Effects of staining and bleaching procedures on the optical and surface properties of CAD-CAM materials.
To examine the effects of coffee staining and bleaching applications on the optical properties of CAD-CAM blocks, and to provide a three-dimensional visualization of surface changes with atomic force microscope (AFM). 80 samples were prepared from four different CAD-CAM blocks: [Cerec (CR), Shofu (SH), Cerasmart (CRS), Lava Ultimate (LU)], and a microhybrid composite resin [Filtek Z250 (Z250)]. After staining, the samples were divided into two subgroups according to bleaching methods: 16% carbamide peroxide (HB), and 40% hydrogen peroxide (OB). Color measurements were performed at baseline (t₀), after staining (t₁), and after bleaching (t₂) to obtain translucency parameters (TP₀₀), color change (ΔE₀₀), and whiteness index (WID) values. Surface roughness analysis (Ra) was performed with AFM after coffee staining and bleaching procedures (at t₁ and t₂). Data were analyzed with Generalized Linear Model, and Bonferroni correction (P< 0.05). TP₀₀ values increased only in the CRS group after the bleaching application, and the effect of method was again observed only in CRS. While bleaching increased WID values of all groups except CRS, no difference was found between bleaching methods. Regardless of evaluation time, the roughest group is Z250, and the only difference between bleaching methods was observed in the CR group. In conclusion, the effects of staining and bleaching applications on the optical and surface properties of CAD-CAM blocks are material-dependent. Effective bleaching of discolored CAD-CAM materials was achieved regardless of the bleaching method used, and without any significant adverse effect on the surface properties of the materials.


Dolichyl-phosphate-glucose is used to make O-glycans on glycoproteins of Trichomonas vaginalis.
Trichomonas vaginalis, the protist that causes vaginal itching, has a huge genome with numerous gene duplications. Recently we found that Trichomonas has numerous genes encoding putative dolichyl-phosphate-glucose (Dol-P-Glc) synthases (encoded by ALG5 genes) despite the fact that Trichomonas lacks the glycosyltransferases (encoded by ALG6, ALG8, and ALG10 genes) that use Dol-P-Glc to glucosylate dolichyl-PP-linked glycans. In addition, Trichomonas does not have a canonical DPM1 gene, encoding a dolichyl-P-mannose (Dol-P-Man) synthase. Here we show Trichomonas membranes have roughly 300 times the Dol-P-Glc synthase activity of Saccharomyces cerevisiae membranes and about one-fifth the Dol-P-Man synthase activity of Saccharomyces membranes. Endogenous Dol-P-hexoses of Trichomonas are relatively abundant and contain 16 isoprene units. Five paralogous Trichomonas ALG5 gene products have Dol-P-Glc synthase activity when expressed as recombinant proteins, and these Trichomonas Alg5s correct a carboxypeptidase N glycosylation defect in a Saccharomyces alg5 mutant in vivo. A recombinant Trichomonas Dpm1, which is deeply divergent in its sequence, has Dol-P-Man synthase activity. When radiolabeled Dol-P-Glc is incubated with Trichomonas membranes, Glc is incorporated into reducing and nonreducing sugars of O-glycans of endogenous glycoproteins. To our knowledge, this is the first demonstration of Dol-P-Glc as a sugar donor for O-glycans on glycoproteins.


Harmonic Alignment.
We propose a novel framework for combining datasets via alignment of their intrinsic geometry. This alignment can be used to fuse data originating from disparate modalities, or to correct batch effects while preserving intrinsic data structure. Importantly, we do not assume any pointwise correspondence between datasets, but instead rely on correspondence between a (possibly unknown) subset of data features. We leverage this assumption to construct an isometric alignment between the data. This alignment is obtained by relating the expansion of data features in harmonics derived from diffusion operators defined over each dataset. These expansions encode each feature as a function of the data geometry. We use this to relate the diffusion coordinates of each dataset through our assumption of partial feature correspondence. Then, a unified diffusion geometry is constructed over the aligned data, which can also be used to correct the original data measurements. We demonstrate our method on several datasets, showing in particular its effectiveness in biological applications including fusion of single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) data measured on the same population of cells, and removal of batch effect between biological samples.


Neutralizing Antibody Response and Efficacy of Novel Recombinant Tetravalent Dengue DNA Vaccine Comprising Envelope Domain III in Mice.
Dengue is a global arboviral threat to humans; causing 390 million infections per year. The availability of safe and effective tetravalent dengue vaccine is a global requirement to prevent epidemics, morbidity, and mortality associated with it. Five experimental groups (6 mice per group) each of 5-week-old BALB/c mice were immunized with vaccine and placebo (empty plasmid) (100 µg, i.m.) on days 0, 14 and 28. Among these, four groups (one group per serotype) of each were subsequently challenged 3 weeks after the last boost with dengue virus (DENV) serotypes 1-4 (100 LD50, 20 µl intracerebrally) to determine vaccine efficacy. The fifth group of each was used as a control. The PBS immunized group was used as mock control. Serum samples were collected before and after subsequent immunizations. EDIII fusion protein expression was determined by Western blot. Total protein concentration was measured by Bradford assay. Neutralizing antibodies were assessed by TCID50-CPE inhibition assay. Statistical analysis was performed using Stata/IC 10.1 software for Windows. One-way repeated measures ANOVA and Mann-Whitney test were used for neutralizing antibody analysis and vaccine efficacy, respectively. The recombinant EDIII fusion protein was expressed adequately in transfected 293T cells. Total protein concentration was almost 3 times more than the control. Vaccine candidate induced neutralizing antibodies against all four DENV serotypes with a notable increase after subsequent boosters. Vaccine efficacy was 83.3% (DENV-1, -3, -4) and 50% (DENV-2). Our results suggest that vaccine is immunogenic and protective; however, further studies are required to improve the immunogenicity particularly against DENV-2.


Adiponectin increases LPL activity via RhoA/ROCK-mediated actin remodelling in adult rat cardiomyocytes.
Cardiomyocyte substrate utilization is important in maintaining optimal cardiac function. Adiponectin has been shown to confer cardioprotective effects in part via regulating glucose and fatty acid uptake and oxidation in cardiomyocytes. Here we investigated mechanisms whereby adiponectin mediates a particular metabolic effect by focusing on lipoprotein lipase (LPL), an enzyme that increases free fatty acid availability to the heart by breakdown of chylomicrons and very-low-density lipoproteins in circulation. We used primary adult rat cardiomyocytes and demonstrate that adiponectin increased LPL translocation to the cell surface where it could be released at least partly in its active form, as evidenced by measuring basal and heparin-releasable LPL activity. Furthermore, these effects of adiponectin were mediated via remodeling of the actin cytoskeleton. We quantitatively assessed the filamentous to globular actin ratio and show that increased stress fiber formation, visualized by rhodamine-phalloidin immunofluorescence, in response to adiponectin, is achieved via stimulating Ras homolog gene family A (RhoA) activity, determined using G-LISA RhoA activation assay kit. We also demonstrate that adiponectin induces phosphorylation and inhibition of cofilin, leading to a reduction in actin treadmilling. Increased cofilin phosphorylation and stress fiber formation in response to adiponectin were prevented by inhibition of either RhoA or its downstream kinase Rho-associated protein kinase. Importantly, inhibition of cytoskeletal remodeling prevented adiponectin-stimulated plasma membrane LPL content detected by immunofluorescence and also subsequent LPL activity. In summary, we show that adiponectin mediates actin cytoskeleton remodeling to translocate LPL and allow subsequent activation.


A long-term experimental test of the dynamic equilibrium model of species diversity.
The dynamic equilibrium model of species diversity predicts that ecosystem productivity interacts with disturbance to determine how many species coexist. However, a robust test of this model requires manipulations of productivity and disturbance over a sufficient timescale to allow competitive exclusion, and such long-term experimental tests of this hypothesis are rare. Here we use long-term (27 years), large-scale (8 × 50-m plots), factorial manipulations of soil resource availability and sheep grazing intensity (disturbance) in grasslands to test the dynamic equilibrium model. As predicted by the model, increased productivity not only reduced plant species richness, but also moderated the effects of grazing intensity, shifting them from negative to neutral with increasing productivity. Reductions in species richness with productivity were associated with dominance by faster growing (i.e. high specific leaf area) and taller plants. Conversely, grazing favoured shorter plants and this effect became stronger with greater productivity, consistent with the view that grazing can lead to weaker asymmetric competition for light. Our study shows that the dynamic equilibrium model can help to explain changes in plant species richness following long-term increases in soil resource availability and grazing pressure, two fundamental drivers of change in grasslands worldwide.


[Effect of the diet enriched in the polyunsaturatted fatty, acids of the fish oil on phospholipid turnover and cognitive function of the old rats].
The aim of this research was to examine possible role of dietary n-3 fatty acids in modulation of the age-related changes in phospholipid exchange in the rat hippocampus and cognitive function. In the hippocampus of fish oil-fed 24-month-old phosphatidylserine (PS) level was found to be increased whereas phosphatidylcholine (PC) and phosphatidylethanolamine (PE) contents decreased as compared with control group. However, fish oil exerted no effect on the PS synthesis de novo and decreased PC and PE synthesis in the hippocampus of old rats. In shuttle box active avoidance test, fish oil-treated rats showed an increase in the number of avoidances in the learning session.


Associations between self-reported symptoms of prenatal maternal infection and post-traumatic stress disorder in offspring: evidence from a prospective birth cohort study.
Consistent evidence has linked a range of prenatal maternal infections with psychotic disorders in later life. However, the potential for this exposure to impact more common disorders requires further investigation. Participants came from the Mater University Study of pregnancy, a longitudinal, pre-birth cohort study which recruited pregnant mothers from a Brisbane hospital between 1981 and 1984. At age 21, 2439 offspring completed the CIDI-Auto. Multivariate logistic regression was used to investigate associations of self-reported symptoms of prenatal infection with a range of DSM-IV anxiety and affective diagnoses, while also testing for gender interactions. In multivariate analyses, self-reported symptoms of prenatal genital infection predicted Post-traumatic stress disorders (OR=2.38, 95% CI: 1.14, 4.95) and social phobias (OR=1.93, 95% CI: 1.03, 3.61), in addition to evidence for a gender interaction by which males (OR=6.04, 95% CI: 2.00, 18.30) but not females were at greater risk for PTSD. Further analyses among those with PTSD revealed the relationship to be stronger when excluding those not exposed to trauma (OR=3.21, 95% CI: 1.53, 6.72). We were unable to clinically or serologically verify the presence and the type of prenatal genital infection. This is the first study to show an association between self-reported symptoms of prenatal genital infections and two highly prevalent anxiety disorders among adult offspring. The relationship with PTSD was particularly strong and suggested that the exposure may primarily impact PTSD in males. Further research with the capacity to assess a fuller-range of specific prenatal infections is warranted to evaluate the potential of reducing the prevalence of these disorders.


