The thorny side of addiction: adaptive plasticity and dendritic spines.
Dendritic spines are morphologically specialized structures that receive the vast majority of central excitatory synaptic inputs. Studies have implicated changes in the size, shape, and number of dendritic spines in activity-dependent plasticity, and have further demonstrated that spine morphology is highly dependent on the dynamic organizational and scaffolding properties of its postsynaptic density (PSD). In vitro and in vivo models of experience-dependent plasticity have linked changes in the localization of glutamate receptors at the PSD with a molecular reorganization of the PSD and alterations in spine morphology. Chronic ethanol consumption results in adaptive changes in neuronal function that manifest as tolerance, physical dependence, and addiction. A potential mechanism supporting these adaptive changes that we recently identified is the homeostatic targeting of NR2B-containing NMDA receptors to the synapse. This increase is associated with and dependent on a corresponding increase in the localization of the scaffolding protein PSD-95 at the PSD, and with an actin-dependent increase in the size of dendritic spines. These observations led us to propose a molecular model for ethanol-induced plasticity at excitatory synapses in which increases in NR2B-containing NMDA receptors and PSD-95 at the PSD provide an expanded scaffolding platform for the recruitment and activation of signaling molecules that regulate spine actin dynamics, protein translation, and synaptic plasticity. This model is consistent with accumulating evidence that glutamatergic modulation of spine actin by the PSD plays a role in the aberrant plasticity of addiction.


Cardiovascular adjustments in breath-hold diving: comparison between divers and non-divers in simulated dynamic apnoea.
The diving response is the sequence of cardiovascular, respiratory and metabolic adjustments produced by apnoea and further strengthened by cooling of the facial area and/or hypoxia. This study aimed at comparing the cardiovascular response to diving of trained divers with that of a control group. In this order, 14 trained divers were compared with 14 non-divers. By means of impedance cardiography and continuous monitoring of arterial pressure, hemodynamic data were collected during three different experimental sessions. Each session included a cycle-ergometer exercise against a workload of 0.5 W kg(-1) of body mass, pedalling in a steady-state condition. During exercise, each subject randomly accomplished 40 s of breath-hold exercise with face immersion (test A) or in air (test B). A control exercise test with normal breathing (test C) was also performed. Divers showed a faster onset of bradycardic response (ANOVA, P < 0.01) and a faster adjustment in systemic vascular resistance (P < 0.001 for divers vs. controls) than did non-divers. Moreover, cardiac output decreased only in divers during the first phase of test A (P < 0.01 for divers vs. controls). The most striking findings were that divers showed a more rapid cardiovascular adjustment with respect to controls, in particular in heart rate and systemic vascular resistance; moreover, with continued apnoea, a delayed increase in myocardial performance and stroke volume occurred and obscured the cardiovascular effects of the diving response.


Targeting BCL2 for the treatment of lymphoid malignancies.
The failure of apoptosis (programmed cell death) underpins the development of many tumors and often renders them resistant to cytotoxic therapies. In hematologic malignancies, this impairment of apoptosis is often caused by overexpression of the pro-survival protein BCL2. Because abnormally high levels of BCL2 sustain these tumors, there has been much interest in targeting BCL2 as a novel approach to treating various hematologic malignancies. One such approach is the development of BH3 mimetic compounds, small molecules that mimic the action of the BH3-only proteins, natural antagonists of BCL2 and its pro-survival relatives. These compounds act by restoring the ability of a cell to undergo apoptotic cell death. Some of them have shown very encouraging results in early-phase clinical trials that are currently underway, particularly in patients with chronic lymphocytic leukemia and some non-Hodgkin lymphomas, diseases marked by BCL2 overexpression. In this review, we discuss the rationale behind targeting BCL2, highlight the recent findings from clinical trials, and pinpoint the next steps in the clinical development of this interesting and promising class of targeted agents, particularly for the treatment of lymphoid malignancies.


Protection from experimental autoimmune encephalomyelitis by polyclonal IgG requires adjuvant-induced inflammation.
Intravenous immunoglobulin (IVIG) proved to be an efficient anti-inflammatory treatment for a growing number of neuroinflammatory diseases and protects against the development of experimental autoimmune encephalomyelitis (EAE), a widely used animal model for multiple sclerosis (MS). The clinical efficacy of IVIG and IVIG-derived F(ab')2 fragments, generated using the streptococcal cysteine proteinase Ide-S, was evaluated in EAE induced by active immunization and by adoptive transfer of myelin-specific T cells. Frequency, phenotype, and functional characteristics of T cell subsets and myeloid cells were determined by flow cytometry. Antibody binding to microbial antigen and cytokine production by innate immune cells was assessed by ELISA. We report that the protective effect of IVIG is lost in the adoptive transfer model of EAE and requires prophylactic administration during disease induction. IVIG-derived Fc fragments are not required for protection against EAE, since administration of F(ab')2 fragments fully recapitulated the clinical efficacy of IVIG. F(ab')2-treated mice showed a substantial decrease in splenic effector T cell expansion and cytokine production (GM-CSF, IFN-γ, IL-17A) 9 days after immunization. Inhibition of effector T cell responses was not associated with an increase in total numbers of Tregs but with decreased activation of innate myeloid cells such as neutrophils, monocytes, and dendritic cells. Therapeutically effective IVIG-derived F(ab')2 fragments inhibited adjuvant-induced innate immune cell activation as determined by IL-12/23 p40 production and recognized mycobacterial antigens contained in Freund's complete adjuvant which is required for induction of active EAE. Our data indicate that F(ab')2-mediated neutralization of adjuvant contributes to the therapeutic efficacy of anti-inflammatory IgG. These findings might partly explain the discrepancy of IVIG efficacy in EAE and MS.


Reporting characteristics of meta-analyses in orthodontics: methodological assessment and statistical recommendations.
Ideally meta-analyses (MAs) should consolidate the characteristics of orthodontic research in order to produce an evidence-based answer. However severe flaws are frequently observed in most of them. The aim of this study was to evaluate the statistical methods, the methodology, and the quality characteristics of orthodontic MAs and to assess their reporting quality during the last years. Electronic databases were searched for MAs (with or without a proper systematic review) in the field of orthodontics, indexed up to 2011. The AMSTAR tool was used for quality assessment of the included articles. Data were analyzed with Student's t-test, one-way ANOVA, and generalized linear modelling. Risk ratios with 95% confidence intervals were calculated to represent changes during the years in reporting of key items associated with quality. A total of 80 MAs with 1086 primary studies were included in this evaluation. Using the AMSTAR tool, 25 (27.3%) of the MAs were found to be of low quality, 37 (46.3%) of medium quality, and 18 (22.5%) of high quality. Specific characteristics like explicit protocol definition, extensive searches, and quality assessment of included trials were associated with a higher AMSTAR score. Model selection and dealing with heterogeneity or publication bias were often problematic in the identified reviews. The number of published orthodontic MAs is constantly increasing, while their overall quality is considered to range from low to medium. Although the number of MAs of medium and high level seems lately to rise, several other aspects need improvement to increase their overall quality.


Effects of antioxidant supplements and nutrients on patients with asthma and allergies.
Asthma and allergic diseases have become a worldwide public health concern because of their increased prevalence. Despite decades of research on risk factors, the causes of these disorders are poorly understood. They are thought to develop through complex interactions between genetic and environmental factors. Because pulmonary and systemic oxidative stress increase inflammatory responses relevant to asthma and allergy, dietary or vitamin supplementation with antioxidants (a broad and varied category) has been proposed as an approach to reducing asthma incidence or morbidity. Meta-analyses of observational epidemiologic studies of variable methodological quality suggest associations of relatively low dietary intake of antioxidants and higher asthma and allergy prevalence. However, there have been few longitudinal studies of maternal or child dietary or vitamin/supplement antioxidant intake and asthma/allergy development. Moreover, there are no clinical trial data to support the use of dietary antioxidants or supplements to prevent asthma or allergy. A few small clinical trials suggest that specific antioxidants from diet or vitamin supplements might improve asthma control or lung function in asthmatic children or adults. Studies suggest that responses to antioxidants might be modified by life stage, genetic susceptibility, and environmental sources of oxidative stress. Large trials of antioxidant vitamin supplementation to prevent cancer suggest an increase in overall mortality with antioxidant vitamin supplementation, at least in populations with sufficient dietary antioxidant intake. This cautionary experience suggests that future trials to assess whether antioxidants reduce asthma incidence or improve asthma control should focus on supplementation of dietary sources of antioxidants. The potential benefits and risks of trials of vitamin supplements might be considered in special situations in which vulnerable populations have marked deficiency in dietary antioxidants, poor access to dietary antioxidants, and high exposure to environmental sources of oxidants.


Disparities in Colorectal Cancer Screening in the United States Before and After Implementation of the Affordable Care Act.
Colorectal cancer (CRC) is major cause of cancer-related mortality in the United States. Screening, however, is suboptimal and there are disparities in outcomes. After health policy changes and national efforts to increase rates of screening and address inequities, we aimed to examine progress towards eliminating racial and ethnic disparities in CRC screening. We conducted a repeated cross-sectional analysis of average-risk adults (age 50-75 years) included in the behavioral risk factors surveillance system survey. The main outcome was CRC screening status. We determined screening rates overall and by race and ethnicity (1 variable) for each survey year from 2008 through 2016 and used Joinpoint analyses to determine significant trends in rates over time by race and ethnicity. We also examined screening modalities used overall and by race and ethnicity. We analyzed data from 1,089,433 respondents. Screening uptake was 61.1% in 2008 and 67.6% in 2016 (P < .001); it was highest among whites and lowest among Hispanics. Only whites, Hispanics, and Asians had significantly higher screening rates in each study year (P < .001). Despite increasing rates among Hispanics, the screening rate disparity between whites and Hispanics was 17% at the end of the study period. Screening rates in blacks did not change with time and were 4.0% lower than the rate in whites in 2016. Other racial and ethnic groups had varying levels of improvement with time. Colonoscopy was the most common modality each year. In a cross-sectional analysis of average-risk adults, we found that although rates of CRC screening have increased overall since 2008, they have increased disproportionately in each racial and ethnic group, and disparities in screening uptake persist.


