Physiological characterization of layer III non-pyramidal neurons in piriform (olfactory) cortex of rat.
We performed whole-cell recordings of layer III non-pyramidal neurons in the piriform cortex of Sprague-Dawley rats. For comparison purposes, recordings were made from deep pyramidal cells, which are also present in layer III. These two cell types could be distinguished both anatomically and physiologically. Anatomically, the layer III non-pyramidal neuron displayed smooth beady dendrites, while deep pyramidal cells showed thicker dendrites with spines. The dendrites of the layer III non-pyramidal neuron also tended to be restricted to layer III while deep pyramidal cells had long apical dendrites that spanned layers I and II. Although the resting membrane potentials of both cell types were very similar, significant differences were noted in other physiological measures. Layer III non-pyramidal neurons typically displayed higher input resistances, faster time constants, smaller spike amplitudes, shorter spike widths, and higher spike thresholds. In addition, layer III non-pyramidal neurons were able to spike at much higher rates when stimulated with the same level of threshold normalized current injection. The most dramatic differences in physiology were seen in the pattern of spiking in response to increasing levels of positive constant current pulses. Layer III non-pyramidal neurons showed qualitatively different responses at low and high levels of stimulation. At low levels, spikes occurred with long latency and the firing frequency increased throughout the duration of the current pulse. At high levels, non-pyramidal neurons started spiking with short latency, followed by a decrease in firing frequency, which in turn was followed by an increase in firing frequency. Deep pyramidal neurons differed dramatically from this pattern, displaying a qualitatively similar response at all levels of current injection. This response was characterized by short latency spikes and spike adaptation for the duration of the current pulse.


A pulsed photolysis procedure for determining oxygen equilibrium parameters of low-affinity noncooperative hemoglobins.
It is often very difficult to obtain precise values for oxygen equilibrium constants for low-affinity noncooperative hemoglobins owing to the ease with which they are oxidized and denatured with even the most gentle stirring or agitation. We have developed a procedure that eliminates this problem by maintaining the hemoglobin as HbCO except during the brief time it is present as Hb, and HbO2 forms following photolysis. Oxygen is continuously removed by an enzyme system. The solution is photolyzed to 100% every 2-3 min during the deoxygenation process to obtain maximum absorbance changes at the Hb-HbCO isosbestic. These maximum absorbance changes at known times during the deoxygenation provide the necessary data for obtaining the oxygen equilibrium constant. These absorbance changes are used with enzyme kinetics equations to obtain calculated times. The simple equations, which neglect heme concentration, will be satisfactory for nearly all conditions, but for generality the complete equations are given. The variance minimizations are with respect to observed and calculated photolysis times. The results for native carp Hb over a range of temperatures are in excellent agreement with results obtained with considerably more material and greater difficulty by other methods.


Validation of the OptiSafe™ eye irritation test.
OptiSafe is an in chemico test method that identifies potential eye irritants based on macromolecular damage following test chemical exposure. The OptiSafe protocol includes a prescreen assessment that identifies test chemicals that are outside the applicability domain of the test method and thus determines the optimal procedure. We assessed the usefulness and limitations of the OptiSafe test method for identifying chemicals not requiring classification for ocular irritation (i.e. bottom-up testing strategy). Seventeen chemicals were selected by the lead laboratory and tested as an independent study. Ninety-five unique coded chemicals were selected by a validation management team to assess the intra- and interlaboratory reproducibility and accuracy of OptiSafe in a multilaboratory, three-phased validation study. Three laboratories (lead laboratory and two naïve laboratories) evaluated 35 chemicals, with the remaining 60 chemicals evaluated by the lead laboratory only. Test method performance was assessed by comparing classifications based on OptiSafe results to classifications based on available retrospective in vivo data, using both the EPA and GHS eye irritation hazard classification systems. No prospective in vivo testing was conducted. Phase I testing of five chemicals showed that the method could be transferred to naïve laboratories; within-lab reproducibility ranged from 93% to 100% for both classification systems. Thirty coded chemicals were evaluated in Phase II of the validation study to demonstrate both intra- and interlaboratory reproducibility. Intralaboratory reproducibility for both EPA and GHS classification systems for Phase II of the validation study ranged from 93% to 99%, while interlaboratory reproducibility was 91% for both systems. Test method accuracy for the EPA and GHS classification systems based on results from individual laboratories ranged from 82% to 88% and from 78% to 88%, respectively, among the three laboratories; false negative rates ranged from 0% to 7% (EPA) and 0% to 15% (GHS). When results across all three laboratories were combined based on the majority classification, test method accuracy and false negative rates were 89% and 0%, respectively, for both classification systems, while false positive rates were 25% and 23% for the EPA and GHS classification systems, respectively. Validation study Phase III evaluation of an additional 60 chemicals by the lead laboratory provided a comprehensive assessment of test method accuracy and defined the applicability domain of the method. Based on chemicals tested in Phases II and III by the lead laboratory, test method accuracy was 83% and 79% for the EPA and GHS classification systems, respectively; false negative rates were 4% (EPA) and 0% (GHS); and false positive rates were 40% (EPA) and 42% (GHS). Potential causes of false positives in certain chemical (e.g. ethers and alcohols) or hazard classes are being further investigated. The OptiSafe test method is useful for identifying nonsurfactant substances not requiring classification for ocular irritancy. OptiSafe represents a new tool for the in vitro assessment of ocular toxicity in a tiered-testing strategy where chemicals can be initially tested and identified as not requiring hazard classification.


Cat-scratch disease.
To discuss the systemic and ocular manifestations, diagnosis and treatment of Bartonella infection. Review of the literature. Bartonella are facultative intracellular Gram-negative rods that infect the erythrocytes or endothelial cells and are related to cat scratch disease (CSD). Bartonella henselae infection has localized or systemic features; the ocular diseases related to Bartonella affect 5--10% of patients with CSD. The diagnosis is based on clinical findings and laboratory tests. The indication of antibiotic therapy depends on the manifestation of the Bartonella infection, the host immunity and the patient's age. Physicians should look for Bartonella henselae in cases of follicular conjuntivitis and regional limphadenopathy, neuroretinitis or retinal infiltrates; currently, serological tests can confirm the clinical suspicion of this infection.


Hepatocyte transplantation in the treatment of acute liver failure: microencapsulated hepatocytes versus hepatocytes attached to an autologous biomatrix.
A liver transplant is considered today to be the only effective therapeutic solution for many otherwise intractable hepatic disorders. However, liver transplantation is beset by shortage of donors. Over the years, many liver support systems have been developed to supply the liver functions, mostly as a bridge to transplantation. Transplantation of isolated hepatocytes (HcTx) instead of whole liver has constituted one of the most appealing possibilities to treat several diseases. We compared two different models of HcTx in a surgical model of acute liver failure in pigs, using microencapsulated hepatocytes (MHcTx) and hepatocytes attached to a porcine biomatrix (PBMHcTx), both transplanted into peritoneum. The collected data were survival, laboratory findings, hemodynamic parameters, light microscopy, histology, MTT, and glycogen content. The group with PBMHcTx has a better outcome than the group with MHcTx (p < 0.05). Histology showed normal morphology of the hepatocytes, high glycogen content, 75% viability, positive MTT, and 95% adhesion of the hepatocytes to the biomatrix. Our biomatrix (PBM) provides cell-to-cell contact and interaction with extracellular matrix, which have been shown to play major roles in hepatocyte survival and physiologic regulation of gene expression, and guarantee a prompt engraftment and an adequate neovascularization. PBMHcTx is a useful method to treat acute liver failure and it indicates a possible liver-direct gene therapy in the treatment of inherited and acquired disorders.


Managing dyslipidemia for CVD prevention: A review of recent clinical practice guidelines.
The American Association of Clinical Endocrinology and the American College of Endocrinology Clinical Practice Guideline is a comprehensive, practical tool that can be used to diagnose and manage dyslipidemia, a major risk for the development and progression of atherosclerotic cardiovascular disease. Effective therapies are available to improve lipid profiles and reduce cardiovascular events.


Safety of Switching from a Vitamin K Antagonist to a Non-Vitamin K Antagonist Oral Anticoagulant in Frail Older Patients with Atrial Fibrillation: Results of the FRAIL-AF Randomized Controlled Trial.
Background: There is ambiguity whether frail patients with atrial fibrillation (AF) managed with vitamin K antagonists (VKAs) should be switched to a non-vitamin K oral anticoagulant (NOAC). Methods: We conducted a pragmatic, multicenter, open-label, randomized controlled superiority trial. Older AF patients living with frailty (age ≥75 years plus a Groningen Frailty Indicator (GFI) score ≥3) were randomized to switch from INR-guided VKA treatment to a NOAC or to continued VKA treatment. Patients with a glomerular filtration rate <30 mL/min/1.73 m2 or with valvular AF were excluded. Follow-up was 12 months. The cause-specific hazard ratio (HR) was calculated for occurrence of the primary outcome which was a major or clinically relevant non-major bleeding complication, whichever came first, accounting for death as a competing risk. Analyses followed the intention-to-treat principle. Secondary outcomes included thromboembolic events. Results: Between January 2018 and June 2022, a total of 2,621 patients were screened for eligibility and 1,330 patients were randomized (mean age 83 years, median GFI 4). After randomization 6 patients in the switch to NOAC arm and 1 patient in the continue with VKA arm were excluded due to the presence of exclusion criteria, leaving 662 patients switched from a VKA to a NOAC and 661 patients continued VKAs in the intention-to-treat population. After 163 primary outcome events (101 in the switch arm, 62 in the continue arm), the trial was stopped for futility according to a prespecified futility analysis. The HR for our primary outcome was 1.69 (95% CI 1.23-2.32). The HR for thromboembolic events was 1.26 (95% CI 0.60 to 2.61). Conclusions: Switching INR-guided VKA treatment to a NOAC in frail older patients with AF was associated with more bleeding complications compared to continuing VKA treatment, without an associated reduction in thromboembolic complications.


