Paramagnetic Singularities of the Orbital Magnetism in Graphene with a Moiré Potential.

The recent detection of the singular diamagnetism of Dirac electrons in a single graphene layer paved a new way of probing 2D quantum materials through the measurement of equilibrium orbital currents which cannot be accessed in usual transport experiments. Among the theoretical predictions is an intriguing orbital paramagnetism at saddle points of the dispersion relation. Here we present magnetization measurements in graphene monolayers aligned on hexagonal boron nitride crystals. Besides the sharp diamagnetic McClure response at the Dirac point, we detect extra diamagnetic singularities at the satellite Dirac points of the moiré lattice. Surrounding these diamagnetic satellite peaks, we also observe paramagnetic peaks located at the chemical potential of the saddle points of the graphene moiré band structure and relate them to the presence of van Hove logarithmic singularities in the density of states. These findings reveal the long ago predicted anomalous paramagnetic orbital response in 2D systems when the Fermi energy is tuned to the vicinity of saddle points.

Epidemiological factors related to hospitalization due to influenza in children below 6 months of age.

The aim of this study was to address the epidemiological factors associated to hospital admissions due to influenza in infants younger than 6 months. A case-control study was performed in a tertiary hospital in Spain. Cases were infants under 6 months of age without comorbidities who were admitted due to influenza between October 2010 and March 2015. Controls were healthy infants younger than 6 months who were hospitalized due to non-respiratory illness or non-infectious diseases (urinary tract infection was included as controls). Data were retrospectively collected from medical records and phone interviews. A total of 88 cases and 122 controls we included. From univariate analysis, differences were found in relation to maternal age (43.1 ± 4.95 vs 32 ± 5.3), paternal age (37 ± 6.4 vs 34.5 ± 6.1), having siblings (79 vs 24%), siblings below 4 years old (54 vs 15%), and having vaccinated grandparents (18 vs 39%) (p < 0.05). After logistic regression, having vaccinated grandparents was an independent protective factor (OR 0.22 [CI95%; 0.05-0.91]), while having siblings was a risk factor (OR 15.8 [CI95% 3.15-79.5]). Vaccination during pregnancy was highly uncommon (3.5 vs 8.3%; p = 0.3). CONCLUSION: This study underlines the importance of increasing influenza immunization among household contacts of infants below 6 months to prevent their influenza admission. What is Known: • Infants younger than 6 months old are considered a high-risk population. • Vaccination against influenza is not licensed in infants below 6 months. What is New: • Increasing vaccination coverage in elderly people could reduce infants' hospitalization rates. • Cocoon immunization strategy may reduce the admission of infants.

A genome-wide association study of pulmonary tuberculosis in Morocco.

Although epidemiological evidence suggests a human genetic basis of pulmonary tuberculosis (PTB) susceptibility, the identification of specific genes and alleles influencing PTB risk has proven to be difficult. Previous genome-wide association (GWA) studies have identified only three novel loci with modest effect sizes in sub-Saharan African and Russian populations. We performed a GWA study of 550,352 autosomal SNPs in a family-based discovery Moroccan sample (on the full population and on the subset with PTB diagnosis at <25 years), which identified 143 SNPs with p < 1 × 10(-4). The replication study in an independent case/control sample identified four SNPs displaying a p < 0.01 implicating the same risk allele. In the combined sample including 556 PTB subjects and 650 controls these four SNPs showed suggestive association (2 × 10(-6) < p < 4 × 10(-5)): rs358793 and rs17590261 were intergenic, while rs6786408 and rs916943 were located in introns of FOXP1 and AGMO, respectively. Both genes are involved in the function of macrophages, which are the site of latency and reactivation of Mycobacterium tuberculosis. The most significant finding (p = 2 × 10(-6)) was obtained for the AGMO SNP in an early (<25 years) age-at-onset subset, confirming the importance of considering age-at-onset to decipher the genetic basis of PTB. Although only suggestive, these findings highlight several avenues for future research in the human genetics of PTB.