Particulate Matter Air Pollution and the Risk of Incident CKD and Progression to ESRD.
Elevated levels of fine particulate matter <2.5 µm in aerodynamic diameter (PM2.5) are associated with increased risk of cardiovascular outcomes and death, but their association with risk of CKD and ESRD is unknown. We linked the Environmental Protection Agency and the Department of Veterans Affairs databases to build an observational cohort of 2,482,737 United States veterans, and used survival models to evaluate the association of PM2.5 concentrations and risk of incident eGFR <60 ml/min per 1.73 m2, incident CKD, eGFR decline ≥30%, and ESRD over a median follow-up of 8.52 years. County-level exposure was defined at baseline as the annual average PM2.5 concentrations in 2004, and separately as time-varying where it was updated annually and as cohort participants moved. In analyses of baseline exposure (median, 11.8 [interquartile range, 10.1-13.7] µg/m3), a 10-µg/m3 increase in PM2.5 concentration was associated with increased risk of eGFR<60 ml/min per 1.73 m2 (hazard ratio [HR], 1.21; 95% confidence interval [95% CI], 1.14 to 1.29), CKD (HR, 1.27; 95% CI, 1.17 to 1.38), eGFR decline ≥30% (HR, 1.28; 95% CI, 1.18 to 1.39), and ESRD (HR, 1.26; 95% CI, 1.17 to 1.35). In time-varying analyses, a 10-µg/m3 increase in PM2.5 concentration was associated with similarly increased risk of eGFR<60 ml/min per 1.73 m2, CKD, eGFR decline ≥30%, and ESRD. Spline analyses showed a linear relationship between PM2.5 concentrations and risk of kidney outcomes. Exposure estimates derived from National Aeronautics and Space Administration satellite data yielded consistent results. Our findings demonstrate a significant association between exposure to PM2.5 and risk of incident CKD, eGFR decline, and ESRD.


Detection of oxidative DNA damage in isolated marine bivalve hemocytes using the comet assay and formamidopyrimidine glycosylase (Fpg).
Organisms in polluted areas can be exposed to complex mixtures of chemicals; however, exposure to genotoxic contaminants can be particularly devastating. DNA damage can lead to necrosis, apoptosis, or heritable mutations, and therefore has the potential to impact populations as well as individuals. Single cell gel electrophoresis (the comet assay) is a simple and sensitive technique used to examine DNA damage in single cells. The lesion-specific DNA repair enzyme formamidopyrimidine glycoslyase (Fpg) can be used in conjunction with the comet assay to detect 8-oxoguanine and other damaged bases, which are products of oxidative damage. Fpg was used to detect oxidative DNA damage in experiments where isolated oyster (Crassostrea virginica) and clam (Mercenaria mercenaria) hemocytes were exposed to hydrogen peroxide. Standard enzyme buffers used with Fpg and the comet assay produced unacceptably high amounts of DNA damage in the marine bivalve hemocytes used in this study necessitating a modification of existing methods. A sodium chloride based reaction buffer was successfully used. Oxidative DNA damage can be detected in isolated oyster and clam hemocytes using Fpg and the comet assay when the sodium chloride reaction buffer and protocols outlined here are employed. The use of DNA repair enzymes, such as Fpg, in conjunction with the comet assay expands the usefulness and sensitivity of this assay, and provides important insights into the mechanisms of DNA damage.


Patient perspectives of maintaining dignity in Indonesian clinical care settings: A qualitative descriptive study.
To gain an understanding towards the perspectives of hospitalized inpatients in Indonesia regarding maintaining dignity during clinical care. Dignity is a basic human right that is crucial for an individual's well-being. Respect for a person as a valuable human is a concept that is comparable to treating a person with dignity. Maintaining patient's dignity is an ethical goal of nursing care. Nevertheless, the concept is highly dependent on cultural context. This issue has not been well studied in Indonesia. This study used a qualitative descriptive design. Thirty-five participants were recruited by purposive sampling from medical to surgical wards of six public hospitals in Eastern Java, Indonesia. Data were collected in 2016 through individual face-to-face semi-structured interviews. Inductive content analysis was applied to the data. Four major categories which described qualities of nursing care essential for maintaining a patient's dignity in clinical care settings were revealed: (1) responsiveness; (2) respectful nurse-patient relationships; (3) caring characteristics and (4) personalized service. Our findings provide a cultural viewpoint of dignity for care recipients in Indonesia. The findings provide empirical support for linking dignified care and person-centred care principles with regards to cultural sensitivity. Nurses must not only be clinically competent but also culturally competent. The ability to provide culturally competent care is important for nurses as a strategy to maintain patient dignity during hospitalized care.


CFD analysis of laboratory scale phase equilibrium cell operation.
For the modeling of multiphase chemical reactors or separation processes, it is essential to predict accurately chemical equilibrium data, such as vapor-liquid or liquid-liquid equilibria [M. Šoóš et al., Chem. Eng. Process Intensif. 42(4), 273-284 (2003)]. The instruments used in these experiments are typically designed based on previous experiences, and their operation verified based on known equilibria of standard components. However, mass transfer limitations with different chemical systems may be very different, potentially falsifying the measured equilibrium compositions. In this work, computational fluid dynamics is utilized to design and analyze laboratory scale experimental gas-liquid equilibrium cell for the first time to augment the traditional analysis based on plug flow assumption. Two-phase dilutor cell, used for measuring limiting activity coefficients at infinite dilution, is used as a test case for the analysis. The Lagrangian discrete model is used to track each bubble and to study the residence time distribution of the carrier gas bubbles in the dilutor cell. This analysis is necessary to assess whether the gas leaving the cell is in equilibrium with the liquid, as required in traditional analysis of such apparatus. Mass transfer for six different bio-oil compounds is calculated to determine the approach equilibrium concentration. Also, residence times assuming plug flow and ideal mixing are used as reference cases to evaluate the influence of mixing on the approach to equilibrium in the dilutor. Results show that the model can be used to predict the dilutor operating conditions for which each of the studied gas-liquid systems reaches equilibrium.


Detection of LINE-1 hypomethylation in cfDNA of Esophageal Adenocarcinoma Patients.
DNA methylation plays an important role in cancer development. Cancer cells exhibit two types of DNA methylation alteration: site-specific hypermethylation at promoter of oncosuppressor genes and global DNA hypomethylation. This study evaluated the methylation patterns of long interspersed nuclear element (LINE-1) sequences which, due to their relative abundance in the genome, are considered a good surrogate indicator of global DNA methylation. LINE-1 methylation status was investigated in the cell-free DNA (cfDNA) of 21 patients, 19 with esophageal adenocarcinoma (EADC) and 2 with Barrett's esophagus (BE). The two BE patients and one EADC patient were also analyzed longitudinally. Methylation status was analyzed using restriction enzymes and DNA amplification. This methodology was chosen to avoid bisulfite conversion, which we considered inadequate for cfDNA analysis. Indeed, cfDNA is characterized by poor quality and low concentration, and bisulfite conversion might worsen these conditions. Results showed that hypomethylated LINE-1 sequences are present in EADC cfDNA. Furthermore, longitudinal studies in BE suggested a correlation between methylation status of LINE-1 sequences in cfDNA and progression to EADC. In conclusion, our study indicated the feasibility of our methodological approach to detect hypomethylation events in cfDNA from EADC patients, and suggests LINE-1 methylation analysis as a new possible molecular assay to integrate into patient monitoring.


Attention without awareness in blindsight.
The act of attending has frequently been equated with visual awareness. We examined this relationship in 'blindsight'--a condition in which the latter is absent or diminished as a result of damage to the primary visual cortex. Spatially selective visual attention is demonstrated when information that stimuli are likely to appear at a specific location enhances the speed or accuracy of detection of stimuli subsequently presented at that location. In a blindsight subject, we showed that attention can confer an advantage in processing stimuli presented at an attended location, without those stimuli entering consciousness. Attention could be directed both by symbolic cues in the subject's spared field of vision or cues presented in his blind field. Cues in his blind field were even effective in directing his attention to a second location remote from that at which the cue was presented. These indirect cues were effective whether or not they themselves elicited non-visual awareness. We concluded that the spatial selection of information by an attentional mechanism and its entry into conscious experience cannot be one and the same process.


Myt3 Mediates Laminin-V/Integrin-β1-Induced Islet-Cell Migration via Tgfbi.
Myt3 is a prosurvival factor in pancreatic islets; however, its role in islet-cell development is not known. Here, we demonstrate that myelin transcription factor 3 (Myt3) is expressed in migrating islet cells in the developing and neonatal pancreas and thus sought to determine whether Myt3 plays a role in this process. Using an ex vivo model of islet-cell migration, we demonstrate that Myt3 suppression significantly inhibits laminin-V/integrin-β1-dependent α- and β-cell migration onto 804G, and impaired 804G-induced F-actin and E-cadherin redistribution. Exposure of islets to proinflammatory cytokines, which suppress Myt3 expression, had a similar effect, whereas Myt3 overexpression partially rescued the migratory ability of the islet cells. We show that loss of islet-cell migration, due to Myt3 suppression or cytokine exposure, is independent of effects on islet-cell survival or proliferation. Myt3 suppression also had no effect on glucose-induced calcium influx, F-actin remodeling or insulin secretion by β-cells. RNA-sequencing (RNA-seq) analysis of transduced islets showed that Myt3 suppression results in the up-regulation of Tgfbi, a secreted diabetogenic factor thought to impair cellular adhesion. Exposure of islets to exogenous transforming growth factor β-induced (Tgfbi) impaired islet-cell migration similar to Myt3 suppression. Taken together, these data suggest a model by which cytokine-induced Myt3 suppression leads to Tgfbi de-repression and subsequently to impaired islet-cell migration, revealing a novel role for Myt3 in regulating islet-cell migration.


