Diagnostic Performance of Airway Ultrasound for the Assessment of Difficult Laryngoscopy: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aimed to review and appraise the evidence regarding airway ultrasound assessment in predicting difficult laryngoscopy in adult patients. DESIGN: A systematic review of the literature was conducted according to the Cochrane collaboration guidelines and the recommendations for the systematic review and meta-analysis of diagnostic studies. Observational studies that evaluated the diagnostic performance of airway ultrasound for the prediction of difficult laryngoscopy were included for consideration. SETTING: Literature searches were performed in 4 databases (PubMed [Medline], Embase, Clinical Trials, and Google Scholar) to identify all observational studies using any ultrasound technique to assess difficult laryngoscopy. The search terms included "sonography," "ultrasound," "airway," "difficult airway," "difficult laryngoscopy," "Cormack," "risk factors," "ultrasound at the point of care," "difficult ventilation," "difficult intubation" and others, combined with sensitive filters. The search was done for studies performed in the last 20 years in English or Spanish. PARTICIPANTS: Adult patients older than 18 years old under general anesthesia for an elective procedure. Evident anatomic airway abnormalities, obstetric populations, those using an alternative imaging method besides ultrasound, and animal studies were excluded. INTERVENTIONS: Preoperative bedside ultrasound measuring distances and ratios from the skin to different reference points, such as the ratio of the hyomental distance in a neutral position (HMDN) and hyomental distance in extension (HMDR), HMDN, and the skin-to-epiglottis distance (SED), the preepiglottic area, and tongue thickness, among others. MEASUREMENTS AND MAIN RESULTS: A total of 24 studies evaluated the prediction of a difficult laryngoscopy using airway ultrasound. The diagnostic performance and the number of ultrasound parameters reported in the studies were variable. Meta-analysis was performed for 3 measurements consistently included in most studies. The SED and the HMDR ratio presented a sensitivity of 75% and 61%, respectively, and a specificity of 86% and 88%, respectively. The ratio of the preepiglottic distance to the epiglottic distance at the midpoint of the vocal cords (pre-E/E-VC) presented the best performance for predicting a difficult laryngoscopy (sensitivity: 82%, specificity: 83%, diagnostic odds ratio: 22.2). CONCLUSION: With the currently available evidence, the 3 commonly used point-of-care ultrasound measures used to identify difficult laryngoscopy, (SED, HMDR, and pre-E/E-VC), showed better sensitivity and similar specificity to clinical measures. Future studies and more data may change the authors' confidence in these conclusions, given the wide variability of measurements noted in studies.

Integrated Environmental and Genomic Analysis Reveals the Drivers of Local Adaptation in African Indigenous Chickens.

Breeding for climate resilience is currently an important goal for sustainable livestock production. Local adaptations exhibited by indigenous livestock allow investigating the genetic control of this resilience. Ecological niche modeling (ENM) provides a powerful avenue to identify the main environmental drivers of selection. Here, we applied an integrative approach combining ENM with genome-wide selection signature analyses (XPEHH and Fst) and genotype-environment association (redundancy analysis), with the aim of identifying the genomic signatures of adaptation in African village chickens. By dissecting 34 agro-climatic variables from the ecosystems of 25 Ethiopian village chicken populations, ENM identified six key drivers of environmental challenges: One temperature variable-strongly correlated with elevation, three precipitation variables as proxies for water availability, and two soil/land cover variables as proxies of food availability for foraging chickens. Genome analyses based on whole-genome sequencing (n = 245), identified a few strongly supported genomic regions under selection for environmental challenges related to altitude, temperature, water scarcity, and food availability. These regions harbor several gene clusters including regulatory genes, suggesting a predominantly oligogenic control of environmental adaptation. Few candidate genes detected in relation to heat-stress, indicates likely epigenetic regulation of thermo-tolerance for a domestic species originating from a tropical Asian wild ancestor. These results provide possible explanations for the rapid past adaptation of chickens to diverse African agro-ecologies, while also representing new landmarks for sustainable breeding improvement for climate resilience. We show that the pre-identification of key environmental drivers, followed by genomic investigation, provides a powerful new approach for elucidating adaptation in domestic animals.

