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    Confirmed presence of aedes (rusticoidus) refiki Medschid, 1928 in a continental dry Mediterranean peri-urban environment in south-central Spain

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    Background The 'snow-melt mosquito' aedes (rusticoidus) refiki is a rare species with a wide distribution in Europe that is usually defined as an aggressive mosquito for mammals, including humans. During a mosquito survey in a peri-urban area in south-central mainland Spain, adult Ae. refiki females were captured and identified by morphological traits. The presence of this species of mosquito has never been molecularly confirmed under continental dry Mediterranean climatic influence with scarce number of days with snow on soil. The aim of this study was to confirm by amplification and sequencing of mitochondrial cytochrome c oxidase subunit I (COI) and internal transcribed spacer 2 (ITS2) region. Results We also successfully amplified and typed the species molecularly by COI and ITS2 regions. The peri-urban area where Ae. refiki was found contrasts with the reported cold, humid and snowy environments required by the species to breed. Conclusions This finding suggests that the species is already adapted to continental dry Mediterranean environments, questioning whether it is a truly stenotopic species of cold snowy environments.S

    Artificial intelligence in COVID-19 evidence syntheses was underutilized, but impactful: a methodological study.

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    A rapidly developing scenario like a pandemic requires the prompt production of high-quality systematic reviews, which can be automated using artificial intelligence (AI) techniques. We evaluated the application of AI tools in COVID-19 evidence syntheses. After prospective registration of the review protocol, we automated the download of all open-access COVID-19 systematic reviews in the COVID-19 Living Overview of Evidence database, indexed them for AI-related keywords, and located those that used AI tools. We compared their journals' JCR Impact Factor, citations per month, screening workloads, completion times (from pre-registration to preprint or submission to a journal) and AMSTAR-2 methodology assessments (maximum score 13 points) with a set of publication date matched control reviews without AI. Of the 3,999 COVID-19 reviews, 28 (0.7%, 95% CI 0.47-1.03%) made use of AI. On average, compared to controls (n = 64), AI reviews were published in journals with higher Impact Factors (median 8.9 vs. 3.5, P  AI was an underutilized tool in COVID-19 systematic reviews. Its usage, compared to reviews without AI, was associated with more efficient screening of literature and higher publication impact. There is scope for the application of AI in automating systematic reviews.S

    Combined Magnetic Hyperthermia and Photothermia with Polyelectrolyte/Gold-Coated Magnetic Nanorods

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    Magnetite nanorods (MNRs) are synthesized based on the use of hematite nanoparticles of the desired geometry and dimensions as templates. The nanorods are shown to be highly monodisperse, with a 5:1 axial ratio, and with a 275 nm long semiaxis. The MNRs are intended to be employed as magnetic hyperthermia and photothermia agents, and as drug vehicles. To achieve a better control of their photothermia response, the particles are coated with a layer of gold, after applying a branched polyethyleneimine (PEI, 2 kDa molecular weight) shell. Magnetic hyperthermia is performed by application of alternating magnetic fields with frequencies in the range 118-210 kHz and amplitudes up to 22 kA/m. Photothermia is carried out by subjecting the particles to a near-infrared (850 nm) laser, and three monochromatic lasers in the visible spectrum with wavelengths 480 nm, 505 nm, and 638 nm. Best results are obtained with the 505 nm laser, because of the proximity between this wavelength and that of the plasmon resonance. A so-called dual therapy is also tested, and the heating of the samples is found to be faster than with either method separately, so the strengths of the individual fields can be reduced. Due to toxicity concerns with PEI coatings, viability of human hepatoblastoma HepG2 cells was tested after contact with nanorod suspensions up to 500 mu g/mL in concentration. It was found that the cell viability was indistinguishable from control systems, so the particles can be considered non-cytotoxic in vitro. Finally, the release of the antitumor drug doxorubicin is investigated for the first time in the presence of the two external fields, and of their combination, with a clear improvement in the rate of drug release in the latter case.This research was funded by Junta de Andalucía, Spain, Consejería de Economía y Conocimiento/Proyectos de I + D + I del Plan Andaluz de Investigación, Desarrollo e Innovación/Grants P20_00346, P20_00233. Ministerio de Ciencia e Innovación, Spain, Plan Estatal I+D+I 2017-2020/Grant EQC2019-005930-P. Ministerio de Economía y Competitividad, Spain, Grant PID2019-109294RB-100.S

    Cerebral metabolic pattern associated with progressive parkinsonism in non-human primates reveals early cortical hypometabolism.

