[Second tumor in lymphogranulomatosis].
The study was concerned with second malignancies which arose from non-hematopoietic tissue in 6 Hodgkin's disease patients. The malignancies were detected within 15-150 months and appeared to be the immediate cause of the death of the patients. The clinical course of Hodgkin's disease and second malignancy, the terms of second malignancy detection v. previous treatment, morphological features of Hodgkin's disease and the effect of splenectomy are discussed. It is concluded that the rise of second malignancy development should be taken into consideration when procedures for treatment of Hodgkin's disease are selected, particularly, in cases with favorable prognosis.


Medical advice for international travelers.
Americans are traveling abroad in increasing numbers. The family physician should review the traveling patient's immunization records and inform him of the risks and hazards of world travel, with particular emphasis on malaria chemoprophylaxis, water decontamination, personal hygiene and accident prevention. A post-trip evaluation is important to assure that any diseases acquired on tour have been adequately treated.


MicroRNAs as ideal biomarkers for the diagnosis of lung cancer.
Lung cancer (LC) is one of the most prevalent causes of cancer death with a high mortality rate worldwide. While various sets of microRNAs (miRNAs) have been found to be highly sensitive and specific biomarkers for the early diagnosis of LC (the first word of abstract), conflicting results on their diagnostic accuracy are still present in individual studies. Thus, we aimed to conduct a systematic review and meta-analysis of the published literature to comprehensively assess the diagnostic value of miRNAs for predicting LC. The sensitivity and specificity of each included study were used to plot the summary receiver operator characteristic (SROC) curve and to calculate the area under the SROC curve (AUC). All analyses were performed using the Stata 12.0 software. Twenty-six articles were involved in our meta-analysis, 18 of which focused on single miRNA assays and 15 on multiple miRNA assays. For single miRNA profiling, the pooled parameters calculated from all studies are as follows: sensitivity (SEN), 0.72; specificity (SPE), 0.74; positive likelihood ratio (PLR), 2.7; negative likelihood ratio (NLR), 0.39; and diagnostic odds ratio (DOR), 7. For multiple miRNA profiling, the pooled estimates for the overall studies are as follows: SEN, 0.81; SPE, 0.84; PLR, 4.9; NLR, 0.23; and DOR, 22, which are significantly better than the diagnostic performance of the single miRNA profiling. In addition, subgroup analyses based on sample types suggested that blood-based multiple miRNA assays were more accurate than non-blood-based studies. In conclusion, the current meta-analysis shows that multiple miRNA assays were more accurate in diagnosing LC than single miRNA assays. However, further large-scale investigations are urgently needed to confirm our results and verify the feasibility of routine clinical utilization.


Coping and depressive symptoms in adults living with heart failure.
This study used process coping theory as the basis for investigating how coping strategies are associated with depressive symptoms in individuals living with heart failure (HF). Demographic factors also were examined as correlates of depressive symptoms. The convenience sample of adults living with HF (n = 75) who participated in this study ranged in age from 27 to 82 years (M = 55). Sixty-nine percent of the participants were men, 59% were married or partnered, with the majority being Caucasian and from the middle class. Subjects were recruited from a comprehensive HF program located within an academic health science center in the southeastern United States. A single wave of data collection occurred. All study questionnaires were verbally administered in a clinic room selected for privacy during a routine HF clinic visit. Individuals who used more planful problem-solving and social support seeking coping strategies had fewer depressive symptoms, whereas individuals who used more escape-avoidance coping (eg, wishful thinking) had more depressive symptoms. When demographic factors also were included in a regression analysis assessing depressive symptoms, marital status, functional impairment, and the coping strategies of planful problem-solving and escape-avoidance were all statistically significant predictors of depression. Single individuals, those who used more escape-avoidance, less planful problem-solving coping, and more functional impairment had more depressive symptoms. These results suggest that psychosocial factors, in addition to physical parameters, and the ways individuals cope with the stressors of living with heart failure may be important predictors of depressive symptoms.


Toxicological findings and manner of death in autopsied users of anabolic androgenic steroids.
With the aim to characterize patterns in toxicological profile and manner of death in deceased users of anabolic androgenic steroids (AAS), a retrospective autopsy protocol study of 52 deceased users of AAS was undertaken. The AAS users were compared to 68 deceased users of amphetamine and/or heroin who were consecutively tested and found to be negative for AAS. Use of AAS was in the majority of cases (79%) associated with concomitant use of psychotropic substances. AAS-related deaths differed in several respects from deaths among users of heroin or amphetamine, most strikingly with regard to: (a) the median age at death, which was significantly lower for AAS users (24.5 years) than for users of heroin and/or amphetamine (34 and 40 years, respectively); (b) the manner of death, with AAS users dying significantly more often from homicide or suicide than users of other drugs; and (c) the body mass index (BMI), with AAS users exhibiting significantly higher BMI than users of other drugs. These results support the earlier reported association between use of AAS and use of other psychoactive substances. In addition, the data suggest that AAS users are more likely to become involved in incidents leading to violent death and have a higher risk of dying at a younger age than users of other drugs.


Combined effect of trifluoperazine and sodium cromoglycate on reducing acute edema and limiting lasting functional impairments after spinal cord injury in rats.
Edema formation is one of the very first events to occur after spinal cord injury (SCI) leading to an increase of the intrathecal pressure and consequently to serious spinal tissue and functional impairments. Current edema treatments are still symptomatic and/or non-specific. Since edema formation mechanisms are mainly described as vasogenic and cytotoxic, it becomes crucial to understand the interplay between these two subtypes. Acting on key targets to inhibit edema formation may reduce secondary damage and related functional impairments. In this study, we characterize the edema kinetic after T9-10 spinal contusion. We use trifluoperazine (TFP) to block the expression and the functional subcellular localization of aquaporin-4 supposed to be implicated in the cytotoxic edema formation. We also use sodium cromoglycate (SCG) to deactivate mast cell degranulation known to be implicated in the vasogenic edema formation. Our results show a significant reduction of edema after TFP treatment and after TFP-SCG combined treatment compared to control. This reduction is correlated with limited onset of initial sensorimotor impairments particularly after combined treatment. Our results highlight the importance of potential synergetic targets in early edema therapy after SCI as part of tissue sparing strategies.


Hydrogels for brain repair: application to Parkinson's disease.
Parkinson's disease is the second most common neurodegenerative disease. Currently, there are no curative therapies, with only symptomatic treatment available. One of the principal reasons for the lack of treatments is the problem of delivering drugs to the brain, mainly due to the blood-brain barrier. Hydrogels are presented as ideal platforms for delivering treatments to the brain ranging from small molecules to cell replacement therapies. The potential application of hydrogel-based therapies for Parkinson's disease is addressed. The desirable composition and mechanical properties of these therapies for brain application are discussed, alongside the preclinical research available with hydrogels in Parkinson's disease. Lastly, translational and manufacturing challenges are presented. Parkinson's disease urgently needs novel therapies to delay its progression and for advanced stages, at which conventional therapies fail to control motor symptoms. Neurotrophic factor-loaded hydrogels with stem cells offer one of the most promising therapies. This approach may increase the striatal dopamine content while protecting and promoting the differentiation of stem cells although the generation of synapses between engrafted and host cells remains an issue to overcome. Other challenges to consider are related to the route of administration of hydrogels and their large-scale production, required to accelerate their translation toward the clinic.


Weight, dietary and physical activity behaviors two years after gastric bypass.
This cross-sectional survey was designed to determine the self-reported weight management, dietary and physical activity behaviors of Roux-en-Y gastric bypass (RYGBP) patients who were 1 to 4 years after the RYGBP operation, and to identify gaps in follow-up nutrition-related chronic disease prevention. Questionnaires including behavioral items from the 2003 and 2004 Behavioral Risk Factor Surveillance System (BRFSS) were mailed to all RYGBP patients in a clinically active outpatient database. Of 212 patients, 140 (66%) returned completed questionnaires. Responders were 24.2 +/- 7.9 months postoperatively. They were older than nonresponders (45.2 +/- 9.9 vs 38.5 +/- 8.9 years, P<.001). Responders had an average weight loss of 55.8 +/- 15.2 kg, and most (81%) reported that they were still trying to lose weight. The most frequently reported dietary behavior for weight loss was decreasing calorie and fat intakes. However, in addition to avoiding sodas and sweet desserts, responders were also excluding nutrient-dense foods high in vitamins and minerals such as milk and dairy products, red meats, breads, cereals and nuts. Remarkably, only 25 (17.9%) engaged in regular exercise activities before surgery, while 116 (82.9%) indicated a moderate level of current physical activity averaging 54.7 +/- 38.5 minutes per episode. Multivariable linear regression analyses identified age, weight at age 21, pre-surgery BMI and time in regular physical activities as the four significant predictors of BMI after weight loss stabilization. Postoperative RYGBP patients engage in various weight management behaviors, some of which could offer greater health benefits with follow-up intervention from dietitians and exercise specialists to prevent adverse outcomes such as weight regain and micronutrient deficiencies.


Oestradiol-17 beta increases pituitary responsiveness by a mechanism that involves the release and the priming effect of luteinizing hormone releasing factor.
We have investigated the mechanism by which oestradiol-17 beta augments pituitary responsiveness to luteinizing hormone releasing factor (LH-RF). Adult rats were ovariectomized on the morning of dioestrus and implanted with either an empty silicone elastomer capsule or a capsule containing oestradiol-17 beta. Twelve hours later the LH response, tested by injecting 50 ng LH-RF/100 g i.v., was significantly greater in animals implanted with an oestradiol capsule compared with that in animals implanted with an empty capsule. The effect of oestradiol was blocked by sodium pentobarbitone administered 4 h before the test, and this block was overcome by infusing LH-RF during the 4 h period at doses which by themselves were not sufficient to evoke a large release of LH. We also measured LH-RF in pituitary stalk blood collected under Althesin anaesthesia between 4-6 and 12-13 h after ovariectomy and capsule implantation. The concentration of LH-RF in stalk plasma fell between these two collection periods in animals implanted with empty but not with oestradiol-filled capsules. The concentrations of LH-RF in stalk plasma, although relatively low, were significantly higher in animals bearing an oestradiol-containing capsule than the concentrations in peripheral plasma from similarly treated animals, and, by comparison with the LH-RF concentrations in peripheral plasma from animals infused with LH-RF, were sufficiently high to increase significantly the responsiveness of the pituitary gland. These data show that as well as acting directly on the pituitary gonadotrophs, oestradiol-17 beta increases the responsiveness of the anterior pituitary gland by a mechanism that involves the release and the priming effect of LH-RF.