Biparatopic single-domain antibodies against Axl achieve ultra-high affinity through intramolecular engagement.

Overexpression of Axl, a TAM-family receptor tyrosine kinase, plays key roles in the formation, growth, and spread of tumors as well as resistance to targeted therapies and chemotherapies. We identified novel llama VHHs against human Axl using multiple complementary phage display selection strategies and characterized a subset of high-affinity VHHs. The VHHs targeted multiple sites in Ig-like domains 1 and 2 of the Axl extracellular domain, including an immunodominant epitope overlapping the site of Gas6 interaction and two additional non-Gas6 competitive epitopes recognized by murine monoclonal antibodies. Only a subset of VHHs cross-reacted with cynomolgus monkey Axl and none recognized mouse Axl. As fusions to human IgG1 Fc, VHH-Fcs bound Axl+ tumor cell lines and mertansine-loaded VHH-Fcs were cytotoxic in vitro against Axl+ cells in proportion to their binding affinities. Engineered biparatopic VHH-VHH heterodimers bound Axl avidly, and a subset of molecules showed dramatically enhanced association rates indicative of intramolecular binding. These VHHs may have applications as modular elements of biologic drugs such as antibody-drug conjugates.

Secondary antibody deficiency is associated with development of infection in kidney transplantation: Results of a multicenter study.

BACKGROUND: We performed a multicenter study to assess the association between secondary antibody deficiency (immunoglobulin G [IgG] hypogammaglobulinemia combined with low levels of specific antibodies) and development of infection in kidney transplantation. METHODS: We prospectively analyzed 250 adult kidney recipients at four centers. The assessment points were before transplantation and 7 and 30 days after transplantation. The immune parameters were as follows: IgG, IgA, and IgM and complement factors C3 and C4 tested by nephelometry; specific IgG antibodies to cytomegalovirus (CMV) and IgG and IgG2 antibodies to pneumococcal polysaccharide (anti-PPS) determined using enzyme-linked immunosorbent assay. The clinical follow-up period lasted 6 months. The clinical outcomes were CMV disease and recurrent bacterial infections requiring antimicrobial therapy. STATISTICS: Multivariate logistic regression. RESULTS: At day 7, IgG hypogammaglobulinemia (IgG levels < 700 mg/dL) combined with low IgG anti-CMV antibody titers (defined as levels < 10 000 units) was present in 12% of kidney recipients. IgG hypogammaglobulinemia combined with low IgG anti-PPS antibody titers (defined as levels < 10 mg/dL) at 1 month after kidney transplantation were recorded in 16% of patients. At day 7 the combination of IgG hypogammaglobulinemia and low anti-CMV titers was independently associated with the development of CMV disease (odds ratio [OR], 6.95; 95% confidence interval [CI], 1.17-41.31; P = .033). At day 30 after transplantation, the combination of IgG < 700 mg/dL and IgG anti-PPS < 10 mg/dL, was independently associated with recurrent bacterial infection (OR, 5.942; 95% CI, 1.943-18.172; P = .002). CONCLUSION: In a prospective multicenter study, early immunologic monitoring of secondary antibody deficiency proved useful for the identification of kidney recipients who developed severe infection.