Detecting the small island effect and nestedness of herpetofauna of the West Indies.
To detect the small island effect (SIE) and nestedness patterns of herpetofauna of the West Indies, we derived and updated data on the presence/absence of herpetofauna in this region from recently published reviews. We applied regression-based analyses, including linear regression and piecewise regressions with two and three segments, to detect the SIE and then used the Akaike's information criterion (AIC) as a criterion to select the best model. We used the NODF (a nestedness metric based on overlap and decreasing fill) to quantify nestedness and employed two null models to determine significance. Moreover, a random sampling effort was made to infer about the degree of nestedness at portions of the entire community. We found piecewise regression with three segments performed best, suggesting the species-area relationships possess three different patterns that resulted from two area thresholds: a first one, delimiting the SIE, and a second one, delimiting evolutionary processes. We also found that taxa with lower resource requirement, higher dispersal ability, and stronger adaptation to the environment generally displayed lower corresponding threshold values, indicating superior taxonomic groups could earlier end the SIE period and start in situ speciation as the increase of island size. Moreover, the traditional two-segment piecewise regression method may cause poor estimations for both slope and threshold value of the SIE. Therefore, we suggest previous SIE detection works that conducted by two-segment piecewise regression method, ignoring the possibility of three segments, need to be reanalyzed. Antinestedness occurred in the entire system, whereas high degree of nestedness could still occur in portions within the region. Nestedness may still be applicable to conservation planning at portions even if it is antinested at the regional scale. However, nestedness may not be applicable to conservation planning at the regional scale even if nestedness does exist among sampling islands from a portion.


Effect of fast-, medium- and slow-growing strains on meat quality of chickens reared under the organic farming method.
The characteristics of meat quality, chemical and fatty acid composition, from fast-growing (FG) and medium-growing (MG) meat-type and slow-growing (SG) egg-type chickens reared under organic conditions were compared. Three-hundred and sixty 1-day-old male chicks, equally divided into three experimental groups represented by strains (FG: Cobb 700, MG: Naked neck Kabir and SG: Brown Classic Lohman) were housed into three poultry houses with outdoor pasture availability of 10 m(2)/bird located in the same Research Centre of the University of Perugia. All the birds were fed ad libitum the same diets formulated according to the European Union (EU) Regulations by using organic raw materials. Birds from the FG and MG groups were raised until 81 days, whereas birds from the SG group were raised until 96 days in order to achieve an acceptable market live weight. SG birds showed significantly (P < 0.01) higher breast meat drip and cook losses, Allo-Kramer shear values and collagen content. In comparison with FG and SG, MG exhibited a higher breast meat pH (5.86% v. 5.79% and 5.78%, respectively; P < 0.01) and a lower lightness (54.88% v. 57.81% and 56.98%, respectively; P < 0.05). Genotype dramatically affected the lipid content as well as the fatty acid composition of both breast and thigh meat. SG exhibited the lowest content of lipid, both in breast and in thigh meat, the lowest proportions of monounsaturated fatty acids (MUFA) and the highest proportions of polyunsaturated fatty acids (PUFA). The total n-3 PUFA of SG breast meat was double that of FG meat and intermediate with respect to MG birds (8.07% v. 4.07% v. 5.14% total fatty acids; P < 0.01). The fatty acid composition of thigh meat is similar to that of breast meat, but the differences among genotypes are less pronounced. Total saturated fatty acids were not affected by the genotype. In conclusion, meat functional properties of FG and MG strains appeared much more attractive both for industry and consumer (lower drip and cook losses and higher tenderness), whereas from a nutritional point of view, meat from SG appeared healthier (less fat and higher content of n-3 PUFA) and thus might better fit with the consumer's expectations of organic products.


Midazolam-Resistant Seizures and Brain Injury after Acute Intoxication of Diisopropylfluorophosphate, an Organophosphate Pesticide and Surrogate for Nerve Agents.
Organophosphates (OP) such as the pesticide diisopropylfluorophosphate (DFP) and the nerve agent sarin are lethal chemicals that induce seizures, status epilepticus (SE), and brain damage. Midazolam, a benzodiazepine modulator of synaptic GABA-A receptors, is currently considered as a new anticonvulsant for nerve agents. Here, we characterized the time course of protective efficacy of midazolam (0.2-5 mg/kg, i.m.) in rats exposed to DFP, a chemical threat agent and surrogate for nerve agents. Behavioral and electroencephalogram (EEG) seizures were monitored for 24 hours after DFP exposure. The extent of brain injury was determined 3 days after DFP exposure by unbiased stereologic analyses of valid markers of neurodegeneration and neuroinflammation. Seizures were elicited within ∼8 minutes after DFP exposure that progressively developed into persistent SE lasting for hours. DFP exposure resulted in massive neuronal injury or necrosis, neurodegeneration of principal cells and interneurons, and neuroinflammation as evident by extensive activation of microglia and astrocytes in the hippocampus, amygdala, and other brain regions. Midazolam controlled seizures, neurodegeneration, and neuroinflammation when given early (10 minutes) after DFP exposure, but it was less effective when given at 40 minutes or later. Delayed therapy (≥40 minutes), a simulation of the practical therapeutic window for first responders or hospital admission, was associated with reduced seizure protection and neuroprotection. These results strongly reaffirm that the DFP-induced seizures and brain damage are progressively resistant to delayed treatment with midazolam, confirming the benzodiazepine refractory SE after OP intoxication. Thus, novel anticonvulsants superior to midazolam or adjunct therapies that enhance its efficacy are needed for effective treatment of refractory SE.


Acceptance in chronic neck pain: associations with disability and fear avoidance beliefs.
Chronic neck pain can result in significant levels of disability. Physiotherapy treatments often aim to modify cognitive factors and this approach benefits some, but not all, patients. Research from other pain conditions suggests that acceptance may be related to disability; however, it is unclear whether these associations exist in patients with neck pain. Moreover, it is unclear to what extent other cognitive factors are related to acceptance. Feasibly, if these factors are related, existing treatments may already be indirectly modifying acceptance. The aim of this study was therefore to establish the associations between acceptance and disability, and between acceptance and other cognitive factors. Cross-sectional data were collected from 149 patients and regression analyses were carried out. In the first analysis, disability was the dependent variable and the proportion of variance explained by two acceptance subscales (activities engagement and pain willingness) was calculated. In the second analyses, the acceptance subscales were the dependent variables. Measures of pain-related fear, catastrophizing and pain vigilance and awareness were entered as explanatory variables and the proportion of variance explained was calculated. In the first analysis, acceptance explained 18% of variance in disability (P<0.001). In the second analysis, cognitive factors explained 7% (P<0.05) of variance in activities engagement and 58% (P<0.001) of pain willingness. On this basis, treatments that enhance acceptance may reduce disability. Moreover, as cognitive factors were strongly related to pain willingness, but not activity engagement, alternative treatments may be required to maximize acceptance. Further studies are warranted to assess acceptance-based treatments in patients with neck pain.


Severity Assessment in CDKL5 Deficiency Disorder.
Pathologic mutations in cyclin-dependent kinase-like 5 cause CDKL5 deficiency disorder, a genetic syndrome associated with severe epilepsy and cognitive, motor, visual, and autonomic disturbances. This disorder is a relatively common genetic cause of early-life epilepsy. A specific severity assessment is lacking, required to monitor the clinical course and needed to define the natural history and for clinical trial readiness. A severity assessment was developed based on clinical and research experience from the International Foundation for CDKL5 Research Centers of Excellence consortium and the National Institutes of Health Rett and Rett-Related Disorders Natural History Study consortium. An initial draft severity assessment was presented and reviewed at the annual CDKL5 Forum meeting (Boston, 2017). Subsequently it was iterated through four cycles of a modified Delphi process by a group of clinicians, researchers, industry, patient advisory groups, and parents familiar with this disorder until consensus was achieved. The revised version of the severity assessment was presented for review, comment, and piloting to families at the International Foundation for CDKL5 Research-sponsored family meeting (Colorado, 2018). Final revisions were based on this additional input. The final severity assessment comprised 51 items that comprehensively describe domains of epilepsy; motor; cognition, behavior, vision, and speech; and autonomic functions. Parental ratings of therapy effectiveness and child and family functioning are also included. A severity assessment was rapidly developed with input from multiple stakeholders. Refinement through ongoing validation is required for future clinical trials. The consensus methods employed for the development of severity assessment may be applicable to similar rare disorders.


NRS2002 assesses nutritional status of leukemia patients undergoing hematopoietic stem cell transplantation.
To discuss whether nutritional risk screening 2002 (NRS2002) is appropriate for nutritional risk screening for leukemia patients before and after hematopoietic stem cell transplantation (HSCT), and whether there are risk differences in other conditions, such as age, gender and matching degree; to find the methods and indicators of nutritional risk screening for these patients before and after HSCT, in order to give timely intervention to guarantee the successful completion of the entire transplantation process. Nutritional risk of 99 leukemia patients was screened with NRS2002 before and after HSCT. The (χ) (2) test was applied to compare the risk differences between groups such as age, gender and matching degree, while the differences of other enumeration data, such as recent (1-3 months) weight loss, reduced food intake within one week and BMI, were compared by continuity correction. Of the 99 leukemia patients, 22 cases (22.2%) had nutritional risk before HSCT, while all patients had nutritional risk after HSCT; there is no significant difference in nutritional risk between male and female, and patients of less than 30 years old, not-full matched, recent (1-3 months) weight loss, reduced food intake within a week or BMI <18.5 were more likely to have nutritional risk; and 77 cases (77.8%) had weight loss, among which 49 patients (63.6%) had more than 5% weight loss within one month. This study showed that leukemia patients should receive the nutritional risk screening conventionally before and after HSCT, and NRS2002 was only appropriate for nutritional risk screening before HSCT. More attention should be paid to the patients less than 30 years old or not-full matched. Weight change was one of the important nutritional indicators for patients after HSCT.


