Biogenesis of circular RNAs and their role in cellular and molecular phenotypes of neurological disorders.

Circular RNA (circRNA) is an unusual class of RNA-like structures composed by exonic and/or intronic sequences that are regulated by the backsplicing mechanism and by the spliceosome-mediated machinery. These circular transcripts tend to accumulate during aging in several human tissues, especially in the mammalian brain, and their expression is correlated with the occurrence of several human pathologies, including a broad spectrum of neurological disorders. Previous findings have also shown that circRNAs are significantly present in the neuronal tissue and are up-regulated during neurogenesis, with a significant number been derived from neural genes, suggesting these circular molecules are involved in the cellular and molecular phenotype of our brain. However, the complete biogenesis, the many types of circRNA molecules, and their involvement with neuronal phenotype and with the occurrence of pathologies are still a challenging avenue for researchers. In this updated review, we discuss the current findings of the biogenesis and the diversity of cirRNAs and their molecular involvement in neurological tissue phenotype. We also discuss how some circRNAs can act as sponge molecules, regulating the activity of microRNA expression over gene translation. Finally, we also show the correlation of altered circRNA expression in neurological disorders.

Downsized: gray whales using an alternative foraging ground have smaller morphology.

Describing individual morphology and growth is key for identifying ecological niches and monitoring the health and fitness of populations. Eastern North Pacific ((ENP), approximately 16 650 individuals) gray whales primarily feed in the Arctic/sub-Arctic regions, while a small subgroup called the Pacific Coast Feeding Group (PCFG, approximately 212 individuals) instead feeds between northern California, USA and British Columbia, Canada. Evidence suggests PCFG whales have lower body condition than ENP whales. Here we investigate morphological differences (length, skull, and fluke span) and compare length-at-age growth curves between ENP and PCFG whales. We use ENP gray whale length-at-age data comprised of strandings, whaling, and aerial photogrammetry (1926-1997) for comparison to data from PCFG whales collected through non-invasive techniques (2016-2022) to estimate age (photo identification) and length (drone-based photogrammetry). We use Bayesian methods to incorporate uncertainty associated with morphological measurements (manual and photogrammetric) and age estimates. We find that while PCFG and ENP whales have similar growth rates, PCFG whales reach smaller asymptotic lengths. Additionally, PCFG whales have relatively smaller skulls and flukes than ENP whales. These findings represent a striking example of morphological adaptation that may facilitate PCFG whales accessing a foraging niche distinct from the Arctic foraging grounds of the broader ENP population.

Self-cleaning cellulose acetate/crystalline nanocellulose/polyvinylidene fluoride/Mg0.975Ni0.025SiO3membrane for removal of diclofenac sodium and methylene blue dye in water.

Recalcitrant pollutants present in wastewater, without an effective treatment, have several effects on aquatic ecosystems and human health due to their chemical structure and persistence. Therefore, it is crucial the development of efficient technologies to eliminate such pollutants in water. Nano-photocatalysts are considered a promising technology for water remediation; however, one common drawback is the difficulty of recovering it after water processing. One effective strategy to overcome such problem is its immobilization into substrates such as polymeric membranes. In this study, a polymeric membrane with embedded Mg0.975Ni0.025SiO3is proposed to remove model pollutants diclofenac sodium and methylene blue dye by synergetic adsorption and photocatalytic processes. Mg0.975Ni0.025SiO3was synthesized by the combustion method. The matrix polymeric blend consisting of a blend of cellulose acetate, crystalline nanocellulose and polyvinylidene fluoride was obtained by the phase inversion method. The composite membranes were characterized by FTIR, x-ray diffraction, and scanning electron microscopy. With pollutant solutions at pH 7, the pollutant adsorption capacity of the membranes reached up to 30% and 45% removal efficiencies for diclofenac sodium and methylene blue, respectively. Under simulated solar irradiation photocatalytic removal performances of 70% for diclofenac sodium pH 7, and of 97% for methylene blue dye at pH 13, were reached. The membrane photocatalytic activity allows the membrane to avoid pollutant accumulation on its surface, given a self-cleaning property that allows the reuse of at least three cycles under sunlight simulator irradiation. These results suggest the high potential of photocatalytic membranes using suitable and economical materials such as cellulosic compounds and magnesium silicates for water remediation.

Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV): Data for the First 5 Years. / Registro de linfomas cutáneos primarios (RELCP) de la AEDV: datos tras 5 años de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas (PCL) are uncommon. Observations based on the first year of data from the Spanish Registry of Primary Cutaneous Lymphomas (RELCP, in its Spanish abbreviation) of the Spanish Academy of Dermatology and Venereology (AEDV) were published in February 2018. This report covers RELCP data for the first 5 years. PATIENTS AND METHODS: RELCP data were collected prospectively and included diagnosis, treatments, tests, and the current status of patients. We compiled descriptive statistics of the data registered during the first 5 years. RESULTS: Information on 2020 patients treated at 33 Spanish hospitals had been included in the RELCP by December 2021. Fifty-nine percent of the patients were men; the mean age was 62.2 years. The lymphomas were grouped into 4 large diagnostic categories: mycosis fungoides/Sézary syndrome, 1112 patients (55%); primary B-cell cutaneous lymphoma, 547 patients (27.1%); primary CD30+lymphoproliferative disorders, 222 patients (11%), and other T-cell lymphomas, 116 patients (5.8%). Nearly 75% of the tumors were registered in stage I. After treatment, 43.5% achieved complete remission and 27% were stable at the time of writing. Treatments prescribed were topical corticosteroids (1369 [67.8%]), phototherapy (890 patients [44.1%]), surgery (412 patients [20.4%]), and radiotherapy (384 patients [19%]). CONCLUSION: The characteristics of cutaneous lymphomas in Spain are similar to those reported for other series. The large size of the RELCP registry at 5 years has allowed us to give more precise descriptive statistics than in the first year. This registry facilitates the clinical research of the AEDV's lymphoma interest group, which has already published articles based on the RELCP data.

Efficient solar removal of acetaminophen contaminant from water using flexible graphene composites functionalized with Ni@TiO2:W nanoparticles.

This work presents the morphological, structural and photocatalytic properties of flexible graphene composites decorated with Ni@TiO2:W nanoparticles (TiNiW NPs) with an average size of 27 ± 2 nm. The TiNiW NPs were immobilized on the surface of a flexible graphene composite using a PVA-based slurry-paste (FG/TiNiW composite). The SEM study showed that the TiNiW NPs remained exposed on the surface of the FG/TiNiW composite, which benefited its photocatalytic activity. The photocatalytic performance for the degradation of acetaminophen (ACT) was evaluated using both the TiNiW powders and the FG/TiNiW composite, obtaining maximum degradation efficiencies of 100 and 86%, respectively, after 3 h under natural solar irradiation. The degradation of ACT was caused mainly by the reactive oxygen species such as OH radicals and h+, which was confirmed by scavenger experiments. Photoluminescence, XPS and absorbance experiments revealed that oxygen vacancy defects were created by i) doping the TiNiW NPs with W and by ii) introducing graphene into the composites. These defects enhanced the absorbance of light in the range of 400-800 nm, which in turn, promoted the photocatalytic degradation of ACT. Moreover, the reuse experiments confirmed that both the TiNiW NPs and FG/TiNiW composite were very stable for the degradation of ACT, since degradation efficiencies >82% were obtained after 4 reuse cycles for both photocatalysts. The experimental findings of this work demonstrate that the flexible TiO2/graphene composites are a feasible option for the removal of pharmaceutical contaminants from water using natural solar irradiation.

Evidence of cooperative calves' care and providers' characteristics in zebu cattle (Bos indicus) raised under extensive conditions.

