Recombinant BRICHOS chaperone domains delivered to mouse brain parenchyma by focused ultrasound and microbubbles are internalized by hippocampal and cortical neurons.

The BRICHOS domain is found in human precursor proteins associated with cancer, dementia (Bri2) and amyloid lung disease (proSP-C). Recombinant human (rh) proSP-C and Bri2 BRICHOS domains delay amyloid-ß peptide (Aß) fibril formation and reduce associated toxicity in vitro and their overexpression reduces Aß neurotoxicity in animal models of Alzheimer's disease. After intravenous administration in wild-type mice, rh Bri2, but not proSP-C, BRICHOS was detected in the brain parenchyma, suggesting that Bri2 BRICHOS selectively bypasses the blood-brain barrier (BBB). Here, our objective was to increase the brain delivery of rh proSP-C (trimer of 18 kDa subunits) and Bri2 BRICHOS (monomer to oligomer of 15 kDa subunits) using focused ultrasound combined with intravenous microbubbles (FUS + MB), which enables targeted and transient opening of the BBB. FUS + MB was targeted to one hemisphere of wild type mice and BBB opening in the hippocampal region was confirmed by magnetic resonance imaging. Two hours after FUS + MB brain histology showed no signs of tissue damage and immunohistochemistry showed abundant delivery to the brain parenchyma in 13 out of 16 cases given 10 mg/kg of proSP-C or Bri2 BRICHOS domains. The Bri2, but not proSP-C BRICHOS domain was detected also in the non-targeted hemisphere. ProSP-C and Bri2 BRICHOS domains were taken up by a subset of neurons in the hippocampus and cortex, and were detected to a minor extent in early endosomes. These results indicate that rh Bri2, but not proSP-C, BRICHOS, can be efficiently delivered into the mouse brain parenchyma and that both BRICHOS domains can be internalized by cell-specific mechanisms.

Pre- and postnatal heat stress abatement affects dairy calf thermoregulation and performance.

Prenatal heat stress during late gestation exerts long-term effects on growth and productivity of the dairy calf. Further, direct exposure to heat stress during the preweaning period impairs calf thermoregulation and performance. We examined the effects of heat stress abatement during the prenatal period, postnatal period, or both on calf performance. We hypothesized that calves exposed to pre- and postnatal heat stress abatement would perform most optimally in terms of thermoregulation, growth, and health responses when compared with calves that are heat-stressed at any time in the pre- or postnatal periods. Holstein calves born to heat-stressed (HT) or cooled (CL) dams during late gestation (44 ± 5 d; prenatal HT or CL) were exposed to heat stress or cooling postnatally for 56 d (postnatal HT or CL), resulting in 4 treatments: HT-HT, HT-CL, CL-HT, and CL-CL; n = 12/treatment. Calves were administered 4 L of pooled colostrum and after 2 d of age allotted 10 L/d milk replacer and up to 3 kg/d concentrate in automatic feeder group pens (n = 6/pen). Postnatal cooling was achieved by 2 fans (average wind speed 2 m/s). Thermoregulatory responses (respiration rate and heart rate; rectal, body, and skin temperature), feed intake, growth parameters including average daily gain and medication events were recorded, and blood samples were collected weekly. Thermoregulatory responses were lower in postnatal CL calves compared with postnatal HT. In the afternoon, HT-HT calves had the highest respiration rate and rectal temperature, HT-CL calves had the lowest respiration rate, and CL-HT calves had the lowest heart rate compared with the other treatment groups. Prenatal CL calves weighed more at birth and weaning with a tendency for greater average daily gain compared with prenatal HT calves, whereas postnatal CL calves had increased milk replacer and concentrate intake and a tendency for reduced fever, infection, and total medication events relative to postnatal HT. Prenatal HT calves were esophageal tube fed more often than prenatal CL. Blood hematocrit and 24-h serum IgG concentration were greater in prenatal CL calves relative to prenatal HT. Prenatal heat stress abatement improves weight gain, hematocrit, and immunoglobulin transfer, whereas postnatal heat stress abatement modulates thermoregulatory responses, feed intake, and calf health. This study is the first to characterize the combined effects of pre- and postnatal heat stress or active cooling on the dairy calf.