Impairment of striatal mitochondrial function by acute paraquat poisoning.

Mitochondria are essential for survival. Their primary function is to support aerobic respiration and to provide energy for intracellular metabolic pathways. Paraquat is a redox cycling agent capable of generating reactive oxygen species. The aim of the present study was to evaluate changes in cortical and striatal mitochondrial function in an experimental model of acute paraquat toxicity and to compare if the brain areas and the molecular mechanisms involved were similar to those observed after chronic exposure. Sprague-Dawley rats received paraquat (25 mg/Kg i.p.) or saline and were sacrificed after 24 h. Paraquat treatment decreased complex I and IV activity by 37 and 21 % respectively in striatal mitochondria. Paraquat inhibited striatal state 4 and state 3 KCN-sensitive respiration by 80 % and 62 % respectively, indicating a direct effect on respiratory chain. An increase of 2.2 fold in state 4 and 2.3 fold in state 3 in KCN-insensitive respiration was observed in striatal mitochondria from paraquat animals, suggesting that paraquat redox cycling also consumed oxygen. Paraquat treatment increased hydrogen peroxide production (150 %), TBARS production (42 %) and cardiolipin oxidation/depletion (12 %) in striatal mitochondria. Also, changes in mitochondrial polarization was induced after paraquat treatment. However, no changes were observed in any of these parameters in cortical mitochondria from paraquat treated-animals. These results suggest that paraquat treatment induced a clear striatal mitochondrial dysfunction due to both paraquat redox cycling reactions and impairment of the mitochondrial electron transport, causing oxidative damage. As a consequence, mitochondrial dysfunction could probably lead to alterations in cellular bioenergetics.

Oxygen metabolism in human placenta mitochondria.

Due to the high metabolic demands of the placental tissue during gestation, we decide to analyzed the mitochondrial bioenergetic functions in the human term placenta. Different mitochondrial morphological parameters, membrane potential and cardiolipin content were determined by flow cytometry. Oxygen uptake, hydrogen peroxide production and cytochrome P450 content, were also measured. Some apoptotic mitochondrial proteins were also analyzed by western blot. Two isolated mitochondrial fractions were observed: large/heavy and small/light with different functional characteristics. Oxygen uptake showed a respiratory control (RC) of 3.4 ± 0.3 for the heavy mitochondria, and 1.1 ± 0.4 for light mitochondria, indicating a respiratory dysfunction in the light fraction. Good levels of polarization were detected in the heavy fraction, meanwhile the light population showed a collapsed ΔΨm. Increased levels of cytochrome P450, higher levels of hydrogen peroxide, and low cardiolipin content were described for the light fraction. Three pro-apoptotic proteins p53, Bax, and cytochrome c were found increased in the heavy mitochondrial fraction; and deficient in the light fraction. The heavy mitochondrial fraction showed an improved respiratory function. This mitochondrial fraction, being probably from cytotrophoblast cells showed higher content of proteins able to induce apoptosis, indicating that these cells can effectively execute an apoptotic program in the presence of a death stimulus. Meanwhile the light and small organelles probably from syncytiotrophoblast, with a low oxygen metabolism, low level of ΔΨm, and increased hydrogen peroxide production, may not actively perform an apoptotic process due to their deficient energetic level. This study contributes to the characterization of functional parameters of human placenta mitochondria in order to understand the oxygen metabolism during the physiological process of gestation.

High-performance liquid chromatography under partially denaturing conditions (dHPLC) is a fast and cost-effective method for screening molecular defects: four novel mutations found in X-linked chronic granulomatous disease.

