Publications by authors named "Carlos Perez"

296 Publications

Volume Matters: Longitudinal Retrospective Cohort Study of Outcomes Following Consultation and Standardization of Adrenal Surgery.

Ann Surg Oncol 2021 Jun 17. Epub 2021 Jun 17.

Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.

Purpose: Subspecialization of adrenal surgery through regionalization has not been adequately evaluated. We assessed implementation of subspecialization and the association of regionalization with adrenalectomy outcomes in a community-based setting.

Methods: In this longitudinal retrospective cohort study, we used an interrupted time series analysis on consecutive adrenal surgeries at Kaiser Permanente Northern California, 2010-2019. The intervention was regionalization of surgery in 2016. Main outcomes include surgical volumes, operative time, length of stay, 30-day return-to-care, and 30-day complications obtained from the electronic medical record. t-Tests and multivariable models were used to analyze time trends in outcomes after accounting for changes in patient and disease characteristics.

Results: In total, 850 adrenal surgery cases were eligible. Between 2010 and 2019, the annual incidence of surgery (per 100,000 persons) increased from 2.4 (95% CI 1.9-3.1) to 4.1 (95% CI 3.5-4.8). Average annual surgeon volume increased from 2.4 (95% CI 1.6-3.1) to 9.9 (95% CI 4.9-14.9), while hospital volume increased from 3.5 (95% CI 2.3-4.6) to 15.4 (95% CI 6.9-24.0). Operative time was 34 (23-45) min faster in 2018-2019 compared with 2010-2011. After regionalization, same-day discharges increased to 64% in 2019 (p < 0.0001). The frequency of return-to-care (p = 0.69) and the overall complication rate (p = 0.31) did not change.

Conclusions: Regionalizing adrenal surgery through surgical subspecialization and standardized care pathways was feasible and decreased operative time, and hospital stay, while increasing the frequency of same-day discharges without increasing return-to-care or complications.
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http://dx.doi.org/10.1245/s10434-021-10297-3DOI Listing
June 2021

Monitoring Parkinson's disease progression based on recorded speech with missing ordinal responses and replicated covariates.

Comput Biol Med 2021 May 28;134:104503. Epub 2021 May 28.

Departamento de Tecnologías de Los Computadores y de Las Comunicaciones, Escuela Politécnica, Universidad de Extremadura, 10003, Cáceres, Spain.

Monitoring Parkinson's Disease (PD) progression is an important task to improve the life quality of the affected people. This task can be performed by extracting features from voice recordings and applying specifically designed statistical models, leading to systems that improve the ability of monitoring the progression of PD in an objective, remote, non-invasive, fast, and economically sustainable way. An experiment has been conducted with 36 subjects to study the progression of the PD over 4 years by using the Hoehn and Yahr (HY) scale and features extracted from the phonation of the vowel/a/. The collected dataset had many missing data, which should be addressed jointly with the non-decreasing nature of the disease and the within-subject variability due to the use of replicated features. In order to handle these issues, a Hidden Markov model for longitudinal data was designed and implemented by using a data augmentation scheme based on different latent variables. Markov chain Monte Carlo methods were used to generate from the posterior distribution. The proposed approach has been tested on simulated data, providing good accuracy rates in the context of a multiclass problem. It also has been applied to the real data obtained from the conducted experiment, providing imputed and predicted HY stages compatible with the progression of PD. The conducted experiment and the proposed approach contribute to fill a gap in the scientific literature on experiments and methodologies for tracking PD progression based on acoustic features and the HY scale. This would help to derive an expert system that can be integrated into the protocols of neurology units in hospital centers.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104503DOI Listing
May 2021

Quantitative Analysis of Practice Size Consolidation in Radiation Oncology: A trend toward bigger and fewer practices.

Pract Radiat Oncol 2021 May 29. Epub 2021 May 29.

Washington University in St. Louis, Department of Radiation Oncology; Leonard Davis Institute of Health Economics, University of Pennsylvania. Electronic address:

Background And Purpose: There is evidence of practice consolidation in US healthcare in recent years. To our knowledge, a detailed quantitative study of recent changes in radiation oncology practice size has not been performed. We aim to evaluate radiation oncology practice size changes between 2012 and 2020 in the US.

Materials And Methods: Using the Medicare Physician Compare Database, we identified practices employing radiation oncologists using their Taxpayer Identification Number and individual radiation oncologists using their National Provider Identifier. We divided individual radiation oncologists into categories by practice size (which includes the number of physicians of all specialties) and compared the number of radiation oncologists in each category between 2012 and 2020. Further analyses by US geographic census region, single-specialty practice, academic practice, and high- and low-population density areas were performed.

Results: Between 2012 and 2020, the total number of practicing radiation oncologists increased by 9%, while the number of practices employing radiation oncologists decreased by 11.5%. The number of radiation oncologists in practices of size 1-2, 3-9, 10-24, and 25-49 decreased by 3.7%, 4.7%, 4.9%, and 2%, respectively, while the number of radiation oncologists in practices of size 50-99, 100-499, and 500+ increased by 1.4%, 2.1%, and 11.8%, respectively (all 500+ practices are multi-specialty groups). The increase in practice size was significant in all regions, for single-specialty and multi-specialty practices, academic and non-academic practices, and for practices in high-, middle-, and low-population density areas (p<0.05 for all comparisons). The proportion of single specialty practices has decreased significantly (p<0.001), while the proportion of academic practices increased significantly (p=0.004). Additionally, the proportion of practices and physicians in high- and low-population density regions remained stable during this period (p > 0.05).