Visual Features in Alzheimer's Disease: From Basic Mechanisms to Clinical Overview.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. It compromises patients' daily activities owing to progressive cognitive deterioration, which has elevated direct and indirect costs. Although AD has several risk factors, aging is considered the most important. Unfortunately, clinical diagnosis is usually performed at an advanced disease stage when dementia is established, making implementation of successful therapeutic interventions difficult. Current biomarkers tend to be expensive, insufficient, or invasive, raising the need for novel, improved tools aimed at early disease detection. AD is characterized by brain atrophy due to neuronal and synaptic loss, extracellular amyloid plaques composed of amyloid-beta peptide (Aß), and neurofibrillary tangles of hyperphosphorylated tau protein. The visual system and central nervous system share many functional components. Thus, it is plausible that damage induced by Aß, tau, and neuroinflammation may be observed in visual components such as the retina, even at an early disease stage. This underscores the importance of implementing ophthalmological examinations, less invasive and expensive than other biomarkers, as useful measures to assess disease progression and severity in individuals with or at risk of AD. Here, we review functional and morphological changes of the retina and visual pathway in AD from pathophysiological and clinical perspectives.

Discarded Livers Find a New Life: Engineered Liver Grafts Using Hepatocytes Recovered From Marginal Livers.

Treatment for end-stage liver failure is restricted by the critical shortage of donor organs; about 4000 people die in the USA while waiting for a transplantable organ. This situation has been a major driving force behind the rise of tissue engineering to build artificial tissues/organs. Recent advancements in creating transplantable liver grafts using decellularized liver scaffolds bring the field closer to clinical translation. However, a source of readily available and highly functional adult hepatocytes in adequate numbers for regenerative liver therapies still remains unclear. Here, we describe a new method to utilize discarded livers to make transplantable new liver grafts. We show that marginal donor livers damaged due to warm ischemia could be treated with machine perfusion to yield 39 million viable hepatocytes per gram of liver, similar to fresh livers, and these cells could be used to repopulate decellularized liver matrix (DLM) scaffolds to make transplantable liver grafts. The hepatocytes from recovered livers sustained their characteristic epithelial morphology while they exhibited slightly lower protein synthesis functions both in plate cultures and in recellularized liver grafts. The dampened protein synthesis was attributed to residual endoplasmic reticulum stress found in recovered cells. The results here represent a unique approach to reengineer transplantable liver grafts solely from discarded organs.

Early intravenous immunoglobulin replacement in hypogammaglobulinemic heart transplant recipients: results of a clinical trial.

BACKGROUND: Immunoglobulin G (IgG) hypogammaglobulinemia (HGG) is a risk factor for development of severe infections after heart transplantation. We performed a clinical trial to preliminarily evaluate the efficacy and safety of early administration of intravenous immunoglobulin (IVIG) for prevention of severe infection in heart recipients with post-transplant IgG HGG. METHODS: Twelve heart recipients with IgG HGG detected in a screening phase of the clinical trial (IgG <500 mg/dL) were recruited. Patients received IVIG (Flebogamma 5%), as follows: 2 doses of 200 mg/kg followed by up to 5 additional doses of 300 mg/kg to maintain IgG >750 mg/dL. IgG and specific antibody titers to distinct microorganisms were tested during follow-up. The primary outcome measure was development of severe infection during the study period. Data on the primary outcome were matched with those of 13 recipients with post-transplant HGG who were not included in the clinical trial and with those of 11 recipients who did not develop HGG during the same study period. RESULTS: Mean time to detection of HGG was 15 days. IgG and specific antibody reconstitution (anti-cytomegalovirus, anti-Haemophilus influenza, and anti-hepatitis B surface antigen antibodies) was observed in IVIG-treated patients. Severe infection was detected in 3 of 12 (25%) IVIG-treated recipients, in 10 of 13 (77%) HGG non-IVIG patients, and in 2 of 11 (18%) non-HGG patients (log-rank, 15.31; P=.0005). No severe IVIG-related side effects were recorded. CONCLUSION: Data from this study demonstrate that prophylactic IVIG replacement therapy safely modulates HGG and specific antimicrobial antibodies. Our data also preliminarily suggest that IVIG replacement therapy might decrease the incidence of severe infection in heart recipients with HGG.

Dielectrophoresis chips improve PCR detection of the food-spoiling yeast Zygosaccharomyces rouxii in apple juice.