Towards the Limits of Existence of Nuclear Structure: Observation and First Spectroscopy of the Isotope

The most remote isotope from the proton dripline (by 4 atomic mass units) has been observed: ^{31}K. It is unbound with respect to three-proton (3p) emission, and its decays have been detected in flight by measuring the trajectories of all decay products using microstrip detectors. The 3p emission processes have been studied by the means of angular correlations of ^{28}S+3p and the respective decay vertices. The energies of the previously unknown ground and excited states of ^{31}K have been determined. This provides its 3p separation energy value S_{3p} of -4.6(2) MeV. Upper half-life limits of 10 ps of the observed ^{31}K states have been derived from distributions of the measured decay vertices.

High-Precision Probe of the Fully Sequential Decay Width of the Hoyle State in

The decay path of the Hoyle state in ^{12}C (E_{x}=7.654 MeV) has been studied with the ^{14}N(d,α_{2})^{12}C(7.654) reaction induced at 10.5 MeV. High resolution invariant mass spectroscopy techniques have allowed us to unambiguously disentangle direct and sequential decays of the state passing through the ground state of ^{8}Be. Thanks to the almost total absence of background and the attained resolution, a fully sequential decay contribution to the width of the state has been observed. The direct decay width is negligible, with an upper limit of 0.043% (95% C.L.). The precision of this result is about a factor 5 higher than previous studies. This has significant implications on nuclear structure, as it provides constraints to 3α cluster model calculations, where higher precision limits are needed.

Scattering of the Halo Nucleus

Angular distributions of the elastic, inelastic, and breakup cross sections of the halo nucleus ^{11}Be on ^{197}Au were measured at energies below (E_{lab}=31.9 MeV) and around (39.6 MeV) the Coulomb barrier. These three channels were unambiguously separated for the first time for reactions of ^{11}Be on a high-Z target at low energies. The experiment was performed at TRIUMF (Vancouver, Canada). The differential cross sections were compared with three different calculations: semiclassical, inert-core continuum-coupled-channels and continuum-coupled-channels ones with including core deformation. These results show conclusively that the elastic and inelastic differential cross sections can only be accounted for if core-excited admixtures are taken into account. The cross sections for these channels strongly depend on the B(E1) distribution in ^{11}Be, and the reaction mechanism is sensitive to the entanglement of core and halo degrees of freedom in ^{11}Be.

Observation and Spectroscopy of New Proton-Unbound Isotopes ³°Ar and ²9Cl: An Interplay of Prompt Two-Proton and Sequential Decay.

Previously unknown isotopes (30)Ar and (29)Cl have been identified by measurement of the trajectories of their in-flight decay products (28)S+p+p and (28)S+p, respectively. The analysis of angular correlations of the fragments provided information on decay energies and the structure of the parent states. The ground states of (30)Ar and (29)Cl were found at 2.25(-0.10)(+0.15) and 1.8±0.1 MeV above the two- and one-proton thresholds, respectively. The lowest states in (30)Ar and (29)Cl point to a violation of isobaric symmetry in the structure of these unbound nuclei. The two-proton decay has been identified in a transition region between simultaneous two-proton and sequential proton emissions from the (30)Ar ground state, which is characterized by an interplay of three-body and two-body decay mechanisms. The first hint of a fine structure of the two-proton decay of (30)Ar*(2(+)) has been obtained by detecting two decay branches into the ground and first-excited states of the (28)S fragment.

Callosal disconnection and limb-kinetic apraxia.

