in Asia; it has also been used as a seasoning agent in several foods and beverages worldwide. In this study, the effect of an aqueous-ethanolic extract of ginger on CYP450-mediated drug metabolism was investigated in vitro to elucidate the herb-drug interactions. A CYP450-specific substrates mixture was incubated with an aqueous-ethanolic extract of ginger in human liver microsomes fortified with an NADPH-generating system, and the metabolites generated from each of the CYP450-specific metabolic reactions were measured by liquid chromatography-tandem mass spectrometry. The ginger extracts were tested at concentrations of 0.05-5 microg/mL. The resulting data showed that the ginger extract inhibited CYP2C19-mediated drug metabolism in a concentration-dependent manner with an IC50 value of 3.8 microg/mL. When the ginger extract was pre-incubated and assessed, the inhibition pattern did not change, indicating that the inhibition of CYP2C19 was competitive rather than mechanism-based. The effects on other CYP isozyme activity were negligible at the concentrations tested. In conclusion, this inhibitory effect of ginger extract could affect the pharmacokinetics and lead to interactions with drugs that are metabolized by CYP2C19.


Upper extremity impairments in type 1 diabetes with long duration; common problems with great impact on daily life.
To investigate the prevalence, activity limitations and potential risk factors of upper extremity impairments in type 1 diabetes in comparison to controls. In a cross-sectional population-based study in the southeast of Sweden, patients with type 1 diabetes <35 years at onset, duration ≥20 years, <67 years old and matched controls were invited to answer a questionnaire on upper extremity impairments and activity limitations and to take blood samples. Seven hundred and seventy-three patients (ages 50 ± 10 years, diabetes duration 35 ± 10 years) and 708 controls (ages 54 ± 9 years) were included. Shoulder pain and stiffness, hand paraesthesia and finger impairments were common in patients with a prevalence of 28-48%, which was 2-4-folds higher than in controls. Compared to controls, the patients had more bilateral impairments, often had coexistence of several upper extremity impairments, and in the presence of impairments, reported more pronounced activity limitations. Female gender (1.72 (1.066-2.272), p = 0.014), longer duration (1.046 (1.015-1.077), p = 0.003), higher body mass index (1.08 (1.017-1.147), p = 0.013) and HbA1c (1.029 (1.008-1.05), p = 0.007) were associated with upper extremity impairments. Compared to controls, patients with type 1 diabetes have a high prevalence of upper extremity impairments, often bilateral, which are strongly associated with activity limitations. Recognising these in clinical practise is crucial, and improved preventative, therapeutic and rehabilitative interventions are needed. Implications for rehabilitation Upper extremity impairments affecting the shoulder, hand and fingers are common in patients with type 1 diabetes, the prevalence being 2-4-fold higher compared to non-diabetic persons. Patients with diabetes type 1 with upper extremity impairments have more pronounced limitations in daily activities compared to controls with similar impairments. Recognising upper extremity impairments and activity limitations are important and improved preventive, therapeutic and rehabilitation methods are needed.


Behavioral Prioritization Enhances Working Memory Precision and Neural Population Gain.
Humans allocate visual working memory (WM) resource according to behavioral relevance, resulting in more precise memories for more important items. Theoretically, items may be maintained by feature-tuned neural populations, where the relative gain of the populations encoding each item determines precision. To test this hypothesis, we compared the amplitudes of delay period activity in the different parts of retinotopic maps representing each of several WM items, predicting the amplitudes would track behavioral priority. Using fMRI, we scanned participants while they remembered the location of multiple items over a WM delay and then reported the location of one probed item using a memory-guided saccade. Importantly, items were not equally probable to be probed (0.6, 0.3, 0.1, 0.0), which was indicated with a precue. We analyzed fMRI activity in 10 visual field maps in occipital, parietal, and frontal cortex known to be important for visual WM. In early visual cortex, but not association cortex, the amplitude of BOLD activation within voxels corresponding to the retinotopic location of visual WM items increased with the priority of the item. Interestingly, these results were contrasted with a common finding that higher-level brain regions had greater delay period activity, demonstrating a dissociation between the absolute amount of activity in a brain area and the activity of different spatially selective populations within it. These results suggest that the distribution of WM resources according to priority sculpts the relative gains of neural populations that encode items, offering a neural mechanism for how prioritization impacts memory precision.


