Are the neglected tropical diseases under control in the tri-border region between Brazil, Argentina, and Paraguay?
Implementation of prevention and control measures for communicable diseases in border regions can be challenging and lead to inefficient attempts to control them. We describe evidences on the strengths, weaknesses, opportunities and challenges regarding implementation of health interventions for control, prevention and treatment of selected neglected tropical diseases (NTD), a group of transmissible diseases typically prevalent in tropical countries and vulnerable populations, in the tri-border between Brazil, Argentina, and Paraguay. A systematic literature review of observational and experimental studies was conducted, using PubMed and Bireme databases. Eligibility criteria were location (tri-border area) and subject (health interventions). Of a total of 595 references identified, 34 studies were included (18 pertaining to leishmaniasis, 11 to dengue, 2 to leprosy, 2 to soil-transmitted helminthiases and 1 to Chagas' disease), with an inclusion rate of 6.4%. The main strengths were the similarity of health interventions between countries and easiness of mobility and communication flows. The main weaknesses were access to rural areas and discrepancies in the number of studies between countries. As for opportunities, we identified increased tourism, economic development and recent increasing research in this field. The main challenges were the absence of studies regarding other prevalent NTD in the region and movement of goods, animals and people across borders. Although epidemiological studies are still needed to better understand and assess the prevalence of NTD in the area, mainly in Paraguay, these findings can inform decision-makers and health managers to plan a common strategy to address NTD.


Sequential chemoradiation in locally advanced head and neck cancer after induction chemotherapy: an induction chemotherapy schedule more suited to a limited resource setting.
In our experience, induction docetaxel, platinum, and fluorouracil (TPF) chemotherapy and sequential chemoradiation in locally advanced head and neck cancer lowers compliance owing to their considerable toxicity. Most of our head and neck cancer patients have locally advanced disease at presentation. Physicians frequently prefer paclitaxel-cisplatin induction chemotherapy instead, because of better patient tolerance. A total of 207 locally advanced head and neck cancer patients receiving paclitaxel and cisplatin prior to chemoradiation from November 2010 to October 2013 were studied retrospectively. Parameters like febrile neutropaenia, treatment compliance, and response rates were compared to our institutional retrospective data with TPF chemotherapy. Response was assessed by Response Evaluation Criteria in Solid Tumours (Recist) version 1.1. Toxicity was assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 during chemotherapy. Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were used for assessment during chemoradiation. Febrile neutropaenia with paclitaxel- cisplatin was significantly lower 3.4% (7/207) versus 44.5% (73/164) with TPF chemotherapy (two-tailed P value < 0.0001). A 95.7 % (198/207) paclitaxel-cisplatin patients completed chemoradiation versus 87% with TPF. The difference was significant (two-tailed P value = 0.0070). Response rate at treatment completion with paclitaxel -cisplatin was 89.7% versus 88% with TPF chemotherapy. No significant differences were observed (two-tailed P value = 0.7007). Induction paclitaxel and cisplatin with sequential chemoradiation in locally advanced head and neck cancer is more suitable in a limited resource setting. Lower toxicity, better compliance, and comparable response are encouraging in our study cohort.


Matrix metalloproteinases -2 and -9 and their endogenous tissue inhibitors in fetal membrane repair following fetoscopy in a rabbit model.
The cellular mechanisms underlying fetal membrane repair are poorly understood. Matrix metalloproteinases (MMP) and the endogenous tissue inhibitors of metalloproteinases (TIMP) play a key role in the control of turnover of extracellular matrix in fetal membranes at normal parturition and preterm prelabour rupture of the fetal membranes (PPROM). The time course of secretion of MMP-2 (72 kDa, gelatinase A) and MMP-9 (92 kDa, gelatinase B) and TIMP into extra-embryonic coelomic, allantoic and amniotic fluids in a rabbit model was examined. Furthermore, to evaluate their role in fetal membrane repair, the changes induced by fetoscopy at mid-gestation (23 days; gestation length is 32 days) were investigated. Zymography showed predominantly secretion of latent MMP-2 at 18, 23 and 30 days of gestation in all gestational compartments. Reverse zymography detected a broad range of TIMP activity with molecular weights of 27-30 kDa (TIMP-1, glycosylated TIMP-3 and TIMP-4), 24 kDa (unglycosylated TIMP-3) and 21 kDa (TIMP-2). Following fetoscopy, both MMP-2 and TIMP increased significantly in amniotic fluid and extra-embryonic coelomic fluid, but not in allantoic fluid, as demonstrated by densitometric analyses. These findings indicate a modulating role for MMP and TIMP in the repair processes following a surgically induced fetal membrane defect.


Encapsulation of Gold-Based Anticancer Agents in Protease-Degradable Peptide Nanofilaments Enhances Their Potency.
We investigated the use of amphiphilic, protease-cleavable peptides as encapsulation moieties for hydrophobic metallodrugs, in order to enhance their bioavailability and consequent activity. Two hydrophobic, gold-containing anticancer agents varying in aromatic ligand distribution (Au(I)-N-heterocyclic carbene compounds 1 and 2) were investigated. These were encapsulated into amphiphilic decapeptides that form soluble filamentous structures with hydrophobic cores, varying supramolecular packing arrangements and surface charge. Peptide sequence strongly dictates the supramolecular packing within the aromatic core, which in turn dictates drug loading. Anionic peptide filaments can effectively load 1, and to a lesser extent 2, while their cationic counterparts could not, collectively demonstrating that loading efficiency is dictated by both aromatic and electrostatic (mis)matching between drug and peptide. Peptide nanofilaments were nontoxic to cancerous and noncancerous cells. By contrast, those loaded with 1 and 2 displayed enhanced cytotoxicity in comparison to 1 and 2 alone, when exposed to Caki-1 and MDA-MB-231 cancerous cell lines, while no cytotoxicity was observed in noncancerous lung fibroblasts, IMR-90. We propose that the enhanced in vitro activity results from the enhanced proteolytic activity in the vicinity of the cancer cells, thereby breaking the filaments into drug-bound peptide fragments that are taken up by these cells, resulting in enhanced cytotoxicity toward cancer cells.


Neurobiology of central angiotensin III and dipsogenesis.
This review provides a synopsis of the physiologic role of central angiotensin III (AIII), the biologically active degradative product of angiotensin II, in dipsogenesis. The integrity of the central noradrenergic system is essential to the elicitation of polydipsia by AIII. It is conceivable that synaptically released norepinephrine may act on the alpha 1-adrenoceptors to potentiate the drinking response to the heptapeptide. This release, however, may be subjected to a tonic inhibition by the alpha 2-adrenoceptors. Chronic intracerebroventricular administration of AIII fails to produce sustained drinking behavior in spontaneously hypertensive rats. Behavioral and electrophysiologic observations suggest that this is because of the development of early desensitization of at least the angiotensin receptors at the subfornical organ, a major target site for AIII-induced dipsogenesis. This process is exacerbated by a suggested dysfunction of the central degradative enzyme for AIII in this strain of rat. Recent results suggest that it is likely that neurons in the caudal hypoglossal nucleus may serve as the final common pathway for AIII-induced drinking response. Furthermore, an excitatory link between the nucleus reticularis gigantocellularis in the medulla oblongata and caudal hypoglossal nucleus may form part of the descending neural pathways that mediate the dipsogenesis elicited by AIII. It is evident that AIII in the brain participates actively in at least the initiation and consummatory phases of water homeostasis. Thus, apart from directly acting on the central machinery for circulatory control, AIII may also influence cardiovascular functions by affecting cardiac output via regulation of fluid volume.


High performance free-standing films by layer-by-layer assembly of graphene flakes and ribbons with natural polymers.
In this work, novel free-standing (FS) films based on chitosan, alginate and graphene oxide (GO) were developed through layer-by-layer assembly. First, GO was synthesized from graphite and multi-walled carbon nanotubes using a modified Hummer's method, yielding oxidized graphene flakes (o-GFs) and oxidized graphene nanoribbons (o-GNRs), respectively, which were then characterized. Then FS films were produced and their morphological, thermal and mechanical properties, as well as the o-GF and o-GNR dispersion along the films were assessed. Their degradation and swelling profiles as well as their biological behavior were evaluated. Graphite and nanotubes were successfully oxidized and exfoliated forming stable suspensions that could be combined with chitosan (CHI) and alginate (ALG) solutions by layer-by-layer processing. The addition of o-GFs and o-GNRs resulted in rougher, hydrophilic FS films with significantly improved mechanical properties relative to CHI/ALG films. The presence of o-GFs or o-GNRs did not affect the thermal stability and the addition of o-GFs resulted in films with enhanced cytocompatibility. The results demonstrate the high potential of the GO reinforced films for biomedical applications, in particular o-GF films, for wound healing, and cardiac and bone engineering applications.


[Risk factors associated with dystocic delivery].
the dystocic delivery is a frequent complication and its perinatal repercussions vary from minor lesions to severe brain damage. It has been reported diverse factors associated with this medical complication. to identify the risk factors with significant association with dystocic delivery. a case-control study was carried out. There were included 750 patients, divided into 250 women with dystocic deliveries (cases) and 500 women with eutocic deliveries (controls). Demographic and clinical variables were registered. The statistical analysis was performed with percentages, arithmetic media, standard deviation, Student t test, chi2 and logistic regression analysis. An alpha value was set at 0.05. the factors with statistical significance were: advanced age (p < 0.001), major patient's height (p < 0.001), major new born's weight (p = 0.009), lower parity (p < 0.001), and prolonged duration of labor (p = 0.04). Other variables such as number of pregnancies, previous cesarean sections, spontaneous abortions, weight of the patient, weight earned during pregnancy, number of medical appointments during antenatal care, previous dystocic delivery, and premature rupture of the membranes, were not significant. there are clinical and demographic risk factors associated with dystocic delivery. To identify this risk factors during the antenatal care could diminish the frequency of dystocic deliveries and therefore to avoid the associated maternal-fetal complications.