According to Liepmann, patients with limb-kinetic apraxia (LKA) have a loss of upper limb deftness-dexterity. Prior studies have revealed in right-handed patients that, whereas injury of the left hemisphere induces an ipsilesional LKA, injury to the right hemisphere does not induce an ipsilesional LKA. There are at least two possible means by which the left hemisphere may influence the deftness of the left hand, either by callosal connections or by ipsilesional corticospinal projections. The purpose of this study was to learn whether a patient with a focal lesion of the corpus callosum had a callosal disconnection LKA. This 57-year-old right-handed man had a memory impairment, and upon brain imaging, was found to have a septum pellucidum cyst, which was causing mild ventricular obstruction to the occipital and temporal horns. He underwent an endoscopic-assisted fenestration of the septum pellucidum. Postoperative imaging revealed a lesion of the mesial portion of his corpus callosum and an assessment of praxis revealed that he had both a limb-kinetic and ideomotor apraxia of his left but not his right hand. The observation that this man had a callosal disconnection LKA of his left hand suggests that in some people it is the left hemisphere's premotor or motor cortex that enables the right hemisphere's motor system to program deft movements of the left hand.

11Li Breakup on 208 at energies around the Coulomb barrier.

The inclusive breakup for the (11)Li + (208)Pb reaction at energies around the Coulomb barrier has been measured for the first time. A sizable yield of (9)Li following the (11)Li dissociation has been observed, even at energies well below the Coulomb barrier. Using the first-order semiclassical perturbation theory of Coulomb excitation it is shown that the breakup probability data measured at small angles can be used to extract effective breakup energy as well as the slope of B(E1) distribution close to the threshold. Four-body continuum-discretized coupled-channels calculations, including both nuclear and Coulomb couplings between the target and projectile to all orders, reproduce the measured inclusive breakup cross sections and support the presence of a dipole resonance in the (11)Li continuum at low excitation energy.

Effect of time windows in LSTM networks for EEG-based BCIs.

People with impaired motor function could be helped by an effective brain-computer interface (BCI) based on a real-time electroencephalogram (EEG) and artificial intelligence algorithms. However, current methodologies for interpreting patient instructions from an EEG are not accurate enough to be completely safe in a real-world situation , where a poor decision would place their physical integrity at risk, such as when traveling in an electric wheelchair in a city. For various reasons, such as the low signal-to-noise ratio of portable EEGs or the effects of signal contamination (disturbances due to user movement, temporal variation of the features of EEG signals, etc.), a long short-term memory network (LSTM) (a type of recurrent neural network) that is able to learn data flow patterns from EEG signals could improve the classification of the actions taken by the user. In this paper, the effectiveness of using an LSTM with a low-cost wireless EEG device in real time is tested, and the time window that maximizes its classification accuracy is studied. The goal is to be able to implement it in the BCI of a smart wheelchair with a simple coded command protocol, such as opening or closing the eyes, which could be executed by patients with reduced mobility. Results show a higher resolution of the LSTM with an accuracy range between 77.61 and 92.14% compared to traditional classifiers (59.71%), and an optimal time window of around 7 s for the task done by users in this work. In addition, tests in real-life contexts show that a trade-off between accuracy and response times is necessary to ensure detection.

Do halo nuclei follow Rutherford elastic scattering at energies below the barrier? The case of 11Li.

The first measurement of the elastic scattering of the halo nucleus 11Li and its core 9Li on 208Pb at energies near the Coulomb barrier is presented. The 11Li+208Pb elastic scattering shows a strong reduction with respect to the Rutherford cross section, even at energies well below the barrier and down to very small scattering angles. This drastic change of the elastic differential cross section observed in 11Li+208Pb is the consequence of the halo structure of 11Li, as it is not observed in the elastic scattering of its core 9Li at the same energies. Four-body continuum-discretized coupled-channels calculations, based on a three-body model of the 11Li projectile, are found to explain the measured angular distributions and confirm that the observed reduction is mainly due to the strong Coulomb coupling to the dipole states in the low-lying continuum of 11Li. These calculations suggest the presence of a low-lying dipole resonance in 11Li close to the breakup threshold.