Communal rearing has been reported in several mammals, including wild ungulates. However, until now, there was no evidence of any alloparental care in the Bos genus. To test the hypothesis that calves' groups are formed under the care of specific cows, a herd of 31 peri-partum zebu cows raised under pasture conditions were used. Groups of ≥ 3 individuals within a 10-m diameter were estimated using aerial pictures taken every other day at 7:00, 10:30, 13:30, 16:00, and 18:00 h, during 6 weeks. Temperament (exit speed, flight distance, intensity of reaction), age, and parity of each cow were registered. A total of 142 groups were observed, and in all of them, at least one calf was present. A total of 75% of the groups were more calves than cows, and in 65.4% of the cases, there were 1 to 3 cows with 2 to 32 calves. While there were no groups integrated only by cows, there were 3.5% integrated only with calves. The most frequent group was formed by 2 calves and 1 cow (14.8%). Parity was positively related with the number of times that a cow was observed in a group (R2 = 0.19, P = 0.01) and with the number of groups in which her calf was present (R2 = 0.16; P = 0.03). The results of the temperament tests were unrelated to the total number of groups in which a cow was observed nor the number of groups with or without its calf. It was concluded that zebu calves congregate in newborn groups in companion with one or more adults, preferably high parity cows, regardless of their temperament.

Beneficial Effects of Soluble Guanylyl Cyclase Stimulation and Activation in Sickle Cell Disease Are Amplified by Hydroxyurea: In Vitro and In Vivo Studies.

The complex pathophysiology of sickle cell anemia (SCA) involves intravascular hemolytic processes and recurrent vaso-occlusion, driven by chronic vascular inflammation, which result in the disease's severe clinical complications, including recurrent painful vaso-occlusive episodes. Hydroxyurea, the only drug frequently used for SCA therapy, is a cytostatic agent, although it appears to exert nitric oxide/soluble guanylyl cyclase (sGC) modulating activity. As new drugs that can complement or replace the use of hydroxyurea are sought to further reduce vaso-occlusive episode frequency in SCA, we investigated the effects of the sGC agonists BAY 60-2770 (sGC activator) and BAY 41-2272 (sGC stimulator) in the presence or absence of hydroxyurea on SCA vaso-occlusive mechanisms and cell recruitment both ex vivo and in vivo. These agents significantly reduced stimulated human SCA neutrophil adhesive properties ex vivo in association with the inhibition of surface ß2-integrin activation. A single administration of BAY 60-2770 or BAY 41-2272 decreased tumor necrosis factor cytokine-induced leukocyte recruitment in a mouse model of SCA vaso-occlusion. Importantly, the in vivo actions of both agonists were significantly potentiated by the coadministration of hydroxyurea. Erythroid cell fetal hemoglobin (HbF) elevation is also a major goal for SCA therapy. BAY 41-2272 but not BAY 60-2770 at the concentrations employed significantly induced γ-globin gene transcription in association with HbF production in cultured erythroleukemic cells. In conclusion, sGC agonist drugs could represent a promising approach as therapy for SCA, for use either as stand-alone treatments or in combination with hydroxyurea. SIGNIFICANCE STATEMENT: This preclinical study demonstrates that stimulators and activators of sGC are potent inhibitors of the adhesion and recruitment of leukocytes from humans and in mice with sickle cell anemia (SCA) and may represent a promising approach for diminishing vaso-occlusive episode frequency in SCA. Hydroxyurea, a drug already frequently used for treating SCA, was found to potentiate the beneficial effects of sGC agonists in in vivo studies, implying that these classes of compounds could be used alone or in combination therapy.

Paediatric nuclear medicine practice: an international survey by the IAEA.

