Aging-associated HELIOS deficiency in naive CD4+ T cells alters chromatin remodeling and promotes effector cell responses.

Immune aging combines cellular defects in adaptive immunity with the activation of pathways causing a low-inflammatory state. Here we examined the influence of age on the kinetic changes in the epigenomic and transcriptional landscape induced by T cell receptor (TCR) stimulation in naive CD4+ T cells. Despite attenuated TCR signaling in older adults, TCR activation accelerated remodeling of the epigenome and induced transcription factor networks favoring effector cell differentiation. We identified increased phosphorylation of STAT5, at least in part due to aberrant IL-2 receptor and lower HELIOS expression, as upstream regulators. Human HELIOS-deficient, naive CD4+ T cells, when transferred into human-synovium-mouse chimeras, infiltrated tissues more efficiently. Inhibition of IL-2 or STAT5 activity in T cell responses of older adults restored the epigenetic response pattern to the one seen in young adults. In summary, reduced HELIOS expression in non-regulatory naive CD4+ T cells in older adults directs T cell fate decisions toward inflammatory effector cells that infiltrate tissue.

Comparison of outcomes for Hispanic and non-Hispanic patients with advanced renal cell carcinoma in the International Metastatic Renal Cell Carcinoma Database.

BACKGROUND: Existing data on the impact of Hispanic ethnicity on outcomes for patients with renal cell carcinoma (RCC) is mixed. The authors investigated outcomes of Hispanic and non-Hispanic White (NHW) patients with advanced RCC receiving systemic therapy at large academic cancer centers using the International Metastatic Renal Cell Carcinoma Database (IMDC). METHODS: Eligible patients included non-Black Hispanic and NHW patients with locally advanced or metastatic RCC initiating systemic therapy. Overall survival (OS) and time to first-line treatment failure (TTF) were calculated using the Kaplan-Meier method. The effect of ethnicity on OS and TTF were estimated by Cox regression hazard ratios (HRs). RESULTS: A total of 1563 patients (181 Hispanic and 1382 NHW) (mostly males [73.8%] with clear cell RCC [81.5%] treated with tyrosine kinase inhibitor [TKI] monotherapy [69.9%]) were included. IMDC risk groups were similar between groups. Hispanic patients were younger at initial diagnosis (median 57 vs. 59 years, p = .015) and less likely to have greater than one metastatic site (60.8% vs. 76.8%, p < .001) or bone metastases (23.8% vs. 33.4%, p = .009). Median OS and TTF was 38.0 months (95% confidence interval [CI], 28.1-59.2) versus 35.7 months (95% CI, 31.9-39.2) and 7.8 months (95% CI, 6.2-9.0) versus 7.5 months (95% CI, 6.9-8.1), respectively, in Hispanic versus NHW patients. In multivariable Cox regression analysis, no statistically significant differences were observed in OS (adjusted hazard ratio [HR], 1.07; 95% CI, 0.86-1.31, p = .56) or TTF (adjusted HR, 1.06; 95% CI, 0.89-1.26, p = .50). CONCLUSIONS: The authors did not observe statistically significant differences in OS or TTF between Hispanic and NHW patients with advanced RCC. Receiving treatment at tertiary cancer centers may mitigate observed disparities in cancer outcomes.

Ablation of the carboxy-terminal end of MAMDC2 causes a distinct muscular dystrophy.

The extracellular matrix (ECM) has an important role in the development and maintenance of skeletal muscle, and several muscle diseases are associated with the dysfunction of ECM elements. MAMDC2 is a putative ECM protein and its role in cell proliferation has been investigated in certain cancer types. However, its participation in skeletal muscle physiology has not been previously studied. We describe 17 individuals with an autosomal dominant muscular dystrophy belonging to two unrelated families in which different heterozygous truncating variants in the last exon of MAMDC2 co-segregate correctly with the disease. The radiological aspect of muscle involvement resembles that of COL6 myopathies with fat replacement at the peripheral rim of vastii muscles. In this cohort, a subfascial and peri-tendinous pattern is observed in upper and lower limb muscles. Here we show that MAMDC2 is expressed in adult skeletal muscle and differentiating muscle cells, where it appears to localize to the sarcoplasm and myonuclei. In addition, we show it is secreted by myoblasts and differentiating myotubes into to the extracellular compartment. The last exon encodes a disordered region with a polar residue compositional bias loss of which likely induces a toxic effect of the mutant protein. The precise mechanisms by which the altered MAMDC2 proteins cause disease remains to be determined. MAMDC2 is a skeletal muscle disease-associated protein. Its role in muscle development and ECM-muscle communication remains to be fully elucidated. Screening of the last exon of MAMDC2 should be considered in patients presenting with autosomal dominant muscular dystrophy, particularly in those with a subfascial radiological pattern of muscle involvement.