The emerging role of psychiatric pharmacists.
The concept of pharmaceutical care has greatly expanded the role of the pharmacist, from that of strictly a drug dispenser to a more integrated member of a patient's healthcare team. In order for pharmaceutical care practice to succeed, the pharmacist must assume a more proactive role, using his or her knowledge of drug therapy and behavioral medicine to assume more responsibility in achieving improvement in patient health outcomes. The pharmacist must also develop open, professional relationships with patients, their families/caregivers, and other members of the healthcare team. Pharmaceutical care comprises 4 components: education, medical-legal issues, drug therapy knowledge, and communication. Through these efforts, and because pharmacists offer greater access to patients and a broader view of patient outcomes, pharmaceutical care affords the opportunity for these professionals to become patient advocates and prevent line-item decision making. Special considerations exist for psychiatric pharmacists practicing pharmaceutical care, especially in documentation and formulary decisions. Psychiatric pharmacists can ensure that patients have access to the safest, most efficacious (and cost-effective) drugs by considering more than just acquisition costs.


Effect of postprandial posture on digestion and absorption of dietary carbohydrate.
The effect of postprandial body posture on digestion and absorption of dietary carbohydrate were examined through breath hydrogen test on 6 female subjects. During the experiment, the participants either sat on a chair or lay on their backs for the first 4 hr (from 08:00 to 12:00) after eating the test breakfast meal. They then remained sedentary on a sofa for 6 hr (12:00 to 18:00). Participants' end alveolar breath samples were collected for 10 hr (every 15 min from 08:00 to 12:30, and then every 30 min until 18:00). The experiment was conducted on two consecutive days using a randomized, crossover study design. The results demonstrated that in the supine position orocecal transit time of the test meal was significantly slower than in the sitting position (260 +/- 21 min and 238 +/- 20 min, respectively, p < 0.01). In addition, afternoon breath hydrogen excretion due to a partial malabsorption of dietary carbohydrate and its fermentation in the colon was significantly larger in the sitting position (144.0 +/- 24.1 ppm.hr) than in the supine position (110.0 +/- 26.1 ppm.hr, p < 0.05). These results support the hypothesis that there was a marked effect of postprandial body posture on the function of the digestive system. The present findings suggest that the postprandial supine position is preferable to the sitting position for the digestion and absorption of dietary carbohydrate.


Computer vision-based assessment of cyclist-tram track interactions for predictive modeling of crossing success.
Single Bicycle Brashes (SBCs) are common, and underreported in official statistics. In urban environments, light rail tram tracks are a frequent factor, however, they have not yet been the subject of engineering analysis. This study employs video-based analysis at nine Dublin city centre locations and introduces a predictive model for crossing success on tram tracks, utilising cyclist crossing angles within a Surrogate Measure of Safety (SMoS) framework. Additionally, Convolutional Neural Networks (CNNs) were explored for automatic estimation of crossing angles. Modelling results indicate that cyclist crossing angle is a strong predictor of crossing success, and that cyclist velocity is not. Findings also highlight the prevalence of external factors which limit crossing angles for cyclists. In particular, kerbs are a common factor, along with passing/approaching vehicles or other cyclists. Furthermore, results indicate that further training on a relatively small sample of 100 domain-specific examples can achieve substantial accuracy improvements for cyclist detection (from 0.31AP0.5 to 0.98AP0.5) and crossing angle inference from traffic camera footage. Ensuring safe crossing angles is important for cyclist safety around tram tracks. Infrastructural planners should aim for intuitive, self-explainable road layouts that allow for and encourage crossing angles of 60° or more - ideally 90°. The SMoS framework and the open-source SafeCross1 application offer actionable insights and tools for enhancing cyclist safety around tram tracks.


The serum metabolomic study of intervention effects of the traditional Chinese medicine Shexiang Baoxin Pill and a multi-component medicine polypill in the treatment of myocardial infarction in rats.
A metabolomic approach based on liquid chromatography coupled with quadrupole time-of-flight detector (LC-Q-TOF/MS) was developed to investigate the therapeutic mechanism of a traditional Chinese medicine (TCM) formula Shexiang Baoxin Pill (SBP) and a multi-component medicine polypill (consisting of simvastatin (Sim), atenolol (Ate), ramipril (Ram), hydrochlorthiazide (Hyd) and aspirin (Asp), named as SARHA). Twenty-seven biomarkers were identified in the serum of MI rats. Thirteen related pathways and 4 main pathological processes including oxidative injury, energy metabolism dysfunction, amino acid metabolism dysfunction and inflammation are involved in MI development. Our study revealed that SBP showed better therapeutic effectiveness than the polypill on MI through regulation of the energy metabolism dysfunction, oxidative injury and inflammation. The combination agent polypill had only certain therapeutic effects on inhibiting oxidative injury and inflammation induced by MI. The reverse effect of the polypill on biomarkers related to MI was much better than mono-therapy groups.


A randomized controlled trial of mindfulness to reduce stress and burnout among intern medical practitioners.
Stress and burnout are highly prevalent among medical doctors, and are associated with negative consequences for doctors, patients, and organizations. The purpose of the current study was to examine the effectiveness of a mindfulness training intervention in reducing stress and burnout among medical practitioners, by means of a Randomised Controlled Trial design. Participants were 44 intern doctors completing an emergency department rotation in a major Australian hospital. Participants were randomly assigned to either an active control (one hour extra break per week) or the 10-week mindfulness training intervention. Measures of stress and burnout were taken pre-, mid- and post intervention. Participants undergoing the 10-week mindfulness training program reported greater improvements in stress and burnout relative to participants in the control condition. Significant reduction in stress and burnout was observed for participants in the mindfulness condition. No such reductions were observed for participants in the control condition. Mindfulness interventions may provide medical practitioners with skills to effectively manage stress and burnout, thereby reducing their experience of these symptoms. It is likely that doctors would benefit from the inclusion of such a training program as a part of their general medical education.


Characterization of lipid in loin and bacon from finishing pigs fed full-fat soybeans or tallow.
This experiment tested whether the lipid composition of pork could be altered by changes in dietary lipid, that what effects these changes would have on production and meat characteristics. Pigs were fed diets containing 10 or 20%+ extruded full-fat soybeans (FFS) or 4% tallow for a 3- or 6-wk finishing period, with a corn-soybean meal diet fed as a control. Seventy barrows and 70 gilts were allotted into seven treatment groups with four pens per group. Analysis was on 28 experimental units, which were composite samples from pens. The significance of treatment, sex, and treatment x sex interaction F-statistics was evaluated on chloroform-methanol extractable total lipid, triacylglycerol, phospholipids, cholesterol, individually fatty acids (FA), and the major classes of FA obtained from longissimus muscle and bacon. Treatment effects (P less than .05) were detected for cholesterol content of longissimus and for total lipid and phospholipid content of bacon. Treatment effects (P less than .01) were detected for monoenoic, dienoic, and polyenoic (P) FA in both tissues, and for saturated (S) FA in bacon (P less than .05). Treatment effects (P less than .001) were detected in both tissues for the P:S ratio. The P:S ratio increased 54% for longissimus and 100% for bacon in the pigs fed FFS for 6 wk compared with pigs consuming a corn-soybean meal diet.


Use of Nitric Oxide and Hydrogen Peroxide for Better Yield of Wheat (Triticum aestivum L.) under Water Deficit Conditions: Growth, Osmoregulation, and Antioxidative Defense Mechanism.
The present experiment was carried out to study the influences of exogenously-applied nitric oxide (NO) donor sodium nitroprusside (SNP) and hydrogen peroxide (H2O2) as seed primers on growth and yield in relation with different physio-biochemical parameters, antioxidant activities, and osmolyte accumulation in wheat plants grown under control (100% field capacity) and water stress (60% field capacity) conditions. During soaking, the seeds were covered and kept in completely dark. Drought stress markedly reduced the plant growth, grain yield, leaf photosynthetic pigments, total phenolic content (TPC), total soluble proteins (TSP), leaf water potential (Ψw), leaf turgor potential (Ψp), osmotic potential (Ψs), and leaf relative water content (LRWC), while it increased the activities of enzymatic antioxidants and the accumulation of leaf ascorbic acid (AsA), proline (Pro), glycine betaine (GB), malondialdehyde (MDA), and H2O2. However, seed priming with SNP and H2O2 alone and in combination mitigated the deleterious effects of water stress on growth and yield by improving the Ψw, Ψs, Ψp, photosynthetic pigments, osmolytes accumulation (GB and Pro), TSP, and the antioxidative defense mechanism. Furthermore, the application of NO and H2O2 as seed primers also reduced the accumulation of H2O2 and MDA contents. The effectiveness was treatment-specific and the combined application was also found to be effective. The results revealed that exogenous application of NO and H2O2 was effective in increasing the tolerance of wheat plants under drought stress in terms of growth and grain yield by regulating plant-water relations, the antioxidative defense mechanism, and accumulation of osmolytes, and by reducing the membrane lipid peroxidation.


On-line hemodiafiltration in the large RISCAVID study.
Despite significant advances in hemodialysis (HD) and medical therapy, mortality rates in patients with chronic kidney disease stage 5 (CKD-5D) remain unacceptably high, with cardiovascular (CV) mortality risk in dialysis patients being several times higher than that of a general population. The CV mortality risk of a 25-to 34-year-old dialysis patient is approximately the same as the one of an otherwise healthy person aged over 85 in the general population. HD patients are not only exposed to the various traditional risk factors valid for the general population but in addition also to the non-traditional risk factors resulting either from uremia per se or from the dialysis treatment. Our understanding of chronic inflammation in CKD-5D and of its influence in the accelerated atherosclerotic process has greatly evolved. Dialysis therapy, performed efficiently, has the potential to provide CKD-5D patients with benefits beyond the life-saving function of removal accumulated waste products and excess fluid. There is sufficient evidence to indicate that on-line hemodiafiltration has the potential to improve chronic inflammation, fluid overload, left ventricular hypertrophy, anemia and quality of life of CKD-5D patients. In the search for more effective, safer and less expensive approaches to the management of the above conditions, an innovative concept of biocompatibility should be broadened to the HD system/patient evaluation. Here, we intend to present new insights obtained from a prospective observational study (RISCAVID, 'RISchio CArdiovascolare nei pazienti afferenti all'Area Vasta In Dialisi') performed on a large HD population in the northwestern region of Tuscany, Italy, on the assessment of the different parameters of chronic inflammation and gross/CV mortality and anemia management.