Comparison of cloacal and oropharyngeal samples for the detection of avian influenza virus in wild birds.
This study was conducted to compare oropharyngeal (OP) and cloacal samples of wild birds (n = 137) for the detection and isolation of avian influenza virus (AIV). A total of 39 (28.5%) cloacal and 85 (62.0%) OP samples were positive for AIV by real-time reverse transcription-PCR (RRT-PCR). The AIV nucleic acid was detected in both cloacal and OP samples from 27 (19.7%) birds, in cloacal samples only from 12 (8.8%) birds, and in OP samples only from 58 (42.3%) birds. Thus, a total of 97 (70.8%) birds were AIV positive by RRT-PCR. The cycle threshold values for the cloacal samples ranged from 16.6 to 36.9 (mean 31.5), and those for OP samples ranged from 18 to 38.9 (mean 34.9). Of the cloacal samples, 12 were positive for H5 subtype influenza virus by RRT-PCR, with one being low pathogenic H5N1. In contrast, five of the OP samples were H5 positive, but none was H5N1. None of the cloacal or OP samples was H7 positive. Eight cloacal samples yielded AIV on inoculation in embryonated chicken eggs, while only one isolate was obtained from OP samples. Thus, from testing of 137 birds, only nine (6.6%) AIV isolates were obtained. The isolates from cloacal samples were subtyped as H6N1 (n = 5), H3N8 (n = 2), and H4N8 (n = 1), and the isolate from OP sample was subtyped as H6N1. No virus was isolated from the corresponding cloacal sample of the bird whose OP sample yielded AIV on virus isolation. These results suggest that surveillance programs for detection of AIV by RRT-PCR may include both sample types (cloacal and OP) to obtain a better picture of AIV prevalence, and OP samples may yield additional isolates of AIV when tested in conjunction with cloacal samples.


Comparison of approaches for estimating prevalence costs of care for cancer patients: what is the impact of data source?
National prevalence costs of medical care can be key inputs in health policy decisions. Cost estimates vary across data sources, patient populations, and methods, however, the objective of this study was to compare 3 approaches for estimating the prevalence costs of colorectal cancer (CRC) care using different data sources, but similar patient populations and methods. We identified prevalent CRC patients aged 65 and older from: (1) linked Surveillance Epidemiology and End Results (SEER) registry-Medicare data, (2) Medicare claims only, and (3) the Medical Expenditure Panel Survey (MEPS). Controls were matched by sex, age-group, and geographic location. Mean per person total and net costs, measured as the difference between patients and controls, were compared for each approach during a similar observation period. The SEER-Medicare approach was our reference, and we evaluated the impact of patient selection criteria with sensitivity analyses. Aggregate prevalence estimates were also compared. We found considerable variability across the different approaches to estimating prevalence costs of CRC. Mean net annual per person estimates in the SEER-Medicare reference were $5341 (95% CI: $5243, $5439), compared with $8736 (95% CI: $8203, $9269) for the Medicare claims only and $11,614 (95% CI: $7566, $15,663) for the MEPS. Aggregate national estimates of net prevalence costs of CRC in 2004 ranged from $4524 million, using the SEER-Medicare approach, to $9629 million, using the MEPS approach. Estimates varied by data source based on the payors included and identification of prevalent CRC patients. CRC prevalence cost estimates vary substantially depending on the data sources. Our findings have implications for estimating prevalence costs for other cancers and other diseases without registry systems that can be used to identify newly diagnosed individuals as well as those diagnosed less recently.


The perception of animacy in young children with autism.
Visual perception may be a developmental prerequisite to some types of social understanding. The ability to perceive social information given visual motion appears to develop early. However, children with autism have profound deficits in social cognitive function and may fail to see social motion in the same way that typically developing children do. We tested the hypothesis that children with autism fail to discriminate animate motion, using a novel paradigm involving simple geometric figures. The subjects were 23 children with autism (c.a. 70.7 mos.), 18 children with other developmental disabilities (c.a. 68.2 mos.), and 18 typically developing children (c.a. 46.4 mos.). Children saw two circles moving on a screen and were rewarded for identifying the one that moved as if animate. A control condition required children to identify the heavier of two objects. Children with autism initially showed a deficit in categorizing objects as animate (though no deficit on the control task), but showed no deficit in this ability after they had reached criterion in the training phase. These results are discussed in terms of the social orienting theory of autism, and the possibility that animacy perception might be preserved in autism, even if it is not used automatically.


Psychosocial Profiles of Temporomandibular Disorder Pain Patients: Proposal of a New Approach to Present Complex Data.
To propose a visual method to screen and assess psychosocial functioning in temporomandibular disorder (TMD) pain patients in comparison with age- and gender-matched healthy controls by forming individual profiles and to evaluate the association between psychosocial profiles and quantitative sensory testing (QST) findings of TMD pain patients. TMD patients (n = 58) and control participants (n = 41) completed a set of questionnaires profiling their psychosocial function, and QST was performed at the temporomandibular joint (TMJ) on both sides of the face in all participants. Psychosocial parameters from the Research Diagnostic Criteria for TMD (RDC/TMD), Oral Health Impact Profile (OHIP), and Pain Catastrophizing Scale (PCS) instruments were transformed into T scores, and QST parameters were transformed into z scores based on reference data. Group differences for psychosocial T scores were analyzed with t tests. T scores of psychosocial parameters and z scores of QST parameters were correlated using Spearman's correlation (ρ). Most (96.6%) TMD pain patients exhibited one or more parameters indicative of psychosocial distress, with psychological disability scores being the scores most frequently encountered outside the reference 95% confidence intervals (CI). TMD patients were psychosocially more distressed with regard to all psychosocial parameters compared with controls (P < .009). After Bonferroni corrections, a significant correlation was detected between the sleep dysfunction parameter and mechanical detection threshold (MDT) in TMD pain patients (ρ = 0.427, P < .001). T score psychosocial profiles created an easy overview of psychosocial function in TMD pain patients. Increased sensitivity to tactile stimuli was associated with higher sleep dysfunction T scores.


Rate of information segregation in developmentally dyslexic children.
Slowed processing of sequential perceptual information is related to developmental dyslexia. We investigated this unimodally and crossmodally in developmentally dyslexic children and controls ages 8-12 years. The participants judged whether two spatially separate trains of brief stimuli, presented at various stimulus onset asynchronies (SOA) in one or two senses, were synchronous or not. The stimulus trains consisted of light flashes in vision, clicks in audition, and indentations of the skin in the tactile sense. The dyslexic readers required longer SOAs than controls for successful performance in all six comparisons. The crossmodal spatiotemporal resolution of the groups differed more than unimodal performance. The dyslexic readers' segregation performance was also less differentiated than that of the controls. Our results show that not only sensory but also polysensory nonverbal information processing is temporally impaired in dyslexic children.


[Post-mastectomy lymphedema: surgical therapy].
After some preliminary remarks concerning epidemiological data about post-mastectomy lymphedema, on the basis of specific etiologic and pathophysiologic aspects, authors report a modern clinical and instrumental staging of lymphedema and an accurate diagnostic protocol, which allows not only to study lymphedema at late stages, but also to individuate the disease at earliest stages. Protocols of medical, physical and rehabilitative treatment mostly used today are schematically described, and they include proper igienic measures for the prevention bacterial and micotic infections, manual lymph drainage, sequential compression therapy, exercises, thermotherapy, bandages and elastic garments. Authors underline above all the importance of Microsurgery in treating post-mastectomy lymphedema, by means of modern methods of lymphatic microsurgery, derivative or reconstructive (multiple lymphatic-venous anastomoses, lymphatic-venous-lymphatic plasty). The operation of multiple lymphatic-venous anastomoses represent the mostly used technique. The registry consists of 194 microsurgical operations, performed in patients treated and followed-up statistically in the last 15 years, with positive result in over 80% of cases.


In vivo estimation of murine iris stiffness using finite element modeling.
The iris plays an important role in certain types of glaucoma, including primary angle-closure glaucoma and pigmentary glaucoma. Iris mechanics are also important in influencing trabecular meshwork deformation in response to intraocular pressure changes in some animal species. Although mice are widely used to study ocular disease, including glaucoma, the in vivo biomechanical properties of the murine iris are unknown. Thus, the primary objective of this study was to estimate murine iris biomechanical stiffness. We used optical coherence tomography (OCT) images of the anterior segment of living mice (n = 13, age = 7.3 ± 3.2 [mean ± SD] months) at sequentially increasing IOP levels, observing IOP-dependent iris deformations. We then used an inverse finite element model to predict iris deformations under the same conditions, estimating iris stiffness by maximizing agreement between OCT data and numerical simulations. Our results show an in vivo murine iris stiffness of 96.1 ± 54.7 kPa (mean ± SD), which did not correlate with age but was dependent on gender. Our results further showed strong evidence of reverse pupillary block, with mean posterior chamber pressure remaining at approximately 12 mmHg even as anterior chamber pressure was set to much higher levels. Our approach to monitoring iris stiffness in vivo is applicable to study potential changes of iris stiffness in various pathophysiological conditions and thus has significant potential for clinical care of ocular disease involving iris biomechanics.


Inhibitor studies of phage T4 wild-type and mutant DNA polymerases. V. A. summary of kinetic and inhibitor data.
The DNA polymerases of phage T4 wild-type, the mutator mutant L98 and the antimutator mutant CB121 were purified about 100-fold free of foreign enzyme activities interfering with the polymerase assay. The enzymes were characterized as to thermostability, exonuclease activity and kinetic data with DNA template primer, deoxythymidine 5' -triphosphate, and a mixture of all four deoxynucleoside 5' -triphosphates. The effects of eight inhibitors of DNA synthesis on the three enzymes were determined (Schroeder and Jantschak 1978 and 1980, Jantschak and Schroeder 1980) and are compared here. The most selective inhibitor, pyridoxal 5' -phosphate, interacts with the active site of the polymerases while the two least discriminating drugs, distamycin A and actinomycin D, do not directly interact with the polymerases at all. The study was intended to test whether specific enzyme inhibitors elicit a differential response in temperature-sensitive structural variants of this enzyme and whether, in principle, structural variants of virus enzymes or the respective ts- mutants in vivo are suitable as a screening system for selective antiviral agents.


