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The aim of this research was to study the relationship between parenting stress and coping strategies of mothers of children with Attention Deficit Hyperactivity Disorder (ADHD). The sample consisted of 143 mothers with a child who had been diagnosed with ADHD. The mothers completed a sociodemographic questionnaire, the Coping Strategies Questionnaire (CAE) and the Parenting Stress Index Short Form (PSI-SF). The results showed that mothers experienced high levels of stress and they tended to use coping strategies focused on problem solving. Meaningful differences were found between parenting stress and coping strategies according to sociodemographic characteristics. Negative correlations between parenting stress and coping strategies showed that coping strategies focused on problem solving were associated with lower levels of stress. Besides, positive correlations between parenting stress and coping strategies showed that higher levels of emotional coping strategies were associated with higher levels of parenting stress.

Whole-genome alignment allows researchers to understand the genomic structure and variations among the genomes. Approaches based on direct pairwise comparisons of DNA sequences require large computational capacities. As a consequence, pipelines combining tools for orthologous gene identification and synteny have been developed. In this manuscript, we present the latest functionalities implemented in NGSEP 4, to identify orthogroups and perform whole genome alignments. NGSEP implements functionalities for identification of clusters of homologus genes, synteny analysis and whole genome alignment, and visualization. Our results showed that the NGSEP algorithm for ortholog identification has competitive accuracy and better efficiency in comparison to commonly used tools. The implementation also includes a visualization of the whole genome alignment based on synteny of the orthogroups that were identified, and a reconstruction of the pangenome based on frequencies of the orthogroups among the genomes. Finally, our software includes a new graphical user interface. We expect that these new developments will be very useful for several studies in evolutionary biology and population genomics.

The aim of this study was to determine color change after accelerated artificial ageing (AAA) of different composite cements that are used with veneers. Five cylindrical test specimens, 15 mm in diameter and 2 mm thick, were made from a single layer of each of the following: RelyX Veneer 3M ESPE (RX), Paracore White Coltene (PC), Solocem White Opaque Coltene (SO), Resin Duo Cement Densell (DC), Panavia V5 Paste Kuraray Noritake (PA) and Panavia F2.0 Kuraray Noritake (PF) (30 specimens altogether). The specimens were light cured following manufacturers’ instructions using a Coltolux LED (Coltene) unit. Initial color was determined using an Easyshade - Vita Zahnfabrik Spectrophotometer. Then, the specimens were subjected to AAA for two weeks (336 hours) with cycles of 4 hours of UV light at 60 °C and 4 hours of vapor condensation at 50 °C, successively, after which color was recorded again. Color change was determined for each specimen according to the difference in shade on the Vita scale before and after AAA. Results were analyzed using Kruskal Wallis test. Mean and standard deviation for each group were: RX 8.40 (1.52); PC 8.60 (3.13); SO 6.40 (3.51); DC 10.00 (0.00); PA 7.60 (3.29); PF 2.00 (0.00). The Kruskal Wallis test showed significant difference for material (p

Introduction We previously conducted a survey study in April 2020 at the beginning of the SARS-CoV-2 (COVID-19) pandemic to understand how it affected patients with myasthenia gravis (MG). Since then, significant advances have occurred in the following areas: knowledge about the SARS-CoV-2 virus, infection risk mitigation, patient management, risks for MG patients, and a global vaccination program. We conducted a follow-up survey in February 2021 to assess how these advances impacted the care and perception of MG patients. Methods We conducted a prospective online survey study of MG patients at a large academic practice in the Duke Health System. Results Seventy-eight patients participated in the survey including 55 from previous survey and 23 newly identified patients. The top reported change in the interaction with healthcare providers was an increase in telemedicine visits (74%). The median satisfaction score (0-100 scale) for telemedicine visits was 74. Ninety-six percent of survey participants expressed concern about pandemic and nearly half of participants showed anxiety based on Generalized Anxiety Disorder-7 score. The top 3 concerns related to COVID-19 were getting hospitalized (62%), exacerbation (62%) and death (53%). Discussion Although the results of follow-up survey were overall similar to the previous study, most of patients switched from in-person clinic visits to telemedicines. The overwhelmingly large portion of patients continue to have concern and anxiety for pandemic but the patients with severe symptoms have higher anxiety scores. Conclusion This follow-up survey demonstrated the adjustment of MG patients to new methods of communication, significant psychological impact of COVID-19 on them and their good healthcare literacy.

Genetic engineering of nanoparticle biosynthesis in bacteria could help facilitate the production of nanoparticles with enhanced or desired properties. However, this process remains limited due to the lack of mechanistic knowledge regarding specific enzymes and other key biological factors. Herein, we report on the ability of small noncoding RNAs (sRNAs) to affect silver nanoparticle (AgNP) biosynthesis using the supernatant from the bacterium Deinococcus radiodurans. Deletion strains of 12 sRNAs potentially involved in the oxidative stress response were constructed, and the supernatants from these strains were screened for their effect on AgNP biosynthesis. We identified several sRNA deletions that drastically decreased AgNP yield compared to the wild-type (WT) strain, suggesting the importance of these sRNAs in AgNP biosynthesis. Furthermore, AgNPs biosynthesized using the supernatants from three of these sRNA deletion strains demonstrated significantly enhanced antimicrobial and catalytic activities against environmentally relevant dyes and bacteria relative to AgNPs biosynthesized using the WT strain. Characterization of these AgNPs using electron microscopy (EM), energy-dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) revealed that the deletion of these small RNAs led to changes within the supernatant composition that altered AgNP properties such as the surface chemistry, surface potential, and overall composition. Taken together, our results demonstrate that modulating specific sRNA levels can affect the composition of supernatants used to biosynthesize AgNPs, resulting in AgNPs with unique material properties and improved functionality; as such, we introduce sRNAs as a new platform for genetically engineering the biosynthesis of metal nanoparticles using bacteria. Many of the sRNAs examined in this work have potential regulatory roles in oxidative stress responses; further studies into their targets could help provide insight into the specific molecular mechanisms underlying bacterial biosynthesis and metal reduction, enabling the production of nanoparticles with enhanced properties.