The human motor neuron axonal transcriptome is enriched for transcripts related to mitochondrial function and microtubule-based axonal transport.
Local axonal translation of specific mRNA species plays an important role in axon maintenance, plasticity during development and recovery from injury. Recently, disrupted axonal mRNA transport and translation have been linked to neurodegenerative disorders. To identify mRNA species that are actively transported to axons and play an important role in axonal physiology, we mapped the axonal transcriptome of human induced pluripotent stem cell (iPSC)-derived motor neurons using permeable inserts to obtain large amounts of enriched axonal material for RNA isolation and sequencing. Motor neurons from healthy subjects were used to determine differences in gene expression profiles between neuronal somatodendritic and axonal compartments. Our results demonstrate that several transcripts were enriched in either the axon or neuronal bodies. Gene ontology analysis demonstrated enrichment in the axonal compartment for transcripts associated with mitochondrial electron transport, microtubule-based axonal transport and ER-associated protein catabolism. These results suggest that local translation of mRNAs is required to meet the high-energy demand of axons and to support microtubule-based axonal transport. Interestingly, several transcripts related to human genetic disorders associated with axonal degeneration (inherited axonopathies) were identified among the mRNA species enriched in motor axons.


Relationship of benign papillomas to cancer induction in mouse skin.
An analysis is presented for evaluating the potency of initiators, promoters, and carcinogens based on the number of tumors that occur as a function of dose and time when compounds are applied topically in an appropriate solvent to mouse skin. A given compound was tested as an initiator (a single dose followed by prolonged promotion), as a whole carcinogen (multiple applications for a prolonged period of time), and as a cocarcinogen (multiple applications for a prolonged period of time in combination with promotion). Compounds tested were 7,12 dimethylbenz(a)anthracene (DMBA), benzo(a)pyrene (B(a)P), 4-nitroquinoline-1-oxide (4-NQO), and betapropriolactone (BPL). The results indicated that various types of papillomas were produced in proportion to the dose applied to DMBA, B(a)P, and BPL. Certain of these papillomas were nonregressible and progressed readily to carcinomas; others regressed and did not progress to cancer. Multiple doses of DMBA and B(a)P produced carcinomas without an antecedent papilloma stage. The latter cancers were produced in proportion to the 2nd or 3rd power of applied carcinogen dose and were accelerated strongly by concomitant action of a promoter. Certain nonregressible papillomas probably represent the first step in a two or three step progression to cancer, although cancers from papillomas occur in proportion to dose.


Distinguishing and grading human gliomas by IR spectroscopy.
As a molecular probe of tissue composition, IR spectroscopy can potentially serve as an adjunct to histopathology in detecting and diagnosing disease. This study demonstrates that cancerous brain tissue (astrocytoma, glioblastoma) is distinguishable from control tissue on the basis of the IR spectra of thin tissue sections. It is further shown that the IR spectra of astrocytoma and glioblastoma affected tissue can be discriminated from one another, thus providing insight into the malignancy grade of the tissue. Both the spectra and the methods employed for their classification reveal characteristic differences in tissue composition. In particular, the nature and relative amounts of brain lipids, including both the gangliosides and phospholipids, appear to be altered in cancerous compared to control tissue. Using a genetic classification approach, classification success rates of up to 89% accuracy were obtained, depending on the number of regions included in the model. The diagnostic potential and practical applications of IR spectroscopy in brain tumor diagnosis are discussed.


Sulfur-dioxide-induced bronchitis in dogs. Effects on airway responsiveness to inhaled and intravenously administered methacholine.
Chronic bronchitis was induced in 7 dogs of mixed breed by chronic exposure to SO2 gas. Within the first 2 to 4 wk of exposure, the dogs developed cough and mucous hypersecretion, chronic airway obstruction (increased pulmonary resistance), and persistent lung inflammation as demonstrated by an increase in the number of neutrophils recovered in the bronchoalveolar lavage (BAL) fluid. Airway responsiveness to methacholine aerosol decreased 2- to 3-fold within 8 wk of SO2 exposure. In contrast, airway responsiveness to intravenous administration of methacholine did not change. The data suggest that the decreased airway responsiveness observed during persistent pulmonary inflammation in SO2-exposed dogs is not due to an altered state of airway contractile elements but likely reflects expression of an inhibitory influence of the mucoepithelial barrier.


Causes of outbreaks associated with drinking water in the United States from 1971 to 2006.
Since 1971, the CDC, EPA, and Council of State and Territorial Epidemiologists (CSTE) have maintained the collaborative national Waterborne Disease and Outbreak Surveillance System (WBDOSS) to document waterborne disease outbreaks (WBDOs) reported by local, state, and territorial health departments. WBDOs were recently reclassified to better characterize water system deficiencies and risk factors; data were analyzed for trends in outbreak occurrence, etiologies, and deficiencies during 1971 to 2006. A total of 833 WBDOs, 577,991 cases of illness, and 106 deaths were reported during 1971 to 2006. Trends of public health significance include (i) a decrease in the number of reported outbreaks over time and in the annual proportion of outbreaks reported in public water systems, (ii) an increase in the annual proportion of outbreaks reported in individual water systems and in the proportion of outbreaks associated with premise plumbing deficiencies in public water systems, (iii) no change in the annual proportion of outbreaks associated with distribution system deficiencies or the use of untreated and improperly treated groundwater in public water systems, and (iv) the increasing importance of Legionella since its inclusion in WBDOSS in 2001. Data from WBDOSS have helped inform public health and regulatory responses. Additional resources for waterborne disease surveillance and outbreak detection are essential to improve our ability to monitor, detect, and prevent waterborne disease in the United States.


[Functional activity of specific antibodies in patients vaccinated against tick-borne encephalitis in relation to different virus strains].
The paper shows variability of the functional activity of the superficial structures of three Far Eastern strains of tick-borne encephalitis (TBE) virus used to study the immunogenicity of different vaccines. The avidity antibodies to the study TBE virus strains were not detected in all of the persons vaccinated with different TBE vaccines even in the year of immunization. Two years after a course of vaccination, immune response and antibody avidity were decreased in the vaccinees. The persons vaccinated with "eastern" vaccines were better protected against Sofjin-like strain P-73 that had led to a fatal outcome in a patient with TBE. Those vaccinated with "western" strain vaccines were found to have a higher affinity for antibodies to the strains P-202 and P-69 that caused inapparent TBE in the year of immunization and 2 years later. A group of persons vaccinated with both "western" and "eastern" vaccines in different periods showed rather high antibody avidities.


Effect of percutaneous ventricular assisted device on post-cardiac arrest myocardial dysfunction in swine model with prolonged cardiac arrest.
It remains unclear if percutaneous left ventricular assist device (pLVAD) reduces post-cardiac arrest myocardial dysfunction. This is a prespecified analysis of a subset of swine that achieved return of spontaneous circulation (ROSC) in a study comparing pLVAD, transient aortic occlusion (AO), or both during cardiopulmonary resuscitation (CPR). Devices were initiated after 24 minutes of ventricular fibrillation cardiac arrest (8 min no-flow and 16 min mechanical CPR). AO was discontinued post-ROSC, and pLVAD support or standard care were continued. Beginning 60 minutes post-ROSC, pLVAD support was weaned to < 1.0 L/min and subsequently removed at 240 minutes. The primary outcome was cardiac index (CI), stroke volume index (SVI), and left ventricular ejection fraction (LVEF) at 240 minutes post-ROSC. Data are shown as mean (standard error). Seventeen swine achieved ROSC without complication and were included in this analysis (pLVAD group, n = 11 and standard care group, n = 6). For the primary outcomes, the pLVAD group had significantly higher CI of 4.2(0.3) vs. 3.1(0.4) L/min/m2 (p = 0.043) and LVEF 60(3) vs. 49(4) % (p = 0.029) at 240 minutes after ROSC when compared with the standard care group, while SVI was not statistically significantly different (32[3] vs. 23[4] mL/min/m2, p = 0.054). During the first 60 minutes post-ROSC, the pLVAD group had significantly higher coronary perfusion pressure, lower LV stroke work index, and total pulmonary resistance index. These results suggest that early pLVAD support after ROSC is associated with better recovery myocardial function compared to standard care after prolonged cardiac arrest.


X-ray absorption spectroscopy study of the hydrogen bond network in the bulk water of aqueous solutions.
We utilized X-ray absorption spectroscopy (XAS) and X-ray Raman scattering (XRS) in order to study the ion solvation effect on the bulk hydrogen bonding structure of water. The fine structures in the X-ray absorption spectra are sensitive to the local environment of the probed water molecule related to the hydrogen bond length and angles. By varying the concentration of ions, we can distinguish between contributions from water in the bulk and in the first solvation sphere. We show that the hydrogen bond network in bulk water, in terms of forming and breaking hydrogen bonds as detected by XAS/XRS, remains unchanged, and only the water molecules in the close vicinity to the ions are affected.


Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids.
Exosomes are naturally occurring biological nanomembranous vesicles (∼40 to 100 nm) of endocytic origin that are released from diverse cell types into the extracellular space. They have pleiotropic functions such as antigen presentation and intercellular transfer of protein cargo, mRNA, microRNA, lipids, and oncogenic potential. Here we describe the isolation, via sequential immunocapture using anti-A33- and anti-EpCAM-coupled magnetic beads, of two distinct populations of exosomes released from organoids derived from human colon carcinoma cell line LIM1863. The exosome populations (A33-Exos and EpCAM-Exos) could not be distinguished via electron microscopy and contained stereotypical exosome markers such as TSG101, Alix, and HSP70. The salient finding of this study, revealed via gel-based LC-MS/MS, was the exclusive identification in EpCAM-Exos of the classical apical trafficking molecules CD63 (LAMP3), mucin 13 and the apical intestinal enzyme sucrase isomaltase and increased expression of dipeptidyl peptidase IV and the apically restricted pentaspan membrane glycoprotein prominin 1. In contrast, the A33-Exos preparation was enriched with basolateral trafficking molecules such as early endosome antigen 1, the Golgi membrane protein ADP-ribosylation factor, and clathrin. Our observations are consistent with EpCAM- and A33-Exos being released from the apical and basolateral surfaces, respectively, and the EpCAM-Exos proteome profile with widely published stereotypical exosomes. A proteome analysis of LIM1863-derived shed microvesicles (sMVs) was also performed in order to clearly distinguish A33- and EpCAM-Exos from sMVs. Intriguingly, several members of the MHC class I family of antigen presentation molecules were exclusively observed in A33-Exos, whereas neither MHC class I nor MHC class II molecules were observed via MS in EpCAM-Exos. Additionally, we report for the first time in any extracellular vesicle study the colocalization of EpCAM, claudin-7, and CD44 in EpCAM-Exos. Given that these molecules are known to complex together to promote tumor progression, further characterization of exosome subpopulations will enable a deeper understanding of their possible role in regulation of the tumor microenvironment.


Transition to parenthood: the role of social interaction and endogenous networks.
Empirical studies indicate that the transition to parenthood is influenced by an individual's peer group. To study the mechanisms creating interdependencies across individuals' transition to parenthood and its timing, we apply an agent-based simulation model. We build a one-sex model and provide agents with three different characteristics: age, intended education, and parity. Agents endogenously form their network based on social closeness. Network members may then influence the agents' transition to higher parity levels. Our numerical simulations indicate that accounting for social interactions can explain the shift of first-birth probabilities in Austria during the period 1984 to 2004. Moreover, we apply our model to forecast age-specific fertility rates up to 2016.


Is Reperfusion Useful in Ischaemic Stroke Patients Presenting with a Low National Institutes of Health Stroke Scale and a Proximal Large Vessel Occlusion of the Anterior Circulation?
In population-based studies, patients presenting with minor or mild stroke symptoms represent about two-thirds of stroke patients, and almost one-third of these patients are unable to ambulate independently at the time of discharge. Although mechanical thrombectomy (MT) has become the standard of care for acute ischaemic stroke with proximal large vessel occlusion (LVO) in the anterior circulation, the management of patients harbouring proximal occlusion and minor-to-mild stroke symptoms has not yet been determined by recent trials. The purpose of this study was to evaluate the impact of reperfusion on clinical outcome in low National Institutes of Health Stroke Scale (NIHSS) patients treated with MT. We analysed 138 consecutive patients with acute LVO of the anterior circulation (middle cerebral artery M1 or M2 segment, internal carotid artery or tandem occlusion) with NIHSS <8, having undergone MT in 3 different centres. Reperfusion was graded using the modified thrombolysis in cerebral infarction (TICI) score and 3 grades were defined, ranging from failed or poor reperfusion (TICI 0, 1, 2A) to complete reperfusion (TICI 3). The primary clinical endpoint was an excellent outcome defined as a modified Rankin score (mRs) 0-1 at 3-months. The impact of reperfusion grade was assessed in univariate and multivariate analyses. The secondary endpoints included favourable functional outcome (90-day mRS 0-2), death and safety concerns. Successful reperfusion was achieved in 81.2% of patients (TICI 2B, n = 47; TICI 3, n = 65). Excellent outcome (mRs 0-1) was achieved in 69 patients (65.0%) and favourable outcome (mRs ≤2) in 108 (78.3%). Death occurred in 7 (5.1%). Excellent outcome increased with reperfusion grades, with a rate of 34.6% in patients with failed/poor reperfusion, 61.7% in patients with TICI 2B reperfusion, and 78.5% in patients with TICI 3 reperfusion (p < 0.001). In multivariate analysis adjusted for patient characteristics associated with excellent outcome, the reperfusion grade remained significantly associated with an increase in excellent outcome; the OR (95% CI) was 3.09 (1.06-9.03) for TICI 2B and 6.66 (2.27-19.48) for TICI 3, using the failed/poor reperfusion grade as reference. Similar results were found regarding favourable outcome (90-day mRs 0-2) or overall mRS distribution (shift analysis). Successful reperfusion is strongly associated with better functional outcome among patients with proximal LVO in the anterior circulation and minor-to-mild stroke symptoms. Randomized controlled studies are mandatory to assess the benefit of MT compared with optimal medical management in this subset of patients.


Identification of a mechanism for increased cardiovascular risk among individuals with low vitamin D concentrations.
The aim of this study was to investigate the plasma concentrations of vitamin D and its association with plasma lipid profiles. Plasma vitamin D3 and lipid concentrations were measured in 119 female cynomolgus monkeys (premenopausal, n = 49; ovariectomized, n = 70) consuming approximately 1,000 IU per day of vitamin D3. In a subset of the ovariectomized monkeys (n = 23), vitamin D3 was remeasured after 6 months. The concentrations of vitamin D3 were analyzed as a continuous variable and were divided at the median into high (≥48 ng/mL) versus low (<48 ng/mL) groupings. Among the 119 monkeys, the range of vitamin D3 concentrations was 24.0 to 95.2 ng/mL (mean ± SD, 48.5 ± 12.7 ng/mL). Plasma vitamin D3 concentration was positively associated with high-density lipoprotein cholesterol (HDL-C; P = 0.003). Monkeys in the high vitamin D3 group had a significantly greater plasma HDL-C concentration (57.9 mg/dL) than did those in the low vitamin D3 group (47.1 mg/dL; P = 0.001). Although the difference was not significant (P = 0.120), the monkeys in the high vitamin D3 group had a decreased total plasma cholesterol-to-HDL-C ratio compared with those in the low vitamin D3 group (5.4 and 6.2, respectively), potentially putting them at lower risk of atherosclerosis development. Given that the monkeys all consumed a diet replete in vitamin D3, it seems that individual differences in vitamin D absorption or metabolism may have determined whether the monkeys had high or low concentrations of vitamin D3. Lower vitamin D3 was associated with a more atherogenic lipid profile, a major risk factor for progressing to coronary artery atherosclerosis in monkeys and human beings.


The anti-cancer drug gefitinib accelerates Fas-mediated apoptosis by enhancing caspase-8 activation in cancer cells.
Fas/CD95 plays a pivotal role in T cell-mediated cytotoxicity. Accumulating evidence has suggested that resistance to Fas-mediated apoptosis contributes to the escape of cancer cells from immune destruction, and allows to undergo proliferation and outgrowth of cancer cells. In this study, we found that the anti-cancer drug gefitinib, a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), has an ability to enhance Fas-mediated cytotoxicity. In the presence of nontoxic concentrations of gefitinib, Fas-induced activation of caspase-8 and subsequent apoptosis was dramatically promoted, suggesting that gefitinib increases the sensitivity to Fas-mediated apoptosis. Interestingly, the effects of gefitinib were observed in EGFR or p53 knockout (KO) cells. These observations indicate that both EGFR and p53 are dispensable for the enhancement. On the other hand, gefitinib clearly downregulated heat shock protein 70 (HSP70) as previously reported. Considering that HSP70 contributes to protection of cells against Fas-mediated apoptosis, gefitinib may increase the sensitivity to Fas-mediated apoptosis by downregulating HSP70. Thus, our findings reveal novel properties of gefitinib, which may provide insight into the alternative therapeutic approaches of gefitinib for Fas-resistant tumors.


Experience with a computer word-entry method in processing Chinese characters by fluent typists.
A 2003 study by Green and Bavelier showed that action video-game playing modified the visual selective attention of habitual players so the present hypothesis was whether processing of Chinese characters became more phonologically or orthographically oriented depending on whether participants were experienced typing with the phonological (zhuyin) or the orthographic (changjie) word-entry method. In Exp. 1, 38 changjie and 40 zhuyin users typed a short text on a computer using the word-entry method they had experienced. Every keystroke was recorded, and typing errors were categorized. In Exp. 2, 25 changjie and 25 zhuyin users had to circle all characters which contained a predesignated radical when they read a short passage. In Exp. 3, 25 changjie and 20 zhuyin users heard pairs of syllables and had to decide whether the two syllables in a pair shared the same onset consonant in one block of trials or the same rhyme in another block of trials. Analysis showed participants with extensive experience using phonological typing displayed more phonologically related typing errors, better sensitivity to the onset and rhyme of a syllable, but poorer sensitivity to the radical of a character. Participants with extensive experience using orthographic typing displayed opposite results. Although the general cognitive system might be similar in the two groups of participants, the specific configuration of the system can vary to meet the demand of a particular design of the artifactual environment.


Instruction-level parallel processing.
The performance of microprocessors has increased steadily over the past 20 years at a rate of about 50% per year. This is the cumulative result of architectural improvements as well as increases in circuit speed. Moreover, this improvement has been obtained in a transparent fashion, that is, without requiring programmers to rethink their algorithms and programs, thereby enabling the tremendous proliferation of computers that we see today. To continue this performance growth, microprocessor designers have incorporated instruction-level parallelism (ILP) into new designs. ILP utilizes the parallel execution ofthe lowest level computer operations-adds, multiplies, loads, and so on-to increase performance transparently. The use of ILP promises to make possible, within the next few years, microprocessors whose performance is many times that of a CRAY-IS. This article provides an overview of ILP, with an emphasis on ILP architectures-superscalar, VLIW, and dataflow processors-and the compiler techniques necessary to make ILP work well.


Biofluid biomarkers of traumatic brain injury.
The purpose of this paper is to review the clinical and research utility and applications of blood, cerebrospinal fluid (CSF), and cerebral microdialysis biomarkers in traumatic brain injury (TBI). Not applicable. A selective review was performed on these biofluid biomarkers in TBI. Neurofilament heavy chain protein (NF-H), glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCHL1), neuron-specific enolase (NSE), myelin basic protein (MBP), tau, and s100β blood biomarkers are elevated during the acute phase of severe head trauma but have key limitations in their research and clinical applications to mild TBI (mTBI). CSF biomarkers currently provide the best reflection of the central nervous system (CNS) pathobiological processes in TBI. Both animal and human studies of TBI have demonstrated the importance of serial sampling of biofluids and suggest that CSF biomarkers may be better equipped to characterize both TBI severity and temporal profiles. The identification of biofluid biomarkers could play a vital role in identifying, diagnosing, and treating the underlying individual pathobiological changes of TBI. CNS-derived exosomes analyzed by ultra-high sensitivity detection methods have the potential to identify blood biomarkers for the range of TBI severity and time course.