Implementing precise techniques in routine diagnosis of chronic granulomatous disease (CGD), which expedite the screening of molecular defects, may be critical for a quick assumption of patient prognosis. This study compared the efficacy of single-strand conformation polymorphism analysis (SSCP) and high-performance liquid chromatography under partially denaturing conditions (dHPLC) for screening mutations in CGD patients. We selected 10 male CGD patients with a clinical history of severe recurrent infections and abnormal respiratory burst function. gDNA, mRNA and cDNA samples were prepared by standard methods. CYBB exons were amplified by PCR and screened by SSCP or dHPLC. Abnormal DNA fragments were sequenced to reveal the nature of the mutations. The SSCP and dHPLC methods showed DNA abnormalities, respectively, in 55% and 100% of the cases. Sequencing of the abnormal DNA samples confirmed mutations in all cases. Four novel mutations in CYBB were identified which were picked up only by the dHPLC screening (c.904 insC, c.141+5 g>t, c.553 T>C, and c.665 A>T). This work highlights the relevance of dHPLC, a sensitive, fast, reliable and cost-effective method for screening mutations in CGD, which in combination with functional assays assessing the phagocyte respiratory burst will contribute to expedite the definitive diagnosis of X-linked CGD, direct treatment, genetic counselling and to have a clear assumption of the prognosis. This strategy is especially suitable for developing countries.

Toxocariasis in migrant children: A 6 years' experience in a reference pediatric unit in Spain.

BACKGROUND: Toxocariasis is a worldwide distributed zoonosis that affects characteristically children. Clinical presentation is highly variable, often asymptomatic, and treatment duration is controversial. METHODS: A retrospective descriptive study (January 2014-December 2019) was performed in a referral Unit for Pediatric Tropical Diseases. Patients younger than 18 years of age diagnosed with toxocariasis were included. RESULTS: Out of 931 children screened for toxocariasis, 49 (5.3%) were seropositive. The median age was 11.0 years, 55.1% male and 30.6% referred contact with puppies. Overall, 34.7% were Latin-American, 24.5% Asiatic, 20.4% European, and 20.4% African. Only 34.7% presented symptoms, gastrointestinal the most common (52.9%). The 57.1% of children presented eosinophilia and 50% elevated total IgE. Most cases (95.9%) corresponded to covert toxocariasis. All children were treated with albendazole for 5, 14 or 21 days, and 4 children required a second course. Follow-up data were available in 32 children (65.3%) for a median of 7 months, showing a progressive decline in eosinophils, IgE-titers and ELISA optical density. CONCLUSION: Toxocariasis is mostly asymptomatic in children and eosinophilia is not always present. Serological tests should be included in migrant health screening and in the diagnostic assessment of eosinophilia. Eosinophil count, IgE-titers and ELISA optical-density could be useful during follow-up.

Continuous Positive Airway Pressure vs. High Flow Nasal Cannula in children with acute severe or moderate bronchiolitis. A systematic review and Meta-analysis.

OBJECTIVE: To compare the safety and effectiveness of Continuous Positive Airway Pressure (CPAP) vs. High Flow Nasal Cannula (HFNC) to prevent therapeutic failure and the need of invasive ventilation in children with acute moderate-severe bronchiolitis. DESIGN: A systematic review and meta-analysis. SETTING: Medline, Embase, Lilacs, Cochrane and gray literature (May 2020) was performed. PARTICIPANTS: Randomized clinical trials patients with moderate to severe bronchiolitis. MAIN VARIABLES: Therapeutic failure, need for invasive ventilation, adverse events, length of PCCU and of hospital stay. INTERVENTION: The quality of the studies was assessed with the Cochrane risk and bias tool. We conducted meta-analysis using fixed effect model and random effects model. RESULTS: Three RCTs were included. Showed less risk of therapeutic failure with CPAP compared with HFNC (RR=0.7; 95%CI 0.5-0.99) developed hours later in patients with CPAP (MD=3.16; 95%CI 1.55-4.77). We did not find differences in other outcomes, such as need of invasive ventilation (RR=0.60; 95%CI 0.25-1.43), apnea (RR=0.40; 95%CI 0.08-1.99), or number of days in the intensive care unit (MD=0.02; 95%CI -0.38 to 0.42), and length of hospitalization (MD=-1.00; 95%IC -2.66 to 0.66). Adverse events (skin lesions) were more common with CPAP (RR 2.47; 95%CI 1.17-5.22). CONCLUSIONS: In moderate/severe bronchiolitis CPAP demonstrated a lower risk of therapeutic failure and a longer time to failure. But more adverse events like nasal injury. There were no differences in other variables.