PURPOSE: The International Atomic Energy Agency (IAEA) decided to initiate a survey to evaluate the current status of the practice of paediatric nuclear medicine worldwide, with the focus mainly on low and middle-income countries specifically in Latin America, Eastern Europe, Africa and Asia. This investigation sought to determine if the practice in paediatric nuclear medicine in these countries differed from that indicated by the survey of the Nuclear Medicine Global Initiative (NMGI) and if nuclear medicine practitioners were following established paediatric nuclear medicine guidelines. METHODS: A total of 133 institutes took part in the survey from 62 different IAEA member states within Africa (29), Asia (39), Europe (29) and Latin America (36). The four most frequent conventional (single-photon) nuclear medicine procedures were 99mTc labelled MDP, DSMA, MAG3 and pertechnetate thyroid scans. In addition, 46 centres provided data on FDG PET/CT, including exposure data for the CT component. Nearly half of the sites (48%) perform less than 200 paediatric nuclear medicine studies per year, while 11% perform more than 1000 such studies per year. RESULTS: Administered activities largely exceeded the recommendations for most of the sites for DMSA, MAG3 and pertechnetate, while compliance with international standards was somehow better for MDP studies. For FDG PET, the results were more uniform than for conventional nuclear medicine procedures. However, the use of CT in PET/CT for paediatric nuclear medicine revealed a high variability and, in some cases, high, dose-length product (DLP) values. This observation indicates that further attention is warranted for optimizing clinical practice in FDG PET/CT. CONCLUSIONS: Overall, in most parts of the world, efforts have been undertaken to comply either with the EANM dosage card or with the North American Consensus Guidelines. However, variability in the practice of paediatric nuclear medicine still exists. The results of this survey provide valuable recommendations for a path towards global standardization of determining the amount of activity to be administered to children undergoing nuclear medicine procedures.

Stroke in systemic lupus erythematosus: epidemiology, mechanism, and long-term outcome.

OBJECTIVE: To determine stroke prevalence, mechanisms, and long-term outcome in a cohort of Hispanic patients with systemic lupus erythematosus (SLE). METHODS: We analyzed demographical data, the timing between SLE diagnosis and stroke onset, stroke type, recurrence, and outcomes from an institutional database of 4451 patients with SLE followed from 1993 to 2018. RESULTS: We observed 139 strokes (3.1%), for an incidence rate of 1.25 per 1000 person-years: 81 (58.3%) acute ischemic stroke (AIS), 19 (13.7%) subarachnoid hemorrhage (SAH), 17 (12.2%) cerebral venous thrombosis, 13 (9.4%) intracerebral hemorrhage (ICH), and 9 (6.5%) transient ischemic attack. Median time from SLE diagnosis to acute stroke was 60 months (interquartile range 12-132 months). AIS had a bimodal presentation with 26% occurring within the first year and 30% >10 years after SLE diagnosis. In contrast, 75% of ICH cases occurred >3 years (and 34% >10 years) after SLE diagnosis. The most important cause of AIS was secondary antiphospholipid syndrome (48%). Hypertension was associated with 69% of ICH cases, while aneurysmal rupture was observed in 78% of SAH cases. Excellent recovery at hospital discharge was observed in 65%. Stroke recurrence was observed in 7%. The long-term all-cause fatality rate was 8%. CONCLUSIONS: The prevalence of stroke in this cohort was 3.1%. Ischemic strokes had a bimodal presentation, occurring either early after SLE diagnosis or after a several-year delay. Half of the hemorrhagic strokes occurred >10 years after the diagnosis of SLE. Clinical outcome was usually good with a relatively low recurrence rate.

Positive prostate biopsy following radiotherapy can predict metastasis-free survival in localized prostate cancer.

BACKGROUND/AIMS: To determine the impact of post-treatment biopsy results on 10-year metastasis-free survival (MFS), overall survival (OS) and cause-specific survival (CSS) in localized prostate cancer (PCa) patients treated with high-dose radiotherapy (RT). MATERIALS/METHODS: Retrospective analysis of 232 patients with T1c-T3bN0M0 PCa who underwent a prostate biopsy 24-36 months after high-dose RT. Biopsies were categorized as positive biopsy (PB) if H&E staining showed evidence of residual malignancy and negative biopsy (NB) if no malignant cells were present. Kaplan-Meier estimates of 10-year MFS, OS and CSS rates were calculated for each group and Cox proportional-hazards models were used to estimate the hazard ratios. The median follow-up was 124 months (range 26-267). RESULTS: Sixty-two of 232 (26.7%) patients had post-treatment positive biopsies (PB). A positive post-treatment biopsy was significantly associated with a lower 10-year MFS (78.4% vs. 95.4%, p = 0.001, HR: 3.9, 95% CI: 1.8-8.3). Although patients with PB had worse outcomes that those with NB, we could not show a statistically significant difference in OS (81.0% vs. 87.9%, p = 0.282, HR: 1.3, 95% CI: 0.7-2.3) or CSS (96.2% vs. 99.4% (p = 0.201, HR. 2.4, 95% CI: 0.6-9.7). After multivariate analysis, the strongest predictor of MFS was the post-treatment biopsy status (p < 0.001, HR: 5.4, 95% CI 2.26-12.85) followed by Gleason score (p = 0.002, HR: 2.24, 95% CI 1.33-3.79). CONCLUSION: A positive biopsy following RT can predict MFS in localized prostate cancer. These data highlight the relevance of achieving a local control and support the use of aggressive local therapeutic interventions for PCa.