Women's compliance with nutrition and lifestyle recommendations before pregnancy: general population cohort study.
To examine the extent to which women planning a pregnancy comply with recommendations for nutrition and lifestyle. Prospective cohort study. Southampton, United Kingdom. 12 445 non-pregnant women aged 20-34 recruited to the Southampton Women's Survey through general practices, 238 of whom became pregnant within three months of being interviewed. Folic acid supplement intake, alcohol consumption, smoking, diet, and physical activity before pregnancy. The 238 women who became pregnant within three months of the interview were only marginally more likely to comply with recommendations for those planning a pregnancy than those who did not become pregnant in this period. Among those who became pregnant, 2.9% (95% confidence interval 1.2% to 6.0%) were taking 400 microg or more of folic acid supplements a day and drinking four or fewer units of alcohol a week, compared with 0.66% (0.52% to 0.82%) of those who did not become pregnant. 74% of those who became pregnant were non-smokers compared with 69% of those who did not become pregnant (P=0.08). Women in both groups were equally likely to consume five or more portions of fruit and vegetables a day (53% in each group, P=1.0), but only 57% of those who became pregnant had taken any strenuous exercise in the past three months compared with 64% in those who did not become pregnant (P=0.03). Only a small proportion of women planning a pregnancy follow the recommendations for nutrition and lifestyle. Greater publicity for the recommendations is needed, but as many pregnancies are unplanned, improved nutrition and lifestyles of women of childbearing age is also required.


Hormone replacement therapy.
By the year 2020, more than 45 million American women will be over the age of 50. Many of these women will wrestle with decisions concerning the use of hormone replacement therapy. This report presents a history of hormone replacement therapy use. The report then addresses the benefits, risks, and relative and absolute contraindications associated with hormone therapy. Concluding sections of the report discuss hormone replacement options which are currently available as well as provider considerations when tailoring a therapy regimen to the needs of the patient.


Sonographic measurement of fetal ear length in Turkish women with a normal pregnancy.
Abnormal fetal ear length is a feature of chromosomal disorders. Fetal ear length measurement is a simple measurement that can be obtained during ultrasonographic examinations. To develop a nomogram for fetal ear length measurements in our population and investigate the correlation between fetal ear length, gestational age, and other standard fetal biometric measurements. Cohort study. Ear lengths of the fetuses were measured in normal singleton pregnancies. The relationship between gestational age and fetal ear length in millimetres was analysed by simple linear regression. In addition, the correlation of fetal ear length measurements with biparietal diameter, head circumference, abdominal circumference, and femur length were evaluated.Ear length measurements were obtained from fetuses in 389 normal singleton pregnancies ranging between 16 and 28 weeks of gestation. A nomogram was developed by linear regression analysis of the parameters ear length and gestational age. Fetal ear length (mm) = y = (1.348 X gestational age)-12.265), where gestational ages is in weeks. A high correlation was found between fetal ear length and gestational age, and a significant correlation was also found between fetal ear length and the biparietal diameter (r=0.962; p<0.001). Similar correlations were found between fetal ear length and head circumference, and fetal ear length and femur length. The results of this study provide a nomogram for fetal ear length. The study also demonstrates the relationship between ear length and other biometric measurements.


Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense.
To further understand the role of cytokine responses in symptom formation and host defenses in influenza infection, we determined the levels of IL-1beta, IL-2, IL-6, IL-8, IFN-alpha, TGF-beta, and TNF-alpha in nasal lavage fluid, plasma, and serum obtained serially from 19 volunteers experimentally infected with influenza A/Texas/36/91 (H1N1) and correlated these levels with various measures of infection and illness severity. We found that IL-6 and IFN-alpha levels in nasal lavage fluids peaked early (day 2) and correlated directly with viral titers, temperature, mucus production, and symptom scores. IL-6 elevations were also found in the circulation at this time point. In contrast, TNF-alpha responses peaked later (day 3 in plasma, day 4 in nasal fluids), when viral shedding and symptoms were subsiding. Similarly, IL-8 peaked late in the illness course (days 4-6) and correlated only with lower respiratory symptoms, which also occurred late. None of IL-1beta, IL-2, or TGF-beta levels increased significantly. These data implicate IL-6 and IFN-alpha as key factors both in symptom formation and host defense in influenza.


Dome formation by a retrovirus-induced lung adenocarcinoma cell line.
A cell line has been established from an alveologenic lung adenocarcinoma that develops in newborn NFS/N mice after i.p. inoculation with a carcinoma-inducing retrovirus. A clonal derivative of this cell line, 3041, forms adenocarcinomas when injected into syngeneic weanling mice and in culture retains several properties typical of alveologenic type 1 cells. These include morphological details, such as tight junctions and interdigitating microvilli in the areas of cell-cell contact, as well as the ability to transport fluid in culture. Fluid transport becomes evident in confluent cultures by the formation of domes or hemicysts. The formation of domes, which is considered to reflect a differentiated function of these secretory epithelial cells, can be enhanced more than 50-fold by treatment with dibutyryl cyclic adenosine 3':5'-monophosphate but only 5- and 3-fold by sodium n-butyrate and dimethyl sulfoxide, respectively. It is anticipated that the secretory alveologenic cell line 3041 described here will be useful for studies of both its pathological and its physiological properties.


Electrodeposition of PANi films on platinum needle type microelectrodes. Application to the oxidation of ascorbate in human plasma.
Needle type (165 microm(2)) and small Pt disc (3-11 microm(2)) microelectrodes were used for the electrodeposition of composite poly(aniline), PANi, films by cyclic voltammetry and chronoamperometry for the oxidation of ascorbate. PANi electroactivity at neutral pH was retained through polymer alkylation or by using large poly-anions, such as poly(vinylsulfonate), PVS, and poly(styrenesulfonate), PSS. Hence the growth of the composite films was studied in the presence of different counter ions such as SO(4)(2-), Cl(-), NaPVS and NaPSS. The morphology of the resulting films was examined by scanning electron microscopy. Results showed that flat PANi films with thicknesses much lower than the microelectrode radius were obtained by potentiodynamic electrodeposition. On the other hand films with mushroom shapes, with significant spill over, were obtained under constant potential. The resulting polymer modified microelectrodes films were shown to be suitable for the oxidation of ascorbate at 0.1 V vs. SCE and pH 7 with a detection limit of 1 microM for PANi/PSS composites. The current was independent of film thickness, mass transport controlled at low ascorbate concentrations and not affected by the presence of common interferences such as uric acid, glutathione or vitamin E. Due to their excellent properties the PANi-PSS film coated microelectrodes were used for the amperometric detection of ascorbate in human plasma. The results are encouraging for the use of small polymer modified Pt needle type microelectrodes for the detection of ascorbate in biological systems.


Immunotherapy for colorectal cancer: Rational strategies and novel therapeutic progress.
There are increasing incidences and mortality rates for colorectal cancer in the world. It is common for chemotherapy and radiation given to patients with colorectal cancer to cause toxicities that limit their effectiveness and cause cancer cells to become resistant to these treatments. Additional targeted treatments are needed to improve patient's quality of life and outcomes. Immunotherapy has rapidly emerged as an incredibly exciting and promising avenue for cancer treatment in recent years. This innovative approach provides novel options for tackling solid tumors, effectively establishing itself as a new cornerstone in cancer treatment. Specifically, in the realm of colorectal cancer (CRC), there is great promise in developing new drugs that target immune checkpoints, offering a hopeful and potentially transformative solution. While immunotherapy of CRC has made significant advances, there are still obstacles and limitations. CRC patients have a poor response to treatment because of the immune-suppressing function of their tumor microenvironment (TME). In addition to blocking inhibitory immune checkpoints, checkpoint-blocking antibodies may also boost immune responses against tumors. The review summarizes recent advances in immune checkpoint inhibitors (ICIs) for CRC, including CTLA-4, PD-1, PD-L1, LAG-3, and TIM-3.


Non-invasive positive pressure ventilation versus endotracheal intubation in treatment of COVID-19 patients requiring ventilatory support.
Initial guidelines recommended prompt endotracheal intubation rather than non-invasive ventilation (NIV) for COVID-19 patients requiring ventilator support. There is insufficient data comparing the impact of intubation versus NIV on patient-centered outcomes of these patients. To compare all-cause 30-day mortality for hospitalized COVID-19 patients with respiratory failure who underwent intubation first, intubation after NIV, or NIV only. Retrospective study of patients admitted in March and April of 2020. A teaching hospital in Brooklyn, New York City. Adult COVID-19 confirmed patients who required ventilator support (non-invasive ventilation and/or endotracheal intubation) at discretion of treating physician, were included. Patients were categorized into three exposure groups: intubation-first, intubation after NIV, or NIV-only. 30-day all-cause mortality, a predetermined outcome measured by multivariable logistic regression. Data are presented with medians and interquartile ranges, or percentages with 95% confidence intervals, for continuous and categorical variables, respectively. Covariates for the model were age, sex, qSOFA score ≥ 2, presenting oxygen saturation, vasopressor use, and greater than three comorbidities. A secondary multivariable model compared mortality of all patients that received NIV (intubation after NIV and NIV-only) with the intubation-first group. A total of 222 were enrolled. Overall mortality was 77.5% (95%CI, 72-83%). Mortality for intubation-first group was 82% (95%CI, 73-89%; 75/91), for Intubation after NIV was 84% (95%CI, 70-92%; 37/44), and for NIV-only was 69% (95%CI, 59-78%; 60/87). In multivariable analysis, NIV-only was associated with decreased all-cause mortality (odds ratio [OR]: 0.30, 95%CI, 0.13-0.69). No difference in mortality was observed between intubation-first and intubation after NIV. Secondary analysis found all patients who received NIV to have lower mortality than patients who were intubated only (OR: 0.44, 95%CI, 0.21-0.95). Utilization of NIV as the initial intervention in COVID-19 patients requiring ventilatory support is associated with significant survival benefit. For patients intubated after NIV, the mortality rate is not worse than those who undergo intubation as their initial intervention.