Dielectrophoretic (DEP) manipulation of cells present in real samples is challenging. We show in this work that an interdigitated DEP chip can be used to trap and wash a population of the food-spoiling yeast Zygosaccharomyces rouxii that contaminates a sample of apple juice. By previously calibrating the chip, the yeast population loaded is efficiently trapped, washed, and recovered in a small-volume fraction that, in turn, can be used for efficient PCR detection of this yeast. DEP washing of yeast cells gets rid of PCR inhibitors present in apple juice and facilitates PCR analysis. This and previous works on the use of DEP chips to improve PCR analysis show that a potential use of DEP is to be used as a treatment of real samples prior to PCR.

Analysis of acquired resistance to metronomic oral topotecan chemotherapy plus pazopanib after prolonged preclinical potent responsiveness in advanced ovarian cancer.

An alternative or follow-up adjunct to conventional maximum tolerated dose (MTD) chemotherapy now in advanced phase III clinical trial assessment is metronomic chemotherapy--the close regular administration of low doses of drug with no prolonged breaks. A number of preclinical studies have shown metronomic chemotherapy can cause long term survival of mice with advanced cancer, including metastatic disease, in the absence of overt toxicity, especially when combined with targeted antiangiogenic drugs. However, similar to MTD chemotherapy acquired resistance eventually develops, the basis of which is unknown. Using a preclinical model of advanced human ovarian (SKOV-3-13) cancer in SCID mice, we show that acquired resistance can develop after terminating prolonged (over 3 months) successful therapy utilizing daily oral metronomic topotecan plus pazopanib, an oral antiangiogenic tyrosine kinase inhibitor (TKI). Two resistant sublines were isolated from a single mouse, one from a solid tumor (called KH092-7SD, referred to as 7SD) and another from ascites tumor cells (called KH092-7AS, referred to as 7AS). Using these sublines we show acquired resistance to the combination treatment is due to tumor cell alterations that confer relative refractoriness to topotecan. The resistant phenotype is heritable, associated with reduced cellular uptake of topotecan and could not be reversed by switching to MTD topotecan or to another topoisomerase-1 inhibitor, CPT-11, given either in a metronomic or MTD manner nor switching to another antiangiogenic drug, e.g. the anti-VEGFR-2 antibody, DC101, or another TKI, sunitinib. Thus, in this case cross resistance seems to exist between MTD and metronomic topotecan, the basis of which is unknown. However, gene expression profiling revealed several potential genes that are stably upregulated in the resistant lines, that previously have been implicated in resistance to various chemotherapy drugs, and which, therefore, may contribute to the drug resistant phenotype.

Anti-Claudin-2 Antibody-Drug Conjugates for the Treatment of Colorectal Cancer Liver Metastasis.

We have demonstrated that Claudin-2 is required for colorectal cancer (CRC) liver metastasis. Expression of Claudin-2 in primary CRC is associated with poor survival and is highly expressed in liver metastases. Claudin-2 also promotes breast cancer liver metastasis by enabling seeding and cancer cell survival. These observations support Claudin-2 as a potential therapeutic target for managing patients with liver metastases. Antibody-drug conjugates (ADCs) are promising anti-tumor therapeutics that combine the specific targeting ability of monoclonal antibodies with the potent cell killing activity of cytotoxic drugs. Here we report the generation of twenty-eight anti-Claudin-2 antibodies for which the binding specificities, the cross-reactivity with Claudin family members and the cross-species reactivity were assessed by flow cytometry analysis. Multiple drug conjugates were tested and PNU was selected for conjugation with anti-Claudin-2 antibodies binding either extracellular loop 1 or extracellular loop 2. Anti-Claudin-2 ADCs were efficiently internalized and effective at killing Claudin-2-expressing CRC cancer cells in vitro. Importantly, PNU-conjugated-anti-Claudin-2 ADCs impaired the development of replacement type CRC liver metastases in vivo, using established CRC cell lines and patient-derived xenograft (PDX) models of CRC liver metastases. Our results suggest that the development of ADCs targeting Claudin-2 is a promising therapeutic strategy for managing CRC liver-metastatic patients that present with replacement type liver metastases.