Presenilin-1-dependent transcriptome changes.
Familial forms of Alzheimer's disease (FADs) are caused by the expression of mutant presenilin 1 (PS1) or presenilin 2. Using DNA microarrays, we explored the brain transcription profiles of mice with conditional knock-out of PS1 (cKO PS1) in the forebrain. In parallel, we performed a transcription profiling of the hippocampus and frontal cortex of the FAD-linked DeltaE9 mutant transgenic (TG) mice and matched controls [TG mice expressing wild-type human PS1 (hPS1)]. When the TG and cKO datasets were cross-compared, the majority of the 30 common expression alterations were in opposite direction, suggesting that the FAD-linked PS1 variant produces transcriptome changes primarily by gain of aberrant function. Our microarray studies also revealed an unanticipated inverse correlation of transcript levels between the brains of mice that coexpress DeltaE9 hPS1+ amyloid precursor protein (APP)695 Swe and DeltaE9 hPS1 single transgenic mice. The opposite directionality of these changes in transcript levels must be a function of APP and/or APP derivatives.


Surgical repair of rib fractures in 14 neonatal foals: case selection, surgical technique and results.
Fractured ribs are encountered quite frequently in newborn Thoroughbred foals, often with fatal outcome. Surgical repair of fractures therefore requires consideration as a means of reducing mortality. To evaluate the repair of rib fractures using internal fixation techniques in foals at 2 different equine hospitals following similar diagnostics and case selection. The records of 14 foals that underwent internal fixation of fracture ribs were reviewed. Subject details, clinical presentation, diagnosis, surgical technique, post operative care and complications were recorded. Follow-up information was obtained in 7 foals. The fractured ribs were reduced and stabilised using reconstruction plate(s), self-tapping cortical screws and cerclage wire in 12 cases, Steinmann pins and cerclage wires in 1 case and both techniques in 1 case. Not every rib was reduced on each case. Surgical reduction was performed on an average of 2 ribs, range 1-3 ribs in each foal. At the time of writing, 4 foals had been sold, one age 2 years was in training and 2 others died from unrelated causes. Our data support the use of surgical stabilisation utilising reconstruction plates, self-tapping cortical screws and cerclage wire for selected cases of thoracic trauma in neonatal foals. The use of Steinmann pins may be suboptimal due to cyclic failure, implant migration and the potential for iatrogenic internal thoracic trauma. Foals with existing extensive internal thoracic trauma resulting from rib fracture(s), or the potential for such trauma, previously considered to have a guarded to poor prognosis for survival, may be successfully managed with internal fixation of selected fracture sites.


Assessing recovery and establishing prognosis following total knee arthroplasty.
Information about expected rate of change after arthroplasty is critical for making prognostic decisions related to rehabilitation. The goals of this study were: (1) to describe the pattern of change in lower-extremity functional status of patients over a 1-year period after total knee arthroplasty (TKA) and (2) to describe the effect of preoperative functional status on change over time. Eighty-four patients (44 female, 40 male) with osteoarthritis, mean age of 66 years (SD=9), participated. Repeated measurements for the Lower Extremity Functional Scale (LEFS) and the Six-Minute Walk Test (6MWT) were taken over a 1-year period. Data were plotted to examine the pattern of change over time. Different models of recovery were explored using nonlinear mixed-effects modeling that accounted for preoperative status and gender. Growth curves were generated that depict the rate and amount of change in LEFS scores and 6MWT distances up to 1 year following TKA. The curves account for preoperative status and gender differences across participants. The greatest improvement occurred in the first 12 weeks after TKA. Slower improvement continued to occur from 12 weeks to 26 weeks after TKA, and little improvement occurred beyond 26 weeks after TKA. The findings can be used by physical therapists to make prognostic judgments related to the expected rate of improvement following TKA and the total amount of improvement that may be expected.


ARID5B Influences Antimetabolite Drug Sensitivity and Prognosis of Acute Lymphoblastic Leukemia.
Treatment outcomes for childhood acute lymphoblastic leukemia (ALL) have improved steadily, but a significant proportion of patients still experience relapse due to drug resistance, which is partly explained by inherited and/or somatic genetic alternations. Recently, we and others have identified genetic variants in the ARID5B gene associated with susceptibility to ALL and also with relapse. In this study, we sought to characterize the molecular pathway by which ARID5B affects antileukemic drug response in patients with ALL. We analyzed association of ARID5B expression in primary human ALL blasts with molecular subtypes and treatment outcome. Subsequent mechanistic studies were performed in ALL cell lines by manipulating ARID5B expression isogenically, in which we evaluated drug sensitivity, metabolism, and molecular signaling events. ARID5B expression varied substantially by ALL subtype, with the highest level being observed in hyperdiploid ALL. Lower ARID5B expression at diagnosis was associated with the risk of ALL relapse, and further reduction was noted at ALL relapse. In isogenic ALL cell models in vitro, ARID5B knockdown led to resistance specific to antimetabolite drugs (i.e., 6-mercaptopurine and methotrexate), without significantly affecting sensitivity to other antileukemic agents. ARID5B downregulation significantly inhibited ALL cell proliferation and caused partial cell-cycle arrest. At the molecular level, the cell-cycle checkpoint regulator p21 (encoded by CDKN1A) was most consistently modulated by ARID5B, plausibly as its direct transcription regulation target. Our data indicate that ARID5B is an important molecular determinant of antimetabolite drug sensitivity in ALL, in part, through p21-mediated effects on cell-cycle progression.


Feminine Hygiene and Vaginal Douche Practices in Middle-aged Women.
The study was done to survey feminine hygiene and vaginal douche practices in middle-aged women to obtain basic information for public health education. With a descriptive survey design, 134 middle-aged women who have menstrual period were recruited via convenience sampling. Survey contents were from the study by Czerwinski (2000) regarding feminine hygiene and vaginal douching practices. After obtaining IRB approval, a self-administered structured questionnaire was distributed to study participants. Mean age of middle-aged women was 46.88 years old. Fifty-six percent of the women practiced vaginal douching. Women performed douching with water (68%), commercial products (13%), soap (12%), and vinegar-mixed water (6%) for clean and fresh feeling, removal of unpleasant odor, and removal of vaginal discharge. Vaginal douche practice was significantly related to a history of vaginitis. The study results indicate that most of the women practiced inadequate feminine hygiene especially in douching, suggesting that is important to develop education programs on feminine hygiene practices for women of all ages, especially regarding douching and hand washing before and after changing pads or tampons.


Fullerene-Based Mimics of Biocatalysts Show Remarkable Activity and Modularity.
The design of catalysts with greater control over catalytic activity and stability is a major challenge with substantial impact on fundamental chemistry and industrial applications. Due to their unparalleled diversity, selectivity, and efficiency, enzymes are promising models for next-generation catalysts, and considerable efforts have been devoted to incorporating the principles of their mechanisms of action into artificial systems. We report a heretofore undocumented catalyst design that introduces fullerenes to the field of biocatalysis, which we refer to as fullerene nanocatalysts, and that emulates enzymatic active sites through multifunctional self-assembled nanostructures. As a proof-of-concept, we mimicked the reactivity of hydrolases using fullerene nanocatalysts functionalized with the basic components of the parent enzyme with remarkable activity. Owing to the versatile amino acid-based functionalization repertoire of fullerene nanocatalysts, these next-generation carbon/biomolecule hybrids have potential to mimic the activity of other families of enzymes and, therefore, offer new perspectives for the design of biocompatible, high-efficiency artificial nanocatalysts.


RfaH enhances elongation of Escherichia coli hlyCABD mRNA.
Escherichia coli hlyCABD operons encode the polypeptide component (Hly A) of an extracellular cytolytic toxin, as well as proteins required for its acylation (HlyC) and sec-independent secretion (HlyBD). Previous reports suggested that the E. coli protein RfaH is required for wild-type hemolysin expression, either by positively activating hly transcript initiation (M. J. A. Bailey, V. Koronakis, T. Schmoll, and C. Hughes, Mol. Microbiol. 6:1003-1012, 1992) or by promoting proper insertion of hemolysin export machinery in the E. coli outer membrane (C. Wandersman and S. Letoffe, Mol. Microbiol. 7:141-150, 1993). RfaH is also required for wild-type levels of mRNA transcribed from promoter-distal genes in the rfaQ-K, traY-Z, and rplK-rpoC gene clusters, suggesting that RfaH is a transcriptional antiterminator. We tested these models by analyzing the effects of rfaH mutations on hlyCABD mRNA synthesis and decay, HlyA protein levels, and hemolytic activity. The model system included a uropathogenic strain of E. coli harboring hlyCABD on the chromosome and E. coli K-12 transformed with the hlyCABD operon on a recombinant plasmid. Our results suggest that RfaH enhances hlyCABD transcript elongation, consistent with the model of RfaH involvement in transcriptional antitermination in E. coli. We also demonstrated that RfaH increases toxin efficacy. Modulation of hemolysin activity may be an indirect effect of RfaH-dependent E. coli outer membrane chemotype, which is consistent with the model of lipopolysaccharide involvement in hemolytic activity.


Simulation in Learning and Using the Nutrition Care Process/Terminology: Experiences and Perceptions of Dietitians in Canada.
Purpose: To investigate experiences with, and perceptions of, simulation in learning and using the Nutrition Care Process/Terminology (NCP/T) of dietitians in Canada. Methods: In February-March 2017, a convenience sample of 382 dietitians in Canada (71.8% in clinical practice) completed an online survey regarding the type(s), setting(s), and perceptions of the simulations in which they engaged in learning and using the NCP/T. Results: A majority (76.7%) of respondents had engaged in NCP/T-related simulation, most commonly case studies (85.3%) and role-play (42.0%), as part of workplace/volunteer training (51.4%) and undergraduate internship/stage/practicum (34.2%). Nearly half (49.5%) of respondents learned all 4 NCP components via simulation, with Nutrition Diagnosis being the most common individual component (57%). Over three-quarters of respondents agreed/strongly agreed that simulation helped them better understand/use the NCP/T and that NCP/T-related knowledge/skills gained through simulation are transferable to the clinical setting/dietetic practice. Conclusions: Dietitians in Canada perceive simulation to have helped them learn and use the NCP/T. Resources should be directed at further developing simulation for teaching the NCP/T in dietetics education and training. Research investigating characteristics, barriers, and facilitators of effective NCP/T-simulation, using objective (vs. perceived) learning outcome measures is needed.