[Infectious endocarditis in the intensive care unit]. / Endocarditis infecciosa en la Unidad de Medicina Intensiva.

OBJECTIVE: To study the characteristics, evolution and prognosis of patients with infectious endocarditis requiring treatment in the Intensive Care Unit. DESIGN: A prospective, observational cohort study of patients admitted due to infectious endocarditis. SETTING: Nuestra Señora de Candelaria University Hospital, a third - level center with a recruitment population of 493,145. PATIENTS: All patients consecutively diagnosed with infectious endocarditis in our center according to the Duke criteria, between 1 January 2005 and 31 July 2011. STUDY VARIABLES: Demographic data, clinical severity scores, microbiological and echocardiographic data, hospital mortality and complications. RESULTS: Out of 102 patients diagnosed with endocarditis, 38 (37%) were admitted to Intensive Care. Compared with those patients not admitted to the ICU, these subjects suffered more frequent mitral valve alterations (OR= 7.13; 95%CI: 2.12-24; p= 0.002) and cerebral embolism (OR= 3.89; 95%CI: 1.06-14.3; p= 0.041). In turn, mortality was greater (42.1% vs 18.8%, p= 0.011), as was the proportion of emergency surgeries (45.8% vs 5.9%, p<0.001). The identified mortality predictors were Staphylococcus aureus infection (OR= 3.49; 95%CI 1.02-11.93; p=0.046), heart failure (OR=4.18; 95%CI: 1.17-14.94; p=0.028), cerebral embolism (OR= 8.45; 95%CI: 1.89-37.74; p=0.005) and the SAPS II upon admission (OR=1.09; 95%CI: 1.04-1.15; p<0.001). CONCLUSIONS: A large proportion of patients with endocarditis require admission to the Intensive Care Unit, presenting a much poorer prognosis. Staphylococcus aureus infection, heart failure, cerebral embolism and SAPS II scores are independent predictors of hospital mortality.

A New PLV-Spatial Filtering to Improve the Classification Performance in BCI Systems.

OBJECTIVE: The performance of an EEG-based brain-computer interface (BCI) system is highly dependent on signal preprocessing. This manuscript presents a filtering method to improve the feature classification algorithms typically used in BCI. METHODS: A graph Laplacian quadratic form using the Phase Locking Value (PLV) is applied to generate a new filtered signal in the preprocessing stage. RESULTS: The accuracy of the classification algorithms improved significantly (up to 27.18% in the BCI Competition IV dataset, and up to 42.56% with records made with an Emotiv EPOC+). In addition, the proposed filtering algorithm has similar or better results when compared with the Filter Bank Common Spatial Pattern (FBCSP), which has disadvantages in a multiclass classification. CONCLUSION: This paper shows how our PLV-based filtering between EEG channels could improve the performance of a BCI.

The impact of stable 27Al in 26Al/10Be meteoric ratio in PM2.5 from an urban area.

Meteoric 10Be and 26Al radionuclides are produced in the atmosphere, and the relationship between them has potential applications in atmospheric and climate research. In particular, the meteoric 26Al/10Be ratio has potential applications such as a chronometer for old ice, a tracer for the air exchange between the lower stratosphere and upper troposphere, production and distribution in the atmosphere of both radionuclides, and the study on solar activity. In this work, their concentrations in the fine fraction of airborne particulate matter from an urban area have been precisely determined using Accelerator Mass Spectrometry (AMS). To obtain new data about the 26Al/10Be ratio and its subsequent applications, PM2.5 in aerosol samples has been analyzed. The average ratio in samples from Mexico City was significantly higher than those previously reported by other authors. The high enrichment factors for stable Aluminum indicate that both resuspended and anthropogenic 27Al content in PM2.5 contributes significantly to the high values of 26Al in the 26Al/10Be ratio. An adjustment of 27Al concentrations from external contributions was carried out, and the corrected 26Al/10Be ratios were similar to those previously reported. In this study, a precise assessment of the possible contribution of other Aluminum sources to the aerosol samples has been carried out. Finally, the obtained ratios indicate the possibility of its future use in applications such as the dating of glaciers.