Conclusions: Our analysis suggests that practice size consolidation has occurred within the US Radiation Oncology workforce from 2012-2020. The impact of this consolidation on quality, cost, and patient access deserves further attention.
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http://dx.doi.org/10.1016/j.prro.2021.05.003DOI Listing
May 2021

Overexpression of the CaHB12 transcription factor in cotton (Gossypium hirsutum) improves drought tolerance.

Plant Physiol Biochem 2021 Aug 17;165:80-93. Epub 2021 May 17.

Embrapa Genetic Resources and Biotechnology, Brasília, DF, 70297-400, Brazil; National Institute of Science and Technology, INCT PlantStress Biotech, EMBRAPA, Brasília, DF, 70297-400, Brazil; Catholic University of Brasília, Brasília, DF, 71966-700, Brazil. Electronic address:

The Coffea arabica HB12 gene (CaHB12), which encodes a transcription factor belonging to the HD-Zip I subfamily, is upregulated under drought, and its constitutive overexpression (35S:CaHB12) improves the Arabidopsis thaliana tolerance to drought and salinity stresses. Herein, we generated transgenic cotton events constitutively overexpressing the CaHB12 gene, characterized these events based on their increased tolerance to water deficit, and exploited the gene expression level from the CaHB12 network. The segregating events Ev8.29.1, Ev8.90.1, and Ev23.36.1 showed higher photosynthetic yield and higher water use efficiency under severe water deficit and permanent wilting point conditions compared to wild-type plants. Under well-irrigated conditions, these three promising transformed events showed an equivalent level of Abscisic acid (ABA) and decreased Indole-3-acetic acid (IAA) accumulation, and a higher putrescine/(spermidine + spermine) ratio in leaf tissues was found in the progenies of at least two transgenic cotton events compared to non-transgenic plants. In addition, genes that are considered as modulated in the A. thaliana 35S:CaHB12 line were also shown to be modulated in several transgenic cotton events maintained under field capacity conditions. The upregulation of GhPP2C and GhSnRK2 in transgenic cotton events maintained under permanent wilting point conditions suggested that CaHB12 might act enhancing the ABA-dependent pathway. All these data confirmed that CaHB12 overexpression improved the tolerance to water deficit, and the transcriptional modulation of genes related to the ABA signaling pathway or downstream genes might enhance the defense responses to drought. The observed decrease in IAA levels indicates that CaHB12 overexpression can prevent leaf abscission in plants under or after stress. Thus, our findings provide new insights on CaHB12 gene and identify several promising cotton events for conducting field trials on water deficit tolerance and agronomic performance.
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http://dx.doi.org/10.1016/j.plaphy.2021.05.009DOI Listing
August 2021

A simplified alternative diagnostic algorithm for SARS-CoV-2 suspected symptomatic patients and confirmed close contacts (asymptomatic): A consensus of Latin American experts.

Int J Infect Dis 2021 May 19. Epub 2021 May 19.

Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.

Introduction: Latin America accounts for one-quarter of global COVID-19 cases and one-third of deaths. Inequalities in the region lead to barriers regarding the best use of diagnostic tests during the pandemic. There is a need for a simplified guideline, considering the region's health resources' low availability, international guidelines, medical literature, and local expertise.

Methods: Nine experts from Latin American countries developed a simplified algorithm for COVID-19 diagnosis, using a modified Delphi method. Twenty-four questions related to diagnostic settings were proposed, followed by discussion of the literature and experts' experience.

Results: The algorithm considers three timeframes (≤7 days, 8-13 days, and ≥ 14 days) and discusses diagnostic options for each one. SARS-CoV-2 rRT-PCR is the test of choice from day 1 to day 14 after symptom onset or close contact, although antigen testing may be used in particular situations, from days 5 to 7. Antibody assays may be used for confirmation, mainly after day 14. If the clinical suspicion is very high, but other tests are negative, these assays may be used as an adjunct to decision-making from day 8 to day 13.

Conclusion: The proposed algorithm aims to support COVID-19 diagnosis decision-making in Latin America.
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http://dx.doi.org/10.1016/j.ijid.2021.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133827PMC
May 2021

Point absorbers in Advanced LIGO.

Appl Opt 2021 May;60(13):4047-4063

Small, highly absorbing points are randomly present on the surfaces of the main interferometer optics in Advanced LIGO. The resulting nanometer scale thermo-elastic deformations and substrate lenses from these micron-scale absorbers significantly reduce the sensitivity of the interferometer directly though a reduction in the power-recycling gain and indirect interactions with the feedback control system. We review the expected surface deformation from point absorbers and provide a pedagogical description of the impact on power buildup in second generation gravitational wave detectors (dual-recycled Fabry-Perot Michelson interferometers). This analysis predicts that the power-dependent reduction in interferometer performance will significantly degrade maximum stored power by up to 50% and, hence, limit GW sensitivity, but it suggests system wide corrections that can be implemented in current and future GW detectors. This is particularly pressing given that future GW detectors call for an order of magnitude more stored power than currently used in Advanced LIGO in Observing Run 3. We briefly review strategies to mitigate the effects of point absorbers in current and future GW wave detectors to maximize the success of these enterprises.
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http://dx.doi.org/10.1364/AO.419689DOI Listing
May 2021

HUMAN COSAVIRUS INFECTION IN HIV SUBJECTS WITH DIARRHOEA: PERSISTENT DETECTION ASSOCIATED WITH FATAL OUTCOME.

J Clin Virol 2021 Jun 16;139:104825. Epub 2021 Apr 16.

Servicio de Infectología. Hospital General del Oeste "Dr. José Gregorio Hernández". Catia, Sector Los Magallanes de Catia. Caracas, Venezuela.