Photoadaptation of two members of the Chlorophyta (Scenedesmus and Chlorella) in laboratory and outdoor cultures: changes in chlorophyll fluorescence quenching and the xanthophyll cycle.
The role of the xanthophyll cycle in the adaptation of two chlorococcal algae Scenedesmus quadricauda and Chlorella sorokiniana to high irradiance was studied under laboratory and outdoor conditions. We wished to elucidate whether the xanthophyll cycle plays a key role in dissipating the excesses of absorbed light, as in higher plants, and to characterise the relationship between chlorophyll fluorescence parameters and the content of xanthophyll-cycle pigments. The xanthophyll cycle was found to be operative in both species; however, its contribution to overall non-photochemical quenching (NPQ) could only be distinguished in Scenedesmus (15-20% of total NPQ). The Scenedesmus cultures showed a larger pool of xanthophyll-cycle pigments than Chlorella, and lower sensitivity to photoinhibition as judged from the reduction of maximum quantum yield of photosystem II. In general, both algae had a larger xanthophyll-cycle pool when grown outdoors than in laboratory cultures. Comparing the two species, Scenedesmus exhibited a higher capacity to adapt to high irradiance, due to an effective quenching mechanism and high photosynthetic capacity; in contrast, Chlorella represents a species with a larger antennae system, less-efficient quenching and lower photosynthetic performance. Non-photochemical quenching (NPQ) induced through the xanthophyll cycle can, to a limited extent, represent a regulatory factor in diluted algal cultures grown in outdoor solar photobioreactors, as well as in natural algal phytoplankton populations exposed transiently to high irradiance. However, it does not play an appreciable role in dense, well-mixed microalgal suspensions.


The Use of Eye Tracking to Discern the Threshold at Which Metopic Orbitofrontal Deformity Attracts Attention.
Surgical treatment for trigonocephaly aims to eliminate a stigmatizing deformity, yet the severity that captures unwanted attention is unknown. Surgeons intervene at different points of severity, eliciting controversy. This study used eye tracking to investigate when deformity is perceived. Three-dimensional photogrammetric images of a normal child and a child with trigonocephaly were mathematically deformed, in 10% increments, to create a spectrum of 11 images. These images were shown to participants using an eye tracker. Participants' gaze patterns were analyzed, and participants were asked if each image looked "normal" or "abnormal." Sixty-six graduate students were recruited. Average dwell time toward pathologic areas of interest (AOIs) increased proportionally, from 0.77 ± 0.33 seconds at 0% deformity to 1.08 ± 0.75 seconds at 100% deformity (P < .0001). A majority of participants did not agree an image looked "abnormal" until 90% deformity from any angle. Eye tracking can be used as a proxy for attention threshold toward orbitofrontal deformity. The amount of attention toward orbitofrontal AOIs increased proportionally with severity. Participants did not generally agree there was "abnormality" until deformity was severe. This study supports the assertion that surgical intervention may be best reserved for more severe deformity.


Effect of patient characteristics on the yield of prolonged baseline head-up tilt testing and the additional yield of drug provocation.
To define the value of tilt testing and hte additional yield of drug provocation over prolonged baseline tilt in different patient subgroups. (Many different protocols are in use for head-up tilt testing in heterogeneous groups of patients. Not all patients in reported series have recurrent syncope, and there is often a wide age range and a variable incidence of structural heart disease.) In a prospective study, baseline 60 degrees head-up tilt testing was undertaken for 45 minutes, initially without drug provocation. Patients who remained symptom free were given intravenous isoprenaline (isoproterenol) and further tilting or edrophonium (10 mg bolus) during tilt, in an order determined randomly before the start of the test. If they were symptom free after the first drug, they were given the other drug. A positive test was recorded when syncope or pre-syncope occurred with a rapid fall (> 30%) in blood pressure. The impact on tilt result of the type of symptoms, presence of significant structural heart disease (SHD), presence of a non-cardiovascular cause of sudden diminished consciousness (SDC), and age was then assessed by subgroup analysis. 145 patients (73 female, mean age 51 (25), range 8-94) with one or more episodes of pre-syncope or syncope. 39 patients (27%, 21 female, age 49 (25) years) had positive tests and 106 (73%, 52 female, age 52 (25) years) negative tests. 27 (69%) had a positive test during baseline tilt at 20.5 (10.8) minutes, five (13%) with isoprenaline infusion, and seven (18%) with edrophonium bolus. Patients with recurrent syncope rather than single syncopal episodes or single or recurrent pre-syncope were more likely to have a positive tilt test (41% v 17%, P < 0.005) and patients with SHD or SDC (69/14 patients) were much less likely than patients without (16% v 42%, P < 0.0001). The yield of positive tests was similar if patients were below (26%) or above (27%) the mean age (50 years). When multiple factors were combined, the yield ranged from 0% for 21 patients under 50 years with SHD or SDC and without recurrent syncope to 73% in 11 patients over 50 years with recurrent syncope and no SHD or SDC. The additional yield in subgroups over 45 minute baseline tilt (70 (11)%) of isoprenaline (13 (10)%) was similar to that of edrophonium (17 (8)%, P = NS), but six (50% of those who were drug positive) patients required a second drug to produce a positive result (two with isoprenaline second, four with edrophonium second). Head-up tilt testing in a heterogeneous population has a low yield. Simple clinical characteristics define the type of patient who is likely to have a positive tilt test and the patient who is not and in whom other investigations should receive priority. The great majority of positive tests will occur during prolonged baseline testing if this is used. Isoprenaline and edrophonium produced similar additional yields of positive tests.


Diagnosis, initial management, and prevention of meningitis.
Although the annual incidence of bacterial meningitis in the United States is declining, it remains a medical emer- gency with a potential for high morbidity and mortality. Clinical signs and symptoms are unreliable in distinguishing bacterial meningitis from the more common forms of aseptic meningitis; therefore, a lumbar puncture with cerebro- spinal fluid analysis is recommended. Empiric antimicrobial therapy based on age and risk factors must be started promptly in patients with bacterial meningitis. Empiric therapy should not be delayed, even if a lumbar puncture cannot be performed because results of a computed tomography scan are pending or because the patient is awaiting transfer. Concomitant therapy with dexamethasone initiated before or at the time of antimicrobial therapy has been demonstrated to improve morbidity and mortality in adults with Streptococcus pneumoniae infection. Within the United States, almost 30 percent of strains of pneumococci, the most common etiologic agent of bacterial meningitis, are not susceptible to penicillin. Among adults in developed countries, the mortality rate from bacterial meningitis is 21 percent. However, the use of conjugate vaccines has reduced the incidence of bacterial meningitis in children and adults.


Parental care masks a density-dependent shift from cooperation to competition among burying beetle larvae.
Studies of siblings have focused mainly on their competitive interactions and to a lesser extent on their cooperation. However, competition and cooperation are at opposite ends on a continuum of possible interactions and the nature of these interactions may be flexible with ecological factors tipping the balance toward competition in some environments and cooperation in others. Here we show that the presence of parental care and the density of larvae on the breeding carcass change the outcome of sibling interactions in burying beetle broods. With full parental care there was a strong negative relationship between larval density and larval mass, consistent with sibling competition for resources. In the absence of care, initial increases in larval density had beneficial effects on larval mass but further increases in larval density reduced larval mass. This likely reflects a density-dependent shift between cooperation and competition. In a second experiment, we manipulated larval density and removed parental care. We found that the ability of larvae to penetrate the breeding carcass increased with larval density and that feeding within the carcass resulted in heavier larvae than feeding outside the carcass. However, larval density did not influence carcass decay.


Anesthetic Management of Laser Lead Extraction for Cardiovascular Implantable Electronic Devices.
Cardiovascular implantable electronic devices (CIEDs) play a significant role in the modern management of cardiovascular disease. CIEDs include implantable pacemakers (PMs), implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices. These devices improve the quality of life of their recipients and help reduce the incidence of sudden cardiac death. Traditionally, CIEDs have been reliant on the use of transvenous endocardial leads to directly connect with the heart. Over time, these endovascular leads may become endothelialized rendering removal extremely difficult. As the indications for CIEDs expands and with the continuing evolution of these devices, the number of patients requiring explantation for device recall, malfunction, and infection continues to increase. In this manuscript, we review the most common CIEDs, the indications and process of lead removal/device explantation, potential complications associated with the procedure and the anesthetic management of these patients.


Is home-based HIV testing universally acceptable? Findings from a case-control study nested within the HPTN 071 (PopART) trial.
The HPTN 071 (PopART) trial is examining the impact of a package including universal testing and treatment on community-level HIV incidence in Zambia and South Africa. We conducted a nested case-control study to examine factors associated with acceptance of home-based HIV testing and counselling (HB-HTC) delivered by community HIV-care providers (CHiPs) in PopART intervention communities. Of 295 447 individuals who were offered testing, random samples of individuals who declined HB-HTC (cases) and accepted HB-HTC (controls), stratified by gender and community, were selected. Odds ratios comparing cases and controls were estimated using multivariable logistic regression. Data from 642 participants (313 cases, 329 controls) were analysed. There were no differences between cases and controls by demographic or behavioural characteristics including age, marital or socio-economic position. Participants who felt they could be open with CHiPs (AOR: 0.46, 95% CI: 0.30-0.71, P < 0.001); self-reported as not previously tested (AOR: 0.64; 95% CI: 0.43-0.95, P = 0.03); considered HTC at home to be convenient (AOR: 0.38, 95% CI: 0.27-0.54, P = 0.001); knowing others who had accepted HB-HTC from the CHiPs (AOR: 0.49, 95% CI: 0.31-0.77, P = 0.002); or were motivated to get treatment without delay (AOR: 0.60, 95% CI: 0.43-0.85, P = 0.004) were less likely to decline the offer of HB-HCT. Those who self-reported high-risk sexual behaviour were also less likely to decline HB-HCT (AOR: 0.61, 95% CI: 0.39-0.93, P = 0.02). Having stigmatising attitudes about HB-HTC was not an important barrier to HB-HCT uptake. Men who reported fear of HIV were more likely to decline HB-HCT (AOR: 2.68, 95% CI: 1.33-5.38, P = 0.005). Acceptance of HB-HTC was associated with lack of previous HIV testing, positive attitudes about HIV services/treatment and perception of high sexual risk. Uptake of HB-HCT among those offered it was similar across a range of demographic and behavioural subgroups suggesting it was 'universally' acceptable.