Peripheral nerve imaging is a helpful and sometimes essential adjunct to clinical history, physical examination, and electrodiagnostic studies. Advances in imaging technology have allowed the visualization of nerve structures and their surrounding tissues. The clinical applications of ultrasound and magnetic resonance imaging (MRI) in the evaluation of peripheral nerve disorders are growing exponentially. This article reviews basics of ultrasound and MRI as they relate to nerve imaging, reviews advantages and limitations of each imaging modality, reviews the applications of ultrasound and MRI in disorders of peripheral nerve, and discusses emerging advances in the field.

Background The immunopathology of autoimmune seronegative myasthenia gravis (SN MG) is poorly understood. Our objective was to determine immune profiles associated with a diagnosis of SN MG. Methods We performed high-dimensional flow cytometry on blood samples from SN MG patients (N = 68), healthy controls (N = 46), and acetylcholine receptor antibody (AChR+) MG patients (N = 27). We compared 12 immune cell subsets in SN MG to controls using logistic modeling via a discovery-replication design. An exploratory analysis fit a multinomial model comparing AChR+ MG and controls to SN MG. Results An increase in CD19+ CD20- CD38hi plasmablast frequencies was associated with lower odds of being a SN MG case in both the discovery and replication analyses (discovery P-value = .0003, replication P-value = .0021). Interleukin (IL) -21 producing helper T cell frequencies were associated with a diagnosis of AChR+ MG (P = .004). Conclusions Reduced plasmablast frequencies are strongly associated with a SN MG diagnosis and may be a useful diagnostic biomarker in the future.

The ongoing coronavirus 2019 disease (COVID-19) pandemic strained medical systems worldwide. We report on the impact on pediatric oncology care in Latin American (LATAM) during its first year.Four cross-sectional surveys were electronically distributed among pediatric onco-hematologists in April/June/October 2020, and April/2021 through the Latin American Society of Pediatric Oncology (SLAOP) email list and St Jude Global regional partners.Four hundred fifty-three pediatric onco-hematologists from 20 countries responded to the first survey, with subsequent surveys response rates above 85%. More than 95% of participants reported that treatment continued without interruption for new and active ongoing patients, though with disruptions in treatment availability. During the first three surveys, respondents reported suspensions of outpatient procedures (54.2%), a decrease in oncologic surgeries (43.6%), radiotherapy (28.4%), stem cell transplants (SCT) (69.3%), and surveillance consultations (81.2%). Logistic regression analysis showed that at the beginning of the first wave, participants from countries with healthcare expenditure below 7% were more likely to report a decrease in outpatient procedures (odds ratio [OR]: 1.84, 95% CI: 1.19-2.8), surgeries (OR: 3, 95% CI: 1.9-4.6) and radiotherapy (OR: 6, 95% CI: 3.5-10.4). Suspension of surveillance consultations was higher in countries with COVID-19 case fatality rates above 2% (OR: 3, 95% CI: 1.4-6.2) and SCT suspensions in countries with COVID-19 incidence rate above 100 cases per 100,000 (OR: 3.48, 95% CI: 1.6-7.45). Paradoxically, at the beginning of the second wave with COVID-19 cases rising exponentially, most participants reported improvements in cancer services availability.Our data show the medium-term collateral effects of the pandemic on pediatric oncology care in LATAM, which might help delineate oncology care delivery amid current and future challenges posed by the pandemic.

Early identification of children at risk for autism spectrum disorder (ASD) is critical to promote optimal outcomes. However disparities in early recognition of ASD based on race, ethnicity, income, and English proficiency persist. Little is known regarding how parents from these groups describe concerns. The study aim was to understand how parents of children from underserved backgrounds at developmental risk describe concerns about child development and behavior. To address this gap, developmental concerns of 204 parents of children at-risk for ASD from underserved communities were analyzed. In this sample, the number and type of parental concerns differed based on parent primary language but not the presence of ASD or ethnicity. Parents whose primary language was Spanish were less likely to express concerns about their child's development or to express ASD-specific concerns. These findings have implications for how clinicians elicit and interpret developmental concerns from underserved families.

Antibiotic-sparing treatments are required to prevent the further emergence of antimicrobial resistance in Neisseria gonorrhoeae. Commensal Neisseria species have previously been found to inhibit the growth of pathogenic Neisseria species. For example, a previous study found that three out of five historical isolates of Neisseria mucosa could inhibit the growth of N. gonorrhoeae. In this study, we used agar overlay assays to assess if 24 circulating and historical isolates of Neisseria mucosa could inhibit the growth of 28 circulating and historical isolates of N. gonorrhoeae. Although pitting around each colony of N. mucosa created an optical illusion of decreased growth of N. gonorrhoeae, we found no evidence of inhibition (n = 24). In contrast, positive controls of Streptococcus pneumoniae and Escherichia coli demonstrated a strong inhibitory effect against the growth of N. gonorrhoeae.