Background: Human cosavirus (HCoSV) is a new member of the Picornaviridae family, geographically widespread among humans. It has been suggested as a causative agent of acute gastroenteritis, but its pathogenicity is not currently certain. In HIV-infected subjects, diarrhoea is one of the most frequent gastrointestinal manifestations, whose aetiology remains often unexplained.

Objectives: To identify the cause of viral diarrhoea among HIV infected patients by molecular assays.

Study Design: A total of 143 stool samples from HIV subjects with and without diarrhoea, were screened for conventional enteric viruses (rotavirus, adenovirus, norovirus and astrovirus) by molecular assays. The presence of HCoSV genome was investigated by nested RT-PCR for the 5'UTR region. Positive samples were further characterized by sequencing and phylogenetic analysis.

Results: Enteric viruses were more frequently found in diarrhoea cases (9/82) than controls (0/61) (p=0.007). HCoSV was detected in five (3.5%) of the subjects affected by diarrhoea. Phylogenetic analysis revealed the predominance of the HCoSV species D. One patient suffered a persistent cosavirus infection with a same strain and after eight months he had a fatal outcome. No other pathogens could be detected.

Conclusions: The results suggest a role of non-conventional enteric viruses, as HCoSV, as a potential opportunistic agent causing persistent infection and deterioration of the clinical conditions in HIV-infected patients. Screening procedures and monitoring including such viruses would be helpful in the clinical management of such patients.
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http://dx.doi.org/10.1016/j.jcv.2021.104825DOI Listing
June 2021

Unique Presentation of Microscopic Polyangiitis: Hearing and Vision Loss, Dysphagia, and Renal Dysfunction.

Cureus 2021 Mar 23;13(3):e14069. Epub 2021 Mar 23.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA.

Microscopic polyangiitis (MPA) is an autoimmune small-vessel vasculitis often positive for perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA), or anti-myeloperoxidase (MPO), that classically affects the lungs, kidneys, and skin. Several atypical presentations of MPA involving other organs have also been reported in the literature. We report a unique case of a patient who presented with rare presentations of MPA: hearing and vision loss, dysphagia, renal dysfunction. Despite the atypical nature of her symptoms, her p-ANCA serology was positive and kidney biopsy was consistent with MPA. Regardless of the bizarre nature of a patient's symptoms, we highlight the importance of considering MPA as a differential diagnosis in the setting of positive p-ANCA serology.
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http://dx.doi.org/10.7759/cureus.14069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062312PMC
March 2021

A Case of Dysembryoplastic Neuroepithelial Tumor in an Adolescent Male.

Cureus 2021 Mar 16;13(3):e13917. Epub 2021 Mar 16.

Division of Multiple Sclerosis and Neuroimmunology, Department of Neurology, University of Texas Health Science Center at Houston, Houston, USA.

Dysembryoplastic neuroepithelial tumors (DNETs) are benign mixed glioneuronal neoplasms that frequently occur in children and young adults. We present the case of a 17-year-old male who arrived at the hospital following seizure-like activity. A magnetic resonance imaging (MRI) scan showed a 10 x 8 x 10 mm, oval-shaped, non-enhancing, well-defined mass within the right hippocampus. The patient underwent a transcortical approach via the middle temporal gyrus for resection of the mass; histopathological examination demonstrated the presence of round, uniform cells in an extensively myxoid background with diffuse reactivity to glial fibrillary acidic protein (GFAP). DNETs are considered benign, non-recurring lesions. Complete surgical resection is associated with a seizure-free outcome in 80% to 100% of cases.
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http://dx.doi.org/10.7759/cureus.13917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051422PMC
March 2021

Thermal Conductivity of Aluminum Scandium Nitride for 5G Mobile Applications and Beyond.

ACS Appl Mater Interfaces 2021 Apr 14;13(16):19031-19041. Epub 2021 Apr 14.

Department of Mechanical Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.

Radio frequency (RF) microelectromechanical systems (MEMS) based on AlScN are replacing AlN-based devices because of their higher achievable bandwidths, suitable for the fifth-generation (5G) mobile network. However, overheating of AlScN film bulk acoustic resonators (FBARs) used in RF MEMS filters limits power handling and thus the phone's ability to operate in an increasingly congested RF environment while maintaining its maximum data transmission rate. In this work, the ramifications of tailoring of the piezoelectric response and microstructure of AlScN films on the thermal transport have been studied. The thermal conductivity of AlScN films (3-8 W m K) grown by reactive sputter deposition was found to be orders of magnitude lower than that for -axis-textured AlN films due to alloying effects. The film thickness dependence of the thermal conductivity suggests that higher frequency FBAR structures may suffer from limited power handling due to exacerbated overheating concerns. The reduction of the abnormally oriented grain (AOG) density was found to have a modest effect on the measured thermal conductivity. However, the use of low AOG density films resulted in lower insertion loss and thus less power dissipated within the resonator, which will lead to an overall enhancement of the device thermal performance.
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http://dx.doi.org/10.1021/acsami.1c02912DOI Listing
April 2021

Tumor-Stromal Interactions in a Co-Culture Model of Human Pancreatic Adenocarcinoma Cells and Fibroblasts and Their Connection with Tumor Spread.

Biomedicines 2021 Mar 31;9(4). Epub 2021 Mar 31.

Laboratory of Clinical and Translational Oncology, Instituto de Investigación Hospital 12 de Octubre (i+12), Av. de Córdoba S/N, 28041 Madrid, Spain.