Molecular analysis of the Smith-Magenis syndrome: a possible contiguous-gene syndrome associated with del(17)(p11.2).
We undertook clinical evaluation (32 cases) and molecular evaluation (31 cases) of unrelated patients affected with Smith-Magenis syndrome (SMS) associated with an interstitial deletion of band p11.2 of chromosome 17. Patients were evaluated both clinically and electrophysiologically for peripheral neuropathy, since markers showing close linkage to one form of Charcot-Marie-Tooth disease (CMT1A) map to this chromosomal region. The common clinical findings were broad flat midface with brachycephaly, broad nasal bridge, brachydactyly, speech delay, and hoarse, deep voice. Fifty-five percent of the patients showed clinical signs (e.g., decreased or absent deep tendon reflexes, pes planus or pes cavus, decreased sensitivity to pain, and decreased leg muscle mass) suggestive of peripheral neuropathy. However, unlike patients with CMT1A, these patients demonstrated normal nerve conduction velocities. Self-destructive behaviors, primarily onychotillomania and polyembolokoilamania, were observed in 67% of the patients, and significant symptoms of sleep disturbance were observed in 62%. The absence of REM sleep was demonstrated by polysomnography in two patients. Southern analysis indicated that most patients were deleted for five 17p11.2 markers--FG1 (D17S446), 1516 (D17S258), pYNM67-R5 (D17S29), pA10-41 (D17S71), and pS6.1-HB2 (D17S445)--thus defining a region which appears to be critical to SMS. The deletion was determined to be of paternal origin in nine patients and of maternal origin in six patients. The apparent random parental origin of deletion documented in 15 patients suggests that genomic imprinting does not play a role in the expression of the SMS clinical phenotype. Our findings suggest that SMS is likely a contiguous-gene deletion syndrome which comprises characteristic clinical features, developmental delay, clinical signs of peripheral neuropathy, abnormal sleep function, and specific behavioral anomalies.


Chemoprevention of tobacco smoke-induced lung tumors by inhalation of an epigallocatechin gallate (EGCG) aerosol: a pilot study.
We investigated whether inhalation of aerosolized epigallocatechin gallate (EGCG) would prevent the development of lung tumors produced by tobacco smoke (TS). Male strain A/J mice were exposed for 5 mo, 6 h/day, 5 days/wk, to a mixture of tobacco sidestream and mainstream smoke. At the end of this exposure, 3 groups were formed: (a) mice exposed to TS and left undisturbed in air; (b) animals exposed to TS and given EGCG aerosol by nose-only inhalation for 30 min per session; and (c) animals exposed to TS and then exposed by nose-only inhalation to water aerosol without any EGCG (sham-exposed group). Three similar groups were formed from animals that previously had been kept in filtered air. In experiment 1, the EGCG concentration in the aerosol was 80 microg/L and administered 3 times a week and in experiment 2 it was 191 microg/L administered twice a week. Inhalation of EGCG did not modulate TS-induced tumorigenesis. In two accompanying positive control experiments, animals treated with the tobacco-specific carcinogen NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] were given the same EGCG or water aerosol treatment. In both experiments, EGCG aerosol significantly reduced lung tumor multiplicity by 20% to 30% However, exposure of NNK-treated animals to water solvent alone (sham exposure) produced an even greater reduction in tumor multiplicities (40%). A reduction of lung tumor multiplicities was also observed in animals exposed nose-only once or five times a week to either water aerosols or to filtered air. It is concluded that water-soluble chemopreventive agents that need to be ingested in comparatively high doses are not the most suitable candidates for administration by inhalation.