Alterations of naïve and memory B-cell subsets are associated with risk of rejection and infection in heart recipients.

Rejection and infection are relevant causes of mortality in heart recipients. We evaluated the kinetics of the maturation status of B lymphocytes and its relationship with acute cellular rejection and severe infection in heart recipients. We analyzed B-cell subsets using 4-color flow cytometry in a prospective follow-up study of 46 heart recipients. Lymphocyte subsets were evaluated at specific times before and up to 1 year after transplantation. Higher percentages of pretransplant class-switched memory B cells (CD19+CD27+IgM-IgD- >14%) were associated with a 74% decrease in the risk of severe infection [Cox regression relative hazard (RH) 0.26, 95% confidence interval (CI), 0.07-0.86; P = 0.027]. Patients with higher percentages of naïve B cells at day 7 after transplantation (CD19+CD27-IgM+IgD+ >58%) had a 91% decrease in the risk of developing acute cellular rejection (RH 0.09; 95% CI, 0.01-0.80; P = 0.02). Patients with infections showed a strong negative correlation between baseline serum B-cell-activating factor (BAFF) concentration and absolute counts of memory class-switched B cells (R = -0.81, P = 0.01). The evaluation of the immunophenotypic maturation status of B lymphocytes could prove to be a useful marker for identifying patients at risk of developing rejection or infection after heart transplantation.

Primary open-angle glaucoma in patients with obstructive sleep apnoea in a Colombian population: a cross-sectional study.

OBJECTIVE: Determine the prevalence, functional and structural alterations of primary open-angle glaucoma (POAG) in patients with obstructive sleep apnoea (OSA). DESIGN: Cross-sectional. SETTING: Tertiary hospital associated with specialised center in ophthalmologic images in Bogota, Colombia. PARTICIPANTS: 150 patients, for a sample of 300 eyes, 64 women (42.7%) and 84 men (57.3%) between 40 and 91 years old with a mean age of 66.8 (±12.1) years. INTERVENTIONS: Visual acuity, biomicroscopy, intraocular pressure, indirect gonioscopy and direct ophthalmoscopy. Patients classified as glaucoma suspects underwent automated perimetry (AP) and optical coherence tomography of the optic nerve OUTCOME MEASURE: The primary outcomes are the determination of prevalence of glaucoma suspects and POAG in patients with OSA. Secondary outcomes are the description of functional and structural alterations in computerised exams of patients with OSA. RESULTS: The prevalence of glaucoma suspect was 12.6%, and for POAG was 17.3%. No alterations in the appearance of the optic nerve was seen in 74.6%, focal or diffuse thinning of the neuroretinal rim (16.6%) was the most frequently finding, followed by asymmetry of the disc>0.2 mm (8.6%) (p=0.005). In the AP, 41% showed arcuate, nasal step and paracentral focal defects. The mean retinal nerve fiber layer (RNFL) was normal (>80 µM) in 74% of the mild OSA group, 93.8% of the moderate group and 17.1% of the severe group. Similarly, normal (P5-90) ganglion cell complex (GCC) in 60%, 68% and 75%, respectively. Abnormal results in the mean RNFL was seen in 25.9%, 6.3% and 23.4% of the mild, moderate and severe groups, respectively. In the GCC, 39.7%, 33.3% and 25% of the patients in the aforementioned groups. CONCLUSION: It was possible to determine the relationship between structural changes in the optic nerve and the severity of OSA. No relationship with any of the other studied variables was identified.

Video Analysis of 26 Cases of Second ACL Injury Events in Collegiate and Professional Athletes.