Injury Risk Analysis among Judo Athletes with Intellectual Disabilities.

The main aim of this study was to evaluate injury prevalence, incidence rate, and burden in judo athletes with intellectual disabilities (ID) who participate in international competitions. This retrospective cross-sectional study analyzed data from the past year for 182 judo athletes with ID. Data was collected using a self-reported questionnaire, adapted from previous research, that included questions about injuries impacting training or competition, injury type, mechanism, severity, diagnosis, and location on the body. The injury prevalence among judo athletes with ID occurred most often during training (68.2%) and primarily affected the lower extremities (35%). Age group and injury prevalence were significantly related (χ2=7.91; P=0.04), while gender, weight, and ability level were not. Results were closer to those previously reported for conventional judo, which is likely due to the lower practice intensity among judo athletes with ID. Injury prevalence was lower than in prior studies, but the incidence rates aligned when considering training time in judo athletes with ID. Injury burden analysis revealed that females had a lower burden than males, while older athletes experienced a higher burden than younger athletes. Most injuries occur during training, which is likely attributable to safety-focused competition rules.

Postoperative Access and Compliance Following Medial Patellofemoral Ligament Reconstruction in Hispanic Adolescents Mirrors the Non-Hispanic Adolescent Population.

BACKGROUND: Disparity in surgical care of patellar instability patients has not been fully investigated in the adolescent Hispanic population. This demographic has been shown to have differences in their care, including a lower rate of surgical treatment for patellar instability. Socioeconomic factors have been cited as a factor that influences patient outcomes and its relationship with ethnicity in context of patellar instability has not been evaluated. METHODS: Review performed of patients <19 years of age who underwent MPFL reconstruction between September 2008 and December 2015. Demographics, patient median household income data, and clinical variables were collected. Generalized linear mixed model (GLMM) with subject as random effects factor was utilized to evaluate differences between ethnicity groups due to nonindependence of data. It was then expanded to incorporate interactions between ethnicity and income. RESULTS: Ninety-five patellar dislocation events met criteria in 85 adolescents (mean age: 15.5 y). Thirty-four (40%) adolescents identified as Hispanic. In univariate analysis no differences were found between Hispanic and non-Hispanic patients. The multivariate GLMM demonstrated a significant interaction between ethnicity and income. The Hispanic group in the >100% State median income category had the highest rate of postoperative clinic appointments attended (P=0.019). The Hispanic group in the <100% State median income category had the lowest rate of physical therapy appointments attended (P=0.044). No differences were observed for duration of follow-up (P=0.57) or final Kujala score (P=0.75). CONCLUSIONS: Hispanic ethnicity alone is not associated with inferior postoperative management after MPFL reconstruction in adolescents. However, when socioeconomic status is considered, Hispanic patients of lower-income backgrounds are found to have lower compliance with postoperative rehab recommendations. LEVEL OF EVIDENCE: Level III.

Increased incidence of Graves' disease during the SARS-CoV2 pandemic.