Recurrent herpes simplex in the mouse: inflammation in the skin and activation of virus in the ganglia following peripheral stimulation.
The originally infected ear of mice latently infected in the cervical ganglia with herpes simplex virus (HSV) was treated with one of five stimuli: stripping with cellophane tape, irradiation with u.v. light, or the application of xylene, dimethyl sulphoxide (DMSO) or retinoic acid. Each of these stimuli induced the appearance of infectious virus in the ganglia 1 to 5 days later, most frequently after 1 to 3 days. Virus was also isolated from the treated ears, most frequently 3 to 5 days after stimulation. In a proportion of mice treated with cellophane tape stripping, xylene, retinoic acid or DMSO, clinical recurrent disease was observed, although in the case of DMSO this proportion was low. Some of the physiological changes induced in the skin by the five stimuli were studied. Treatment with DMSO, cellophane tape stripping or xylene induced almost immediate inflammation in the skin as judged by extravasation of Evans blue dye. Studies with inhibitors suggested that this was mediated by a neurogenic factor together with histamine or 5-hydroxytryptamine, or both of these. In addition, with the exception of mice treated with DMSO, the levels of prostaglandins of the E and F classes in the skin of the ear were elevated 1 to 3 days after treatment. These results are discussed with reference to the mechanisms by which recurrent herpetic disease develops.


scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila.
Cancer is a multistep process involving cooperation between oncogenic or tumor suppressor mutations and interactions between the tumor and surrounding normal tissue. Here we present the first description of cooperative tumorigenesis in Drosophila, by using a system that mimics the development of tumors in mammals. We have used the MARCM system to generate mutant clones of the apical-basal cell polarity tumor suppressor gene, scribble, in the context of normal tissue. We show that scribble mutant clones in the eye disc exhibit ectopic expression of cyclin E and ectopic cell cycles, but do not overgrow due to increased cell death mediated by the JNK pathway and the surrounding wild-type tissue. In contrast, when oncogenic Ras or Notch is expressed within the scribble mutant clones, cell death is prevented and neoplastic tumors develop. This demonstrates, for the first time in Drosophila, that activated alleles of Ras and Notch can act as cooperating oncogenes in the development of epithelial tumors, and highlights the importance of epithelial polarity regulators in restraining oncogenes and preventing tumor formation.


Bone mineral density in hypoparathyroid women on LT4 suppressive therapy. Effect of calcium and 1,25(OH)2 vitamin D3 treatment.
Our aim was to study the bone mineral density (BMD) of patients with chronic hypoparathyroidism (hypoPTH) after longterm calcium and vitamin D treatment. Twenty hypoPTH women (mean-/+SD, aged 50-/+15 years, IPTH 4-/+6 pg/ml) and 20 matched euparathyroid women (euPTH) after near total thyroidectomy for thyroid cancer, completed with I-131 ablation and on suppressive therapy with L-Thyroxine (LT(4)), were studied. In addition eight hypoPTH patients who were receiving LT(4) replacement therapy after surgery for compressive goiter were simultaneously studied. The hypoPTH patients were on calcium and 1,25(OH)(2) vitamin D(3) therapy to normalize serum calcium. Bone mineral density (BMD) (DXA, at the lumbar spine [L(2)- L(4), LS], femoral neck [FN] and Ward triangle [WT]), serum and urine calcium, serum phosphorus, TOTALALP and osteocalcin were measured. Patients with hypoPTH showed greater lumbar BMD than euPTH patients on suppressive therapy (Z-score; 1.01-/+1.34 vs. -0.52-/+0.70, p<0.05). Serum osteocalcin levels were higher in hypoPTH patients on suppressive therapy compared to hypoPTH patients on replacement therapy. The LS BMD from hypoPTH patients correlated with calcium supplements (r=0.439; p=0.02), 1,25(OH)(2)D(3) dose (r=0.382; p=0.04) and LT(4) dose (r=0.374; p=0.05). Our data suggest that long-term treatment with calcium and 1,25(OH)(2) vitamin D3 supplements in hypoPTH patients on suppressive LT4 therapy results in increased BMD when compared with patients with normal PTH levels.


Innovative surfaces and alloys for dental implants: What about biointerface-safety concerns?
The present review article aimed to discuss the recent technologies employed for the development of dental implants, mainly regarding innovative surface treatments and alternative alloys, emphasizing the bio-tribocorrosion processes. An electronic search applying specific MeSH terms was carried out in PubMed and Google Scholar databases to collect data until August 2021, considering basic, pre-clinical, clinical and review studies. The relevant articles (n=111), focused on innovative surface treatments for dental implants and their potential undesirable biological effects, were selected and explored. Novel texturization methodologies for dental implants clearly provided superficial and structural atomic alterations in micro- and nanoscale, promoting different mechanical-chemical interactions when applied in the clinical set. Some particulate metals released from implant surfaces, their degradation products and/or contaminants exhibited local and systemic reactions after implant installation and osseointegration, contributing to unexpected treatment drawbacks and adverse effects. Therefore, there is an urgent need for development of pre-clinical and clinical platforms for screening dental implant devices, to predict the biointerface reactions as early as possible during the development phases. Modern surface treatments and innovative alloys developed for dental implants are not completely understood regarding their integrity during long-term clinical function, especially when considering the bio-tribocorrosion process. From this review, it is possible to assume that degradation and contamination of dental surfaces might be associated within peri-implant inflammation and cumulative long-lasting systemic toxicity. The in-depth comprehension of the biointerface modifications on these novel surface treatments might preclude unnecessary expenses and postoperative complications involving osseointegration failures.


Evidence for a link between mortality in acute COPD and hospital type and resources.
The 1997 BTS/RCP national audit of acute care of chronic obstructive pulmonary disease (COPD) found wide variations in mortality between hospitals which were only partially explained by known audit indicators of outcome. It was hypothesised that some of the unexplained variation may result from differences in hospital type, organisation and resources. This pilot study examined the hypothesis as a factor to be included in a future national audit programme. Thirty hospitals in England and Wales were randomly selected by geographical region and hospital type (teaching, large district general hospital (DGH), small DGH). Data on process and outcome of care (death and length of stay) were collected retrospectively at 90 days on all prospectively identified COPD admissions over an 8 week period. Each centre completed a questionnaire relating to organisation and resources available for the care of COPD patients. Eleven teaching hospitals, nine large DGHs, and 10 small DGHs provided data on 1274 cases. Mortality was high (14%) with wide variation between centres (IQR 9-19%). Small DGHs had a higher mortality (17.5%) than teaching hospitals (11.9%) and large DGHs (11.2%). When corrected for confounding factors, an excess of deaths in small DGHs was still observed (OR 1.56 (CI 1.04 to 2.35)) v teaching hospitals. Analysis of resource and organisational factors suggested higher mortality was associated with fewer doctors (OR 1.5) and with fewer patients being under the care of a specialist physician (OR 1.8). Small DGHs had fewest resources. Significant differences in mortality may exist between hospital types. The findings justify further study in a proposed national audit.


Anti-epidermal growth factor receptor antibodies inhibit the autocrine-stimulated growth of MDA-468 human breast cancer cells.
The response of malignant and nonmalignant human breast cell lines to the growth inhibitory effects of monoclonal antibodies against the epidermal growth factor (EGF) receptor was studied. A series of human breast cell lines, which express EGF receptor, were used: MDA-468, MDA-231, and Hs578T human breast cancer cells and the transformed human mammary epithelial cell lines 184A1N4 and 184A1N4-T that have been benzo[a]pyrene immortalized and further transformed with SV40T, respectively. Four antibodies of two different classes were tested: 225 immunoglobulin G (IgG), 108.4 IgG, 96 immunoglobulin M (IgM), and 42 IgM. All four antibodies inhibited the anchorage-dependent and -independent, EGF-stimulated growth of 184A1N4 and 184A1N4-T cells, respectively, and this growth inhibition could be reversed by the addition of increasing concentrations of EGF. In contrast, the antibodies inhibited the anchorage-dependent and -independent growth of MDA-468 cells in the absence of exogenous EGF suggesting that the antibodies were acting to block access of an endogenously produced ligand to the EGF receptor. In the presence of antibody and increasing concentrations of EGF, MDA-468 cell growth was first stimulated then inhibited as the EGF concentration increased, thus, uncovering the growth stimulatory potential of low concentrations of EGF in these cells. Data is presented that indicates MDA-468 cells secrete a transforming growth factor with autocrine growth stimulatory capabilities. The growth of MDA-231 and Hs578T cells, which contain activated ras oncogenes, was not inhibited by the antibodies and the growth of these cell lines was not stimulated by EGF. Of the cell lines studied only MDA-468 cells appear to possess an autocrine growth stimulatory capacity.


Radio frequency based label-free detection of glucose.
We investigated the frequency based mediator-free glucose sensor in the radio-frequency (RF) range. Frequency dependent power signal showed clear dependence on the glucose concentration with free enzymatic condition. Also, the passive electrical components such as the resistance, inductance, shunt conductance, and capacitance were extracted based on the transmission line model for further analysis. These various parameters proposed by the signal processing provided more effective verification for instant multi-components in-situ readings without any added supporters. Additionally the residual signal (RS), impedance (Z), and propagation constant (γ) were also calculated from measured S-parameters for glucose analysis. These parameters basically showed amplitude variation and interestingly, some parameters such as inductance and impedance showed frequency shift of resonance dip. The results support that the frequency based sensing technique including the parameter based analysis can enable effective multi-dimensional detection of glucose. Moreover, this technique showed that glucose sensing is also possible over a diabetic patient's serum.


[New data on the biological action of normal immunoglobulins].
Experiments on 2,520 CBA mice (CBA X X C57BL) F1 nice have shown that the injection of homologous serum immunoglobulins (obtained from intact and blood-stimulated animals), made 2 hours after gamma irradiation from a 60Co source, prevents the development of intestinal dysbacteriosis and endogenous infection. The injection of mouse and human immunoglobulins to nonirradiated mice improved their resistance to experimental infection with Escherichia coli live culture, increased the expression of receptors to the Fc-fragments of IgG in peritoneal macrophages and enhanced the physical working capacity of the animals. The preparations containing normal antitissular antibodies have proved to be particularly effective. In mice, rabbits and dogs the preparations under test have produced no changes in the general state of the animals, no local reactions and no disturbances in the cardiovascular activity.


High-Q microfluidic cavities in silicon-based two-dimensional photonic crystal structures.
We demonstrate postprocessed microfluidic double-heterostructure cavities in silicon-based photonic crystal slab waveguides. The cavity structure is realized by selective fluid infiltration of air holes using a glass microtip, resulting in a local change of the average refractive index of the photonic crystal. The microcavities are probed by evanescent coupling from a silica nanowire. An intrinsic quality factor of 57,000 has been derived from our measurements, representing what we believe to be the largest value observed in microfluidic photonic crystal cavities to date.


An ultra-linear piezo-floating-gate strain-gauge for self-powered measurement of quasi-static-strain.
In this paper we describe a self-powered sensor that can be used for in-vivo measurement of the quasi-static-strain and also for in-vivo measurement of the L1 norm of the strain signal. At the core of the proposed design is a linear floating-gate injector that can achieve more than 13 bits of precision in sensing, signal integration and non-volatile storage. The injectors are self-powered by the piezoelectric transducers that convert mechanical energy from strain-variations into electrical energy. A differential injector topology is used to measure the quasi-static strain by integrating the difference between the L1 norm of the piezoelectric signal generated during the positive and negative strain-cycles. The linear floating-gate injectors are integrated with charge-pumps, digital calibration circuits and digital programming circuits to form a system-on-chip solution that can interface with a standard bio-telemetry platform. We demonstrate the proof-of-concept self-powered measurement of quasi-static strain and L1 norm of the strain signal using sensor prototypes fabricated in a 0.5- μm standard CMOS process and validated using a bench-top biomechanical test setup.