The human NADPH oxidase: primary and secondary defects impairing the respiratory burst function and the microbicidal ability of phagocytes.

Phagocytes, such as granulocytes and monocytes/macrophages, contain a membrane-associated NADPH oxidase that produces superoxide leading to other reactive oxygen species with microbicidal, tumoricidal and inflammatory activities. Primary defects in oxidase activity in chronic granulomatous disease (CGD) lead to severe, life-threatening infections that demonstrate the importance of the oxygen-dependent microbicidal system in host defence. Other immunological disturbances may secondarily affect the NADPH oxidase system, impair the microbicidal activity of phagocytes and predispose the host to recurrent infections. This article reviews the primary defects of the human NADPH oxidase leading to classical CGD, and more recently discovered immunological defects secondarily affecting phagocyte respiratory burst function and resulting in primary immunodeficiencies with varied phenotypes, including susceptibilities to pyogenic or mycobacterial infections.

Mitochondrial dysfunction as a mediator of hippocampal apoptosis in a model of hepatic encephalopathy.

In this study, we describe the presence of apoptosis, associated with a mitochondrial dysfunction in the hippocampus of animals in an experimental model defined as minimal hepatic encephalopathy (MHE). This experimental model was studied after 10 days of induced portal vein calibrated stricture, leading to portal hypertension and to a moderate hyperammonemia, without the presence of other evident central nervous system changes. The molecular mechanisms here proposed indicate the presence of apoptotic intrinsic pathways that point to hippocampal mitochondria as an important mediator of apoptosis in this experimental model. In this model of MHE, the presence of DNA fragmentation is documented by 2.3-times increased number of TUNEL-positive cells. These findings together with a higher ratio of the Bcl-2 family members Bax/Bcl-xL in the outer mitochondrial membrane of the MHE animals together with 11% of cytochrome c release indicate the presence of apoptosis in this experimental model. A detailed analysis of the hippocampal mitochondrial physiology was performed after mitochondrial isolation. The determination of the respiratory rate in the presence of malate plus glutamate and ADP showed a 45% decrease in respiratory control in MHE animals as compared with the sham group. A marked decrease of cytochrome oxidase (complex IV of the electron transport chain) was also observed, showing 46% less activity in hippocampal mitochondria from MHE animals. In addition, mitochondria from these animals showed less ability to maintain membrane potential (ΔΨ (m)) which was 13% lower than the sham group. Light scattering experiments showed that mitochondria from MHE animals were more sensitive to swell in the presence of increased calcium concentrations as compared with the sham group. In addition, in vitro studies performed in mitochondria from sham animals showed that mitochondrial permeability transition (MPT) could be a mitochondrial mediator of the apoptotic signaling in the presence of NH(4) (+) and calcium.

Bacille Calmette-Guérin lymphadenitis and recurrent oral candidiasis in an infant with a new mutation leading to interleukin-12 receptor beta-1 deficiency.

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare syndrome characterized by predisposition to infections caused by weakly virulent mycobacteria, such as those in bacille Calmette-Guérin (BCG) vaccine and environmental mycobacteria. Salmonellosis has been reported in almost half of affected patients. Patients are also vulnerable to Mycobacterium tuberculosis infection. Several other infectious diseases may occur, albeit rarely. Mucocutaneous candidiasis is more common. Interleukin-12 receptor beta1 (IL-12Rbeta1) deficiency is the most frequent genetic cause of MSMD. Here, we describe an infant with a single episode of BCG lymphadenitis who also suffered from recurrent oral candidiasis. Genetic analysis revealed a new homozygous mutation (64+1G>T) in the IL12RB1 gene that caused complete IL-12R1beta1 deficiency. IL-12Rbeta1 deficiency should be considered in patients with BCG infection, even in those who experience a single episode of BCG lymphadenitis or recurrent mucocutaneous candidiasis. Every attempt should be made to heighten awareness in countries where BCG vaccination is performed.