Neurodevelopmental attributes of joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type: Update and perspectives.
In the last decade, increasing attention has been devoted to the extra-articular and extra-cutaneous manifestations of joint hypermobility syndrome, also termed Ehlers-Danlos syndrome, hypermobility type (i.e., JHS/EDS-HT). Despite the fact that the current diagnostic criteria for both disorders remain focused on joint hypermobility, musculoskeletal pain and skin changes, medical practice and research have started investigating a wide spectrum of visceral, neurological and developmental complications, which represent major burdens for affected individuals. In particular, children with generalized joint hypermobility often present with various neurodevelopmental issues and can be referred for neurological consultation. It is common that investigations in these patients yield negative or inconsistent results, eventually leading to the exclusion of any structural neurological or muscle disorder. In the context of specialized clinics for connective tissue disorders, a clear relationship between generalized joint hypermobility and a characteristic neurodevelopmental profile affecting coordination is emerging. The clinical features of these patients tend to overlap with those of developmental coordination disorder and can be associated with learning and other disabilities. Physical and psychological consequences of these additional difficulties add to the chief manifestations of the pre-existing connective tissue disorder, affecting the well-being and development of children and their families. In this review, particular attention is devoted to the nature of the link between joint hypermobility, coordination difficulties and neurodevelopmental issues in children. Presumed pathogenesis and management issues are explored in order to attract more attention on this association and nurture future clinical research.


Anthrax in Lake Rukwa Valley, Tanzania: a persistent problem.
An epidemic of 239 human cases of anthrax is reported in the Rukwa Valley area of Tanzania. Although the infecting source was meat from animals dying of the disease, no intestinal cases occurred. Those infected were predominantly males between 15 and 35. The epidemic was seasonal, reaching a peak towards the end of the dry period when cattle were close grazing, and declining rapidly once the rains started and the grass began to grow. The increasing magnitude of annual epidemics suggests that the problem will get worse unless major efforts are made to vaccinate cattle before the epidemic period.


[Experts in 'dying well': causa mortis, rituals, and hierarchies at a monastery in colonial Rio de Janeiro].
Benedictine monks, who settled in Portuguese America in the late sixteenth century, made it their tenet to always have death in mind. The article describes diverse aspects of the Benedictine approach towards death as displayed at an eighteenth-century monastery in Rio de Janeiro. Relying on documentation stored at the monastery and highlighting performance-like activities, the article analyzes hierarchical arrangements, the ways death was represented, and the forms of sociability manifested at the time of burials. Focusing on the relations that were established, including the reciprocities that were invented and re-invented throughout the rituals, it is demonstrated that these events provided a basis for the distinction earned by clerics in a society ruled in part by the logics of the Ancién Regime.


Ecological validity of virtual environments to assess human navigation ability.
Route memory is frequently assessed in virtual environments. These environments can be presented in a fully controlled manner and are easy to use. Yet they lack the physical involvement that participants have when navigating real environments. For some aspects of route memory this may result in reduced performance in virtual environments. We assessed route memory performance in four different environments: real, virtual, virtual with directional information (compass), and hybrid. In the hybrid environment, participants walked the route outside on an open field, while all route information (i.e., path, landmarks) was shown simultaneously on a handheld tablet computer. Results indicate that performance in the real life environment was better than in the virtual conditions for tasks relying on survey knowledge, like pointing to start and end point, and map drawing. Performance in the hybrid condition however, hardly differed from real life performance. Performance in the virtual environment did not benefit from directional information. Given these findings, the hybrid condition may offer the best of both worlds: the performance level is comparable to that of real life for route memory, yet it offers full control of visual input during route learning.


Characterization of the major secreted zinc metalloprotease- dependent glycerophospholipid:cholesterol acyltransferase, PlaC, of Legionella pneumophila.
Legionella pneumophila, an intracellular pathogen causing a severe pneumonia, possesses distinct lipolytic activities which have not been completely assigned to specific enzymes so far. We cloned and characterized a gene, plaC, encoding a protein with high homology to PlaA, the major secreted lysophospholipase A of L. pneumophila and to other hydrolytic enzymes belonging to the GDSL family. Here we show that L. pneumophila plaC mutants possessed reduced phospholipase A and lysophospholipase A activities and lacked glycerophospholipid:cholesterol acyltransferase activity in their culture supernatants. The mutants' reduced phospholipase A and acyltransferase activities were complemented by reintroduction of an intact copy of plaC. Additionally, plaC conferred increased lysophospholipase A and glycerophospholipid:cholesterol acytransferase activities to recombinant Escherichia coli. Furthermore, PlaC was shown to be another candidate exported by the L. pneumophila type II secretion system and was activated by a factor present in the bacterial culture supernatant dependent on the zinc metalloprotease. Finally, the role of plaC in intracellular infection of Acanthamoeba castellanii and U937 macrophages with L. pneumophila was assessed, and plaC was found to be dispensable. Thus, L. pneumophila possesses another secreted lipolytic enzyme, a protein with acyltransferase, phospholipase A, and lysophospholipase A activities. This enzyme is distinguished from the previously characterized phospholipases A and lysophospholipases A by its capacity not only to cleave fatty acids from lipids but to transfer them to cholesterol. Cholesterol is an important compound of eukaryotic membranes, and an acyltransferase might be a tool for host cell modification to fit the needs of the bacterium.


Spatial position information accumulates steadily over time.
One of the more enduring mysteries of neuroscience is how the visual system constructs robust maps of the world that remain stable in the face of frequent eye movements. Here we show that encoding the position of objects in external space is a relatively slow process, building up over hundreds of milliseconds. We display targets to which human subjects saccade after a variable preview duration. As they saccade, the target is displaced leftwards or rightwards, and subjects report the displacement direction. When subjects saccade to targets without delay, sensitivity is poor; but if the target is viewed for 300-500 ms before saccading, sensitivity is similar to that during fixation with a strong visual mask to dampen transients. These results suggest that the poor displacement thresholds usually observed in the "saccadic suppression of displacement" paradigm are a result of the fact that the target has had insufficient time to be encoded in memory, and not a result of the action of special mechanisms conferring saccadic stability. Under more natural conditions, trans-saccadic displacement detection is as good as in fixation, when the displacement transients are masked.


Brain monoamines and peptides: role in the control of eating behavior.
Studies of brain monoamines and neuropeptides have provided extensive evidence in support of their role in the control of normal eating behavior. In this process, the medial and lateral portions of the hypothalamus, working in conjunction with forebrain and hindbrain sites and with peripheral autonomic-endocrine systems, have a critical responsibility in balancing signals for hunger and satiety. Via its rich and biologically active neurotransmitter substances, the hypothalamus monitors and integrates the complex sensory and metabolic input concerning the nutritional status of the organism and transduces this information into appropriate quantitative and qualitative adjustments in food intake. The specific neurotransmitters for which there is the most extensive evidence for a physiological function include the eating-stimulatory substances norepinephrine (alpha 2), opioid peptides, pancreatic polypeptides, growth hormone-releasing factor, and gamma-aminobutyric acid; the eating-inhibitory substances dopamine, epinephrine, serotonin, cholecystokinin, neurotensin, calcitonin, glucagon, and corticotropin-releasing factor; and possibly other gut-brain peptides. From biochemical, pharmacological, and anatomical studies, hypotheses have been generated to explain the role of these various monoamines and neuropeptides in controlling total energy intake, in determining the amount and pattern of macronutrient selection, and in maintaining normal energy and nutrient stores under fluctuating conditions within the external environment.


Incidence, etiology, timing, and risk factors for clinical failure in hospitalized patients with community-acquired pneumonia.
The etiology of clinical failure in hospitalized patients with community-acquired pneumonia (CAP) may be related or unrelated to pulmonary infection. The objective of this study was to define the incidence, etiology, timing, and risk factors associated with clinical failures related to CAP vs those unrelated to CAP. Observational retrospective study of consecutive CAP patients. All patients who experienced clinical failure were identified. Cases were presented to a review committee that defined, by consensus, etiology, timing, and risk factors for clinical failures related to CAP. Among 500 patients who were enrolled in the study, clinical failure was identified in 67 (13%). Clinical failure was related to CAP in 54 patients (81%). The most common etiologies for clinical failure related to CAP were severe sepsis (33%), acute myocardial infarction (28%), and progressive pneumonia (19%). All cases of severe sepsis occurred in the first 72 h of hospitalization. The most common etiology for clinical failure unrelated to CAP was the development of hospital-acquired pneumonia (45%). At the time of hospital admission, factors associated with clinical failure related to CAP were advanced age, congestive heart failure, hypotension, abnormal gas exchange, acidosis, hypothermia, thrombocytopenia, and pleural effusion. The development of severe sepsis early during hospitalization is the primary etiology for clinical failure related to CAP. To achieve early treatment intervention, physicians should maintain a high index of suspicion for severe sepsis in hospitalized patients with CAP. To decrease the number of clinical failures unrelated to CAP, interventions need to be developed at the local level to improve the processes of care for patients with pneumonia.


Ecological Risk Assessment of Underwater Sounds from Dredging Operations.
There is an increasing international focus to understand and quantify the potential ecological risks of low-frequency underwater sounds produced from anthropogenic activities (e.g., commercial shipping, dredging, construction, and offshore energy production). For dredge operations, a risk-based approach has been proposed for identifying, assessing, and managing risks; however, specific details of the framework and demonstration of the approach are lacking. Thus, the goal of this study was to provide a practical, concise, and reliable framework for assessing the effects of dredging sounds on aquatic life. The specific objectives were to 1) further specify a risk assessment approach for assessing underwater sounds from dredging operations, 2) demonstrate the utility of the approach in practice using a case study, and 3) document the strengths and challenges of the approach. The risk framework was adapted for underwater sounds to include a project formulation step, an analysis step to analyze and assess exposure and biological responses, a risk characterization process in which the preceding steps are integrated and uncertainty is addressed, and a risk management step. A key beneficial component of this framework is the use of a phased approach, whereby a screening step offers a process that utilizes existing or readily available information to evaluate risk. In general, a limitation of evaluating risks due to dredge operations is the degree of uncertainty surrounding effect thresholds for many marine species; however, this approach emphasizes the importance of documenting and communicating uncertainty to regulators, stakeholders, and practitioners in the decision-making process. A case study example is included to illustrate how the framework can be applied in practice. The primary strength of this method is the intrinsic flexibility of the framework to adapt as the scientific understanding improves and new data become available in the rapidly evolving field of underwater acoustics. Integr Environ Assess Manag 2020;16:481-493. © 2020 SETAC.


Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial.
A phase II study (ClinicalTrials.gov identifier: NCT00628251) showed activity of olaparib capsules versus pegylated liposomal doxorubicin in patients with germline BRCA-mutated platinum-resistant or partially platinum-sensitive relapsed ovarian cancer. We conducted a phase III trial (SOLO3) of olaparib tablets versus nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy. In this randomized, open-label trial, patients were randomly assigned 2:1 to olaparib 300 mg twice a day or physician's choice single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). The primary end point was objective response rate (ORR) in the measurable disease analysis set assessed by blinded independent central review (BICR). The key secondary end point was progression-free survival (PFS) assessed by BICR in the intent-to-treat population. Of 266 randomly assigned patients, 178 were assigned to olaparib and 88 to chemotherapy. In patients with measurable disease (olaparib, n = 151; chemotherapy, n = 72), the BICR-assessed ORR was significantly higher with olaparib than with chemotherapy (72.2% v 51.4%; odds ratio [OR], 2.53 [95% CI, 1.40 to 4.58]; P = .002). In the subgroup who had received 2 prior lines of treatment, the ORR was 84.6% with olaparib and 61.5% with chemotherapy (OR, 3.44 [95% CI, 1.42 to 8.54]). BICR-assessed PFS also significantly favored olaparib versus chemotherapy (hazard ratio, 0.62 [95% CI, 0.43 to 0.91]; P = .013; median, 13.4 v 9.2 months). Adverse events were consistent with the established safety profiles of olaparib and chemotherapy. Olaparib resulted in statistically significant and clinically relevant improvements in ORR and PFS compared with nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy.


Post-ictal recognition memory predicts laterality of temporal lobe seizure focus: comparison with post-operative data.
Standardized verbal and visuo-spatial memory recognition were obtained on 15 patients with unilateral temporal lobe epilepsy (TLE), using a reference group of 43 (12 males, 31 females) subjects with no previous history of neurological disease. Inter-ictal measures on these two tasks failed to differentiate between those patients with left vs right seizure foci. When eight of these patients were tested post-ictally (within 1 hr of seizure), seven showed the expected selective memory impairment when compared to inter-ictal performance. Left TLE patients showed a relative lowering of verbal memory, whereas patients with right TLE showed a relative visuo-spatial memory impairment. A similar result was also found in the patients when a comparison between pre-operative (inter-ictal) and post-operative performance was made, thereby further substantiating the validity of the tasks. This significant association between side of seizure focus and selective impairment of post-ictal memory performance provides evidence of a more direct method of neuropsychological diagnosis in TLE patients prior to surgery.


Pluripotency-related, valproic acid (VPA)-induced genome-wide histone H3 lysine 9 (H3K9) acetylation patterns in embryonic stem cells.
Embryonic stem cell (ESC) chromatin is characterized by a unique set of histone modifications, including enrichment for H3 lysine 9 acetylation (H3K9ac). Recent studies suggest that histone deacetylase (HDAC) inhibitors promote pluripotency. Here, using H3K9ac ChIP followed by high throughput sequencing analyses and gene expression in E14 mouse ESCs before and after treatment with a low level of the HDAC inhibitor valproic acid, we show that H3K9ac is enriched at gene promoters and is highly correlated with gene expression and with various genomic features, including different active histone marks and pluripotency-related transcription factors. Curiously, it predicts the cellular location of gene products. Treatment of ESCs with valproic acid leads to a pervasive genome-wide and time-dependent increase in H3K9ac, but this increase is selectively suppressed after 4 h in H3K4me3/H3K27me3 bivalent genes. H3K9ac increase is dependent on the promoter's chromatin state and is affected by the binding of P300, various transcription factors, and active histone marks. This study provides insights into the genomic response of ESCs to a low level of HDAC inhibitor, which leads to increased pluripotency. The results suggest that a mild (averaging less than 40%) but global change in the chromatin state is involved in increased pluripotency and that specific mechanisms operate selectively in bivalent genes to maintain constant H3K9ac levels. Our data support the notion that H3K9ac has an important role in ESC biology.


High-Responsivity, High-Detectivity, Ultrafast Topological Insulator Bi2Se3/Silicon Heterostructure Broadband Photodetectors.
As an exotic state of quantum matter, topological insulators have promising applications in new-generation electronic and optoelectronic devices. The realization of these applications relies critically on the preparation and properties understanding of high-quality topological insulators, which however are mainly fabricated by high-cost methods like molecular beam epitaxy. We here report the successful preparation of high-quality topological insulator Bi2Se3/Si heterostructure having an atomically abrupt interface by van der Waals epitaxy growth of Bi2Se3 films on Si wafer. A simple, low-cost physical vapor deposition (PVD) method was employed to achieve the growth of the Bi2Se3 films. The Bi2Se3/Si heterostructure exhibited excellent diode characteristics with a pronounced photoresponse under light illumination. The built-in potential at the Bi2Se3/Si interface greatly facilitated the separation and transport of photogenerated carriers, enabling the photodetector to have a high light responsivity of 24.28 A W(-1), a high detectivity of 4.39 × 10(12) Jones (Jones = cm Hz(1/2) W(-1)), and a fast response speed of aproximately microseconds. These device parameters represent the highest values for topological insulator-based photodetectors. Additionally, the photodetector possessed broadband detection ranging from ultraviolet to optical telecommunication wavelengths. Given the simple device architecture and compatibility with silicon technology, the topological insulator Bi2Se3/Si heterostructure holds great promise for high-performance electronic and optoelectronic applications.


Geographic and maternal characteristics associated with alcohol use in pregnancy.
To date, no studies have used population-level data to investigate whether maternal location of residence (metropolitan vs. regional/remote populations) is associated with alcohol use in pregnancy. This information has important implications for appropriate service provision. Information on all live births in New South Wales, Australia, was linked to records of alcohol-related admissions for mothers of these births over a 6-year period (2000 to 2006). Cases were women who had at least 1 alcohol-related hospital admission during pregnancy or at birth. Controls were women who had at least 1 live birth over that same time period but no alcohol-related hospital admissions during that time. Admissions were considered to be alcohol-related based on the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Australian Modification (ICD-10-AM) code. Demographic, obstetric, and neonatal variables were compared. A total of 417,464 singleton birth records were analyzed, 488 of which were coded positive for at least 1 alcohol-related ICD-10-AM diagnosis. Characteristics associated with alcohol-related admissions in pregnancy were residence in a remote/very remote area, being Australian-born, having had a previous pregnancy, smoking in the current pregnancy, and presenting late to antenatal care. Alcohol-exposed pregnancies were associated with a range of poor obstetric and neonatal outcomes, with no geographic differences noted. However, women in regional/remote areas were less likely to attend specialist obstetric hospitals. This study shows the need for standardized screening programs for alcohol use in pregnancy and where problematic use is detected, for clear clinical guidelines on management and referral.


[HACCP (Hazard Analysis and Critical Point system) at a catering service: checklist and microbiological examination].
The A.A. carried out a survey on the functioning of a catering service in Rome. The risk analysis assessment was performed by means of a checklist that collected systematically all data about the environment, the operators, the food and the catering process. The results of the microbiological analysis carried out in the CCP's showed that the general conditions of the catering service were not satisfactory, but also indicated the validity of the checklist used. This method showed a high predictive value and can be useful to improve the application of the HACCP system.


Psychophysiological responses to subliminal auditory suggestions for activation.
The aim of this study was to characterize further the experimental procedure proposed by Borgeat and Goulet in 1983. Subliminal activation auditory suggestions were expected to increase heart rate and skin conductance in presence of a stressing task. 20 subjects were alternately exposed to activating or neutral (random numbers) 25-dB suggestions masked by a 40-dB white noise. Analyses of variance and covariance indicated an effect of the activating suggestions on heart rate but not on skin conductance. Partly confirming previous results, the data support the reliability of heart rate and the importance of a stressing factor to reveal the effects of preconscious or subliminal stimulations.


A feed-forward regulation of endothelin receptors by c-Jun in human non-pigmented ciliary epithelial cells and retinal ganglion cells.
c-Jun, c-Jun N-terminal kinase(JNK) and endothelin B (ETB) receptor have been shown to contribute to the pathogenesis of glaucoma. Previously, we reported that an increase of c-Jun and CCAAT/enhancer binding protein β (C/EBPβ) immunohistostaining is associated with upregulation of the ETB receptor within the ganglion cell layer of rats with elevated intraocular pressure (IOP). In addition, both transcription factors regulate the expression of the ETB receptor in human non-pigmented ciliary epithelial cells (HNPE). The current study addressed the mechanisms by which ET-1 produced upregulation of ET receptors in primary rat retinal ganglion cells (RGCs) and HNPE cells. Treatment of ET-1 and ET-3 increased the immunocytochemical staining of c-Jun and C/EBPβ in primary rat RGCs and co-localization of both transcription factors was observed. A marked increase in DNA binding activity of AP-1 and C/EBPβ as well as elevated protein levels of c-Jun and c-Jun-N-terminal kinase (JNK) were detected following ET-1 treatment in HNPE cells. Overexpression of ETA or ETB receptor promoted the upregulation of c-Jun and also elevated its promoter activity. In addition, upregulation of C/EBPβ augmented DNA binding and mRNA expression of c-Jun, and furthermore, the interaction of c-Jun and C/EBPβ was confirmed using co-immunoprecipitation. Apoptosis of HNPE cells was identified following ET-1 treatment, and overexpression of the ETA or ETB receptor produced enhanced apoptosis. ET-1 mediated upregulation of c-Jun and C/EBPβ and their interaction may represent a novel mechanism contributing to the regulation of endothelin receptor expression. Reciprocally, c-Jun was also found to regulate the ET receptors and C/EBPβ appeared to play a regulatory role in promoting expression of c-Jun. Taken together, the data suggests that ET-1 triggers the upregulation of c-Jun through both ETA and ETB receptors, and conversely c-Jun also upregulates endothelin receptor expression, thereby generating a positive feed-forward loop of endothelin receptor activation and expression. This feed-forward regulation may contribute to RGC death and astrocyte proliferation following ET-1 treatment.


