Acute eosinophilic pneumonia triggered by secondhand cigarette smoke exposure in an elderly man.
The spectrum of eosinophilic lung diseases comprises a diverse group of pulmonary disorders associated with tissue or peripheral eosinophilia. [Acute eosinophilic pneumonia (AEP)] is an uncommon eosinophilic lung disease that can be idiopathic, but identifiable causes include medications, inhalational exposures and infections. Most cases in the literature are associated with first-time cigarette smoking or resuming smoking. Herein, we present a case of AEP in an elderly man triggered by exposure to secondhand tobacco smoke, in whom a transbronchial biopsy was diagnostic. The patient recovered fully with glucocorticoid therapy without recurrence after avoiding further secondhand smoke.


Fully automated deconvolution method for on-line analysis of time-resolved fluorescence spectroscopy data based on an iterative Laguerre expansion technique.
Time-resolved fluorescence spectroscopy (TRFS) is a powerful analytical tool for quantifying the biochemical composition of organic and inorganic materials. The potential of TRFS for tissue diagnosis has been recently demonstrated. To facilitate the translation of TRFS to the clinical arena, algorithms for online TRFS data analysis are essential. A fast model-free TRFS deconvolution algorithm based on the Laguerre expansion method has previously been introduced. One limitation of this method, however, is the need to heuristically select two parameters that are crucial for the accurate estimation of the fluorescence decay: the Laguerre parameter alpha and the expansion order. Here, a new implementation of the Laguerre deconvolution method is introduced, in which a nonlinear least-square optimization of the Laguerre parameter alpha is performed, and the optimal expansion order is selected based on a minimum description length criterion (MDL). In addition, estimation of the zero-time delay between the recorded instrument response and fluorescence decay is also performed based on normalized mean square error criterion (NMSE). The method is validated on experimental data from fluorescence lifetime standards, endogenous tissue fluorophores, and human tissue. The proposed automated Laguerre deconvolution method will facilitate online applications of TRFS, such as real-time clinical tissue diagnosis.


The Obesity Paradox in Emergency General Surgery Patients.
Operative management of emergency general surgery (EGS) diagnoses involves a range of procedures which can carry high morbidity and mortality. Little is known about the impact of obesity on patient outcomes. The aim of this study was to examine the association between body mass index (BMI) >30 kg/m2 and mortality for EGS patients. We hypothesized that obese patients would have increased mortality rates. A regional integrated health system EGS registry derived from The American Association for the Surgery of Trauma EGS ICD-9 codes was analyzed from January 2013 to October 2015. Patients were stratified into BMI categories based on WHO classifications. The primary outcome was 30-day mortality. Longer-term mortality with linkage to the Social Security Death Index was also examined. Univariate and multivariable analyses were performed. A total of 60 604 encounters were identified and 7183 (11.9%) underwent operative intervention. Patient characteristics include 53% women, mean age 58.2 ± 18.7 years, 64.2% >BMI 30 kg/m2, 30.2% with chronic obstructive pulmonary disease, 19% with congestive heart failure, and 31.1% with diabetes. The most common procedure was laparoscopic cholecystectomy (36.4%). Overall, 90-day mortality was 10.9%. In multivariable analysis, all classes of obesity were protective against mortality compared to normal BMI. Underweight patients had increased risk of inpatient (OR = 1.9, CI = 1.7-2.3), 30-day (OR = 1.9, CI = 1.7-2.1), 90-day (OR = 1.8, CI 1.6-2.0), 1-year (OR = 1.8, CI = 1.7-2.0), and 3-year mortality (OR = 1.7, CI = 1.6-1.9). When stratified by BMI, underweight EGS patients have the highest odds of death. Paradoxically, obesity appears protective against death, even when controlling for potentially confounding factors. Increased rates of nonoperative management in the obese population may impact these findings.


Mortality of Spanish Former Elite Soccer Players and Coaches.
We analyzed whether male Spanish elite soccer players live longer than the general population. Secondly, we compared their mortality with a cohort of soccer players who continued working as soccer elite coaches after retirement. Using age and calendar-date adjusted life tables, we analyzed the mortality hazard ratio of 1333 Spanish male players born before 1950, and who played in elite leagues from 1939, compared with the Spanish population. Using Cox proportional hazards model we compared their mortality with a cohort of 413 players who continued as coaches. Players showed significantly lower mortality than the general population, but this advantage decreased with advanced age, disappearing after 80 years. Coaches showed a similar pattern. Comparing players versus coaches, date of birth and years as professional were associated with survival, but debut age and player position were not. Unadjusted median survival time was 79.81 years (IQR 72.37-85.19) for players and 81.8 years (IQR 74.55-86.73) for coaches. Kaplan-Meier estimator adjusted for covariables showed no difference between cohorts (p=0.254). In conclusion, former Spanish male players showed lower mortality than the general population, but this effect disappeared after 80 years of age. Continuing their career as coaches after retirement from playing did not confer major benefits.


IVGTT glucose minimal model covariate selection by nonlinear mixed-effects approach.
Population approaches, traditionally employed in pharmacokinetic-pharmacodynamic studies, have shown value also in the context of glucose-insulin metabolism models by providing more accurate individual parameters estimates and a compelling statistical framework for the analysis of between-subject variability (BSV). In this work, the advantages of population techniques are further explored by proposing integration of covariates in the intravenous glucose tolerance test (IVGTT) glucose minimal model analysis. A previously published dataset of 204 healthy subjects, who underwent insulin-modified IVGTTs, was analyzed in NONMEM, and relevant demographic information about each subject was employed to explain part of the BSV observed in parameter values. Demographic data included height, weight, sex, and age, but also basal glycemia and insulinemia, and information about amount and distribution of body fat. On the basis of nonlinear mixed-effects modeling, age, visceral abdominal fat, and basal insulinemia were significant predictors for SI (insulin sensitivity), whereas only age and basal insulinemia were significant for P2 (insulin action). The volume of distribution correlated with sex, age, percentage of total body fat, and basal glycemia, whereas no significant covariate was detected to explain variability in SG (glucose effectiveness). The introduction of covariates resulted in a significant shrinking of the unexplained BSV, especially for SI and P2 and considerably improved the model fit. These results offer a starting point for speculation about the physiological meaning of the relationships detected and pave the way for the design of less invasive and less expensive protocols for epidemiological studies of glucose-insulin metabolism.


Eicosanoid production by human monocytes: does COX-2 contribute to a self-limiting inflammatory response?
The eicosanoids, prostaglandin E2 (PGE2) and thromboxane A2 (TXA2), are involved in inflammatory events. TXA2 has potentially pro-inflammatory actions and PGE2 has actions which can be considered both pro- and antiinflammatory. Therefore, it is potentially significant that production of TXA2 and PGE2 by stimulated monocytes have very different time courses. TXA2 synthesis is immediate and dependent on cyclooxygenase Type 1 (COX-1) activity whereas PGE2 synthesis is delayed and dependent on COX-2 activity. These apparent COX-isotype dependencies of TXA2 and PGE2 synthesis can be explained by differences in the affinities of TXA synthase and PGE synthase for the common substrate, PGH2. The findings have implications for the use of NSAIDs and selective COX-2 inhibitors whose actions can increase the monocyte TXA2/PGE2 ratio.


Nucleoside conjugates. 15. Synthesis and biological activity of anti-HIV nucleoside conjugates of ether and thioether phospholipids.
A series of the anti-HIV nucleoside conjugates of either (1-O-alkyl) and thioether (1-S-alkyl) lipids linked by a pyrophosphate diester bond has been synthesized as micelle-forming prodrugs of the nucleosides to improve their therapeutic efficiency. These include AZT 5'-diphosphate-rac-1-S-octadecyl-2-O-palmitoyl-1-thioglycerol (1), 3'-azido-2',3'-dideoxyuridine 5'-diphosphate-rac-1-S-octadecyl-2-O-palmitoyl-1-thioglycerol (2) 2',3'-dideoxycytidine 5'-diphosphate-rac-1-S-octadecyl-2-O-palmitoyl-1-thioglycerol (3), and AZT 5'-diphosphate-rac-1-O-tetradecyl-2-O-palmitoylglycerol (4). The conjugates form micelles by sonication (mean diameters ranging 6.8-55.5 nm). Conjugate 1 protected 80% of HIV-infected CEM cells as low as 0.58 microM and lost the protection at 180 microM due to prevailing cytotoxicity, while the conjugate started to show the cytotoxicity at 100 microM. Pharmacokinetics studies showed a significant increase of half-life values (t1/2) of AZT and AZddU2 (respective t1/2 = 5.69 and 6.5 h) after administration of conjugates 1 and 2, while those after administration of AZT and AZddU were 0.28 and 0.89 h, respectively. The fractions of the prodrugs 1 and 2 converted to the parent compounds AZT and AZddU were 36% and 55%, respectively. The results indicate that AZT and AZddU thioether lipid conjugates 1 and 2 warrant further investigation.


Effect of adhesive luting on the fracture resistance of zirconia compared to that of composite resin and lithium disilicate glass ceramic.
The purpose of this study was to evaluate the effect of adhesive luting on the fracture resistance of zirconia compared to that of a composite resin and a lithium disilicate glass ceramic. The specimens (dimension: 2 mm × 2 mm × 25 mm) of the composite resin, lithium disilicate glass ceramic, and yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) were prepared. These were then divided into nine groups: three non-luting groups, three non-adhesive luting groups, and three adhesive luting groups, for each restorative material. In the non-luting groups, specimens were placed on the bovine tooth without any luting agents. In the non-adhesive luting groups, only zinc phosphate cement was used for luting the specimen to the bovine tooth. In the adhesive luting groups, specimens were pretreated, and the adhesive luting procedure was performed using a self-adhesive resin cement. For all the groups, a flexural test was performed using universal testing machine, in which the fracture resistance was measured by recording the force at which the specimen was fractured. The fracture resistance after adhesive luting increased by approximately 29% in the case of the composite resin, 26% in the case of the lithium disilicate glass ceramic, and only 2% in the case of Y-TZP as compared to non-adhesive luting. The fracture resistance of Y-TZP did not increased significantly after adhesive luting as compared to that of the composite resin and the lithium disilicate glass ceramic.