Detection of graphene's divergent orbital diamagnetism at the Dirac point.

The electronic properties of graphene have been intensively investigated over the past decade. However, the singular orbital magnetism of undoped graphene, a fundamental signature of the characteristic Berry phase of graphene's electronic wave functions, has been challenging to measure in a single flake. Using a highly sensitive giant magnetoresistance (GMR) sensor, we have measured the gate voltage­dependent magnetization of a single graphene monolayer encapsulated between boron nitride crystals. The signal exhibits a diamagnetic peak at the Dirac point whose magnetic field and temperature dependences agree with long-standing theoretical predictions. Our measurements offer a means to monitor Berry phase singularities and explore correlated states generated by the combined effects of Coulomb interactions, strain, or moiré potentials.

Intestinal giardiasis in children: Five years' experience in a reference unit.

BACKGROUND: Giardiasis is highly prevalent in children and is often mildly symptomatic. First-line treatment is metronidazole, but treatment failure is not uncommon. We describe a paediatric series, to identify risk factors for treatment failure and to analyse the safety and effectiveness of other treatment strategies. METHODS: Retrospective observational study, including children diagnosed with giardiasis from 2014 to 2019. Diagnosis was based on direct visualisation by microscopy after concentration using an alcohol-based fixative, antigen detection and/or DNA detection by polymerase chain reaction in stool. Treatment failure was considered when GI was detected 4 weeks after treatment. RESULTS: A total of 120 patients were included, 71.6% internationally adopted, median age 4.2 (2.3-7.3) years. Only 50% presented with symptoms, mainly diarrhoea (35%) and abdominal pain (14.1%); co-parasitism was frequent (45%). First-line treatment failure after a standard dose of metronidazole was 20%, lowering to 8.3% when a higher dose was administered (p < 0.001). Quinacrine was administered in 10 patients, with 100% effectiveness. Children <2 years were at higher risk of treatment failure (OR 3.49; 95% CI 1.06-11.53; p = 0.040). CONCLUSIONS: In children with giardiasis, treatment failure is frequent, especially before 2 years of age. Quinacrine can be considered as a second-line treatment. After treatment, eradication should be confirmed.

Liver transplant with controlled donors after circulatory death with normothermic regional perfusion and brain dead donors: A multicenter cohort study of transfusion, one-year graft survival and mortality.

BACKGROUND: Controlled donation after circulatory death (cDCD) has expanded the donor pool for liver transplantation (LT). However, transfusion requirements and perioperative outcomes should be elucidated. The aim of this multicenter study was to assess red blood cell (RBC) transfusions, one-year graft and patient survival after LT after cDCD with normothermic regional perfusion (NRP) compared with donors after brain death (DBD). METHODS: 591 LT carried out in ten centers during 2019 were reviewed. Thromboelastometry was used to manage coagulation and blood product transfusion in all centers. Normothermic regional perfusion was the standard technique for organ recovery. RESULTS: 447 patients received DBD and 144 cDCD with NRP. Baseline MCF Extem was lower in the cDCD group There were no differences in the percentage of patients (63% vs. 61% p = 0.69), nor in the number of RBC units transfused (4.7 (0.2) vs 5.5 (0.4) in DBD vs cDCD, p = 0.11. Twenty-six patients (6%) died during admission for LT in the DBD group compared with 3 patients (2%) in the cDCD group (p = 0.15). To overcome the bias due to a worse coagulation profile in cDCD recipients, matched samples were compared. No differences in baseline laboratory data, or in intraoperative use of RBC or one-year outcome data were observed between DBD and cDCD recipients. CONCLUSIONS: cDCD with NRP is not associated with increased RBC transfusion. No differences in graft and patient survival between cDCD and DBD were found. Donors after controlled circulatory death with NRP can increasingly be utilized with safety, improving the imbalance between organ donors and the ever-growing demand.