Obesity and psychotropics.
Weight gain is on the rise in the United States as is the diagnosis and treatment of mental disorders. These two phenomena are distinctly separate but tend to overlap in that most psychotropic agents approved for use in the United States are associated with the potential to induce weight gain. Metabolic disorders such as diabetes, hypercholesterolemia, and hypertension are also on the rise and often associated with weight gain and clearly associated with certain psychotropic medications. This article serves to provide a succinct review regarding the epidemiology, etiology, and treatment options for psychotropic-induced obesity.


PICU Autopsies: Rates, Patient Characteristics, and the Role of the Medical Examiner.
Autopsy rates in North American Children's hospitals have not been recently evaluated. Our objectives were 1) to determine the autopsy rates from patients cared for in PICUs during a portion of their hospital stay, 2) to identify patient characteristics associated with autopsies, and 3) to understand the relative role of medical examiner cases. Secondary analysis of data prospectively collected from a sample of patients (n = 10,078) admitted to PICUs affiliated with the Collaborative Pediatric Critical Care Research Network between December 2011 and April 2013. Eight quaternary care PICUs. Patients in the primary study were less than 18 years old, admitted to a PICU and not moribund on PICU admission. Patients included in this analysis were those who died during their hospital stay. None. Sociodemographic, clinical, hospital, and PICU data were compared between patients who had autopsies conducted and those who did not and between medical examiner and nonmedical examiner autopsies. Of 10,078 patients, 275 died of which 36% (n = 100) had an autopsy performed. Patients with cancer who died were less likely to receive autopsies (p = 0.005), whereas those who died after trauma or cardiac arrest had autopsies performed more often (p < 0.01). Autopsies were more common in patients with greater physiologic instability at admission (p < 0.001), and those who received more aggressive PICU care. Medical examiner cases comprised nearly half of all autopsies (n = 47; 47%) were conducted in patients presenting with greater physiologic instability (p < 0.001) and more commonly after catastrophic events such as cardiac arrest or trauma (p < 0.001). In this first multicenter analysis of autopsy rates in children, 36% of deaths had autopsies conducted, of which nearly half were conducted by the medical examiner. Deaths with autopsy are more likely to be previously healthy children that had catastrophic events prior to admission.


Stresses in the metastatic cascade: molecular mechanisms and therapeutic opportunities.
Metastasis is the ultimate "survival of the fittest" test for cancer cells, as only a small fraction of disseminated tumor cells can overcome the numerous hurdles they encounter during the transition from the site of origin to a distinctly different distant organ in the face of immune and therapeutic attacks and various other stresses. During cancer progression, tumor cells develop a variety of mechanisms to cope with the stresses they encounter, and acquire the ability to form metastases. Restraining these stress-releasing pathways could serve as potentially effective strategies to prevent or reduce metastasis and improve the survival of cancer patients. Here, we provide an overview of the tumor-intrinsic, microenvironment- and treatment-induced stresses that tumor cells encounter in the metastatic cascade and the molecular pathways they develop to relieve these stresses. We also summarize the preclinical and clinical studies that evaluate the potential therapeutic benefit of targeting these stress-relieving pathways.


Genomic characterization of the LEED..PEEDs, a gene family unique to the medicago lineage.
The LEED..PEED (LP) gene family in Medicago truncatula (A17) is composed of 13 genes coding small putatively secreted peptides with one to two conserved domains of negatively charged residues. This family is not present in the genomes of Glycine max, Lotus japonicus, or the IRLC species Cicer arietinum. LP genes were also not detected in a Trifolium pratense draft genome or Pisum sativum nodule transcriptome, which were sequenced de novo in this study, suggesting that the LP gene family arose within the past 25 million years. M. truncatula accession HM056 has 13 LP genes with high similarity to those in A17, whereas M. truncatula ssp. tricycla (R108) and M. sativa have 11 and 10 LP gene copies, respectively. In M. truncatula A17, 12 LP genes are located on chromosome 7 within a 93-kb window, whereas one LP gene copy is located on chromosome 4. A phylogenetic analysis of the gene family is consistent with most gene duplications occurring prior to Medicago speciation events, mainly through local tandem duplications and one distant duplication across chromosomes. Synteny comparisons between R108 and A17 confirm that gene order is conserved between the two subspecies, although a further duplication occurred solely in A17. In M. truncatula A17, all 13 LPs are exclusively transcribed in nodules and absent from other plant tissues, including roots, leaves, flowers, seeds, seed shells, and pods. The recent expansion of LP genes in Medicago spp. and their timing and location of expression suggest a novel function in nodulation, possibly as an aftermath of the evolution of bacteroid terminal differentiation or potentially associated with rhizobial-host specificity.


Jiangella muralis sp. nov., from an indoor environment.
A Gram-stain-positive, non-spore-forming actinobacterium, designated 15-Je-017(T), was isolated from wall material of an indoor environment. The isolate formed a rudimentary substrate mycelium that fragmented into rod-shaped cells. On the basis of 16S rRNA gene sequence analysis, strain 15-Je-017(T) was shown to belong to the genus Jiangella and was most closely related to Jiangella alba YIM 61503(T) (99.7 % 16S rRNA gene sequence similarity), Jiangella alkaliphila D8-87(T) (99.0 %) and Jiangella gansuensis YIM 002(T) (99.0 %). The predominant menaquinone was MK-9(H(4)). Whole-cell hydrolysates contained ll-diaminopimelic acid as the diagnostic diamino acid in the cell wall and rhamnose and glucose as the main sugars. Mycolic acids were absent. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside and seven unknown phospholipids. The fatty acid profile contained major amounts (>5 %) of anteiso-C(15 : 0), iso-C(16 : 0), iso-C(15 : 0), iso-C(17 : 0), anteiso-C(17 : 0) and C(17 : 1)ω8c, which supported the affiliation of strain 15-Je-017(T) to the genus Jiangella. DNA-DNA relatedness and physiological and biochemical tests allowed the differentiation of strain 15-Je-017(T) from the type strains of the three known Jiangella species. Strain 15-Je-017(T) represents a novel Jiangella species, for which we propose the name Jiangella muralis sp. nov., with type strain 15-Je-017(T) (=DSM 45357(T) =CCM 7680(T)).


Degradation of mating factor by alpha-mating type cells of Saccharomyces cerevisiae.
The change of the mating factor activity during the culture of Saccharomyces cerevisiae X-2180 1B, an alpha-mating type haploid strain, were followed. The activity increased rapidly during the exponential phase of growth, reached a maximum during the early stationary phase and then decreased. Oligopeptides comprising partial sequences of the mating factor were isolated from the culture fluids at various phases of cell growth. We concluded that the mating factor, a tridecapeptide, was degraded during culture into two peptides, Trp-His-Trp-Leu-Gln-Leu and Lys-Pro-Gly-Gln-Pro-Met-Tyr, by cleavage of the peptide bond between Leu-6 and Lys-7 of the mating factor. A dodecapeptide lacking the N-terminal Trp residue was not detected at any stage of cell growth examined.


Multi-layer mucilage of Plantago ovata seeds: Rheological differences arise from variations in arabinoxylan side chains.
Mucilages are hydrocolloid solutions produced by plants for a variety of functions, including the creation of a water-holding barrier around seeds. Here we report our discovery of the formation of three distinct mucilage layers around Plantago ovata seeds upon their hydration. Each layer is dominated by different arabinoxylans (AXs). These AXs are unusual because they are highly branched and contain β-1,3-linked xylose in their side chains. We show that these AXs have similar monosaccharide and linkage composition, but vary in their polymer conformation. They also exhibit distinct rheological properties in aqueous solution, despite analytical techniques including NMR showing little difference between them. Using enzymatic hydrolysis and chaotropic solvents, we reveal that hydrogen bonding and side chain distribution are key factors underpinning the distinct rheological properties of these complex AXs.


Regulation of blood flow through the ductus venosus.
The ductus venosus, which is situated within the liver parenchyma, is a vascular shunt unique to the fetal and neonatal circulations. In fetal life, the ductus venosus allows variable portions of the umbilical and portal venous blood flows to bypass the liver microcirculation. After birth, when the umbilical circulation ceases, blood flow through the ductus venosus decreases substantially. The purposes of this review are to summarize the data currently available on the regulation of ductus venosus blood flow in fetal and neonatal life and to identify those factors that affect ductus venosus closure after birth. Most recent experiments indicate that mechanical factors exert the major influence on the fetal ductus venosus shunt. In the fetal sheep, for example, pressure and resistance differences across the liver are important determinants of the umbilical venous blood flow through the ductus venosus. In addition, ductus venosus blood flow can passively in response to alterations in the systemic circulation. Shortly after birth, blood flow and blood pressure in the umbilical sinus decrease abruptly. This causes the orifice of the ductus venosus to retract and narrow, resulting in functional closure of the vascular shunt. Permanent structural closure, consisting of connective tissue deposition within the entire ductus lumen, starts within days after birth and is completed by 1-3 months of age.


Impact of an acute medical admission unit on length of hospital stay, and emergency department 'wait times'.
While many UK hospitals have introduced an acute medical admissions unit (AMAU) to facilitate an efficient emergency admission process and reduce length of hospital stay (LOS), there is a lack of such data in the Republic of Ireland. To determine the impact of an AMAU on emergency department (ED) wait times for a hospital bed, consultant practice, and LOS. Retrospective analysis of data recorded in the hospital in-patient enquiry (HIPE) system. We studied all emergency medical patients admitted to St James' Hospital Dublin between 1 January 2002 and 31 December 2003. In 2002, patients were admitted directly to a variety of wards, many of which were not affiliated with a medical specialty, under the care of a named consultant physician. In 2003, two centrally located wards were re-configured to function as an AMAU, and all emergency patients were admitted to this unit. For all physician teams, median LOS shortened significantly from 2002 to 2003 (6 vs. 5 days, p<0.0001). Overall, patients seen by general physicians had a shorter LOS (5 days) than that of those seen by sub-specialists (6 days) (p<0.0001). The number of patients waiting in the ED for a hospital bed was reduced by 30% from 2002 to 2003 (p<0.001). Extrapolated cost savings for the hospital with the introduction of the AMAU were estimated at approximately 4039 bed-days and 1 714 152. Introduction of the AMAU speeded access to acute medical service and reduced costs.