The aim of this study was to determine color change after accelerated artificial ageing (AAA) of different composite cements that are used with veneers. Five cylindrical test specimens, 15 mm in diameter and 2 mm thick, were made from a single layer of each of the following: RelyX Veneer 3M ESPE (RX), Paracore White Coltene (PC), Solocem White Opaque Coltene (SO), Resin Duo Cement Densell (DC), Panavia V5 Paste Kuraray Noritake (PA) and Panavia F2.0 Kuraray Noritake (PF) (30 specimens altogether). The specimens were light cured following manufacturers' instructions using a Coltolux LED (Coltene) unit. Initial color was determined using an Easyshade - Vita Zahnfabrik Spectrophotometer. Then, the specimens were subjected to AAA for two weeks (336 hours) with cycles of 4 hours of UV light at 60 °C and 4 hours of vapor condensation at 50 °C, successively, after which color was recorded again. Color change was determined for each specimen according to the differenceinshadeon the Vita scale before and after AAA. Results were analyzed using Kruskal Wallis test. Mean and standard deviation for each group were: RX 8.40 (1.52); PC 8.60 (3.13); SO 6.40 (3.51); DC 10.00 (0.00); PA 7.60 (3.29); PF 2.00 (0.00). The Kruskal Wallis test showed significant difference for material (p0.05), and comparison of means showed difference between Panavia F2.0 and the other materials. A table providing equivalence between the Vita Classic and CIELAB scales was used to transfer the recorded colors to the CIELAB scale, and the color difference ΔE was calculated for each group, where ΔL, Δa and Δb are the differences in the L, a and b values before and after the AAA. The mean and standard deviation were analyzed statistically by the ANOVA test and Tukey's test. Mean and standard deviation for each group were: RX 14.94 (2.02); PC 14.51 (4.02); SO 12.08 (4.53); DC 16.31 (0.00); PA 10.9 (3.38); PF 7.24 (0.00). The ANOVA test showed significantdifferenceformaterial (p0.05). Tukey's test showed two groups (PF-DC, RX, PA). Under the experimental conditions of this study, it can be concluded that accelerated ageing significantly affects the color stability of the resin based cements tested.El objetivo de este trabajo fue determinar el cambio de coloración de distintos medios de fijación a base de resinas con indicación para carillas estéticas luego de someterse al envejecimiento artificial acelerado (AAA). Se confeccionaron 30 probetas cilíndricas de 15 mm de diámetro y 2 mm de espesor con RelyX Veneer 3M ESPE (RX), Paracore White Coltene (PC), Solocem White Opaque Coltene (SO), Resin Duo Cement Densell (DC), Panavia V5 Paste Kuraray Noritake (PA) y Panavia F2.0 Kuraray Noritake (PF) de una sola capa de material. Se polimerizaron según las indicaciones del fabricante con unidad de curado Coltolux LED (Coltene). Cada grupo quedó conformado con 5 probetas de cada material. Se tomó el color con el espectrofotómetro Easyshade de Vita Zahnfabrik. A continuación, se sometieron a AAA por dos semanas (336 horas) con ciclos de 4 horas de radiaciones ultravioletas a 60°C Y 4 horas de condensación de vapor de agua a 50°C sucesivamente. Unavezterminado esteproceso se volvió a registrar el color. El cambio de color se evaluó dentro de la escala de color, ordenada en función del valor. El dato registrado fue la diferencia en la posición inicial y final en esta escala. Los resultados obtenidos para cada grupo fueron analizados por medio de la prueba de Kruskal Wallis. Los valores de media y desvío estándar de cada grupo fueron: RX 8,40 (1,52); PC 8,60 (3,13); SO 6,40 (3,51); DC 10,00 (0,00); PA 7,60 (3,29); PF 2,00 (0,00). El análisis con la prueba de Kruskal Wallis mostró diferencia significativa para el factor material (p0.05) y la comparación de medias mostró diferencia entre PF y el resto de los materiales. Por otra parte, con una tabla de equivalencia entre los colores en escala de Vita Classic y CIE Lab, se hicieron el pasaje de los valores registrados a la escala de CIE Lab y se calculó la diferencia de color ΔE de cada grupo antes y después del AAA. La media y el desvío estándarfueronanalizadosestadísticamente por el test de ANOVA y prueba de Tukey. Los valores de media y desvío estándar de cada grupo fueron: RX 14,94 (2,02); PC 14,51 (4,02); SO 12,08 (4,53); DC 16,31 (0,00); PA 10,9 (3,38); PF 7,24 (0,00). En la evaluación de los resultados con ANOVA se encontró diferencia significativa entre los materiales evaluados (p0,05). La comparación de medias con prueba de Tukey mostró la presencia de dos grupos (PF-DC, RX, PA). En las condiciones experimentales de este trabajo puede concluirse que el envejecimiento acelerado afecta significativamente la estabilidad de color de los cementos utilizados en este trabajo.

One known adverse event associated with dimethyl fumarate (DMF) is grade III lymphopenia which usually resolves within 2–3 months upon DMF discontinuation. Here, we report a case of a 50-year-old woman with MS who developed grade III lymphopenia within 6 months of DMF initiation, and despite treatment cessation within the next 6 months, she has continued to have severe persistent lymphopenia for over 5 years. Our observation suggests prolonged and possibly irreversible lymphopenia as a possible adverse event of DMF, and it emphasizes the need for monitoring lymphocyte numbers, and to cease dosing promptly after onset of grade III lymphopenia.

We used agar overlay assays to assess if 24 circulating and historical isolates of Neisseria mucosa could inhibit the growth of 28 circulating and historical isolates of N. gonorrhoeae. We found no evidence of inhibition by N. mucosa (n=24). Positive controls Streptococcus pneumoniae and Escherichia coli demonstrated a strong inhibitory effect against the growth of N. gonorrhoeae.

A 38-year-old woman with uncontrolled type 1 diabetes (HbA1c 12.8%) was admitted for diabetic ketoacidosis (731 mg/dL blood glucose). Hyperglycemia was corrected within 24 hours to 129 mg/dL. Upon presentation, her sodium and potassium levels were 139 and 3.9 mmol/L, respectively, remaining stable until discharge. There was no history of malnutrition or alcohol abuse.