3.5D dynamic PET image reconstruction incorporating kinetics-based clusters.
Standard 3D dynamic positron emission tomographic (PET) imaging consists of independent image reconstructions of individual frames followed by application of appropriate kinetic model to the time activity curves at the voxel or region-of-interest (ROI). The emerging field of 4D PET reconstruction, by contrast, seeks to move beyond this scheme and incorporate information from multiple frames within the image reconstruction task. Here we propose a novel reconstruction framework aiming to enhance quantitative accuracy of parametric images via introduction of priors based on voxel kinetics, as generated via clustering of preliminary reconstructed dynamic images to define clustered neighborhoods of voxels with similar kinetics. This is then followed by straightforward maximum a posteriori (MAP) 3D PET reconstruction as applied to individual frames; and as such the method is labeled '3.5D' image reconstruction. The use of cluster-based priors has the advantage of further enhancing quantitative performance in dynamic PET imaging, because: (a) there are typically more voxels in clusters than in conventional local neighborhoods, and (b) neighboring voxels with distinct kinetics are less likely to be clustered together. Using realistic simulated (11)C-raclopride dynamic PET data, the quantitative performance of the proposed method was investigated. Parametric distribution-volume (DV) and DV ratio (DVR) images were estimated from dynamic image reconstructions using (a) maximum-likelihood expectation maximization (MLEM), and MAP reconstructions using (b) the quadratic prior (QP-MAP), (c) the Green prior (GP-MAP) and (d, e) two proposed cluster-based priors (CP-U-MAP and CP-W-MAP), followed by graphical modeling, and were qualitatively and quantitatively compared for 11 ROIs. Overall, the proposed dynamic PET reconstruction methodology resulted in substantial visual as well as quantitative accuracy improvements (in terms of noise versus bias performance) for parametric DV and DVR images. The method was also tested on a 90 min (11)C-raclopride patient study performed on the high-resolution research tomography. The proposed method was shown to outperform the conventional method in visual as well as quantitative accuracy improvements (in terms of noise versus regional DVR value performance).


From data to optimal decision making: a data-driven, probabilistic machine learning approach to decision support for patients with sepsis.
A tantalizing question in medical informatics is how to construct knowledge from heterogeneous datasets, and as an extension, inform clinical decisions. The emergence of large-scale data integration in electronic health records (EHR) presents tremendous opportunities. However, our ability to efficiently extract informed decision support is limited due to the complexity of the clinical states and decision process, missing data and lack of analytical tools to advice based on statistical relationships. Development and assessment of a data-driven method that infers the probability distribution of the current state of patients with sepsis, likely trajectories, optimal actions related to antibiotic administration, prediction of mortality and length-of-stay. We present a data-driven, probabilistic framework for clinical decision support in sepsis-related cases. We first define states, actions, observations and rewards based on clinical practice, expert knowledge and data representations in an EHR dataset of 1492 patients. We then use Partially Observable Markov Decision Process (POMDP) model to derive the optimal policy based on individual patient trajectories and we evaluate the performance of the model-derived policies in a separate test set. Policy decisions were focused on the type of antibiotic combinations to administer. Multi-class and discriminative classifiers were used to predict mortality and length of stay. Data-derived antibiotic administration policies led to a favorable patient outcome in 49% of the cases, versus 37% when the alternative policies were followed (P=1.3e-13). Sensitivity analysis on the model parameters and missing data argue for a highly robust decision support tool that withstands parameter variation and data uncertainty. When the optimal policy was followed, 387 patients (25.9%) have 90% of their transitions to better states and 503 patients (33.7%) patients had 90% of their transitions to worse states (P=4.0e-06), while in the non-policy cases, these numbers are 192 (12.9%) and 764 (51.2%) patients (P=4.6e-117), respectively. Furthermore, the percentage of transitions within a trajectory that lead to a better or better/same state are significantly higher by following the policy than for non-policy cases (605 vs 344 patients, P=8.6e-25). Mortality was predicted with an AUC of 0.7 and 0.82 accuracy in the general case and similar performance was obtained for the inference of the length-of-stay (AUC of 0.69 to 0.73 with accuracies from 0.69 to 0.82). A data-driven model was able to suggest favorable actions, predict mortality and length of stay with high accuracy. This work provides a solid basis for a scalable probabilistic clinical decision support framework for sepsis treatment that can be expanded to other clinically relevant states and actions, as well as a data-driven model that can be adopted in other clinical areas with sufficient training data.


Factor structure of the critical consciousness scale in juvenile legal system-involved boys and girls.
The Critical Consciousness Scale (CCS) is a recently developed and validated measure for use with low-income, diverse adolescents. However, research on the psychometric properties of this scale with juvenile legal system-involved youth is lacking. This study examines the psychometric properties of the critical reflection subscales of the CCS in a cross-sectional sample of 206 youth (48% girls) involved in the juvenile legal system to investigate (a) the factor structure of the critical reflection subscales of the CCS compared to existing adolescent samples, and (b) the extent to which critical reflection demonstrates measurement equivalence between boys and girls. Findings indicate (a) congruence with the previous literature on critical reflection but for system-involved girls, and (b) a difference in the structural relationships between perceived inequality and egalitarianism by gender. This study contributes to the nascent, psychometric literature on measures of critical consciousness in an underrepresented and unique adolescent population.


Assistive robots for socialization in elderly people: results pertaining to the needs of the users.
Technological solutions can support the elderly, improve their quality of life and reduce isolation and loneliness. The Euro-Japan ACCRA (Agile Co-Creation for Robots and Aging) project has the objective of building a reference co-creation methodology for the development of robotic solutions for ageing. The aim of this study is to provide a pilot qualitative analysis of the real needs of elderly people and their caregivers when exposed to conversational activities with robots and to identify priority needs that should be developed from end-user perspectives. A qualitative research design was adopted to define a pre-structured questionnaire that was administered to the elderly taking part in the piloting sessions. Three groups of end-users were included: subjects with an age ≥ 60 years, informal caregivers and formal caregivers. The interviews were carried out in Italy and Japan. A total of 17 elderly and 36 caregivers were recruited. Common needs in the two sites were categorized into 3 groups: Communication; Emotion Detection and Safety. General robot acceptance level is good and perception is positive among participants in the pilot sites. A positive perception of the elderly on the application of a robotic solution was found and many are the needs that could be addressed by an appropriate and careful robotic development taking into account the real needs and capabilities of the involved subjects.


Placental pathology in trap sequence: clinical and pathogenetic implications.
Twin reversed arterial perfusion sequence (TRAP) resulting in an acardiac twin is a rare occurrence. Acardia requires the presence of arterial-arterial anastomosis, with retrograde perfusion of poorly oxygenated blood from the normal twin to the acardiac twin, venous-venous anastomosis carrying blood back from the acardiac to the normal twin, and circulatory failure of the acardiac twin. Although vascular anastomoses in cases of TRAP have been well described, there is little published literature on the microscopic changes in the placenta in TRAP sequence. We report a case of monochorionic monozygotic twins with an acardiac twin, large arterial-arterial anastomosis, and direct continuity of the umbilical cord veins. The placenta showed villous immaturity, striking villous calcifications, and extensive fetal thrombotic vasculopathy of the umbilical vein of the donor twin and the chorionic plate vessels. Thrombi in the umbilical vessels of the acardiac twin have been reported, and trombi in donor twin organs have been seen after fetal demise in utero. But to our knowledge there is no previously reported thrombi in the donor twin umbilical vessels or the chorionic plate veins. This may have implications not only as a possible factor in the etiology of TRAP, but also and more important as a possible risk factor for thrombotic events in the donor twin. Further studies with clinico-pathological correlation are needed to explore this issue.


Spontaneous internal jugular vein thrombosis: primary manifestation of a colorectal adenocarcinoma in a very old woman.
We report the history of a very old woman with a spontaneous internal jugular vein thrombosis as the presenting feature of an occult adenocarcinoma of the caecum. Spontaneous internal jugular vein thrombosis is an unusual form of venous thrombosis. Doppler ultrasound and Computed Tomography or Magnetic Resonance Imaging should confirm signs and symptoms suggesting thrombosis. Immediate anticoagulation with heparin followed by oral anticoagulation is mandatory to reduce associated mortality and morbidity. If no risk factors for internal jugular vein thrombosis are present, a work-up for hypercoagulable states and a careful search for distant malignancy should been obtained. If screening shows no obvious malignancy, further follow-up is necessary.


Improved one-shot learning for feedforward associative memories with application to composite pattern association.
The local identical index (LII) associative memory (AM) proposed by the authors in a previous paper is a one-shot feedforward structure designed to exhibit no spurious attractors. In this paper we relax the latter design constraint in exchange for enlarged basins of attraction and we develop a family of modified LII AM networks that exhibit improved performance, particularly in memorizing highly correlated patterns. The new algorithm meets the requirement of no spurious attractors only in a local sense. Finally, we show that the modified LII family of networks can accommodate composite patterns of any size by storing (memorizing) only the basic (prime) prototype patterns. The latter property translates to low learning complexity and a simple network structure with significant memory savings. Simulation studies and comparisons illustrate and support the the optical developments.


Field trials with a bivalent vaccine (HVT and SB-1) against Marek's disease.
White leghorn chickens on five farms were given a bivalent Marek's disease (MD) vaccine consisting of turkey herpesvirus (HVT) and SB-1 (a nononcogenic MD virus); other chickens received only HVT. The farms had histories of "vaccination failures," presumably owing to an exceptionally virulent challenge MD virus. The bivalent vaccine uniformly protected chickens better than HVT alone between 12 and 16-20 weeks of age, when serious MD losses occurred. During that period, total mortality in groups given both viruses ranged from 0.39 to 1.26% (mean 0.86%), whereas that in HVT-vaccinated groups not exposed to SB-1 varied from 1.92 to 7.44% (mean 3.43%). Chickens in pens or rows with close contact to those given bivalent vaccine also had low MD mortality rates (0.46-1.06%, mean 0.77%), probably from the spread of SB-1.