Fatal streptokinase-induced intracerebral haemorrhage in cerebral amyloid angiopathy.
A fatal intracerebral haemorrhage (ICH) associated with streptokinase (SK) treatment of an acute myocardial infarction is described. Autopsy examination showed a lobar ICH and severe cerebral amyloid angiopathy (CAA). The close temporal relationship between SK administration and intracranial haemorrhage, the absence of pretreatment risk factors for ICH, and the presence of CAA suggests that these are related phenomena. Accordingly: 1. There may be a synergistic relationship between CAA and intracranial haemorrhage induced by fibrinolytic agents; 2. Thrombolytic agents may induce more frequent than expected intracranial haemorrhage in conditions associated with a high incidence of CAA, notably old age and Alzheimer's disease; 3. A regional defect in haemostasis other than vessel fragility may contribute to the intracranial haemorrhagic predisposition of CAA; 4. Autopsy examination of cases of ICH is an essential part of the audit of clinical trials of fibrinolytic agents.


Back pain in industry. A prospective survey.
Eight hundred and two subjects employed in N.W. England have been interviewed and examined after episodes of back or sciatic pain, using a standardized procedure. Data on recurrence of symptoms leading to further treatment or absence from work in the following two 12-month periods were obtained by postal questionary. Residual pain in the leg and a number of positive clinical signs of return to work, longer sickness--absence for the current attack, and two or more previous attacks were all associated with recurrence or persistence of symptoms. The prognosis also varied according to the cause of back pain, falls being associated not only with longer periods of absence in the current attack but with a higher rate of recurrence. The results have underlined the significance of a thorough examination on return to work after back pain for the industrial medical officer, as well as the epidemiological importance of this phase in the natural history of back and sciatic pain.


Effects of low-molecular-weight organic acids on the acute lethality, accumulation, and enzyme activity of cadmium in Eisenia fetida in a simulated soil solution.
In the present study, the effects of low-molecular-weight organic acids (LMWOAs) on the toxicity of cadmium (Cd) to Eisenia fetida were investigated in a simulated soil solution. The LMWOAs protected E. fetida from Cd toxicity, as indicated by the increased median lethal concentration (LC50) values and the increased activity of superoxide dismutase. In addition, Cd concentrations in E. fetida decreased dramatically in the presence of LMWOAs. These results were likely because of the complexation between Cd and LMWOAs, which decreased the bioavailability and consequential toxicity of Cd to E. fetida. Notably, LMWOAs reduced Cd toxicity in decreasing order (ethylenediamine tetraacetic acid [EDTA] > citric acid > oxalic acid > malic acid > acetic acid), which was consistent with the decreasing complexation constants between LMWOAs and Cd. These results advance our understanding of the interactions between Cd and LMWOAs in soil. Environ Toxicol Chem 2017;36:1005-1011. © 2016 SETAC.


HIPAA for cancer educators: are you correctly using PHI?
Privacy and confidentiality policies and practices, including Health Insurance Portability and Accountability Act (HIPAA) policies, may vary from institution to institution because they are developed to be institution-specific. HIPAA privacy and security regulations represent the minimum standards, and the expectation is that institutions will develop policies and practices that are reasonable and appropriate for their institution. These privacy and information security safeguards impact the use of sensitive and protected data often used by cancer educators. Therefore, it is important for cancer educators to be familiar with the policies, rules, and guidelines their institution has developed to comply with HIPAA. However, despite institutional differences, certain principles related to the confidentiality, protection, and uses of a patient's health information remain consistent. HIPAA provides two sets of regulations that directly impact the work of many cancer educators: privacy and information security. The HIPAA Privacy Rule includes some security requirements, and HIPAA Security Regulations were designed to ensure privacy of the patient's protected health information (PHI). This paper focuses primarily on the privacy factors.


[Expression of vascular endothelial growth factor and its receptors in endometrial carcinoma].
To study the expression of vascular endothelial growth factor (VEGF) and its receptors, the fms-like tyrosine-1 (flt-1) and kinase insert domain-containing receptor (KDR) in endometrial carcinoma and investigate the functions of VEGF and its receptors for endometrial carcinoma angiogenesis and its relation to the grade of tumor. Immunocytochemistry and in situ hybridization technique were used to measure the level of VEGF, flt-1, KDR protein and mRNA in endometrial carcinoma tissue from 23 patients and endometrial samples from 6 normal menopausal women. A few endometrial carcinoma samples were homogenized for Western blot analysis. The blood vessel density was estimated by counting blood vessels stained with endothelial marker VIII factor. The VEGF and its receptors were widely expressed in the cytoplasm of endothelial cells and tumor cells of endometrial carcinoma. The level of VEGF protein in endothelial cells and endometrial cancer cells of grade II and III tumor tissues was higher than that in grade I and normal menopausal endometrium (P < 0.05). VEGF mRNA did not show higher expression with the increase of tumor grade but its expression in normal tissue was lower than that in cancer (P < 0.05). The expression of flt-1 protein and mRNA in endothelial cells got higher in III than in grade II and I (P < 0.05), but invariable in cancer cells (P > 0.05), flt-1 expression in cancer was higher than that in normal menopausal endometrium either in endothelial cells or in cancer cells (P < 0.05). The expression of KDR protein in endothelial and cancer cell was high but did not alter with the increase of tumor grade (P > 0.05), the level of its mRNA was higher in cancer than that in normal tissue (P < 0.05). The microvascular density in grade III (48 +/- 12) was higher than that in grade II (26 +/- 16), grade I (27 +/- 14) and normal menopausal tissue (26 +/- 11, P < 0.05). The expression pattern of VEGF, flt-1 and KDR protein and mRNA increased with the increase of tumor grade in endometrial carcinoma indicates that VEGF and its receptors contribute to the neovascularization of tumors and is one of the factors that relate to rapid tumor growth of endometrial carcinoma.


Postoperative complications and hospital costs following small bowel resection surgery.
Postoperative complications after major gastrointestinal surgery are a major contributor to hospital costs. Thus, reducing postoperative complications is a key target for cost-containment strategies. We aimed to evaluate the relationship between postoperative complications and hospital costs following small bowel resection. Postoperative complications were recorded for 284 adult patients undergoing major small bowel resection surgery between January 2013 and June 2018. Complications were defined and graded according to the Clavien-Dindo classification system. In-hospital cost of index admission was calculated using an activity-based costing methodology; it was reported in US dollars at 2019 rates. Regression modeling was used to investigate the relationships among a priori selected perioperative variables, complications, and costs. The overall complication prevalence was 81.6% (95% CI: 85.7-77.5). Most complications (69%) were minor, but 22.9% of patients developed a severe complication (Clavien-Dindo grades III or IV). The unadjusted median total hospital cost for patients with any complication was 70% higher than patients without complications (median [IQR] USD 19,659.64 [13,545.81-35,407.14] vs. 11,551.88 [8,849.46-15,329.87], P < 0.001). The development of 1, 2, 3, and ≥ 4 complications increased hospital costs by 11%, 41%, 50%, and 195%, respectively. Similarly, more severe complications incurred higher hospital costs (P < 0.001). After adjustments were made (for the Charlson Comorbidity Index, anemia, surgical urgency and technique, intraoperative fluid administration, blood transfusion, and hospital readmissions), a greater number and increased severity of complications were associated with a higher adjusted median hospital cost. Patients who experienced complications had an adjusted additional median cost of USD 4,187.10 (95% CI: 1,264.89-7,109.31, P = 0.005) compared to those without complications. Postoperative complications are a key target for cost-containment strategies. Our findings demonstrate a high prevalence of postoperative complications following small bowel resection surgery and quantify their associated increase in hospital costs. Australian Clinical Trials Registration number: 12620000322932.


Measurement of respiratory mechanics using the Siemens Servo Ventilator 900C.
The interrupter technique involves measuring the pressure changes at the airway opening during sudden cessation of flow and has been advocated for monitoring respiratory mechanics in artificially ventilated patients. The Siemens Servo Ventilator 900C has the ability to make airway occlusions without interrupting the patient's respiratory support. This study was performed to determine the suitability of the end-inspiratory occlusion facility of the ventilator for interrupter measurements of respiratory resistance and compliance. Measurements were made in a physical model of the respiratory system consisting of two parallel compartments, whose individual resistances and elastances were independently determined. The accuracy of the resistance measurements made using the ventilator were found to be dependent on the inspiratory flow. With an inspiratory flow of 100 ml/s, the resistance of the system could be measured to within 18% of the true value, and the static compliance could be measured to within 26% of the true value. Much of the error in these determinations was due to the finite closure time of the valve in the ventilator, and to the compliance of the gas in the tubing connecting the ventilator with the model. We conclude that the Siemens Servo Ventilator 900C can be used to conveniently obtain estimates of resistance and compliance in ventilated patients.


REDUCE - Indication catalogue based ordering of chest radiographs in intensive care units.
To advance a transition towards an indication-based chest radiograph (CXR) ordering in intensive care units (ICUs) without compromising patient safety. Single-center prospective cohort study with a retrospective reference group including 857 ICU patients. The routine group (n = 415) received CXRs at the discretion of the ICU physician, the restrictive group (n = 442) if specified by an indication catalogue. Documented data include number of CXRs per day and CXR radiation dose as primary outcomes, re-intubation and re-admission rates, hours of mechanical ventilation and ICU length of stay. CXR numbers were reduced in the restrictive group (964 CXRs in 2479 days vs. 1281 CXRs in 2318 days) and median radiation attributed to CXR per patient was significantly lowered in the restrictive group (0.068 vs. 0.076 Gy x cm2, P = 0.003). For patients staying ≥24 h, median number of CXRs per day was significantly reduced in the restrictive group (0.41 (IQR 0.21-0.61) vs. 0.55 (IQR 0.34-0.83), P < 0.001). Survival analysis proved non-inferiority. Secondary outcome parameters were not significantly different between the groups. CXR reduction was significant even for patients in most critical conditions. A substantial reduction of the number of CXRs on ICUs was feasible and safe using an indication catalogue thereby improving resource management. DRKS00015621, German Clinical Trials Register.


Importance of plaque volume and composition for the prediction of myocardial ischaemia using sequential coronary computed tomography angiography/positron emission tomography imaging.
Coronary atherosclerosis with a large necrotic core has been postulated to reduce the vasodilatory capacity of vascular tissue. In the present analysis, we explored whether total plaque volume and necrotic core volume on coronary computed tomography angiography (CCTA) are independently associated with myocardial ischaemia on positron emission tomography (PET). From a registry of symptomatic patients with suspected coronary artery disease and clinically indicated CCTA with sequential [15O]H2O PET myocardial perfusion imaging, we quantitatively measured diameter stenosis, total and compositional plaque volumes on CCTA. Primary endpoint was myocardial ischaemia on PET, defined as an absolute stress myocardial blood flow ≤2.4 mL/g/min in ≥1 segment. Multivariable prediction models for myocardial ischaemia were consecutively created using logistic regression analysis (stenosis model: diameter stenosis ≥50%; plaque volume model: +total plaque volume; plaque composition model: +necrotic core volume). A total of 493 patients (mean age 63 ± 8 years, 54% men) underwent sequential CCTA/PET imaging. In 153 (31%) patients, myocardial ischaemia was detected on PET. Diameter stenosis ≥50% (P < 0.001) and necrotic core volume (P = 0.029) were independently associated with myocardial ischaemia, while total plaque volume showed borderline significance (P = 0.052). The plaque composition model (χ2 = 169) provided incremental value for the prediction of ischaemia when compared with the stenosis model (χ2 = 138, P < 0.001) and plaque volume model (χ2 = 164, P = 0.021). The volume of necrotic core on CCTA independently and incrementally predicts myocardial ischaemia on PET, beyond diameter stenosis alone.


