In situ and in vitro evaluation of two antiseptics for blood bank based on chlorhexidine gluconate/isopropyl alcohol and povidone-iodine.

BACKGROUND: Poor disinfection is the main cause of blood contamination, so its elimination is key to limiting the entry of bacteria into the collection system. With the advancement of antiseptic technology, antiseptics with sterile, disposable applicators are now available. AIM: To evaluate in situ two antiseptics (with and without applicators) for blood banks and to demonstrate in vitro antiseptic activity on bacterial biofilms of importance in transfusion medicine. METHODS: Antiseptic A (2% sterile solution of chlorhexidine gluconate/70% isopropyl alcohol provided with applicator) and bulk antiseptic B (10% povidone-iodine) were evaluated. The deferred blood donor arms were subjected to disinfection with antiseptics A and B and the contralateral arms were cultured to determine the baseline bacterial load (control). Antiseptic activity was assessed by ANOVA and logaritmic reduction values (LRV) and percentage reduction values (PRV) were calculated. Finally, the in vitro activity of antiseptic A was analyzed by confocal laser scanning microscopy (CLSM) on biofilm models. RESULTS: Prior to disinfection tests, commensal and clinically important bacteria were identified; antiseptic A showed post-disinfection bacterial growth rates of zero compared to controls (p < 0.0001). The frequency of bacterial growth with antiseptic B was 74%. A significant difference was identified between both antiseptics, where antiseptic A showed higher activity (p < 0.5468). LRV and PRV were 0.6-2.5/100% and 0.3-1.7/66.7-99.7% for antiseptics A and B, respectively. Through CLSM, disinfectant A (without applicator) showed lower in vitro antiseptic activity on the tested biofilms at the exposure times recommended by the manufacturer. CONCLUSIONS: Sterile solution of chlorhexidine gluconate/isopropyl alcohol with applicator showed advantages disinfection in deferred blood donors over povidone-iodine.

Arthrodesis vs arthroplasty for moderate and severe Hallux rigidus: Systematic review.

Hallux rigidus is the most frequent arthritis of the foot, due to multiple factors. Arthrodesis and interposition arthroplasty are treatments considered in advanced stages of the disease, when conservative treatment has failed. Although arthrodesis may be considered the technique recommended by multiple authors, for patients in whom joint mobility is to be preserved, arthroplasty could represent a reliable alternative. The purpose of this systematic review is to investigate and compare the clinical outcomes and complications of arthrodesis and interposition arthroplasty for moderate and severe stages of hallux rigidus. METHODS: For this systematic review we searched COCHRANE, EMBASE, PUBMED databases. Twenty-six research papers were obtained, with a total of 1348 feet, which were included for qualitative analysis. The following groups were included: Cartiva hemiarthroplasty (286), double stem silicone arthroplasty (276), total metallic arthroplasty (394) and arthrodesis (392). RESULTS: In the arthrodesis group, the AOFAS-HMI score was the most used, ranging from 36 to 45 in the preoperative period and from 79 to 89 in the postoperative period. The greatest improvement in the VAS PAIN score was from 86 to 4. The fusion rate was 98.6% of the total number of cases, the most frequent complication was pain due to material discomfort. In the total metallic arthroplasty group, the ROTO-GLIDE system reported an AOFAS score of 95 points, with low complication rates; but, with the TOEFIT-PLUS and BIOMED-MERCK systems, despite the good postoperative value, they report 37% and 15% revision due to aseptic loosening in the series with the longest follow-up, respectively. The Cartiva group showed a significative increase in FAAM ADL and FAAM SPORT from 59.4 to 90.4 and from 60.9 to 89.7, respectively; similarly, 20.5% implant removal and conversion to arthrodesis were reported. Finally, the double stem silicone arthroplasty group, in the series with the longest follow-up, it manages to improve the MOXFQ score from 78.1 to 11.0, with an average range of mobility of 22.3 degrees. Lysis was reported in 10% of cases. CONCLUSIONS: Arthrodesis has proven to be the best option for the treatment of advanced hallux rigidus. Arthroplasty can be a valid option for patients who demand to maintain the range of mobility of the joint; however, it is important to inform about the complications that may arise in the short and medium term. LEVEL OF CLINICAL EVIDENCE: II.

