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BackgroundHeart failure (HF) significantly impacts healthcare systems due to high rates of hospital bed utilization and readmission rates. Chronic HF often leads to frequent hospitalizations due to recurrent exacerbations and a decline in patient health status. Intravenous (IV) diuretic administration is essential for treating worsening HF. Emerging strategies include home-based IV diuretic therapy administration; however, limited practical implementation guidance is available. This scoping review aims to summarize the literature on home IV diuretic administration for HF patients, focusing on the interventions' characteristics, and facilitators and barriers to its implementation.MethodsThis review followed the scoping review framework proposed by Arksey and O'Malley and PRIMSA-ScR. A comprehensive search was conducted across six databases (CINAHL, the Cochrane Library, EMBASE, MEDLINE, PsychINFO and Scopus) and grey literature to identify English studies from inception to April 13, 2024. Two independent reviewers screened articles and resources for inclusion and data was extracted using a form created by the authors in Covidence.ResultsThe search yielded 2,049 results, with nine studies meeting the inclusion criteria. Studies varied in design, including feasibility, pilot, observational, and pre/post-intervention evaluations. The majority were conducted in European countries, with sample sizes ranging from 12 to 96 patients receiving home IV diuretics for HF. Key implementation challenges include appropriate patient selection, IV cannulation competency of healthcare providers, and multi-disciplinary and multi-agency collaboration.ConclusionsEvidence on home IV diuretic administration practices for HF management remains limited. However, this scoping review suggests that commonalities across studies could form the basis for developing standard protocols in outpatient settings. Despite the lack of formal evidence-based guidelines, the findings also suggest that tailored, community-specific approaches and safe infusion guidance documents could enhance the efficacy and scalability of home IV diuretic therapy. Future research should focus on refining these strategies and exploring diuretic escalation methods beyond traditional acute care administration to optimize patient outcomes.

Background and objective: One of the functions attributed to the auditory efferent system is related to the processing of acoustic stimuli in noise backgrounds. However, clinical implications and the neurophysiological mechanisms of this system are not yet understood, especially on higher regions of the central nervous system. Only a few researchers studied the effects of noise on cortical auditory evoked potentials (CAEP), but the lack of studies in this area and the contradictory results, especially in children, point to the need to investigate different protocols and parameters that could allow the study of top-down activity in humans. For this reason, the aim of this study was to analyze the effect of varying levels of contralateral noise on efferent activity in children by recording CAEPs with tone burst stimuli. Additionally, we aimed at verifying the effects of contralateral noise on cortical processing of speech stimuli. Methods: Monaural CAEPs were recorded using tone burst stimuli in quiet and with contralateral white noise at 60 dB and at 70 dB in 65 typically developing school-aged children (experiment 1), and using speech stimuli with contralateral white noise at 60 dB in 41 children (experiment 2). Results: In experiment 1, noise induced changes were observed only for P1 and P300 components. P1 latency was prolonged at both noise level conditions, P300 latency was prolonged only in the condition with noise at 70 dB, and P300 amplitude was reduced only in the condition with noise at 60 dB. In experiment 2, noise induced latency delays were observed on P1, P2, N2, and P300 components and amplitude reduction was observed only for N1. Conclusion: The effects of noise stimulation were observed on all CAEP components elicited by speech, but the same was not observed in the experiment with tone bursts. The study of noise effects on CAEPs can provide electrophysiological evidence on how difficult listening situations affect sound discrimination and stimulus evaluation at thalamocortical regions. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) significantly impacts healthcare systems due to high rates of hospital bed utilization and readmission rates. Chronic HF often leads to frequent hospitalizations due to recurrent exacerbations and a decline in patient health status. Intravenous (IV) diuretic administration is essential for treating worsening HF. Emerging strategies include home-based IV diuretic therapy administration; however, limited practical implementation guidance is available. This scoping review aims to summarize the literature on home IV diuretic administration for HF patients, focusing on the interventions' characteristics, and facilitators and barriers to its implementation. Methods: This review followed the scoping review framework proposed by Arksey and O'Malley and PRIMSA-ScR. A comprehensive search was conducted across six databases (CINAHL, the Cochrane Library, EMBASE, MEDLINE, PsychINFO and Scopus) and grey literature to identify English studies from inception to April 13, 2024. Two independent reviewers screened articles and resources for inclusion and data was extracted using a form created by the authors in Covidence. Results: The search yielded 2,049 results, with nine studies meeting the inclusion criteria. Studies varied in design, including feasibility, pilot, observational, and pre/post-intervention evaluations. The majority were conducted in European countries, with sample sizes ranging from 12 to 96 patients receiving home IV diuretics for HF. Key implementation challenges include appropriate patient selection, IV cannulation competency of healthcare providers, and multi-disciplinary and multi-agency collaboration. Conclusions: Evidence on home IV diuretic administration practices for HF management remains limited. However, this scoping review suggests that commonalities across studies could form the basis for developing standard protocols in outpatient settings. Despite the lack of formal evidence-based guidelines, the findings also suggest that tailored, community-specific approaches and safe infusion guidance documents could enhance the efficacy and scalability of home IV diuretic therapy. Future research should focus on refining these strategies and exploring diuretic escalation methods beyond traditional acute care administration to optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Older adults with cognitive impairment often experience low mobility and functional decline in hospital, transfer to facility-based transitional care programs, and have poorer outcomes compared to those without cognitive impairment. This protocol paper describes a study which aims to determine the feasibility of, satisfaction with, and efficacy of a nurse-led mobility intervention (OASIS Walking Intervention) for older adults with cognitive impairment in facility-based transitional care programs in Ontario, Canada. A quasi-experimental one-group time series feasibility study will be conducted. A sample size of 26 participants will be recruited from two transitional care programs in Ontario, Canada. Participants will receive the OASIS Walking Intervention for up to 45 minutes per session, 5 sessions per week, for 6 weeks. The intervention consists of: 1) a patient-centered communication care plan; 2) sit to stand activity; and 3) a walking program. Feasibility will be determined by: a) recruitment rate; b) retention rate; and c) adherence. Efficacy of the intervention will be determined by the change over time in older adults' lower extremity muscle strength, mobility, and functional status and by their discharge destination (home vs. nursing home). Satisfaction will be measured using the Client Satisfaction Questionnaire. Efficacy outcomes will be measured before the start of the intervention, after 3 weeks of the intervention, and immediately after 6-week intervention. Descriptive statistics will be used for measures of feasibility, satisfaction, and discharge destination. Repeated measures analysis of variance (RM-ANOVA) will be used to analyze efficacy. Ethics approval has been received for this study. Findings from the study will be used to refine the intervention for use in a definitive pilot trial. Results will be disseminated via peer-reviewed publications, international conferences, through group presentations at the study sites, and through the study site networks. Trial registration: The trial has been registered on Clinicaltrials.gov (NCT06150339). [ABSTRACT FROM AUTHOR]