Near-barrier fusion of the 8B + 58Ni proton-halo system.

Fusion cross sections were measured for the exotic proton-halo nucleus 8B incident on a 58Ni target at several energies near the Coulomb barrier. This is the first experiment to report on the fusion of a proton-halo nucleus. The resulting excitation function shows a striking enhancement with respect to expectations for normal projectiles. Evidence is presented that the sum of the fusion and breakup yields saturates the total reaction cross section.

[Evolution of antimicrobial resistance and mortality in Staphylococcus aureus endocarditis during 15 years in a university hospital]. / Evolución de la resistencia antimicrobiana y mortalidad en la endocarditis por Staphylococcus aureus durante 15 años en un hospital universitario.

OBJECTIVE: One of the most aggressive microorganisms in infective endocarditis (IE) is Staphylococcus aureus. We analyse the resistance of S. aureus to antibiotics and its impact on the clinical course of IE in a recent 15-year period. METHODS: Retrospective study of patients with IE in a university hospital from 2005 to 2019. Bivariate and multivariate analysis of severity at admission, comorbidities, minimum inhibitory concentrations (MIC) and mortality. RESULTS: Of the 293 IE cases, 66 (22.5%) were due to S. aureus, and 21 (7.2%) were methicillin-resistant S. aureus (MRSA). The prevalence of strains with a MIC to vancomycin ≥ 1mg/L increased from 4.8% to 63.6% (p <0.001) and the cases of MRSA from 38 to 27.3% (p = 0.045). Older age (p= 0.02), comorbidity (p <0.01) and nosohusial origin (p = 0.01), were factors associated with MRSA. But the antimicrobial resistance and severity on admission were not associated with exitus; predictive factors were the right-sided IE (OR = 0.08; 95% CI: 0.01-0.51), comorbidities (OR per Charlson index point = 1.30; 95% CI: 1.01-1.69) and creatinine on admission (OR per mg / dL = 1.56; 95% CI = 1.01- 2.35; p = 0.04). CONCLUSIONS: We have experienced an increase in IE cases with MIC to vancomycin ≥ 1mg/L, without significant variation in infections due to MRSA. Antimicrobial resistance was not associated with mortality, but comorbidity and left involvement were predictive factors.

Elastic scattering and reaction mechanisms of the halo nucleus 11Be around the Coulomb barrier.

Collisions induced by (9,10,11)Be on a 64Zn target at the same c.m. energy were studied. For the first time, strong effects of the 11Be halo structure on elastic-scattering and reaction mechanisms at energies near the Coulomb barrier are evidenced experimentally. The elastic-scattering cross section of the 11Be halo nucleus shows unusual behavior in the Coulomb-nuclear interference peak angular region. The extracted total-reaction cross section for the 11Be collision is more than double the ones measured in the collisions induced by (9,10)Be. It is shown that such a strong enhancement of the total-reaction cross section with 11Be is due to transfer and breakup processes.

Elemental sulfur-based autotrophic denitrification in stoichiometric S0/N ratio: Calibration and validation of a kinetic model.

The inclusion of S0 hydrolysis in a kinetic model of autotrophic denitrification has been recently proposed; however the model has not been calibrated or validated yet. Thus, a new methodology was developed and applied to calibrate and validate this kinetic model for the first time. An inoculum adapted from a poultry wastewater treatment plant at stoichiometric S0/NO3- ratio was used. The model was calibrated with batch data (initial nitrate concentrations of 50 and 6.25 mg NO3--N/L) at an S0/N ratio = 2.29 mg S/mg N and validated with seven different batch data. The sensitivity analysis showed that the most sensitive parameters are related to S0 hydrolysis. The kinetic model was successfully calibrated with the new methodology and validated, with Theil inequality coefficient values lower than 0.21. Thus, the proposed model and methodology were proved to be well suited for the simulation of elemental sulfur-based autotrophic denitrification in batch systems.