Detection of signatures of selective sweeps in the Blonde d'Aquitaine cattle breed.
Identifying recent positive selection signatures in domesticated animals could provide information on genome response to strong directional selection from domestication and artificial selection and therefore could help in identifying mutations responsible for improved traits. We used genotyping data generated using Illumina's BovineSNP50 Genotyping BeadChips to identify selection signatures in the Blonde d'Aquitaine breed, a well-muscled French beef breed. For this purpose, we employed a hidden Markov model-based test, which detects selection by studying local variations in the allele frequency spectrum along the genome, within a single population. Three regions containing selective sweeps were identified. Annotation of genes located within these regions revealed interesting candidate genes. For example, myostatin (also known as GDF8), a known muscle growth factor inhibitor, is located within the selection signature region found on chromosome 2. In addition, we have identified chromosomal regions that show some evidence of selection within QTL regions for economically important traits. The results of this study could help to better understand the mechanisms related to the selection of the Blonde d'Aquitaine breed.


Effect of eicosapentaenoic acid on cholesterol gallstone formation in C57BL/6J mice.
The present study investigated the preventive effect of ω-3 fatty acids against cholesterol gallstone (CG) formation. CG formation was induced in C57BL/6J mice using a lithogenic diet (LD). The mice were divided into four treatment groups: i) LD, ii) LD plus eicosapentaenoic acid (EPA), iii) LD plus docosahexaenoic acid (DHA) and iv) LD plus EPA plus DHA. Subsequent to feeding the mice the LD for four weeks, EPA and/or DHA (70 mg/kg/day) were orally administered for eight weeks. The mice in the EPA treatment groups exhibited significantly less gallstone formation than those in the LD group. By contrast, DHA treatment only slightly suppressed gallstone formation. The expression of mucin 2, 5AC, 5B and 6 was significantly decreased in the gallbladders of mice in the EPA groups (70-90%) and the LD plus DHA group (30-50%), compared with that in the mice in the LD group. In addition, the mRNA expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase was significantly decreased in the livers of mice in the EPA treatment group compared with that in the livers of mice in the LD group. In conclusion, EPA was found to have a dominant anti-lithogenic effect in C57BL/6J mice.


Extracellular matrix-glial abnormalities in the amygdala and entorhinal cortex of subjects diagnosed with schizophrenia.
Chondroitin sulfate proteoglycans (CSPGs), a main component of the brain extracellular matrix, regulate developmental and adult neural functions that are highly relevant to the pathogenesis of schizophrenia. Such functions, together with marked expression of CSPGs in astrocytes within the normal human amygdala and evidence of a disruption of astrocytic functions in this disease, point to involvement of CSPG-glial interactions in schizophrenia. Chondroitin sulfate proteoglycan-related abnormalities involve glial cells and extracellular matrix pericellular aggregates (perineuronal nets) in the amygdala and entorhinal cortex of subjects with schizophrenia. Postmortem case-control study. The Translational Neuroscience Laboratory at McLean Hospital, Harvard Medical School. Specimens were obtained from the Harvard Brain Tissue Resource Center at McLean Hospital. Two separate cohorts of healthy control (n = 15; n = 10) and schizophrenic (n = 11; n = 10) subjects and a cohort of subjects with bipolar disorder (n = 11). Quantitative, immunocytological, and histological postmortem investigations. Numerical densities of CSPG-positive glial cells and perineuronal nets, glial fibrillary acidic protein-positive astrocytes, and total numbers of parvalbumin-positive neurons in the deep amygdala nuclei and entorhinal cortex. In schizophrenia, massive increases in CSPG-positive glial cells were detected in the deep amygdala nuclei (419%-1162%) and entorhinal cortex (layer II; 480%-1560%). Perineuronal nets were reduced in the lateral nucleus of the amygdala and lateral entorhinal cortex (layer II). Numerical densities of glial fibrillary acidic protein-positive glial cells and total numbers of parvalbumin-positive neurons were unaltered. Changes in CSPG-positive elements were negligible in subjects with bipolar disorder. Marked changes in functionally relevant molecules in schizophrenia point to a pivotal role for extracellular matrix-glial interactions in the pathogenesis of this disease. Disruption of these interactions, unsuspected thus far, may represent a unifying factor contributing to disturbances of neuronal migration, synaptic connectivity, and GABAergic, glutamatergic, and dopaminergic neurotransmission in schizophrenia. The lack of CSPG abnormalities in bipolar disorder points to a distinctive aspect of the pathophysiology of schizophrenia in key medial temporal lobe regions.


Anti-HIF-1alpha antibody-conjugated pluronic triblock copolymers encapsulated with Paclitaxel for tumor targeting therapy.
Targeted uptake of nanoscale controlled release polymer micelles encapsulated with drugs represents a potential powerful therapeutic technology. Herein we reported the development of anti-HIF-1alpha antibody-conjugated unimolecular polymer nano micelles filled with Paclitaxel for cancer targeting therapy. Pluronic triblock copolymers(Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol), PEO-block-PPO-block-PEO) P123 were functionalized with terminal carboxylic groups, and were characterized by infrared (IR) spectroscopy, nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), and differential scanning calorimetric (DSC). The amphiphilic copolymer nano micelles encapsulated with Paclitaxel were fabricated by self-assembly means, and then were conjugated with anti-HIF-1alpha antibody, the resultant anti-HIF-1alpha conjugated nano micelles filled with PTX (anti-HIF-1alpha-NMs-PTX nanocomposites) were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and incubated with stomach cancer MGC-803 cells and HDF fibroblast cells, these treated cells were analyzed by MTT and cell-ELISA. The nanocomposites composed of anti-HIF-1alpha conjugated nano micelles filled with CdTe quantum dots were also prepared, and incubated with stomach cancer MGC-803 cells and HDF fibroblast cells for 24 h, then were observed by fluorescent microscope. Results showed that the anti-HIF-1alpha-NMs-PTX nanocomposites were successfully prepared, bound with stomach cancer MGC-803 cells specifically, were internalized, and released PTX inside cancer cells, and selectively killed cancer cells. In conclusion, unique anti-HIF-1alpha antibody-conjugated nano micelles filled with Paclitaxel can target and selectively kill cancer cells with over-expression of HIF-1alpha, and has great potential in clinical tumor targeting imaging and therapy.


Impaired muscle glycogen resynthesis after a marathon is not caused by decreased muscle GLUT-4 content.
Our purpose was to investigate whether the slow rate of muscle glycogen resynthesis after a competitive marathon is associated with a decrease in the total muscle content of the muscle glucose transporter (GLUT-4). Seven well-trained marathon runners participated in the study, and muscle biopsies were obtained from the lateral head of the gastrocnemius muscle before, immediately after, and 1, 2, and 7 days after the marathon, as were venous blood samples. Muscle GLUT-4 content was unaltered over the experimental period. Muscle glycogen concentration was 758 +/- 53 mmol/kg dry weight before the marathon and decreased to 148 +/- 39 mmol/kg dry weight immediately afterward. Despite a carbohydrate-rich diet (containing at least 7 g carbohydrate.kg body mass-1.day-1), the muscle glycogen concentration remained 30% lower than before-race values 2 days after the race, whereas it had returned to before-race levels 7 days after the race. We conclude that the total GLUT-4 protein content is unaltered in the lateral gastrocnemius after a competitive marathon and that the slow recovery of muscle glycogen after the race apparently involves factors other than changes in the total content of this protein.


In medicine, how do we machine learn anything real?
Machine learning has traditionally operated in a space where data and labels are assumed to be anchored in objective truths. Unfortunately, much evidence suggests that the "embodied" data acquired from and about human bodies does not create systems that function as desired. The complexity of health care data can be linked to a long history of discrimination, and research in this space forbids naive applications. To improve health care, machine learning models must strive to recognize, reduce, or remove such biases from the start. We aim to enumerate many examples to demonstrate the depth and breadth of biases that exist and that have been present throughout the history of medicine. We hope that outrage over algorithms automating biases will lead to changes in the underlying practices that generated such data, leading to reduced health disparities.


Inhibition of phosphoenolpyruvate carboxylase by malate.
Malate has been noted to be a ;mixed' inhibitor of phosphoenolpyruvate (PEP) carboxylase. The competitive portion of this inhibition appears to be fairly constant regardless of the condition of the enzyme being measured, but the noncompetitive (V-type) inhibition is subject to variation depending on the source of the enzyme, its storage condition, the presence or absence of various ligands, and differences in pH. In the case of the maize (Zea mays L.) phosphoenolpyruvate carboxylase (PEPC), the V-type inhibition by malate is much less pronounced at pH 8 than at pH 7. Examination of the response of the maize PEPC to PEP concentration reveals a pronounced cooperativity at pH 8 which is not present at pH 7, and which results in the disappearance of the V-type inhibition at pH 8. The ability of high concentrations of PEP to convert PEPC from a form readily inhibited by malate to one resistant to malate inhibition has been previously demonstrated and we attribute the cooperativity shown at pH 8 to this response to high levels of PEP. Support for this proposal is provided by studies of the enzyme at pH 7 and pH 8 run in 20% glycerol. In this case there was no V-type inhibition of PEPC at either pH. Treatment with 20% glycerol has been shown to result in the aggregation of maize PEPC.