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    Dopaminergic denervation in patients with Parkinson's disease is associated with changes in brain metabolism. Cerebral in-vivo mapping of glucose metabolism has been studied in severe stable parkinsonian monkeys, but data on brain metabolic changes in early stages of dopaminergic depletion of this model is lacking. Here, we report cerebral metabolic changes associated with progressive nigrostriatal lesion in the pre-symptomatic and symptomatic stages of the progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model of Parkinson's Disease. Monkeys (Macaca fascicularis) received MPTP injections biweekly to induce progressive grades of dopamine depletion. Monkeys were sorted according to motor scale assessments in control, asymptomatic, recovered, mild, and severe parkinsonian groups. Dopaminergic depletion in the striatum and cerebral metabolic patterns across groups were studied in vivo by positron emission tomography (PET) using monoaminergic ([11C]-dihydrotetrabenazine; 11C-DTBZ) and metabolic (2-[18F]-fluoro-2-deoxy-d-glucose; 18F-FDG) radiotracers. 11C-DTBZ-PET analysis showed progressive decrease of binding potential values in the striatum of monkeys throughout MPTP administration and the development of parkinsonian signs. 18F-FDG analysis in asymptomatic and recovered animals showed significant hypometabolism in temporal and parietal areas of the cerebral cortex in association with moderate dopaminergic nigrostriatal depletion. Cortical hypometabolism extended to involve a larger area in mild parkinsonian monkeys, which also exhibited hypermetabolism in the globus pallidum pars interna and cerebellum. In severe parkinsonian monkeys, cortical hypometabolism extended further to lateral-frontal cortices and hypermetabolism also ensued in the thalamus and cerebellum. Unbiased histological quantification of neurons in Brodmann's area 7 in the parietal cortex did not reveal neuron loss in parkinsonian monkeys versus controls. Early dopaminergic nigrostriatal depletion is associated with cortical, mainly temporo-parietal hypometabolism unrelated to neuron loss. These findings, together with recent evidence from Parkinson's Disease patients, suggest that early cortical hypometabolism may be associated and driven by subcortical changes that need to be evaluated appropriately. Altogether, these findings could be relevant when potential disease modifying therapies become available.S

    Diagnostic accuracy of sliding sign for detecting pouch of Douglas obliteration and bowel involvement in women with suspected endometriosis: systematic review and meta-analysis.

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    The aim of this systematic review and meta-analysis was to evaluate the diagnostic accuracy of the sliding sign on transvaginal ultrasound (TVS) in detecting pouch of Douglas obliteration and bowel involvement in patients with suspected endometriosis, using laparoscopy as the reference standard. A search for studies evaluating the role of the sliding sign in the assessment of pouch of Douglas obliteration and/or bowel involvement using laparoscopy as the reference standard published from January 2000 to October 2021 was performed in PubMed/MEDLINE, Web of Science, CINAHL, The Cochrane Library, ClinicalTrials.gov and SCOPUS databases. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to evaluate the quality of the studies. Analyses were performed using MIDAS and METANDI commands in STATA. A total of 334 citations were identified. Eight studies were included in the analysis, resulting in 938 and 963 patients available for analysis of the diagnostic accuracy of the sliding sign for pouch of Douglas obliteration and bowel involvement, respectively. The mean prevalence of pouch of Douglas obliteration was 37% and the mean prevalence of bowel involvement was 23%. The pooled estimated sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of the sliding sign on TVS for detecting pouch of Douglas obliteration were 88% (95% CI, 81-93%), 94% (95% CI, 91-96%), 15.3 (95% CI, 10.2-22.9), 0.12 (95% CI, 0.07-0.21) and 123 (95% CI, 62-244), respectively. The heterogeneity was moderate for sensitivity and low for specificity for detecting pouch of Douglas obliteration. The pooled estimated sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of the sliding sign on TVS for detecting bowel involvement were 81% (95% CI, 64-91%), 95% (95% CI, 91-97%), 16.0 (95% CI, 9.0-28.6), 0.20 (95% CI, 0.10-0.40) and 81 (95% CI, 34-191), respectively. The heterogeneity for the meta-analysis of diagnostic accuracy for bowel involvement was high. The sliding sign on TVS has good diagnostic performance for predicting pouch of Douglas obliteration and bowel involvement in women with suspected endometriosis. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology

    Clinical Characteristics and Prognostic Relevance of Different Types of Caregivers for Elderly Patients with Acute Heart Failure-Analysis from the RICA Registry.