One key feature of pancreatic ductal adenocarcinoma (PDAC) is a dense desmoplastic reaction that has been recognized as playing important roles in metastasis and therapeutic resistance. We aim to study tumor-stromal interactions in an in vitro coculture model between human PDAC cells (Capan-1 or PL-45) and fibroblasts (LC5). Confocal immunofluorescence, Enzyme-Linked Immunosorbent Assay (ELISA), and Western blotting were used to evaluate the expressions of activation markers; cytokines arrays were performed to identify secretome profiles associated with migratory and invasive properties of tumor cells; extracellular vesicle production was examined by ELISA and transmission electron microscopy. Coculture conditions increased FGF-7 secretion and α-SMA expression, characterized by fibroblast activation and decreased epithelial marker E-cadherin in tumor cells. Interestingly, tumor cells and fibroblasts migrate together, with tumor cells in forming a center surrounded by fibroblasts, maximizing the contact between cells. We show a different mechanism for tumor spread through a cooperative migration between tumor cells and activated fibroblasts. Furthermore, IL-6 levels change significantly in coculture conditions, and this could affect the invasive and migratory capacities of cells. Targeting the interaction between tumor cells and the tumor microenvironment might represent a novel therapeutic approach to advanced PDAC.
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http://dx.doi.org/10.3390/biomedicines9040364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065458PMC
March 2021

The Angiopoietin-Like Protein 3 and 8 Complex Interacts with Lipoprotein Lipase and Induces LPL Cleavage.

ACS Chem Biol 2021 03 3;16(3):457-462. Epub 2021 Mar 3.

Centro de Investigación Lilly S.A., 28108 Alcobendas, Spain.

Lipoprotein lipase (LPL) is the key enzyme that hydrolyzes triglycerides from triglyceride-rich lipoproteins. Angiopoietin-like proteins (ANGPTL) 3, 4, and 8 are well-characterized protein inhibitors of LPL. ANGPTL8 forms a complex with ANGPTL3, and the complex is a potent endogenous inhibitor of LPL. However, the nature of the structural interaction between ANGPTL3/8 and LPL is unknown. To probe the conformational changes in LPL induced by ANGPTL3/8, we found that HDX-MS detected significantly altered deuteration in the lid region, ApoC2 binding site, and furin cleavage region of LPL in the presence of ANGPTL3/8. Supporting this HDX structural evidence, we found that ANGPTL3/8 inhibits LPL enzymatic activities and increases LPL cleavage. ANGPTL3/8-induced effects on LPL activity and LPL cleavage are much stronger than those of ANGPTL3 or ANGPTL8 alone. ANGPTL3/8-mediated LPL cleavage is blocked by both an ANGPTL3 antibody and a furin inhibitor. Knock-down of furin expression by siRNA significantly reduced ANGPT3/8-induced cleavage of LPL. Our data suggest ANGPTL3/8 promotes furin-mediated LPL cleavage.
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http://dx.doi.org/10.1021/acschembio.0c00954DOI Listing
March 2021

Excited-State Properties of Defected Halide Perovskite Quantum Dots: Insights from Computation.

J Phys Chem Lett 2021 Jan 20;12(3):1005-1011. Epub 2021 Jan 20.

Theoretical Physics and Chemistry of Materials, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, United States.

CsPbBr quantum dots (QDs) have been recently suggested for their application as bright green light-emitting diodes (LEDs); however, their optical properties are yet to be fully understood and characterized. In this work, we utilize time-dependent density functional theory to analyze the ground and excited states of the CsPbBr clusters in the presence of various low formation energy vacancy defects. Our study finds that the QD perovskites retain their defect tolerance with limited perturbance to the simulated UV-vis spectra. The exception to this general trend is that Br vacancies must be avoided, as they cause molecular orbital localization, resulting in trap states and lower LED performance. Blinking will likely still plague CsPbBr QDs, given that the charged defects critically perturb the spectra via red-shifting and lower absorbance. Our study provides insight into the tunability of CsPbBr QDs optical properties by understanding the nature of the electronic excitations and guiding improved development for high-performance LEDs.
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http://dx.doi.org/10.1021/acs.jpclett.0c03317DOI Listing
January 2021

A stage-based approach to allocating water quality monitoring stations based on the WorldQual model: The Jubba River as a case study.

Sci Total Environ 2021 Mar 17;762:144162. Epub 2020 Dec 17.

Hydrological Engineering and Water Resources Management, Ruhr-Universität Bochum, Universitätsstraße 150, 44801 Bochum, Germany. Electronic address:

Ensuring adequate freshwater quality is an important aspect of integrated environmental management and sustainable development. One contribution towards this end is to monitor the water quality of river basins. An important issue in constructing a water quality monitoring network is how to allocate the stations. This is usually done by using in situ measurements of pollutants together with other information. A stage-based optimization approach has been developed to find the optimal sites to allocate the monitoring stations. The proposed approach constructs a network in a sequence of stages without the need for in situ pollution measurements. Instead, it uses pollutant estimates from the WorldQual model together with other social and hydrological criteria. The approach is computationally efficient and provides an ordered list of stations that can be used to initialize or augment a water quality network. This is especially relevant for consideration by developing countries since, with this approach, they can get an overview of their river basins, and then prioritize the initial distributions of the networks. The approach was applied successfully to the 741,751 km of the Jubba River basin, but it is applicable to river basins of any size.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144162DOI Listing
March 2021

On the origin of ultraslow spontaneous Na fluctuations in neurons of the neonatal forebrain.

J Neurophysiol 2021 02 25;125(2):408-425. Epub 2020 Nov 25.

Department of Physics, University of South Florida, Tampa, Florida.