Eosinophils Recruited during Pulmonary Vaccination Regulate Mucosal Antibody Production.

Eosinophils have been previously shown to be able to regulate early humoral responses during systemic vaccination. Here we investigated the role of eosinophils during pulmonary vaccination, comparing vaccine-induced responses in eosinophil-deficient (ΔdblGATA) and wild-type mice using a Th2 adjuvant. We observed that eosinophils were needed to induce a complete vaccine response, thereby eliciting specific antibody-secreting plasma cells in the regional lymph nodes and antibody secretion in the BAL at the early stage of the immune response. Reintroduction of eosinophils in the lungs of ΔdblGATA mice during the priming stage enhanced both specific IgM and IgG plasma cells but not specific IgA plasma cells. Upon vaccination, eosinophils migrated to the lungs and secreted cytokines involved in B-cell activation, which might promote antibody production. Importantly, however, the absence of eosinophils did not impair late immune responses in a prime/boost protocol because, in that setup, we uncovered a compensating mechanism involving a Th17 pathway. In conclusion, our data demonstrate for the first time a new role for eosinophils during lung mucosal vaccination, whereby they accelerate early immune responses (IgM and IgG) while regulating IgA production at the late stages.

Mediterranean songbirds show pronounced seasonal variation in thermoregulatory traits.

Addressing the patterns of variation in thermal traits is crucial to better predict the potential effects of climate change on organisms. Here, we assessed seasonal (winter vs summer) adjustments in key thermoregulatory traits in eight Mediterranean-resident songbirds. Overall, songbirds increased whole-animal (by 8%) and mass-adjusted (by 9%) basal metabolic rate and decreased (by 56%) thermal conductance below the thermoneutral zone during winter. The magnitude of these changes was within the lower values found in songbirds from northern temperate areas. Moreover, songbirds increased (by 11%) evaporative water loss within the thermoneutral zone during summer, while its rate of increase above the inflection point of evaporative water loss (i.e., the slope of evaporative water loss versus temperature) decreased by 35% during summer - a value well above that reported for other temperate and tropical songbirds. Finally, body mass increased by 5% during winter, a pattern similar to that found in many northern temperate species. Our findings support the idea that physiological adjustments might enhance the resilience of Mediterranean songbirds to environmental changes, with short-term benefits by saving energy and water under thermally stressful conditions. Nevertheless, not all species showed the same patterns, suggesting different strategies in their thermoregulatory adaptations to seasonal environments.

Heat tolerance limits of Mediterranean songbirds and their current and future vulnerabilities to temperature extremes.

Songbirds are one of the groups most vulnerable to extreme heat events. Although several recent studies have assessed their physiological responses to heat, most of them have focused solely on arid-zone species. We investigated thermoregulatory responses to heat in eight small-sized songbirds occurring in the Mediterranean Basin, where heatwaves are becoming more frequent and intense. Specifically, we determined their heat tolerance limits (HTLs) and evaporative cooling efficiency, and evaluated their current and future vulnerabilities to heat in southwestern Iberia, a Mediterranean climate warming hotspot. To do this, we exposed birds to an increasing profile of air temperatures (Ta) and measured resting metabolic rate (RMR), evaporative water loss (EWL), evaporative cooling efficiency (the ratio between evaporative heat loss and metabolic heat production) and body temperature (Tb). HTL ranged between 40 and 46°C across species, and all species showed rapid increases in RMR, EWL and Tb in response to increasing Ta. However, only the crested lark (Galerida cristata) achieved an evaporative cooling efficiency greater than 1. The studied songbirds currently experience summer Ta maxima that surpass the upper critical temperatures of their thermoneutral zone and even their HTL. Our estimates indicate that five of the eight species will experience moderate risk of lethal dehydration by the end of the century. We argue that the limited heat tolerance and evaporative cooling efficiency of small-sized Mediterranean songbirds make them particularly vulnerable to heatwaves, which will be exacerbated under future climate change scenarios.

The apical annuli of Toxoplasma gondii are composed of coiled-coil and signalling proteins embedded in the inner membrane complex sutures.