Prediction of molecular mechanism of processed ginseng in the treatment of heart failure based on network pharmacology and molecular docking technology.
Heart failure (HF) is the most common cardiovascular disease in clinics. Processed Panax ginseng C.A. Mey. Products have significant therapeutic effects on HF. Therefore, it is of great significance to explore the mechanism of action of Processed Panax ginseng C.A. Mey. Products in the treatment of HF. The saponin-like constituents of 3 different ginseng preparations were characterized by UPLC/QE-MS and the identified saponin constituents were subjected to network pharmacological analysis. Protein-protein interaction analyses of the targets of different ginseng preparations for the treatment of heart failure (HF) were performed using the STRING database, Gene Ontology enrichment analyses and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the DAVID database, and the results of the network pharmacological analyses were validated using the Autodock software. Finally, the relative quantitative content of 5 major ginsenosides in 3 processed ginseng products was evaluated. A total of 40 saponin compounds were identified based on mass spectrometry data. Network pharmacology and molecular docking analyses were used to predict the major targets of these sapions compounds and the key pathways mediating their anti-HF effects. After conducting a thorough screening, the study identified 5 primary ingredients of ginseng products ginsenoside Rh4, ginsenoside Rk3, ginsenoside Rk1, ginsenoside Rg5, and ginsenoside CK that can potentially target 22 essential proteins: EGFR, AKT1, ERBB2, STAT3, TNF, ESR1, MTOR, HRAS, MMP9, and PIK3CA, etc. Additionally, the Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that ginseng products can be beneficial in treating HF by interacting with pathways such as the PI3K-Akt signaling pathway, the TNF signaling pathway, the mTOR signaling pathway, and others. The present study revealed that the treatment of HF with different processed ginseng products may be related to the regulation of the PI3K-Akt signaling pathway, TNF signaling pathway, apoptosis pathway, mTOR signaling pathway, etc, and that the key active ingredients may be concentrated in black ginseng, which provides a theoretical basis and direction for the further study of the mechanism of action of ginseng. This provides a theoretical basis and research direction for further in-depth study of its mechanism of action.


Anterior chamber-associated immune deviation promotes corneal allograft survival.
To determine whether anterior chamber-associated immune deviation (ACAID) promotes corneal allograft survival. CB6F1 mice were grafted with orthotopic corneal transplants from C3H donors (mismatch at the entire major histocompatibility complex plus multiple minor histocompatibility loci) and from NZB donors (mismatch only at multiple minor histocompatibility loci). ACAID was induced by priming in the anterior chamber (AC) with either Ia- spleen cells, Ia+ spleen cells, corneal endothelial cells, or corneal epithelial cells from corneal allograft donors before orthotopic transplantation. The role of ACAID in promoting corneal allograft survival was examined by determining the fate of corneal allografts in splenectomized and eusplenic mice. Anterior chamber priming produced a modest enhancement of the survival of fully allogeneic C3H corneal allografts. By contrast, AC priming with Ia- NZB spleen cells or NZB corneal endothelial cells results in the permanent acceptance of NZB corneal grafts in 60% and 90% of the CB6F1 hosts, respectively. Abolition of ACAID by splenectomy resulted in a sharp increase in the incidence of graft rejection in donor-host combinations involving multiple minor histocompatibility disparity. Anterior chamber priming with alloantigens promotes corneal allograft survival in nonimmune and preimmune hosts. Disruption of the camero-splenic axis prevents the induction of ACAID and greatly increases the risk for corneal allograft rejection.


Tetherin Inhibits Cell-Free Virus Dissemination and Retards Murine Leukemia Virus Pathogenesis.
The relative contributions of cell-free virion circulation and direct cell-to-cell transmission to retroviral dissemination and pathogenesis are unknown. Tetherin/Bst2 is an antiviral protein that blocks enveloped virion release into the extracellular milieu but may not inhibit cell-to-cell virus transmission. We developed live-cell imaging assays which show that tetherin does not affect Moloney murine leukemia virus (MoMLV) spread, and only minimally affects vesicular stomatitis virus (VSV) spread, to adjacent cells in a monolayer. Conversely, cell-free MLV and VSV virion yields and VSV spread to distal cells were dramatically reduced by tetherin. To elucidate the roles of tetherin and cell-free virions during in vivo viral dissemination and pathogenesis, we developed mice carrying an inducible human tetherin (hTetherin) transgene. While ubiquitous hTetherin expression was detrimental to the growth and survival of mice, restriction of hTetherin expression to hematopoietic cells gave apparently healthy mice. The expression of hTetherin in hematopoietic cells had little or no effect on the number of MoMLV-infected splenocytes and thymocytes. However, hTetherin expression significantly reduced cell-free plasma viremia and also delayed MoMLV-induced disease. Overall, these results suggest that MoMLV spread within hematopoietic tissues and cell monolayers involves cell-to-cell transmission that is resistant to tetherin but that virion dissemination via plasma is inhibited by tetherin and is required for full MoMLV pathogenesis.IMPORTANCE Retroviruses are thought to spread primarily via direct cell-to-cell transmission, yet many have evolved to counteract an antiviral protein called tetherin, which may selectively inhibit cell-free virus release. We generated a mouse model with an inducible tetherin transgene in order to study how tetherin affects retroviral dissemination and on which cell types its expression is required to do so. We first developed a novel in vitro live-cell imaging assay to demonstrate that while tetherin does indeed dramatically reduce cell-free virus spreading, it has little to no effect on direct cell-to-cell transmission of either vesicular stomatitis virus (VSV) or the retrovirus MoMLV. Using our transgenic mouse model, we found that tetherin expression on hematopoietic cells resulted in the specific reduction of MoMLV cell-free plasma viremia but not the number of infected hematopoietic cells. The delay in disease associated with this scenario suggests a role for cell-free virus in retroviral disease progression.


Immunological assessment of patients with rheumatoid arthritis--evaluation of the effects of propranolol.
Some humoral and cellular immune functions were evaluated in a group of 10 patients with rheumatoid arthritis before and after 3 months of treatment with the beta-blocking agent propranolol. Humoral parameters measured were serum immunoglobulins including IgE, auto-antibodies, C-reactive protein, total haemolytic complement activity and the complement components C3 and C4. Cellular functions assessed were polymorphonuclear leucocyte chemotaxis, phagocytosis and postphagocytic nitroblue tetrazolium reduction, hexose monophosphate shunt activity and myeloperoxidase-mediated iodination of ingested protein; lymphocyte transformation to the mitogens phytohaemagglutinin and concanavalin A was also investigated. No alteration of humoral factors and neutrophil functions was observed following propranolol administration (40 mg 3 times a day), but lymphocyte transformation was significantly increased. Improved lymphocyte function did not correlate with clinical improvement.


The amino acid sequence around the reactive cysteine residue in human plasma Factor XII.
1. Activated human plasma factor XIII was 65% inhibited by iodo[(14)C]acetate and incorporated 0.6 mol of label into the alpha subunit, which eventually was allowed to form a precipitate. 2. All the label was recovered as S-carboxymethylcysteine in a tetra-peptide of sequence Gly-Gln-Cys-Trp.


Cerebrospinal fluid metabolomic and proteomic characterization of neurologic post-acute sequelae of SARS-CoV-2 infection.
The mechanism by which SARS-CoV-2 causes neurological post-acute sequelae of SARS-CoV-2 (neuro-PASC) remains unclear. Herein, we conducted proteomic and metabolomic analyses of cerebrospinal fluid (CSF) samples from 21 neuro-PASC patients, 45 healthy volunteers, and 26 inflammatory neurological diseases patients. Our data showed 69 differentially expressed metabolites and six differentially expressed proteins between neuro-PASC patients and healthy individuals. Elevated sphinganine and ST1A1, sphingolipid metabolism disorder, and attenuated inflammatory responses may contribute to the occurrence of neuro-PASC, whereas decreased levels of 7,8-dihydropterin and activation of steroid hormone biosynthesis may play a role in the repair process. Additionally, a biomarker cohort consisting of sphinganine, 7,8-dihydroneopterin, and ST1A1 was preliminarily demonstrated to have high value in diagnosing neuro-PASC. In summary, our study represents the first attempt to integrate the diagnostic benefits of CSF with the methodological advantages of multi-omics, thereby offering valuable insights into the pathogenesis of neuro-PASC and facilitating the work of neuroscientists in disclosing different neurological dimensions associated with COVID-19.


The evolution and importance of spinal and chiropractic research.
From its discovery in 1895 to its current status, in which the World Federation of Chiropractic Meeting may be considered a prestigious international scientific conference, the evaluation of chiropractic can be viewed as a compression of the phases which medical and scientific evolution have followed over a much longer period. Chiropractic theory started primarily as a vitalistic philosophy justifying its treatment while the medical scientific community was rejecting vitalism. Both chiropractic and medical spine specialists went through a period of speculative theory in the first half of this century based upon either perceived neurological or pathological observations. There was a period of single-theory preoccupation by chiropractors (the subluxation) and medical specialists (disc herniation) which brought these professions into conflict. The past decade has led to greater scientific exploration by both professions, with more national scientific discussion of the causes and treatment of spinal problems. The next decade, however, appears likely to require greater emphasis on social research into clinical effectiveness of treatments, prevention of back pain, patient satisfaction and quality assurance. This evolution should be considered the normal maturation of a health care profession.


Construct validation of the hospital anxiety and depression scale with clinical populations.
the hospital anxiety and depression scale (HADS) attempts to measure anxiety and depression without confounding by somatic symptoms of physical disorder, and is widely used for this purpose. This paper addresses three questions about the validity of the HADS concerning its independence of physical symptoms, the extent to which its items robustly measure the identified constructs with varying clinical populations and situations, and its capacity to differentiate anxiety and depression. data from patients with breast disease, myocardial infarction (MI), and stroke were examined using factor analytic and psychometric analyses. using exploratory factor analysis in patients with breast disease, 13 of the 14 HADS items fell on a psychological factor and loadings on the psychological factor were higher than loadings on the somatic factor for all items. The HADS showed high levels of internal consistency and there was little evidence that removing items would improve it. Confirmatory factor analyses (CFA) in MI and stroke groups confirmed the separation of anxiety and depression. Analyses indicated items, which were performing poorly for these clinical groups. there was support for the validity of the HADS for all three questions. However, there were some evidences of individual items performing poorly. Given the ease of administration and the acceptability of this measure to ill or weak respondents, the HADS continues to perform satisfactorily.