Acute Effects of Cannabis Concentrate on Motor Control and Speed: Smartphone-Based Mobile Assessment.
Background: The use of cannabis concentrate is dramatically rising and sparking major safety concerns. Cannabis concentrate contains tetrahydrocannabinol (THC) potencies up to 90%, yet there has been little research on motor impairment after concentrate use (commonly referred to as "dabbing"). This study measured postural control and motor speed after the use of high potency concentrates in males and females. Methods: Experienced concentrate users (N = 65, Female: 46%, 17 ± 11 days/month of concentrate use) were assessed for motor performance in a mobile laboratory before, immediately after, and 1 h after ad-libitum cannabis concentrate use. Plasma levels of THC were obtained via venipuncture at each timepoint. We used a remotely deployable motor performance battery to assess arm and leg movement speed, index finger tapping rate, and balance. The sensors on a smart device (iPod Touch) attached to the participant provided quantitative measures of movement. Results: Arm speed slowed immediately after concentrate use and remained impaired after 1 h (p < 0.001), leg speed slowed 1 h after use (p = 0.033), and balance decreased immediately after concentrate use (eyes open: p = 0.017, eyes closed: p = 0.013) but not at 1 h post-use. These effects were not different between sexes and there was no effect of concentrate use on finger tapping speed. Acute changes in THC plasma levels after use of concentrates were minimally correlated with acute changes in balance performance. Conclusions: Use of cannabis concentrates in frequent users impairs movement speed and balance similarly in men and women. The motor impairment is largely uncorrelated with the change in THC plasma levels. These results warrant further refinement of cannabis impairment testing and encourage caution related to use of cannabis concentrates in work and driving settings.


Identification of a two-link flexible manipulator using adaptive time delay neural networks.
This paper deals with identification of a two-link flexible manipulator belonging to a class of multi-input, multi-output (MIMO) nonlinear systems, by using adaptive time delay neural networks (ATDNNs). Two neuro-dynamic identifiers are proposed. The capabilities of the proposed structures for representing the nonlinear input-output map of the flexible manipulator are shown analytically. Selection criteria for specifying the fixed structural parameters as well as the adaptation laws for updating the adjustable parameters of the networks are provided. During identification, the two-link flexible manipulator is under nonlinear control and the input-output data sets are generated for different desired trajectories. Simulation results reveal that the proposed neuro-dynamic structures are capable of successfully identifying a highly nonlinear system without any a priori information about the nonlinearities of the system and without any off-line training.


Anxiety and depression in asthma patients: impact on asthma control.
There is evidence that asthma is associated with an increase in psychiatric symptoms and mental disorders. This association can make it difficult to achieve asthma control. The purpose of this study was to determine whether the level of asthma control is associated with anxiety and depression. A crosssectional study involving 78 patients with confirmed moderate or severe asthma and under regular treatment at the Asthma Outpatient Clinic of the Federal University of São Paulo Hospital São Paulo, in the city of São Paulo, Brazil. The patients were divided into two groups by asthma control status, as assessed by the asthma control test, and were subsequently compared in terms of demographic, clinical, and spirometric data, as well as scores for asthma quality of life and hospital anxiety/depression. The sample was predominantly female. Of the 78 patients, 49 (63%) were classified as having uncontrolled asthma. The prevalence of anxiety and of anxiety+depression was significantly higher among patients with uncontrolled asthma than among those with controlled asthma (78% and 100%; p = 0.04 and p = 0.02, respectively), whereas there were no differences between the two groups in terms of the prevalence of depression, spirometry results, or quality of life score. In this sample, the prevalence of anxiety symptoms was higher in the patients with uncontrolled asthma than in those with controlled asthma.In the evaluation of asthma patients, the negative impact of mood states ought to be taken into consideration when asthma control strategies are being outlined.


The Japanese version of the Material Values Scale: construct assessment and relationship with age, personality, and subjective well-being.
Materialism indicates the extent to which an individual's life is focused on consumerism, or the acquisition of money and possessions. The Material Values Scale (MVS), comprising the factors "success," "centrality," and "happiness," is a well-known rating scale for materialism. However, a Japanese version of the materialism scale has not yet been established, and the details of the factors and effects related to materialism have not yet been clarified in Japan. The purpose of this study is to develop and evaluate the Japanese version of the MVS (J-MVS). We developed the translated J-MVS using a back-translation process. To validate and evaluate the scale based on an online survey, we recruited 500 people, with 100 participants (50 men, 50 women) in five age groups, from 20 to 69 years. We compared and evaluated several factor structure models based on exploratory and confirmatory factor analysis. To evaluate the external criterion-referenced validity of the developed J-MVS scale, we examined the relationship between age, personality, and well-being, which have shown stable relationships with materialism in previous studies. We developed two six-item dual-factor models. Both models showed significant positive correlations with social comparison orientation and neuroticism, and had significant negative correlations with various subjective well-being indices, suggesting sufficient external criterion-referenced validity. The J-MVS comprising six positive-worded items (J-MVS-P6; without any reverse-worded items) showed a higher correlation with other indicators than the version comprising six items representing all item types and was considered to have higher external criterion-referenced validity. We propose the J-MVS-P6 for use as a materialism scale in Japan. Compared with the findings from other countries, materialism in Japan may be more closely related to subjective well-being. This scale may be used to examine the effectiveness of various intervention methods for improving individuals' happiness, based on changes in factors closely related to materialism in Japan.


Expression of the cold-induced wheat gene Wcs120 and its homologs in related species and interspecific combinations.
Low-temperature response was measured at the whole plant and at the molecular level in wheat-rye amphiploids and in other interspecific combinations. Cold tolerance of interspecifics whose parents diverged widely in hardiness levels resembled the less hardy higher ploidy level wheat parent. Expression of the low-temperature induced Wcs120 gene of wheat (Triticum aestivum L. em. Thell.) has been associated with freezing tolerance and was used here to study mRNA and protein accumulation in interspecific and parental lines during cold acclimation. Northern and Western analyses showed that homologous mRNAs and proteins were present in all the related species used in the experiments. Cold-tolerant rye (Secale cereale L.) produced a strong mRNA signal that was sustained throughout the entire 49-day cold-acclimation period. The wheats produced a mRNA signal that had diminished after 49 days of low-temperature exposure. The wheat-rye triticales did not exhibit the independent accumulation kinetics of the cold-tolerant rye parent but, rather, more closely resembled the wheat parent in that the mRNA signal was greatly diminished after 49 days of low-temperature exposure. The influence of the rye genome was manifest in slightly greater mRNA and protein accumulation in earlier stages of acclimation. Protein accumulations in the triticales were also maintained to a somewhat greater extent than found in the wheats at the end of the 49-day acclimation period. Protein accumulations in the wheat-crested wheatgrass (Agropyron cristatum L. Gaertner) interspecific resembled that of the wheat parent. The influence of the higher ploidy level wheats of the expression of homologous gene families from wheat-related hardy diploids in interspecific combinations may in part explain the poor cold tolerance observed.


Sonolysis and sono-Fenton oxidation for removal of ibuprofen in (waste)water.
Two sonochemical processes were compared for the removal of ibuprofen in different water matrixes (distilled water and effluent from wastewater treatment plant). The effect of various operating parameters, such as pH (2.6-8.0), ultrasound power density (25-100W/L), sonication frequency (12-862kHz), addition of radical promoters (H2O2 and Fenton's reagent) or scavengers (n-butanol and acetic acid), was evaluated. Sono-degradation of ibuprofen followed a first-order kinetic trend, whose rate constant increased with ultrasound density and frequency. For this hydrophobic and low volatile molecule, a free-radical mechanism at the bubble interface was established. Coupling ultrasound with Fenton reaction showed a positive synergy, especially in terms of mineralization yield, while adding H2O2 alone had no significant beneficial effect. Dedicated experiments proved this synergy to be due to the enhanced regeneration of ferrous ions by ultrasound. Efficacy of the sonolysis process was hampered in wastewater matrix, mainly as the consequence of higher pH increasing the molecule solubility. However, after convenient acidification, sono-Fenton oxidation results remained almost unchanged, indicating no significant radical scavenging effects from the effluent compounds.


Effect of Hevea brasiliensis latex sap gel on healing of acute skin wounds induced on the back of rats.
to evaluate the effect of topical delivery of latex cream-gel in acute cutaneous wounds induced on the back of rats. we subjected sixteen rats to dermo-epidermal excision of a round dorsal skin flap, with 2.5cm diameter. We divided the animals into two groups: Latex Group: application of cream-gel-based latex throughout the wound bed on postoperative days zero, three, six and nine; no treatment on the wound. Photographs of the lesions were taken on the procedure day and on the 6th and 14th postoperative days, for analyzing the area and the larger diameter of the wound. We carried out euthanasia of all animals on the 14th postoperative day, when we resected he dorsal skin and the underlying muscle layer supporting the wound for histopathological study. there was no statistically significant difference in the percentage of wound closure, in the histopathological findings or in the reduction of the area and of the largest diameter of the wounds among the groups studied on the 14th postoperative day. according to the experimental conditions in which the study was conducted, latex cream-gel did not interfere in the healing of acute cutaneous wounds in rats.


Treble clef finger--a functionally diverse zinc-binding structural motif.
Detection of similarity is particularly difficult for small proteins and thus connections between many of them remain unnoticed. Structure and sequence analysis of several metal-binding proteins reveals unexpected similarities in structural domains classified as different protein folds in SCOP and suggests unification of seven folds that belong to two protein classes. The common motif, termed treble clef finger in this study, forms the protein structural core and is 25-45 residues long. The treble clef motif is assembled around the central zinc ion and consists of a zinc knuckle, loop, beta-hairpin and an alpha-helix. The knuckle and the first turn of the helix each incorporate two zinc ligands. Treble clef domains constitute the core of many structures such as ribosomal proteins L24E and S14, RING fingers, protein kinase cysteine-rich domains, nuclear receptor-like fingers, LIM domains, phosphatidylinositol-3-phosphate-binding domains and His-Me finger endonucleases. The treble clef finger is a uniquely versatile motif adaptable for various functions. This small domain with a 25 residue structural core can accommodate eight different metal-binding sites and can have many types of functions from binding of nucleic acids, proteins and small molecules, to catalysis of phosphodiester bond hydrolysis. Treble clef motifs are frequently incorporated in larger structures or occur in doublets. Present analysis suggests that the treble clef motif defines a distinct structural fold found in proteins with diverse functional properties and forms one of the major zinc finger groups.