The apical annuli are among the most intriguing and understudied structures in the cytoskeleton of the apicomplexan parasite Toxoplasma gondii. We mapped the proteome of the annuli in Toxoplasma by reciprocal proximity biotinylation (BioID), and validated five apical annuli proteins (AAP1-5), Centrin2, and an apical annuli methyltransferase. Moreover, inner membrane complex (IMC) suture proteins connecting the alveolar vesicles were also detected and support annuli residence within the sutures. Super-resolution microscopy identified a concentric organisation comprising four rings with diameters ranging from 200 to 400 nm. The high prevalence of domain signatures shared with centrosomal proteins in the AAPs together with Centrin2 suggests that the annuli are related and/or derived from the centrosomes. Phylogenetic analysis revealed that the AAPs are conserved narrowly in coccidian, apicomplexan parasites that multiply by an internal budding mechanism. This suggests a role in replication, for example, to provide pores in the mother IMC permitting exchange of building blocks and waste products. However, presence of multiple signalling domains and proteins are suggestive of additional functions. Knockout of AAP4, the most conserved compound forming the largest ring-like structure, modestly decreased parasite fitness in vitro but had no significant impact on acute virulence in vivo. In conclusion, the apical annuli are composed of coiled-coil and signalling proteins assembled in a pore-like structure crossing the IMC barrier maintained during internal budding.

Going to sleep with a full belly: Thermal substitution by specific dynamic action in shorebirds.

Many bird species occupy habitats where environmental temperatures fall well below their thermoneutral zone (TNZ), so they must deal with high energy costs of thermoregulation to keep in heat balance. In such circumstances, specific dynamic action (SDA) - also referred to as heat increment of feeding - could be used to substitute for these high thermoregulatory costs. If birds ingest food before going to roost in cold environments, the SDA will be beneficial as an energy-conserving mechanism by thermal substitution. We investigated the magnitude and duration of SDA in a small-sized shorebird, the dunlin Calidris alpina, while feeding on living prey. We simulated in the aviary the food availability of a semidiurnal tidal cycle, and calculated the thermal substitution by SDA below their TNZ at the beginning of the "high tide" (resting period), after feeding ad libitum during the "low tide" (feeding period). Within TNZ (25 °C), dunlins consumed 12% (2.15 kJ) of the gross energy intake in excess by the SDA, with a duration of ~95 min. At 10 °C, i.e. below the lower critical limit of TNZ, SDA magnitude and duration were reduced by 29% and 31%, respectively. The amount of food ingested significantly affected the duration and magnitude of SDA, as well as the dunlin's body temperature. Thermal substitution by SDA saved 11% of the dunlin's theoretical daily energy requirement during winter. This thermal substitution could be commonly used by birds going to roost in cold climates. Interacting with other different behavioral and/or physiological strategies would help to maintain lower energetic costs and enhance survival in cold environments.

Vimentin as a Marker of Early Differentiating, Highly Motile Corneal Epithelial Cells.

Vimentin (Vim), a cytoskeletal intermediate filament, is part of a naturally occurring reversible program, the Epithelial-Mesenchymal Transition (EMT), which converts epithelial cells into mesenchymal-like derivatives. Based on previous results showing that epithelial cells co-express Vim and keratin (Krt) as part of a cytoskeletal network which confers them a highly motile phenotype, we explored the role of Vim in rabbit corneal epithelial cells or RCE1(5T5) cells, an established model of corneal epithelial differentiation. Vim and keratin filaments were co-expressed in cells localized at the proliferative/migratory rim of the growing colonies, but not in basal cells from the center of the colonies nor at suprabasal cell layers. Flow cytometry and qPCR demonstrated that there was a decrease in Krt+ /Vim+ cell number and ΔNp63α expression when cells reached confluence and formed a 4-5 layered epithelium, while there was a concomitant increase of both Pax-6 expression and Krt+ /Vim- cells. Inhibition of cell proliferation with mitomycin C did not modify cell motility nor the expression of Vim. We studied the distribution and expression of α6 integrin, a protein also involved in cell migration. The results demonstrated that α6 integrin had a distribution which was, in part, co-linear with Vim at the proliferative/migratory rim of cell colonies, suggesting an indirect interaction between these proteins. Immunoprecipitation and immunostaining assays indicated that plectin might be mediating such interaction. These data suggest that Vim expression in corneal epithelium is found in a cell population composed of highly motile cells with a Vim+ /Krt+ /ΔNp63α+ /Pax-6low /α6 integrin+ phenotype. J. Cell. Physiol. 232: 818-830, 2017. © 2016 Wiley Periodicals, Inc.