BackgroundConcentrations of fluoroquinolones up to 200-fold lower than the MIC have been shown to be able to select for antimicrobial resistance in E. coli and Salmonella spp. (the minimum selection concentration – MSC). We aimed to i) establish what the ciprofloxacin MSC is for Neisseria gonorrhoeae and ii) Assess at a country level if the prevalence of gonococcal ciprofloxacin resistance is associated with the concentration of quinolones used in food animal production (an important determinant of long-term low dose ciprofloxacin exposures in humans).Methodsi). To assess if sub-inhibitory ciprofloxacin concentrations could select for de novo generated resistant mutants, susceptible WHO-P was serially passaged at 1, 1/10, 1/100 and 1/1000 of the ciprofloxacin MIC of WHO-P (0.004mg/L) on GC agar plates. ii) Spearman’s correlation was used to assess the association between the prevalence of ciprofloxacin resistance in N. gonorrhoeae and the two independent variables – quinolone use for animals and quinolone consumption by humans.ResultsCiprofloxacin concentrations as low as 1/1000 of the MIC of WHO-P were able to select for ciprofloxacin resistance. The prevalence of ciprofloxacin resistance in N. gonorrhoeae was positively associated with quinolone use for food animals (ρ=0.47; P=0.004; N=34).ConclusionFurther individual level research is required to assess if low doses of ciprofloxacin from ingested foodstuffs are able to select for ciprofloxacin resistance in N. gonorrhoeae and other species.

No necesita de un resumen.

Background: The role of retinal imaging with optical coherence tomography (OCT) in assessing individuals with radiologically isolated syndrome (RIS) remains largely unexplored. Objective: To assess retinal layer thicknesses in RIS and examine their associations with clinical features suggestive of increased risk for conversion to multiple sclerosis (MS). Methods: A total of 30 RIS subjects and 60 age- and sex-matched healthy controls (HC) underwent retinal imaging with spectral-domain OCT, followed by automated segmentation of retinal layers. Results: Overall, retinal layer thicknesses did not differ between RIS and HC. However, RIS subjects with spinal cord (SC) lesions had lower ganglion cell + inner plexiform layer (GCIP) thickness compared to HC (−4.41 μm; p = 0.007) and RIS without SC lesions (–3.53 μm; p = 0.041). Similarly, RIS subjects with infratentorial (IT) brain lesions had lower GCIP thickness compared to HC (–4.07 μm; p Conclusion: The presence of SC or IT lesions in RIS may be associated with retinal neuro-axonal loss, supporting the presence of more disseminated disease.

Dear Editor, Asymptomatic striatocapsular slit-like hemorrhage (SSH) has been recently described as a potential new radiological marker for hypertensive cerebral small vessel disease (cSVD). We herein report a case of a young patient with a left acute putaminal hemorrhage associated with no other cSVD marker than a contralateral asymptomatic SSH. [...]

Background: Commensal Neisseria species (spp). represent an important reservoir of antimicrobial resistance genes for pathogenic Neisseria spp. In this systematic review, we aimed to assess the antimicrobial susceptibility of commensal Neisseria spp. and how this has evolved over time. We also aimed to assess if commensal Neisseria spp. showed intrinsic resistance to four antimicrobials -penicillin, azithromycin, ceftriaxone and ciprofloxacin.Methods: Pubmed and Google Scholar were searched following the PRISMA guidelines. Articles reporting MICs of commensal Neisseria spp. were included according to inclusion/exclusion criteria, and the quality of the articles was assessed using a pre-designed tool. Individual and summary measures of penicillin, azithromycin, ceftriaxone and ciprofloxacin MICs were collected. Additional data was sought to perform a comparison between the MICs of pathogenic and commensal Neisseria spp.Results: A total of 15 studies met our criteria.We found no evidence of intrinsic AMR in commensal Neisseria spp. We did find evidence of an increasing trend in MICs of commensal Neisseria spp. over time for all antimicrobials assessed. These findings were similar in various countries. Eight additional studies were included to compare pathogenic and commensal Neisseria spp.Conclusion: The MICs of commensal Neisseria spp. appear to be increasing in multiple countries. Surveillance of MICs in commensals could be used as an early warning system for antimicrobial resistance emergence in pathogens. Our findings underline the need for antibiotic stewardship interventions, particularly in populations with high antimicrobial consumption.

Ribose 5-phosphate isomerase type B (RPI-B) is a key enzyme of the pentose phosphate pathway that catalyzes the isomerization of ribose 5-phosphate (R5P) and ribulose 5-phosphate (Ru5P). Trypanosoma cruzi RPI-B (TcRPI-B) appears to be a suitable drug-target mainly due to: (i) its essentiality (as previously shown in other trypanosomatids), (ii) it does not present a homologue in mammalian genomes sequenced thus far, and (iii) it participates in the production of NADPH and nucleotide/nucleic acid synthesis that are critical for parasite cell survival. In this survey, we report on the competitive inhibition of TcRPI-B by a substrate – analogue inhibitor, Compound B (Ki = 5.5 ± 0.1 μM), by the Dixon method. This compound has an iodoacetamide moiety that is susceptible to nucleophilic attack, particularly by the cysteine thiol group. Compound B was conceived to specifically target Cys-69, an important active site residue. By incubating TcRPI-B with Compound B, a trypsin digestion LC-MS/MS analysis revealed the identification of Compound B covalently bound to Cys-69. This inhibitor also exhibited notable in vitro trypanocidal activity against T. cruzi infective life-stages co-cultured in NIH-3T3 murine host cells (IC50 = 17.40 ± 1.055 μM). The study of Compound B served as a proof-of-concept so that next generation inhibitors can potentially be developed with a focus on using a prodrug group in replacement of the iodoacetamide moiety, thus representing an attractive starting point for the future treatment of Chagas’ disease.