Spontaneous neuronal and astrocytic activity in the neonate forebrain is believed to drive the maturation of individual cells and their integration into complex brain-region-specific networks. The previously reported forms include bursts of electrical activity and oscillations in intracellular Ca concentration. Here, we use ratiometric Na imaging to demonstrate spontaneous fluctuations in the intracellular Na concentration of CA1 pyramidal neurons and astrocytes in tissue slices obtained from the hippocampus of mice at (P2-4). These occur at very low frequency (∼2/h), can last minutes with amplitudes up to several millimolar, and mostly disappear after the first postnatal week. To further investigate their mechanisms, we model a network consisting of pyramidal neurons and interneurons. Experimentally observed Na fluctuations are mimicked when GABAergic inhibition in the simulated network is made depolarizing. Both our experiments and computational model show that blocking voltage-gated Na channels or GABAergic signaling significantly diminish the neuronal Na fluctuations. On the other hand, blocking a variety of other ion channels, receptors, or transporters including glutamatergic pathways does not have significant effects. Our model also shows that the amplitude and duration of Na fluctuations decrease as we increase the strength of glial K uptake. Furthermore, neurons with smaller somatic volumes exhibit fluctuations with higher frequency and amplitude. As opposed to this, larger extracellular to intracellular volume ratio observed in neonatal brain exerts a dampening effect. Finally, our model predicts that these periods of spontaneous Na influx leave neonatal neuronal networks more vulnerable to seizure-like states when compared with mature brain. Spontaneous activity in the neonate forebrain plays a key role in cell maturation and brain development. We report spontaneous, ultraslow, asynchronous fluctuations in the intracellular Na concentration of neurons and astrocytes. We show that this activity is not correlated with the previously reported synchronous neuronal population bursting or Ca oscillations, both of which occur at much faster timescales. Furthermore, extracellular K concentration remains nearly constant. The spontaneous Na fluctuations disappear after the first postnatal week.
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http://dx.doi.org/10.1152/jn.00373.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948148PMC
February 2021

Impaired θ-γ Coupling Indicates Inhibitory Dysfunction and Seizure Risk in a Dravet Syndrome Mouse Model.

J Neurosci 2021 01 24;41(3):524-537. Epub 2020 Nov 24.

Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.

Dravet syndrome (DS) is an epileptic encephalopathy that still lacks biomarkers for epileptogenesis and its treatment. Dysfunction of Na1.1 sodium channels, which are chiefly expressed in inhibitory interneurons, explains the epileptic phenotype. Understanding the network effects of these cellular deficits may help predict epileptogenesis. Here, we studied θ-γ coupling as a potential marker for altered inhibitory functioning and epileptogenesis in a DS mouse model. We found that cortical θ-γ coupling was reduced in both male and female juvenile DS mice and persisted only if spontaneous seizures occurred. θ-γ Coupling was partly restored by cannabidiol (CBD). Locally disrupting Na1.1 expression in the hippocampus or cortex yielded early attenuation of θ-γ coupling, which in the hippocampus associated with fast ripples, and which was replicated in a computational model when voltage-gated sodium currents were impaired in basket cells (BCs). Our results indicate attenuated θ-γ coupling as a promising early indicator of inhibitory dysfunction and seizure risk in DS.
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http://dx.doi.org/10.1523/JNEUROSCI.2132-20.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821857PMC
January 2021

Physical activity, dietary habits and sleep quality before and during COVID-19 lockdown: A longitudinal study.

Appetite 2021 03 5;158:105019. Epub 2020 Nov 5.

Well-Move Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), Faculty of Education and Sport Science, Department of Special Didactics, University of Vigo, Campus a Xunqueira, S/n, 36005, Pontevedra, Spain. Electronic address:

The COVID-19 pandemic has forced the health public authorities to impose a lockdown as an epidemiological containment strategy. This study aimed to provide information regarding the impact of the mandatory confinement on the physical activity, eating disorders risk, sleep quality and well-being on a Spanish sample. An online survey that included the Minnesota Leisure Time Physical Activity Questionnaire, the Eating Attitude Test-26, and Pittsburgh Sleep Quality Index was administered two days after the state of alarm was stablished in Spain and five days after such measures began to be eased. Out of the 693 people who answered the first questionnaire, 161 completed the second one. These participants spent a total of 48 days locked at home, a period during which a significant worsening in all the variables assessed except for the risk of developing eating disorders, was observed: weight (kg), 67.3 ± 14.8 vs 67.7 ± 15.1, p = 0.012; physical activity (MET minutes per week), 8515.7 ± 10260.0 vs 5053.5 ± 5502.0, p < 0.001; sleep problems (total score), 6.2 ± 3.5 vs 7.2 ± 3.9, p < 0.001; self-perceived well-being (score), 4 (3-4) vs 3 (3-4), p < 0.001. The confinement had a significant differential effect on physically active participants, who experienced a significant decline (p < 0.05) on their physical activity levels, quality of sleep and well-being; whereas physically inactive participants did not experience significant changes. Findings from this longitudinal study indicate that a lockdown period due to COVID-19 had a negative impact on the physical activity levels, sleep quality and well-being in a group of physically active Spanish adults. Public health authorities should be aware that people who usually lead an active lifestyle, might be particularly susceptible to such disruptions.
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http://dx.doi.org/10.1016/j.appet.2020.105019DOI Listing
March 2021

Levorphanol in the Perioperative Setting: Decreasing Opioid Requirements While Improving Pain Management.

J Pain Res 2020 29;13:2721-2727. Epub 2020 Oct 29.

Department of Anesthesiology, Stony Brook University Hospital, Stony Brook, NY, USA.