Stability of cervical esophagogastrostomy via hand-sewn anastomosis after esophagectomy for esophageal cancer.
The aim of the present study is to evaluate the outcome of hand-sewn esophagogastric anastomosis during radical esophagectomy for esophageal cancer. The outcomes of 467 consecutive esophageal cancer patients who underwent cervical esophagogastric anastomosis using interrupted and double-layered sutures after radical esophagectomy via right thoracotomy or thoracoscopic surgery were retrospectively reviewed. Anastomotic leakage, including conduit necrosis, occurred in 11 of 467 patients (2.4%); 7 of 11 (63.6%) cases experienced only minor leakage, whereas the other four (36.4%) patients had major leakage that required surgical or radiologic intervention, including two patients of conduit necrosis. Anastomotic leakages were more frequently observed after retrosternal reconstruction compared with the posterior mediastinal route (P < 0.0001). The median time to healing of leakage was 40 days (range: 14-97 days). Two patients (2/467, 0.4%) died in the hospital due to sepsis caused by the leakage and conduit necrosis. Twelve patients (2.6%) developed anastomotic stenosis, which was improved by dilatation in all patients. Hand-sewn cervical esophagogastric anastomosis is a stable and highly safe method of radical esophagectomy for esophageal cancer.


Corneal deformation measurement using Scheimpflug noncontact tonometry.
To determine the intraexaminer repeatability and intersession reproducibility of corneal deformation measurement using Scheimpflug noncontact tonometry (Corvis ST) on normal subjects. Thirty-seven adults aged 20 to 48 years were invited to have their corneal deformation and curvature measurements taken using Corvis ST and Pentacam, respectively. Three consecutive measurements were taken for each instrument between 9:00 and 11:00 AM for intraexaminer repeatability analysis. Participants returned between 3:00 and 5:00 PM the same day for intersession reproducibility analysis. The most repeatable corneal parameter measured by Corvis ST was central corneal thickness ([CCT] ICC, 0.96; precision, 10.85 μm; repeatability, 15.34 μm; CV, 1.01%), followed by deformation amplitude ([DA] ICC, 0.80; precision, 0.08 mm; repeatability, 0.13 mm; CV, 4.33%), first applanation time ([1st A-time] ICC, 0.77; precision, 0.22 milliseconds; repeatability, 0.31 milliseconds; CV, 1.42), and intraocular pressure ([IOP] ICC, 0.75; precision, 1.39 mm Hg; repeatability, 1.97 mm Hg; CV, 4.98). Other parameters showed poor repeatability. The DA and 1st A-time showed good intersession reproducibility. The 95% limits of agreement were +0.13 to -0.13 mm for DA and +0.27 to -0.33 milliseconds for 1st A-time. The DA was negatively correlated with central corneal thickness (r = -0.53, p < 0.001) but not with corneal curvatures (flattest curvature, r = 0.13, p = 0.46; steepest curvature, r = 0.05, p = 0.75). Corneal deformation parameters DA and 1st A-time were repeatable and reproducible. A thinner cornea was associated with a higher corneal deformation. Measurement of DA serves as an indicator of corneal biomechanical properties.


Acceptance and commitment therapy for older people with treatment-resistant generalised anxiety disorder: the FACTOID feasibility study.
Generalised anxiety disorder, characterised by excessive anxiety and worry, is the most common anxiety disorder among older people. It is a condition that may persist for decades and is associated with numerous negative outcomes. Front-line treatments include pharmacological and psychological therapy, but many older people do not find these treatments effective. Guidance on managing treatment-resistant generalised anxiety disorder in older people is lacking. To assess whether or not a study to examine the clinical effectiveness and cost-effectiveness of acceptance and commitment therapy for older people with treatment-resistant generalised anxiety disorder is feasible, we developed an intervention based on acceptance and commitment therapy for this population, assessed its acceptability and feasibility in an uncontrolled feasibility study and clarified key study design parameters. Phase 1 involved qualitative interviews to develop and optimise an intervention as well as a survey of service users and clinicians to clarify usual care. Phase 2 involved an uncontrolled feasibility study and qualitative interviews to refine the intervention. Participants were recruited from general practices, Improving Access to Psychological Therapies services, Community Mental Health Teams and the community. Participants were people aged ≥ 65 years with treatment-resistant generalised anxiety disorder. Participants received up to 16 one-to-one sessions of acceptance and commitment therapy, adapted for older people with treatment-resistant generalised anxiety disorder, in addition to usual care. Sessions were delivered by therapists based in primary and secondary care services, either in the clinic or at participants' homes. Sessions were weekly for the first 14 sessions and fortnightly thereafter. The co-primary outcome measures for phase 2 were acceptability (session attendance and satisfaction with therapy) and feasibility (recruitment and retention). Secondary outcome measures included additional measures of acceptability and feasibility and self-reported measures of anxiety, worry, depression and psychological flexibility. Self-reported outcomes were assessed at 0 weeks (baseline) and 20 weeks (follow-up). Health economic outcomes included intervention and resource use costs and health-related quality of life. Fifteen older people with treatment-resistant generalised anxiety disorder participated in phase 1 and 37 participated in phase 2. A high level of feasibility was demonstrated by a recruitment rate of 93% and a retention rate of 81%. A high level of acceptability was found with respect to session attendance (70% of participants attended ≥ 10 sessions) and satisfaction with therapy was adequate (60% of participants scored ≥ 21 out of 30 points on the Satisfaction with Therapy subscale of the Satisfaction with Therapy and Therapist Scale-Revised, although 80% of participants had not finished receiving therapy at the time of rating). Secondary outcome measures and qualitative data further supported the feasibility and acceptability of the intervention. Health economic data supported the feasibility of examining cost-effectiveness in a future randomised controlled trial. Although the study was not powered to examine clinical effectiveness, there was indicative evidence of improvements in scores for anxiety, depression and psychological flexibility. Non-specific therapeutic factors were not controlled for, and recruitment in phase 2 was limited to London. There was evidence of high levels of feasibility and acceptability and indicative evidence of improvements in symptoms of anxiety, depression and psychological flexibility. The results of this study suggest that a larger-scale randomised controlled trial would be feasible to conduct and is warranted. Current Controlled Trials ISRCTN12268776. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 54. See the NIHR Journals Library website for further project information.


Regulated interactions between dynamin and the actin-binding protein cortactin modulate cell shape.
The dynamin family of large GTPases has been implicated in the formation of nascent vesicles in both the endocytic and secretory pathways. It is believed that dynamin interacts with a variety of cellular proteins to constrict membranes. The actin cytoskeleton has also been implicated in altering membrane shape and form during cell migration, endocytosis, and secretion and has been postulated to work synergistically with dynamin and coat proteins in several of these important processes. We have observed that the cytoplasmic distribution of dynamin changes dramatically in fibroblasts that have been stimulated to undergo migration with a motagen/hormone. In quiescent cells, dynamin 2 (Dyn 2) associates predominantly with clathrin-coated vesicles at the plasma membrane and the Golgi apparatus. Upon treatment with PDGF to induce cell migration, dynamin becomes markedly associated with membrane ruffles and lamellipodia. Biochemical and morphological studies using antibodies and GFP-tagged dynamin demonstrate an interaction with cortactin. Cortactin is an actin-binding protein that contains a well defined SH3 domain. Using a variety of biochemical methods we demonstrate that the cortactin-SH3 domain associates with the proline-rich domain (PRD) of dynamin. Functional studies that express wild-type and mutant forms of dynamin and/or cortactin in living cells support these in vitro observations and demonstrate that an increased expression of cortactin leads to a significant recruitment of endogenous or expressed dynamin into the cell ruffle. Further, expression of a cortactin protein lacking the interactive SH3 domain (CortDeltaSH3) significantly reduces dynamin localization to the ruffle. Accordingly, transfected cells expressing Dyn 2 lacking the PRD (Dyn 2(aa)DeltaPRD) sequester little of this protein to the cortactin-rich ruffle. Interestingly, these mutant cells are viable, but display dramatic alterations in morphology. This change in shape appears to be due, in part, to a striking increase in the number of actin stress fibers. These findings provide the first demonstration that dynamin can interact with the actin cytoskeleton to regulate actin reorganization and subsequently cell shape.


Epidemiological correlates of virulence genotype and phylogenetic background among Escherichia coli blood isolates from adults with diverse-source bacteremia.
Associations of virulence genotype and phylogenetic background with epidemiological factors (primary source of bacteremia, host compromise status, and hospital versus community origin) were assessed among 182 Escherichia coli blood isolates from adults with diverse-source bacteremia in comparison with fecal controls from the E. coli Reference collection. A continuum of virulence was found, from urinary and pulmonary source bacteremia isolates (high virulence), through "other" or unknown source bacteremia isolates (intermediate virulence), to fecal isolates (low virulence), with a corresponding graded phylogenetic distribution from predominantly group B2 to predominantly groups A and B1. Associations of bacterial traits with clinical factors varied considerably, depending on subgroup and statistical method. However, certain putative virulence genes (including several "nontraditional" markers, such as pathogenicity island-associated malX) repeatedly emerged as significant epidemiological predictors, which provided evidence of their possible relevance in host-pathogen interactions and hence as potential targets for preventive interventions against extraintestinal infections due to E. coli.