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    Background: Patients with heart failure encompass a heterogeneous group, but they are mostly elderly patients with a large burden of comorbid conditions. Objective: The aim of this study was to compare the clinical characteristics and the prognostic impact on hospital admissions and mortality in a population of patients with HF with different types of caregivers (family members, professionals, and the patient himself). Methods: We conducted an observational study from a prospective registry. Patients from the National Registry of Heart Failure (RICA), which belongs to the Working Group on Heart Failure and Atrial Fibrillation of the Spanish Society of Internal Medicine (SEMI), were included. Patients with heart failure were classified, according to the type of main caregiver, into four groups: the patient himself/herself, a partner, children, or a professional caregiver. A bivariable analysis was performed between the clinical, analytical, therapeutic, and prognostic characteristics of the different groups. The endpoints of the study were all-cause mortality at 1 year; mortality at 120 days; and the readmission rate for HF at 30 days, 120 days, and 1 year of follow-up. In all cases, the level of statistical significance was set at p< 0.05. Results: A total of 2147 patients were enrolled in this study; women represented 52.4%, and the mean age was 81 years. The partner was the caregiver for 703 patients, children were caregivers for 1097 patients, 199 patients had a professional caregiver, and only 148 patients were their own caregivers. Women were more frequently cared for by their children (65.8%) or a professional caregiver (61.8%); men were more frequently cared for by their spouses (68.7%) and more frequently served as their own caregivers (59.5%) (p < 0.001). No statistically significant differences were observed in relation to readmissions or mortality at one year of follow-up between the different groups. A lower probability of readmission and death was observed for patients who received care from a partner or children/relative, with log-rank scores of 11.2 with p= 0.010 and 10.8 with p = 0.013. Conclusions: Our study showed that the presence of a family caregiver for elderly patients with heart failure was associated with a lower readmission rate and a lower mortality rate at 120 days of follow-up. Our study also demonstrated that elderly patients with good cognitive and functional status can be their own caregivers, as they obtained good health outcomes in terms of readmission and mortality. More prospective studies and clinical trials are needed to evaluate the impact of different types of caregivers on the outcomes of patients with heart failure.S

    Responsiveness of the new index muscular echotexture in women with metastatic breast cancer: an exercise intervention study.

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    Ultrasound imaging texture analyses may provide information on tissue homogeneity changes in metastatic breast cancer (MBC) through second-order analyzes based on the gray-level co-occurrence matrix. This study aimed to analyze the responsiveness and correlations of biomarkers of muscular and fat echotexture after an exercise intervention in women with MBC. A 12-week exercise intervention was conducted in 2019, including aerobic and strength training. Echotexture variables were obtained at baseline and after intervention from the quadriceps (Q) and biceps brachii and brachialis. Mean differences were calculated using the T-Student parametric test for dependent samples of the differences in the means (P = 0.05; 95% CI). Data obtained from 13 MBC women showed significant differences in some echotexture variables after the intervention. QLQ-BR23 questionnaire correlated with several echotexture variables from muscle and subcutaneous fat. PFS-R scale correlated positively with the Q Subcutaneous Fat Non-Contraction Homogeneity (R = 0.43, P &lt; 0.05). Q Muscle Non-Contraction Energy and Q Muscle Non-Contraction Textural Correlation explained 90% of the variance of QLQ-BR23. Some muscle and subcutaneous fat echotexture biomarkers showed good responsiveness after the exercise intervention. Additionally, some muscle and subcutaneous fat variables correlated with QLQ-BR23 and cancer-related fatigue measured by PFS-R scale in MBC patients.S

    Study of Oligonucleotides Access and Distribution in Human Peripheral Blood Mononuclear Cells.

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    Therapeutic oligonucleotides have achieved great clinical interest since their approval as drug agents by regulatory agencies but their access and distribution in blood cells are not completely known. We evaluated by flow cytometry the ability of short fluorescent scramble oligonucleotides (ON*) to access human peripheral blood mononuclear cells (PBMC) after incubating with ON* during 1 h and 7 days of culture follow-up 'in vitro'. Blood samples were treated with chemically modified oligonucleotides (phosphorothioate backbone and 2' O-Me ends) to resist nuclease digestion under culture conditions. The ON* internalization was determined after discarding the membrane-associated fluorescence by trypan blue quenching. Whereas the oligonucleotide accessed neutrophils and monocytes rapidly, achieving their maximum in 1 h and 24 h, respectively, lymphocytes required 7 days to achieve the maximum (80% of cells) transfection. The ON*ability to access lymphocyte types (T, B, and NK) and T cell subtypes (CD4+, CD8+, and CD4-CD8-) were similar, with T cells being more accessible. Regulatory CD4+ and CD8+ T cells were classified in low and high Foxp3 expressers, whose expression proved not to alter the ON* internalization during the first hour, achieving 53% of CD4+Foxp3+ and 40% of CD8+Foxp3+ cells. Our results contribute to understanding and improving the management of therapeutic ONs.S

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