INTRODUCTION: COVID-19 has a wide spectrum of clinical severity and there is evidence that SARS-Cov2 affects several organs and systems. Among the organs affected since the beginning of the pandemic, the relationship between SARS-CoV-2 infection and thyroid involvement has been demonstrated. Novel and highly effective messenger RNA and DNA-based vaccines have been rapidly developed to decrease SARS-CoV-2 morbidity and mortality. Early after mass vaccinations, cases of thyroid dysfunction mainly including episodes of subacute thyroiditis, began to be reported like adverse effects. The objective of this study is to determine the impact of the pandemic, both due to SARS-CoV2 infections and vaccinations, on the incidence of Graves' disease (GD). METHODS: Cross-sectional, observational study comparing incidence of GD in adult population (over 18 years) before (2017-2019) and after (2020-2021) Covid-19 pandemic. Only patients with new cases of GD, no relapsed diseases, were included. SARS-CoV-2 diagnosis was based on nucleic acid amplification tests on nasopharyngeal swabs or measurement of class M and class G antibodies to SARS-CoV-2 by highly specific assays. Data on incidence and vaccination related to SARS-CoV-2 infection were obtained from the public records from Castilla y León autonomous regional government. RESULTS: A total of 180 subjects were diagnosed and treated for GD during the study period. We observed a notable increase in expected GD cases in 2021 compared to 2017-19. The number of GD cases was higher in the second (Q2) quarter. Among 2021 GD cases, 42/66 patients (63.6%) had been vaccinated in the 90 days before symptom onset, but none of them in the first quarter of the year. A total of 97.7% were women with a mean age of 48.9 (SD 15.6) years. On average they were diagnosed 19.9 (SD 17.6) days after receiving the vaccine. A total of 7/42 (16.67%) had another previously diagnosed autoimmune disease and 11/42 (26.19%) were smokers. DISCUSSION: Our results show a notable increase in the incidence of GD during the year 2021, specially in women with a history of smoking. Hyper activation of the immune system induced by SARS-CoV2 and by the recently released SARS-COV-2 vaccines has been highlighted in recent months. To assess whether this observed increase in the incidence of GD is sustained in the coming years or has simply been a precipitous trigger for individuals who were already predisposed to develop the disease, future studies will be needed.

Enzyme-Assisted Extraction of Ulvan from the Green Macroalgae Ulva fenestrata.

Ulvan is a sulfated polysaccharide extracted from green macroalgae with unique structural and compositional properties. Due to its biocompatibility, biodegradability, and film-forming properties, as well as high stability, ulvan has shown promising potential as an ingredient of biopolymer films such as sustainable and readily biodegradable biomaterials that could replace petroleum-based plastics in diverse applications such as packaging. This work investigates the potential of Ulva fenestrata as a source of ulvan. Enzyme-assisted extraction with commercial cellulases (Viscozyme L and Cellulysin) and proteases (Neutrase 0.8L and Flavourzyme) was used for cell wall disruption, and the effect of the extraction time (3, 6, 17, and 20 h) on the ulvan yield and its main characteristics (molecular weight, functional groups, purity, and antioxidant capacity) were investigated. Furthermore, a combined process based on enzymatic and ultrasound extraction was performed. Results showed that higher extraction times led to higher ulvan yields, reaching a maximum of 14.1% dw with Cellulysin after 20 h. The combination of enzymatic and ultrasound-assisted extraction resulted in the highest ulvan extraction (17.9% dw). The relatively high protein content in U. fenestrata (19.8% dw) makes the residual biomass, after ulvan extraction, a potential protein source in food and feed applications.

X-box binding protein 1-mediated COL4A1s secretion regulates communication between vascular smooth muscle and stem/progenitor cells.

Vascular smooth muscle cells (VSMCs) contribute to the deposition of extracellular matrix proteins (ECMs), including Type IV collagen, in the vessel wall. ECMs coordinate communication among different cell types, but mechanisms underlying this communication remain unclear. Our previous studies have demonstrated that X-box binding protein 1 (XBP1) is activated and contributes to VSMC phenotypic transition in response to vascular injury. In this study, we investigated the participation of XBP1 in the communication between VSMCs and vascular progenitor cells (VPCs). Immunofluorescence and immunohistology staining revealed that Xbp1 gene was essential for type IV collagen alpha 1 (COL4A1) expression during mouse embryonic development and vessel wall ECM deposition and stem cell antigen 1-positive (Sca1+)-VPC recruitment in response to vascular injury. The Western blot analysis elucidated an Xbp1 gene dose-dependent effect on COL4A1 expression and that the spliced XBP1 protein (XBP1s) increased protease-mediated COL4A1 degradation as revealed by Zymography. RT-PCR analysis revealed that XBP1s in VSMCs not only upregulated COL4A1/2 transcription but also induced the occurrence of a novel transcript variant, soluble type IV collagen alpha 1 (COL4A1s), in which the front part of exon 4 is joined with the rear part of exon 42. Chromatin-immunoprecipitation, DNA/protein pulldown and in vitro transcription demonstrated that XBP1s binds to exon 4 and exon 42, directing the transcription from exon 4 to exon 42. This leads to transcription complex bypassing the internal sequences, producing a shortened COL4A1s protein that increased Sca1+-VPC migration. Taken together, these results suggest that activated VSMCs may recruit Sca1+-VPCs via XBP1s-mediated COL4A1s secretion, leading to vascular injury repair or neointima formation.