Background and purposeThrombotic microangiopathy (TMA) is a group of microvascular occlusive disorders that presents with neurological involvement in up to 87% of the cases. Although the central nervous system (CNS) is an important target organ in TMA, the role of neurological manifestations in the disease clinical course is not well established. In this study, we described the neurological manifestations and CNS radiological aspects in patients with a first, acute TMA event. We also examined the association between severe neurological involvement and adverse clinical outcomes in TMA.MethodsA cohort of patients diagnosed with a first TMA event between 1995 and 2016 was included, their medical charts and imaging tests were retrospectively evaluated.ResultsA total of 49 patients were included, 85.7% were women and the mean age was 36.5 years-old (SD 13.0). Neurological manifestations were described in 85.7% of the patients, most of them (88%) were considered severe and consisted of confusion, compromised sensorimotor function, stupor, seizures, and personality change. Imaging tests were performed in 62% of the patients with neurological manifestations and detected acute CNS lesions, such as posterior reversible encephalopathy syndrome, hemorrhagic and ischemic stroke were observed, in 7 (27%) of them. While the need for intensive care unit admission was greater and longer among patients with severe neurological manifestations, the number of plasma exchange sessions, the total duration of hospitalization and in-hospital death were similar between groups.ConclusionsSevere neurological manifestations are common in first TMA events and are responsible for a worse disease presentation at admission. While the effect of neurological manifestations on acute TMA clinical course seems to be modest, these manifestations may have an important impact on the development of chronic cognitive impairment, which highlights the need for proper diagnosis and treatment.