Electrocardiographic findings at presentation and clinical outcome in patients with SARS-CoV-2 infection.
The main severe complications of SARS-CoV-2 infection are pneumonia and respiratory distress syndrome. Recent studies, however, reported that cardiac injury, as assessed by troponin levels, is associated with a worse outcome in these patients. No study hitherto assessed whether the simple standard electrocardiogram (ECG) may be helpful for risk stratification in these patients. We studied 324 consecutive patients admitted to our Emergency Department with a confirmed diagnosis of SARS-CoV-2 infection. Standard 12-lead ECG recorded on admission was assessed for cardiac rhythm and rate, atrioventricular and intraventricular conduction, abnormal Q/QS wave, ST segment and T wave changes, corrected QT interval, and tachyarrhythmias. At a mean follow-up of 31 ± 11 days, 44 deaths occurred (13.6%). Most ECG variables were significantly associated with mortality, including atrial fibrillation (P = 0.002), increasing heart rate (P = 0.002), presence of left bundle branch block (LBBB; P < 0.001), QRS duration (P <0 .001), a QRS duration of ≥110 ms (P < 0.001), ST segment depression (P < 0.001), abnormal Q/QS wave (P = 0.034), premature ventricular complexes (PVCs; P = 0.051), and presence of any ECG abnormality [hazard ratio (HR) 4.58; 95% confidence interval (CI) 2.40-8.76; P < 0.001]. At multivariable analysis, QRS duration (P = 0.002), QRS duration ≥110 ms (P = 0.03), LBBB (P = 0.014) and presence of any ECG abnormality (P = 0.04) maintained a significant independent association with mortality. Our data show that standard ECG can be helpful for an initial risk stratification of patients admitted for SARS-CoV-2 infectious disease.


Trichoscopy in genetic hair shaft abnormalities.
Diagnosis of hair shaft abnormalities is based on light microscopic examination of more than 50 plucked hairs. The aim of this study was to verify whether hair shaft abnormalities may be visualized by trichoscopy (hair and scalp videodermoscopy) and to analyze trichoscopic features of common genetic hair shaft dysplasias. Patients with known genetic hair shaft disorders were included into the study. Trichoscopy was performed with the use of Fotofinder II videodermoscope. Images performed at 20-fold and 70-fold magnification were analysed. In selected cases 160-fold magnification was used for better visualization of hair shafts. Our results show that characteristic light microscopy features of Netherton syndrome, monilethrix, woolly hair syndrome, pili torti, pili annulati and trichothiodystrophy may be visualized by trichoscopy. Genetic hair shaft abnormalities may be diagnosed by trichoscopy in a single diagnostic session without the need of plucking or cutting them for diagnostic purposes.


[Water in oil microemulsions containing NaCl for transdermal delivery of fluorouracil].
This study is to prepare the W/O microemulsion containing NaCl and fluorouracil (5-Fu) as a model drug to investigate the transdermal characteristics and skin irritation of the microemulsion in vitro. Isopropylmyristate (IPM) acting as oil phase, Aerosol-OT (AOT) as surfactant, Tween 85 as cosurfactant, NaCl solution was added dropwise to the oil phase to prepare W/O microemulsion at room temperature using magnetic stirring, and then 5-Fu powder was added. According to the area of microemulsion based on the pseudo-tertiary phase diagrams, the optimum formulation was screened initially. And the permeation flux of fluorouracil across excised mice skin was determined in vitro using Franz diffusion cells to study the influence of the amount of water and the drug loading capacity and optimize the formulation further. Refer to 5-Fu cream, the irritation of microemulsion on the rat skin was studied. The optimum formulation was composed of 0.7% (w/v) 5-Fu, 50% NaCl solution (0.05 mol x L(-1)), 20% mix-surfactant (AOT/Tween 85, K(m) = 2) and 29.3% oil (IPM). The cumulative amount of fluorouracil permeated in 12 h was (2 013.4 +/- 41.6) microg x cm(-2), 20.23 folds and 10.38 folds more than 0.7% fluorouracil aqueous solution and 2.5% (w/w) fluorouracil cream, respectively. Microemulsion exhibited some irritation, but could be reversed after drug withdrawal. The addition of NaCl significantly increased the content of water and the drug loading in microemulsion systems. The NaCl/AOT-Tween 85/IPM microemulsion system promoted the permeation of fluorouracil greatly, which may be a promising vehicle for the transdermal delivery of fluorouracil and other hydrophilic drug.


Lysophosphatidylcholine promotes P-selectin expression in platelets and endothelial cells. Possible involvement of protein kinase C activation and its inhibition by nitric oxide donors.
Lysophosphatidylcholine (LysoPC), an atherogenic lysophospholipid contained in oxidized low-density lipoprotein (LDL), has been shown to stimulate protein kinase C (PKC). Since PKC activators are suggested to elicit rapid P-selectin expression in platelets and endothelial cells, we examined whether LysoPc promotes P-selectin expression in platelets and P-selectin-mediated leukocyte adherence to endothelial cells via a mechanism involving PKC activation. LysoPc, but not phosphatidylcholine (PC), which is a major phospholipid component in native LDL, significantly upregulated P-selectin on cat platelets by flow cytometric analysis. This P-selectin upregulation by LysoPC was significantly attenuated by two PKC inhibitors, 7-hydroxystaurosporine (UCN-01) and N,N,N-trimethylsphingosine, and by two NO donors, CAS1609 and sodium nitroprusside. Submicellar concentrations of LysoPc significantly activated PKC in platelets, and this was inhibited by either UCN-01 or CAS1609. LysoPC, but not PC, significantly increased adherence of autologous cat polymorphonuclear leukocytes to coronary vascular endothelium, which was also markedly attenuated by UCN-01 and by CAS1609. LysoPC induced P-selectin expression on the surface of cat coronary vascular endothelium as assessed by immunohistochemical analysis. These results suggest that LysoPC, an atherogenic lysophospholipid contained in oxidized LDL, rapidly induces P-selectin expression in both platelets and endothelial cells at least partially via PKC activation. Furthermore, NO-generating agents may inhibit P-selectin upregulation by LysoPC. Since P-selectin may play an important role in initiating atherosclerosis, our data provide further insight into the mechanism of early stages of atherogenesis and of NO-mediated inhibition of atherosclerosis.


[Identification of bacteria using DNA probes].
Since the microbial specificity of periodontal diseases is well established, having a valid microbial diagnostic test is essential for a correct and a coherent treatment planning. DNA probe will be used to identify and quantify the oral pathogens, most commonly associated with periodontitis. This test utilizes innovative DNA probe technology to identify unique segments of DNA in each of the following bacteria: Bacteroides gingivalis, Bacteroides intermedius, Actinobacillus actinomycetemcomitans, Wollinella recta, Fusobacterium nucleatum and the spirochete, Treponema denticola.


From Molecular to Cluster Properties: Rotational Spectroscopy of 2-Aminopyridine and of Its Biomimetic Cluster with Water.
We report the observation and analysis of the rotational spectrum of a 1:1 cluster between 2-aminopyridine and water (AMW) carried out with supersonic expansion Fourier transform microwave spectroscopy at 4.7-16.5 GHz. Measurements of the 2-aminopyridine monomer (AMP) were also extended up to 333 GHz for the room-temperature rotational spectrum and to resolved hyperfine splitting resulting from the presence of two 14N quadrupolar nuclei. Supersonic expansion measurements for both AMP and AMW were also carried out for two synthesized isotopic species with single deuteration on the phenyl ring. Nuclear quadrupole hyperfine structure has also been resolved for AMW and the derived splitting constants were used as an aid in structural analysis. The structure of the AMW cluster was determined from the three sets of available rotational constants and the hydrogen bonding configuration is compared with those for clusters with water of similarly sized single-ring molecules. Experimental results aided by quantum chemistry computations allow the conclusion that the water molecule is unusually strongly bound by two hydrogen bonds, OH...N and O...HN, to the NCNH atomic chain of AMP with the potential to replace hydrogen bonds to the identical structural segment in cytosine and adenine in CT and AT nucleic acid base pairs.


[Takotsubo syndrome (stress-induced cardiomyopathy)].
The article presents published and own data about Takotsubo syndrome, a relatively rare heart disease that is similar to acute coronary syndrome, but without significant damage of coronary arteries. The leading pathogenetic factor is the catecholamine-induced stress damage of myocardium with involvement of microvessels. There is a certain underestimation of Takotsubo syndrome by both clinicians and pathologists, so some cases of Takotsubo syndrome are misdiagnosed as acute coronary syndrome. Morphological manifestations of Takotsubo syndrome are characterized by mucoid edema of interstitial myocardial tissue, round-cell infiltration of stroma and focal damage of cardiomyocytes.


Adhesion of spherical polyelectrolyte brushes on mica: an in situ AFM investigation.
We demonstrate that the adsorption of cationic spherical polyelectrolyte brushes (SPB) on negatively charged mica substrates can be controlled in situ by the ionic strength of the suspension. The SPB used in our experiments consist of colloidal core particles made of polystyrene. Long cationic polyelectrolyte chains are grafted onto these cores that have diameters in the range of 100 nm. These particles are suspended in aqueous solution with a fixed ionic strength. Atomic force microscopy (AFM) in suspension as well as in air was used for surface characterization. In pure water the polymer particles exhibit a strong adhesion to the mica surface. AFM investigations of the dry samples show that the particles occupy the identical positions as they did in liquid. They were not removed by the capillary forces within the receding water front during the drying process. The strong interaction between the particles and the mica surface is corroborated by testing the adhesion of individual particles on the dried surface by means of the AFM tip: after a stepwise increase of the force applied to the surface by the AFM tip, the polymer particles still were not removed from the surface, but they were cut through and remained on the substrate. Moreover, in situ AFM measurements showed that particles which adsorb under liquid in a stable manner are easily desorbed from the surface after electrolyte is added to the suspension. This finding is explained by a decreasing attractive particle-substrate interaction, and the removal of the particles from the surface is due to the significant reduction of the activation barrier of the particle desorption. All findings can be explained in terms of the counterion release force.


Metabolic Specialization and Codon Preference of Lignocellulolytic Genes in the White Rot Basidiomycete Ceriporiopsis subvermispora.
Ceriporiopsis subvermispora is a white-rot fungus with a high specificity towards lignin mineralization when colonizing dead wood or lignocellulosic compounds. Its lignocellulose degrading system is formed by cellulose hydrolytic enzymes, manganese peroxidases, and laccases that catalyze the efficient depolymerization and mineralization of lignocellulose. To determine if this metabolic specialization has modified codon usage of the lignocellulolytic system, improving its adaptation to the fungal translational machine, we analyzed the adaptation to host codon usage (CAI), tRNA pool (tAI, and AAtAI), codon pair bias (CPB), and the number of effective codons (Nc). These indexes were correlated with gene expression of C. subvermispora, in the presence of glucose and Aspen wood. General gene expression was not correlated with the index values. However, in media containing Aspen wood, the induction of expression of lignocellulose-degrading genes, showed significantly (p < 0.001) higher values of CAI, AAtAI, CPB, tAI, and lower values of Nc than non-induced genes. Cellulose-binding proteins and manganese peroxidases presented the highest adaptation values. We also identified an expansion of genes encoding glycine and glutamic acid tRNAs. Our results suggest that the metabolic specialization to use wood as the sole carbon source has introduced a bias in the codon usage of genes involved in lignocellulose degradation. This bias reduces codon diversity and increases codon usage adaptation to the tRNA pool available in C. subvermispora. To our knowledge, this is the first study showing that codon usage is modified to improve the translation efficiency of a group of genes involved in a particular metabolic process.