Clinical and molecular characterization of five new individuals with WAC-related intellectual disability: Evidence of pathogenicity for a novel splicing variant.

WAC-related intellectual disability (ID) is a rare genetic condition characterized by a spectrum of neurodevelopmental disorders of varying severity, including global developmental delay (GDD), ID, and autism spectrum disorder. Here, we describe five affected individuals, age range 9-20 years, and provide proof of pathogenicity of a novel splicing variant. All individuals presented with GDD, some degree of ID, and variable dysmorphism. Except for feeding difficulties, all patients were healthy without major congenital malformations or medical comorbidities. All individuals were heterozygous for de novo, previously unreported, loss of function variants in WAC. Three unrelated patients from different ethnic backgrounds shared the intronic variant c.381+4_381+7delAGTA, which was predicted to alter splicing and was initially classified as a variant of uncertain significance. Reverse transcription-polymerase chain reaction analysis from one patient's cells confirmed aberrant splicing of the WAC transcript resulting in premature termination and a truncated protein p.(Gly92Alafs*2). These functional studies and the identification of several nonrelated individuals provide sufficient evidence to classify this variant as pathogenic. The clinical description of these five individuals and the three novel variants expand the genotypic and phenotypic spectrum of this ultrarare disease.

Transcriptome profiles discriminate between Gram-positive and Gram-negative sepsis in preterm neonates.

BACKGROUND: Genome-wide expression profiles have been previously employed as clinical research diagnostic tools for newborn sepsis. We aimed to determine if transcriptomic profiles could discriminate between Gram-positive and Gram-negative bacterial sepsis in preterm infants. METHODS: Prospective, observational, double-cohort study was conducted in very low birth weight infants with clinical signs and culture-positive sepsis. Blood samples were collected when clinical signs became apparent. Total RNA was processed for transcriptomic analysis. Results were validated by both reverse-transcription polymerase chain reaction and a mathematical model. RESULTS: We included 25 septic preterm infants, 17 with Gram-positive and 8 with Gram-negative bacteria. The principal component analysis identified these two clusters of patients. We performed a predictive model based on 21 genes that showed an area under the receiver-operating characteristic curve of 1. Eight genes were overexpressed in Gram-positive septic infants: CD37, CSK, MAN2B2, MGAT1, MOB3A, MYO9B, SH2D3C, and TEP1. The most significantly overexpressed pathways were related to metabolic and immunomodulating responses that translated into an equilibrium between pro- and anti-inflammatory responses. CONCLUSIONS: The transcriptomic profile allowed identification of whether the causative agent was Gram-positive or Gram-negative bacteria. The overexpression of genes such as CD37 and CSK, which control cytokine production and cell survival, could explain the better clinical outcome in sepsis caused by Gram-positive bacteria. IMPACT: Transcriptomic profiles not only enable an early diagnosis of sepsis in very low birth weight infants but also discriminate between Gram-positive and Gram-negative bacteria as causative agents. The overexpression of some genes related to cytokine production and cell survival could explain the better clinical outcome in sepsis caused by Gram-positive bacteria, and could lead us to a future, targeted therapy.

Oxygen sensor of the heart.