An interspecific mosquito model for the mesenteronal infection barrier to western equine encephalomyelitis virus (Culex tarsalis and Culex pipiens).
Culex tarsalis, a putative mosquito vector of western equine encephalomyelitis (WEE) virus, is susceptible to peroral infection by WEE virus. The nonvector mosquito, Culex pipiens, has a very high peroral threshold of infection and is considered to be refractory. By parenteral inoculation, both mosquito species are equally susceptible. Thus, Cx. tarsalis and Cx. pipiens represent an excellent model system to examine the mechanisms for the mesenteronal infection barrier to WEE virus. Diethylaminoethyl (DEAE)-dextran (1.6 mg/ml), when added to a pledget bloodmeal that contained high concentrations of WEE virus, enhanced peroral infection rates of Cx. pipiens. In Cx. tarsalis, a reduction in infection rates was observed when low WEE concentrations of virus were ingested. DEAE-dextran had no apparent effects on the dissemination of WEE after infection of either mosquito species. It is suggested that the peroral enhancement of WEE viral infection observed with Cx. pipiens may be related to random, nonspecific mechanisms of infection, since it requires high titers of ingested WEE virus. Interference with specific binding of WEE virus to cellular receptor sites is suggested to explain the reduction in WEE viral infection rates in Cx. tarsalis. Altering the pH of the ingested infectious bloodmeal did not affect the WEE viral infection rate of Cx. pipiens, within the range of 6.0-8.5. Cx. tarsalis was optimally infected when the infectious bloodmeal was pH 8.0, and the infection rate was significantly reduced when the infectious blood was at either extreme of the pH range tested. This is again interpreted to indicate that different mechanisms control the peroral infection of Cx. tarsalis and Cx. pipiens with WEE virus. The mesenteronal infection barrier to WEE virus in Cx. pipiens is associated with an inability of the virus to adsorb and/or penetrate mesenteronal epithelial when administered perorally. The barrier is not related to an inability of the Cx. pipiens mesenteronal epithelial cells to support viral multiplication since these cells become infected when the virus is administered parenterally.


Chronic effects of repeated low-dose cisplatin treatment in mouse kidneys and renal tubular cells.
Cisplatin is a commonly used chemotherapeutic drug for cancer treatment, but its nephrotoxicity may lead to the deterioration of renal function. Previous work has been focused on cisplatin-induced acute kidney disease, whereas the mechanism of chronic kidney disease after cisplatin chemotherapy is largely unknown. In the present study, we have characterized the mouse model of chronic kidney defects induced by repeated low-dose cisplatin treatment. We have also established a relevant cell culture model. In the animal model, C57 mice were given weekly injection of 8 mg/kg cisplatin for 4 wk. This led to a sustained decline of kidney function. These mice showed loss of kidney mass, interstitial fibrosis, continued activation of inflammatory cytokines, and appearance of atubular glomeruli. In the cell model, the BUMPT mouse proximal tubular cell line was treated four times with 1-2 μM cisplatin, resulting in low levels of apoptosis and the expression of fibrosis proteins and profibrotic factors. These data suggest that repeated treatment with low-dose cisplatin causes long-term renal pathologies with characteristics of chronic kidney disease.


Predilution versus postdilution for continuous arteriovenous hemofiltration.
When compared to the postdilution mode, the predilution mode has the following advantages and disadvantages: A significant increase in net urea clearance when compared to the postdilution mode: This study, showing a net 18% increase, confirms the conclusions of our preliminary studies 15, 16. It allows for a more liberal use of suction-assist: The combination of predilution and suction-assist can yield a 60% increase in net urea clearance without the generation of prohibitively high hematocrits and protocrits. A potential increase in effective filter life by dilution of prefilter hematocrit, clotting factors, and platelet count. Disadvantages: Increased cost of replacement fluid: This is usually modest, approximately a 10 to 30% increase in total volume needed. With a total output of 20 L/day this would represent approximately 6 L. In the manner prepared (Table 4, Ref 6) this represents approximately $10 a day and must be contrasted with the potential for increased filter life, the replacement of which represents the major cost of CAVH therapy. Furthermore, and perhaps more important, is that this modest increase in replacement fluid costs yields a substantial increase in urea clearance, especially when used with suction-assist, thus eliminating the need for intermittent hemodialysis and the costs it incurs. The filtrate chemistries can no longer be used to monitor the patient's plasma values: Although the potential savings in blood drawing is real, experience with the postdilution mode suggests that filtrate values are rarely considered adequate by the attending medical staff.


Upper Limb Motor Improvement after Traumatic Brain Injury: Systematic Review of Interventions.
Traumatic brain injury (TBI) is a leading cause of adult morbidity and mortality. Individuals with TBI have impairments in both cognitive and motor domains. Motor improvements post-TBI are attributable to adaptive neuroplasticity and motor learning. Majority of the studies focus on remediation of balance and mobility issues. There is limited understanding on the use of interventions for upper limb (UL) motor improvements in this population. We examined the evidence regarding the effectiveness of different interventions to augment UL motor improvement after a TBI. We systematically examined the evidence published in English from 1990-2020. The modified Downs and Black checklist helped assess study quality (total score: 28). Studies were classified as excellent: 24-28, good: 19-23, fair: 14-18, and poor: ≤13 in quality. Effect sizes helped quantify intervention effectiveness. Twenty-three studies were retrieved. Study quality was excellent (n = 1), good (n = 5) or fair (n = 17). Interventions used included strategies to decrease muscle tone (n = 6), constraint induced movement therapy (n = 4), virtual reality gaming (n = 5), non-invasive stimulation (n = 3), arm motor ability training (n = 1), stem cell transplant (n = 1), task-oriented training (n = 2), and feedback provision (n = 1). Motor impairment outcomes included Fugl-Meyer Assessment, Modified Ashworth Scale, and kinematic outcomes (error and movement straightness). Activity limitation outcomes included Wolf Motor Function Test and Motor Activity Log (MAL). Effect sizes for majority of the interventions ranged from medium (.5-.79) to large (≥.8). Only ten studies included retention testing. There is preliminary evidence that using some interventions may enhance UL motor improvement after a TBI. Answers to emergent questions can help select the most appropriate interventions in this population.


Approximate additivity of anion-pi interactions: an ab initio study on anion-pi, anion-pi(2) and anion-pi(3) complexes.
We have studied the additivity of the anion-pi interaction using high level ab initio calculations. We have optimized chloride and bromide complexes with one, two and three aromatic units (such as trifluoro-s-triazine and s-triazine). We have analyzed the interaction using the atoms in molecules theory and studied the charge transfer using several methods for deriving atomic charges. The results revealed additivities of both the geometries and the binding energies. We have also proposed a neutral receptor for chloride based on multiple anion-pi interactions. Finally, we have simulated solvent effects within the self-consistent reaction field model.


Targeted Protein Degradation: Principles, Strategies, and Applications.
Protein degradation is a general process to maintain cell homeostasis. The intracellular protein quality control system mainly includes the ubiquitin-proteasome system and the lysosome pathway. Inspired by the physiological process, strategies to degrade specific proteins have developed, which emerge as potent and effective tools in biological research and drug discovery. This review focuses on recent advances in targeted protein degradation techniques, summarizing the principles, advantages, and challenges. Moreover, the potential applications and future direction in biological science and clinics are also discussed.


Development and psychometric validation of social cognitive theory scales in an oral health context.
This study aimed to develop and evaluate scales reflecting potentially modifiable social cognitive theory-based risk indicators associated with homeless populations' oral health. The scales are referred to as the social cognitive theory risk scales in an oral health context (SCTOH) and are referred to as SCTOH(SE), SCTOH(K) and SCTOH(F), respectively. The three SCTOH scales assess the key constructs of social cognitive theory: self-efficacy, knowledge and fatalism. The reliability and validity of the three scales were evaluated in a convenience sample of 248 homeless participants (age range 17-78 years, 79% male) located in a metropolitan setting in Australia. The scales were supported by exploratory factor analysis and established three distinct and internally consistent domains of social cognition: oral health-related self-efficacy, oral health-related knowledge and oral health-related fatalism, with Cronbach's alphas of 0.95, 0.85 and Spearman's-Brown ρ of 0.69. Concurrent ability was confirmed by each SCTOH scale's association with oral health status in the expected directions. The three SCTOH scales appear to be internally valid and reliable. If confirmed by further research, these scales could potentially be used for tailored educational and cognitive-behavioural interventions to reduce oral health inequalities among homeless and other vulnerable populations.


Development of miconazole nitrate containing chitosan microcapsules and their anti-Aspergillus niger activity.
In this article, we report the development of chitosan/miconazole nitrate microcapsules. Four miconazole nitrate ratios including 12.5, 25, 50 and 100 mg were performed in the chitosan-based microencapsulation system. Chitosan microcapsules with the drug input of 25 mg showed the highest encapsulation efficiency (52.47%) and acceptable mean particle size (5.65 µm) when compared with those of 12.5, 50 and 100 mg. Fourier transform infrared spectroscopic spectrum proved the entrapment of miconazole nitrate into chitosan microcapsules. The antifungal result demonstrated that microcapsules containing 75 µg miconazole nitrate possessed comparable anti-Aspergillus niger activity as the commercial ointment. The growth inhibition of miconazole nitrate containing chitosan microcapsules towards human skin keratinocytes was found to be dose dependent. A total of 75 µg of miconazole nitrate containing microcapsules revealed about 25% of growth inhibition while that of 150 µg showed approximately 70% of growth inhibition. Special monitoring should be taken if a higher dose of miconazole nitrate was used to develop the microcapsules.


Self-assembly of semifluorinated n-alkanethiols on {111}-oriented Au investigated with scanning tunneling microscopy experiment and theory.
The adsorption of semifluorinated alkanethiols on Au/mica was studied by scanning tunneling microscopy (STM). The adlayer structure produced is based on a p(2 x 2) structure though lines of molecules displayed extensive kinks and bends. In addition, a considerable variation in the contrast of molecular features is found. Molecular modeling calculations confirm that, for the fluorinated thiols, inequivalently adsorbed molecules within a p(2 x 2) registry are present, an aspect that endows the local structure of the adlayer with a higher flexibility in comparison to nonfluorinated thiols, where one adsorption site is strongly favored in a (radical 3 x radical 3) R30 degrees structure. Simulated STM imaging on the optimized systems successfully recovered the effects on the molecular feature contrast induced by the flexibility of the fluorinated thiol adlayer.