Background:Rituximab and ocrelizumab are anti-CD20 monoclonal antibodies that have shown a marked reduction in multiple sclerosis (MS) inflammatory activity. However, their real-world safety profile has not been adequately compared.Objective:To investigate the adverse event (AE) profile of rituximab and ocrelizumab reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database.Methods:The FAERS database was filtered by indication (MS) and drug (rituximab or ocrelizumab). Disproportionality analyses including but not limited to reporting odds ratio (ROR) were conducted to identify drug–AE associations. A signal was detected if the lower limit of the 95% confidence interval of ROR (ROR025) exceeded 1.Results:There were 623 and 7948 reports for rituximab and ocrelizumab, respectively. The most frequent AEs with rituximab and ocrelizumab were infusion-related reaction (4.82%) and urinary tract infection (10.52%), respectively. The strongest drug–AE association for rituximab and ocrelizumab were ear pruritus (ROR025: 47.53) and oral herpes (ROR025: 38.99), respectively. Ocrelizumab was associated with an almost two times higher frequency of infections than rituximab (21.93% vs 11.05%, respectively).Conclusion:This study revealed differences in reporting AEs between rituximab and ocrelizumab. Infections were reported more frequently with ocrelizumab. Although speculative, a potentially different or more extensive B-cell depletion by ocrelizumab might explain these findings. Additional pharmacovigilance studies need to be performed to better characterize differences in the AE profile in B-cell-depleting therapies.

Human papillomavirus (HPV)-associated cervical cancer represents one of the leading causes of cancer death worldwide. Although low-middle income countries are disproportionately affected, our knowledge of the disease predominantly originates from populations in high-income countries. Using the largest multi-omic analysis of cervical squamous cell carcinoma (CSCC) to date, totalling 643 tumours and representing patient populations from the USA, Europe and Sub-Saharan Africa, we identify two CSCC subtypes (C1 and C2) with differing prognosis. C1 tumours are largely HPV16-driven, display increased cytotoxic T-lymphocyte infiltration and frequently harbour PIK3CA and EP300 mutations. C2 tumours are associated with shorter overall survival, are frequently driven by HPVs from the HPV18-containing alpha-7 clade, harbour alterations in the Hippo signalling pathway and increased expression of immune checkpoint genes, B7-H3 (also known as CD276) and NT5E (also known as CD73) and PD-L2 (also known as PDCD1LG2). In conclusion, we identify two novel, therapy-relevant CSCC subtypes that share the same defining characteristics across three geographically diverse cohorts.

Supplemental material, Supplementary_Table_1a for Adverse event profile differences between rituximab and ocrelizumab: Findings from the FDA Adverse Event Reporting Database by Natalia Gonzalez Caldito, Afsaneh Shirani, Amber Salter and Olaf Stuve in Multiple Sclerosis Journal

The potential utilization of extremophiles as robust chassis for metabolic engineering applications has prompted interest in the use of Deinococcus radiodurans for bioremediation efforts, but current applications are limited by the lack of availability of genetic tools, such as promoters. In this study, we used a combined computational and experimental approach to identify and screen 30 predicted promoters for expression in D. radiodurans using a fluorescent reporter assay. The top eight candidates were further characterized, compared to currently available promoters, and optimized for engineering through minimization for use in D. radiodurans. Of these top eight, two promoter regions, DR_1261 and rpmB, were stronger and more consistent than the most widely used promoter sequence in D. radiodurans, PgroES. Furthermore, half of the top eight promoters could be minimized by at least 20% (to obtain final sequences that are approximately 24-177 bp) and several of the putative promoters either showed activity in E. coli, or were D. radiodurans-specific, broadening the use of the promoters for various applications. Overall, this work introduces a suite of novel, well-characterized promoters for protein production and metabolic engineering in D. radiodurans. Importance The tolerance of the extremophile, Deinococcus radiodurans, to numerous oxidative stresses makes it ideal for bioremediation applications, but many of the tools necessary for metabolic engineering are lacking in this organism compared to model bacteria. Although native and engineered promoters have been used to drive gene expression for protein production in D. radiodurans, very few have been well-characterized. Informed by bioinformatics, this study expands the repertoire of well-characterized promoters for D. radiodurans via thorough characterization of eight putative promoters with varying strengths. These results will help facilitate tunable gene expression, as these promoters demonstrate strong and consistent performance compared to the current standard, PgroES. This study also provides a methodology for high-throughput promoter identification and characterization using fluorescence in D. radiodurans. The promoters identified in this study will facilitate metabolic engineering of D. radiodurans and enable its use in biotechnological applications ranging from bioremediation to synthesis of commodity chemicals.

In this paper a reflective structure is proposed and modeled by the authors to increase the irradiance on solar panels. In such a way, an increase irradiance factor is obtained and it can be used to analyze the behavior of the panel in terms of efficiency, output power and temperature. The proposed reflective structure consists of mirrors whose magnitudes at both orientation and dimensions will be determined through mathematical equations. During the modeling process, factors of great importance have been considered, such as the behavior of the different types of solar concentrators currently in existence, in order to analyze the reflective effect of the same and apply it. The proposed solution can increase solar panel irradiation in up to 60%.

For a sorted set S from a universe [1.u] received under the streaming model (i.e., elements are received one at a time, in sorted order), such that at a given time it contains n elements {x 1 , …, x n }, and whose characteristic bit vector is $C_{S}=0^{\sigma_{1}}11\cdots 10^{\sigma_{2}}11\cdots 1\cdots 0^{\sigma_{g}}11\cdots 1$ (i.e., the set elements are actually arranged in g ≤ n intervals of size ≥ 1), we propose a compact data structure that answers operations select and rank in $\Theta(\mathrm{lg}(q/\mathrm{lg}\ q)$ ) worst-case time, and append in $O(1)$ amortized time, using $2q\ \mathrm{lg} \frac{u-n}{a}+q\ \mathrm{lg} \frac{n}{a}+o(q\ \mathrm{lg}\quad \mathrm{lg}\ q)$ bits of space. The structure is suitable in cases where g $q .