Bacillus subtilis spores as delivery system for nasal Plasmodium falciparum circumsporozoite surface protein immunization in a murine model.
Malaria remains a widespread public health problem in tropical and subtropical regions around the world, and there is still no vaccine available for full protection. In recent years, it has been observed that spores of Bacillus subtillis can act as a vaccine carrier and adjuvant, promoting an elevated humoral response after co-administration with antigens either coupled or integrated to their surface. In our study, B. subtillis spores from the KO7 strain were used to couple the recombinant CSP protein of P. falciparum (rPfCSP), and the nasal humoral-induced immune response in Balb/C mice was evaluated. Our results demonstrate that the spores coupled to rPfCSP increase the immunogenicity of the antigen, which induces high levels of serum IgG, and with balanced Th1/Th2 immune response, being detected antibodies in serum samples for 250 days. Therefore, the use of B. subtilis spores appears to be promising for use as an adjuvant in a vaccine formulation.


Indole-3-acetic acids and horseradish peroxidase: a new prodrug/enzyme combination for targeted cancer therapy.
The radical-cations formed on one-electron oxidation of indole-3-acetic acid (IAA) and its ring-substituted derivatives rapidly fragment, eliminating carbon dioxide from the sidechain and forming a carbon-centred free radical (3-indolylmethyl or skatolyl, or analogues). This radical is reactive towards DNA and possibly other targets in anoxia, but in oxic or hypoxic cells rapidly adds oxygen to form a peroxyl radical. Subsequent products include 3-methylene-2-oxindole or analogues, reactive towards cellular nucleophiles such as thiols and DNA. The one-electron oxidation of indole-3-acetic acids is efficiently achieved by horseradish peroxidase (HRP), not requiring added hydrogen peroxide cofactor. The combination of IAA and HRP is cytotoxic towards mammalian cells, including human tumour cells. Unexpectedly, some halogen-substituted derivatives of IAA are very cytotoxic with HRP even though they are more difficult to oxidize. IAA is tolerated by humans in high doses and HRP is a robust enzyme meeting many of the requirements for targeting to tumours by coupling to antibodies or polymers, or by gene transfection. It is suggested that the indole acetic acids merit further evaluation as potential prodrugs for use in cancer therapy based on targeted delivery of HRP to tumours.


Recursive mean-squared-error algorithm for iterative discrete on-axis encoded holograms.
A hybrid-algorithm has been developed that uses the concept of a rapid recursive mean-squared-error (RMSE) function combined with the annealed, multiphase, on-axis capabilities of iterative discrete on-axis (IDO) encoding. High diffraction efficiency and computational speed are obtained through the use of the RMSE algorithm with a constant weighting coefficient in the error function and an iterative initial process for determining phase codes in the output plane. Results for large even spot arrays are presented, and comparisons are made for diffraction efficiency, spot uniformity, and computation speed between the original IDO and the RMSE-based IDO encoding.


A dose-response study of glutamate supplementation in isolated, perfused rat hearts undergoing ischaemia and cold cardioplegia.
Several studies have reported superior post-cardioplegic recovery after glutamate supplementation. The optimum dose of glutamate supplementation is unknown. The purpose of this study was to find the optimal protective concentration of glutamate supplementation in a model of ischaemia/cardioplegia and reperfusion. Isolated rat hearts (n = 77) were perfused with the Krebs-Henseleit buffer. After stabilization, the hearts were subjected to 25 min of normothermic ischaemia followed by a single 3-min infusion of cold (4-6 °C) St. Thomas' Hospital II cardioplegia and 87 min of cardioplegic ischaemic arrest and 60 min of reperfusion. Sodium-l-glutamate was added to the perfusate (control group had zero glutamate) in increasing concentrations (0.01, 0.1, 1, 10, 20, 30 and 100 mM) and given throughout perfusion. Corresponding concentrations were added to the cardioplegic solution. A balloon in the left ventricle inserted via the left atrium measured left ventricular pressures isometrically. Left ventricular developed pressure was calculated. Myocardial exchange of glucose and lactate was measured prior to ischaemia and during reperfusion. Myocardial content of glycogen and glutamate was measured at the end of reperfusion. During reperfusion left ventricular developed pressure increased (P < 0.0001) in groups supplemented with 0.1, 1.0, 10, 20 and 30 mM glutamate, whereas left ventricular end-diastolic pressure was attenuated (P = 0.008) when compared with the controls. No additional benefit on the continuous data left ventricular developed pressure and left ventricular end-diastolic pressure was observed with glutamate concentrations above 1 mM. Onset of LV pressure rise during the period of ischaemia was delayed by 100 mM of glutamate (P = 0.02). Myocardial content of glutamate was increased in a dose-related manner in Groups 10, 20, 30 and 100 compared with the control hearts (P < 0.0001). Glycogen was increased in the hearts supplemented with 100 mM of glutamate (P = 0.02). Even low concentrations of l-glutamate improved postischaemic and post-cardioplegic heart function and 1 mM seems to be optimal.


Granulocyte-Macrophage Colony-Stimulating Factor Inhalation Therapy for Severe Pulmonary Alveolar Proteinosis.
Some patients with pulmonary alveolar proteinosis (PAP) still present with high recurrence rate after large-volume whole lung lavage (WLL). Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been proved to be effective for PAP, but clinical research on GM-CSF inhalation therapy combined with WLL for severe PAP is rare in Asia. This study aimed to investigate the clinical efficacy of GM-CSF inhalation combined with WLL in Chinese patients with PAP. We performed regression analysis on 33 patients with severe PAP who underwent WLL alone or WLL combined with GM-CSF inhalation. The patients were put into 2 groups, WLL group and GM-CSF/WLL group. Physiologic, serologic, and radiologic features of the 2 groups at different time points after treatment and the recurrence rates at 1-year follow-up were compared. There were no significant differences in lung function, blood gas analysis indices, and lung CT between the 2 groups after 1-week treatment (P > 0.05). After 3-month treatment, the GM-CSF/WLL group showed significantly faster improvement in FEV1%Pred (P = 0.028), FVC%Pred (P = 0.014), PaO2 (P = 0.022), PA-aO2 (P = 0.009), PaO2/FiO2 (P = 0.025), 6-minute walking test (P = 0.002), and lung CT parameters (P < 0.05) compared with the WLL group. The recurrence rate at the 1-year follow-up in the GM-CSF/WLL group (5.5%) was significantly higher than that in the WLL group (46.67%; P < 0.05). GM-CSF inhalation therapy combined with WLL is an effective treatment for patients with severe PAP, with further improvement in lung function at the base of WILL as well as reduction on re-WLL incidence.


Mesoporous silica nanoparticles as antigen carriers and adjuvants for vaccine delivery.
Vaccines have been at the forefront of improving human health for over two centuries. The challenges faced in developing effective vaccines flow from complexities associated with the immune system and requirement of an efficient and safe adjuvant to induce a strong adaptive immune response. Development of an efficient vaccine formulation requires careful selection of a potent antigen, efficient adjuvant and route of delivery. Adjuvants are immunological agents that activate the antigen presenting cells (APCs) and elicit a strong immune response. In the past decade, the use of mesoporous silica nanoparticles (MSNs) has gained significant attention as potential delivery vehicles for various biomolecules. In this review, we aim to highlight the potential of MSNs as vaccine delivery vehicles and their ability to act as adjuvants. We have provided an overview on the latest progress on synthesis, adsorption and release kinetics and biocompatibility of MSNs as next generation antigen carriers and adjuvants. A comprehensive summary on the ability of MSNs to deliver antigens and elicit both humoral and cellular immune responses is provided. Finally, we give insight on fundamental challenges and some future prospects of these nanoparticles as adjuvants.


Increased tumor oxygenation and radiation sensitivity in two rat tumors by a hemoglobin-based, oxygen-carrying preparation.
The rat 13762 mammary carcinoma and the rat 9L gliosarcoma were grown subcutaneously in a hind limb of female, Fisher 344 rats. The oxygen content of the tumors was determined using an Eppendorf pO2 histograph. Fifty-to-sixty oxygen measurements were made per tumor and there were 8-to-10 animals per group. The percent of pO2 readings < or = 5 mmHg in the mammary carcinoma was 49%, this was decreased to 34% by administration of the hemoglobin preparation (8 ml/kg) and further decreased to 29% when carbogen (95% O2/5% CO2) breathing was added to administration of the hemoglobin preparation. The percent of pO2 readings < or = 5 mmHg in the gliosarcoma was 49%, this was decreased to 24% by administration of the hemoglobin preparation and further decreased to 0% when carbogen breathing was added to administration of the hemoglobin preparation. Therapeutic response was assessed over a single-dose range of radiation therapy (10, 20 and 30 Gray). The dose modifying factor produced by the hemoglobin preparation/air was 1.6 and by the hemoglobin preparation/carbogen was 2.7 in the rat 13762 mammary carcinoma. The dose modifying factor produced by the hemoglobin preparation/air was 1.9 and by the hemoglobin preparation/carbogen was 2.9 in the rat 9L gliosarcoma. Administration of a hemoglobin-based oxygen carrier reduced tumor hypoxia and increased tumor response to radiation therapy.


The Beneficial Effects of Beta Blockers on the Long-Term Prognosis of Patients With Premature Atrial Complexes.
Premature atrial complexes (PACs) have been reported to increase the risk of adverse cardiovascular outcomes. Beta blockers at low dosages may help to reduce PAC symptoms, but it is unclear whether they can improve long-term outcomes. Patients enrolled from a Holter cohort in a medical referral center were stratified into high-burden (≥100 beats/24 h) and low-burden (<100 beats/24 h) sub-cohorts, and propensity score matching between treatment groups and non-treatment groups was conducted for each sub-cohort. In the high-burden sub-cohort, after propensity score matching, the treatment group and non-treatment group respectively had 208 and 832 patients. The treatment group had significantly lower mortality rates than the non-treatment group [hazard ratio (HR) = 0.521, 95% confidence interval (CI) = 0.294-0.923, p = 0.025], but there was no difference in new stroke (HR = 0.830, 95% CI = 0.341-2.020, p = 0.681), and new atrial fibrillation (HR = 1.410, 95% CI = 0.867-2.292, p = 0.167) events. In the low-burden sub-cohort, after propensity score matching, there were 614 patients in the treatment group and 1,228 patients in the non-treatment group. Compared to the non-treatment group, up to 40% risk reduction in mortality was found in the treatment group (HR = 0.601, 95% CI = 0.396-0.913, p = 0.017), but no differences in new stroke (HR =0.969, 95% CI = 0.562-1.670, p = 0.910) or atrial fibrillation (HR = 1.074, 95% CI = 0.619-1.863, p = 0.800) were found. Beta blockers consistently decreased long-term mortality in high-burden and low-burden patients. Interestingly, this effect was not achieved through reduction of new-onset stroke or AF, and further research is warranted.