Hepatocyte growth factor is a potential biomarker for osteoproliferation and osteoporosis in ankylosing spondylitis.

We explored relations between serum hepatocyte growth factor (HGF), disease activity, osteoproliferation, and bone mineral density (BMD) in ankylosing spondylitis (AS), in comparison with healthy controls. HGF was increased especially in male AS patients and smokers and associated with both lower BMD and more chronic radiographic changes in the spine. INTRODUCTION: Ankylosing spondylitis (AS) is characterized by both osteoproliferation and increased bone loss. Biomarkers are requested to predict the processes. The aims of this study were to compare serum levels of hepatocyte growth factor (HGF), matrix metalloproteinase-3 (MMP-3), and vascular endothelial growth factor (VEGF) in AS patients with healthy controls (HC) and to explore the associations with disease activity, osteoproliferation, and bone mineral density (BMD). METHODS: Serum from AS patients (modified NY-criteria) and HC was analyzed for HGF, MMP-3, and VEGF with ELISA. Disease activity parameters were collected. Osteoproliferation was assessed with modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and BMD was measured in femoral neck. RESULTS: Totally, 204 AS patients and 80 sex and age matched HC were included. Serum HGF was higher in the AS patients compared with the HC, whereas serum MMP-3 and VEGF were not. Serum HGF was also higher in smokers and in the male AS patients positively correlated with age, BASMI, and mSASSS, and negatively correlated with BMD. The biomarkers were all positively associated with ESR, CRP, and WBC. In multiple linear regression analysis serum HGF remained associated with higher mSASSS and lower BMD, after adjusting for age, sex, CRP, smoking, and body mass index. CONCLUSIONS: Serum HGF was increased in male AS patients and associated with higher mSASSS and lower BMD. In addition, serum HGF was positively associated with risk factors for osteoproliferation such as age, CRP and smoking. HGF could be a potential biomarker of importance for the bone metabolism in AS. TRIAL REGISTRATION: NCT00858819.

Discrete-choice experiment to analyse preferences for centralizing specialist cancer surgery services.

BACKGROUND: Centralizing specialist cancer surgery services aims to reduce variations in quality of care and improve patient outcomes, but increases travel demands on patients and families. This study aimed to evaluate preferences of patients, health professionals and members of the public for the characteristics associated with centralization. METHODS: A discrete-choice experiment was conducted, using paper and electronic surveys. Participants comprised: former and current patients (at any stage of treatment) with prostate, bladder, kidney or oesophagogastric cancer who previously participated in the National Cancer Patient Experience Survey; health professionals with experience of cancer care (11 types including surgeons, nurses and oncologists); and members of the public. Choice scenarios were based on the following attributes: travel time to hospital, risk of serious complications, risk of death, annual number of operations at the centre, access to a specialist multidisciplinary team (MDT) and specialist surgeon cover after surgery. RESULTS: Responses were obtained from 444 individuals (206 patients, 111 health professionals and 127 members of the public). The response rate was 52·8 per cent for the patient sample; it was unknown for the other groups as the survey was distributed via multiple overlapping methods. Preferences were particularly influenced by risk of complications, risk of death and access to a specialist MDT. Participants were willing to travel, on average, 75 min longer in order to reduce their risk of complications by 1 per cent, and over 5 h longer to reduce risk of death by 1 per cent. Findings were similar across groups. CONCLUSION: Respondents' preferences in this selected sample were consistent with centralization.