Levorphanol is a Food and Drug Administration (FDA)-approved long-acting opioid. Most information on perioperative use of levorphanol comes from the early- and mid-1950s when this drug emerged in the field of experimental pharmacology and anesthesia. It was mainly studied during this period with some additional data being generated in the 1960s and 70s. Since this time, perioperative use has declined and research is limited. This review of literature aims to provide pharmacologic and historic description of levorphanol as a tool for perioperative pain management and as an aid to potentially decrease total postoperative opioid use during the current opioid crisis.
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http://dx.doi.org/10.2147/JPR.S271456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605938PMC
October 2020

A new species of Zygophylax (Quelch, 1885) (Cnidaria, Hydrozoa) from South Africa, with taxonomic notes on the southern African species of the genus.

Zootaxa 2020 May 21;4779(4):zootaxa.4779.4.5. Epub 2020 May 21.

Programa de Pós-Graduação em Biologia Animal, Departamento de Zoologia, Centro de Biociências, Universidade Federal de Pernambuco. Av. Professor Moraes Rego, 1235, Recife, Pernambuco, Brazil. CEP: 50670-420.

The genus Zygophylax is a genus of leptothecate hydroids considerably rich in the number of species in the deep sea. In this study we review five species, Z. africana, Z. crozetensis, Z. infundibulum, Z. millardae and Z. geminocarpa, from southern Africa based on available material from several collections, describing and illustrating materials from type series or additional material. Additionally, we describe Zygophylax naomiae sp. nov. collected in South Africa at a depth of 287 m, distinguished from its congeners by the strong pattern of annulations of the pedicels of the hydrotheca and the nematotheca.
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http://dx.doi.org/10.11646/zootaxa.4779.4.5DOI Listing
May 2020

IMA Genome - F13: Draft genome sequences of , and .

IMA Fungus 2020 24;11:19. Epub 2020 Sep 24.

Department of Biochemistry, Genetics and Microbiology, Forestry and Agricultural Biotechnology Institute (FABI), University of Pretoria, Private Bag x20, Hatfield, Pretoria, 0028 South Africa.

Draft genomes of the fungal species , and are presented. is an important lichen forming fungus and is an ambrosia beetle symbiont. and are agriculturally relevant plant pathogens that cause leaf-spots in brassicaceous vegetables and cucurbits respectively. causes severe leaf blight and defoliation of trees. These genomes provide a valuable resource for understanding the molecular processes in these economically important fungi.
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http://dx.doi.org/10.1186/s43008-020-00039-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513301PMC
September 2020

First-in-Human Study with Eight Patients Using an Absorbable Vena Cava Filter for the Prevention of Pulmonary Embolism.

J Vasc Interv Radiol 2020 Nov 29;31(11):1817-1824. Epub 2020 Sep 29.

Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: To prospectively evaluate the initial human experience with an absorbable vena cava filter designed for transient protection from pulmonary embolism (PE).

Materials And Methods: This was a prospective, single-arm, first-in-human study of 8 patients with elevated risk of venous thromboembolism (VTE). Seven absorbable IVC filters (made of polydioxanone that breaks down into HO and CO in 6 mo) were placed prophylactically before orthopedic (n = 5) and gynecologic (n = 2) surgeries, and 1 was placed in a case of deep vein thrombosis. Subjects underwent CT cavography and abdominal radiography before and 5, 11, and 36 weeks after filter placement to assess filter migration, embolization, perforation, and caval thrombosis and/or stenosis. Potential PE was assessed immediately before and 5 weeks after filter placement by pulmonary CT angiography.

Results: No symptomatic PE was reported throughout the study or detected at the planned 5-week follow-up. No filter migration was detected based on the fixed location of the radiopaque markers (attached to the stent section of the filter) relative to the vertebral bodies. No filter embolization or caval perforation was detected, and no caval stenosis was observed. Throughout the study, no filter-related adverse events were reported.

Conclusions: Implantation of an absorbable vena cava filter in a limited number of human subjects resulted in 100% clinical success. One planned deployment was aborted as a result of stenotic pelvic veins, resulting in 89% technical success. No PE or filter-related adverse events were observed.
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http://dx.doi.org/10.1016/j.jvir.2020.07.021DOI Listing
November 2020

Investigating counterfeiting of an artwork by XRF, SEM-EDS, FTIR and synchrotron radiation induced MA-XRF at LNLS-BRAZIL.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Feb 9;246:118925. Epub 2020 Sep 9.

Laboratório de Instrumentação e Simulação Computacional, LISCOMP/IFRJ-CPAR, 26600-000 Paracambi, Brazil. Electronic address:

In this work, a painting suspected of counterfeiting was analyzed using the synchrotron-based scanning macro X-ray fluorescence (MA-XRF) technique. The canvas has erasures including a signature erasure; however, some visible numbers indicate that the artwork may be from the 17th century. Through the studies' elemental maps, Cl-K and Ca-K were observed, which allowed us to reconstruct the signature present in the painting. Elemental maps of Ba-K, Ti-K, Fe-K, Zn-K, and Pb-K were also obtained from the painting, which made possible to visualize how the pigments based on these elements were used in the creative composition of the painting. In addition to the signature region, a region of the painting with dimensions of approximately 120 mm × 120 mm was investigated by synchrotron radiation induced MA-XRF, while keeping a high spatial resolution and elemental sensitivity. The measurements were carried out at the D09B micro-XRF beamline of the Brazilian Synchrotron Light Laboratory (LNLS), part of the Brazilian Center of Research in Energy and Materials, in Campinas Brazil. The painting was also investigated by SEM-EDS, and FTIR techniques. Those results, in addition to the supporting elemental maps, allowed additional information to be obtained, such as the binders used on the painting.
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http://dx.doi.org/10.1016/j.saa.2020.118925DOI Listing
February 2021

Looking ahead: The risk of neurologic complications due to COVID-19.