TRPV4 Regulates Tight Junctions and Affects Differentiation in a Cell Culture Model of the Corneal Epithelium.

TRPV4 (transient receptor potential vanilloid 4) is a cation channel activated by hypotonicity, moderate heat, or shear stress. We describe the expression of TRPV4 during the differentiation of a corneal epithelial cell model, RCE1(5T5) cells. TRPV4 is a late differentiation feature that is concentrated in the apical membrane of the outmost cell layer of the stratified epithelia. Ca2+ imaging experiments showed that TRPV4 activation with GSK1016790A produced an influx of calcium that was blunted by the specific TRPV4 blocker RN-1734. We analyzed the involvement of TRPV4 in RCE1(5T5) epithelial differentiation by measuring the development of transepithelial electrical resistance (TER) as an indicator of the tight junction (TJ) assembly. We showed that TRPV4 activity was necessary to establish the TJ. In differentiated epithelia, activation of TRPV4 increases the TER and the accumulation of claudin-4 in cell-cell contacts. Epidermal Growth Factor (EGF) up-regulates the TER of corneal epithelial cultures, and we show here that TRPV4 activation mimicked this EGF effect. Conversely, TRPV4 inhibition or knock down by specific shRNA prevented the increase in TER. Moreover, TRPP2, an EGF-activated channel that forms heteromeric complexes with TRPV4, is also concentrated in the outmost cell layer of differentiated RCE1(5T5) sheets. This suggests that the EGF regulation of the TJ may involve a heterotetrameric TRPV4-TRPP2 channel. These results demonstrated TRPV4 activity was necessary for the correct establishment of TJ in corneal epithelia and as well as the regulation of both the barrier function of TJ and its ability to respond to EGF. J. Cell. Physiol. 232: 1794-1807, 2017. © 2016 Wiley Periodicals, Inc.

Immunoreactive cortisone in droppings reflect stress levels, diet and growth rate of gull-billed tern chicks.

Blood levels of corticosterone have been traditionally analyzed to assess stress levels in birds; however, measuring steroid hormone metabolites in feces and droppings has gained much interest as a noninvasive technique successfully used for such purposed in vertebrates. Diet may affect these fecal metabolite levels (e.g., due to nutritional stress), however, this variable has not been taken into account in studies with chicks despite the great dietary flexibility of many avian species. In this study, we addressed for the first time this key issue and validated the technique in wild gull-billed tern chicks (Gelochelidon nilotica). Several enzyme immunoassays were used to determine the most appropriate test to measure the stress response. Subsequently, we performed an experiment in captivity to assess adrenocortical activity in gull-billed tern chicks fed with two diets: piscivorous vs. insectivorous. Finally, the relation between the chicks' growth rate and excreted immunoreactive glucocorticoid metabolites (EGMs) was also evaluated. We found the immunoreactive cortisone metabolites to be a good index of stress (as being an index of adrenocortical reactivity) in chicks of this species. Fish-fed chicks had higher levels of cortisone metabolites when comparing both concentration and total daily excreted metabolites. Within each treatment diet, cortisone metabolite levels and growth rates were negatively correlated. These findings suggest that the diet should be considered when using this technique for comparative purposes and highlight the trade-off between stress levels and chicks growth rates.

[Domestic violence in patients and caregivers dyads in neurological diseases]. / Violencia doméstica en díadas paciente-cuidador de enfermedades neurológicas.

INTRODUCTION: Patients with neurological diseases are susceptible to abuse and neglect. Studies on violence in this context have mainly focused on abuse perpetrated by a caregiver to the patient directionally. In this study we describe violence in dyads of caregivers and patients with neurological disorders according to frequency, directionality, and type of relation. METHODS: One-hundred-and-eighty-five caregiver-patient dyads were assessed by means of the National Survey of Violence Against Women (NSVAW) guidelines and the Zarit and Pfeiffer questionnaires. Bivariate analysis and Spearman correlation tests were performed. RESULTS: Violence was reported by 32.5% of caregivers and 33.5% of patients. In both groups, psychological abuse was the most common. Mutual violence (54.5%) is the most common type of abuse and the caregiver reported as having more violent behavior is the intimate partner. Epilepsy was the neurological disorder where violence was more prevalent (47.6%). CONCLUSIONS: The prevalence of violence in our sample is higher than the one for the general population of 21%, as reported by the NSVAW. Clinical neurologists and healthcare services are key elements for the detection of abuse in this context.