Background: Significant effort has gone into the identification and quantification of the underlying mechanisms of primary ACL injury. Secondary ACL injury is observed in approximately 1/4 to 1/3 of athletes who return to sport following ACL reconstruction. However, little has been done to evaluate the mechanisms and playing circumstances surrounding these repeat injuries. Hypothesis/Purpose: The purpose of this study was to characterize the mechanisms of non-contact secondary ACL injuries using video analysis. It was hypothesized that in video recordings of secondary ACL injury, athletes would exhibit greater frontal plane hip and knee angles, but not greater hip and knee flexion, at 66 ms following initial contact (IC) as compared to at IC and 33ms following IC. Study Design: Cross-Sectional Study. Methods: Twenty-six video recordings of competitive athletes experiencing secondary ACL ruptures via noncontact mechanisms were analyzed for lower extremity joint kinematics, playing situation, and player attention. Kinematics were assessed at IC as well as 33 ms (1 broadcast frame) and 66 ms (2 broadcast frames) following IC. Results: Knee flexion and knee frontal plane angles were greater at 66 ms than IC (p ≤ 0.03). Hip, trunk, and ankle frontal plane angles were not greater at 66 ms than IC (p ≥ 0.22). Injuries were distributed between attacking play (n=14) and defending (n=8). Player attention was most commonly focused on the ball (n=12) or an opponent (n=7). A single-leg landing accounted for just over half of the injuries (54%), while a cutting motion accounted for the remainder of the injuries (46%). Conclusion: Secondary ACL injury was most likely to occur during landing or a sidestep cut with player attention external to their own body. Knee valgus collapse combined with limited hip motion was identified in the majority of secondary injuries. Level of Evidence: Level IIIb.

Clinical Findings and Genetic Analysis of Nine Mexican Families with Bartter Syndrome.

BACKGROUND: Bartter's syndrome (BS) is a group of salt-wasting tubulopathies characterized by hypokalemia, metabolic alkalosis, hypercalciuria, secondary hyperaldosteronism, and low or normal blood pressure. Loss-of-function variants in genes encoding for five proteins expressed in the thick ascending limb of Henle in the nephron, produced different genetic types of BS. AIM: Clinical and genetic analysis of families with Antenatal Bartter syndrome (ABS) and with Classic Bartter syndrome (CBS). METHODS: Nine patients from unrelated non-consanguineous Mexican families were studied. Massive parallel sequencing of a gene panel or whole-exome sequencing was used to identify the causative gene. RESULTS: Proband 1 was homozygous for the pathogenic variant p.Arg302Gln in the SLC12A1 gene encoding for the sodium-potassium-chloride NKCC2 cotransporter. Proband 3 was homozygous for the nonsense variant p.Cys308* in the KCNJ1 gene encoding for the ROMK potassium channel. Probands 7, 8, and 9 showed variants in the CLCKNB gene encoding the chloride channel ClC-Kb: proband 7 was compound heterozygous for the deletion of the entire gene and the missense change p.Arg438Cys; proband 8 presented a homozygous deletion of the whole gene and proband 9 was homozygous for the nonsense mutation p.Arg595*. A heterozygous variant of unknown significance was detected in the SLC12A1 gene in proband 2, and no variants were found in SLC12A1, KCNJ1, BSND, CLCNKA, CLCNKB, and MAGED2 genes in probands 4, 5, and 6. CONCLUSIONS: Genetic analysis identified loss-of-function variants in the SLC12A1, KCNJ1, and CLCNKB genes in four patients with ABS and in the CLCNKB gene in two patients with CBS.

A glyco-engineering approach for site-specific conjugation to Fab glycans.