Do Pilates-based exercises following total knee arthroplasty improve postural control and quality of life?
The aim of this prospective, randomized, controlled study was to investigate the effects of the addition of Pilates-based exercises to standard exercise programs performed after total knee arthroplasty on quality of life and balance. Forty-six volunteers were divided into two groups. The control group (n = 17) was assigned a standard exercise program after discharge; the study group (n = 17) was assigned Pilates-based exercises along with the standard exercise program. We carried out clinical evaluations of all patients on the day of discharge and after the completion of the 6-week exercise program. We also recorded sociodemographic data, Berg Balance test scores, and Short Form-36 (SF-36) health-related quality of life measurements. When we compared the differences between pre- and post-treatment balance scores of the groups, we found a significant change in favor of the Pilates-based exercise group (13.64 ± 1.45; p < 0.01). The changes in the pre- and post-treatment SF-36 scores of the Pilates-based exercises group were found to be significant in terms of physical function (p = 0.001), physical role restriction (p = 0.01), and physical component score (p = 0.001). Pilates-based exercises performed along with standard exercise programs were more effective for improving balance and quality of life than standard exercise programs alone.


Redox-active iron released during machine perfusion predicts viability of ischemically injured deceased donor kidneys.
Redox-active iron, catalyzing the generation of reactive oxygen species, has been implicated in experimental renal ischemia-reperfusion injury. However, in clinical transplantation, it is unknown whether redox-active iron is involved in the pathophysiology of ischemic injury of non-heart-beating (NHB) donor kidneys. We measured redox-active iron concentrations in perfusate samples of 231 deceased donor kidneys that were preserved by machine pulsatile perfusion at our institution between May 1998 and November 2002 using the bleomycin detectable iron assay. During machine pulsatile perfusion, redox-active iron was released into the preservation solution. Ischemically injured NHB donor kidneys had significantly higher perfusate redox-active iron concentrations than heart-beating (HB) donor kidneys that were not subjected to warm ischemia (3.9 +/- 1.1 vs. 2.8 +/- 1.0 micromol/L, p = 0.001). Moreover, redox-active iron concentration was an independent predictor of post-transplant graft viability (odds ratio 1.68, p = 0.01) and added predictive value to currently available donor and graft characteristics. This was particularly evident in uncontrolled NHB donor kidneys for which there is the greatest uncertainty about transplant outcomes. Therefore, perfusate redox-active iron concentration shows promise as a novel viability marker of NHB donor kidneys.


Reflections on written comments by women on their abuse.
In a study to differentiate injuries of physical abuse from non-physical abuse, 103 women wrote uninvited comments that were analyzed in two ways: Q-sort and phenomenology analyses. Q-sort identified two categories: helplessness and assertiveness. Comparisons with subject responses about current or previous violence indicated that women who wrote assertive comments were less likely to be in a violent relationship than women who wrote helpless comments. Phenomenological analysis indicated that women who were categorized as silent, received or subjective were in abusive relationships; some had been abused on the day of admission. Two women wrote comments considered subjective procedural; both were living with their abuser and stated that the abuse no longer occurred. Health-care professionals must question the appropriate goal to counsel abused women. Whether these two continua reflect a readiness to leave the relationship or result from having left, the comments by two women who say they are no longer being abused are more assertive and appear to show higher levels of knowing.


Incidental possible diagnosis by 18F-fluorocholine PET/CT of Meckel's diverticulum and potential pitfalls.
A 61 years old man with a history of prostate cancer Gleason 3+4, treated with radical prostatectomy, underwent fluorine-18-fluorocholine positron emission tomography/computed tomography ((18)F-FCH PET/CT) imaging to investigate rising serum prostate specific antigen (PSA) levels. (18)F-FCH PET/CT showed a focus of linear increased uptake by a possible Meckel's diverticulum in the right hemi-pelvis, which was an incidental finding in this asymptomatic patient. Uptake of (18)F-FCH by Meckel's diverticulum has not been reported before and thus the mechanism of uptake has not been established. Two postulations may explain this uptake. First, since Meckel's diverticulum is a true diverticulum containing all layers of the intestinal wall, the uptake may be related to physiological bowel-related uptake. Second, the uptake may be due to heterotopic pancreatic tissue in Meckel's diverticulum, especially since the intensity of uptake we have noticed was similar to that of physiological pancreatic uptake. As (18)F-FCH PET/CT scan is often used for evaluating prostate cancer, (18)F-FCH uptake by Meckel's diverticulum in the pelvis or lower abdomen may be mistaken for tumor involvement/recurrence. The identification by imaging of Meckel's diverticulum relies on the identification of a blind ending tubular structure, arising from the distal ileum. The identification of this structure may be best appreciated on the axial, coronal or sagittal plane. In this particular case, we managed to clearly demonstrate the presence of a tubular blind ending structure arising from the distal ileum on the sagittal images. The careful identification of this structure indicated that tracer uptake was in a Meckel's diverticulum and not within a pelvic lymph node or pelvic organ hence excluding recurrent disease.


Diagnostic Value of Procalcitonin Levels in Acute Mesenteric Ischemia.
Acute mesenteric ischemia (AMI) is a potentially fatal disease. Difficulties in diagnosis make it essential to find early biomarkers. This study investigated the diagnostic value of procalcitonin (PCT) levels in AMI. Animal experimentation. Rats were divided into six groups of six animals each. In the experimental group, an experimental ischemia model was established by clamping the superior mesenteric artery from the aortic outflow tract. Blood and tissue specimens were collected from rats in the experimental mesenteric ischemia model at 30 min and 2 and 6 h, and these were compared with specimens from the respective control groups. PCT levels were compared at 30 min and 2 and 6 h. PCT levels were 185.3 pg/mL in the control group and 219.3 pg/mL in the study group, 199.6 pg/mL in the control group and 243.9 pg/mL in the study group, and 201.9 pg/mL in the control group and 286.9 pg/mL in the study group, respectively, at 30 minute, 2 and 6 hours. Significant differences were determined between 6-h control group and ischemia group PCT levels (p=0.005). The absence of a significant increase in PCT levels in the early period, while a significant difference was detected in the later period (6 h), shows that PCT levels rise late in mesenteric ischemia and can be a marker in the late period.


Compulsive attentive behavior after lesion of the ventral striatum in the cat: a behavioral and electrophysiological study.
Bilateral lesions of the nucleus accumbens in cat elicited the following changes: preservation in tests requiring focused attention, with difficulty to shift to other targets; paucity of movements, animals displaying moderate hypokinesia and loss of reaction to changes in the environment. These symptoms were accompanied by a significant increase in the amount of beta rhythms, an activity that has been shown to be concomitant with the development of focused attentive behavior. The observed behavioral and electrocortical modifications are opposite those that have been previously obtained in the same species after lesions of the ventral tegmental area.


Urine cytology as a screening test for bladder infiltration in cervical cancer.
Ultrasound is currently used as a screening test for bladder infiltration in patients with advanced-stage cervical cancer at our institution. Cystoscopy is reserved for patients with abnormal bladder ultrasound findings. This study was undertaken to reevaluate this policy and to compare the results of different screening tests. The study was carried out in Pretoria academic complex. All newly diagnosed cervical carcinoma patients stage II and above were included in this study. The standard staging investigations were done on all patients. In addition, urine midstream and catheter specimens were sent for cytology. Cystoscopy and biopsy were performed on all patients. Two hundred twenty-eight patients were enrolled into this study. At cystoscopy, 47 patients had bladder mucosa suspicious of malignant infiltration, of which 17 had bladder mucosa infiltration diagnosed on histology. Urine catheter cytology has a sensitivity of 94% and specificity of 82% for bladder mucosa infiltration. The predictive value of a positive test is 31% and for a negative test is 99%. Catheter urine cytology is a very useful screening test for bladder infiltration in patients with cervical cancer. Cystoscopy should be reserved for patients with abnormal urine cytology in resource-poor settings with a large burden of disease.


Targeted Metabolomics Analysis and Identification of Biomarkers for Predicting Browning of Fresh-Cut Lettuce.
The metabolism of phenolic compounds is a key factor in the development of wound-induced enzymatic browning of fresh-cut lettuce. In the present study, the lettuce midribs discriminant metabolites, selected in a previous untargeted metabolomics study, were thoroughly identified. Our results showed that their basal contents correlated with browning developed after 5 days of storage. 5- trans-Chlorogenic acid and 5- cis-chlorogenic acid were positively correlated with browning, while sinapaldehyde and its 4-β-d-glucoside and 4-(6'-malonyl)-β-d-glucoside conjugates were negatively correlated. Using targeted metabolomics, the metabolites were analyzed in lettuce heads with different degrees of development and different browning susceptibility and these biomarkers were confirmed. Despite the large variability in the browning process of lettuce, the chlorogenic acids/sinapaldehyde derivatives ratio showed a linear correlation ( r2 = 0.79) with the fresh-cut lettuce browning developed in 24 Romaine lettuce cultivars, validating the relevance of these biomarkers. These results show that the analysis of the basal content of these metabolites could be used in lettuce breeding programs to select cultivars that are more appropriate for the fresh-cut industry.


Identification of novel tumor markers in prostate, colon and breast cancer by unbiased methylation profiling.
DNA hypermethylation is a common epigenetic abnormality in cancer and may serve as a useful marker to clone cancer-related genes as well as a marker of clinical disease activity. To identify CpG islands methylated in prostate cancer, we used methylated CpG island amplification (MCA) coupled with representational difference analysis (RDA) on prostate cancer cell lines. We isolated 34 clones that corresponded to promoter CpG islands, including 5 reported targets of hypermethylation in cancer. We confirmed the data for 17 CpG islands by COBRA and/or pyrosequencing. All 17 genes were methylated in at least 2 cell lines of a 21-cancer cell line panel containing prostate cancer, colon cancer, leukemia, and breast cancer. Based on methylation in primary tumors compared to normal adjacent tissues, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS and NSE1 are candidate biomarkers for prostate cancer (methylation range 50%-85%). The combination of NSE1 or SPOCK2 hypermethylation showed a sensitivity of 80% and specificity of 95% in differentiating cancer from normal. Similarly NKX2-5, SPOCK2, SLC16A12, DPYS and GALR2 are candidate biomarkers for colon cancer (methylation range 60%-95%) and GALR2 hypermethylation showed a sensitivity of 85% and specificity of 95%. Finally, SLC16A12, GALR2, TOX, SPOCK2, EGFR5 and DPYS are candidate biomarkers for breast cancer (methylation range 33%-79%) with the combination of EGFR5 or TOX hypermethylation showing a sensitivity of 92% and specificity of 92%. Expression analysis for eight genes that had the most hypermethylation confirmed the methylation associated silencing and reactivation with 5-aza-2'-deoxycytidine treatment. Our data identify new targets of transcriptional silencing in cancer, and provide new biomarkers that could be useful in screening for prostate cancer and other cancers.