Background Fear of autism has led to a decline in childhood-immunization uptake and to a resurgence of preventable infectious diseases. Identifying characteristics of parents who believe in a causal role of vaccines for autism spectrum disorder (ASD) in their child may help targeting educational activities and improve adherence to the immunization schedule. Objectives To compare caregivers of children with ASD who agree or disagree that vaccines play an etiological role in autism for 1) socio-demographics characteristics and 2) developmental and clinical profiles of their children. Methods Data from 16,525 participants with ASD under age 18 were obtained from SPARK, a national research cohort started in 2016. Caregivers completed questionnaires at registration that included questions on beliefs about the etiologic role of childhood immunizations and other factors in ASD. Data were available about family socio-demographic characteristics, first symptoms of autism, developmental regression, co-occurring psychiatric disorders, seizures, and current levels of functioning. Results Participants with ASD were 80.4% male with a mean age of 8.1 years (SD = 4.1). Overall, 16.5% of caregivers endorsed immunizations as perceived causes of autism. Compared to caregivers who disagreed with vaccines as a cause for ASD, those who believed in vaccine causation came disproportionately from ethnic minority, less educated, and less wealthy backgrounds. More often their children had experienced developmental regression involving language and other skills, were diagnosed earlier, had lost skills during the second year of life, and had worse language, adaptive, and cognitive outcomes. Conclusion One in six caregivers who participate in a national research cohort believe that child immunizations could be a cause of autism in their child. Parent social background (non-White, less educated) and child developmental features (regression in second year, poorer language skills, and worse adaptive outcomes) index caregivers who are more likely to harbor these beliefs and could benefit from targeted educational activities.

The potential utilization of extremophiles as a robust chassis for metabolic engineering applications has prompted interest in the use of Deinococcus radiodurans for bioremediation efforts, but current applications are limited by the lack of availability of genetic tools, such as promoters. In this study, we used a combined computational and experimental approach to identify and screen 30 predicted promoters for expression in D. radiodurans using a fluorescent reporter assay. The top eight candidates were further characterized, compared to currently available promoters, and optimized for engineering through minimization for use in D. radiodurans. Of these top eight, two promoter regions, PDR_1261 and PrpmB, were stronger and more consistent than the most widely used promoter sequence in D. radiodurans, PgroES. Furthermore, half of the top eight promoters could be minimized by at least 20% (to obtain final sequences that are approximately 24 to 177 bp), and several of the putative promoters either showed activity in Escherichia coli or were D. radiodurans specific, broadening the use of the promoters for various applications. Overall, this work introduces a suite of novel, well-characterized promoters for protein production and metabolic engineering in D. radiodurans. IMPORTANCE The tolerance of the extremophile, Deinococcus radiodurans, to numerous oxidative stresses makes it ideal for bioremediation applications, but many of the tools necessary for metabolic engineering are lacking in this organism compared to model bacteria. Although native and engineered promoters have been used to drive gene expression for protein production in D. radiodurans, very few have been well characterized. Informed by bioinformatics, this study expands the repertoire of well-characterized promoters for D. radiodurans via thorough characterization of eight putative promoters with various strengths. These results will help facilitate tunable gene expression, since these promoters demonstrate strong and consistent performance compared to the current standard, PgroES. This study also provides a methodology for high-throughput promoter identification and characterization using fluorescence in D. radiodurans. The promoters identified in this study will facilitate metabolic engineering of D. radiodurans and enable its use in biotechnological applications ranging from bioremediation to synthesis of commodity chemicals.

OBJECTIVES: Using optic coherence tomography (OCT), to determine relationships with visual function (VF) and disability in patients with multiple sclerosis (MS) and a) ganglion cell-inner plexiform layer (GCIPL) b) peripapillary retinal nerve fiber layer (pRNFL); and c) Bruch’s membrane opening minimum rim width (BMO-MRW) thicknesses. METHODS: Sixty-eight MS patients and 22 healthy controls (HCs) underwent spectral-domain OCT, and 100%-contrast visual acuity (VA), 2.5%-, and 1.25%-contrast letter-acuity (LA), and Expanded Disability Status Scale (EDSS) testing. Mixed-effects linear regression models, accounting for within-subject, inter-eye correlations, were used to assess relationships. RESULTS: The MS cohort exhibited significantly lower BMO-MRW (p=0.01), pRNFL at 3.7 mm, 4.1 mm, and 4.7 mm diameters surrounding the optic disc (p

Highlights • Neuromuscular ultrasound (NMUS) augments clinicians’ diagnostic capabilities. • NMUS requires a basic understanding of ultrasound technology and relevant anatomy. • Uses include evaluation of neuropathies, myopathies, and motor neuron diseases., Neuromuscular ultrasound (NMUS) is becoming a standard element in the evaluation of peripheral nerve and muscle disease. When obtained simultaneously to electrodiagnostic studies, it provides dynamic, structural information that can refine a diagnosis or identify a structural etiology. NMUS can improve patient care for those with mononeuropathies, polyneuropathy, motor neuron disease and muscle disorders. In this article, we present a practical guide to the basics of NMUS and its clinical application. Basic ultrasound physics, scanning techniques and clinical applications are reviewed, along with current challenges.