Authors:
Carlos A Pérez

Neurol Clin Pract 2020 Aug;10(4):371-374

Division of Multiple Sclerosis and Neuroimmunology, Department of Neurology, University of Texas Health Science Center at Houston, Houston, TX.

The rapid spread of Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has become a public health emergency of international concern. The outbreak was characterized as a pandemic by the World Health Organization (WHO) in March 2020. The most characteristic symptom of patients with COVID-19 is respiratory distress. Some patients may also show neurologic signs and symptoms ranging from headache, nausea, vomiting, and confusion to anosmia, ageusia, encephalitis, and stroke. Coronaviruses are known pathogens with neuroinvasive potential. There is increasing evidence that coronavirus infections are not always confined to the respiratory tract. CNS involvement can occur in susceptible individuals and may contribute overall morbidity and mortality in the acute setting. In addition, postinfectious, immune-mediated complications in the convalescent period are possible. Awareness and recognition of neurologic manifestations is essential to guide therapeutic decision-making because the current outbreak continues to unfold.
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http://dx.doi.org/10.1212/CPJ.0000000000000836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508336PMC
August 2020

Assessment of Racial/Ethnic Disparities in Volumetric MRI Correlates of Clinical Disability in Multiple Sclerosis: A Preliminary Study.

J Neuroimaging 2021 01 19;31(1):115-123. Epub 2020 Sep 19.

Division of Multiple Sclerosis and Neuroimmunology, Department of Neurology, McGovern Medical School (UT Health), University of Texas Health Science Center at Houston, Houston, TX.

Background And Purpose: Although global and regional brain volume has been established as a relevant measure to define and predict multiple sclerosis (MS) severity, characterization of specific trends by race/ethnicity is currently lacking. We aim to (1) characterize racial disparities in disability-specific patterns of brain MRI volumetric measures between Hispanic and Caucasian individuals with MS and (2) explore the relevance of these measures as predictors of clinical disability progression.

Methods: Brain MRI scans from 94 Hispanic and 94 age- and gender-matched Caucasian MS patients were analyzed using automatic and manual segmentation techniques. Select global and regional volume measures were correlated to Expanded Disability Status Scale (EDSS) scores at baseline and subsequent follow-up visits.

Results: Hispanic patients had a higher baseline median EDSS score (interquartile range [IQR], 2.0; [1.0-3.5]) compared to Caucasians (median [IQR], 1.0 [.0-2.0]) and an increased risk of requiring ambulatory assistance (hazard ratio [HR], 9.7; 95% confidence interval [CI], 2.8-32.5). Normalized thalamic volume was moderately associated with EDSS scores (r   = -.42,  P < .001 in Hispanics; r   = -.32, P  = .002 in Caucasians) and was the best predictor of sustained disability worsening in both racial groups in a time-to-event analysis.

Conclusions: The confounding impact of race on quantitative brain volume measures may affect the interpretation of outcome measures in MS clinical trials.
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http://dx.doi.org/10.1111/jon.12788DOI Listing
January 2021

Assessment of Racial/Ethnic Disparities in Volumetric MRI Correlates of Clinical Disability in Multiple Sclerosis: A Preliminary Study.

J Neuroimaging 2021 01 19;31(1):115-123. Epub 2020 Sep 19.

Division of Multiple Sclerosis and Neuroimmunology, Department of Neurology, McGovern Medical School (UT Health), University of Texas Health Science Center at Houston, Houston, TX.

Background And Purpose: Although global and regional brain volume has been established as a relevant measure to define and predict multiple sclerosis (MS) severity, characterization of specific trends by race/ethnicity is currently lacking. We aim to (1) characterize racial disparities in disability-specific patterns of brain MRI volumetric measures between Hispanic and Caucasian individuals with MS and (2) explore the relevance of these measures as predictors of clinical disability progression.

Methods: Brain MRI scans from 94 Hispanic and 94 age- and gender-matched Caucasian MS patients were analyzed using automatic and manual segmentation techniques. Select global and regional volume measures were correlated to Expanded Disability Status Scale (EDSS) scores at baseline and subsequent follow-up visits.

Results: Hispanic patients had a higher baseline median EDSS score (interquartile range [IQR], 2.0; [1.0-3.5]) compared to Caucasians (median [IQR], 1.0 [.0-2.0]) and an increased risk of requiring ambulatory assistance (hazard ratio [HR], 9.7; 95% confidence interval [CI], 2.8-32.5). Normalized thalamic volume was moderately associated with EDSS scores (r   = -.42,  P < .001 in Hispanics; r   = -.32, P  = .002 in Caucasians) and was the best predictor of sustained disability worsening in both racial groups in a time-to-event analysis.

Conclusions: The confounding impact of race on quantitative brain volume measures may affect the interpretation of outcome measures in MS clinical trials.
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http://dx.doi.org/10.1111/jon.12788DOI Listing
January 2021

Coccolithophore community response to ocean acidification and warming in the Eastern Mediterranean Sea: results from a mesocosm experiment.

Sci Rep 2020 07 28;10(1):12637. Epub 2020 Jul 28.

Institute of Environmental Science and Technology (ICTA), Universitat Autònoma de Barcelona (UAB), 08193, Bellaterra, Spain.