['Magdalena fevers': medicine and society in the construction of a Colombian medical notion, 1859-1886].
In this article, I explore the theoretical, social and ideological bases of the emergence and consolidation of the Colombian medical notion of the 'Magdalena fevers'. Firstly I show how, in the late 1850s, the emerging Colombian body of medical doctors elaborated peculiar notions on fevers by articulating the European medical theories (i.e. the miasmatic theory and the climatic determination of diseases) with the negative valuation of the hot climate. Secondly, I explain how free trade policies in the mid-1800s, and the economic and ideological impacts of the agricultural export of tobacco and indigo determined doctors' interest in the epidemics occurring in the production centers and also, therefore, the emergence of the notion of 'Magdalena fevers'. I also show how doctors established a causal association between the productive process of those goods and the fevers.


An evidence-based definition of anemia for singleton, uncomplicated pregnancies.
The definition for anemia in pregnancy is outdated, derived from Scandinavian studies in the 1970's to 1980's. To identity women at risk of blood transfusion, a common cause of Severe Maternal Morbidity, a standard definition of anemia in pregnancy in a modern, healthy United States cohort is needed. To define anemia in pregnancy in a United States population including a large county vs. private hospital population using uncomplicated patients. Inclusion criteria were healthy women with the first prenatal visit before 20 weeks. Exclusion criteria included preterm birth, preeclampsia, hypertension, diabetes, short interval pregnancy (<18 months), multiple gestation, abruption, and fetal demise. All women had iron fortification (Ferrous sulfate 325 mg daily) recommended. The presentation to care and pre-delivery hematocrits were obtained, and the percentiles determined. A total of 2000 patients were included, 1000 from the public county hospital and 1000 from the private hospital. Each cohort had 250 patients in each 2011, 2013, 2015, and 2018. The cohorts were compared for differences in the fifth percentile for each antepartum epoch. Student's t-test and chi-squared statistical tests were used for analysis, p-value of ≤0.05 was considered significant. In the public and private populations, 777 and 785 women presented in the first trimester while 223 and 215 presented in the second. The women at the private hospital were more likely to be older, Caucasian race, nulliparous, and present earlier to care. The fifth percentile was compared between the women in the private and public hospitals and were clinically indistinguishable. When combining the cohorts, the fifth percentile for hemoglobin/hematocrit was 11 g/dL/32.8% in the first trimester, 10.3 g/dL/30.6% in the second trimester, and 10.0 g/dL/30.2% pre-delivery. Fifth percentile determinations were made from a combined cohort of normal, uncomplicated pregnancies to define anemia in pregnancy. Comparison of two different cohorts confirms that the same definition for anemia is appropriate regardless of demographics or patient mix.


Paget Schroetter Syndrome and Chylothorax After Rhinoplasty.
Paget-Schroetter syndrome is a rare clinical condition characterized by subclavian vein thrombosis following repetitive upper extremity effort. In this case, we presented a 35-year-old female patient who underwent septorhinoplasty in our clinic. A swelling of the left part of the neck extending to the clavicle was detected 4 hours after the operation. Computed tomography of the thorax revealed a pleural effusion at the base of the left lung and a computed tomography angiogram demonstrated a recanalized left subclavian vein thrombosis. History of the patient clarified that she had moved to another house and had lifted heavy furnitures 4 days before the surgery. The patient was diagnosed with Paget Schroetter syndrome followed by chylothorax. Paget-Schroetter syndrome followed by chylothorax could be presented after a surgical intervention of the head and neck. Early diagnosis is essential to reduce the risk of ongoing morbidity and mortality.


A metabolic index of ischemic injury for perfusion-recovery of cadaveric rat livers.
With over 110,000 patients waiting for organ transplantation, the current crisis in organ transplantation is based on a lack of donors after brain-death (DBD). A very large alternative pool of donor organs that remain untapped are the donors after cardiac death (DCD), recovered after cardiac activity has ceased and therefore sustained some ischemic injury. Machine perfusion has been proposed as a novel modality of organ preservation and treatment to render such cadaveric organs, and in particular livers, transplantable. Two key issues that remain unaddressed are how to assess whether a DCD liver is damaged beyond repair, and whether machine perfusion has rendered an injured organ sufficiently viable for transplantation. In this work, we present a metabolic analysis of the transient responses of cadaveric rat livers during normothermic machine perfusion (NMP), and develop an index of ischemia that enables evaluation of the organ ischemic injury level. Further, we perform a discriminant analysis to construct a classification algorithm with >0.98 specificity to identify whether a given perfused liver is ischemic or fresh, in effect a precursor for an index of transplantability and a basis for the use of statistical process control measures for automated feedback control of treatment of ischemic injury in DCD livers. The analyses yield an index based on squared prediction error (SPE) as log(SPE) >1.35 indicating ischemia. The differences between metabolic functions of fresh and ischemic livers during perfusion are outlined and the metabolites that varied significantly for ischemic livers are identified as ornithine, arginine, albumin and tyrosine.


The development of a standardised diet history tool to support the diagnosis of food allergy.
The disparity between reported and diagnosed food allergy makes robust diagnosis imperative. The allergy-focussed history is an important starting point, but published literature on its efficacy is sparse. Using a structured approach to connect symptoms, suspected foods and dietary intake, a multi-disciplinary task force of the European Academy of Allergy and Clinical Immunology developed paediatric and adult diet history tools. Both tools are divided into stages using traffic light labelling (red, amber and green). The red stage requires the practitioner to gather relevant information on symptoms, atopic history, food triggers, foods eaten and nutritional issues. The amber stage facilitates interpretation of the responses to the red-stage questions, thus enabling the practitioner to prepare to move forward. The final green stage provides a summary template and test algorithm to support continuation down the diagnostic pathway. These tools will provide a standardised, practical approach to support food allergy diagnosis, ensuring that all relevant information is captured and interpreted in a robust manner. Future work is required to validate their use in diverse age groups, disease entities and in different countries, in order to account for differences in health care systems, food availability and dietary norms.


When emotion and expression diverge: The social costs of Parkinson's disease.
Patients with Parkinson's disease (PD) are perceived more negatively than their healthy peers, yet it remains unclear what factors contribute to this negative social perception. Based on a cohort of 17 PD patients and 20 healthy controls, we assessed how naïve raters judge the emotion and emotional intensity displayed in dynamic facial expressions as adults with and without PD watched emotionally evocative films (Experiment 1), and how age-matched peers naïve to patients' disease status judge their social desirability along various dimensions from audiovisual stimuli (interview excerpts) recorded after certain films (Experiment 2). In Experiment 1, participants with PD were rated as significantly more facially expressive than healthy controls; moreover, ratings demonstrated that PD patients were routinely mistaken for experiencing a negative emotion, whereas controls were rated as displaying a more positive emotion than they reported feeling. In Experiment 2, results showed that age-peers rated PD patients as significantly less socially desirable than control participants. Specifically, PD patients were rated as less involved, interested, friendly, intelligent, optimistic, attentive, and physically attractive than healthy controls. Taken together, our results point to a disconnect between how PD patients report feeling and attributions that others make about their emotions and social characteristics, underlining significant social challenges of the disease. In particular, changes in the ability to modulate the expression of negative emotions may contribute to the negative social impressions that many PD patients face.


Platelet activation by alpha-thrombin is a receptor-mediated event.
Computer-assisted data analysis of binding isotherms (LIGAND) has shown that human platelets have binding sites for alpha-thrombin of high (Kd 0.3 nM), moderate (Kd 10 nM), and low affinities (Kd 3 microM). Application of similar techniques has shown that TLCK-thrombin does not, whereas PPACK-thrombin does, bind to the high-affinity binding site accessible to alpha-thrombin, but that both bind to the moderate and low-affinity sites. Treatment of platelets with Serratia marcescens protease destroys the high-affinity site but does not affect moderate-affinity binding. In accordance with this model, both modified thrombins compete with alpha-thrombin for platelet activation at the moderate-affinity site, but only PPACK-thrombin competes at the high-affinity site. These results establish that platelet activation by either low or moderate concentrations of thrombin are receptor-mediated events and explain the paradox of the differential effects of TLCK-thrombin on the binding and activation of platelets by alpha-thrombin.


Electrically controlled topological micro cargo transportation.
We demonstrate electrically controlled linear translation and precision positioning of a colloidal particle in a soft matter device. The basis of transportation is the time dependent electric field reconfiguration and manipulation of a topological line defect between two distinct hybrid aligned nematic liquid crystal domains having opposing tilt orientations. Deliberately tuning an applied voltage relative to a low threshold value (5.7 V at 1 kHz) permits defect trapping of the colloidal particle and allows subsequent control over the particle's velocity and bidirectional linear movement over millimeter distances, without the need for externally imposed flow nor for lateral confining walls.