The comparison of pleurodesis effects of iodopovidone at different concentrations and magnesium silicate: An experimental study.
This experimental study aims to investigate the pleurodesis effects of iodopovidone at different concentrations (2% and 4%) and sterile talc in a rat model. Forty male Wistar Albino rats were randomly divided into four equal groups including 10 rats in each group. Groups 1, 2, and 3 were designed as the study, and Group 4 as the control group. In Group 1, 4 g sterile talc was given in the slurry form at 20 mL 0.9% saline solution, in Group 2 and Group 3 10% iodopovidone solution were given at 4% and 2% concentrations, respectively, and in Group 4, 0.9% saline was only administrated as 3 mL into the pleural space. All rats were sacrificed on Day 30 and evaluated for macroscopic and microscopic examination. Microscopic evaluation was performed for alveolar collapse, alveolar hemorrhage, alveolar infiltration and fibrosis. Brain, liver, and kidney tissues were also examined. Iodopovidone macroscopically caused a significant adhesion similar to sterile talc at a concentration of 4%. The pleurodesis effect of iodopovidone at a concentration of 4% was significantly similar to talc, when microscopic parameters were evaluated. Granulomas due to sterile talc were observed in the opposite hemithorax. Brain, liver, and kidney examinations revealed no systemic distribution for both agents. Iodopovidone is a powerful alternative to sterile talc with its easy accessibility and low cost. In this study, 4% iodopovidone was found to provide effective and safe pleurodesis in rats. We believe that the use of this concentration in clinical studies would provide more effective results.


Cyclooxygenase-2 expression in clear cell renal cell carcinoma.
Cyclooxygenase-2 (COX-2) promotes carcinogenesis by inducing proliferation and angiogenesis while decreasing apoptosis and immunosuppressive activity. It is overexpressed in many malignancies including renal cell carcinoma (RCC). The aim of this study was to investigate COX-2 expression in clear cell RCC and its association with tumour grades and demographic parameters. Thirty-six clear cell RCC cases were selected. There were 21 (58.3%) men and 15 (41.7%) women with median age of 56.6 years (range: 16-74 years). Chinese constituted 16 (44.4%) of the cases; Malays 14 (38.9%) cases and Indian 6 (16.7%) cases. There were 6 (16.7%) grade 1, 20 (55.6%) grade 2, 10 (27.8%) grade 3 and none was grade 4. The paraffin embedded tissues were cut at 4 μm thick and stained with COX-2 monoclonal antibody. Eighteen (50%) of the RCC cases were immunopositive, of which all showed strong positivity. The immunopositive cases showed cytoplasmic membrane positivity. There was no significant association between COX-2 expression with grade, age, sex and ethnicity (p=0.457, p=0.054, p=0.389 and p=0.568 respectively). Strong positivity of COX-2 suggest that COX-2 may play a role in cell proliferation and in carcinogenesis.


Substitution bias, rapid saturation, and the use of mtDNA for nematode systematics.
Only relatively recently have researchers turned to molecular methods for nematode phylogeny reconstruction. Thus, we lack the extensive literature on evolutionary patterns and phylogenetic usefulness of different DNA regions for nematodes that exists for other taxa. Here, we examine the usefulness of mtDNA for nematode phylogeny reconstruction and provide data that can be used for a priori character weighting or for parameter specification in models of sequence evolution. We estimated the substitution pattern for the mitochondrial ND4 gene from intraspecific comparisons in four species of parasitic nematodes from the family Trichostrongylidae (38-50 sequences per species). The resulting pattern suggests a strong mutational bias toward A and T, and a lower transition/transversion ratio than is typically observed in other taxa. We also present information on the relative rates of substitution at first, second, and third codon positions and on relative rates of saturation of different types of substitutions in comparisons ranging from intraspecific to interordinal. Silent sites saturate extremely quickly, presumably owing to the substitution bias and, perhaps, to an accelerated mutation rate. Results emphasize the importance of using only the most closely related sequences in order to infer patterns of substitution accurately for nematodes or for other taxa having strongly composition-biased DNA. ND4 also shows high amino acid polymorphism at both the intra- and interspecific levels, and in higher level comparisons, there is evidence of saturation at variable amino acid sites. In general, we recommend using mtDNA coding genes only for phylogenetics of relatively closely related nematode species and, even then, using only nonsynonymous substitutions and the more conserved mitochondrial genes (e.g., cytochrome oxidases). On the other hand, the high substitution rate in genes such as ND4 should make them excellent for population genetics studies, identifying cryptic species, and resolving relationships among closely related congeners when other markers show insufficient variation.


Simultaneous epidural functional near-infrared spectroscopy and cortical electrophysiology as a tool for studying local neurovascular coupling in primates.
Simultaneous measurements of intra-cortical electrophysiology and hemodynamic signals in primates are essential for relating human neuroimaging studies with intra-cortical electrophysiology in monkeys. Previously, technically challenging and resourcefully demanding techniques such as fMRI and intrinsic-signal optical imaging have been used for such studies. Functional near-infrared spectroscopy is a relatively less cumbersome neuroimaging method that uses near-infrared light to detect small changes in concentrations of oxy-hemoglobin (HbO), deoxy-hemoglobin (HbR) and total hemoglobin (HbT) in a volume of tissue with high specificity and temporal resolution. FNIRS is thus a good candidate for hemodynamic measurements in primates to acquire local hemodynamic signals during electrophysiological recordings. To test the feasibility of using epidural fNIRS with concomitant extracellular electrophysiology, we recorded neuronal and hemodynamic activity from the primary visual cortex of two anesthetized monkeys during visual stimulation. We recorded fNIRS epidurally, using one emitter and two detectors. We performed simultaneous cortical electrophysiology using tetrodes placed between the fNIRS sensors. We observed robust and reliable responses to the visual stimulation in both [HbO] and [HbR] signals, and quantified the signal-to-noise ratio of the epidurally measured signals. We also observed a positive correlation between stimulus-induced modulation of [HbO] and [HbR] signals and strength of neural modulation. Briefly, our results show that epidural fNIRS detects single-trial responses to visual stimuli on a trial-by-trial basis, and when coupled with cortical electrophysiology, is a promising tool for studying local hemodynamic signals and neurovascular coupling.


Anastomotic pseudoaneurysms. A continuing late complication of vascular reconstructive procedures.
Anastomotic pseudoaneurysms continue to be a late complication of vascular grafting procedures. We reviewed the records of 48 patients who presented with 65 abdominal or lower extremity anastomotic pseudoaneurysms during 1977 to 1985. The interval between the original operation and the development of a pseudoaneurysm was 6.2 years (range, 2.5 months to 19 years). Most patients underwent resection of the involved segment of graft and artery with placement of an interposition graft. Graft patency was 97.5% during a mean follow-up of 2.4 years (range, two months to five years), and one operative mortality occurred. Four patients had emergency procedures; one patient underwent reconstruction, and three others underwent resection of the pseudoaneurysms alone. Two of those patients died, and the one survivor eventually required a high amputation. We recommend aggressive diagnosis and surgical reconstruction in these patients usually by interposition grafts or anastomotic revisions because the short- and long-term results are excellent. Morbidity and mortality are greatly increased when these procedures are done emergently.


Balneotherapy for osteoarthritis. A cochrane review.
Balneotherapy (or spa therapy, mineral baths) for patients with arthritis is one of the oldest forms of therapy. We assessed effectiveness of balneotherapy for patients with osteoarthritis (OA). We performed a broad search strategy to retrieve eligible studies, selecting randomized controlled trials comparing balneotherapy with any intervention or with no intervention. Two authors independently assessed quality and extracted data. Disagreements were solved by consensus. In the event of clinical heterogeneity or lack of data we refrained from statistical pooling. Seven trials (498 patients) were included in this review: one performed an intention-to-treat analysis, 2 provided data for our own analysis, and one reported a "quality of life" outcome. We found silver-level evidence of mineral baths compared to no treatment (effect sizes 0.34-1.82). Adverse events were not measured or found in included trials. We found silver-level evidence concerning the beneficial effects of mineral baths compared to no treatment. Of all other balneological treatments, no clear effects were found. However, the scientific evidence is weak because of the poor methodological quality and the absence of an adequate statistical analysis and data presentation.


CAR NK Cell Therapy for the Treatment of Metastatic Melanoma: Potential & Prospects.
Melanoma is among the most lethal forms of cancer, accounting for 80% of deaths despite comprising just 5% of skin cancer cases. Treatment options remain limited due to the genetic and epigenetic mechanisms associated with melanoma heterogeneity that underlie the rapid development of secondary drug resistance. For this reason, the development of novel treatments remains paramount to the improvement of patient outcomes. Although the advent of chimeric antigen receptor-expressing T (CAR-T) cell immunotherapies has led to many clinical successes for hematological malignancies, these treatments are limited in their utility by their immune-induced side effects and a high risk of systemic toxicities. CAR natural killer (CAR-NK) cell immunotherapies are a particularly promising alternative to CAR-T cell immunotherapies, as they offer a more favorable safety profile and have the capacity for fine-tuned cytotoxic activity. In this review, the discussion of the prospects and potential of CAR-NK cell immunotherapies touches upon the clinical contexts of melanoma, the immunobiology of NK cells, the immunosuppressive barriers preventing endogenous immune cells from eliminating tumors, and the structure and design of chimeric antigen receptors, then finishes with a series of proposed design innovations that could improve the efficacy CAR-NK cell immunotherapies in future studies.