Clinical and nerve conduction features in Guillain-Barré syndrome associated with Zika virus infection in Cúcuta, Colombia.

BACKGROUND AND PURPOSE: Zika virus (ZIKV) infection has been associated with an increased incidence of Guillain-Barré syndrome (GBS) but the relative frequency of acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and axonal GBS subtypes is controversial. METHODS: Twenty GBS patients diagnosed according to the Brighton criteria during the ZIKV outbreak in Cúcuta, Colombia, were evaluated clinically and electrophysiologically. The electrodiagnosis of GBS subtypes was made according to a recently described criteria set that demonstrated a high diagnostic accuracy on the basis of a single test. The electrophysiological features of 34 Italian AIDP patients were used as control. RESULTS: All patients had symptoms compatible with ZIKV infection before the onset of GBS and ZIKV infection was laboratory confirmed through a plaque reduction neutralization test (PRNT90 ) in 100% of patients. The median time from onset of ZIKV infection symptoms to GBS was 5 days (interquartile range 1-6 days). Cranial nerve palsy was present in 85% of patients (facial palsy in 75%, bulbar nerve involvement in 60%), autonomic dysfunction in 85%, and 50% of patients required invasive mechanical ventilation. AIDP was diagnosed in 70% of patients. 40% of nerves of AIDP patients showed a prevalent distal demyelinating involvement but this pattern was not different from the Italian AIDP patients without ZIKV infection. CONCLUSIONS: Guillain-Barré syndrome associated with ZIKV infection in Cúcuta is characterized by a high frequency of cranial nerve involvement, autonomic dysfunction and requirement of mechanical ventilation indicating an aggressive and severe course. AIDP is the most frequent electrophysiological subtype. Demyelination is prevalent distally but this pattern is not specific for ZIKV infection.

Transorbital ultrasonography for measuring optic nerve atrophy in multiple sclerosis.

OBJECTIVE: we aimed to evaluate the utility of transorbital ultrasonography (TOS) in optic nerve assessment and quantification of ON atrophy in MS patients, and to determine whether ON atrophy correlates with the disease duration and disability measured on the Kurtzke Expanded Disability Status Scale (EDSS). MATERIALS AND METHODS: Prospective, multicentre, blinded cohort study of 59 patients diagnosed with relapsing-remitting MS and 36 controls. RESULTS: When measured with TOS, the diameter of both the right (2.69 ± 0.30 mm in cases; 3.20 ± 0.19 mm in controls, P < .0001) and left (2.71 ± 0.26 mm in cases; 3.24 ± 0.15 mm controls, P < .0001) ON of study patients was smaller than controls. We observed a negative correlation between EDSS and both right (ρ = .524) and left (ρ = .469) ON diameter. We also observed a negative correlation between disease duration and both right (r = .602) and left (r = .538) ON diameter. No difference was observed in the diameter of both ON among patients with a history of optic neuritis (right OND 2.68 ± 0.29 mm; left OND 2.69 ± 0.25 mm) and patients with no history of optic neuritis (right OND 2.70 ± 0.30 mm; left OND 2.73 ± 0.27 mm) (P = .805; P = .651). CONCLUSIONS: The thickness of ON measured with TOS is correlated with EDSS and the duration of the disease without being interfered by the previous history of optic neuritis. TOS could be a reliable technique for measuring ON atrophy in MS.

Directional control of charge and valley currents in a graphene-based device.

We propose a directional switching effect in a metallic device. To this end we exploit a graphene-based device with a three-terminal geometry in the presence of a magnetic field. We show that unidirectional charge and valley currents can be controlled by the Fermi energy and the magnetic field direction in the active device. Interestingly, unidirectional transport of charges and valleys is generated between two-terminals at the same bias voltage. Furthermore, we quantify the valley depolarization as a function of disorder concentration. Our results open a way for active graphene-based valleytronics devices.