Long-term effects of hydrolyzed protein infant formulas on growth--extended follow-up to 10 y of age: results from the German Infant Nutritional Intervention (GINI) study.
Previous analysis in a prospective, population-based cohort reported reduced weight gain in children fed extensively hydrolyzed casein (eHF-C) formula during the first year of life but showed no effect on growth between 1 and 6 y of life. No studies have been conducted in children up to the age of 10 y. The objective was to investigate potential differences in body mass index (BMI) over the first 10 y of life between infants fed within the intervention period of the first 16 wk of life with partially hydrolyzed whey (pHF-W), extensively hydrolyzed whey (eHF-W), eHF-C, or cow-milk formula (CMF) and infants exclusively breastfed (BF) within the intervention period. This was a prospective, randomized, double-blind trial in full-term neonates with atopic heredity in the German birth cohort German Infant Nutritional Intervention (GINI) followed through the first 10 y of life. Analyses of absolute and World Health Organization (WHO)-standardized BMI trajectories for 1840 infants [pHF-W (n = 253), eHF-W (n = 265), eHF-C (n = 250), CMF (n = 276), and BF (n = 796)] were conducted according to intention-to-treat principles. Except for the previously reported slower BMI gain in infants fed with eHF-C formula within the first year of life, no significant differences in absolute or WHO-standardized BMI trajectories were shown between the pHF-W, eHF-W, eHF-C, CMF, and BF groups thereafter up to the age of 10 y. Extension of the follow-up period from 6 to 10 y for this randomized controlled trial showed no long-term consequences on BMI for the 4 infant formulas considered. These data need to be confirmed in future studies.


Vigor to Frailty as a Continuum - A new approach in the Study of Muscle, Mobility and Aging (SOMMA) Cohort.
Frailty can occur in older adults without disability or multimorbidity. Current methods focus on the most frail, but poorly discriminate among those "not frail". The Study of Muscle, Mobility and Aging (SOMMA) included 879 adults aged 70 years and older without mobility disability. We operationalized frailty domains using: peak oxygen consumption (endurance), digit symbol substitution test (speed), leg power (strength), perceived fatigability, D3 creatine dilution (sarcopenia) and accelerometry (sedentary behavior) to construct a frailty score of 0-12 summing tertiles (0-2) of each component. We used linear or logistic regression with and without adjustment for confounders to examine associations with age, reported and performance function. The SOMMA frailty score distribution was broad and strongly associated with age (r=0.33, p<0.0001). Each point was associated with a 30-50% higher odds of having reported difficulty with activities of daily living or mobility. After grouping the total score (0-3, 4-7 and 8-12) those in the highest group were 9-31 times more likely to have functional limitation, and at least 8 times more likely to have poorer function after full adjustment. Higher scores identified those less likely to report ease of walking or higher physical activity. Peak oxygen consumption, leg power, fatigability and digit symbol score contributed most to these associations. The SOMMA frailty score characterizes frailty as a continuum from frail to vigorous with assessments that are amenable to change. Associations with age and function suggest utility for distinguishing a wide range of vigor and vulnerability in relatively well functioning older adults.


Testisin, a glycosyl-phosphatidylinositol-linked serine protease, promotes malignant transformation in vitro and in vivo.
Human testisin, a serine protease, is highly expressed in ovarian cancer and premeiotic spermatocytes with relatively little expression in other normal tissues. We first showed that testisin was localized on the surface of cultured tumor cells as a glycosyl-phosphatidylinositol-linked protein. We next explored the biological function of testisin in malignant transformation through manipulation of testisin expression in cell culture model systems. Small interfering RNA-mediated knockdown of endogenous testisin mRNA and protein expression in tumor cell lines led to increased apoptosis and diminished growth in soft agar. Conversely, overexpression of testisin in an epithelial cell line induced colony formation in soft agar as well as s.c. tumor growth in severe combined immunodeficient mice. A catalytic domain mutant was unable to induce soft-agar growth indicating that testisin protease activity is required for transformation. Ectopic expression of testisin in a human ovarian cancer cell line without endogenous testisin expression, led to the formation of larger tumors in severe combined immunodeficient mice. Data presented here provide the first demonstration that testisin can promote cellular processes that drive malignant transformation. Our functional data coupled with the restricted normal tissue distribution of testisin and its overexpression in a majority of ovarian cancers validates this cell surface protein as a target for therapeutic intervention.


Mating-type locus rearrangements and shifts in thallism states in Citrus-associated Phyllosticta species.
Currently, eight Phyllosticta species are known to be associated with several Citrus hosts, incorporating diverse lifestyles: while some of them are endophytic (P. capitalensis and P. citribraziliensis), others are pathogenic (P. citriasiana, P. citricarpa, P. citrichinaensis and P. paracitricarpa). Sexual reproduction plays a key role in the interaction between these Phyllosticta species and their Citrus hosts, especially for the spread and persistence of the pathogenic species in the environment. Given this, differences in sexual reproduction strategies could be related to the differences in lifestyles. To evaluate this hypothesis, we characterized the mating-type loci of six Citrus-associated Phyllosticta species from whole genome assemblies. Mating-type genes in the Citrus-associated Phyllosticta species are highly variable in their sequence content, but the genomic locations and organization of the mating-type loci are conserved. Phyllosticta citriasiana, P. citribraziliensis, P. citricarpa and P. paracitricarpa are heterothallic, while P. capitalensis and P. citrichinaensis are homothallic. In addition, the P. citrichinaensis MAT1-2 idiomorph occurs in a separate location from the mating-type locus. Ancestral state reconstruction suggests that homothallism is the ancestral thallism state in Phyllosticta, with a shift to heterothallism in Phyllosticta species that are pathogenic to Citrus. Moreover, the homothallic strategies of P. capitalensis and P. citrichinaensis result from independent evolutionary events, as P. capitalensis locus likely represents the ancestral state, and P. citrichinaensis homothallism has risen through a reversion in a heterothallic ancestor and underwent remodelling events. As the pathogenic species P. citriasiana, P. citricarpa and P. paracitricarpa are heterothallic and incapable of selfing, disease management practices focused in preventing the occurrence of sexual reproduction could assist in the control of Citrus Black Spot and Citrus Tan Spot diseases. This study emphasizes the importance of studying Citrus-Phyllosticta interactions under evolutionary and genomic perspectives, as these approaches can provide valuable information about the association between Phyllosticta species and their hosts, and also serve as guidance for the improvement of disease management practices.


Estrogen regulates estrogen receptors and antioxidant gene expression in mouse skeletal muscle.
Estrogens are associated with the loss of skeletal muscle strength in women with age. Ovarian hormone removal by ovariectomy in mice leads to a loss of muscle strength, which is reversed with 17beta-estradiol replacement. Aging is also associated with an increase in antioxidant stress, and estrogens can improve antioxidant status via their interaction with estrogen receptors (ER) to regulate antioxidant gene expression. The purpose of this study was to determine if ER and antioxidant gene expression in skeletal muscle are responsive to changes in circulating estradiol, and if ERs regulate antioxidant gene expression in this tissue. Adult C57BL/6 mice underwent ovariectomies or sham surgeries to remove circulating estrogens. These mice were implanted with placebo or 17beta-estradiol pellets acutely or chronically. A separate experiment examined mice that received weekly injections of Faslodex to chronically block ERs. Skeletal muscles were analyzed for expression of ER genes and proteins and antioxidant genes. ERalpha was the most abundant, followed by Gper and ERbeta in both soleus and EDL muscles. The loss of estrogens through ovariectomy induced ERalpha gene and protein expression in the soleus, EDL, and TA muscles at both the acute and chronic time points. Gpx3 mRNA was also induced both acutely and chronically in all 3 muscles in mice receiving 17beta-estradiol. When ERs were blocked using Faslodex, Gpx3 mRNA was downregulated in the soleus muscle, but not the EDL and TA muscles. These data suggest that Gpx3 and ERalpha gene expression are sensitive to circulating estrogens in skeletal muscle. ERs may regulate Gpx3 gene expression in the soleus muscle, but skeletal muscle regulation of Gpx3 via ERs is dependent upon muscle type. Further work is needed to determine the indirect effects of estrogen and ERalpha on Gpx3 expression in skeletal muscle, and their importance in the aging process.


[New guidelines on functional and somatoform disorders].
The S3 guideline "Dealing with patients with non-specific, functional and somatoform bodily symptoms" emphasizes the similarities in the management of the manifold manifestations of so called "medically unexplained symptoms" and gives recommendations for a stepped and collaborative diagnostic and therapeutic approach in all subspecialties and all levels of health care. It has a special focus on recommendations regarding attitude, physician-patient-relationship, communication, the parallelization of somatic and psychosocial diagnostics and a stepped therapeutic approach. The "Evidence-based guideline psychotherapy in somatoform disorders and associated syndromes" provides a differentiated analysis of the current evidence regarding the effectiveness of various psychotherapeutic interventions for the most relevant manifestations of functional and somatoform disorders. In combination, both guidelines pose important advances for treatment quality in Germany, but also illustrate remarkable structural and research deficits.


SIX1 Regulates Aberrant Endometrial Epithelial Cell Differentiation and Cancer Latency Following Developmental Estrogenic Chemical Exposure.
Early-life exposure to estrogenic chemicals can increase cancer risk, likely by disrupting normal patterns of cellular differentiation. Female mice exposed neonatally to the synthetic estrogen diethylstilbestrol (DES) develop metaplastic and neoplastic uterine changes as adults. Abnormal endometrial glands express the oncofetal protein sine oculis homeobox 1 (SIX1) and contain cells with basal [cytokeratin (CK)14+/18-] and poorly differentiated features (CK14+/18+), strongly associating SIX1 with aberrant differentiation and cancer. Here, we tested whether SIX1 expression is necessary for abnormal endometrial differentiation and DES-induced carcinogenesis by using Pgr-cre to generate conditional knockout mice lacking uterine Six1 (Six1 d/d). Interestingly, corn oil (CO) vehicle-treated Six1 d/d mice develop focal endometrial glandular dysplasia and features of carcinoma in situ as compared with CO wild-type Six1 (Six1 +/+) mice. Furthermore, Six1 d/d mice neonatally exposed to DES had a 42% higher incidence of endometrial cancer relative to DES Six1 +/+ mice. Although DES Six1 d/d mice had >10-fold fewer CK14+/18- basal cells within the uterine horns as compared with DES Six1 +/+ mice, the appearance of CK14+/18+ cells remained a feature of neoplastic lesions. These findings suggest that SIX1 is required for normal endometrial epithelial differentiation, CK14+/18+ cells act as a cancer progenitor population, and SIX1 delays DES-induced endometrial carcinogenesis by promoting basal differentiation of CK14+/18+ cells. In human endometrial biopsies, 35% of malignancies showed CK14+/18+ expression, which positively correlated with tumor stage and grade and was not present in normal endometrium. IMPLICATIONS: Aberrant epithelial differentiation is a key feature in both the DES mouse model of endometrial cancer and human endometrial cancer. The association of CK14+/18+ cells with human endometrial cancer provides a novel cancer biomarker and could lead to new therapeutic strategies.