If the price is right: vagueness and values clarification in contingent valuation.
The use of willingness to pay to value the benefits of health care is increasing. Much of this work assumes that health preferences are well formed or 'complete' and readily revealed if the right question is asked in the right way. We examined this assumption, seeking evidence in a mixed-methods study that explored the meaning and implications of vague responses to a payment-scale based willingness to pay exercise.One-half of the sample said that their vagueness meant that their maximum willingness to pay was actually greater than the amount that they had previously said it was. Thirty percent agreed that they would probably pay pound 10 more than a sum that they had previously said they would most definitely not pay, if they found this to be the cost of the vaccine. Interview data supported the view that the payment scale had failed to elicit the maximum willingness to pay and that some participants used the information on cost to help clarify their values, in contrast to the theory underpinning willingness to pay. The results suggest a need to consider values-clarification in health economic evaluations.


Side reactions of nitroxide-mediated polymerization: N-O versus O-C cleavage of alkoxyamines.
Free energies for the homolysis of the NO-C and N-OC bonds were compared for a large number of alkoxyamines at 298 and 393 K, both in the gas phase and in toluene solution. On this basis, the scope of the N-OC homolysis side reaction in nitroxide-mediated polymerization was determined. It was found that the free energies of NO-C and N-OC homolysis are not correlated, with NO-C homolysis being more dependent upon the properties of the alkyl fragment and N-OC homolysis being more dependent upon the structure of the aminyl fragment. Acyclic alkoxyamines and those bearing the indoline functionality have lower free energies of N-OC homolysis than other cyclic alkoxyamines, with the five-membered pyrrolidine and isoindoline derivatives showing lower free energies than the six-membered piperidine derivatives. For most nitroxides, N-OC homolysis is normally favored above NO-C homolysis only when a heteroatom that is α to the NOC carbon center stabilizes the NO-C bond and/or the released alkyl radical is not sufficiently stabilized. As part of this work, accurate methods for the calculation of free energies for the homolysis of alkoxyamines were determined. Accurate thermodynamic parameters to within 4.5 kJ mol(-1) of experimental values were found using an ONIOM approximation to G3(MP2)-RAD combined with PCM solvation energies at the B3-LYP/6-31G(d) level.


Continuing professional development and Irish hospital doctors: a survey of current use and future needs.
Doctors rate clinical relevance and applicability as the most important determinants of continuing professional development (CPD) course selection. This study examined patterns of current CPD practice and perceived CPD needs among hospital doctors in Ireland across various clinical specialties. A cross-sectional survey was administered to doctors, focusing on the areas of training needs analysis, CPD course content and preferred course format. In total, 547 doctors identified doctor-patient communication as the skill ranked highest for importance and level of current performance. Workload/time organisation and stress management were areas where a skills deficiency was identified. Non-clinical CPD topics, including resilience training, management and communication skills, were preferred areas for future CPD offerings. All respondents favoured interactive, hands-on sessions. CPD course completion and preference patterns differed significantly across clinical specialties. These results highlight the importance of considering the individual needs and preferences of clinicians across clinical specialties to facilitate more effective CPD programmes.


The performance of fine-grained and coarse-grained elastic network models and its dependence on various factors.
In a recent work we developed a method for deriving accurate simplified models that capture the essentials of conventional all-atom NMA and identified two best simplified models: ssNMA and eANM, both of which have a significantly higher correlation with NMA in mean square fluctuation calculations than existing elastic network models such as ANM and ANMr2, a variant of ANM that uses the inverse of the squared separation distances as spring constants. Here, we examine closely how the performance of these elastic network models depends on various factors, namely, the presence of hydrogen atoms in the model, the quality of input structures, and the effect of crystal packing. The study reveals the strengths and limitations of these models. Our results indicate that ssNMA and eANM are the best fine-grained elastic network models but their performance is sensitive to the quality of input structures. When the quality of input structures is poor, ANMr2 is a good alternative for computing mean-square fluctuations while ANM model is a good alternative for obtaining normal modes.


Improving the detection and treatment of schizophrenia.
Schizophrenia is a debilitating, often chronic, psychotic disorder with early onset and a lifetime prevalence of 7.2/1,000. The longer the period without treatment, the worse the outcome. In the UK, the mean duration of untreated psychosis is one to two years. The new NICE guidelines for schizophrenia recommend that all patients who are distressed and have a decline in social functioning accompanied by psychotic symptoms or behaviour suggesting psychosis should be comprehensively assessed by a specialist mental health service. Antipsychotic medication remains the cornerstone of treatment in schizophrenia for the acute and the stabilisation-maintenance phase. The NICE guidelines recommend the use of psychological, social, occupational and educational interventions early in treatment. Mortality rates in schizophrenia are high and the majority of premature deaths are accounted for by physical illnesses. These include cardiovascular disease, diabetes mellitus, COPD, certain cancers and infectious diseases e.g. HIV, hepatitis C, and tuberculosis. Primary care has a significant role to play in monitoring mental state and physical health. Monitoring mental state is crucial. When relapse is threatened because of poor response to treatment, non-adherence to medication, intolerable side effects from medication, comorbid substance misuse, or if risk to self or others is suspected, GPs should refer the patient to the mental health team. GPs should provide a comprehensive health check yearly or more often if there is an indication.


Residual feed intake is related with metabolic and inflammatory response during the pre-weaning period in Italian Simmental calves.
Residual Feed Intake (RFI) is defined as the difference between measured and predicted intake. Understanding its biological regulators could benefit farm profit margins. The most-efficient animals (M-Eff) have observed intake smaller than predicted resulting in negative RFI, whereas the least-efficient (L-Eff) animals have positive RFI. Hence, this observational study aimed at retrospectively comparing the blood immunometabolic profile in calves with divergent RFI during the preweaning period. Twenty-two Italian Simmental calves were monitored from birth through 60 d of age. Calves received 3 L of colostrum from their respective dams. From 2 to 53 d of age, calves were fed a milk replacer twice daily, whereas from 54 to 60 d (i.e., weaning) calves were stepped down to only one meal in the morning. Calves had ad libitum access to concentrate and intakes were recorded daily. The measurement of BW and blood samples were performed at 0, 1, 7, 14, 21, 28, 35, 45, 54, and 60 d of age. Calves were ranked and categorized as M-Eff or L-Eff according to the median RFI value. Median RFI was -0.06 and 0.04 kg of DMI/d for M-Eff and L-Eff, respectively. No evidence for group differences was noted for colostrum and plasma IgG concentrations. Although growth rate was not different, as expected, [0.67 kg/d (95% CI = 0.57 ‒ 0.76) for both L-Eff and M-Eff) throughout the entire pre-weaning period (0-60 d), starter intake was greater in L-Eff compared with M-Eff calves (+36%). Overall, M-Eff calves had a greater gain-to-feed ratio compared with L-Eff calves (+16%). Plasma ceruloplasmin, myeloperoxidase, and reactive oxygen metabolites concentrations were greater in L-Eff compared with M-Eff calves. Compared with L-Eff, M-Eff calves had an overall greater plasma concentration of globulin, and γ-glutamyl transferase (indicating a better colostrum uptake) and Zn at 1 d. Retinol and urea were overall greater in L-Eff. The improved efficiency in nutrient utilization observed in M-Eff was paired with a lower grade of oxidative stress and systemic inflammation. L-Eff may have had greater energy expenditure to support the activation of the immune system.


Expression profiling of familial breast cancers demonstrates higher expression of FGFR2 in BRCA2-associated tumors.
BRCA1- and BRCA2-associated tumors appear to have distinct molecular signatures. BRCA1-associated tumors are predominantly basal-like cancers, whereas BRCA2-associated tumors have a predominant luminal-like phenotype. These two molecular signatures reflect in part the two cell types found in the terminal duct lobular unit of the breast. To elucidate novel genes involved in these two spectra of breast tumorigenesis we performed global gene expression analysis on breast tumors from germline BRCA1 and BRCA2 mutation carriers. Breast tumor RNAs from 7 BRCA1 and 6 BRCA2 mutation carriers were profiled using UHN human 19K cDNA microarrays. Supervised univariate analyses were conducted to identify genes differentially expressed between BRCA1 and BRCA2-associated tumors. Selected discriminatory genes were validated using real time reverse transcription polymerase chain reaction in the tumor RNAs, and/or by immunohistochemistry (IHC) or by in situ hybridization (ISH) on tissue microarrays (TMAs) containing an independent set of 58 BRCA1 and 64 BRCA2-associated tumors. Genes more highly expressed in BRCA1-associated tumors included stathmin, osteopontin, TGFbeta2 and Jagged 1 in addition to genes previously identified as characteristic of basal-like breast cancers. BRCA2-associated cancers were characterized by the higher relative expression of FGF1 and FGFR2. FGFR2 protein was also more highly expressed in BRCA2-associated cancers (P = 0.004). BRCA1-associated tumours demonstrated increased expression of component genes of the Notch and TGFbeta pathways whereas the higher expression of FGFR2 and FGF1 in BRCA2-associated cancers suggests the existence of an autocrine stimulatory loop.


Transcatheter (TAVR) versus surgical (AVR) aortic valve replacement: occurrence, hazard, risk factors, and consequences of neurologic events in the PARTNER trial.
All neurologic events in the PARTNER randomized trial comparing transcatheter aortic valve replacement (TAVR) with surgical aortic valve replacement (AVR) were analyzed. High-risk patients with aortic stenosis were stratified into transfemoral (TF, n = 461) or transapical (TA, n = 196) strata based on their arterial anatomy and randomized: 657 received treatment assigned ("as treated"), 313 underwent AVR, and 344 TAVR. Neurologic events were prospectively adjudicated by an independent Clinical Events Committee. Multivariable, multiphase hazard analysis elucidated factors associated with increased likelihood of neurologic events. Forty-nine neurologic events (15 transient ischemic attacks, 34 strokes) occurred in 47 patients (TAVR, n = 31; AVR, n = 16). An early peaking high hazard phase occurred within the first week, which declined to a constant late hazard phase out to 2 years. The risk in the early phase was higher after TAVR than AVR, and in the TAVR arm in patients with a smaller aortic valve area index. In the late risk phase, the likelihood of neurologic event was linked to patient-related factors in both arms ("non-TF candidate," history of recent stroke or transient ischemic attack, and advanced functional disability), but not by treatment (TAVR vs AVR) or any intraprocedural variables. The likelihood of sustaining a neurologic event was lowest in the AVR subgroup in the TF stratum during all available follow-up. After either treatment, there were 2 distinct hazard phases for neurologic events that were driven by different risk factors. Neurologic complications occurred more frequently after TAVR than AVR early, but thereafter the risk was influenced by patient- and disease-related factors.