The Vibration of a Linear Carbon Chain in Carbon Nanotubes.
An explicit solution for the vibration of a carbon chain inside carbon nanotubes (CNTs) was obtained using continuum modeling of the van der Waals (vdW) interactions between them. The effect of the initial tensile force and the amplitude of the carbon chain as well as the radii of the CNTs on the vibration frequency were analyzed in detail, respectively. Our analytical results show that the vibration frequency of the carbon chain in a (5,5) CNT could be around two orders of magnitude higher than that of an independent carbon chain without initial tensile force. For a given CNT radius, the vibration frequency nonlinearly increases with increasing amplitude and initial tensile force. The obtained analytical cohesive energy and vibration frequency are reasonable by comparison of present molecular dynamics (MD) simulations. These findings will be a great help towards understanding the vibration property of a nanowire in nanotubes, and designing nanoelectromechanical devices.


Using genetic tools to estimate the prevalence of non-native red deer (Cervus elaphus) in a Western European population.
Game species like the red deer have been subjected to anthropogenic impacts for centuries. Translocations are often carried out-sometimes illegally-not only for sporting purposes, but also to increase trophy quality, reduce inbreeding, or mitigate bottlenecks after excessive persecution. Apart from the blurring of large-scale genetic structure, translocations without adequate quarantine measure risk introducing pathogens into potentially immunologically naïve populations. It is therefore important to understand the frequency of clandestine translocations. Identification of non-autochthonous animals and their potential origin is often difficult and, in red deer, has been hampered by the lack of large-scale genotypic datasets for comparison. In the present study, we make use of a recently published European-wide microsatellite dataset to detect and quantify the presence of non-autochthonous red deer in a large population sample (n = 1,780) from Central Europe (Belgium). Using factorial correspondence analysis, assignment tests and Bayesian clustering algorithms we arrive at an estimate of 3.7% non-autochthonous animals (or their descendants). Some of these animals were assigned to a nearby French population and may have immigrated into Belgium naturally, but the large majority must have been introduced by humans. Our analysis pointed to the British Isles and Germany/Poland as the potential origin of many introduced deer, regions known to have been source populations for translocations in Europe and beyond. We found evidence for recreational hunters using carcasses from farmed deer to fulfill mandatory hunting quotas. Our study is the first to quantify the extent of human-mediated introductions in a European game species at such a large scale with large and representative sample sizes.


The brain network underlying the recognition of hand gestures in the blind: the supramodal role of the extrastriate body area.
The visual perception of others' body parts is critical for understanding and imitating their behavior. The visual cortex in humans includes the extrastriate body area (EBA), which is a large portion of the occipitotemporal cortex that is selectively responsive to visually perceived body parts. Previous neuroimaging studies showed that the EBA not only receives sensory inputs regarding others' body information but also receives kinesthetic feedback regarding one's own actions. This finding raised the possibility that the EBA could be formed via nonvisual sensory modalities. However, the effect of visual deprivation on the formation of the EBA has remained largely unknown. Here, we used fMRI to investigate the effect of vision loss on the development of the EBA. Blind and sighted human subjects performed equally well in a haptic-identification task involving three categories of objects (hand shapes, toy cars, and teapots). The superior part (i.e., the middle temporal gyrus and angular gyrus) of the EBA and the supramarginal gyrus showed greater sensitivity to recognized hand shapes than to inanimate objects, regardless of the sensory modality and visual experience. Unlike the superior part of the EBA, the sensitivity of the inferior part (i.e., the inferior temporal sulcus and middle occipital gyrus) depended on visual experience. However, this vision-dependent sensitivity explained minor individual differences in hand-recognition performance. These results indicate that nonvisual modalities drive the development of the cortical network underlying the recognition of hand gestures with a node in the visual cortex.


Life stressors, social resources, and coping skills in youth: applications to adolescents with chronic disorders.
After setting out a conceptual framework that focuses on how personal and social resources aid adolescents in managing acute and chronic stressors, I describe methods by which to assess adolescents' family environments and specific life stressors and social resources, and the approach and avoidance coping responses adolescents use to manage life stressors. I then review some research that employs these concepts and methods to focus on the families and life contexts, and coping skills, of youth with chronic medical disorders, including juvenile rheumatic disease (JRD). I close by drawing implications for assessment and intervention and describing some fruitful areas for future research, such as examining the reciprocal linkages between parental and youth behavior, how adolescents' personal characteristics shape their life context, and how life crises and transitions enhance adolescents' development and maturation.


Three-Year Results from the Venovo Venous Stent Study for the Treatment of Iliac and Femoral Vein Obstruction.
To assess safety and patency of the Venovo venous stent for the treatment of iliofemoral vein obstruction. Twenty-two international centers enrolled 170 patients in the VERNACULAR study (93 post-thrombotic syndrome; 77 non-thrombotic iliac vein lesions). Primary outcome measures were major adverse events at 30 days and 12-month primary patency (freedom from target vessel revascularization, thrombotic occlusion, or stenosis > 50%). Secondary outcomes included the Venous Clinical Severity Score Pain Assessment and Chronic Venous Quality-of-Life Questionnaire assessments (hypothesis tested). Secondary observations included primary patency, target vessel and lesion revascularization (TVR/TLR), and assessment of stent integrity through 36 months. Freedom from major adverse events through 30 days was 93.5%, statistically higher than a pre-specified performance goal of 89% (p = 0.032) while primary patency at 12 months was 88.6%, also statistically higher than a performance goal of 74% (p < 0.0001). Mean quality-of-life measures were statistically improved compared to baseline values at 12 months (p < 0.0001). Primary patency at 36 months was 84% (Kaplan-Meier analysis) while freedom from TVR/TLR was 88.1%. There was no stent embolization/migration, and no core laboratory assessed stent fractures reported through 36 months. Six deaths were reported; none adjudicated as device or procedure related. The Venovo venous stent was successfully deployed in obstructive iliofemoral vein lesions and met the pre-specified primary outcome measures through 12 months. At 3 years, primary patency was 84%, reintervention rates were low, standardized quality-of-life and pain measures improved from baseline, and there was no stent migration or fractures. Level 2-prospective, multicenter, controlled clinical study without a concurrent control or randomization. Pre-specified endpoints were hypothesis-tested to performance goals derived from peer-reviewed clinical literature. REGISTRATION CLINICALTRIALS.GOV: Unique Identifier NCT02655887.


Solubilization of enzymes and nucleic acids in hydrocarbon micellar solutions.
The present state of the field of biopolymers solubilized in apolar solvents via reverse micelles is reviewed. First, an extensive discussion of the physical and chemical properties of reverse micelles is presented. Particular attention is devoted to the nature of water in the water pools of reverse micelles; to the structure and shape of the micellar aggregates; and to the dynamic properties of the reverse micelles. In the second part of the paper, the mechanism of solubilization of proteins and nucleic acids in hydrocarbon reverse micelles is discussed. Spectroscopic data, mostly circular dichroism and fluorescence, are reviewed in order to clarify the conformational changes which the biopolymers undergo upon their uptake into the micellar environment and determine the location of the biopolymers inside the reverse micelles. Data from neutron scattering, light scattering, ultracentrifugation, and electron microscopy of the protein-containing micelles are reviewed and discussed with the aim of illustrating the structure of the micellar aggregates containing the biopolymer as guest molecules. The activity of enzymes and nucleic acids is discussed, with emphasis on the influence upon the chemical reactivity brought about by the micellar parameters. Finally, a brief review of the applications and potentialities of biopolymer-containing reverse micelles is presented.


Determinants of COVID-19 disease severity in patients with cancer.
As of 10 April 2020, New York State had 180,458 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 9,385 reported deaths. Patients with cancer comprised 8.4% of deceased individuals1. Population-based studies from China and Italy suggested a higher coronavirus disease 2019 (COVID-19) death rate in patients with cancer2,3, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-194. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. From 10 March to 7 April 2020, 423 cases of symptomatic COVID-19 were diagnosed at Memorial Sloan Kettering Cancer Center (from a total of 2,035 patients with cancer tested). Of these, 40% were hospitalized for COVID-19, 20% developed severe respiratory illness (including 9% who required mechanical ventilation) and 12% died within 30 d. Age older than 65 years and treatment with immune checkpoint inhibitors (ICIs) were predictors for hospitalization and severe disease, whereas receipt of chemotherapy and major surgery were not. Overall, COVID-19 in patients with cancer is marked by substantial rates of hospitalization and severe outcomes. The association observed between ICI and COVID-19 outcomes in our study will need further interrogation in tumor-specific cohorts.


What every hospitalist should know about the post-bariatric surgery patient.
Obesity is a growing worldwide epidemic, increasingly addressed through surgical options for weight loss. Benefits of these operations, such as weight loss and improvement or reversal of obesity-related comorbidities, are well established; however, postoperative complications do occur. This article will evaluate common causes for hospital admissions in the post-bariatric surgery population as they relate to the hospitalist who is often responsible for their care. Here we provide an overview of the most common bariatric procedures currently performed, early postoperative complications, late medical complications (ie, abdominal complaints, weight fluctuations, nutritional deficiencies, and metabolic bone disease), and late surgical complications that often affect these patients and result in hospital admissions. Special attention will be paid to radiologic pearls that can assist in the initial evaluation and diagnosis of these patients.


Arginine Metabolism in Supragingival Oral Biofilms as a Potential Predictor of Caries Risk.
Ammonia production via the arginine deiminase system (ADS) of oral bacteria can function to reduce the cariogenicity of oral biofilms by neutralizing glycolytic acids that cause tooth demineralization. This cohort study investigated the relationship between ADS activity and bacterial profile changes of supragingival biofilms with caries experience among children over time. A total of 79 children aged 2 to 7 y at baseline were assessed every 6 mo for a period of 18 mo. Children were grouped as caries free (CF), caries active with enamel lesions (CAE), or caries active with dentin lesions (CA). Supragingival plaque samples were collected from caries-free surfaces (PF) and from enamel (PE) and dentin (PD) lesions. Plaque ADS activity was measured by monitoring citrulline production from arginine and compared with ribosomal 16S rRNA-derived taxonomic profiles for the same samples. At baseline, 37% of the children were CF, 34% CAE, and 29% CA. At 18 mo, 26% were CF, 41% CAE, 23% CA, and 10% were caries experienced (new restorations but no caries activity). Throughout the study period, ADS activity was significantly higher in the CF group than the CA group (P < 0.0001), and ADS activity in the PF samples was significantly higher than in the PE and PD samples (P < 0.0001). Distance-based redundancy analysis showed that the bacterial communities could be differentiated when plaque samples are grouped into levels of high and low ADS activity. There is a positive correlation between caries activity and low arginolytic capacity of the supragingival oral biofilms of children and tooth surfaces over time. Measurements of arginine metabolism via ADS may be useful to differentiate the caries risk of individuals and tooth surfaces. Findings from this study support the development of new strategies for caries risk assessment and prevention based on modulation of the virulence of the oral microbiome through arginine metabolism in supragingival biofilms.