A novel and facile approach to fabricate a conductive and biomimetic fibrous platform with sub-micron and micron features.
The demands of multifunctional scaffolds have exceeded the passive biocompatible properties previously considered sufficient for tissue engineering. Herein, a novel and facile method used to fabricate a core-shell structure consisting of a conducting fiber core and an electrospun fiber shell is presented. This multifunctional structure simultaneously provides the high conductivity of conducting polymers as well as the enhanced interactions between cells and the sub-micron topographical environments provided by highly aligned cytocompatible electrospun fibers. Unlimited lengths of PEDOT:PSS-Chitosan-PLGA fibers loaded with an antibiotic drug, ciprofloxacin hydrochloride, were produced using this method. The fibers provide modulated drug release with excellent mechanical properties, electrochemical performance and cytocompatibility, which hold great promise for the application of conductive electrospun scaffolds in regenerative medicine.


Safety of dipeptidyl peptidase 4 inhibitors for treatment of type 2 diabetes.
Dipeptidyl peptidase 4 (DPP-4) inhibitors are a new class of drugs introduced in 2006 for treatment of type 2 diabetes. In clinical trials lasting up to 2 years, these agents are well tolerated. Incidence of hypoglycemia associated with the use of DPP-4 inhibitors is similar to placebo, but is markedly increased when used in conjunction with sulfonylureas (SUs). DPP-4 inhibitors have neutral effect on body weight but their combination with a thiazolidinedione (TZD) results in slight weight gain averaging 0.5 to 1.3 kg compared with placebo. Other adverse effects recorded more commonly with DPP-4 inhibitors versus placebo are mild, and include nasopharyngitis, headache, and possibly urinary tract infections (UTIs). In the postmarketing period, new adverse effects are reported such as angioedema, increased rates of infection, and skin toxicity. Pancreatitis is inconsistently reported in relationship to sitagliptin, and one analysis links this agent to elevated risk of pancreatic cancer. Pancreatitis is also a rare adverse effect observed in linagliptin clinical studies. There is no evidence that DPP-4 inhibitors increase cardiovascular events or death. Overall, although short-term safety of DPP-4 inhibitors is reassuring, their safety needs to be established by long-term clinical trials and close surveillance during the postmarketing period.


Judgments about deservingness.
A twenty-one-year-old known gang member presented to the emergency room late on a Friday night with multiple gunshot wounds, including one to his hand, with multiple open fractures and extensive soft-tissue injury. After evaluation by the on-call resident, the orthopaedic attending physician was notified and the decision was made to bring the patient to the operating room for surgical treatment.Due to the extensive nature of the trauma, the surgical reconstruction took several hours. In the middle of the operation, one member of the operating-room staff began to complain about the late hour and commented that the surgeon need not be so meticulous as the patient was not going to use the hand to play piano; he would likely be using it to shoot a gun. The attending physician replied that we could not know whether or not the patient played piano, nor whether he might take it up after surgery. The surgery was completed, and the patient was brought to the intensive care unit for postoperative monitoring of his other injuries.


Implications of proposed changes in bulk tank somatic cell count regulations.
Several changes in bulk tank SCC (BTSCC) regulations were proposed at the 1998 annual meeting of the National Conference of Interstate Milk Shippers (NCIMS) by the National Mastitis Council and other proponents. Proposals included 1) using a geometric mean BTSCC in place of the arithmetic mean, reducing the current limit for BTSCC from 750,000 to 400,000, and modifying current regulatory protocols. The purpose of this research was to evaluate possible impacts of proposed changes upon producers in warm climates. Data were monthly BTSCC values, provided by state regulatory agencies in West Texas, Louisiana, and Mississippi. Fifty producers from each state were selected by lot, and all 1998 monthly records were included (n = 1602). Computer simulation was used to compare regulatory actions that would have resulted under current and proposed regulations. Possible regulatory actions were 1) notification of noncompliance and 2) suspension of permits to sell milk. At the 750,000 BTSCC limit, both programs resulted in 41 regulatory actions, but the proposed program had a higher rate of suspensions to notices. A twofold increase in regulatory actions per 100,000 incremental decrease in BTSCC limit below 750,000 resulted under both programs. Actual results could be lower due to the assumption that no management adjustments were made by producers in response to changes in regulations. However, the magnitude of increased actions against producers indicated that lowering limits quickly could be disruptive if producers failed to adjust management quickly and effectively to comply with lower limits.


Neurophysiological assessment for evaluating residual cognition in vegetative and minimally conscious state patients: a pilot study.
The aim of this study was to assess residual cognitive function and perform outcome evaluation in vegetative state (VS) and minimally conscious state (MCS) patients, using Neurowave, a system able to monitor event-related potentials (ERPs) induced by neurosensory stimulation. Eleven VS and five MCS patients underwent neurological examination and clinical evaluation performed using validated clinical and behavioral scales; they also underwent neurosensory stimulation, which consisted of administration of target images (rare stimuli), relevant to the patient's personal history and having emotional significance, alternated with nontarget images ("standard" stimuli), which had no emotional significance. All simultaneous ERP responses at baseline (T0) and at three months from T0 (T1) were recorded. At T0 we found significant differences between the VS and MCS patients for the N200 (p=0.02) and P300 (p=0.04) waves. The neurophysiological analysis at T1 showed a significant difference only for P300 (p=0.02), probably due to the improvements observed in the VS subjects for the N100 (p=0.009) and N200 (p=0.02) sensory components. Neurophysiological assessment for evaluating residual cognition in vegetative and minimally conscious state patients: a pilot study Our findings seem to show the value of ERP monitoring in VS and MCS patients as a means of investigating residual cognitive function. This approach could guide early therapeutic and rehabilitation interventions, and contribute to identifying better diagnostic and prognostic markers for use in unresponsive or low-responsive patients.


European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy.
Treatment options for older patients with acute myeloid leukemia (AML) who are not considered suitable for intensive chemotherapy are limited. We assessed the second-generation purine nucleoside analog, clofarabine, in two similar phase II studies in this group of patients. Two consecutive studies, UWCM-001 and BIOV-121, recruited untreated older patients with AML to receive up to four or six 5-day courses of clofarabine. Patients in UWCM-001 were either older than 70 years or 60 to 69 years of age with poor performance status (WHO > 2) or with cardiac comorbidity. Patients in BIOV-121 were >or= 65 years of age and deemed unsuitable for intensive chemotherapy. A total of 106 patients were treated in the two monotherapy studies. Median age was 71 years (range, 60 to 84 years), 30% had adverse-risk cytogenetics, and 36% had a WHO performance score >or= 2. Forty-eight percent had a complete response (32% complete remission, 16% complete remission with incomplete peripheral blood count recovery), and 18% died within 30 days. Interestingly, response and overall survival were not inferior in the adverse cytogenetic risk group. The safety profile of clofarabine in these elderly patients with AML who were unsuitable for intensive chemotherapy was manageable and typical of a cytotoxic agent in patients with acute leukemia. Patients had similar prognostic characteristics to matched patients treated with low-dose cytarabine in the United Kingdom AML14 trial, but had significantly superior response and overall survival. Clofarabine is active and generally well tolerated in this patient group. It is worthy of further evaluation in comparative trials and might be of particular use in patients with adverse cytogenetics.


Serum annexin A2 levels in acute brucellosis and brucellar spondylodiscitis.
Brucellosis is a chronic granulomatous infection and may present with various clinical manifestations. Brucellar spondylodiscitis symptoms are initially subtle and nonspecific. Annexin A2 (ANXA2) is involved in various biological functions, including osteoclast formation, bone resorption, and cell growth regulation. In this study, we aimed to determine the clinical significance of serum ANXA2 levels in acute brucellosis and brucellar spondylodiscitis. This prospective study included 96 acute brucellosis patients and 51 healthy controls. Acute brucellosis was diagnosed by a 1/160 or higher titer in a standard tube agglutination (STA) test or a four-fold increase in titers between two STA tests performed two weeks apart in the presence of clinical symptoms within the last eight weeks and/or growth of Brucella spp. in appropriately prepared culture media. ANXA2 levels were determined with an enzyme-linked immunosorbent assay (ELISA). Forty (41.7 %) of 96 acute brucellosis patients were male and 56 (58.3 %) were female. Serum ANXA2 levels were elevated in patients compared to healthy controls (p = 0.001). Eighteen of 96 (18.7 %) acute brucellosis patients had brucellar spondylodiscitis. The serum ANXA2 levels of patients with brucellar spondylodiscitis were higher than those of patients with acute disease without brucellar spondylodiscitis (p = 0.001). ANXA2, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) values were elevated in the brucellar spondylodiscitis group compared to patients without brucellar spondylodiscitis. Serum ANXA2 measurement together with ESR and CRP is thought to be indicative in the diagnosis of brucellar spondylodiscitis, a common complication of brucellosis.


Integration of HIV and cervical cancer screening perceptions and preferences of communities in Uganda.
Despite the fact that HIV-positive women carry an increased risk of developing cervical cancer (CC) in comparison with HIV-negative women, HIV and CC screening programs in many developing countries have remained unintegrated. The objective of this study is to explore perceptions and preferences of community members in Uganda, including women, men, and village health teams, regarding the integration of HIV and CC screening services in a single-visit approach. This qualitative study was conducted in three districts in Uganda. Data were collected through focus group discussions with women and village health teams, and individual interviews with men. Respondents were purposely selected from among those linked to three CC clinics in the three districts. The content analysis method was used to analyze the data. Three themes emerged from the data, namely appreciating the benefits of integration, worrying about the challenges of integration, and preferences for integration. The women endorsed the benefits. However, there were worries that integration would prolong the waiting time at the health facility and induce tiredness in both the healthcare providers and the women. There were also fears of being found positive for both HIV and CC and the consequences such as stress, self-isolation, and social conflicts. Participants, particularly the women, considered the challenges of screening integration to be manageable by, for example, taking a day off work to visit the hospital, delegating house chores to other family members, or taking a packed lunch on visiting the hospital. The community members in Uganda perceive the benefits of HIV and CC screening integration to outweigh the challenges, and expect that the challenges can be minimized or managed by the women. Therefore, when considering HIV and CC screening integration, it is important to not only recognize the benefits but also take into consideration the perceived challenges and preferences of community members.