Outcome comparison of thoracic endovascular aortic repair performed outside versus inside proximal landing zone length recommendation.
Success of thoracic endovascular aortic repair (TEVAR) relies heavily on the proximal landing zone (PLZ) sealing. Most instructions for use of thoracic endografts recommend a PLZ length of at least 2 cm. Because of the complex aortic anatomic features, TEVAR landing in zone 1 to zone 3 may not meet this requirement. The aim of this study was to examine whether 2-cm PLZ nonadherence was related to adverse outcomes after TEVAR. A retrospective review was performed of patients who underwent zone 1, zone 2, and zone 3 landing TEVAR at a single institution between November 2013 and October 2018. Preoperative and postoperative computed tomography angiography images were analyzed using three-dimensional reconstruction. The patients were categorized into two groups: PLZ ≥2 cm (adherence group) and PLZ <2 cm (nonadherence group). Collected data included patient and anatomic characteristics. Primary outcomes were type IA endoleak, retrograde dissection, and graft migration. The cohort comprised 63 patients (18 in the adherence group and 45 in the nonadherence group) with a mean age of 53.3 ± 20.6 years. Indications for TEVAR were blunt thoracic aortic injury (65.1%), thoracic aneurysm (23.8%), penetrating ulcer (9.5%), and type B dissection (1.6%). Mean PLZ length was significantly shorter for the nonadherence group (8 ± 7 mm for the nonadherence group vs 34 ± 15 mm for the adherence group; P < .0001). PLZ location (2 zone 1, 15 zone 2, 46 zone 3) and oversizing (19.4% ± 8.3% for the adherence group; 20.3% ± 10.2% for the nonadherence group; P = .7) were similar between the groups. The mean PLZ aortic diameter of the adherence group was significantly larger than that of the nonadherence group (29 ± 5 mm for the adherence group; 25 ± 5 mm for the nonadherence group; P = .004). Mean follow-up time was 126.7 days (range, 0-644 days) for the adherence group and 233.8 days (range, 0-1750 days) for the nonadherence group (P = .2). During the study period, no primary outcome was observed in the adherence group, whereas 12 adverse events occurred in 10 patients in the nonadherence group (type IA endoleak, n = 10; graft migration, n = 1; retrograde dissection, n = 1). Of 10 type IA endoleaks, five were immediate (4 resolved spontaneously, 1 remained persistent) and five were delayed (1 resolved spontaneously, 1 remained persistent, 1 ruptured causing death, 2 required total arch replacement). Achieving recommended sealing zone of 2-cm centerline length is paramount to avoid device-related adverse outcomes. We recommend careful surveillance in patients undergoing urgent TEVAR with <2-cm PLZ.


Toward a quantitative description of microscopic pathway heterogeneity in protein folding.
How many structurally different microscopic routes are accessible to a protein molecule while folding? This has been a challenging question to address experimentally as single-molecule studies are constrained by the limited number of observed folding events while ensemble measurements, by definition, report only an average and not the distribution of the quantity under study. Atomistic simulations, on the other hand, are restricted by sampling and the inability to reproduce thermodynamic observables directly. We overcome these bottlenecks in the current work and provide a quantitative description of folding pathway heterogeneity by developing a comprehensive, scalable and yet experimentally consistent approach combining concepts from statistical mechanics, physical kinetics and graph theory. We quantify the folding pathway heterogeneity of five single-domain proteins under two thermodynamic conditions from an analysis of 100 000 folding events generated from a statistical mechanical model incorporating the detailed energetics from more than a million conformational states. The resulting microstate energetics predicts the results of protein engineering experiments, the thermodynamic stabilities of secondary-structure segments from NMR studies, and the end-to-end distance estimates from single-molecule force spectroscopy measurements. We find that a minimum of ∼3-200 microscopic routes, with a diverse ensemble of transition-path structures, are required to account for the total folding flux across the five proteins and the thermodynamic conditions. The partitioning of flux amongst the numerous pathways is shown to be subtly dependent on the experimental conditions that modulate protein stability, topological complexity and the structural resolution at which the folding events are observed. Our predictive methodology thus reveals the presence of rich ensembles of folding mechanisms that are generally invisible in experiments, reconciles the contradictory observations from experiments and simulations and provides an experimentally consistent avenue to quantify folding heterogeneity.


Membrane Phospholipid Analogues as Molecular Rulers to Probe the Position of the Hydrophobic Contact Point of Lysophospholipid Ligands on the Surface of G-Protein-Coupled Receptor during Membrane Approach.
When lipid mediators bind to G-protein-coupled receptors (GPCRs), the ligand first enters the lipid bilayer, then diffuses laterally in the cell membrane to make hydrophobic contact with the receptor protein, and finally enters the receptor's binding pocket. In this process, the location of the hydrophobic contact point on the surface of the receptor has been little discussed even in cases in which the crystal structure has been determined, because the ligand binding pocket is buried inside the transmembrane (TM) domains. Here, we coupled an activator ligand to a series of membrane phospholipid surrogates, which constrain the depth of entry of the ligand into the lipid bilayer. Consequently, via measurement of the receptor-activating activity as a function of the depth of entry into the membrane, these surrogates can be used as molecular rulers to estimate the location of the hydrophobic contact point on the surface of GPCR. We focused on lysophosphatidylserine (LysoPS) receptor GPR34 and prepared a series of simplified membrane-lipid-surrogate-conjugated lysophospholipid analogues by attaching alkoxy amine chains of varying lengths to the hydrophobic tail of a potent GPR34 agonist. As expected, the activity of these lipid-conjugated LysoPS analogues was dependent on chain length. The predicted contact position matches the position of the terminal benzene ring of a nonlipidic ligand that protrudes between TMs 4 and 5 of the receptor. We further found that the nature of the terminal hydrophilic functional group of the conjugated membrane lipid surrogate strongly influences the activity, suggesting that lateral hydrophilic contact of LysoPS analogues with the receptor's surface is also crucial for ligand-GPCR binding.


Sensitization to docetaxel in prostate cancer cells by green tea and quercetin.
Chemotherapy with docetaxel (Doc) is a standard treatment for metastatic and castration-resistant prostate cancer. However, chemoresistance and side effects of Doc limit its clinical success. We investigated whether natural products green tea (GT) and quercetin (Q), a flavonoid from apples and onions, will enhance the efficacy of Doc in androgen-independent (AI) prostate cancer cells. Two cell lines including LAPC-4-AI and PC-3 were treated in vitro with 40 μM of (-)-epigallocatechin gallate (EGCG), 5 μM of Q, 2 or 5 nM of Doc alone or in combination. The mixture of EGCG+Q+Doc increased the antiproliferative effect by threefold in LAPC-4-AI cells and eightfold in PC-3 cells compared to Doc alone. EGCG, Q and Doc in combination significantly enhanced cell cycle arrest at G2/M phase and increased apoptosis in both LAPC-4-AI and PC-3 cells compared to Doc alone. The mixture increased the inhibition of PI3K/Akt and the signal transducer and activator of transcription (Stat) 3 signaling pathways compared to Doc alone, and decreased the protein expression of multidrug resistance-related protein. In addition, the combination with EGCG and Q increased the inhibition of tumor cell invasion and colony formation in both LAPC-4-AI and PC-3 cells compared to Doc alone, and decreased the percentage of CD44(+)/CD24(-) stem-like LAPC-4-AI cells. In summary, GT and Q enhanced the therapeutic effect of Doc in castration-resistant prostate cancer cells through multiple mechanisms including the down-regulation of chemoresistance-related proteins. This study provides a novel therapeutic modality to enhance the efficacy of Doc in a nontoxic manner.


Lack of extracellular signal-regulated kinase mitogen-activated protein kinase signaling shows a new type of melanoma.
The majority of human melanomas harbor activating mutations of either N-RAS or its downstream effector B-RAF, which cause activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase and the ERK MAPK cascade. The melanoma-relevant effectors of ERK activation, however, are largely unknown. In this work, we show that increased ERK activation correlates strongly with mutational status of N-RAS or B-RAF in 21 melanoma cell lines. Melanoma lines that were wild-type for RAS/RAF showed low levels of ERK activation comparable with primary human melanocytes. Through supervised analysis of RNA expression profiles, we identified 82 genes, including TWIST1, HIF1alpha, and IL-8, which correlated with ERK activation across the panel of cell lines and which decreased with pharmacologic inhibition of ERK activity, suggesting that they are ERK transcriptional targets in melanoma. Additionally, lines lacking mutations of N-RAS and B-RAF were molecularly distinct and characterized by p53 inactivation, reduced ERK activity, and increased expression of epithelial markers. Analysis of primary human melanomas by tissue microarray confirmed a high correlation among expression of these epithelial markers in a heterogeneous sample of 570 primary human tumors, suggesting that a significant frequency of primary melanomas is of this "epithelial-like" subtype. These results show a molecularly distinct melanoma subtype that does not require ERK activation or epithelial-mesenchymal transformation for progression.


Effects of diet on gut microbiota profile and the implications for health and disease.
Gut microbes are present in large concentrations on the human intestinal mucosal surface and play important roles in health and disease of the host. Numerous groups of gut microbes are associated with immunological and metabolic diseases and in maintaining health status of the host. Among these health- and disease-associated gut microbes, Bacteroides, Clostridium and Bifidobacterium appear regularly in the list. Scientific and clinical evidence available to date indicates that diet is a major driving factor for the establishment of the gut microbiome. Slow digestible carbohydrates (human milk glycan, inulin and fructooligosaccharide), insoluble complex carbohydrates and protein diets favor the growth of Bacteroides, Clostridium and Bifidobacterium. Fat on the other hand suppresses the number of Bacteroides, Clostridium and Bifidobacterium; whereas polyphenols in general suppress Bacteroides and Clodtridium but enhance the Bifodobacterium. The implication is that dietary habits could be a major determinant of health and disease susceptibility. Dietary strategies could be an effective means of potentially inducing changes in intestinal microbiota and are certainly achievable, thus facilitating correction of intestinal microbiome aberrations or imbalances to improve our health. Most of the physiological and functional interactions between individual dietary components and the concoction of foods in a meal and gut microbiota have not yet been well studied. A concerted effort is required to acquire better understanding of their interaction in order to rationally maintain our intestinal microbiome homeostasis and general health through dietary intervention.