Background Postnatal mental health problems affect 10–15% of women and can adversely impact on mother-infant interactions and bonding, the mother’s mood, and feelings of competence. There is evidence that attending performing arts activities, such as singing, dancing, and listening to music, may improve maternal mental health with potential for an effect on postnatal depression. Methods A systematic review will be conducted to assess the effect of mother-infant group music classes on postnatal depression compared to standard care, no control or wait list control. Studies will be included that report on postnatal depression. Further outcomes of interest include anxiety, stress, parenting competence, confidence and self-efficacy, perceived social support and mother-infant bonding. Infant and child outcomes measuring cognitive development, behaviour and social and emotional development will be included. Search databases to be used will be Medline, EMBASE, CINAHL, PsycINFO, Scopus, CENTRAL, Web of Science, Maternity and Infant Care and discipline-specific journals for music. The Cochrane’s Template for Intervention description and replication (TIDieR) checklist and guide will be utilised to aid a detailed description, standardised assessment and quality assurance. Risk of bias will be assessed by the authors using the Cochrane Handbook for Systematic Reviews of Interventions risk of bias tool. If sufficient studies are available, meta-analyses will be conducted to combine, compare and summarise the results of the studies for more precise estimates of effects. Where meta-analysis is not possible, results for each individual study will be reported through qualitative narrative data synthesis. Discussion This systematic review will identify and synthesise evidence of the measured effect of postnatal mother-infant interventions involving music on maternal psychological and psychosocial outcomes and infant/child outcomes. Systematic review registration This protocol was registered with Prospero on 18 October 2021 (registration number CRD42021283691). https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021283691.

IntroductionDuring COVID-19 pandemic, Internal Medicine Units (IMUs) accounted for about 70% of patients hospitalized. Although a large body of data has been published regarding the so-called first wave of the pandemic, little is known about the characteristics and predictors of worse outcomes of patients managed in IMUs during the second wave.MethodsWe prospectively assessed demographics, comorbidities, treatment and outcomes, including ventilation support (VS) and death, in patients admitted to our IMU for SARS-CoV-2 between October 13th, 2020 and January 21st, 2021. Clinical evolution and biochemical testing 1, 7 and 14 days after COVID-19 diagnosis were recorded.ResultsWe studied 120 patients (M/F 56/64, age 71±14.5 years) admitted to our IMU. Most of them had at least one comorbidity (80%). Patients who died were older, more frequently underweight, affected by malignant neoplasms and on statin therapy compared to patients eventually discharged. Both worse outcome groups (VS and death) presented higher neutrophils, ferritin, IL-6 and lower total proteins levels than controls. Age was significantly associated with mortality but not with VS need. The multivariate analysis showed age and gender independent association of mortality with underweight, malignancy and antibiotics use at the admission. With regard to biochemical parameters, both unfavourable outcomes were positively associated with high WBC count, neutrophils, blood urea nitrogen and low serum total proteins.ConclusionsOur study identified inflammation, underweight, malignancy and a marked catabolic state as the main predictors for worse outcomes in COVID-19 patients admitted to IMU during the so-called second wave of the pandemic.

ObjectiveTo contribute to the validation of AudBility, an online central auditory processing screening program, considering the tasks for age between 6 and 8 years-old, from the investigation of sensitivity and specificity, as well as to suggest a minimum central auditory processing (CAP) screening protocol in this age group.MethodIn the first stage of the study, 154 schoolchildren were screened. Children were aged between 6 and 8 years old, native speakers of Brazilian Portuguese. The auditory tasks of AudBility analyzed in this study were: sound localization (SL), auditory closure (AC), figure-ground (FG), dichotic digits-binaural integration (DD), temporal resolution (TR) and temporal frequency ordering (TO-F). In the second stage, 112 children attended to CAP assessment in the institution's laboratory. The calculation of efficacy (sensitivity/specificity) was obtained through the construction of the ROC curve for the tests with more than five children altered in the diagnosis.ResultsFor the 6-7-year-old age group the accuracy values were: AC (76.9%); FG (61.6%); DD 78.8% for the right ear and 84.4% for the left ear in females and 63.2% for the left ear in males; TR (77.1%) and TO-F (74.4% for the right ear and 82.4% for the left ear). For the 8-year-old age group the values were: FF (76.5%); DD (71.7% for the left ear for females and 77% for the right ear for males); TR (56.5%) and TO-F (54.1% for the right ear and 70% for the left ear).ConclusionsAudBility showed variations in sensitivity and specificity values between the auditory tasks and age groups, with better effectiveness in schoolchildren between the ages of 6 and 7 than eight-year-olds, except for the FG task. For screening purposes, the application of the protocol involving five tasks for the 6 to 7-year-olds group and with four tasks for the 8-year-olds group is suggested.