How oxygen is sensed by the heart and what mechanisms mediate its sensing remain poorly understood. As recent reports show that low PO2 levels are detected by the cardiomyocytes in a few seconds, the rapid and short applications of low levels of oxygen (acute hypoxia), which avoid multiple effects of chronic hypoxia, may be used to probe the oxygen-sensing pathway of the heart. Here, we explored the oxygen-sensing pathway, focusing primarily on cellular surface membrane proteins that were first exposed to low PO2. Such studies suggest that acute hypoxia primarily targets the cardiac calcium channels, where either the channel itself or moieties closely associated with it, for instance heme-oxygenase-2 (HO-2) interacting through kinase phosphorylation, signal the α-subunit of the channel to the altered levels of PO2. Amino acids 1572-1651, the CaMKII phosphorylation sites (S1487 and S1545), CaM-binding sites (I1624 and Q1625), and Ser1928 of the carboxyl tail of the α-subunit appear to be critical residues that sense oxygen. Future studies on HO-2 knockout mice or CRISPR/Cas9 gene-edited human-induced pluripotent stem-cell-derived cardiomyocytes that reduce CaM-binding affinity are likely to provide deeper insights into the O2-sensing mechanisms.

Perception of pediatric residents from a tertiary hospital in the city of México regarding their training during the COVID-19 pandemic.

BACKGROUNDS: On March 11, 2020, the World Health Organization (WHO) declared the novel coronavirus (COVID-19) outbreak a global pandemic, which changed the residents' teaching and learning process. The purpose of this study was to determine residents' satisfaction and impressions on their training during the pandemic in a tertiary pediatric hospital. METHODS: This was a descriptive cross-sectional study. An online survey was designed to determine residents' demographic and personal characteristics, as well as their perception about the theoretical and practical training, as well as about their emotional situation. The analysis separated medical students from surgical students in order to identify any differences existing between these groups, for which χ2 was calculated. RESULTS: Overall, 148 of 171 residents (86.5%) responded to the questionnaire; 75% belonged to the medical specialty and 25% to the surgical specialty. Statistically significant differences were found in terms of those training aspects they were concerned about during the pandemic (p < 0.001) and about the difficulties associated with online learning (p = 0.001). Differences were also found regarding their satisfaction toward the time needed to complete their thesis (p = 0.059) and activities outside the hospital (p = 0.029). Regarding their degree of satisfaction in general, most medical specialty students felt slightly satisfied (43.2%) and surgical specialty students felt mostly neutral (37.8%). Regarding their feelings about their mental health, statistically significant differences were found between both groups (p = 0.038) although both groups reported the same percentage of overall dissatisfaction (2.7%) in this area. CONCLUSION: The COVID-19 pandemic has brought significant challenges to medical education systems. Lack of practice in decision-making and maneuver execution are concerns for residents and may affect their future professional performance.

Epidural empyema following nBCA embolization of the middle meningeal artery for the treatment of a chronic subdural hematoma.

Chronic subdural hematomas (CSDHs) are a common neurosurgical disease for which middle meningeal artery (MMA) embolization is emerging as an attractive and efficacious endovascular treatment modality. We present the first known case of a Streptococcus intermedius epidural abscess that resulted following MMA embolization for a left-sided CSDH that required evacuation and washout through a craniotomy. Intracranial infections can be a potentially devastating complication from MMA embolization in this patient population.

Agricultural pesticide residues in water from a karstic aquifer in Yucatan, Mexico, pose a risk to children's health.

Yucatan is a region with a high impact of water contamination since it has a karst type soil favoring contaminants entry into the phreatic level, the only source of freshwater in the area. However, no studies report pesticides in water for human consumption or the risk it represents. The objective of this study was to detect and measure pesticide concentrations in domestic tap water to estimate the risk (carcinogenic and non-carcinogenic) to health. A non-probabilistic sampling was applied of 48 tap water sources, and then pesticide detection with solid-phase extraction gas chromatography coupled to the electron capture and flame photometric detectors allowed the estimation of risk through hazard ratios. The present results suggest that aldrin, heptachlor, and ß-BHC residues in domestic tap water from Ticul, Yucatan, pose a risk to children's health, particularly for potential carcinogenic risks.

Antioxidant and anti-proliferative activity of free, conjugates and bound phenolic compounds from tomato and industrial tomato by-product.