Production of carotenoids from aromatics and pretreated lignocellulosic biomass by Novosphingobium aromaticivorans.
There is economic and environmental interest in generating commodity chemicals from renewable resources, such as lignocellulosic biomass, that can substitute for chemicals derived from fossil fuels. The bacterium Novosphingobium aromaticivorans is a promising microbial platform for producing commodity chemicals from lignocellulosic biomass because it can produce these from compounds in pretreated lignocellulosic biomass, which many industrial microbial catalysts cannot metabolize. Here, we show that N. aromaticivorans can be engineered to produce several valuable carotenoids. We also show that engineered N. aromaticivorans strains can produce these lipophilic chemicals concurrently with the extracellular commodity chemical 2-pyrone-4,6-dicarboxylic acid when grown in a complex liquor obtained from alkaline pretreated lignocellulosic biomass. Concurrent microbial production of valuable intra- and extracellular products can increase the economic value generated from the conversion of lignocellulosic biomass-derived compounds into commodity chemicals and facilitate the separation of water- and membrane-soluble products.


Homeostatic shutdown of long-term potentiation in the adult hippocampus.
Homeostasis is a key concept in biology. It enables ecosystems, organisms, organs, and cells to adjust their operating range to values that ensure optimal performance. Homeostatic regulation of the strength of neuronal connections has been shown to play an important role in the development of the nervous system. Here we investigate whether mature neurons also possess mechanisms to prevent the strengthening of input synapses once the limit of their operating range has been reached. Using electrophysiological recordings in hippocampal slices, we show that such a mechanism exists but comes into play only after a considerable number of synapses have been potentiated. Thus, adult neurons can sustain a substantial amount of synaptic strengthening but, once a certain threshold of potentiation is exceeded, homeostatic regulation ensures that no further strengthening can occur.


High-Performance Hydrogel Sensors Enabled Multimodal And Accurate Human-Machine Interaction System for Active Rehabilitation.
Human-machine interaction (HMI) technology shows an important application prospect in rehabilitation medicine, but it is greatly limited by the unsatisfactory recognition accuracy and wearing comfort. Here, we developed a fully flexible, conformable, and functionalized multimodal HMI interface consisting of hydrogel-based sensors and a self-designed flexible printed circuit board. Thanks to the component regulation and structural design of the hydrogel, both electromyogram (EMG) and forcemyography (FMG) signals can be collected accurately and stably, so that they are later decoded with the assistance of artificial intelligence (AI). Compared with traditional multi-channel electromyographic (EMG) signals, the multimodal human-machine interaction method based on the combination of EMG and FMG signals significantly improves the efficiency of human-machine interaction by increasing the information entropy of the interaction signals. The decoding accuracy of the interaction signals from only two channels for different gestures reaches 91.28%. The resulting AI-powered active rehabilitation system can control a pneumatic robotic glove to assist stroke patients in completing movements according to the recognized human motion intention. Moreover, this HMI interface is further generalized and applied to other remote sensing platforms, such as manipulators, intelligent cars, and drones, paving the way for the design of future intelligent robot systems. This article is protected by copyright. All rights reserved.


Couples Match in Emergency Medicine.
The Match is a daunting process for everyone, but it can be exceedingly more complicated for couples. Accordingly, the Couples Match was introduced by the National Residency Match Program in 1984 and has been witnessing a steady increase in the number of participating couples over the past 30 years. The highest number of couples participating in the match, and the highest match rate among them, was recorded in 2018. In this article, we provide couples considering the Couples Match, with one or both partners planning to apply to emergency medicine, with insights on this process. Although it may initially appear to be complicated, the Couples Match enables partners to obtain postgraduate training in geographic proximity to one another. With good communication between the partners and their advisors, an exciting joint venture can unfold that is fueled by the strength of the couple.


Polarization properties of substrate-mode holographic interconnects.
The polarization properties of cascaded substrate-mode holographic optical elements are analyzed and demonstrated. The design criteria for polarization selective and nonselective elements are given and verified with experimental volume holograms formed in dichromated gelatin emulsions. Using the experimental grating parameters, it is estimated that a reconfigurable optical bus with eight nodes can be made. Improved control of hologram construction parameters can increase this to more than 500 nodes. Use of this device with a reconfigurable interchange coupler and a multistage optical bus is also examined.


Safety and Tolerability of V114 Pneumococcal Vaccine in Infants: A Phase 3 Study.
Disease caused by Streptococcus pneumoniae is associated with considerable morbidity and mortality in children. Pneumococcal conjugate vaccines (PCVs) are well tolerated and effective at reducing pneumococcal disease caused by vaccine serotypes. VAXNEUVANCE (V114) is a 15-valent PCV containing 13 serotypes in Prevnar 13 (PCV13), plus serotypes 22F and 33F. This large phase 3 study evaluated safety and tolerability of V114 in infants. In total, 2409 infants were randomized to receive V114 or PCV13 at 2, 4, 6, and 12 to 15 months of age. Safety was evaluated as the proportion of participants with adverse events (AEs). Solicited and unsolicited injection-site and systemic AEs were collected for 14 days after each study vaccination, and serious AEs up to 6 months after the last PCV dose. The proportions of participants with injection-site, systemic, vaccine-related, and serious AEs were generally comparable between recipients of V114 and PCV13. The most frequently reported AEs were solicited, with irritability and somnolence being the most frequent in both groups. Although the incidence of some AEs was higher in the V114 group, the between-group differences were small. The majority of experienced AEs were of mild-to-moderate intensity and lasted ≤3 days. There were 2 vaccine-related serious AEs of pyrexia in the V114 group, and 2 nonvaccine-related deaths, 1 in each group. No participant discontinued study vaccine because of AEs. V114 is well tolerated and has a generally comparable safety profile to that of PCV13. These study results support routine use of V114 in infants.


Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1.
Acute lung injury (ALI) is a severe inflammatory disease for which no specific treatment exists. As glucocorticoids have potent immunosuppressive effects, their application in ALI is currently being tested in clinical trials. However, the benefits of this type of regimen remain unclear. Here we identify a mechanism of glucocorticoid action that challenges the long-standing dogma of cytokine repression by the glucocorticoid receptor. Contrarily, synergistic gene induction of sphingosine kinase 1 (SphK1) by glucocorticoids and pro-inflammatory stimuli via the glucocorticoid receptor in macrophages increases circulating sphingosine 1-phosphate levels, which proves essential for the inhibition of inflammation. Chemical or genetic inhibition of SphK1 abrogates the therapeutic effects of glucocorticoids. Inflammatory p38 MAPK- and mitogen- and stress-activated protein kinase 1 (MSK1)-dependent pathways cooperate with glucocorticoids to upregulate SphK1 expression. Our findings support a critical role for SphK1 induction in the suppression of lung inflammation by glucocorticoids, and therefore provide rationales for effective anti-inflammatory therapies.


Pedometry methods for assessing free-living adults.
The purpose of this review is to update the methodological aspects of pedometry to encourage the consistent use of pedometers for assessment, to decrease sources of error, and to facilitate comparison and interpretation of results. The specific measurement topics addressed include: instrument choice, metric choice, validity, reliability, data collection and retrieval, time worn, day-to-day variability, monitoring time frame, reactivity, and data treatment. A wide variety of valid and reliable instruments are commercially available and we can expect continued evolutions in value-added features as supporting technology improves. Data collection and retrieval has been achieved through various methods, including face-to-face contact, fax, e-mail, website, and conventional mail, and sometimes a combination of these. Day-to-day variation is not random, as would be expected from inconsistent pedometer performance, but rather exposes true behavior instability that can be explained by other factors and described using a coefficient of variation. Data reduction should be conducted cautiously and only after a full discovery (and disclosure) of its impact on aggregated group statistics and their relationship with other parameters. We have no doubt that research with pedometers will continue to yield new and important insights in the coming years.


Uterine epithelioid trophoblastic tumour in a red-tailed guenon (Cercopithecus ascanius).
Epithelioid trophoblastic tumour (ETT), a rare neoplasm of chorionic-type intermediate trophoblastic cells in the human female, was diagnosed in the uterus of a red-tailed guenon, a non-human primate. The animal, having had two live births, had a recent history of heavy vaginal bleeding. Four years after the last known pregnancy, the animal developed a large invasive mass involving the uterus, right ovary and abdominal wall. The tumour was removed surgically, but at necropsy 1.5 years later was found to have a recurrent neoplasm. Histologically, the original mass consisted of nests and cords of mononuclear intermediate trophoblastic cells whose borders were accentuated by intimately associated eosinophilic hyaline extracellular proteinaceous material. Extensive coalescing areas of necrosis with mineralization surrounding islands of viable neoplastic cells created a "geographical" pattern of necrosis. Immunohistochemical examination revealed that neoplastic cells were diffusely strongly positive for cytokeratin 18, and focally positive for human placental lactogen. The histopathological and immunolabelling patterns were consistent with ETT in human beings. This is the first reported case of epithelioid trophoblastic tumour in a non-human species.