BackgroundCOVID-19 is a multisystemic disorder that frequently causes acute kidney injury (AKI). However, the precise clinical and biochemical variables associated with AKI progression in patients with severe COVID-19 remain unclear.MethodsWe performed a retrospective study on 278 hospitalized patients who were admitted to the ward and intensive care unit (ICU) with COVID-19 between March 2020 and June 2020, at the University Hospital, São Paulo, Brazil. Patients aged ≥ 18 years with COVID-19 confirmed on RT-PCR were included. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. We evaluated the incidence of AKI, several clinical variables, medicines used, and outcomes in two sub-groups: COVID-19 patients with AKI (Cov-AKI), and COVID-19 patients without AKI (non-AKI). Univariate and multivariate analyses were performed.ResultsFirst, an elevated incidence of AKI (71.2%) was identified, distributed across different stages of the KDIGO criteria. We further observed higher levels of creatinine, C-reactive protein (CRP), leukocytes, neutrophils, monocytes, and neutrophil-to-lymphocyte ratio (NLR) in the Cov-AKI group than in the non-AKI group, at hospital admission. On univariate analysis, Cov-AKI was associated with older age (>62 years), hypertension, CRP, MCV, leucocytes, neutrophils, NLR, combined hydroxychloroquine and azithromycin treatment, use of mechanical ventilation, and vasoactive drugs. Multivariate analysis showed that hypertension and the use of vasoactive drugs were independently associated with a risk of higher AKI in COVID-19 patients. Finally, we preferentially found an altered erythrocyte and leukocyte cellular profile in the Cov-AKI group compared to the non-AKI group, at hospital discharge.ConclusionsIn our study, the development of AKI in patients with severe COVID-19 was related to inflammatory blood markers and therapy with hydroxychloroquine/azithromycin, with vasopressor requirement and hypertension considered potential risk factors. Thus, attention to the protocol, hypertension, and some blood markers may help assist doctors with decision-making for the management of COVID-19 patients with AKI.

BACKGROUND/OBJECTIVE:The effects of otitis media on the function of the central auditory nervous system in different populations is unknown. Understanding how the history of otitis media affects children from different nations will guide health professionals worldwide on the importance of adequate auditory stimulus in childhood. For this reason, the aim of the present study was to investigate the long-term auditory effects of middle ear disease on temporal processing and P300 in two different populations of children: Australian and Brazilian. METHODS:Temporal processing tests (Frequency Pattern Tests-FPT and Gaps in noise-GIN) and P300 were measured in 68 Brazilian and Australian children, aged between 8 to 14 years. The Brazilian otitis media group (BrOM) and Australian otitis media group (AusOM) consisted of 20 children each who had a documented history of otitis media. Control groups of 14 children (BrControl and AusControl) were also recruited from each country, all with no documented history of otitis media. RESULTS:The BrOM group showed significantly poorer performance (p

Insect pollinator communities are thought to transition from bee-dominated communities at low elevations to fly-dominated communities at high elevations. We predicted that increased tree canopy cover and a subsequent decrease in meadows and flowering plants would limit bees but not flies at higher elevations. We tested and supported this prediction by examining changes in both abundance and species richness for 128 bee species and 96 fly species at key points along an elevational gradient in Northern Arizona represented by distinct vegetation life zones. In addition to an increase in fly species and abundance relative to bees with increasing elevation, there were changes in community structure). To better understand factors that might influence this transition we examined how tree canopy cover changed along the elevational gradient and how this influenced the change in insect pollinator communities. While bee communities were progressively divergent between forest and meadow habitats with increasing elevation and tree canopy cover, there was no significant pattern with flies between meadow and forest habitats. However, fly abundance did increase with increasing elevation relative to bees. Along a comparable elevational gradient on an adjacent mountain with no tree canopy cover (i.e., a fire burned mountain), the bee-to-fly transition did not occur; bees persisted as the dominant pollinator into the highest life zone. This suggests that tree canopy cover can in part explain the transition from bee-to fly-dominated communities. In conclusion, this is the first study in North America to document a bee-fly transition for both abundance and species richness and show that tree canopy cover may play a role in determining pollinator community composition, by restricting bees to open meadow habitats.

Heme has been characterized as potent trigger of inflammation. In hemostasis, although heme has been shown to both induce and inhibit different compartments of hemostasis, its net effect on the hemostatic balance, and the biological relevance of these effects remain to be determined. Herein we evaluated the effect of heme on hemostasis using a global assay able to generate clinically relevant data in several other complex hemostatic diseases. Citrated whole blood samples from healthy participants were stimulated by heme or vehicle and incubated for 4h at 37°C. Rotational thromboelastometry was immediately performed. The participation of tissue factor in coagulation activation was evaluated using inhibitory antibody. Heme was able of inducing ex vivo coagulation activation in whole blood, affecting predominantly parameters associated with the initial phases of clot formation. This activation effect was at least partially dependent on hematopoietic tissue factor, since the effects of heme were partially abrogated by the inhibition of human tissue factor. In conclusion, using a global hemostasis assay, our study confirmed that heme is able to activate coagulation in whole blood, in a tissue factor-dependent way. These findings could explain the disturbance in hemostatic balance observed in conditions associated with the release of heme such as sickle cell disease.