The aim of this study was to evaluate the antioxidant and anti-proliferative activity of different fractions of phenolic compounds from tomato and tomato by-product. Soluble free phenolics and bound phenolics (BP) fractions from saladette tomato and industrial tomato by-product as well as, conjugated acid-hydrolysable phenolics (AHP) and alkaline-hydrolysable phenolics (AKHP) from saladette tomato, grape tomato and industrial tomato by-product, were tested. The scavenging effects of phenolic fractions on superoxide anion were determined using the PMS-NADH-NBT system. The myoglobin protection ratios of samples against hydroxyl radical were evaluated and the anti-proliferative effects in the MCF-7 breast cancer cell line were determined. AHP fraction from tomato by-product and AKHP fraction from grape and saladette tomato showed the highest inhibitory capacity of the superoxide anion (p ≤ 0.05). All samples had a myoglobin protection ratio from 30 to 50%. Regarding to cytotoxicity assays, all phenolic fractions from tomato by-product, as well as, BP, AHP, AKHP from saladette tomato and AHP from grape tomato showed important anti-proliferative activity against MCF-7 breast cancer cell line (IC50 < 20 µg/mL). From the results, we can conclude that tomato and tomato by-product are a good source of natural compound with important antioxidant and anti-proliferative activity.

Design and implementation of an online tool for managing the availability of high-cost perishable medicines.

Introduction: Due to their impact on healthcare systems, the sustainability and optimization of high-cost drugs is an issue of concern for several countries. Different strategies have been implemented such as centralized purchasing to optimize budgetary resources. However, there is still a need for a mechanism to optimize these drugs further. Methods: We conducted this prospective multicenter intervention study in five hospitals in the Andalusian Public Health System of Cádiz (Spain) between July 2019 and September 2021. We developed an online website (Farmastock) and implemented it to determine the availability of high-cost, low-use, and near-expiry medicines in each hospital. We used a simple analysis using operational variables to assess the project intervention's savings impact on managing these high-cost drugs. Results: The implementation of Farmastock in Cádiz resulted in savings of 675,757.52 € for the Andalusian Public Health System, with 238 medicines transferred out of the 373 available. Of these medicines offered, the most considerable percentage were medicines used for pathologies with high clinical instability and accounted for nearly 80% of the medicines optimized by the tool. Conclusions: Farmastock allowed the Andalusian Public Health System to make substantial financial savings by not making new purchases of high-cost drugs available in other centers of this health network that were not being used. Therefore, this tool is a very efficient measure to contribute to the sustainability of the APHS and could be implemented in more hospitals soon.

Evolution of lbx spinal cord expression and function.

Ladybird homeobox (Lbx) transcription factors have crucial functions in muscle and nervous system development in many animals. Amniotes have two Lbx genes, but only Lbx1 is expressed in spinal cord. In contrast, teleosts have three lbx genes and we show here that zebrafish lbx1a, lbx1b, and lbx2 are expressed by distinct spinal cell types, and that lbx1a is expressed in dI4, dI5, and dI6 interneurons, as in amniotes. Our data examining lbx expression in Scyliorhinus canicula and Xenopus tropicalis suggest that the spinal interneuron expression of zebrafish lbx1a is ancestral, whereas lbx1b has acquired a new expression pattern in spinal cord progenitor cells. lbx2 spinal expression was probably acquired in the ray-finned lineage, as this gene is not expressed in the spinal cords of either amniotes or S. canicula. We also show that the spinal function of zebrafish lbx1a is conserved with mouse Lbx1. In zebrafish lbx1a mutants, there is a reduction in the number of inhibitory spinal interneurons and an increase in the number of excitatory spinal interneurons, similar to mouse Lbx1 mutants. Interestingly, the number of inhibitory spinal interneurons is also reduced in lbx1b mutants, although in this case the number of excitatory interneurons is not increased. lbx1a;lbx1b double mutants have a similar spinal interneuron phenotype to lbx1a single mutants. Taken together these data suggest that lbx1b and lbx1a may be required in succession for correct specification of dI4 and dI6 spinal interneurons, although only lbx1a is required for suppression of excitatory fates in these cells.

Aicardi-Goutières syndrome may present with positive newborn screen for X-linked adrenoleukodystrophy.