Altered neuronal network and rescue in a human MECP2 duplication model.

Increased dosage of methyl-CpG-binding protein-2 (MeCP2) results in a dramatic neurodevelopmental phenotype with onset at birth. We generated induced pluripotent stem cells (iPSCs) from patients with the MECP2 duplication syndrome (MECP2dup), carrying different duplication sizes, to study the impact of increased MeCP2 dosage in human neurons. We show that cortical neurons derived from these different MECP2dup iPSC lines have increased synaptogenesis and dendritic complexity. In addition, using multi-electrodes arrays, we show that neuronal network synchronization was altered in MECP2dup-derived neurons. Given MeCP2 functions at the epigenetic level, we tested whether these alterations were reversible using a library of compounds with defined activity on epigenetic pathways. One histone deacetylase inhibitor, NCH-51, was validated as a potential clinical candidate. Interestingly, this compound has never been considered before as a therapeutic alternative for neurological disorders. Our model recapitulates early stages of the human MECP2 duplication syndrome and represents a promising cellular tool to facilitate therapeutic drug screening for severe neurodevelopmental disorders.

Clinical and microbiological profile of chronic Burkholderia cepacia complex infections in a cystic fibrosis reference hospital in Brazil.

Burkholderia sp. infections are extremely complex in cystic fibrosis (CF) patients, especially considering the lack of knowledge regarding its behavior, its relationship with prognosis, as well as its transmissibility and multidrug resistance features. This study evaluated the frequency of chronic infection by Burkholderia, using microbiological and clinical data. Ninety-eight patients with CF attended from July 2011 to April 2014 in a Brazilian reference hospital were included. Antimicrobial activity, molecular epidemiology, Shwachman score, body mass index, exacerbations, and lung function were analyzed. Nine patients had chronic colonization, and all of them showed preserved pulmonary function levels, body mass index, and Shwachman score. Meropenem was the most effective antibiotic; however, divergent results were shown by other studies. Cross-contamination may have occurred in only two unrelated patients of different ages, who were colonized by B. vietnamiensis, which does not occur frequently. Twelve new sequence types (STs) were identified and three STs have presented intercontinental distribution. None of the patients presented known epidemic strains. In conclusion, a relatively low number of patients with chronic colonization and suspected cross-infection were identified. Different from other studies that have found CF patients chronically colonized with Burkholderia sp. having a greater deterioration of lung function, more frequent antibiotic therapy, and increased mortality, in the current study, the patients showed good clinical outcomes and favorable options for antibiotics therapy. This study also updated the epidemiological database, which facilitates the multicentric collaborative analysis and assists in the control of global infection by these pathogens.

Cost-Effectiveness Methods and Newborn Screening Assessment.

Nowadays, health funding decisions must be supported by sound arguments in terms of both effectiveness and economic criteria. After more than half a century of newborn screening for rare diseases, the appropriate economic evaluation framework for these interventions is still challenging. The validity of standard methods for economic evaluation heavily relies on the availability of robust evidence, but collection of such evidence is precluded by the rareness of the conditions that may benefit from screening. Furthermore, there are a series of conceptual and methodological limitations that warrant further careful consideration when assessing the cost-effectiveness of newborn screening programs. In this chapter we provide a general overview of current economic evaluation methods and the challenges for their application to newborn screening programs.

Autoinflammatory Diseases in Pediatric Dermatology-Part 2: Histiocytic, Macrophage Activation, and Vasculitis Syndromes. / Enfermedades autoinflamatorias en dermatología pediátrica. Parte 2: síndromes histiocítico-macrofágicos y síndromes vasculopáticos.

The discovery of new autoinflammatory syndromes and novel mutations has advanced at breakneck speed in recent years. Part 2 of this review focuses on vasculitis syndromes and the group of histiocytic and macrophage activation syndromes. We also include a table showing the mutations associated with these autoinflammatory syndromes and treatment alternatives.