SNP Array as a Tool for Prenatal Diagnosis of Congenital Heart Disease Screened by Echocardiography: Implications for Precision Assessment of Fetal Prognosis.
This study aimed to examine the effectiveness of the SNP array for the prenatal diagnosis of congenital heart disease (CHD) screened by echocardiography. A total of 356 pregnant women with fetal congenital heart malformations revealed by echocardiography at the Center for Prenatal Diagnosis of Fujian Maternal and Children Hospital during the period from November 2016 through July 2019 were recruited. The fetuses were assigned into three cohorts, including 142 with a single cardiac malformation, 106 with multiple cardiac malformations and 108 with cardiac and extracardiac malformations. All fetuses underwent chromosomal karyotyping and SNP array simultaneously, and the effectiveness of the SNP array for the prenatal diagnosis of CHD was evaluated. The overall prevalence of abnormal karyotypes was 9.3% among the 356 fetuses with CHD, and a higher proportion was found in fetuses with cardiac and extracardiac malformations (18.5%) than in those with single (5.6%) or multiple cardiac malformations (4.7%) (P<0.05). Consistent with karyotype analysis, SNP array detected an additional 25 fetuses with pathogenic copy number variations (CNVs), seven with variant of unknown significance (VOUS) and seven with benign CNVs, and a lower proportion of abnormal CNV was found in fetuses with a single cardiac malformation (4.2%) than in those with multiple cardiac malformations (9.4%) or cardiac and extracardiac malformations (14.8%) (P<0.05). Among the 33 fetuses with chromosomal abnormality, postnatal follow-up showed termination of pregnancy in 25 with pathogenic CNVs, one with VOUS, and six with normal karyotypes and SNP array findings but severe multiple malformations by ultrasonography. SNP array increases the overall detection of abnormal CNVs by 9%, which improves the detection of CNVs associated with CHD. SNP array may serve as a tool for prenatal diagnosis of CHD that facilitates the discovery of pathogenic genes associated with CHD and provide valuable insights into the precision assessment of fetal prognosis during the prenatal counseling.


The IgG subclasses of antibodies to castor bean allergen in patients with allergic asthma: detection of a high incidence of antibodies of the IgG4 subclass.
Sera from patients with allergic asthma to castor bean dust were tested for specific antibodies in the red cell linked antigen-antiglobulin reaction (RCLAAR) using antiglobulin sera specific for IgE and the four subclasses of IgG. Approximately one-third of the patients with specific IgG antibodies had an antibody response that was predominantly in the IgG4 subclass. Two patients who were thought not to be sensitive to castor bean allergen, despite long exposure to the dust, did not have detectable IgE antibodies, but had high titres of IgG antibodies that were predominantly IgG4. Specific IgG4 antibodies to castor bean allergen were heat stable, did not appear to passively sensitize monkey skin in the PCA reaction and did not passively sensitize human basophils for the rosette reaction with castor bean-coated red cells.


Staphylococcus aureus Resistance Patterns in Wisconsin: 2018 Surveillance of Wisconsin Organisms for Trends in Antimicrobial Resistance and Epidemiology (SWOTARE) Program Report.
Surveillance of antimicrobial resistance patterns on a local level can reveal paradigms not obvious on a regional or national scale. Data collection from this perspective may potentially impact local prescribing patterns and empiric treatment guidelines. The objective of this study was to establish a baseline Staphylococcus aureus antibiogram for the state of Wisconsin and to elucidate potential geographic and demographic factors associated with antimicrobial resistance. Multi-center laboratory surveillance, with testing at a single site utilizing standardized media and susceptibility testing protocols. 309 isolates of clinically-significant S. aureus were collected from hospital microbiology laboratories across Wisconsin in 2018, with distribution across seven geographic regions. Each isolate was tested using reference broth microdilution methods against a panel of 15 antimicrobial agents. Percentage susceptibility data, as well as median and 90th percentile minimum inhibitory concentration (MIC) values, were computed for each antimicrobial agent as a function of geographic region or demographic category. Increased resistance to penicillin (≥ 86.0% of isolates), erythromycin (≥ 56.8%), cefoxitin (≥ 45.5%), levofloxacin (≥ 25.0%), and clindamycin (≥ 20.5%) was observed in the Southcentral, Lake Winnebago, and Southeast regions of Wisconsin. In addition, isolates phenotypically classified as methicillin-resistant S. aureus (MRSA) were found to have increased rates of resistance to clindamycin, erythromycin, and levofloxacin as compared to S. aureus isolates susceptible to cefoxitin. S. aureus isolates demonstrated nearly 100% in vitro susceptibility to ceftaroline, dalbavancin, and telavancin. Statewide S. aureus isolates exhibited a vancomycin MIC90 of 1 μg/mL. S. aureus isolates from patients aged 20-39 years were more likely to demonstrate cefoxitin resistance when compared to other age groups (P ≤ 0.03), while isolates from patients ≥ 80 years were more likely to exhibit resistance to levofloxacin and clindamycin (P ≤ 0.046). Several antimicrobial agents continue to demonstrate in vitro efficacy against clinical isolates of S. aureus (including MRSA) throughout Wisconsin, including three agents with recently-published susceptibility testing guidelines. However, continued surveillance efforts may be necessary in the Lake Winnebago, Southeast, and Southcentral regions to further assess higher rates of resistance to a number of antimicrobial agents.


Analysis of nutrition of children aged 13-36 months in Poland: a nation-wide study.
The aim of the study was to analyse the diets of children aged 13-36 months in Poland compared to nutritional recommendations. The questionnaire study was conducted between June and September 2010 on a representative, nation-wide sample of children aged 13-36 months. The study concerned 400 children from across Poland. They were selected by means of drawing their PESEL (personal identity) number. The nutritional status of children was assessed using anthropometric data, i.e. their current weight and height. The relative body mass index BMI (kg/m2) and the BMI z-score were calculated for each child and compared with the WHO child growth standards. The diets of children were assessed using an original questionnaire with 3-day diet records. Nutritional value was calculated using Dieta 4.0 computer programme. The study demonstrated that 45.5% of children were in the normal BMI z-score range (from -1.0 to +1.0). Underweight children accounted for 12.5% (BMI z-score between -2.0 and -1.0) and severely underweight for 14.5% (BMI z-score < -2.0) of the studied group. The share of overweight and obese children was 14.5% and 13.0%, respectively. Large individual variation in food intake was observed in diets of the children. The intake of cereal products, meat, poultry and cold meats in daily diets was twice higher than recommended. The children ate significantly less vegetables and fruits and drank less milk and fermented milk beverages than recommended in model food rations. Energy and nutritional value of an average daily food ration differed considerably from the standards for majority of nutrients. The intake of proteins was three times higher than the current norms. The diets of children aged 13-36 months differed from current recommendations but the nutritional status evaluated based on BMI was normal in 45.5% of children from the analysed group. The content of majority of macronutrients, in particular protein, in average daily food rations was incompliant with nutritional norms, which in long term may increase the risk of diet-related diseases. Current nutritional recommendations concerning the diets of children in the post-infancy period need to be verified and disseminated.


Kallikrein-related peptidase 6 orchestrates astrocyte form and function through proteinase activated receptor-dependent mechanisms.
Kallikrein-related peptidase 6 (Klk6) is the most abundant serine proteinase in the adult central nervous system (CNS), yet we know little regarding its physiological roles or mechanisms of action. Levels of Klk6 in the extracellular environment are dynamically regulated in CNS injury and disease positioning this secreted enzyme to affect cell behavior by potential receptor dependent and independent mechanisms. Here we show that recombinant Klk6 evokes increases in intracellular Ca2+ in primary astrocyte monolayer cultures through activation of proteinase activated receptor 1 (PAR1). In addition, Klk6 promoted a condensation of astrocyte cortical actin leading to an elongated stellate shape and multicellular aggregation in a manner that was dependent on the presence of either PAR1 or PAR2. Klk6-evoked changes in astrocyte shape were accompanied by translocation of β-catenin from the plasma membrane to the cytoplasm. These data are exciting because they demonstrate that Klk6 can influence astrocyte plasticity through receptor-dependent mechanisms. Furthermore, this study expands our understanding of the mechanisms by which kallikreins can contribute to neural homeostasis and remodeling and point to both PAR1 and PAR2 as new therapeutic targets to modulate astrocyte form and function.


Predictive coding and stochastic resonance as fundamental principles of auditory phantom perception.
Mechanistic insight is achieved only when experiments are employed to test formal or computational models. Furthermore, in analogy to lesion studies, phantom perception may serve as a vehicle to understand the fundamental processing principles underlying healthy auditory perception. With a special focus on tinnitus-as the prime example of auditory phantom perception-we review recent work at the intersection of artificial intelligence, psychology and neuroscience. In particular, we discuss why everyone with tinnitus suffers from (at least hidden) hearing loss, but not everyone with hearing loss suffers from tinnitus. We argue that intrinsic neural noise is generated and amplified along the auditory pathway as a compensatory mechanism to restore normal hearing based on adaptive stochastic resonance. The neural noise increase can then be misinterpreted as auditory input and perceived as tinnitus. This mechanism can be formalized in the Bayesian brain framework, where the percept (posterior) assimilates a prior prediction (brain's expectations) and likelihood (bottom-up neural signal). A higher mean and lower variance (i.e. enhanced precision) of the likelihood shifts the posterior, evincing a misinterpretation of sensory evidence, which may be further confounded by plastic changes in the brain that underwrite prior predictions. Hence, two fundamental processing principles provide the most explanatory power for the emergence of auditory phantom perceptions: predictive coding as a top-down and adaptive stochastic resonance as a complementary bottom-up mechanism. We conclude that both principles also play a crucial role in healthy auditory perception. Finally, in the context of neuroscience-inspired artificial intelligence, both processing principles may serve to improve contemporary machine learning techniques.


Differentiation of Alkyl- and Plasmenyl-phosphatidylcholine by Endogenous Sphingomyelin RT-XLOGP3 Regression for Coronary Artery Disease Plasma Lipidomics Analysis.
Accurate identification between alkyl- and plasmenyl-phosphatidylcholine (PC(O-) and PC(P-)) isomers is a major analytical challenge in lipidomics studies due to a lack of structure-specific ions in conventional tandem mass spectrometry (MS/MS) methods and the absence of universal retention time (RT) references. Given the importance of PC(O-) and PC(P-), an easy-to-apply method for current research is urgently needed. In this study, we present a quadratic RT-XLOGP3SM regression model that uses endogenous sphingomyelin (SM) species in blood samples as retention time (RT) indicators to predict the RTs of PC(O-) and PC(P-) species by coupling their calculated partition coefficients based on XLOGP3. The prediction results were obtained with a root-mean-square error (RMSE) of 0.12 min (1.3%) for the RRHD (rapid resolution high definition) nonlinear LC condition. A lipidomic analysis with RT-XLOGP3SM regression was used to study lipid regulation in coronary artery disease (CAD) outpatient plasma samples, and we found that the types of exhibited regulation were highly dependent on the lipid subclasses in comparison to the healthy control group. In conclusion, given that the quadratic RT-XLOGP3SM regression model predicts the RTs of PC species based on the relative value of XLOGP3 and the RTs of endogenous SM species, it can be expected that most of the C18-based lipidomics analyses could apply this method to increase the identification ability of the PC(O-) and PC(P-) subclasses and to improve the understanding of their physiological functions.