We report three unrelated probands, two male and one female, diagnosed with Aicardi-Goutières syndrome (AGS) after screening positive on California newborn screening (CA NBS) for X-linked adrenoleukodystrophy (X-ALD) due to elevated C26:0 lysophosphatidylcholine (C26:0-LPC). Follow-up evaluation was notable for elevated C26:0, C26:1, and C26:0/C22:0 ratio, and normal red blood cell plasmalogens levels in all three probands. Diagnoses were confirmed by molecular sequencing prior to 12 months of age after clinical evaluation was inconsistent with X-ALD or suggestive of AGS. For at least one proband, the early diagnosis of AGS enabled candidacy for enrollment into a therapeutic clinical trial. This report demonstrates the importance of including AGS on the differential diagnosis for individuals who screen positive for X-ALD, particularly infants with abnormal neurological features, as this age of onset would be highly unusual for X-ALD. While AGS is not included on the Recommended Universal Screening Panel, affected individuals can be identified early through state NBS programs so long as providers are aware of a broader differential that includes AGS. This report is timely, as state NBS algorithms for X-ALD are actively being established, implemented, and refined.

Hollow fiber liquid-phase microextraction combined with supercritical fluid chromatography coupled to mass spectrometry for multiclass emerging contaminant quantification in water samples.

The hollow fiber liquid-phase microextraction allows highly selective concentration of organic compounds that are at trace levels. The determination of those analytes through the supercritical fluid chromatography usage is associated with many analytical benefits, which are significantly increased when it is coupled to a mass spectrometry detector, thus providing an extremely sensitive analytical technique with minimal consumption of organic solvents. On account of this, a hollow fiber liquid-phase microextraction technique in two-phase mode combined with supercritical fluid chromatography coupled to mass spectrometry was developed for quantifying 19 multiclass emerging contaminants in water samples in a total chromatographic time of 5.5 min. The analytical method used 40 µL of 1-octanol placed in the porous-walled polypropylene fiber as the acceptor phase, and 1 L of water sample was the donor phase. After extraction and quantification techniques were optimized in detail, a good determination coefficient (r2 > 0.9905) in the range of 0.1 to 100 µg L-1, for most of the analytes, and an enrichment factor in the range of 7 to 28,985 were obtained. The recovery percentage (%R) and intraday precision (%RSD) were in the range of 80.80-123.40%, and from 0.48 to 16.89%, respectively. Limit of detection and quantification ranged from 1.90 to 35.66 ng L-1, and from 3.41 to 62.11 ng L-1, respectively. Finally, the developed method was successfully used for the determination of the 19 multiclass emerging contaminants in superficial and wastewater samples.

Comparison of semiology in patients with psychogenic nonepileptic seizures or with epilepsy in Puerto Rico.

PURPOSE: The aims of this study were to develop a descriptive profile of patients with psychogenic nonepileptic seizures (PNES) in Puerto Rico who have been evaluated using an epilepsy monitoring unit. The other aim was to establish comparisons between the clinical manifestation of PNES and events of generalized epilepsy (GE). METHOD: A retrospective study was conducted to evaluate the information of patients who passed through the Epilepsy Unit in Caguas, Puerto Rico. In the first phase, sociodemographic information of 100 patients with PNES was collected. In the second phase, a sample of 51 cases was obtained; 37 cases with a final diagnosis of PNES and 14 cases with the diagnosis of GE. Observations were made with the objective of viewing and comparing the semiology and clinical manifestation presented through video encephalograms (vEEG) in both subsamples. RESULTS: Patients with PNES and epilepsy demonstrated different semiological patterns. Psychogenic nonepileptic seizures is predominant in females (95%). Most patients with epilepsy presented a relatively short seizure (<2 min) compared with patients with PNES (79% vs. 46%). Patients with epilepsy showed a slow return to their baseline manifestation (100% vs. 11%). Specifically, having their eyes closed, extreme asynchronous limb movements, and rigidity were statistically significant. CONCLUSION: These findings provide evidence that the semiology of patients with PNES is different from those displaying an epileptic seizure. This study supports the idea that the semiology of Latino patients with PNES is similar to the characteristics reported in other countries.