Palatal swelling in a young adult.
The presence of numerous minor salivary gland tissues in the posterior part of hard palate increases the possibility of salivary gland neoplasms. Minor salivary gland tumor accounts for about 15% of all the salivary gland neoplasms, of which mucoepidermoid carcinoma (MEC) accounts for about 35.9%. Although a wide range of the differential diagnosis is made by the clinicians toward a single palatal swelling without any other specific changes on inspection, a prompt "histopathological" diagnosis is of utmost importance in case of lesions like "MEC." By taking the case study of a 23-year-old male patient who was complaining of difficulties in eating and speaking due to a swelling in the palate that was not associated with pain, etc., this case report highlights the need for an early clinical examination and prompt histopathological diagnosis of such clinically benign looking lesions, as such an action can play an ameliorating role in reducing the chances of postoperative morbidity.


From membrane to mineralization: the curious case of the ABCC6 transporter.
ATP-binding cassette subfamily C member 6 gene/protein (ABCC6) is an ATP-dependent transmembrane transporter predominantly expressed in the liver and the kidney. ABCC6 first came to attention in human medicine when it was discovered in 2000 that mutations in its encoding gene, ABCC6, caused the autosomal recessive multisystemic mineralization disease pseudoxanthoma elasticum (PXE). Since then, the physiological and pathological roles of ABCC6 have been the subject of intense research. In the last 20 years, significant findings have clarified ABCC6 structure as well as its physiological role in mineralization homeostasis in humans and animal models. Yet, several facets of ABCC6 biology remain currently incompletely understood, ranging from the precise nature of its substrate(s) to the increasingly complex molecular genetics. Nonetheless, advances in our understanding of pathophysiological mechanisms causing mineralization lead to several treatment options being suggested or already tested in pilot clinical trials for ABCC6 deficiency. This review highlights current knowledge of ABCC6 and the challenges ahead, particularly the attempts to translate basic science into clinical practice.


Characterisation and calibration of active sampling Solid Phase Microextraction applied to sensitive determination of gaseous carbonyls.
A characterisation of a system designed for active sampling of gaseous compounds with Solid Phase Microextraction (SPME) fibres is described. This form of sampling is useful to automate sampling while considerably reducing the sampling times. However, the efficiency of this form of sampling is also prone to be affected by certain undesirable effects such as fibre saturation, competition or displacement effects between analytes, to which particular attention should be paid especially at high flow rates. Yet, the effect of different parameters on the quantitivity of the results has not been evaluated. For this reason, in this study a careful characterisation of the influence of the parameters involved in active sampling SPME has been performed. A versatile experimental set-up has been designed to test the influence of air velocities and fluid regime on the quantitivity and reproducibility of the results. The mathematical model applied to the calculation of physical parameters at the sampling points takes into consideration the inherent characteristics of gases, distinctive from liquids and makes use of easily determined experimental variables as initial/boundary conditions to get the model started. The studies were carried out in the high-volume outdoor environmental chambers, EUPHORE. The sample subjected to study was a mixture of three aldehydes: pentanal, hexanal and heptanal and the determination methodology was O-(2,3,4,5,6-pentafluorobenzyl)-hydroxylamine hydrochloride (PFBHA) on-fibre derivatisation. The present work proves that the determination procedure is quantitative and sensitive, independent from experimental conditions: temperature, relative humidity or ozone levels. With our methodology, the influence on adsorption of three inter-related variables, i.e., air velocity, flow rate and Reynolds numbers can be separated, since a change can be exerted in one of them while keeping the others constant.


Extended workshifts and excessive fatigue.
Studies of overtime have pointed to fatigue as a potential factor producing, for example, a three-fold increase in accident rate after 16 h of work, increases in back injuries, hospital outbreaks of bacterial infection, or nuclear-power plant safety compromises. Fatigue has been measured more directly in studies of scheduled long workshifts, where performance decrements in both work-related tasks and laboratory-type behavioural tests have been observed, and significant loss of sleep and increases in subjective sleepiness have been reported. Analyses of accidents or injuries during scheduled extended workshifts, however, have produced equivocal results. Factors which could compound the fatiguing effects of extended workshifts, such as workload, noise, chemical exposure, or duties and responsibilities outside of the workplace, rarely have been studied systematically. It is concluded that extended workshift schedules should be instituted cautiously and evaluated carefully, with appropriate attention given to staffing levels, workload, job rotation, environmental exposures, emergency contingencies, rest breaks, commuting time, and social or domestic responsibilities.


Clinical significance of the ophthalmic artery in carotid artery disease.
A total of 141 subjects with tight stenosis (> or = 75%) or occlusion of internal carotid artery were followed up at intervals 3-6 months regularly for 40 +/- 16 months. The direction of ophthalmic artery flow was used as a parameter of risk indicator on cerebral ischemic events. Eleven patients with bilateral carotid tight stenosis/occlusion were excluded in the analysis. Thus, the 130 carotid arteries were divided into three groups: (1) carotid artery with ipsilateral hemispheric TIA or stroke (85 patients), (2) carotid arteries with contralateral hemispheric TIA/stroke or VBI (15 patients), and (3) carotid arteries of asymptomatic patients (30 patients). The symptomatic carotid artery group (group 1) had significantly more often reversed ophthalmic flow than the other two groups (group 2 and 3, p < 0.001). During follow-up prospectively for four years, 41 patients had cerebral ischemic events, three had cardiac ischemic events and six died of malignancy. Patients with reversed OA flow had more often subsequent cerebral ischemic events than those with forward flow (27 vs 14, p = 0.010). However, the difference remained significant only in the asymptomatic patients (group 3, 4 vs 0, P < 0.001), not for groups 1 and 2, after further analysis. Our work supported that the clinical role of ophthalmic artery collateral varied between asymptomatic and symptomatic patients.


Psychometric assessment of the Health Care Alliance Questionnaire with women in prenatal care.
The current study assessed the reliability and validity of the Health Care Alliance Questionnaire, which was developed using a Delphi process and embedded in an ongoing perinatal outcomes study. The Health Care Alliance Questionnaire exhibited content and face validity and high reliability. Results indicated concurrent validity in relation to satisfaction with practitioner and discriminant validity in relation to interpersonal sensitivity and posttraumatic stress disorder. The Health Care Alliance Questionnaire demonstrated predictive validity in relation to perceptions of practitioner's care during labor and postpartum depression. Overall, results suggest that alliance may be an important factor in maternity care processes and outcomes. Further psychometric work is warranted.


Role of Intracardiac Defibrillation During the Ablation Procedure as a Predictor of Atrial Fibrillation Recurrence After Catheter Ablation.
Intracardiac defibrillation (IDF) is performed to restore sinus rhythm (SR) during radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). This study aimed to investigate the change in the IDF threshold before and after RFCA during the ablation procedure and determine whether the IDF threshold after RFCA was associated with the AF substrate and AF recurrence. A total of 141 consecutive patients with drug-refractory persistent AF (age 62.5 ± 10.3 years, 84.4% male) were enrolled in this study. Before RFCA, we initially performed IDF with an output of 1 J. When IDF failed to restore SR, the output was gradually increased to 30 J. After RFCA, we attempted pacing-induced AF to provoke other focuses of AF. When AF was induced, we performed IDF again to terminate AF with outputs of 1 to 30 J. The change in the IDF threshold to restore SR before and after RFCA was evaluated. After RFCA, the IDF threshold for restoring SR significantly decreased (from 11.5 ± 8.6 J to 4.0 ± 3.8 J, P < 0.001). During the follow-up (24.3 ± 12.2 months), SR was maintained in 107 patients (75.9%). The multivariate analysis using a Cox proportional-hazards model revealed that an IDF threshold of > 5 J after RFCA was significantly associated with the AF recurrence (HR, 3.99; 95% confidence interval 1.93-8.22; P = 0.0001). RFCA decreased the IDF threshold for restoring SR in patients with persistent AF. The IDF output of > 5 J after RFCA could be a predictor of AF recurrence independent of the AF substrate.


[The morphous analyses of three different characteristics cells growing in soft agar.].
Soft agar assay was usually used in colony formation observation of cells, while it was also be empolyed in detecting bionomics of inferior creature. In this article the feasibility of soft agar assay in detecting mammalian cell phenotype is investigated. Three different characteristic cells(L cell NIH3T3;higher metastatic human lung adenocarcinoma cell line Anip973;higher invasive potential human lung adenocarcinoma cell line L18) were seed into soft agar. The morphology of cells was obserned in the first day, the fifth day and the fourteenth day,respectively. In the fifth day, morphology of the three kinds cells appeared difference and in the fourteenth day the difference became more notable. NIH3T3 cell clones were ellipse and moderate size, their boundary were distinct; Anip973 cell clones were surrounded with plenty of migratory cells, which was consistent with higher metastatic characteristics of the cells. L18 cell clones showed lots of branchs and extended toward environment. Soft agar assay is a good method in evaluating and observed biological property of mammalian cells according to their phenotypes.


[Opposable medical references of the ANDEM concerning hyperlipidemia and its treatment].
Cardiovascular diseases are the main cause of morbidity and mortality in France, and frequently result from hyperlipidemia. Physicians are therefore often faced with the diagnosis and treatment of hyperlipidemia. However, this issue must be considered within the general context of the global vascular risk of a given subject. Even though French health laws recently introduced do not take place of literature search to help guide the diagnosis and implement treatment, they may be considered as relevant summaries and guidelines with regard to current scientific knowledge. These laws mainly concern hypercholesterolemia and mixed hyperlipidemia and remind the physician that the patient's diet, values above which treatment is necessary and treatment objectives should be assessed before introducing any hypolipidemic treatment. These new French laws are also an initial approach to treatment of hyperlipidemia, even though some ambiguities and issues are still unanswered. They should be considered as guidelines subject to modifications related to new findings.