Squamous cell carcinoma of the head and neck (SCCHN) comprises a large group of cancers in the oral cavity and nasopharyngeal area that typically arise in older males in association with alcohol/tobacco usage. Within the oral cavity, the mobile tongue is the most common site for tumour development. The incidence of tongue squamous cell carcinoma (TSCC) is increasing in younger people, which has been suggested to associate with a viral aetiology. Two common human oncogenic viruses, human papilloma virus (HPV) and Epstein-Barr virus (EBV) are known causes of certain types of SCCHN, namely the oropharynx and nasopharynx, respectively. EBV infects most adults worldwide through oral transmission and establishes a latent infection, with sporadic productive viral replication and release of virus in the oral cavity throughout life. In view of the prevalence of EBV in the oral cavity and recent data indicating that it infects tongue epithelial cells and establishes latency, we examined 98 cases of primary squamous cell carcinoma of the mobile tongue and 15 cases of tonsillar squamous cell carcinoma for the presence of EBV-encoded RNAs (EBERs), EBV DNA and an EBV-encoded protein, EBNA-1. A commercially available in situ hybridisation kit targeting EBER transcripts (EBER-ISH) showed a positive signal in the cytoplasm and/or nuclei of tumour cells in 43% of TSCCs. However, application of control probes and RNase A digestion using in-house developed EBER-ISH showed identical EBER staining patterns, indicating non-specific signals. PCR analysis of the BamH1 W repeat sequences did not identify EBV genomes in tumour samples. Immunohistochemistry for EBNA-1 was also negative. These data exclude EBV as a potential player in TSCC in both old and young patients and highlight the importance of appropriate controls for EBER-ISH in investigating EBV in human diseases.

In being at the base of the marine food web, phytoplankton is particularly important for marine ecosystem functioning (e.g., biodiversity). Strong anthropization, over-exploitation of natural resources, and climate change affect the natural amount of phytoplankton and, therefore, represent a continuous threat to the biodiversity in marine waters. In particular, a concerning risks for coastal waters is the increase in nutrient inputs of terrestrial/anthropogenic origin that can lead to undesirable modifications of phytoplankton concentration (i.e., eutrophication). Monitoring chlorophyll (Chl) concentration, which is a proxy of phytoplankton biomass, is an efficient tool for recording and understanding the response of the marine ecosystem to human pressures and thus for detecting eutrophication. Here, we compute Chl trends over the Mediterranean Sea by using satellite data, also highlighting the fact that remote sensing may represent an efficient and reliable solution to synoptically control the "good environmental status" (i.e., the Marine Directive to achieve Good Environmental Status of EU marine waters by 2020) and to assess the application of international regulations and environmental directives. Our methodology includes the use of an ad hoc regional (i.e., Mediterranean) algorithm for Chl concentration retrieval, also accounting for the difference between offshore (i.e., Case I) and coastal (i.e., Case II) waters. We apply the Mann-Kendall test and the Sens's method for trend estimation to the Chl concentration de-seasonalized monthly time series, as obtained from the X-11 technique. We also provide a preliminary analysis of some particular trends by evaluating their associated inter-annual variability. The high spatial resolution of our approach allows a clear identification of intense trends in those coastal waters that are affected by river outflows. We do not attempt to attribute the observed trends to specific anthropogenic events. However, the trends that we document are consistent with the findings of several previous studies.