Effective processes for synthesizing antibody-drug conjugates (ADCs) require: 1) site-specific incorporation of the payload to avoid interference with binding to the target epitope, 2) optimal drug/antibody ratio to achieve sufficient potency while avoiding aggregation or solubility problems, and 3) a homogeneous product to facilitate approval by regulatory agencies. In conventional ADCs, the drug molecules are chemically attached randomly to antibody surface residues (typically Lys or Cys), which can interfere with epitope binding and targeting, and lead to overall product heterogeneity, long-term colloidal instability and unfavorable pharmacokinetics. Here, we present a more controlled process for generating ADCs where drug is specifically conjugated to only Fab N-linked glycans in a narrow ratio range through functionalized sialic acids. Using a bacterial sialytransferase, we incorporated N-azidoacetylneuraminic acid (Neu5NAz) into the Fab glycan of cetuximab. Since only about 20% of human IgG1 have a Fab glycan, we extended the application of this approach by using molecular modeling to introduce N-glycosylation sites in the Fab constant region of other therapeutic monoclonal antibodies. We used trastuzumab as a model for the incorporation of Neu5NAz in the novel Fab glycans that we designed. ADCs were generated by clicking the incorporated Neu5NAz with monomethyl auristatin E (MMAE) attached to a self-immolative linker terminated with dibenzocyclooctyne (DBCO). Through this process, we obtained cetuximab-MMAE and trastuzumab-MMAE with drug/antibody ratios in the range of 1.3 to 2.5. We confirmed that these ADCs still bind their targets efficiently and are as potent in cytotoxicity assays as control ADCs obtained by standard conjugation protocols. The site-directed conjugation to Fab glycans has the additional benefit of avoiding potential interference with effector functions that depend on Fc glycan structure.

Qualitative Study of Barriers and Facilitators to Care Among Children in Immigrant Families.

OBJECTIVES: Children in immigrant families comprise ∼25% of US children and live in families with high levels of poverty and food insecurity. Studies suggest a decline in public benefit enrollment among children in immigrant families. We aimed to explore perspectives on barriers and facilitators in accessing care among immigrant caregivers of hospitalized children. METHODS: With a general qualitative descriptive design, we developed a semistructured interview guide using an iterative process informed by literature and content expertise. Using purposive sampling, we recruited immigrant caregivers of hospitalized children in March 2020 and conducted interviews in English or Spanish. Interviews were recorded, transcribed, and translated to English. Three authors coded transcripts using Dedoose and identified themes via thematic analysis. RESULTS: Analysis of 12 caregiver interviews revealed barriers and facilitators in accessing healthcare and public benefit use. Barriers included healthcare system barriers, immigration-related fear, and racism and discrimination. Within healthcare system barriers, subthemes included language barriers, cost, complexity of resource application, and lack of guidance on available benefits. Within immigration-related fear, subthemes included fear of familial separation, fear of deportation, fear that benefit use affects immigration status, and provider distrust. Healthcare system facilitators of resource use included recruiting diverse workforces, utilizing language interpretation, guidance on benefit enrollment, legal services, and mental health services. Participants also recommended hospital partnership with trusted information sources, including media stations and low-cost clinics. CONCLUSIONS: Immigrant caregivers of hospitalized children identified barriers and facilitators in access to care. Further research is needed to assess the efficacy of caregiver-suggested interventions.

Recent Advances in the Microencapsulation of Essential Oils, Lipids, and Compound Lipids through Spray Drying: A Review.

In recent decades, the microcapsules of lipids, compound lipids, and essential oils, have found numerous potential practical applications in food, textiles, agricultural products, as well as pharmaceuticals. This article discusses the encapsulation of fat-soluble vitamins, essential oils, polyunsaturated fatty acids, and structured lipids. Consequently, the compiled information establishes the criteria to better select encapsulating agents as well as combinations of encapsulating agents best suited to the types of active ingredient to be encapsulated. This review shows a trend towards applications in food and pharmacology as well as the increase in research related to microencapsulation by the spray drying of vitamins A and E, as well as fish oil, thanks to its contribution of omega 3 and omega 6. There is also an increase in articles in which spray drying is combined with other encapsulation techniques, or modifications to the conventional spray drying system.

Robust Descriptor of Pancreatic Tissue for Automatic Detection of Pancreatic Cancer in Endoscopic Ultrasonography.