A rare GC mutant in horses disclosed by isoelectric focusing and subsequent immunoprinting.
An apparent incompatibility in the GC/DBP system in a mare and her colt was found after classification by polyacrylamide gel electrophoresis. Because of this observation an analysis of the equine GC/DBP system by isoelectric focusing and subsequent immunoprinting was initiated. Further GC subtypes, however, were not encountered: the three phenotypes GC F, FS and S were also delineated by this method. The GC types in the case of disputed descent were dissolved: GC S was found in the mare and GC FS in her colt as well as in another of her male offspring. It is proposed that a rare GC mutant is responsible for this observation, namely a GC S* component which is readily classified by isoelectric focusing and immunoprinting and difficult to disclose by polyacrylamide gel electrophoresis.


Impact of different stages of chronic kidney disease on the severity of Willis-Ekbom disease.
Willis-Ekbom disease (WED)/restless legs syndrome (RLS) is a disorder in which the patient has neurologic features such as urge of rhythmic limb movement that may decrease or stop when the limb is moved. In this study, we had tried to compare the severity of WED in different stages of chronic kidney disease (CKD). In this study, a total of 300 patients with CKD who were >18 years of age were included. All the participants were subjected to questionnaire for the diagnosis of RLS (essential clinical criteria for the diagnosis of RLS) and a questionnaire on International Restless Legs Syndrome Study Group Rating Scale for its severity. Our study showed a prevalence of 20% of WED in patients with CKD. Patients with CKD on hemodialysis had significantly more WED than the conservative group (P = 0.0001). Patients with a history of diabetes mellitus showed significant correlation with WED (P = 0.026), while patients who had a history of hypertension showed both diabetes mellitus and hypertension and smoking had no significant relation with WED (P = 0.27, P = 0.23, and P = 0.22, respectively). The different stages of CKD showed significant correlation with WED (P = 0.002), with more WED among patients with stage V CKD. WED was more in patients on hemodialysis (P = 0.0001). The correlation of different stages of CKD with the severity of WED was statistically significant (P = 0.029), with WED being more severe among stage V CKD. WED was more prevalent among patients with CKD who are on maintenance hemodialysis and diabetes mellitus. However, no such relation could be established for hypertension alone. Patients with higher grades of CKD were more prone to have WED symptoms, and the severity of these symptoms increases with the stages of CKD.


Studies on bio-chemical profiling of Indian gooseberry (Emblica officinalis) for genetic diversity.
Biochemical profiling of physiologically mature fruits of 51 diverse Indian gooseberry (Emblica officinalis Gaertn) germplasm accessions was collected from Vindhyan hill region of Madhya Pradesh, with a view to select nutraceutically rich genotypes based on important biochemical traits. The mean ascorbic acid and total phenol (tannin) content amongst different accessions was recorded as 496.47 mg 100 g⁻¹ and 4.88% with highest value found in CISH A-12 (654.50 mg 100 g⁻¹) and CISH A-30 (7.18%), respectively. Apart from the above, wide range of variability in the composition of other important biochemical attributes viz., total soluble solids (8.60-17.70°Brix), acidity (1.61-2.94%), total sugar (4.15-9.17), reducing sugar (2.19-4.45%) and TSS/acid ratio (3.89-8.33) was also recorded. Highest significant and positive correlation was observed between total sugar and TSS (0.895) followed by reducing sugar and TSS (0.882). Significant positive correlation between ascorbic acid and tannins (0.551) was an indication to be associated with binding capacity of ascorbic acid over a longer period of storage.


Simultaneous quantification of sinigrin, sinalbin, and anionic glucosinolate hydrolysis products in Brassica juncea and Sinapis alba seed extracts using ion chromatography.
Although mustards such as Sinapis alba and Brassica juncea contain glucosinolates (sinalbin and sinigrin, respectively) that hydrolyze to form biopesticidal products, routine quality control methods to measure active ingredients in seed and seed meals are lacking. We present a simple and fast ion chromatography method for the simultaneous quantification of sinigrin, sinalbin, and anionic hydrolysis products in mustard seed to assess biological potency. Optimum conditions include isocratic elution with 100 mM NaOH at a flow rate of 0.9 mL/min on a 4 × 210 mm hydroxide-selective anion-exchange column. All anion analytes including sinigrin, sinalbin, SO4(2-), and SCN(-) yielded recoveries ranging from 83 to 102% and limits of detection ≤0.04 mM, with samples displaying little interference from plant matrix components. Sample preparation is minimized and analysis times are shortened to <90 min as compared with previous methods that took days and multiple instruments.


The Ecological Resilience Framework: The Justice Ambassadors Youth Council as a model for community-based resilience.
We present an 'Ecological Resilience Framework' (ERF) to demonstrate how resilience is created through the Justice Ambassadors Youth Council (JAYC) program. JAYC is a platform in which New York government representatives collaboratively learn and develop policy solutions alongside emerging adults who are criminal legal system impacted and reside in predominantly Black and Hispanic communities characterized by chronically high levels of poverty, violence, and incarceration. We focus our work on the process of developing resilience in the context of structural social inequity and injustice. We argue that resilience can best be understood in the context of the adversity to which it is a response, not as an isolated individual quality. Therefore, resilience science is at its best when it incorporates a multi-disciplinary scientific perspective, one that addresses a continuum from individual- to community- to society-level physical, cognitive, relationship, and mental health variables. To demonstrate how our ERF incorporates this approach, we outline how JAYC not only supports young adult participants in understanding their individual life trajectories and narrative identity, but also actively connects them within a diverse social network of mentors and to various opportunities that support a healthy transition to adult resilience.


Isolated central nervous system relapse in an adolescent with acute myelomonocytic leukemia, Charcot Marie Tooth syndrome, and paraneoplastic autoantibody.
A 17-year-old boy, with acute myelomonocytic leukemia and inversion 16(p13q22) developed polyneuropathy and isolated central nervous system relapse. Scoliosis and high-arched feet suggested a diagnosis of Charcot Marie Tooth (CMT) syndrome and genetic testing confirmed duplication at the PMP22 locus at chromosome 17p11.12. No mutation was found in another CMT gene, the CMT C1 LITAF locus at 16p13.2, to suggest that this association is anything more than chance. Titres to VGKC, a paraneoplastic autoantibody, were elevated, suggesting an additional mechanism for the polyneuropathy. This case extends the clinical spectrum of cancer with CMT, and of paraneoplastic disorders.


The Safety and Feasibility of Laparoscopic Surgery for Very Low Rectal Cancer: A Retrospective Analysis Based on a Single Center's Experience.
In this work we intend to validate the long-term oncologic outcomes for very low rectal cancer over the past 20 years and to determine whether laparoscopic procedures are useful options for very low rectal cancer. A total of 327 patients, who electively underwent laparoscopic rectal cancer surgery for a lesion within 5 cm from the anal verge, were enrolled in this study and their long-term outcomes were reviewed retrospectively. Of 327 patients, 70 patients underwent laparoscopic low anterior resection (LAR), 164 underwent laparoscopic abdominal transanal proctosigmoidocolectomy with coloanal anastomosis (LATA), and 93 underwent laparoscopic abdominoperineal resection (APR). The conversion rate was 1.22% (4/327). The overall postoperative morbidity rate was 26.30% (86/327). The 5-year disease free survival (DFS), 5-year overall survival (OS), and 3-year local recurrence (LR) were 64.3%, 79.7%, and 9.2%, respectively. The CRM involvement was a significant independent factor for DFS (p = 0.018) and OS (p = 0.042) in multivariate analysis. Laparoscopic APR showed poorer 5-year DFS (47.8%), 5-year OS (64.0%), and 3-year LR (17.6%) than laparoscopic LAR (74.1%, 86.4%, 1.9%) and laparoscopic LATA (69.2%, 83.6%, 9.2%). Laparoscopic procedures for very low rectal cancer including LAR, LATA, and APR could be good surgical options in selective patients with very low rectal cancer.


Effects of sidestream smoke exposure and age on pulmonary function and airway reactivity in developing rats.
Children exposed to environmental tobacco smoke (ETS) in their homes have increased cough, respiratory illness, airway obstruction, and hyperreactivity. Since an animal model is needed to understand the mechanism by which this occurs, our study was designed to determine if immature rats develop airway obstruction and increased airway reactivity when exposed to sidestream smoke (SSS, respirable suspended particulate concentration 1.00 +/- 0.03 mg/m3, CO concentration 6.48 +/- 0.29 ppm). In the first of 3 studies, rats were exposed to filtered air (FA) or SSS for 6 hr/day, 5 days/week from day 2 to week 8 or week 15 of life (n = 6-8 in each group). SSS exposure did not change lung resistance (RL), dynamic lung compliance (CLdyn), lung weight/body weight ratio (LW/BW), pulmonary artery pressure (PPA), body weight, or airway reactivity to methacholine (all P > 0.2, 2-way ANOVA). Regardless of exposure, lungs from younger rats were relatively heavier and more reactive to methacholine than lungs from older rats (P < 0.05, 2-way ANOVA). In the second study, 15-week-old rats were exposed to FA or SSS for 3 hr or for 4 days (6 hr/day, n = 6 in each group). SSS exposure again had no effect on CLdyn, RL, LW/BW, PPA, or airway reactivity to methacholine (all P > 0.2, ANOVA). In the third study, rats were exposed to FA or SSS from day 2 to week 11 of life (n = 7 in each group). SSS exposure reduced airway (P = 0.004) but not pulmonary artery (P = 0.63) reactivity to serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)


Localized medial triquetral-hamate instability: anatomy and operative reconstruction-augmentation.
Localized medial triquetral-hamate instability (LTHMI) is a relatively uncommon form of wrist instability. After an initial traumatic lesion elongating the triquetral-hamate (TH) complex (TH medial ligament and floor of the extensor carpi ulnaris [ECR] sheath), pain occurs during professional activities demanding ulno-radial movements (polo, tennis, music playing). Imbrication of the TH complex and augmentation with the ECU tendon is suggested for LTHMI.


0.52-11.86 Gbit/s OFDM modulation for power-sharing VLC transmission by using VCSEL laser.
In this paper, we propose employing a 682 nm vertical-cavity surface-emitting laser (VCSEL) with 1 GHz bandwidth for high-speed and power-sharing wireless visible light communication (VLC) in the different transmission distances of 2 to 5 m. In the measurement, the data rate of 0.52 to 11.86 Gbit/s (0.44 to 10.8 Gbit/s in a net data rate) can be achieved by using spectral-efficient orthogonal frequency division multiplexing (OFDM) modulation with bit-loading algorithm. Therefore, 4- to 256-quadrature amplitude modulations (QAMs) are employed simultaneously in the modulation bandwidth for VCSEL-based VLC. The proposed power-sharing VLC system can be divided to four end-users, when three beam splitters (BSs) are used simultaneously. Moreover, all of the measured bit error rates (BERs) are below the forward error correction (FEC) threshold (BER = 3.8 × 10-3).