Luminescent colloidal nanocrystals (NCs) are emerging as a new tool in neuroscience field, representing superior optical probes for cellular imaging and medical diagnosis of neurological disorders with respect to organic fluorophores. However, only a limited number of studies have, so far, explored NC applications in primary neurons, glia and related cells. Indeed astrocytes, as resident cells in the central nervous system (CNS), play an important pathogenic role in several neurodegenerative and neuroinflammatory diseases, therefore enhanced imaging tools for their thorough investigation are strongly amenable. Here, a comprehensive and systematic study on the in vitro toxicological effect of core-shell type luminescent CdSe@ZnS NCs incorporated in polyethylene glycol (PEG) terminated phospholipid micelles on primary cultures of rat astrocytes was carried out. Cytotoxicity response of empty micelles based on PEG modified phospholipids was compared to that of their NC containing counterpart, in order to investigate the effect on cell viability of both inorganic NCs and micelles protecting NC surface. Furthermore, since the surface charge and chemistry influence cell interaction and toxicity, effect of two different functional groups terminating PEG-modified phospholipid micelles, namely amine and carboxyl group, respectively, was evaluated against bare micelles, showing that carboxyl group was less toxic. The ability of PEG-lipid micelles to be internalized into the cells was qualitatively and quantitatively assessed by fluorescence microscopy and photoluminescence (PL) assay. The results of the experiments clearly demonstrate that, once incorporated into the micelles, a low, not toxic, concentration of NCs is sufficient to be distinctly detected within cells. The overall study provides essential indications to define the optimal experimental conditions to effectively and profitably use the proposed luminescent colloidal NCs as optical probe for future in vivo experiments.

BACKGROUND AND OBJECTIVE:The auditory cortex modulates auditory afferents through the olivocochlear system, which innervates the outer hair cells and the afferent neurons under the inner hair cells in the cochlea. Most of the studies that investigated the efferent activity in humans focused on evaluating the suppression of the otoacoustic emissions by stimulating the contralateral ear with noise, which assesses the activation of the medial olivocochlear bundle. The neurophysiology and the mechanisms involving efferent activity on higher regions of the auditory pathway, however, are still unknown. Also, the lack of studies investigating the effects of noise on human auditory cortex, especially in peadiatric population, points to the need for recording the late auditory potentials in noise conditions. Assessing the auditory efferents in schoolaged children is highly important due to some of its attributed functions such as selective attention and signal detection in noise, which are important abilities related to the development of language and academic skills. For this reason, the aim of the present study was to evaluate the effects of noise on P300 responses of children with normal hearing. METHODS:P300 was recorded in 27 children aged from 8 to 14 years with normal hearing in two conditions: with and whitout contralateral white noise stimulation. RESULTS:P300 latencies were significantly longer at the presence of contralateral noise. No significant changes were observed for the amplitude values. CONCLUSION:Contralateral white noise stimulation delayed P300 latency in a group of school-aged children with normal hearing. These results suggest a possible influence of the medial olivocochlear activation on P300 responses under noise condition.

Recent evidence suggests that humans can form and later retrieve new semantic relations unconsciously by way of hippocampus-the key structure also recruited for conscious relational (episodic) memory. If the hippocampus subserves both conscious and unconscious relational encoding/retrieval, one would expect the hippocampus to be place of unconscious-conscious interactions during memory retrieval. We tested this hypothesis in an fMRI experiment probing the interaction between the unconscious and conscious retrieval of face-associated information. For the establishment of unconscious relational memories, we presented subliminal (masked) combinations of unfamiliar faces and written occupations ("actor" or "politician"). At test, we presented the former subliminal faces, but now supraliminally, as cues for the reactivation of the unconsciously associated occupations. We hypothesized that unconscious reactivation of the associated occupation-actor or politician-would facilitate or inhibit the subsequent conscious retrieval of a celebrity's occupation, which was also actor or politician. Depending on whether the reactivated unconscious occupation was congruent or incongruent to the celebrity's occupation, we expected either quicker or delayed conscious retrieval process. Conscious retrieval was quicker in the congruent relative to a neutral baseline condition but not delayed in the incongruent condition. fMRI data collected during subliminal face-occupation encoding confirmed previous evidence that the hippocampus was interacting with neocortical storage sites of semantic knowledge to support relational encoding. fMRI data collected at test revealed that the facilitated conscious retrieval was paralleled by deactivations in the hippocampus and neocortical storage sites of semantic knowledge. We assume that the unconscious reactivation has pre-activated overlapping relational representations in the hippocampus reducing the neural effort for conscious retrieval. This finding supports the notion of synergistic interactions between conscious and unconscious relational memories in a common, cohesive hippocampal-neocortical memory space.