Bridging language and attention: brain basis of the impact of bilingualism on cognitive control.

Using two languages on an everyday basis appears to have a positive effect on general-purpose executive control in bilinguals. However, the neural correlates of this effect remain poorly understood. To investigate the brain bases of the bilingual advantage in executive control, we tested 21 Spanish monolinguals and 19 Spanish-Catalan early bilinguals in a non-verbal task-switching paradigm. As expected based on previous experiments on non-verbal task switching, we found activation in the right inferior frontal cortex and the anterior cingulate of monolingual participants. While bilingual participants showed a reduced switching cost, they activated the left inferior frontal cortex and the left striatum, a pattern of activation consistent with networks thought to underlie language control. Overall, these results support the hypothesis that bilinguals' early training in switching back and forth between their languages leads to the recruitment of brain regions involved in language control when performing non-linguistic cognitive tasks.

[Applied anatomy of the fontanelles]. / Anatomía aplicada de las fontanelas.

OBJECTIVE: To make a description of the anatomy of fontanelles and to update what is currently known about their applications. METHOD: 7 cadaveric heads, 2 dry skulls and 2 frontal bones of foetus were used, and 48 anterior fontanelles from paediatric patients with or without associated pathology were examined. Surgical cases and neurosonography were also used. All the structures were measured and subsequently analysed. RESULTS: The size, structure and limits of the fontanelles were evidenced in the cadaveric head and skulls, as well as the evaluation of paediatric patients and the size of their fontanelles in different pathologies. CONCLUSION: Owing to their anatomical characteristics, fontanelles are a true window to the inside of the skull, which determines their multiple clinical and surgical applications.

Continuous Positive Airway Pressure vs. High Flow Nasal Cannula in children with acute severe or moderate bronchiolitis. A systematic review and Meta-analysis.

OBJECTIVE: To compare the safety and effectiveness of Continuous Positive Airway Pressure (CPAP) vs. High Flow Nasal Cannula (HFNC) to prevent therapeutic failure and the need of invasive ventilation in children with acute moderate-severe bronchiolitis. DESIGN: A systematic review and meta-analysis. SETTING: Medline, Embase, Lilacs, Cochrane and gray literature (May 2020) was performed. PARTICIPANTS: Randomized clinical trials patients with moderate to severe bronchiolitis. MAIN VARIABLES: Therapeutic failure, need for invasive ventilation, adverse events, length of PCCU and of hospital stay. INTERVENTION: The quality of the studies was assessed with the Cochrane risk and bias tool. We conducted meta-analysis using fixed effect model and random effects model. RESULTS: Three RCTs were included. Showed less risk of therapeutic failure with CPAP compared with HFNC (RR=0.7; 95%CI 0.5-0.99) developed hours later in patients with CPAP (MD=3.16; 95%CI 1.55-4.77). We did not find differences in other outcomes, such as need of invasive ventilation (RR=0.60; 95%CI 0.25-1.43), apnea (RR=0.40; 95%CI 0.08-1.99), or number of days in the intensive care unit (MD=0.02; 95%CI -0.38 to 0.42), and length of hospitalization (MD=-1.00; 95%IC -2.66 to 0.66). Adverse events (skin lesions) were more common with CPAP (RR 2.47; 95%CI 1.17-5.22). CONCLUSIONS: In moderate/severe bronchiolitis CPAP demonstrated a lower risk of therapeutic failure and a longer time to failure. But more adverse events like nasal injury. There were no differences in other variables.