Mesocosm experiments have been fundamental to investigate the effects of elevated CO and ocean acidification (OA) on planktic communities. However, few of these experiments have been conducted using naturally nutrient-limited waters and/or considering the combined effects of OA and ocean warming (OW). Coccolithophores are a group of calcifying phytoplankton that can reach high abundances in the Mediterranean Sea, and whose responses to OA are modulated by temperature and nutrients. We present the results of the first land-based mesocosm experiment testing the effects of combined OA and OW on an oligotrophic Eastern Mediterranean coccolithophore community. Coccolithophore cell abundance drastically decreased under OW and combined OA and OW (greenhouse, GH) conditions. Emiliania huxleyi calcite mass decreased consistently only in the GH treatment; moreover, anomalous calcifications (i.e. coccolith malformations) were particularly common in the perturbed treatments, especially under OA. Overall, these data suggest that the projected increase in sea surface temperatures, including marine heatwaves, will cause rapid changes in Eastern Mediterranean coccolithophore communities, and that these effects will be exacerbated by OA.
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http://dx.doi.org/10.1038/s41598-020-69519-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387480PMC
July 2020

Unveiling the role of bioturbation on bacterial activity in metal-contaminated sediments.

Sci Total Environ 2020 Nov 18;744:140988. Epub 2020 Jul 18.

Graduate Program in Oceans and Earth Dynamics, Federal Fluminense University, Niterói, RJ, Brazil; Graduate Program in Marine Biology and Coastal Environments, Federal Fluminense University, Niterói, RJ, Brazil.

The processes permeating the relationships between bioturbation and microorganisms remain poorly understood due to the difficulty of traditional techniques in quantifying their two- and three-dimensional aspects. We used cutting-edge technologies to address the macro- and microorganisms' interactions under metal-contamination. Bioturbation (mucus-lined gallery perimeter, mucus-lined gallery surface area, and gallery water volume) positively influence the carbohydrate consumption rate by the bacterial consortium, elevating bacterial metabolic activity, despite metal-contamination. Synchrotron-based 2D-μXRF revealed that the mucous lining by marine worm during bioturbation as the primary carbon source enhances metal immobilization by bacterial biofilm, improving the bacterial metabolic activity. Bioturbation thus can positively affect bacterial consortium that can use the mucus as a carbon source, which enhances the resistance to metals through biofilm formation in metal-contaminated sediments.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140988DOI Listing
November 2020

Concurrent chemo-radiotherapy with proton therapy: reduced toxicity with comparable oncological outcomes vs photon chemo-radiotherapy.

Br J Cancer 2020 09 18;123(6):869-870. Epub 2020 Jun 18.

Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Concurrent chemo-radiotherapy is a commonly employed curative treatment approach for locally advanced cancers but is associated with considerable morbidity. Chemo-radiotherapy using proton therapy may be able to reduce side effects of treatment and improve efficacy, but this remains an area of controversy and data are relatively limited. We comment on recently published studies and discuss future directions for proton therapy.
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http://dx.doi.org/10.1038/s41416-020-0919-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493883PMC
September 2020

Tumefactive Demyelinating Lesions in Children: A Rare Case of Conus Medullaris Involvement and Systematic Review of the Literature.

J Child Neurol 2020 09 19;35(10):690-699. Epub 2020 Jun 19.

McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.

Tumefactive demyelinating lesions are an uncommon manifestation of demyelinating disease that mimic primary central nervous system neoplasms and can pose a diagnostic challenge in patients without a pre-existing diagnosis of multiple sclerosis. Although a biopsy may be required to distinguish TDL from neoplasms or infection, certain ancillary and radiographic findings may preclude the need for invasive diagnostic procedures. We describe the case of a 15-year-old boy with a tumefactive demyelinating lesion involving the conus medullaris. An exhaustive systematic literature search of pediatric cases of TDL yielded an additional 78 cases. This review summarizes the current knowledge and recommendations for the diagnosis and management of this condition, highlighting the clinical, demographic, and radiologic features of 79 reported cases, including our own. Furthermore, it underscores areas of the literature where evidence is still lacking. Further research is needed to optimize clinical detection and medical management of this condition.
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http://dx.doi.org/10.1177/0883073820924147DOI Listing
September 2020

Management of primary skin cancer during a pandemic: Multidisciplinary recommendations.

Cancer 2020 09 1;126(17):3900-3906. Epub 2020 Jun 1.

Division of Dermatologic Surgery, Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

During the coronavirus disease 2019 (COVID-19) pandemic, providers and patients must engage in shared decision making regarding the pros and cons of early versus delayed interventions for localized skin cancer. Patients at highest risk of COVID-19 complications are older; are immunosuppressed; and have diabetes, cancer, or cardiopulmonary disease, with multiple comorbidities associated with worse outcomes. Physicians must weigh the patient's risk of COVID-19 complications in the event of exposure against the risk of worse oncologic outcomes from delaying cancer therapy. Herein, the authors have summarized current data regarding the risk of COVID-19 complications and mortality based on age and comorbidities and have reviewed the literature assessing how treatment delays affect oncologic outcomes. They also have provided multidisciplinary recommendations regarding the timing of local therapy for early-stage skin cancers during this pandemic with input from experts at 11 different institutions. For patients with Merkel cell carcinoma, the authors recommend prioritizing treatment, but a short delay can be considered for patients with favorable T1 disease who are at higher risk of COVID-19 complications. For patients with melanoma, the authors recommend delaying the treatment of patients with T0 to T1 disease for 3 months if there is no macroscopic residual disease at the time of biopsy. Treatment of tumors ≥T2 can be delayed for 3 months if the biopsy margins are negative. For patients with cutaneous squamous cell carcinoma, those with Brigham and Women's Hospital T1 to T2a disease can have their treatment delayed for 2 to 3 months unless there is rapid growth, symptomatic lesions, or the patient is immunocompromised. The treatment of tumors ≥T2b should be prioritized, but a 1-month to 2-month delay is unlikely to worsen disease-specific mortality. For patients with squamous cell carcinoma in situ and basal cell carcinoma, treatment can be deferred for 3 months unless the individual is highly symptomatic.
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http://dx.doi.org/10.1002/cncr.32969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301000PMC
September 2020