Stigma experience of people with epilepsy in Mexico and views of health care providers.

Epilepsy is a neurological disorder with neurobiological, cognitive, psychological, and social consequences. Epilepsy stigma is a social determinant of ill health that affects the quality of life of people who suffer from epilepsy and that renders a poor social prognosis even worse than the clinical one. From a phenomenological approach, between January and July 2011, we explored the experience of epilepsy stigma through 25 in-depth qualitative interviews with 10 persons with temporal lobe epilepsy (PWE) (we avoided terms such as "epileptics" or "epileptic patients" because they can be labeling and stigmatizing), 10 carers (CEs) of PWE who attended the epilepsy clinic of the Institute of Neurology and Neurosurgery of Mexico, and 5 physicians specialized in epilepsy. The objective of the study was to identify the following: perceptions that could indicate any form of discrimination due to having epilepsy, reactions of people in front of a person having seizures, and social functioning of PWE since epilepsy onset, particularly their interpersonal relationships and participation in educational or working activities. Through the health providers' narratives, we explored the mainstream care practices, their perspectives on epilepsy, and their views about how the disease should be addressed. Thematic guidelines were elaborated for each type of participant. All information was processed with the use of the computer-assisted data analysis, Atlas.ti5. We made a codification of broad themes that corresponded to the main topics of the interview guidelines and then proceeded to finer categorization to elaborate the analytical categories. Epilepsy was attached to a powerful stereotype that includes notions of contamination, danger, sin, divine punishment, supernatural forces, and madness. Internalized, interpersonal, and institutional stigma prevents PWE from participating in school and employment and reduces their opportunities to establish peer and couple relationships. Mexican's overt impunity of structural discrimination towards PWE shows a lack of available legal resources that protect their human rights. The narrow biomedical concept that physicians have of epilepsy is consistent with the limited medical practices that are offered to treat epilepsy at the health services in Mexico. Comprehensive treatment and integrated services for epilepsy must incorporate psychosocial programs that include epilepsy stigma as a major component of the disease.

Anion binding studies on receptors derived from the indolo[2,3-a]carbazole scaffold having different binding cavity sizes.

The indolo[2,3-a]carbazole scaffold is a fused polyheteroaromatic system bearing two NH groups which suitably converge as hydrogen bond donor sites for the recognition of anions. A simple derivatisation of the indolocarbazole system at positions 1 and 10 with different functional groups, namely alcohols and amides, has contributed to modulate the anion binding selectivity and sensibility. A particularly good response has been obtained for the benzoate anion.

Workload of on-call emergency room neurologists in a Spanish tertiary care centre. A one-year prospective study.

INTRODUCTION: Population ageing, the rising demand for healthcare, and the establishment of acute stroke treatment programs have given rise to increases in the number and complexity of neurological emergency cases. Nevertheless, many centres in Spain still lack on-call emergency neurologists. METHODS: We conducted a retrospective study to describe the role of on-call neurologists at Hospital General Universitario Gregorio Marañón, a tertiary care centre in Madrid, Spain. Sociodemographic characteristics, most common pathologies, diagnostic tests, and destination of the patients attended were recorded daily using a computer database. Results were compared with the general care data from the emergency department. RESULTS: The team attended 3234 patients (3.48% of the emergency department total). The mean number of patients seen per day was 11.15. The most frequent pathologies were stroke (34%), epilepsy (16%) and headache (8%). The mean stay in the emergency department was 7.17 hours. Hospital admission rate was 40% (7.38% of emergency hospital admissions). The main destinations for admitted patients were the stroke unit (39.5%) and the neurology department (33%). Endovascular or thrombolytic therapies were performed on 76 occasions. Doctors attended 70% of the patients during on-call hours. CONCLUSIONS: Emergency neurological care is varied, complex, and frequently necessary. Neurological cases account for a sizeable percentage of both patient visits to the emergency room and the total number of emergency admissions. The current data confirm that on-call neurologists available on a 24-hour basis are needed in emergency departments.