Background: The effects of disease-modifying therapies (DMTs) on region-specific brain atrophy in multiple sclerosis (MS) are unclear. Objective: To determine the effects of higher versus lower efficacy DMTs on rates of brain substructure atrophy in MS. Methods: A non-randomized, observational cohort of people with MS followed with annual brain magnetic resonance imaging (MRI) was evaluated retrospectively. Whole brain, subcortical gray matter (GM), cortical GM, and cerebral white matter (WM) volume fractions were obtained. DMTs were categorized as higher (DMT-H: natalizumab and rituximab) or lower (DMT-L: interferon-beta and glatiramer acetate) efficacy. Follow-up epochs were analyzed if participants had been on a DMT for ⩾6 months prior to baseline and had at least one follow-up MRI while on DMTs in the same category. Results: A total of 86 DMT epochs (DMT-H: n = 32; DMT-L: n = 54) from 78 participants fulfilled the study inclusion criteria. Mean follow-up was 2.4 years. Annualized rates of thalamic (−0.15% vs −0.81%; p = 0.001) and putaminal (−0.27% vs −0.73%; p = 0.001) atrophy were slower during DMT-H compared to DMT-L epochs. These results remained significant in multivariate analyses including demographics, clinical characteristics, and T2 lesion volume. Conclusion: DMT-H treatment may be associated with slower rates of subcortical GM atrophy, especially of the thalamus and putamen. Thalamic and putaminal volumes are promising imaging biomarkers in MS.

Optical Mark Recognition (OMR) is the process of electronically extracting intended data from marked fields, such as squares and bubbles fields, on printed forms. OMR is useful for applications in which large numbers of hand-filled forms need to be processed quickly and with a high degree of accuracy, for instance, reading the answer sheets of high-stakes tests. Nowadays, image processing techniques and advancement in computing could help to read the answer sheets, quickly and reducing operational costs. This work introduces a systematic procedure of image processing with two segmentation steps that conclude in the extraction and recognition of marks of answer sheets of Colombian High-Stakes Tests. Some preliminary results show that the accuracy is 99.83%, on average, in the first calibration stage, with 4 blocks of about 400 images, each one. A sampling procedure was performed to determine an adequate number of images to verify the performance of the method in the scenario of the application Saber 11 in the second semester of 2018. The conclusion of the exercise, with around 65.000 images, was 99.7% of accuracy, which was run in an 8 logical processors pc architecture, getting an average speed of 8 sheets per second. Thus making it suitable for real applications or for performing a labeling process for deep learning training.

In recent years, AtheroscleroticCardiovascular Disease (ACVD), Obesity and Diabetes, have increase exponentially worldwide. In the present work, we evaluate the genoprotective effect of consuming a flavonoids-rich chocolate and the improvement in the biochemical parameters related to the prevention and treatment of cardiovascular risk and metabolic syndrome in young Mexican adults. A randomized, placebo-controlled, double-blind study was undertaken in the Autonomous University of Baja California. The treatments were a daily intake of 2 grams of dark chocolate containing 70% cooca or milk chocolate. Total phenolic compounds and flavonoids were evaluated in both chocolates. Anthropometrical and Biochemical parameters were measured in the 84 participants before and after the study. Buccal epithelial genotoxicity was also evaluated from the beginning to the end of the experiment in the participants. Result suggested that flavonoids of cocoa intake have protective effects against DNA damage, and Biochemical parameters (total cholesterol, triglycerides, and LDL-cholesterol level in blood) and anthropometrical parameters (waist circumference) were also improved after six months of daily intake of 2 grams of dark chocolate with a 70% of cocoa.

IntroductionField identification of ST-elevation myocardial infarction (STEMI) and advanced hospital notification decreases first-medical-contact-to-balloon (FMC2B) time. A recent study in this system found that electrocardiogram (ECG) transmission following a STEMI alert was frequently unsuccessful.HypothesisInstituting weekly test ECG transmissions from paramedic units to the hospital would increase successful transmission of ECGs and decrease FMC2B and door-to-balloon (D2B) times.MethodsThis was a natural experiment of consecutive patients with field-identified STEMI transported to a single percutaneous coronary intervention (PCI)-capable hospital in a regional STEMI system before and after implementation of scheduled test ECG transmissions. In November 2014, paramedic units began weekly test transmissions. The mobile intensive care nurse (MICN) confirmed the transmission, or if not received, contacted the paramedic unit and the department’s nurse educator to identify and resolve the problem. Per system-wide protocol, paramedics transmit all ECGs with interpretation of STEMI. Receiving hospitals submit patient data to a single registry as part of ongoing system quality improvement. The frequency of successful ECG transmission and time to intervention (FMC2B and D2B times) in the 18 months following implementation was compared to the 10 months prior. Post-implementation, the time the ECG transmission was received was also collected to determine the transmission gap time (time from ECG acquisition to ECG transmission received) and the advanced notification time (time from ECG transmission received to patient arrival).ResultsThere were 388 patients with field ECG interpretations of STEMI, 131 pre-intervention and 257 post-intervention. The frequency of successful transmission post-intervention was 73% compared to 64% prior; risk difference (RD)=9%; 95% CI, 1-18%. In the post-intervention period, the median FMC2B time was 79 minutes (inter-quartile range [IQR]=68-102) versus 86 minutes (IQR=71-108) pre-intervention (P=.3) and the median D2B time was 59 minutes (IQR=44-74) versus 60 minutes (IQR=53-88) pre-intervention (P=.2). The median transmission gap was three minutes (IQR=1-8) and median advanced notification time was 16 minutes (IQR=10-25).ConclusionImplementation of weekly test ECG transmissions was associated with improvement in successful real-time transmissions from field to hospital, which provided a median advanced notification time of 16 minutes, but no decrease in FMC2B or D2B times.D’ArcyNT, BossonN, KajiAH, BuiQT, FrenchWJ, ThomasJL, ElizarrarazY, GonzalezN, GarciaJ, NiemannJT. Weekly checks improve real-time prehospital ECG transmission in suspected STEMI. Prehosp Disaster Med. 2018;33(3):245–249.