Nursing student perceptions of nurse-to-nurse collaboration in dedicated education units and in traditional clinical instruction units.
Changes within the health care system have created opportunities for emerging models of care delivery, including collaborative nursing teams. Collaboration between RNs and interprofessional teams supports improved care delivery outcomes. One promising strategy to enhance collaboration is the use of dedicated education units, which are academic-clinical partnerships that facilitate nursing student learning. This descriptive, quantitative study described and compared perceptions of nursing students about nurse-to-nurse collaboration witnessed in dedicated education units and traditional clinical units. Data gathered with the Nurse-to-Nurse Collaboration Scale (NNCS) were analyzed using descriptive statistics and t tests. Findings demonstrate a significant difference on the visual analogue scales for nurse-to-nurse and nurse-to-nursing student collaboration, by type of unit. The NNCS findings indicated differences in the shared processes, coordination, communication, and conflict management subdomains. Further research in the area of collaboration among nurses and dedicated education units is recommended.


Lancing: quo vadis?
Today, lancing fingertips or alternative sites for obtaining a blood sample for self-monitoring of blood glucose (SMBG) is a standard procedure for most patients with diabetes. The need for frequent lancing and associated discomfort and pain can be seen as a key hurdle for patients to comply with SMBG regimens. This article provides an overview of the status quo and future of lancing, focusing on key areas for future developments driven by customer and market needs. We also review technical issues and provide a background for possible improvements. The act of puncturing the skin with a lancet to obtain a blood sample seems to remain the standard procedure for the foreseeable future, because alternate ways of providing a blood sample have not demonstrated overall superiority (e.g., with laser technology). Other methods, which avoid lancing entirely, have also not gained broad market acceptance (e.g., minimally invasive continuous glucose monitoring) or not shown technical viability (e.g., noninvasive glucose monitoring). In relation to blood glucose (BG) meters and test strips, lancing has been a "stepchild" with regards to commercial attention and development efforts. Nevertheless, significant technological improvements have been made in this field to address key customer needs, including better performance (regarding pain, wound healing, and long-term sensitivity), reduced cost, and higher integration with other components of BG monitoring (e.g., integration of the lancing device with the glucose monitor). From a technical perspective, it is apparent that highly comfortable lancing can be accomplished; however, this still requires fairly advanced and complex devices. New developments are necessary to achieve this level of sophistication and performance with less intricate and costly system designs. Manufacturers' motivation to pursue these developments is compromised by the fact that they might not recoup their development cost on commercial advanced lancing systems through direct profits, but only through its positive influence on adherence and increased more profitable sensor utilization. We believe that two main driving forces will continue to push the evolution of lancing and sampling technology: (1) the need for maximum lancing comfort and (2) the advent of fully integrated systems, realizing a device in which all steps for SMBG are incorporated, thus providing a "one-step" experience. Rendering lancing a "nonissue" will eliminate a key barrier to adherence with appropriate SMBG regimens. Providing sophisticated lancing devices that allow the highest level of comfort and/or seamless blood sampling is key to improving user acceptance. This may have a greater impact on metabolic control than many of the new and expensive antidiabetic drugs.


Estimating the Effect of Early Treatment Initiation in Parkinson's Disease Using Observational Data.
Both patients and physicians may choose to delay initiation of dopamine replacement therapy in Parkinson's disease (PD) for various reasons. We used observational data to estimate the effect of earlier treatment in PD. Observational data offer a valuable source of evidence, complementary to controlled trials. We studied the Parkinson's Progression Markers Initiative cohort of patients with de novo PD to estimate the effects of duration of PD treatment during the first 2 years of follow-up, exploiting natural interindividual variation in the time to start first treatment. We estimated the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (primary outcome) and several functionally relevant outcomes at 2, 3, and 4 years after baseline. To adjust for time-varying confounding, we used marginal structural models with inverse probability of treatment weighting and the parametric g-formula. We included 302 patients from the Parkinson's Progression Markers Initiative cohort. There was a small improvement in MDS-UPDRS Part III scores after 2 years of follow-up for patients who started treatment earlier, and similar, but nonstatistically significant, differences in subsequent years. We found no statistically significant differences in most secondary outcomes, including the presence of motor fluctuations, nonmotor symptoms, MDS-UPDRS Part II scores, and the Schwab and England Activities of Daily Living Scale. Earlier treatment initiation does not lead to worse MDS-UPDRS motor scores and may offer small improvements. These findings, based on observational data, are in line with earlier findings from clinical trials. Observational data, when combined with appropriate causal methods, are a valuable source of additional evidence to support real-world clinical decisions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Tailoring 3D single-walled carbon nanotubes anchored to indium tin oxide for natural cellular uptake and intracellular sensing.
The ability to monitor intracellular events in real time is paramount to advancing fundamental biological and clinical science. We present the first demonstration of a direct interface of vertically aligned single-walled carbon nanotubes (VASWCNTs) with eukaryotic cells, RAW 264.7 mouse macrophage cell line. The cells were cultured on indium tin oxide with VASWCNTs. VASWCNTs entered the cells naturally without application of any external force and were shown to sense the intracellular presence of a redox active moiety, methylene blue. The technology developed provides an alluring platform to enable electrochemical study of an intracellular environment.


Rapid Recanalization Using TrevoProVue through a 4.2 Fr Catheter without a Guiding Catheter via Transbrachial Approach: A Case Report.
Mechanical thrombectomy with a stent retriever has been reported to achieve high rates of successful recanalization, and reduce disability and mortality in patients with acute ischemic stroke (AIS) due to proximal vessel occlusion. However, in a few cases, the treatment is difficult due to artery tortuosity or other factors. The authors present a case of a 94-year-old man presenting with acute right middle cerebral artery occlusion. We attempted to treat using a stent retriever via transfemoral approach, but failed to advance the guiding catheter into the right internal carotid artery due to femoral artery tortuosity and a type III arch. By changing approaches from transfemoral to transbrachial and by using TrevoProVue through a 4.2 Fr Simmons-type catheter without a guiding catheter, we were able to achieve rapid recanalization in only 26 minutes from brachial artery puncture to reperfusion. In conclusion, rapid reperfusion in an AIS patient was successfully achieved by combining a stent retriever with a 4.2 Fr catheter (without a guiding catheter) and a transbrachial approach (as opposed to a transfemoral approach). When the transfemoral approach is not feasible, we recommend consideration of this strategy as an alternative.


Associations between socioeconomic status and environmental toxicant concentrations in adults in the USA: NHANES 2001-2010.
Low level chronic exposure to toxicants is associated with a range of adverse health effects. Understanding the various factors that influence the chemical burden of an individual is of critical importance to public health strategies. We investigated the relationships between socioeconomic status (SES) and bio-monitored chemical concentration in five cross-sectional waves of the U.S. National Health and Nutrition Examination Survey (NHANES). We utilised adjusted linear regression models to investigate the association between 179 toxicants and the poverty income ratio (PIR) for five NHANES waves. We then selected a subset of chemicals associated with PIR in 3 or more NHANES waves and investigated potential mediating factors using structural equation modelling. PIR was associated with 18 chemicals in 3 or more NHANES waves. Higher SES individuals had higher burdens of serum and urinary mercury, arsenic, caesium, thallium, perfluorooctanoic acid, perfluorononanoic acid, mono(carboxyoctyl) phthalate and benzophenone-3. Inverse associations were noted between PIR and serum and urinary lead and cadmium, antimony, bisphenol A and three phthalates (mono-benzyl, mono-isobutyl, mono-n-butyl). Key mediators included fish and shellfish consumption for the PIR, mercury, arsenic, thallium and perfluorononanoic acid associations. Sunscreen use was an important mediator in the benzophenone-3/PIR relationship. The association between PIR and cadmium or lead was partially mediated by smoking, occupation and diet. These results provide a comprehensive analysis of exposure patterns as a function of socioeconomic status in US adults, providing important information to guide future public health remediation measures to decrease toxicant and disease burdens within society.


Differences in attitudes regarding teaching and research orientations between allied health faculty and administrators in academic health centers.
The congruence between faculty's and administrators' attitudes toward teaching, research, and the rewards associated with them has implications for the practices the groups follow and for the decisions they make related to promotion, tenure, and merit. This article reports the findings from a national study of allied health faculty and administrators at public academic health centers regarding their attitudes toward teaching, research, and the reward systems related to both. The administrators and faculty at the participating academic health centers did not differ in their views regarding research orientation and rewards related to research. The faculty, including tenured and tenure-track, and department chairs indicated a higher teaching orientation than did the deans, while tenure-track faculty expressed less belief that rewards influence teaching than did tenured faculty, department chairs, and deans.


Effects of whole-body vibration with or without localized radiofrequency on anthropometry, body composition, and motor performance in young nonobese women.
The study investigated the effect of whole-body vibration (WBV) alone and in association with localized radiofrequency on fat deposits in young nonobese subjects. Forty-four (44) healthy, nonobese women aged 25.3±5.26 years, body-mass index (BMI) 21.7±2.47 kg/m(2) were randomly assigned to an 8-week trial of WBV (2 sessions per week) or WBV plus localized radiofrequency (WBV+RF) in the abdominal, buttock, and thigh region. Anthropometry, body composition (dual-energy x-ray absorptiometry, DXA), and motor performance were assessed before and after the trial. Data were analyzed by one-way analysis of variance (ANOVA) or ANOVA for repeated measures (group×time). Valid data were obtained for 36 women (WBV, n=18; WBV+RF, n=18). Body mass and BMI did not change after trial. Body circumferences were unchanged or slightly reduced, with no difference between groups. Skinfold thickness was significantly reduced at several sites in the whole study population (n=36), reduction being higher at the thigh site in the WBV+RF group. According to DXA analysis, total body lean mass increased (p=0.009) and total body fat mass decreased (p=0.036) in the whole study population after trial with no significant difference between the WBV and WBV+RF group in spite of larger absolute changes in the latter. Standing long jump improved after trial with no change in flamingo balance test. An 8-week WBV training is effective in inducing positive body composition changes as well as increased muscle strength in women; it could be recommended as an alternative/complementary tool in physical activity or fitness programs as it is well tolerated. The current data give limited support to the association of localized RF treatment and WBV training as synergistic in inducing body fat mass loss; such a beneficial effect should be further investigated in subject with larger subcutaneous fat deposits (i.e., overweight or obese).