Uterine Septum and Other Müllerian Anomalies in a Recurrent Pregnancy Loss Population: Impact on Reproductive Outcomes.
To study the impact of Müllerian anomalies on reproductive outcomes in a recurrent pregnancy loss (RPL) population and to evaluate the effect of surgical correction of uterine septum on the odds of achieving live birth in RPL patients with a septate uterus. A retrospective cohort study. A specialized RPL clinic at a tertiary center. RPL patients with ≥ 2 pregnancy losses before 20 weeks' gestation who attended a specialized RPL clinic. We aimed to assess the association between a possible risk factor (Müllerian anomalies) and reproductive outcomes and that between having surgery for septate uterus and achieving a live birth. The primary outcome is live birth rate in RPL patients with Müllerian anomalies compared with those without; secondary outcome measures include rates of full-term live birth, preterm live birth, first and second trimester pregnancy loss, and stillbirth. After adjusting for patient age at the initial RPL visit, the number of pregnancy losses, and the presence of any other abnormal RPL investigation, the odds of achieving live birth were on average 49.4% lower for patients with a septate uterus than those without Müllerian anomalies (odds ratio, 0.51; 95% confidence interval, 0.30-0.86) in the studied cohort (n = 377). A subanalysis of 72 patients with septate uterus demonstrated a higher likelihood of live birth in those who underwent septum resection (46/72; 63.9%) than those who elected to go for expectant management (26/72; 36.1%), yet this study was underpowered to establish a significant difference (52.2% vs 34.6%; p = .22). In RPL patients, having a septate uterus significantly decreased the chances of achieving live birth. Patients with septate uterus who received hysteroscopic septum division had a higher tendency to achieve more live births than those who elected expectant management. However, our study was underpowered to detect a statistically significant difference.


Late incidence of chronic venous insufficiency after deep vein harvest.
The deep veins (DV) of the thigh have proven to be versatile autogenous conduits for arterial reconstruction. Harvesting DV poses a theoretical risk of compromising venous outflow of the limb, which could predispose to chronic venous morbidity. The purpose of this study was to define the late incidence of chronic venous insufficiency (CVI) and to characterize the long-term alterations in venous physiology after DV harvest. Since 1991, 269 patients have undergone arterial reconstructions using DV at our facility. Patients with DV harvest at least 43 months prior to the study (n = 151) were eligible for inclusion. Eighty-nine patients were excluded (deceased = 70; lost to follow-up = 19). Forty-six patients who declined formal testing were queried by phone for signs and symptoms of CVI. The current study presents a case-control series of 16 patients (27 limbs) after DV harvest and six age- and gender-matched control patients (12 limbs) who underwent examination and venous testing. At a mean follow-up of 70.1 +/- 5.6 months, 23 of 27 limbs (85.2%) had no significant CVI (CEAP C(0) to C(2)). Four limbs (14.8%) had significant venous morbidity (C(3) to C(6)), including edema alone (C(3); n = 2 limbs), edema with skin changes (C(4); n = 1 limb), and a healed venous ulceration (C(5); n = 1 limb). APG testing confirmed relative venous outflow obstruction after DV harvest (mean outflow fraction: harvested limbs = 38.4 +/- 3.9% vs control limbs = 51.7 +/- 4.3%; P = .04). Despite the relative outflow obstruction, the mean VFI was not significantly different between harvested and control limbs (harvested limbs = 1.08 +/- 0.15% vs control limbs = 0.77 +/- 0.16%; P = .19). DV harvest resulted in no significant changes in calf ejection fraction (harvested limbs = 67.4 +/- 6.4% vs control limbs = 86.8 +/- 9.5%; P = .09) or residual volume fraction measured (harvested limbs = 32.3 +/- 6.4% vs control limbs = 47.7 +/- 11.6%; P = .22). Of the 46 patients interviewed by phone, five (10.9%) reported bilateral amputations, seven (15.2%) reported chronic edema in their harvested limbs (C(3)), and 34 (73.9%) reported no signs of CVI in their harvested limbs (C(0)). Deep vein harvest produces few symptoms of chronic venous insufficiency, and venous ulceration is infrequent. Despite relative venous outflow obstruction, noninvasive indices of chronic venous insufficiency on APG are often normal, suggesting that the risk of developing venous ulceration is low in the majority of patients after DV harvest.