Auditory Environments and Hearing Aid Feature Activation Among Younger and Older Listeners in an Urban and Rural Area.
The purpose of this study was to investigate differences in auditory environments and hearing aid feature activation between younger listeners with normal hearing and older listeners with hearing loss in an urban and rural location. We hypothesized that (1) urban dwellers and younger listeners would encounter more diverse and demanding auditory environments than rural dwellers and older listeners, respectively; (2) the advanced hearing aid features (noise reduction and directional microphone) of urban dwellers and younger listeners would be activated more frequently than rural dwellers and older listeners, respectively. The design of this study was cross-sectional with repeated measures. A total of 12 older adults with hearing loss (OHL-U) and 11 younger adults with normal hearing (YNH-U) were recruited from an urban area (Berkeley, California) and 13 older adults with hearing loss (OHL-R) and 10 YNH-U were recruited from a rural area (Iowa City, Iowa). Participants wore hearing aids that recorded data about their listening environments and completed ecological momentary assessments for 1 week. The YNH-U group experienced higher sound pressure levels and hearing aid features were activated more frequently than in the OHL groups. The OHL-R group experienced significantly less diverse sound pressure levels than the YNH-U group. The YNH-R group had sound levels between the YNH-U group and the OHL groups but without significant differences from any other group. The YNH groups showed a greater likelihood of hearing aid feature activation than the OHL-R group. Demographics affect auditory environments and the activation of hearing aid features. Younger urban dwellers have the most diverse or demanding auditory environments and hearing aid feature activation, and older, rural dwellers with hearing loss have the least diverse or demanding auditory environments and hearing aid feature activation. Future studies of real-world auditory environments and audiology intervention effectiveness should consider location in recruitment and interpretation of results.


Cécile Morette and the Les Houches summer school for theoretical physics; or, how Girl Scouts, the 1944 Caen bombing and a marriage proposal helped rebuild French physics (1951-1972).
The aftermath of the Second World War represented a major turning point in the history of French and European physical sciences. The physicist's profession was profoundly restructured, and in this transition the role of internationalism changed tremendously. Transnational circulation became a major part of research training. This article examines the conditions of possibility for this transformation, by focusing on the case of the summer school for theoretical physics created in 1951 by the young Cécile Morette (1922-2017), just in front of Mont Blanc, at Les Houches. First I show that ultimately it was only thanks to extremely specific and intertwined social positions and dispositions, in terms of class and gender (derived from her socialization as an expected dame de la bourgeoisie), and through the interactions between such social attributes and a dramatic life event, that Morette managed to gather a network diverse, powerful and transnational enough to create this institution. Then, following the first years of this school, I show how it became an international model, paving the way to new articulations between the local, the national and the global scales, even beyond the Cold War oppositions.


Impact of sleep and movement on gastro-oesophageal reflux in healthy, newborn infants.
Seventy four normal, healthy newborn babies were studied to examine the relationship between gastro-oesophageal reflux, sleep state, and movement. Multichannel pen recordings were made to determine sleep state, movement, breathing, and reflux. The mean number of reflux episodes per hour was highest in wakefulness, followed by active and indeterminate sleep. In quiet sleep reflux rarely occurred. The mean duration of reflux episodes per hour was longest in active sleep followed by wakefulness, indeterminate and quiet sleep. There was a strong positive correlation between duration of reflux and movement time for wakefulness, active and indeterminate sleep. Movement preceded 88% of all reflux episodes. Physiological reflux occurs in most newborn infants but is clinically inapparent. The results suggest that state and movement are related to the incidence and duration of reflux. Sleep state is therefore an important variable in determining normal values for reflux in infancy since developmentally the amount of sleep time lessens but quiet sleep proportionally increases.


Life on the Margins.
This editorial reviews the events of Creative Nursing's 2023 publication year, importantly our transition to Sage Publishing, and the expanded opportunities this new relationship provides in 2024 and beyond. The 11 articles in this theme issue about marginalization are summarized and connected.


Pneumococcal type 22f polysaccharide absorption improves the specificity of a pneumococcal-polysaccharide enzyme-linked immunosorbent assay.
The specificity of the immune response to the 23-valent pneumococcal-polysaccharide (PS) vaccine in healthy adults and to a pneumococcal conjugate vaccine in infants was examined by measuring immunoglobulin G (IgG) antibody titers by enzyme-linked immunosorbent assay (ELISA) and the opsonophagocytosis assay. ELISA measures total antipneumococcal IgG titers including the titers of functional and nonfunctional antibodies, while the opsonophagocytosis assay measures only functional-antibody titers. Twenty-four pairs of pre- and post-pneumococcal vaccination sera from adults were evaluated (ELISA) for levels of IgG antibodies against serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. Twelve of the pairs were also examined (opsonophagocytosis assay) for their functional activities. The correlation coefficients between assay results for most types ranged from 0.75 to 0.90, but the correlation coefficient was only about 0.6 for serotypes 4 and 19F. The specificities of these antibodies were further examined by the use of competitive ELISA inhibition. A number of heterologous polysaccharides (types 11A, 12F, 15B, 22F, and 33A) were used as inhibitors. Most of the sera tested showed cross-reacting antibodies, in addition to those removed by pneumococcal C PS absorption. Our data suggest the presence of a common epitope that is found on most pneumococcal PS but that is not absorbed by purified C PS. Use of a heterologous pneumococcal PS (22F) to adsorb the antibodies to the common epitope increased the correlation between the IgG ELISA results and the opsonophagocytosis assay results. The correlation coefficient improve from 0.66 to 0.92 for type 4 and from 0.63 to 0.80 for type 19F. These common-epitope antibodies were largely absent in infants at 7 months of age, suggesting the carbohydrate nature of the epitope.


Distinct Gut Microbiota Induced by Different Fat-to-Sugar-Ratio High-Energy Diets Share Similar Pro-obesity Genetic and Metabolite Profiles in Prediabetic Mice.
Gut microbiota play important roles in host metabolism, especially in diabetes. However, why different diets lead to similar diabetic states despite being associated with different microbiota is not clear. Mice were fed two high-energy diets (HED) with the same energy density but different fat-to-sugar ratios to determine the associations between the microbiota and early-stage metabolic syndrome. The two diets resulted in different microbiota but similar diabetic states. Interestingly, the microbial gene profiles were not significantly different, and many common metabolites were identified, including l-aspartic acid, cholestan-3-ol (5β, 3α), and campesterol, which have been associated with lipogenesis and inflammation. Our study suggests that different metabolic-syndrome-inducing diets may result in different microbiota but similar microbiomes and metabolomes. This suggests that the metagenome and metabolome are crucial for the prognosis and pathogenesis of obesity and metabolic syndrome.IMPORTANCE Various types of diet can lead to type 2 diabetes. The gut microbiota in type 2 diabetic patients are also different. So, two questions arise: whether there are any commonalities between gut microbiota induced by different pro-obese diets and whether these commonalities lead to disease. Here we found that high-energy diets with two different fat-to-sugar ratios can both cause obesity and prediabetes but enrich different gut microbiota. Still, these different gut microbiota have similar genetic and metabolite compositions. The microbial metabolites in common between the diets modulate lipid accumulation and macrophage inflammation in vivo and in vitro This work suggests that studies that only use 16S rRNA amplicon sequencing to determine how the microbes respond to diet and associate with diabetic state are missing vital information.


Functional Characterization of DNA N-Glycosylase Ogg1 and Ntg1 in DNA Damage Stress of Cryptococcus neoformans.
Reactive oxygen species induce DNA strand breaks and DNA oxidation. DNA oxidation leads to DNA mismatches, resulting in mutations in the genome if not properly repaired. Homologous recombination (HR) and non-homologous end-joining (NHEJ) are required for DNA strand breaks, whereas the base excision repair system mainly repairs oxidized DNAs, such as 8-oxoguanine and thymine glycol, by cleaving the glycosidic bond, inserting correct nucleotides, and sealing the gap. Our previous studies revealed that the Rad53-Bdr1 pathway mainly controls DNA strand breaks through the regulation of HR- and NHEJ-related genes. However, the functional roles of genes involved in the base excision repair system remain elusive in Cryptococcus neoformans. In the present study, we identified OGG1 and NTG1 genes in the base excision repair system of C. neoformans, which are involved in DNA oxidation repair. The expression of OGG1 was induced in a Hog1-dependent manner under oxidative stress. On the other hand, the expression of NTG1 was strongly induced by DNA damage stress in a Rad53-independent manner. We demonstrated that the deletion of NTG1, but not OGG1, resulted in elevated susceptibility to DNA damage agents and oxidative stress inducers. Notably, the ntg1Δ mutant showed growth defects upon antifungal drug treatment. Although deletion of OGG1 or NTG1 did not increase mutation rates, the mutation profile of each ogg1Δ and ntg1Δ mutant was different from that of the wild-type strain. Taken together, we found that DNA N-glycosylase Ntg1 is required for oxidative DNA damage stress and antifungal drug resistance in C. neoformans.


Formulation techniques for nanofluids.
Fluids with suspended nanoparticles, commonly known as nanofluids, may be formulated to improve the thermal performance of industrial heat transfer systems and applications. Nanofluids may show enhanced thermal and electrical properties such as thermal conductivity, viscosity, heat transfer coefficient, dielectric strength, etc. However, stability problems may arise as nanoparticles usually have the tendency to agglomerate and sediment producing deterioration in the increment of these properties. In this review, we discuss patents that report advances in the formulation of nanofluids including: production methods, selection of components (nanoparticles, base fluid and surfactants), their chemical compositions and morphologies, and characterization techniques. Finally, current and future directions in the development of nanofluid formulation are discussed.


Studies of fowl plague virus temperature-sensitive mutants with defects in transcription.
Two fowl plague virus temperature-sensitive (ts) mutants belonging to different complementation groups were studied. Both were defective in the syntheses of unpolyadenylated complementary RNA [A(-)cRNA] and virus RNA (vRNA) at non-permissive temperature whereas primary transcription was unaffected. In addition, ts 29, in which the ts mutation is in gene 1 coding for polypeptide P3, has a defect in 'secondary' synthesis of mRNA at non-permissive temperature whereas inhibition of mRNA synthesis by ts 131, in which the ts mutation is in gene 2 coding for polypeptide P1, appeared to result from a defect in vRNA synthesis. These results indicate, therefore, that different enzymes are responsible for the syntheses of virus mRNAs and A(-)cRNAs, which is consistent with the apparent differences in initiation and termination of transcription in the two reactions. The patterns of synthesis of the various types of virus RNA during infection are discussed.