Effect of ultra-fine friction grinding on the physical and chemical properties of curcuma (Curcuma longa L.) suspensions.

Curcuma longa is a rhizome used for the extraction of curcumin, a yellow colorant that only represents 3 wt% of the dried rhizome. To increase the possibility of using the entire rhizome as a food colorant, in the present investigation, the effect of ultra-fine friction grinding (supermasscolloider) to obtain turmeric suspensions was evaluated. To achieve this goal, two distances between the grinding stones or Gap were evaluated (G of -1 and -1.5), and the obtained suspensions were characterized by infrared spectroscopy and through the determination of curcumin content, color, particle size, sedimentation index, serum cloudiness, and microstructure. The results establish that a lower G contributes to an increase in the release of curcumin in the suspension up to 21%, which is related to a greater tendency for yellow coloration, observed in the increase of the * b coordinate of color (from 61.588 to 66.497). Additionally, it was found that a lower G generates smaller particle sizes, which is related to a lower turbidity. PRACTICAL APPLICATION: This research shows that ultra-fine friction grinding (UFFG) has great potential for the development of turmeric suspensions. The results have applications in the food industry sector, because UFFG could be used to produce different types of vegetable suspensions.

Mite sensitization among Latina women in New York, where dust-mite allergen levels are typically low.

UNLABELLED: In New York (NY), Latinos often have greater asthma morbidity than other ethnicities, and dust-mite sensitization is common despite low allergen levels. We investigated mite allergen exposure and sensitization in atopic and/or asthmatic women, the majority being Puerto Rican. Women (n = 274) recruited for a birth cohort study were visited postnatally. Dust from their homes was analyzed for mite allergens (Der f 1, Der p 1, and Blo t 5). Serum was analyzed for total and allergen-specific IgE. Thirty-seven percent were sensitized to Dermatophagoides pteronyssinus, 34% to Dermatophagoides farinae, and 21% to Blomia tropicalis. Only 5% of NY homes had levels of Der f 1 >2 microg/g; none had Blo t 5 or Der p 1 above this level. Caribbean or Latin American birthplace (a proxy for childhood exposure) was not associated with mite sensitization. Sensitization to D. pteronyssinus and D. farinae was associated with a report of doctor-diagnosed asthma [Odds ratio (OR) = 3.27, P = 0.003; OR = 2.81, P = 0.010, respectively]; sensitization to any mite was associated with asthma medication use in the past 12 months (OR = 3.12, P = 0.004). These associations held even after adjustment for cockroach, mouse, and cat sensitization. PRACTICAL IMPLICATIONS: Despite the low concentrations of mite allergen in our community, many of the women in the atopically enriched cohort were sensitized to mites, even Blomia tropicalis which is typically found only in tropical environments.

Immunotherapy in oncology: a new challenge for radiologists. / Inmunoterapia en oncología: un nuevo desafío radiológico.

OBJECTIVE: In patients with oncologic disease, immunotherapy has become established as an alternative or complementary therapy to traditional treatment options (surgery, radiotherapy, and chemotherapy). Currently available immunotherapy modes can be divided into two types: passive and active. The active type strengthens the immune system's response to tumor cells by activating both humoral immunity and cell-mediated immunity, using the adaptive response. This article aims to analyze the radiologic patterns of the response to immunotherapy through immune-response-related criteria and to describe the main adverse effects associated with this treatment approach. CONCLUSION: Imaging tests play a fundamental role in the follow-up of oncologic patients and in the assessment of their response to treatment. Immunotherapy represents a challenge for radiologists both in the evaluation of the response to immunotherapy and in the detection of the adverse effects associated with this treatment approach.