BackgroundImmunological non-responders (INRs) lacked CD4 increase despite HIV-viremia suppression on HAART and had an increased risk of disease progression. We assessed immune reconstitution profile upon intensification with maraviroc in INRs.MethodsWe designed a multi-centric, randomized, parallel, open label, phase 4 superiority trial. We enrolled 97 patients on HAART with CD4+ResultsBy W48 both groups displayed a CD4 increase without a significant inter-group difference. A statistically significant change in CD8 favored patients in arm HAART+maraviroc versus HAART at W12 (p=.009) and W48 (p=.025). The CD4>200/µL and CD4>200/µL + CD4 gain ≥ 25% end-points were not satisfied at W12 (p=.24 and p=.619) nor at W48 (p=.076 and p=.236). Patients continuing HAART displayed no major changes in parameters of T-cell homeostasis and activation. Maraviroc-receiving patients experienced a significant rise in circulating IL-7 by W48 (p=.01), and a trend in temporary reduction in activated HLA-DR+CD38+CD4+ by W12 (p=.06) that was not maintained at W48.ConclusionsMaraviroc intensification in INRs did not have a significant advantage in reconstituting CD4 T-cell pool, but did substantially expand CD8. It resulted in a low rate of treatment discontinuations.Trial registrationClinicalTrials.gov NCT00884858 http://clinicaltrials.gov/show/NCT00884858.

Mutations in MYO7A cause autosomal recessive Usher syndrome type IB (USH1B), one of the most frequent conditions that combine severe congenital hearing impairment and retinitis pigmentosa. A promising therapeutic strategy for retinitis pigmentosa is gene therapy, however its pre-clinical development is limited by the mild retinal phenotype of the shaker1 (sh1(-/-)) murine model of USH1B which lacks both retinal functional abnormalities and degeneration. Here we report a significant, early-onset delay of sh1(-/-) photoreceptor ability to recover from light desensitization as well as a progressive reduction of both b-wave electroretinogram amplitude and light sensitivity, in the absence of significant loss of photoreceptors up to 12 months of age. We additionally show that subretinal delivery to the sh1(-/-) retina of AAV vectors encoding the large MYO7A protein results in significant improvement of sh1(-/-) photoreceptor and retinal pigment epithelium ultrastructural anomalies which is associated with improvement of recovery from light desensitization. These findings provide new tools to evaluate the efficacy of experimental therapies for USH1B. In addition, although AAV vectors expressing large genes might have limited clinical applications due to their genome heterogeneity, our data show that AAV-mediated MYO7A gene transfer to the sh1(-/-) retina is effective.

OBJECTIVES: (1) To examine relationships among changes in physical activity, physical fitness and some psychosocial determinants of activity behavior in a clinical sample of obese children involved in a multi-component program; (2) to investigate the causal relationship over time between physical activity and one of its strongest correlates (i.e. perceived physical ability). METHODS: Self-reported physical activity and health-related fitness tests were administered before and after a 9-month intervention in 24 boys and 20 girls aged 8 to 11 years. Individuals' perceptions of strength, speed and agility were assessed using the Perceived Physical Ability Scale, while body image was measured using Collins' Child Figure Drawings. RESULTS: Findings showed that body mass index, physical activity, performances on throwing and weight-bearing tasks, perceived physical ability and body image significantly improved after treatment among obese children. Gender differences were found in the correlational analyses, showing a link between actual and perceived physical abilities in boys, but not in girls. For the specific measurement interval of this study, perception of physical ability was an antecedent and not a potential consequence of physical activity. CONCLUSIONS: Results indicate that a multi-component activity program not based merely on a dose-effect approach enhances adherence of the participants and has the potential to increase the lifelong exercise skills of obese children. Rather than focusing entirely on diet and weight loss, findings support the inclusion of interventions directed toward improving perceived physical ability that is predictive of subsequent physical activity.

Buchnera aphidicola is an obligate symbiotic bacterium that sustains the physiology of aphids by complementing their exclusive phloem sap diet. In this study, we reappraised the transport function of different Buchnera strains, from the aphids Acyrthosiphon pisum, Schizaphis graminum, Baizongia pistaciae and Cinara cedri, using the re-annotation of their transmembrane proteins coupled with an exploration of their metabolic networks. Although metabolic analyses revealed high interdependencies between the host and the bacteria, we demonstrate here that transport in Buchnera is assured by low transporter diversity, when compared to free-living bacteria, being mostly based on a few general transporters, some of which probably have lost their substrate specificity. Moreover, in the four strains studied, an astonishing lack of inner-membrane importers was observed. In Buchnera, the transport function has been shaped by the distinct selective constraints occurring in the Aphididae lineages. Buchnera from A. pisum and S. graminum have a three-membraned system and similar sets of transporters corresponding to most compound classes. Transmission electronic microscopic observations and confocal microscopic analysis of intracellular pH fields revealed that Buchnera does not show any of the typical structures and properties observed in integrated organelles. Buchnera from B. pistaciae seem to possess a unique double membrane system and has, accordingly, lost all of its outer-membrane integral proteins. Lastly, Buchnera from C. cedri revealed an extremely poor repertoire of transporters, with almost no ATP-driven active transport left, despite the clear persistence of the ancestral three-membraned system.