Rap1 and Canoe/afadin are essential for establishment of apical-basal polarity in the Drosophila embryo.
The establishment and maintenance of apical-basal cell polarity is critical for assembling epithelia and maintaining organ architecture. Drosophila embryos provide a superb model. In the current view, apically positioned Bazooka/Par3 is the initial polarity cue as cells form during cellularization. Bazooka then helps to position both adherens junctions and atypical protein kinase C (aPKC). Although a polarized cytoskeleton is critical for Bazooka positioning, proteins mediating this remained unknown. We found that the small GTPase Rap1 and the actin-junctional linker Canoe/afadin are essential for polarity establishment, as both adherens junctions and Bazooka are mispositioned in their absence. Rap1 and Canoe do not simply organize the cytoskeleton, as actin and microtubules become properly polarized in their absence. Canoe can recruit Bazooka when ectopically expressed, but they do not obligatorily colocalize. Rap1 and Canoe play continuing roles in Bazooka localization during gastrulation, but other polarity cues partially restore apical Bazooka in the absence of Rap1 or Canoe. We next tested the current linear model for polarity establishment. Both Bazooka and aPKC regulate Canoe localization despite being "downstream" of Canoe. Further, Rap1, Bazooka, and aPKC, but not Canoe, regulate columnar cell shape. These data reshape our view, suggesting that polarity establishment is regulated by a protein network rather than a linear pathway.


Concurrent Lateral Condyle Mass Fracture With Olecranon Fracture: A Case Report and Brief Review of Literature.
There is very limited literature describing the association of lateral condyle mass (LCM) fracture of the distal humerus associated concurrently with olecranon fracture. Herein, a case is reported of a displaced LCM fracture with displaced olecranon fracture, due to complex trauma while getting out of a vehicle, which was managed by open reduction and internal fixation. A 4.5- year- old boy suffered severe pain and swelling around his right elbow due to trauma which he suffered while trying to get out of a vehicle which was in motion. Plain radiographs of the anteroposterior, lateral, and oblique views showed a displaced lateral mass fracture associated with a displaced olecranon fracture. Open reduction and internal fixation was carried out and near normal function was achieved. In view of the paucity of literature and rare incidence of this injury, this case report highlights the need to be aware of other injuries which can occur in association with LCM fractures in children.


Management of complications of surgery for anterior shoulder instability.
Both operative and nonoperative management of the unstable shoulder requires a thorough understanding of the natural history of instability, as well as the normal anatomy and biomechanics of the shoulder joint. Failure of management may occur at any time during the course of treatment, and may be a result of either physician or patient error, or a combination of both. The correct diagnosis allows for selection of the most appropriate treatment, and the success of surgical treatment depends on proper recognition of the pattern of instability and technically adequate anatomic capsulolabral reconstruction. Complications that can occur include making the shoulder too loose or too tight, injury to the neurovascular elements about the shoulder, and articular injury from hardware usage about the shoulder.


Species composition and seasonal dynamics of mosquitoes in the Belek region of Turkey.
The species composition and seasonal population dynamics of mosquitoes trapped in the Belek Region of Turkey are described. Eight traps (four New Jersey light traps and four CO2 baited traps) were activated weekly at four different sampling sites (wooded area, open field, village, and road edge). Between May and December, 1997, 4,542 specimens representing seven species (Culex pipiens, Culex tritaeniorhynchus, Aedes caspius, Aedes cretinus, Aedes dorsalis, Aedes vexans, and Culiseta annulata) were collected. The most abundant species was Cx. pipiens (26.7% of total catch) followed by Cx. tritaeniorhynchus (23.8%), Ae. caspius (23.4%), Ae. cretinus (10.7%), Ae. dorsalis (8.7%), Cs. annulata (6.2%), and Ae. vexans (0.1%). This is the first record of Ae. cretinus in the area since 1984. The species was captured throughout the study period, although it was most abundant in late summer. Culex tritaeniorhynchus reached its highest density in August, while Cx. pipiens was found in high numbers throughout most of the study period.


[The Aĭna/1448 serotype of the tick-borne encephalitis virus].
The antigenic structure of 48 tick-borne encephalitis virus (TBE) strains isolated in the Irkutsk region and the Buryat ASSR in 1960-1981 was studied. Antigenic analysis was performed by the agar gel diffusion-precipitation test using adsorption of the immune sera. A new group of 31 TBE virus strains was found to belong to the Aina/1448 antigenic type. Close ecological relationship between this serotype and Muridae was found. Ix. persulcatus ticks are vectors of 2 TBE virus serotypes, Aina/1448 and eastern serotype. Data on combined circulation of these 2 serotypes of TBE virus in the Irkutsk region and the Buryat ASSR were obtained, the Aina/1448 serotype definitely dominating in 3 areas of the Irkutsk region. The areas of circulation of the Aina/1448 serotype strains are associated with forest and forest-steppe landscapes disturbed by human economic activity.


Patellar tendon versus quadrupled bone-semitendinosus anterior cruciate ligament reconstruction: a prospective clinical investigation in athletes.
Patellar tendon and hamstrings are both used in anterior cruciate ligament (ACL) reconstruction, and comparisons have been reported with different results. The purpose of this clinical study was to compare the results of ACL reconstruction in athletes with 2 different graft types, both using bone-to-bone healing: bone-patellar tendon-bone graft and a quadrupled bone-semitendinosus graft. Outcomes study. From 1994 to 1997, 2 groups of 40 athletes who underwent ACL replacement with patellar tendon and quadrupled bone-semitendinosus grafts were prospectively evaluated. Preinjury activity level, age, and gender were comparable in both groups. All patients were operated on by the same surgeon within 5 months from injury and underwent group-specific rehabilitation programs. An independent examiner performed the final evaluations at 36 months. Review included clinical examination, radiographs, computed analysis, isokinetic and functional strength tests, and subjective and objective evaluation with standard knee scores. Additional procedures were recorded. Statistical analysis was performed with both parametric and nonparametric tests. Average surgical time was longer with the semitendinosus graft, and postoperative pain was higher in the patellar tendon group. Standard knee evaluation scores and subjective assessment revealed no significant differences. Isokinetic testing of flexion-extension and internal-external rotation showed lower quadriceps strength and a mild deficit of external rotation in the patellar tendon group and slightly lower flexor strength in the semitendinosus group at 12 months. Computerized laxity analysis showed no difference between the 2 groups with 90% of patients having less than 3 mm side-to-side difference, with a gender difference in the semitendinosus group. Kneeling pain was higher in patellar tendon group. The bone-patellar tendon-bone and quadrupled bone-semitendinosus autograft provide excellent grafts for ACL reconstruction. Both techniques are comparable regarding final stability, but in patients with extensor mechanism problems or those who engage in sports with a high incidence of patellar tendonitis, the semitendinosus graft should be considered.


Cholesterol sulfate alters substrate preference of matrix metalloproteinase-7 and promotes degradations of pericellular laminin-332 and fibronectin.
Localization of secreted matrix metalloproteinases (MMPs) on the cell surface is required not only for processing of cell surface proteins, but also for controlled degradation of the extracellular matrix (ECM). Our previous study demonstrated that binding of MMP-7 (matrilysin) to cell surface cholesterol sulfate (CS) is essential for the cell membrane-associated proteolytic action of this MMP. In this study, we investigated the role of CS in the MMP-7-catalyzed degradation of protein components of ECM. We found that the degradation of laminin-332 (laminin-5) catalyzed by MMP-7 was accelerated dramatically in the presence of CS, whereas the sulfated lipid inhibited the degradation of casein catalyzed by the protease. The MMP-7-catalyzed degradation of fibronectin was partially inhibited in the presence of low concentrations of CS, whereas it was accelerated significantly at high concentrations of the lipid. Therefore, it is likely that CS alters the substrate preference of MMP-7. We also found that the proteins of which MMP-7-catalyzed degradation were accelerated by CS also had affinities for CS, suggesting that CS facilitates the proteolyses by cross-linking MMP-7 to its substrates. Moreover, MMP-7 tethered to cancer cell surface via CS degraded fibronectin and laminin-332 coated on a culture plate. The degradations of the adhesive proteins led to significant detachment of the cells from the plate. Taken together, our findings provide a novel mechanism in which cell surface CS promotes the proteolytic activities of MMP-7 toward selective substrates in the pericellular ECM, thereby contributing to cancer cell migration and metastasis.


Importance of local immunity in enteric infection.
Evidence suggests that protection against intestinal infections is mediated by an immune system that is unique in many ways. The predominant intestinal immunoglobulin differs in structure, function, and site of origin from those immunoglobulins found in the blood-stream. Cell-mediated intestinal immune responses also may arise separately from those of the rest of the body. Further studies are necessary to characterize the local immune response to many human bacterial, viral, and protozoal pathogens, and to clarify the mechanism of "homing" of immunocompetent cells to the large and small intestine, mammary glands, and other external mucosal surfaces.


The satisfaction of patients hospitalized in the surgical departments of a general hospital. Case study of Sahloul hospital in Sousse (Tunisia).
Measure the overall and specific satisfaction rates of patients hospitalized in surgical services in Sahloul University Hospital in Sousse during the year 2018. The study population was recruited by a quota sample of hospitalized patients in the surgical departments of Sahloul University Hospital in Sousse. Data collection was done via a patient satisfaction questionnaire, administered to outgoing patients. The questionnaire was composed of 33 items exploring technical, administrative, logistical and relational dimensions. Overall patient satisfaction, called "reactivity", was defined by a concomitant positive response to the three questions exploring satisfaction, recommendation and loyalty. A total of 735 patients hospitalized in six surgical departments were included (general surgery, orthopedics, maxillofacial surgery, urology, neurosurgery and cardiovascular surgery). The rates of "satisfaction", "recommendation" and "loyalty" of the patients were 71%, 70% and 69% respectively, equivalent to an "overall positive reactivity" of 62%, 95% CI [58,5%-65.5%], particularly low in the orthopedic department (43%). The logistics dimension was the least appreciated by patients, including room's condition, with almost 23% overall and 17% in the orthopedic department. The responsiveness of patients hospitalized in the surgical services of Sahloul University Hospital was low, particularly for items related to the hotel services in the hospital. Furthermore, plans to improve the quality of care and support the performance of public hospitals should pay close attention to the logistical dimension of patients' hospital stays.