Mealtime energy intake and feeding behaviour in children who fail to thrive: a population-based case-control study.
The essential link between energy needs and energy intake is feeding behaviour, yet few studies have directly observed feeding behaviour in children who have failed to thrive. A cohort of 961 term infants was screened to identify children with first year weight gain below the 5th centile in order to examine their feeding behaviour and food intake. A nested case-control study was used with direct observation at 13-21 months over two lunchtime meals, one consisting of finger foods and the other of 'spoon foods'. Thirty children who failed to thrive and 57 controls were studied. The video-tapes were coded for feeding behaviour using a behavioural coding inventory which distinguishes between children feeding themselves and responding to being fed by their mother. The main outcome measures were counts of five feeding actions (give, accept, feedself, refuse, reject) and measures of energy intake, the weight of food eaten and meal duration. There were systematic differences in feeding behaviour between meal types, with mothers feeding their child more often at meals comprising spoon foods and children feeding themselves more often at meals comprising finger foods. By weight, more food was consumed at the spoon food meals, but energy intake was no higher, showing that the children compensated for the differing energy yields of the foods. Children who failed to thrive took in less energy than controls, and were less likely to sit in a highchair throughout the meal, but there were no clear differences in other aspects of feeding behaviour. Food type is an important variable when studying childhood feeding behaviour. Children who fail to thrive take in less energy than controls of the same age, despite there being no major differences in mealtime feeding behaviour.


Measuring Relevant Information in Health Social Network Conversations and Clinical Diagnosis Cases.
The Internet and social media is an enormous source of information. Health social networks and online collaborative environments enable users to create shared content that afterwards can be discussed. The aim of this paper is to present a novel methodology designed for quantifying relevant information provided by different participants in clinical online discussions. The main goal of the methodology is to facilitate the comparison of participant interactions in clinical conversations. A set of key indicators for different aspects of clinical conversations and specific clinical contributions within a discussion have been defined. Particularly, three new indicators have been proposed to make use of biomedical knowledge extraction based on standard terminologies and ontologies. These indicators allow measuring the relevance of information of each participant of the clinical conversation. Proposed indicators have been applied to one discussion extracted from PatientsLikeMe, as well as to two real clinical cases from the Sanar collaborative discussion system. Results obtained from indicators in the tested cases have been compared with clinical expert opinions to check indicators validity. The methodology has been successfully used for describing participant interactions in real clinical cases belonging to a collaborative clinical case discussion tool and from a conversation from a health social network. This work can be applied to assess collaborative diagnoses, discussions among patients, and the participation of students in clinical case discussions. It permits moderators and educators to obtain a quantitatively measure of the contribution of each participant.


Cerebral abnormalities in adults with ataxia-telangiectasia.
Ataxia-telangiectasia, an autosomal recessive disorder caused by defect of the ataxia-telangiectasia mutated gene, is characterized by progressive neurologic impairment with cerebellar atrophy, ocular and cutaneous telangiectasia, immunodeficiency, heightened sensitivity to ionizing radiation and susceptibility to developing lymphoreticular malignancy. Supratentorial brain abnormalities have been reported only rarely. In this study, brain MRI was performed in 10 adults with ataxia-telangiectasia having stable neurologic impairment. Intracerebral telangiectasia with multiple punctate hemosiderin deposits were identified in 60% of subjects. These lesions were apparently asymptomatic. They are similar in appearance to radiation-induced telangiectasia and to cryptogenic vascular malformations. Also noted, in the 2 oldest subjects, was extensive white matter T2 hyperintensity, and in 1 of these a space-occupying fluid collection consistent with transudative capillary leak and edema as evidenced by reduced levels of metabolites on MR spectroscopic imaging. Asymptomatic supratentorial vascular abnormalities appear to be common in adults with ataxia-telangiectasia.


Tracking surface evolution using ligand-assisted dissolution of cobalt oxyhydroxide.
The use of surface-specific reactions to probe reactive surface area is a promising direction in materials research. The work presented herein examines how the kinetics of dissolution can be used to quantify particle growth as well as the evolution of site-specific reactive surface area. The dissolution of heterogenite (β-CoOOH) by IDA results in two geometric isomers of Co(IDA)(2)(-): the s-fac and u-fac isomers. The heterogenite particles studied here can generally be described as cylindrical plates, and the relative amount of s-fac isomer produced is found to increase as the height of the plates increases. The quantity of each isomer produced is shown to correlate with the relative number of two different types of surface sites, designated as edge and corner sites, while basal sites are seemingly unreactive. It is hypothesized that u-fac isomer results from the more accessible Co centers at the corner sites, while the s-fac isomer results from the less accessible edge sites. An empirical relationship is developed between the fraction of s-fac isomer produced and the height of the β-CoOOH particles, and this relationship is used to quantify particle growth by analysis of kinetic data. Finally, this new information is used to modify a previously proposed pH-dependent growth model, resulting in a significant improvement in the fit and physical relevance of the model.


"Hang in There!": Mental Health in a Sample of the Italian Civil Protection Volunteers during the COVID-19 Health Emergency.
Few studies have been conducted on civil volunteers and their emotional conditions concerning the current COVID-19 pandemic. The present study aimed to evaluate the impact of the COVID-19 emergency on the mental health (general well-being, depression level, and post-traumatic distress), coping strategies, and training needs in an Italian sample of 331 Civil Protection volunteers of the L'Aquila province, during the first nationwide "lockdown" (8 March-3 June 2020). The rate of respondents to the online survey was limited (11.5%), presumably because displaying distress would be considered a sign of "weakness", making volunteers unable to do their jobs. More than 90% of the volunteers showed good mental health conditions and a wide utilization of positive coping strategies, with the less experienced displaying better emotional conditions compared to colleagues with 10 or more years of experience. The type of emergency, the relatively few cases of contagion and mortality in the territory compared to the rest of Italy, and the sense of helping the community, together with the awareness of their group identity, could have contributed to the reported well-being. These results may help to identify the needs of volunteers related to this new "urban" emergency to improve both their technical and emotional skills.


[Sagittal equilibrium of the pelvis: analysis of the inclination of the ischio-pubic ramus from the horizontal].
The sagittal equilibrium of the spine and pelvis has been examined in numerous studies looking for the origin of certain posture disorders of the spine and the cause of lower back pain. Sagittal x-rays of the pelvis provide an analysis of the degree of inclination of the pelvis from the horizontal and the bi-coxo-femoral axis and information on the form of the sacrum. There is no radiographic parameter however which analyzes the transition between the pelvis-sacrum component and the femoral component, i.e. the periacetabular region. In the sagittal plane, a line tangent to the ischio-pubic ramus would appear to best reflect the orientation of the periacetabular region and the muscular forces applied to this region. The purpose of this work was to analyze the inclination of the ischio-pubic ramus from the horizontal and its relations with other sagittal radiographic parameters in a population of growing children with spinal disorders. The study population included 100 children with spinal disorders who underwent a teleradiographic series with lateral view in the upright position. Most of the children had scoliosis (80 cases), 7 had kyphoscoliosis, 4 isthmic spondylolysis with spondylolisthesis, 1 spondylodiscitis and 4 lower back pain. Mean age was 13 years (range 2.5-22 years). We measured 7 radiographic parameters: lumbo-sacral angle, slope of the sacrum, pelvic version, incidence, thickness, overhang, and inclination of the ischio-pubic ramus from the horizontal. Data were analyzed to search for correlations between radiographic parameters and between radiographic parameters and clinical features. Mean inclination of the ischio-pubic ramus from the horizontal was 33.9 degrees (SD =5.9 degrees ). The only positive statistical correlation between the inclination of the ischio-pubic ramus and the clinical data was a relationship with the position of the arms compared with the horizontal (p =0.04). There was no correlation with age, sex, ethnic background, etiology. There was no correlation between the inclination of the ischio-pubic ramus and the other radiographic parameters (coefficient r ranging from 0.06 to 0.43). The interdependence of sagittal radiographic parameters of the pelvis and the spine have been largely demonstrated. Certain pathological situations (isthmic spondylolysis with spondylolisthesis, lower back pain, etc.) can be explained by the value of these parameters, particularly incidence. The inclination of the ischio-pubic ramus from the horizontal reflects the periacetabular region. When analyzed in the sagittal plane, it was found to be a more stable parameter, independent of most clinical criteria (particularly age, and etiology) and of the other radiographic parameters studied. The only determining factor appears to be acquisition of the upright position. The consistency of this parameter constrasts with the variability of the other radiographic parameters of the pelvis and the spine, particularly incidence, although the inclination of the ischio-pubis ramus is an expression of a region different than the pelvis. This study suggests that the periacetabular region plays a key role in acquisition of the upright position in humans. The periacetabular region would be a fixed point around which the lower limbs and spine describe varying orientations.


Local networks from different parts of the human cerebral cortex generate and share the same population dynamic.
A major goal of neuroscience is to reveal mechanisms supporting collaborative actions of neurons in local and larger-scale networks. However, no clear overall principle of operation has emerged despite decades-long experimental efforts. Here, we used an unbiased method to extract and identify the dynamics of local postsynaptic network states contained in the cortical field potential. Field potentials were recorded by depth electrodes targeting a wide selection of cortical regions during spontaneous activities, and sensory, motor, and cognitive experimental tasks. Despite different architectures and different activities, all local cortical networks generated the same type of dynamic confined to one region only of state space. Surprisingly, within this region, state trajectories expanded and contracted continuously during all brain activities and generated a single expansion followed by a contraction in a single trial. This behavior deviates from known attractors and attractor networks. The state-space contractions of particular subsets of brain regions cross-correlated during perceptive, motor, and cognitive tasks. Our results imply that the cortex does not need to change its dynamic to shift between different activities, making task-switching inherent in the dynamic of collective cortical operations. Our results provide a mathematically described general explanation of local and larger scale cortical dynamic.