Bronchiectasis: new approaches to diagnosis and management.
Non-cystic fibrosis (CF) bronchiectasis is a common, potentially serious, condition. Further investigations should be performed in an attempt to identify the underlying cause because it may lead to a change in therapy and have significant prognostic implications. MRI is being investigated as a radiation free alternative to high-resolution CT scan of the chest. Many of the treatment recommendations for non-CF bronchiectasis have not been studied in randomized controlled trials but have been extrapolated from the management recommendations for CF. Studies are beginning to inform decisions regarding the management of non-CF bronchiectasis, and an understanding of the best treatment options is beginning to emerge.


Dual frequency dielectrophoresis with interdigitated sidewall electrodes for microfluidic flow-through separation of beads and cells.
This paper presents a novel design and separation strategy for lateral flow-through separation of cells/particles in microfluidics by dual frequency coupled dielectrophoresis (DEP) forces enabled by vertical interdigitated electrodes embedded in the channel sidewalls. Unlike field-flow-fractionation-DEP separations in microfluidics, which utilize planar electrodes on the microchannel floor to generate a DEP force to balance the gravitational force and separate objects at different height locations, lateral separation is enabled by sidewall interdigitated electrodes that are used to generate non-uniform electric fields and balanced DEP forces along the width of the microchannel. In the current design, two separate AC electric fields are applied to two sets of independent interdigitated electrode arrays fabricated in the sidewalls of the microchannel to generate differential DEP forces that act on the cells/particles flowing through. Individual particles (cells or beads) will experience DEP forces differently due to the difference in their dielectric properties. The balance of the differential DEP forces from the electrode arrays will position dissimilar particles at distinct equilibrium planes across the width of the channel. When coupled with fluid flow, this results in lateral separation along the width of the microchannel and the separated particles can thus be automatically directed into branched channel outlets leading to different reservoirs for downstream processing. In this paper, we present the design and analysis of lateral separation enabled by dual frequency coupled DEP, and cell/bead and cell/cell separations are demonstrated with this lateral separation strategy. With vertical interdigitated electrodes on the sidewall, the height of the microchannel can be increased without losing the electric field strength in contrast to other multiple frequency DEP devices with planar electrodes. As a result, populations of cells can be separated simultaneously instead of one by one to enable high-throughput sorting microfluidic devices.


Associations between mental health, substance use, and sexual abuse experiences among Latinas.
This study examined self-reported sexually abusive experiences in childhood and adulthood as correlates of current drug use, alcohol abuse, and depression and posttraumatic stress disorder (PTSD) symptoms. Participants were 204 Latina women 18-34 years old. Results indicated significant relationships between history of sexual abuse (regardless of age of occurrence), depression symptoms, PTSD symptoms, alcohol abuse, and drug use. When examined separately, childhood sexual abuse was associated with symptoms of depression, PTSD, and substance use but not alcohol abuse behaviors. Experiencing sexual abuse in adulthood was associated with symptoms of depression, alcohol abuse behaviors, and substance use but not PTSD symptoms. Structural equation modeling showed that substance use partially mediated the relationship between sexual abuse and mental health outcomes. These findings suggest mental health and substance use services should incorporate treatment for trauma, which may be the root of comorbid mental health and substance use issues.