New technology and partner notification--why aren't we using them?
Partner notification is crucial to the effective control of sexually transmissible infections (STIs) and has not changed substantially over recent years. New technology for communication has been rapidly adopted in our communities but little work has been carried out about its role in contact tracing. Text messaging, emails and the Internet could be useful tools for both provider and patient referral but considerable ethical considerations are involved. Technology is available to help protect the basic tenets of confidentiality and privacy but more thorough exploration of these methods is required to establish efficacy and appropriateness in contact tracing. This research is important if we are to procure an evidence base for future contact tracing strategies rather than allowing these methods to become commonplace at the initiation of our clients.


Ultrafast growth of horizontal GaN nanowires by HVPE through flipping the substrate.
Recently, horizontal nanowires (NWs) have attracted much attention due to their increased compatibility with NW-based integrated nanoelectronic and nanophotonic systems. However, it still remains challenging to synthesize horizontal NWs efficiently. Here we introduce a novel method towards controllable growth of horizontal GaN NWs using HVPE with an Au/Ni thin film as the catalyst. By simply flipping the substrate, horizontal GaN NWs with various growth directions and cross sections have been obtained on a sapphire substrate with various facet orientations. Benefiting from the high decomposition frequency of GaCl precursors, the growth rate for the horizontal NWs is as fast as 400 μ h-1. Our results show that the facing orientation of the loaded substrate affects the flow of the local precursor, which determines the growth mode of the GaN NWs, i.e., no matter whether the substrate is facing downward or upwards. Photoluminescence measurements of the horizontal NWs show a finite blue shift of the band edge-related emission. It indicates the presence of compressed stress and is confirmed by the geometrical phase analysis (GPA) further. Our work opens up a new route and sheds light on the horizontal GaN NWs and will advance the development of horizontal NW-based nanoelectronic and nanophotonic devices and systems.


AZD5438, an inhibitor of Cdk1, 2, and 9, enhances the radiosensitivity of non-small cell lung carcinoma cells.
Radiation therapy (RT) is one of the primary modalities for treatment of non-small cell lung cancer (NSCLC). However, due to the intrinsic radiation resistance of these tumors, many patients experience RT failure, which leads to considerable tumor progression including regional lymph node and distant metastasis. This preclinical study evaluated the efficacy of a new-generation cyclin-dependent kinase (Cdk) inhibitor, AZD5438, as a radiosensitizer in several NSCLC models that are specifically resistant to conventional fractionated RT. The combined effect of ionizing radiation and AZD5438, a highly specific inhibitor of Cdk1, 2, and 9, was determined in vitro by surviving fraction, cell cycle distribution, apoptosis, DNA double-strand break (DSB) repair, and homologous recombination (HR) assays in 3 NSCLC cell lines (A549, H1299, and H460). For in vivo studies, human xenograft animal models in athymic nude mice were used. Treatment of NSCLC cells with AZD5438 significantly augmented cellular radiosensitivity (dose enhancement ratio rangeing from 1.4 to 1.75). The degree of radiosensitization by AZD5438 was greater in radioresistant cell lines (A549 and H1299). Radiosensitivity was enhanced specifically through inhibition of Cdk1, prolonged G(2)-M arrest, inhibition of HR, delayed DNA DSB repair, and increased apoptosis. Combined treatment with AZD5438 and irradiation also enhanced tumor growth delay, with an enhancement factor ranging from 1.2-1.7. This study supports the evaluation of newer generation Cdk inhibitors, such as AZD5438, as potent radiosensitizers in NSCLC models, especially in tumors that demonstrate variable intrinsic radiation responses.


Hormonal therapy for metastatic male breast cancer.
Forty-one men with metastatic breast cancer were treated with 70 trials of hormone therapy. These included 25 orchiectomies and 45 additive hormonal treatments. The overall response rate was 31%. The response rate was 32% to orchiectomy, 17% to estrogens, 43% to steroids, 25% to tamoxifen citrate, and 60% to androgens. The response to additive hormonal therapy was 31% and was not affected by prior orchiectomy (33% v 30%). Median overall response duration was 12 months, 17.5 months following orchiectomy, 8.5 months following additive hormonal therapy, five months following estrogens, 11 months following steroids, and eight months following androgens. Median survival from first metastasis was significantly prolonged in patients responding to orchiectomy and additive hormonal therapy. Patients with a disease-free interval (DFI) longer than 12 months had a 59% response rate to hormonal therapy compared with 9% of those with a DFI no more than 12 months. Response to one form of hormonal therapy did not predict later hormonal response. Ablative and additive hormonal therapy offer effective palliation to one third of male breast cancer patients, produce little toxic effects and morbidity, and improve survival duration after metastasis in responders.


To lube or not to lube: experiences and perceptions of lubricant use in women with and without dyspareunia.
There are few studies examining the relationship between lubricant use and sexual functioning, and no studies have examined this relationship in women with dyspareunia. Vaginal dryness is a prevalent complaint among women of all ages. There is an association between vaginal dryness and painful intercourse; therefore, women with dyspareunia represent a particularly relevant sample of women in which to investigate lubricant use. The aim of this study was to examine differences between women with and without dyspareunia in self-reported natural lubrication and attitudes toward and use of personal lubricants. Respondents completed an online survey including questions on demographics, gynecological/medical history, sexual functioning, and lubricant use and attitudes. The main outcome measures used were the Female Sexual Function Index (FSFI) and questions regarding attitudes toward and use of lubricants. Controls scored higher on the lubrication subscale of the FSFI than women with dyspareunia (P < 0.001). Women with dyspareunia reported greater frequency of lubricant use during sexual activity over the last year (P < 0.01). They were also more likely to use lubricant prior to penetration (P < 0.05). The most common use for controls was to enhance sexual experiences. This was also a common answer for women with dyspareunia; however, in this group, the most common reason was to reduce/alleviate pain. Lubricants were rated as less effective among women with dyspareunia vs. controls across all reported reasons for use. Nevertheless, lubricant use was still rated as being moderately effective in alleviating pain for women with dyspareunia. Women with dyspareunia have more difficulty with natural lubrication; it is consequently not surprising that they reported using lubricant more frequently than control women. Women with dyspareunia reported using lubricants more often than controls to try to prevent or alleviate pain and reported this as being a moderately effective strategy, suggesting that it may be a useful tool for some women with dyspareunia.


Contractility and conformation.
Contractility in fibers can arise from changes of macromolecular conformation caused by changes in some thermodynamic variable such as temperature, pH, or solvent composition. Illustrations are given of contractile processes in fibers and of changes in macromolecular conformation in dilute solution. These may involve order-disorder transitions, e.g. of the type exhibited by the helix-coil transition. A statistical mechanical treatment of the helix-coil transition involves the assignment of statistical weights to various states and the proper counting of these statistical weights in the formation and evaluation of the partition function; the thermodynamic properties of the system are derivable from the partition function. The counting procedure involved in the consideration of the alpha-helix and random coil is described. In addition, the factors affecting the relative stabilities of various helical conformations are discussed. These considerations of macromolecular conformation provide a basis for discussing contractile mechanisms in which changes of conformation are involved.


Epidemiology of autism spectrum disorders in adults in the community in England.
To our knowledge, there is no published information on the epidemiology of autism spectrum disorders (ASDs) in adults. If the prevalence of autism is increasing, rates in older adults would be expected to be lower than rates among younger adults. To estimate the prevalence and characteristics of adults with ASD living in the community in England. A stratified, multiphase random sample was used in the third national survey of psychiatric morbidity in adults in England in 2007. Survey data were weighted to take account of study design and nonresponse so that the results were representative of the household population. General community (ie, private households) in England. Adults (people 16 years or older). Autism Diagnostic Observation Schedule, Module 4 in phase 2 validated against the Autism Diagnostic Interview-Revised and Diagnostic Interview for Social and Communication Disorders in phase 3. A 20-item subset of the Autism-Spectrum Quotient self-completion questionnaire was used in phase 1 to select respondents for phase 2. Respondents also provided information on sociodemographics and their use of mental health services. Of 7461 adult participants who provided a complete phase 1 interview, 618 completed phase 2 diagnostic assessments. The weighted prevalence of ASD in adults was estimated to be 9.8 per 1000 (95% confidence interval, 3.0-16.5). Prevalence was not related to the respondent's age. Rates were higher in men, those without educational qualifications, and those living in rented social (government-financed) housing. There was no evidence of increased use of services for mental health problems. Conducting epidemiologic research on ASD in adults is feasible. The prevalence of ASD in this population is similar to that found in children. The lack of an association with age is consistent with there having been no increase in prevalence and with its causes being temporally constant. Adults with ASD living in the community are socially disadvantaged and tend to be unrecognized.


An ensembling approach for optic cup detection based on spatial heuristic analysis in retinal fundus images.
Optic cup detection remains a challenging task in retinal image analysis, and is of particular importance for glaucoma evaluation, where disease severity is often assessed by the size of the optic cup. In this paper, we propose spatial heuristic ensembling (SHE), an approach which aims to fuse the advantages of each method based on the specific performance in each defined sector. In this way, we generate an ensembled optic cup which is obtained from the optimal combination of the component methods. We conduct experiments on the ORIGA data set of 650 retinal images and show that the ensemble approach performs better than the individual segmentations, reducing the relative overlap error, and CDR errors by as much as 0.04 CDR units. The results are promising for the continued development of such an approach for improving optic cup segmentation.