The ICF syndrome is a rare autosomal recessive disorder, the most common symptoms of which are immunodeficiency, facial anomalies and cytogenetic defects involving decondensation and instability of chromosome 1, 9 and 16 centromeric regions. ICF is also characterised by significant hypomethylation of the classical satellite DNA, the major constituent of the juxtacentromeric heterochromatin. Here we report the first attempt at analysing some of the defining genetic and epigenetic changes of this syndrome from a nuclear architecture perspective. In particular, we have compared in ICF (Type 1 and Type 2) and controls the large-scale organisation of chromosome 1 and 16 juxtacentromeric heterochromatic regions, their intra-nuclear positioning, and co-localisation with five specific genes (BTG2, CNN3, ID3, RGS1, F13A1), on which we have concurrently conducted expression and methylation analysis. Our investigations, carried out by a combination of molecular and cytological techniques, demonstrate the existence of specific and quantifiable differences in the genomic and nuclear organisation of the juxtacentromeric heterochromatin in ICF. DNA hypomethylation, previously reported to correlate with the decondensation of centromeric regions in metaphase described in these patients, appears also to correlate with the heterochromatin spatial configuration in interphase. Finally, our findings on the relative positioning of hypomethylated satellite sequences and abnormally expressed genes suggest a connection between disruption of long-range gene-heterochromatin associations and some of the changes in gene expression in ICF. Beyond its relevance to the ICF syndrome, by addressing fundamental principles of chromosome functional organisation within the cell nucleus, this work aims to contribute to the current debate on the epigenetic impact of nuclear architecture in development and disease.

Loss of genome-wide methylation is a common feature of cancer, and the degree of hypomethylation has been correlated with genomic instability. Global methylation of repetitive elements possibly arose as a defense mechanism against parasitic DNA elements, including retrotransposons and viral pathogens. Given the alterations of global methylation in both viral infection and cancer, we examined genome-wide methylation levels in head and neck squamous cell carcinoma (HNSCC), a cancer causally associated with human papilloma virus (HPV). We assayed global hypomethylation levels in 26 HNSCC samples, compared with their matched normal adjacent tissue, using Pyrosequencing-based methylation assays for LINE repeats. In addition, we examined cell lines derived from a variety of solid tumors for LINE and SINE (Alu) repeats. The degree of LINE and Alu hypomethylation varied among different cancer cell lines. There was only moderate correlation between LINE and Alu methylation levels, with the range of variation in methylation levels being greater for the LINE elements. LINE hypomethylation was more pronounced in HPV-negative than in HPV-positive tumors. Moreover, genomic instability, as measured by genome-wide loss-of-heterozygosity (LOH) single nucleotide polymorphism (SNP) analysis, was greater in HNSCC samples with more pronounced LINE hypomethylation. Global hypomethylation was variable in HNSCC. Its correlation with both HPV status and degree of LOH as a surrogate for genomic instability may reflect alternative oncogenic pathways in HPV-positive versus HPV-negative tumors.

Mutations in MYO7A cause autosomal recessive Usher syndrome type IB (USH1B), one of the most frequent conditions that combine severe congenital hearing impairment and retinitis pigmentosa. A promising therapeutic strategy for retinitis pigmentosa is gene therapy, however its pre-clinical development is limited by the mild retinal phenotype of the shaker1 (sh1−/−) murine model of USH1B which lacks both retinal functional abnormalities and degeneration. Here we report a significant, early-onset delay of sh1−/− photoreceptor ability to recover from light desensitization as well as a progressive reduction of both b-wave electroretinogram amplitude and light sensitivity, in the absence of significant loss of photoreceptors up to 12 months of age. We additionally show that subretinal delivery to the sh1−/− retina of AAV vectors encoding the large MYO7A protein results in significant improvement of sh1−/− photoreceptor and retinal pigment epithelium ultrastructural anomalies which is associated with improvement of recovery from light desensitization. These findings provide new tools to evaluate the efficacy of experimental therapies for USH1B. In addition, although AAV vectors expressing large genes might have limited clinical applications due to their genome heterogeneity, our data show that AAV-mediated MYO7A gene transfer to the sh1−/− retina is effective. [ABSTRACT FROM AUTHOR]