Effects of excessive ethanol consumption on the diagnosis of the metabolic syndrome using its clinical diagnostic criteria.
Various morbid conditions constituting the metabolic syndrome could be also caused by excessive ethanol consumption. Thus, it is conceivable that excessive ethanol consumption may affect the diagnosis of the metabolic syndrome using its current diagnostic criteria. Here, we investigated this. A cross-sectional study involving 2,130 Japanese man subjects aged 20 to 65 was performed. The rate of subjects judged to have metabolic syndrome using its diagnostic criteria for Japanese was 15.7%. However, the prevalence was significantly higher in excessive drinkers who consume more than 20 grams of ethanol per day (n=473, 22.0%) than average drinkers (n=1,657, 13.9%, chi2=18.0, p<0.0001). The rate of subjects who satisfied each component of the criteria of the metabolic syndrome, namely that of an excessive waist circumference, hypertension, dyslipidemia, or hyperglycemia was significantly higher in the former than in the latter, respectively. When subjects with a waist circumferences of 85 cm or more were selectively studied, the prevalence of the metabolic syndrome was still higher in excessive drinkers (39.2%) than in average drinkers (32.4%, chi2=4.0, p=0.049), whereas the waist circumference was not significantly different between the two groups. Excessive ethanol consumption is associated with an increased prevalence of the metabolic syndrome following the current clinical diagnostic criteria. Excessive ethanol consumption could simply be a factor worsening the metabolic syndrome. However, we must be aware of another possibility that excessive ethanol consumption increases the number of subjects regarded as the metabolic syndrome via mechanisms differing from visceral fat accumulation.


Cockayne syndrome with tetralogy of Fallot: a case report.
Cockayne syndrome (CS) is a rare autosomal recessive disorder characterized by growth retardation, senile-like appearance, loss of subcutaneous adipose tissue, photosensitive dermatitis, microcephaly, deafness, pigmentary degeneration of retina, disproportionately long limbs, skeletal malformations with knee contractures and neurologic abnormalities. This is a description of a three-year-old boy with typical features of Cockayne syndrome complicated with tetralogy of Fallot, pneumonia and hepato-splenomegaly. He had been suffering from frequent attacks of pneumonia and had been hospitalized for several times since birth. Tetralogy of Fallot was diagnosed under echocardiography study and he died suddenly in hospital during a mydriatic procedure in the Ophthalmologic Clinic.


Online sonification improves cycling performance through kinematic and muscular reorganisations.
Based on a previous study that demonstrated the beneficial effects of sonification on cycling performance, this study investigated which kinematic and muscular activities were changed to pedal effectively. An online error-based sonification strategy was developed, such that, when negative torque was applied to the pedal, a squeak sound was produced in real-time in the corresponding headphone. Participants completed four 6-min cycling trials with resistance values associated with their first ventilatory threshold. Different auditory display conditions were used for each trial (Silent, Right, Left, Stereo), where sonification was only presented for 20 s at the start of minutes 1, 2, 3, and 4. Joint kinematics and right leg muscular activities of 10 muscles were simultaneously recorded. Our results showed participants were more effective at pedalling when presented sonification, which was consistent with previously reported findings. In comparison to the Silent condition, sonification significantly limited ankle and knee joint ranges of motion and reduced muscular activations. These findings suggest performance-based sonification significantly affected participants to reduce the complexity of the task by altering the coordination of the degrees of freedom. By making these significant changes to their patterns, participants improved their cycling performance despite lowering joint ranges of motion and muscular activations.


Prognostic values of the mRNA expression of natural killer receptor ligands and their association with clinicopathological features in breast cancer patients.
Natural killer (NK) cells are lymphocytes of the innate immune system that have potent cytotoxic activity against tumor cells. NK cell recognition and activity towards cancer cells are regulated by an integrated interplay between numerous inhibitory and activating receptors acting in concert to eliminate tumor cells expressing cognate ligands. Despite strong evidence supporting the role of NK cells in breast cancer (BC) control, BC still develops and progresses to form large tumors and metastases. A major mechanism of BC escape from NK immunity is the alteration of the expression of NK receptor ligands. The aim of this study was to determine whether NK receptor ligands' mRNA expression might influence prognosis in BC patients and whether these effects differ by molecular subtypes and clinicopathological features. We used the KM plotter platform to analyze the correlation between mRNA expression of 32 NK receptor ligands and relapse-free survival (RFS) and overall survival (OS) in 3951 and 1402 BC patients, respectively. The association with tumor subtypes and clinicopathological features was determined. BC samples were split into high and low expression groups according to the best cutoff value and the two patient cohorts were compared by Kaplan-Meier survival plots. The hazard ratios with 95% confidence intervals and log rank P values were calculated and FDR-adjusted for multiple testing correction. The data was considered to be statistically significant when FDR-adjusted P value < 0.05. High mRNA expression of around 80% of ligands for NK activating and inhibitory receptors associated with better RFS, which correlated with longer OS for only about half of the NK-activating ligands but for most NK-inhibitory ligands. Also, five NK-activating ligands correlated with worse prognosis. These prognostic values were differentially associated with the BC clinical criteria. In addition, the favorable prognostic influence of NK-activating ligands' upregulation, as a whole, was mainly significantly associated with HER2-positive and basal-like subtypes, lymph node positive phenotype, and high-grade tumors. NK receptor ligands appear to play an important role in defining BC patient prognosis. Identification of a group of patients with worse prognosis expressing high levels of NK-activating ligands and low levels of NK-inhibitory ligands makes them ideal potential candidates for NK-based immunotherapy to eliminate residual tumor cells, prevent relapse and improve patient survival.


Swept confocally-aligned planar excitation (SCAPE) microscopy for high speed volumetric imaging of behaving organisms.
We report a new 3D microscopy technique that allows volumetric imaging of living samples at ultra-high speeds: Swept, confocally-aligned planar excitation (SCAPE) microscopy. While confocal and two-photon microscopy have revolutionized biomedical research, current implementations are costly, complex and limited in their ability to image 3D volumes at high speeds. Light-sheet microscopy techniques using two-objective, orthogonal illumination and detection require a highly constrained sample geometry, and either physical sample translation or complex synchronization of illumination and detection planes. In contrast, SCAPE microscopy acquires images using an angled, swept light-sheet in a single-objective, en-face geometry. Unique confocal descanning and image rotation optics map this moving plane onto a stationary high-speed camera, permitting completely translationless 3D imaging of intact samples at rates exceeding 20 volumes per second. We demonstrate SCAPE microscopy by imaging spontaneous neuronal firing in the intact brain of awake behaving mice, as well as freely moving transgenic Drosophila larvae.


Loss of heterozygosity of the short arm of chromosomes 3 and 9 in oral cancer.
Loss of heterozygosity (LOH) on chromosomes 3p and 9p has been documented in a variety of malignancies, which suggests the presence of tumor suppressor gene loci on these chromosomes. We have studied 77 oral carcinomas for LOH using 16 microsatellite markers distributed over 5 human chromosomes. Fifty-five (71%) of these tumors showed LOH at one or more loci. A significant proportion of LOH at the informative tumors was observed at chromosomes 3p and 9p: 58% and 48%, respectively. A majority of the tumors showed losses at multiple loci on chromosomes 3p or 9p or on both. Our results suggest that tumor suppressor genes located on the short arms of chromosomes 3 and 9 may be involved in the pathogenesis of oral carcinoma. These regions of deletion observed in oral cancers overlap those reported in other neoplasms. However, we did not find any evidence of these changes in tumor margins with early pathological changes.


Differential effects of taurine treatment and taurine deficiency on the outcome of renal ischemia reperfusion injury.
Taurine possesses membrane stabilization, osmoregulatory and antioxidant properties, aspects of relevance to ischemic injury. We tested the hypothesis that body taurine status is a determinant of renal ischemic injury. Accordingly, renal function and structure were examined in control (C), taurine-treated (TT) and taurine deficient (TD) rats that were subjected to bilateral renal ischemia (60 min) followed by reperfusion (IR); sham operated rats served as controls. Baseline urine osmolality was greater in the TD group than in the control and the TT groups, an effect associated with increased renal aquaporin 2 level. The IR insult reduced urine osmolality (i.e., day-1 post insult); the TD/IR group displayed a more marked recovery in urine osmolality by day-6 post insult than the other two groups. Fluid and sodium excretions were lower in the TD/IR group, suggesting propensity to retention. Histopathological examination revealed the presence of tubular necrotic foci in the C/IR group than sham controls. While renal architecture of the TD/IR group showed features resembling sham controls, the TT/IR group showed dilated tubules, which lacked immunostaining for aquaporin 2, but not 1, suggestive of proximal tubule origin. Finally, assessment of cell proliferation and apoptosis revealed lower proliferation but higher apoptotic foci in the TT/IR group than other IR groups. Collectively, the results indicate that body taurine status is a major determinant of renal IR injury.


N-acetyl cysteine, inulin and the two as a combined therapy ameliorate cognitive decline in testosterone-deprived rats.
Our previous studies reported that testosterone-deprived rats developed cognitive decline as a result of increased brain oxidative stress, microglia hyperactivity, and hippocampal dysplasticity. In addition, gut dysbiosis occurred in these rats. Previous studies demonstrated that n-acetyl cysteine (NAC) and a prebiotic (inulin) improved cognition in several pathological conditions. However, its effects on cognition in the testosterone-deprived condition have never been investigated. This study hypothesized that the administration of NAC, inulin, and a combined therapy improved cognition in castrated rats. Here we report that metabolic disturbance was not observed in the ORX rats, but gut dysbiosis was found in these rats. ORX rats developed blood-brain-barrier (BBB) breakdown, and increased brain oxidative stress as indicated by increased hippocampal production of reactive oxygen species (ROS) and an increase in brain malondialdehyde level. ORX rats also demonstrated glia hyperactivation, resulting in hippocampal apoptosis, hippocampal dysplasticity, and cognitive decline. All treatments equally ameliorated cognitive decline by improving gut dysbiosis, alleviating BBB dysfunction, decreasing hippocampal ROS production, decreasing hippocampal apoptosis, and reducing microglia and astrocyte activity. These findings suggest that NAC, inulin, and the combined therapy ameliorated the deleterious effects on the brain in castrated male rats similar to those treated with testosterone.