BAY-9835: Discovery of the First Orally Bioavailable ADAMTS7 Inhibitor.

The matrix metalloprotease ADAMTS7 has been identified by multiple genome-wide association studies as being involved in the development of coronary artery disease. Subsequent research revealed the proteolytic function of the enzyme to be relevant for atherogenesis and restenosis after vessel injury. Based on a publicly known dual ADAMTS4/ADAMTS5 inhibitor, we have in silico designed an ADAMTS7 inhibitor of the catalytic domain, which served as a starting point for an optimization campaign. Initially our inhibitors suffered from low selectivity vs MMP12. An X-ray cocrystal structure inspired us to exploit amino acid differences in the binding site of MMP12 and ADAMTS7 to improve selectivity. Further optimization composed of employing 5-membered heteroaromatic groups as hydantoin substituents to become more potent on ADAMTS7. Finally, fine-tuning of DMPK properties yielded BAY-9835, the first orally bioavailable ADAMTS7 inhibitor. Further optimization to improve selectivity vs ADAMTS12 seems possible, and a respective starting point could be identified.

Validation of prognostic and predictive value of total tumoral load after primary systemic therapy in breast cancer using OSNA assay.

PURPOSE: This study aimed to validate the classification of breast cancer (BC) patients in progression risk groups based on total tumor load (TTL) value to predict lymph node (LN) affectation after neo-adjuvant systemic therapy (NAST) obtained in the NEOVATTL study. METHODS/PATIENTS: This was an observational, retrospective, international, multicenter study including patients with infiltrating BC who received NAST followed by sentinel lymph node biopsy (SLNB) analyzed with one-step nucleic acid amplification (OSNA) from nine Spanish and two Italian hospitals. Patients were classified into three groups according to the progression risk, measured as disease-free survival (DFS), based on TTL values (> 250, 250-25,000, and > 25,000 copies/µL). The previous (NEOVATTL study) Cox regression model for prognosis was validated using prognostic index (PI) and Log ratio test (LRT) analyses; the value of TTL for axillary non-SLN affectation was assessed using receiver operating characteristic (ROC) curves. RESULTS: We included 263 patients with a mean age of 51.4 (± SD 10.5) years. Patients with TTL > 25,000 copies/µL had a shorter DFS (HR 3.561 [95% CI 1.693-7.489], p = 0.0008 vs. TTL ≤ 25,000). PI and LRT analyses showed no differences between the two cohorts (p = 0.2553 and p = 0.226, respectively). ROC analysis showed concordance between TTL and non-SLN involvement (area under the curve 0.828), with 95.7% sensitivity and 92.9% specificity at a TTL cut-off of > 15,000 copies/µL. CONCLUSIONS: In BC patients who had received NAST and underwent SLNB analysis using OSNA, a TTL value of > 25,000 copies/µL was associated with a higher progression risk and > 15,000 copies/µL was predictive of non-SLN involvement.

Plasma Photoinactivation of Bacterial Isolated from Blood Donors Skin: Potential of Security Barrier in Transfusional Therapy.

The presence of skin bacteria capable of forming biofilm, exhibiting antibiotic resistance, and displaying virulence represents a significant challenge in the field of transfusion medicine. This underscores the necessity of enhancing the microbiological safety of blood and blood components against pathogens with virulent characteristics. The aim of this work was to demonstrate bacterial inactivation in plasma by using a photoinactivation method against virulent bacteria and to evaluate coagulation factors before and after treatment. Logarithmic loads of biofilm-producing, antibiotic-resistant, and virulent bacteria isolated from skin (Enterobacter cloacae, Klebsiella ozaenae, and Staphylococcus epidermidis) were used in artificial contamination assays of fresh frozen plasma bags and subjected to photoreduction. FVIII and FI activity were evaluated before and after photoinactivation. The photoinactivation of plasma was demonstrated to be an effective method for the elimination of these bacteria. However, the efficiency of this method was found to be dependent on the bacterial load and the type of test microorganism. Conversely, decay of coagulation factors was observed with net residual activities of 61 and 69% for FVIII and FI, respectively. The photoinactivation system could have a bias in its effectiveness that is dependent on the test pathogen. These findings highlight the importance of employing technologies that increase the safety of the recipient of blood and/or blood components, especially against virulent bacteria, and show the relevance of the role of photoinactivation systems as an option in transfusion practice.