On average, African Americans with multiple sclerosis demonstrate higher inflammatory disease activity, faster disability accumulation, greater visual dysfunction, more pronounced brain tissue damage and higher lesion volume loads compared to Caucasian Americans with multiple sclerosis. Neurodegeneration is an important component of multiple sclerosis, which in part accounts for the clinical heterogeneity of the disease. Brain atrophy appears to be widespread, although it is becoming increasingly recognized that regional substructure atrophy may be of greater clinical relevance. Patient race (within the limitations of self-identified ancestry) is regarded as an important contributing factor. However, there is a paucity of studies examining differences in neurodegeneration and brain substructure volumes over time in African Americans relative to Caucasian American patients. Optical coherence tomography is a non-invasive and reliable tool for measuring structural retinal changes. Recent studies support its utility for tracking neurodegeneration and disease progression in vivo in multiple sclerosis. Relative to Caucasian Americans, African American patients have been found to have greater retinal structural injury in the inner retinal layers. Increased thickness of the inner nuclear layer and the presence of microcystoid macular pathology at baseline predict clinical and radiological inflammatory activity, although whether race plays a role in these changes has not been investigated. Similarly, assessment of outer retinal changes according to race in multiple sclerosis remains incompletely characterized. Twenty-two African Americans and 60 matched Caucasian Americans with multiple sclerosis were evaluated with brain MRI, and 116 African Americans and 116 matched Caucasian Americans with multiple sclerosis were monitored with optical coherence tomography over a mean duration of 4.5 years. Mixed-effects linear regression models were used in statistical analyses. Grey matter (-0.9%/year versus -0.5%: P =0.02), white matter (-0.7%/year versus -0.3%: P =0.04) and nuclear thalamic (-1.5%/year versus -0.7%/year: P =0.02) atrophy rates were approximately twice as fast in African Americans. African Americans also exhibited higher proportions of microcystoid macular pathology (12.1% versus 0.9%, P =0.001). Retinal nerve fibre layer (-1.1% versus -0.8%: P =0.02) and ganglion cell+ inner plexiform layer (-0.7%/year versus -0.4%/year: P =0.01) atrophy rates were faster in African versus Caucasian Americans. African Americans on average exhibited more rapid neurodegeneration than Caucasian Americans and had significantly faster brain and retinal tissue loss. These results corroborate the more rapid clinical progression reported to occur, in general, in African Americans with multiple sclerosis and support the need for future studies involving African Americans in order to identify individual differences in treatment responses in multiple sclerosis.

Purpose To review the clinical and research value of optical coherence tomography angiography (OCTA) in the field of neurology. Methods Current literature involving OCTA were reviewed through PubMed using the search terms “optical coherence tomography angiography”, with “multiple sclerosis”, “Alzheimer’s disease”, “optic neuropathy”, or other closely-related terms. Results OCTA has been applied in research to advance our understanding of the pathobiology of neurological disorders. OCTA-derived blood flow and vessel density measures are altered in multiple sclerosis (MS), Alzheimer’s disease (AD), and various optic neuropathies (ON) in varying regions of the posterior segment vasculature of the eye. These emerging research findings support the occurrence of retinal vascular alterations across a host of neurological disorders and raise the possibility that vasculopathy can be clinically relevant since it contributes to the pathobiology of several neurological disorders. Conclusion OCTA may be beneficial for neurological research. Additional investigations using OCTA in neurological disorders will help to further validate its clinical and research utilities in terms of characterizing the role of vasculopathy in neurological disorders.

PURPOSE: Optical coherence tomography (OCT) is a reliable method used to quantify discrete layers of the retina. Spectralis OCT is a device used for this purpose. Spectralis OCT macular scan imaging acquisition can be obtained either on the horizontal or vertical plane. The vertical protocol has been proposed as favorable, due to postulated reduction in confound of Henle’s fibers on segmentation derived metrics. Yet, agreement of segmentation measures of horizontal and vertical macular scans remains unexplored. Our aim was to determine this agreement. MATERIALS AND METHODS: Horizontal and vertical macular scans on Spectralis OCT were acquired in 20 healthy controls (HCs) and 20 multiple sclerosis (MS) patients. All scans were segmented using Heidelberg software and a Johns Hopkins University (JHU) developed method. Agreement was analyzed using Bland Altman analyses and intra-class correlation coefficients (ICCs). RESULTS: Using both segmentation techniques, mean differences (agreement at the cohort level) in thicknesses of all macular layers derived from both acquisition protocols in MS patients and HCs were narrow (

The inhibition of specific flavonoid on the in vitro platelet aggregation induced by collagen, arachidonic acid and thromboxane A2 (TxA2) agonist, seems to be related mostly to their ability to compete for binding to the TxA2 receptor (TP). The aim of this study was to analyze the effect of soy isoflavone and equol in terms of inhibiting the platelet aggregation and sCD40L release stimulated by ristocetin, an in vitro-activator of glycoprotein Ib/IX/V, in platelets from postmenopausal women. When platelets were stimulated by 0.75 mg/ml ristocetin, equol (10 μM) exhibited a greater inhibitory activity on platelet aggregation (~68%) than genistein or daidzein. The effect of equol was dependent on the concentration of platelet aggregation agonist. In the presence of ristocetin (0.75 mg/ml, 1.125 mg/ml and 1.5 mg/ml), the inhibitory effect of 10 μM equol was 68% ± 5%, 54% ± 4% and 31% ± 5%, respectively. Equol (10 μM) was a potent inhibitor (~35%) of sCD40L release when stimulated with 1.5 mg/ml ristocetin. However, no significant differences were noted in platelets incubated in the presence of genistein or daidzein and stimulated by ristocetin. On the other hand, SQ29548, a high TP antagonist, also inhibited the sCD40L release stimulated by ristocetin. Finally, 10 μM of genistein, daidzein or equol did not significantly affect the thromboxane B2 production when platelets were incubated with 1.5 mg/ml ristocetin. The relevance of this study was to find that equol exhibits a potent activity by inhibiting ristocetin-induced sCD40L release, suggesting that soy isoflavone has important biological effects on the hemostatic system. However, clinical trials will be necessary to assess the effect of equol on platelet and their impact on inflammatory markers.