Development of an ionic-liquid-based dispersive liquid-liquid microextraction method for the determination of antichagasic drugs in human breast milk: Optimization by central composite design.
Chagas disease constitutes a major public health problem in Latin America. Human breast milk is a biological sample of great importance for the analysis of therapeutic drugs, as unwanted exposure through breast milk could result in pharmacological effects in the nursing infant. Thus, the goal of breast milk drug analysis is to inquire to which extent a neonate may be exposed to a drug during lactation. In this work, we developed an analytical technique to quantify benznidazole and nifurtimox (the two antichagasic drugs currently available for medical treatment) in human breast milk, with a simple sample pretreatment followed by an ionic-liquid-based dispersive liquid-liquid microextraction combined with high-performance liquid chromatography and UV detection. For this technique, the ionic liquid 1-octyl-3-methylimidazolium hexafluorophosphate has been used as the "extraction solvent." A central composite design was used to find the optimum values for the significant variables affecting the extraction process: volume of ionic liquid, volume of dispersant solvent, ionic strength, and pH. At the optimum working conditions, the average recoveries were 77.5 and 89.7%, the limits of detection were 0.06 and 0.09 μg/mL and the interday reproducibilities were 6.25 and 5.77% for benznidazole and nifurtimox, respectively. The proposed methodology can be considered sensitive, simple, robust, accurate, and green.


Pregabalin Treatment of a Patient With Complex Regional Pain Syndrome.
Complex regional pain syndrome (CRPS) is a painful and disabling neurovascular condition. There is no consensus on the etiopathogenesis or the treatment. We present a patient with CRPS type 1 accompanied by a psychiatric disorder to discuss the relationship between CRPS and psychiatric disease and to emphasize the response of this case to treatment with pregabalin. A 15-year-old girl presented with swelling, severe pain, edema, hyperesthesia, allodynia, and sweating changes in the left arm and was diagnosed as CRPS type 1. The presence of disturbed family relations was revealed on psychiatric examination, and a diagnosis of major depression was made. Her symptoms did not respond to selective serotonin reuptake inhibitors and noradrenergic and specific serotonergic antidepressives, gabapentin, or stellate ganglion blockage, but the patient's pain resolved with pregabalin. Symptom-oriented measures and psychiatric support enabled ongoing treatment. A social services evaluation led to her being placed in the care of social services to protect her from the chaotic and traumatic family life. Detailed psycological and psychiatric evaluation is recommended in individuals with CRPS because psychiatric support and improvement of associated psychosocial concerns in addition to pregabalin seems to facilitate treatments in some patients.


Transurethral ultrasound-guided oocyte retrieval for in vitro fertilization.
Thirty-nine follicular aspirations for in vitro fertilization were performed in 30 patients. Oocyte retrieval was performed by laparoscopy in 21 cases and ultrasound-guided transurethral aspiration in 18 cases. All procedures were performed by the same ovarian stimulation protocol and the same aspirating needle. In the laparoscopy group 150 oocytes were recovered from 177 follicles aspirated (85%). The fertilization rate was 69% (104/150) and cleavage rate, excluding triploidy, was 82% (85/104) for oocytes obtained by laparoscopy. Five clinical pregnancies occurred in the laparoscopy group for a pregnancy rate of 24% per cycle and 25% per transfer. In the transurethral ultrasound-guided group 77 oocytes were recovered from 103 follicles aspirated (75%). The fertilization rate was 79% (61/77) and cleavage rate, excluding triploidy, was 90% (55/61). Three pregnancies occurred for a pregnancy rate of 17% per cycle and 18% per transfer. None of these differences were statistically significant. Transurethral ultrasound-guided oocyte retrieval is a feasible alternative to laparoscopy for in vitro fertilization.


Detection of weak chaos in infant respiration.
This paper concerns the application of newly developed methods for decomposition of an infant respiratory signal into locally stable nonsinusoidal periodic components. Each estimated component has dynamical variation in its three periodicity attributes, i.e., periodicity, scaling factors, and the waveform or pattern associated with the successive segments. Earlier, it has been reported with the application of conventional surrogate analysis and with the cylindrical basis function modeling that the underlying system is distinctly different from linearly filtered Gaussian process, and most probably the human respiratory system behaves as a nonlinear periodic oscillator with two or three degrees of freedom being driven by a high-dimensional noise source. Here, the surrogate analysis is extended and four new types of nonlinear surrogates have been proposed, which are produced by randomizing one or multiple periodicity attributes while preserving certain individual relationships. In this way, a new type of dissection of dynamics is possible, which can lead to a proper understanding of couplings between different controlling parameters.


Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy.
HIV-associated nephropathy is a clinicopathologic entity that includes proteinuria, focal segmental glomerulosclerosis often of the collapsing variant, and microcystic tubulointerstitial disease. Increasing evidence supports a role for HIV-1 infection of renal epithelium in the pathogenesis of HIV-associated nephropathy. Using in situ hybridization, we previously demonstrated HIV-1 gag and nef mRNA in renal epithelial cells of patients with HIV-associated nephropathy. Here, to investigate whether renal epithelial cells were productively infected by HIV-1, we examined renal tissue for the presence of HIV-1 DNA and mRNA by in situ hybridization and PCR, and we molecularly characterized the HIV-1 quasispecies in the renal compartment. Infected renal epithelial cells were removed by laser-capture microdissection from biopsies of two patients, DNA was extracted, and HIV-1 V3-loop or gp120-envelope sequences were amplified from individually dissected cells by nested PCR. Phylogenetic analysis of kidney-derived sequences as well as corresponding sequences from peripheral blood mononuclear cells of the same patients revealed evidence of tissue-specific viral evolution. In phylogenetic trees constructed from V3 and gp120 sequences, kidney-derived sequences formed tissue-specific subclusters within the radiation of blood mononuclear cell-derived viral sequences from both patients. These data, along with the detection of HIV-1-specific proviral DNA and mRNA in tubular epithelium cells, argue strongly for localized replication of HIV-1 in the kidney and the existence of a renal viral reservoir.


Disruption of the mauna loa magma system by the 1868 hawaiian earthquake: geochemical evidence.
To test whether a catastrophic earthquake could affect an active magma system, mean abundances (adjusted for "olivine control") of titanium, potassium, phosphorus, strontium, zirconium, and niobium of historic lavas erupted from Mauna Loa Volcano, Hawaii, after 1868 were analyzed and were found to decrease sharply relative to lavas erupted before 1868. This abrupt change in lava chemistry, accompanied by a halved lava-production rate for Mauna Loa after 1877, is interpreted to reflect the disruptive effects of a magnitude 7.5 earthquake in 1868. This interpretation represents a documentable case of changes in magmatic chemical variations initiated or accelerated by a major tectonic event.


Rheological characterization of nephila spidroin solution.
We report the results of an investigation into the rheology of solutions of natural spider silk dope (spinning solution). We demonstrate that dilute dope solutions showed only shear thinning as the shear rate increased while more concentrated solutions showed an initial shear thinning followed by a shear thickening and a subsequent decline in viscosity. The critical shear rate for shear thickening depended on dope concentration and was very low in concentrated solutions. This helps to explain how spiders are able to spin silk at very low draw rates and why they use a very concentrated dope solution. We also show that the optimum shear rate for shear thickening in moderately concentrated solutions occurred at pH 6.3 close to the observed pH at the distal end of the spider's spinning duct. Finally, we report that the addition of K(+) ions to dilute dope solutions produced a spontaneous formation of nanofibrils that subsequently aggregated and precipitated. This change was not seen after the addition of other common cations. Taken together, these observations support the hypothesis that the secretion of H(+) and K(+) by the spider's duct together with moderate strain rates produced during spinning induce a phase separation in the silk dope in which the silk protein (spidroin) molecules are converted into insoluble nanofibrils.


Dosimetry in nuclear medicine therapy: radiobiology application and results.
The linear quadratic model (LQM) has largely been used to assess the radiobiological damage to tissue by external beam fractionated radiotherapy and more recently has been extended to encompass a general continuous time varying dose rate protocol such as targeted radionuclide therapy (TRT). In this review, we provide the basic aspects of radiobiology, from a theoretical point of view, starting from the "four Rs" of radiobiology and introducing the biologically effective doses, which may be used to quantify the impact of a treatment on both tumors and normal tissues. We also present the main parameters required in the LQM, and illustrate the main models of tumor control probability and normal tissue complication probability and summarize the main dose-effect responses, reported in literature, which demonstrate the tentative link between targeted radiotherapy doses and those used in conventional radiotherapy. A better understanding of the radiobiology and mechanisms of action of TRT could contribute to describe the clinical data and guide the development of future compounds and the designing of prospective clinical trials.


Clinical evaluation and pathomechanism of urticaria-like skin eruption in systemic lupus erythematosus.
Clinical observations of 10 SLE patients having urticaria-like skin symptoms showed that the clinical process of urticaria found in patients suffering from SLE differs from the classic one. On the basis of histological and immunohistological studies in 5 cases, a characteristic histological manifestation of leukocytoclastic vasculitis of small veins in the upper third of the cutis was found. The various urticaria-like skin symptoms in SLE are caused by immunocomplexes of various components. The continuous presence of urticaria is caused by C-activating formation of anaphylatoxin. The appearance of urticaria in SLE patients is an unfavourable precursor which has been confirmed by statistical analysis.


Fully Photoswitchable Phototransistor Memory Comprising Perovskite Quantum Dot-Based Hybrid Nanocomposites as a Photoresponsive Floating Gate.
Tremendous research efforts have been dedicated into the field of photoresponsive nonvolatile memory devices owing to their advantages of fast transmitting speed, low latency, and power-saving property that are suitable for replacing current electrical-driven electronics. However, the reported memory devices still rely on the assistance of gate bias to program them, and a real fully photoswitchable transistor memory is still rare. Herein, we report a phototransistor memory device comprising polymer/perovskite quantum dot (QD) hybrid nanocomposites as a photoresponsive floating gate. The perovskite QDs offer an effective discreteness with an excellent photoresponse that are suitable for photogate application. In addition, a series of ultraviolet (UV)-sensitive insulating polymer hosts were designed to investigate the effect of UV light on the memory behavior. We found that a fully photoswitchable memory device was fulfilled by using the independent and sequential photoexcitation between a UV-sensitive polymer host and a visible light-sensitive QD photogates, which produced decent photoresponse, memory switchability, and highly stable memory retention with a memory ratio of 104 over 104 s. This study not only unraveled the mystery in the fully photoswitchable functionality of nonvolatile memory but also enlightened their potential in the next-generation electronics for light-fidelity application.