Accidental exposure to Brucella abortus vaccines and occupational brucellosis among veterinarians in Minas Gerais state, Brazil.
Brucellosis is an important occupational disease, mainly among veterinarians, because of their frequent contact with sick animals, contaminated secretions and live attenuated anti-Brucella vaccines. This study aimed to determine the prevalence of accidental exposure to S19 and RB51 vaccine strains and occupational brucellosis among veterinarians registered to administer vaccinations in Minas Gerais, Brazil, as well as to identify the risk factors associated with accidental exposure to anti-Brucella abortus vaccines. Data were collected through an online questionnaire. Three hundred and twenty-nine veterinarians were included in the analyses using stratified random sampling. A multivariate logistic regression analysis was used to evaluate the predictors of accidental exposure to S19 and RB51 strains. Nearly one third of the veterinarians registered to administer bovine brucellosis vaccination in Minas Gerais, 32.83% (108/329) (95% confidence interval [CI]: 27.78-38.19%), reported having been accidentally exposed to S19 or RB51 vaccine strains. The exposure factors associated with this outcome included a score of personnel protective equipment (PPE) use during work (odds ratio [OR], 0.94; 95% CI: 0.89-0.98) and a score of knowledge about brucellosis symptoms, classified as poor (base category), intermediate (OR, 0.26; 95% CI: 0.07-0.87) or good (OR, 0.22; 95% CI: 0.07-0.62). In addition, 4.56% (15/329) (95% CI: 2.57-7.41%) of veterinarians reported that they had brucellosis, of which 46.67% (7/15) considered that the disease was due to accidental exposure to anti-B. abortus live attenuated vaccine. The prevalence of accidental exposure to B. abortus vaccine strains among veterinarians from Minas Gerais enrolled in the control of bovine brucellosis was high. The reduced knowledge about human brucellosis symptoms and lack of appropriate PPE use were risk factors from unintentional contact with S19 and RB51 vaccine strains.


High-3He Plume Origin and Temporal-Spatial Evolution of the Siberian Flood Basalts.
An olivine nephelinite from the lower part of a thick alkalic ultrabasic and mafic sequence of volcanic rocks of the northeastern part of the Siberian flood basalt province (SFBP) yielded a (40)Ar/(39)Ar plateau age of 253.3 +/- 2.6 million years, distinctly older than the main tholeiitic pulse of the SFBP at 250.0 million years. Olivine phenocrysts of this rock showed (3)He/(4)He ratios up to 12.7 times the atmospheric ratio; these values suggest a lower mantle plume origin. The neodymium and strontium isotopes, rare earth element concentration patterns, and cerium/lead ratios of the associated rocks were also consistent with their derivation from a near-chondritic, primitive plume. Geochemical data from the 250-million-year-old volcanic rocks higher up in the sequence indicate interaction of this high-(3)He SFBP plume with a suboceanic-type upper mantle beneath Siberia.


The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion.
Mutations in the gene encoding hepatocyte nuclear factor-4alpha (HNF-4alpha) result in maturity-onset diabetes of the young (MODY). To determine the contribution of HNF-4alpha to the maintenance of glucose homeostasis by the beta cell in vivo, we derived a conditional knockout of HNF-4alpha using the Cre-loxP system. Surprisingly, deletion of HNF-4alpha in beta cells resulted in hyperinsulinemia in fasted and fed mice but paradoxically also in impaired glucose tolerance. Islet perifusion and calcium-imaging studies showed abnormal responses of the mutant beta cells to stimulation by glucose and sulfonylureas. These phenotypes can be explained in part by a 60% reduction in expression of the potassium channel subunit Kir6.2. We demonstrate using cotransfection assays that the Kir6.2 gene is a transcriptional target of HNF-4alpha. Our data provide genetic evidence that HNF-4alpha is required in the pancreatic beta cell for regulation of the pathway of insulin secretion dependent on the ATP-dependent potassium channel.


Scoliosis in familial dysautonomia.
Scoliosis is an almost constant finding in patients with familial dysautonomia who survive their first few years. Spinal deformity is frequently progressive and can add a serious problem to the complicated disease with its already high morbidity and mortality. Because of the associated physiological disturbances, conservative treatment frequently does not control the problem and surgery by spine fusion is indicated. Our experience suggests that the operative should be performed relatively early, before the appearance of a major curvature.


[ORL emergencies at a hospital. Descriptive study. Degree of adequacy of the demand in relation to hospital ORL care].
We present a descriptive study of 6,522 ENT emergencies in our universitary hospital in 1987. They are analysed under different parameters, which include the reason for emergency, seriousness, surgery, hospitalization and interexaminations. We expose the correlation among the different parameters and the evaluation of the adequacy between hospitalary emergency services and the demand.