Bis(carbazolyl)ureas as selective receptors for the recognition of hydrogenpyrophosphate in aqueous media.

Recognition properties of the novel bis(carbazole) tris-ureidic-based receptors 1 and 2 toward different anions have been studied by (1)H NMR and absorption and emission spectroscopy, as well as by DFT calculations. Receptor 1, in which the two urea-functionalized arms are decorated with p-nitrophenyl rings, behaves as a highly selective chromogenic molecular probe for hydrogenpyrophosphate anion in a competitive medium (acetonitrile/water, 70/30). Receptor 2, bearing two urea arms decorated with photoactive pyrenyl rings, acts as a highly selective fluorescent molecular probe for hydrogenpyrophosphate anion in either acetonitrile or an aqueous mixture (acetonitrile/water, 85/15). Receptor 2 exhibits a dual monomer-excimer emission spectrum and undergoes a remarked ratiometry in acetonitrile in the presence of hydrogenpyrophosphate: the excimer band disappears, whereas the monomer band is slightly increased. However, in the aqueous mixture, a strong increase of the excimer emission band was observed, while the monomer emission bands remained almost unaffected. The resulting binding modes and spectroscopic features are explained by suitable structures of model complexes for both receptors. In such complexes, a peripheral cooperative effect was found, alleviating the excess of negative charge in the guest toward the outer surface of the host, as well as the required enlargement on its internal cavity.

Effects of salinity on the immune response of an 'osmotic generalist' bird.

Salt stress can suppress the immune function of fish and other aquatic animals, but such an effect has not yet been examined in air-breathing vertebrates that frequently cope with waters (and prey) of contrasting salinities. We investigated the effects of seawater salinity on the strength and cost of mounting an immune response in the dunlin Calidris alpina, a long-distance migratory shorebird that shifts seasonally from freshwater environments during the breeding season to marine environments during migration and the winter period. Phytohaemagglutinin (PHA)-induced skin swelling, basal metabolic rate (BMR), body mass, fat stores, and plasma ions were measured in dunlins acclimated to either freshwater or seawater (salinity: 0.3 and 35.0 ‰, respectively). Seawater-acclimated dunlins mounted a PHA-induced swelling response that was up to 56 % weaker than those held under freshwater conditions, despite ad libitum access to food. Freshwater-acclimated dunlins significantly increased their relative BMR 48 h after PHA injection, whereas seawater-acclimated dunlins did not. However, this differential immune and metabolic response between freshwater- and seawater-acclimated dunlins was not associated with significant changes in body mass, fat stores or plasma ions. Our results indicate that the strength of the immune response of this small-sized migratory shorebird was negatively influenced by the salinity of marine habitats. Further, these findings suggest that the reduced immune response observed under saline conditions might not be caused by an energy or nutrient limitation, and raise questions about the role of osmoregulatory hormones in the modulation of the immune system.

Psychosocial Interventions for the Treatment of Cancer-Related Fatigue: An Umbrella Review.

Cancer-related fatigue is one of the most common symptoms of cancer and one of those referred by patients as the most disabling. However, we still do not have enough evidence to allow us to recommend effective and personalized approaches. GOAL: To provide evidence on the efficacy of ASCO-recommended psychosocial interventions for reducing cancer-related fatigue. METHODOLOGY: A general quantitative systematic review for nonprimary clinical interventions that allows the collection, synthesis and analysis of already published reviews. Systematic reviews of RTCs were selected as these make up the body of knowledge that provides the most evidence in an umbrella format. The results do not provide clear or comparable evidence regarding the different interventions, with moderate evidence standing out for cognitive interventions and mindfulness. CONCLUSIONS: Research gaps, study biases and the need for further research to ask more precise questions and to make reliable recommendations to mitigate the impact of cancer-related fatigue are evident.