Effectiveness of trivalent flu vaccine in healthy young children.
There are few studies evaluating the effectiveness of trivalent influenza vaccination (TIV) in young children, particularly in children <2 years. The Western Australian Influenza Vaccine Effectiveness Study commenced in 2008 to evaluate a program providing TIV to children aged 6 to 59 months. An observational study enrolling children with influenza-like illness presenting to a tertiary pediatric hospital was conducted (2008-2012). Vaccination status was determined by parental questionnaire and confirmed via the national immunization register and/or vaccine providers. Respiratory virus polymerase chain reaction and culture were performed on nasopharyngeal samples. The test-negative design was used to estimate vaccine effectiveness (VE) by using 2 control groups: all influenza test-negative subjects and other-virus-detected (OVD) subjects. Adjusted odds ratios were estimated from models with season, month of disease onset, age, gender, indigenous status, prematurity, and comorbidities as covariates. Subjects enrolled in 2009 were excluded from VE calculations. Of 2001 children enrolled, influenza was identified in 389 (20.4%) children. Another respiratory virus was identified in 1134 (59.6%) children. Overall, 295 of 1903 (15.5%) children were fully vaccinated and 161 of 1903 (8.4%) children were partially vaccinated. Vaccine uptake was significantly lower in 2010-2012 after increased febrile adverse events observed in 2010. Using test-negative controls, VE was 64.7% (95% confidence interval [CI]: 33.7%-81.2%). No difference in VE was observed with OVD controls (65.8%; 95% CI: 32.1%-82.8%). The VE for children <2 years was 85.8% (95% CI: 37.9%-96.7%). This study reveals the effectiveness of TIV in young children over 4 seasons by using test-negative and OVD controls. TIV was effective in children aged <2 years. Despite demonstrated vaccine effectiveness, uptake of TIV remains suboptimal.


The Role of the S40 Gene Family in Leaf Senescence.
Senescence affect different traits of plants, such as the ripening of fruit, number, quality and timing of seed maturation. While senescence is induced by age, growth hormones and different environmental stresses, a highly organized genetic mechanism related to substantial changes in gene expression regulates the process. Only a few genes associated to senescence have been identified in crop plants despite the vital significance of senescence for crop yield. The S40 gene family has been shown to play a role in leaf senescence. The barley HvS40 gene is one of the senescence marker genes which shows expression during age-dependent as well as dark-induced senescence. Like barley HvS40, the Arabidopsis AtS40-3 gene is also induced during natural senescence as well as in response to treatment with abscisic acid, salicylic acid, darkness and pathogen attack. It is speculated that rice OsS40 has a similar function in the leaf senescence of rice.


[The Spanish version of the Short Form 36 Health Survey: a decade of experience and new developments].
The Short Form-36 Health Survey (SF-36) is one of the most widely used and evaluated generic health-related quality of life (HRQL) questionnaires. After almost a decade of use in Spain, the present article critically reviews the content and metric properties of the Spanish version, as well as its new developments. A review of indexed articles that used the Spanish version of the SF-36 was performed in Medline (PubMed), the Spanish bibliographic databases IBECS and IME. Articles that provided information on the measurement model, reliability, validity, and responsiveness to change of the instrument were selected. Seventy-nine articles were found, of which 17 evaluated the metric characteristics of the questionnaire. The reliability of the SF-36 scales was higher than the suggested standard (Cronbach's alpha) of 0.7 in 96% of the evaluations. Grouped evaluations obtained by meta-analysis were higher than 0.7 in all cases. The SF-36 showed good discrimination among severity groups, moderate correlations with clinical indicators, and high correlations with other HRQL instruments. Moreover, questionnaire scores predicted mortality and were able to detect improvement due to therapeutic interventions such as coronary angioplasty, benign prostatic hyperplasia surgery, and non-invasive positive pressure home ventilation. The new developments (norm-based scoring, version 2, the SF-12 and SF-8) improved both the metric properties and interpretation of the questionnaire. The Spanish version of the SF-36 and its recently developed versions is a suitable instrument for use in medical research, as well as in clinical practice.


Delayed-choice quantum eraser with thermal light.
We report a random delayed-choice quantum eraser experiment. In a Young's double-slit interferometer, the which-slit information is learned from the photon-number fluctuation correlation of thermal light. The reappeared interference indicates that the which-slit information of a photon, or wave packet, can be "erased" by a second photon or wave packet, even after the annihilation of the first. Different from an entangled photon pair, the jointly measured two photons, or wave packets, are just two randomly distributed and randomly created photons of a thermal source that fall into the coincidence time window. The experimental observation can be explained as a nonlocal interference phenomenon in which a random photon or wave packet pair, interferes with the pair itself at distance.


Prevalence and correlates of sexual morbidity in long-term breast cancer survivors.
Breast cancer survivors report adverse sexual effects (sexual morbidity) such as disrupted sexual function, sexual distress and body dissatisfaction. However, most studies have failed to evaluate the persistence of these effects in long-term survivors. The present study comprehensively assessed the prevalence and predictors of sexual/body image problems among survivors three or more years post diagnosis. Eighty-three breast cancer survivors completed surveys a median of seven years post diagnosis. Survey items probed demographic, diagnostic and clinical information, in addition to sexual activity, sexual function (Female Sexual Function Index [FSFI]), body image, and distress regarding body changes and sexual problems (Female Sexual Distress Scale-revised; FSDS-R). Seventy-seven percent of all participants and 60% of sexually active participants qualified for sexual dysfunction based on the FSFI. Between 37 and 51% met criteria for female sexual dysfunction, based on two FSDS-R clinical cut-offs. Body satisfaction was worse than normative values, while body change stress was mid-range. Notable sexual morbidity predictors included mastectomy, which was associated with worse sexual/body change distress, and post-treatment weight gain, which predicted greater body dissatisfaction/body change stress. Breast cancer survivors report substantial sexual morbidity years after treatment, especially after mastectomy or post-treatment weight gain. Breast cancer patients and their providers should be aware of these potential sexual effects.


Registered nurses' work with sick leave questions by telephone in primary health care.
To describe registered nurses' work with sick leave questions by telephone. In Sweden, when a sick person needs to request a sickness certification, it is common to contact the primary healthcare centre. The main access to primary health care is by telephone, with a registered nurse answering the care seeker's questions, triaging and helping care seekers to the right level of care. Registered nurses' work with sick leave questions has not been studied, except for two qualitative interview studies. A descriptive cross-sectional study. A questionnaire with 120 questions was distributed to 185 registered nurses in one county in central Sweden. Descriptive statistics were used for analysis. Response rate was 62% (n = 114). Registered nurses (n = 105) in this study talked weekly to persons on, or at risk, for sick leave. A large part (n = 78) felt they had a role in the care of persons on sick leave, consisting of booking appointments as well as acting as a pilot, advisor, caretaker and coordinator. For 74 of 114 registered nurses, it was problematic to handle the phone calls weekly. Measures were 'often' booking appointments with physicians (n = 67) and 'seldom' providing information on social insurance rules ('never' n = 51). The registered nurses expressed a great need for more education. Registered nurses in this study reported having a role in the care of persons on sick leave when handling sick leave questions by telephone. The telephone calls were problematic to handle, and the registered nurses expressed a great need for education and training in social insurance medicine. There is a need to educate and train registered nurses in social insurance medicine to provide high-quality nursing for patients on or at risk for sick leave.


Increasing load carriage and running speed differentially affect the magnitude, variability and coordination patterns of muscle forces.
The study aims to investigate the effects of different loads and speed during running on inter- and intra-individual muscle force amplitudes, variabilities and coordination patterns. Nine healthy participants ran on an instrumentalized treadmill with an empty weight vest at two velocities (2.6 m/s and 3.3 m/s) or while carrying three different loads (4.5, 9.1, 13.6 kg) at 2.6 m/s while kinematics and kinetics were synchronously recorded. The major lower limb muscle forces were estimated using a musculoskeletal model. Muscle force amplitudes and variability, as well as coordination patterns were compared at the group and at the individual level using respectively statistical parametric mapping and covariance matrices combined with multidimensional scaling. Increasing the speed or the load during running increased most of the muscle force amplitudes (p < 0.01). During the propulsion phase, increasing the load increased muscle force variabilities around the ankle joint (modification of standard deviation up to 5% of body weight (BW), p < 0.05) while increasing the speed decreased variability for almost all the muscle forces (up to 10% of BW, p < 0.05). Each runner has a specific muscle force coordination pattern signature regardless of the different experimental conditions (p < 0.05). Yet, this individual pattern was slightly adapted in response to a change of speed or load (p < 0.05). Our results suggest that adding load increases the amplitude and variability of muscle force, but an increase in running speed decreases the variability. These findings may help improve the design of military or trail running training programs and injury rehabilitation by progressively increasing the mechanical load on anatomical structures.


Is Music Therapy an Effective Intervention for Dementia?A Meta-Analytic Review of Literature.
A recent qualitative review of literature in the area of music/ music therapy and dementias published since 1985 suggested that music/music therapy is an effective intervention for maintaining and improving active involvement, social, emotional and cognitive skills, and for decreasing behavioral problems of individuals with dementias (Brotons, Koger, & Pickett-Cooper, 1997). The present analysis sought to update and quantify this relationship, and investigate the extent to which methodological variables influenced treatment effectiveness. Twenty-one empirical studies, with a total of 336 subjects suffering from symptoms of dementia, were included in the meta-analysis. Overall, the effect of music/music therapy was found to be highly significant. A homogeneity analysis determined that the effect sizes were not consistent across studies; thus, a series of moderating variable analyses were conducted. We were unable to determine the source of variability between studies by analyzing type of therapeutic intervention (active or passive), music (live or taped), therapist's training (trained music therapist vs. other professional), dependent variable (behavioral, cognitive, or social), or length of treatment. Although the published literature demonstrates that music/music therapy is an effective method overall for treating symptoms of dementia, systematic variation of treatment protocols is necessary to identify the underlying mechanisms and delineate the most effective techniques.