Pancreatic cancer (PC) has a reported mortality of 98% and a 5-y survival rate of 6.7%. Experienced gastroenterologists detect 80% of those with early-stage PC by endoscopic ultrasonography (EUS). Here we propose an automatic second reader strategy to detect PC in an entire EUS procedure, rather than focusing on pre-selected frames, as the state-of-the-art methods do. The method unmasks echo tumoral patterns in frames with a high probability of tumor. First, speeded up robust features define a set of interest points with correlated heterogeneities among different filtering scales. Afterward, intensity gradients of each interest point are summarized by 64 features at certain locations and scales. A frame feature vector is built by concatenating statistics of each feature of the 15 groups of scales. Then, binary classification is performed by Support Vector Machine and Adaboost models. Evaluation was performed using a data set comprising 55 participants, 18 of PC class (16,585 frames) and 37 subjects of non-PC class (49,664 frames), randomly splitting 10 times. The proposed method reached an accuracy of 92.1%, sensitivity of 96.3% and specificity of 87.8.3%. The observed results are also stable in noisy experiments while deep learning approaches fail to maintain similar performance.

Seizure exacerbation with anti-seizure medications in adult patients with epilepsy.

There are numerous reports of seizure exacerbation related to specific anti-seizure medications (ASMs); however, a quantitative analysis with clearly defined parameters for seizure exacerbation in an outpatient setting is lacking. This retrospective study examines adult patients starting a single ASM and follows patient outcomes over the course of treatment, with quantitative evaluation of the incidence of paradoxical seizure exacerbation. In this study, outpatient encounters with five epileptologists at the Baylor College of Medicine Comprehensive Epilepsy Center were evaluated over a 10-month period. Seizure exacerbation was defined as an increase in seizure frequency at least 2 times greater than the baseline seizure frequency after initiation of an ASM, with return to baseline after ASM discontinuation. Patients were stratified into four categories: (1) probable ASM-induced seizure exacerbation; (2) possible ASM-induced seizure exacerbation; (3) non-ASM induced seizure exacerbation; or (4) no seizure exacerbation. Out of a total of 236 encounters where an ASM was initiated, we found that 5.5% of patients experienced some form of seizure exacerbation. However, only 1.3% of patients had probable ASM-induced seizure exacerbation. Consistent with prior studies, our data indicate seizure exacerbation in adults is rare with the initiation of ASMs. However, further studies with a larger sample size are necessary to better understand what factors may predispose patients to potential medication-induced seizure exacerbation.

[Conjunctival mass as the first manifestation of Epstein Barr virus infection]. / Masa conjuntival como primera manifestación de infección por virus del Epstein Barr.

The Epstein Barr virus is an infectious disease with a high worldwide prevalence, which can present multiple systemic manifestations. The ophthalmological findings are the least frequent and nonspe cific and, therefore, its diagnosis is complicated and delayed; however, it should always be considered as a diagnostic possibility in the presence of atypical ocular and periocular inflammatory clinical pictures. OBJECTIVE: To describe the clinical case of a patient with the presence of a conjunctival mass as the first finding in Epstein Barr virus infection. CLINICAL CASE: A 4-year-old boy with a 4-day history of left upper eyelid edema and ptosis associated with a large, fast-growing, elevated, painful, and salmon-colored upper bulbar conjunctival mass with extension to the upper fornix associated with bilateral cervical and inguinal lymphadenopathy. Initially, a lymphoproliferative disorder was suspected, with blood count with lymphocytosis and atypical lymphocytes, elevated lactate dehydro genase, peripheral blood smear with an increase in white blood cells and some atypical lymphocytes, bone marrow aspirate with a predominance of granulocytes and predominantly CD8-positive T lym phocytes and an increase in Gamma-Delta T lymphocytes. The orbit CT scan showed thickening of the left upper eyelid with peripheral enhancement and the abdominal CT scan showed splenomegaly. Biopsy confirmed chronic Epstein Barr virus infection with positive IgM and indeterminate IgG anti bodies. Symptomatic management was indicated with satisfactory evolution and complete resolution of the conjunctival lesion and lymphadenopathy. CONCLUSION: Epstein Barr virus infection should be considered as a possible diagnosis in atypical ocular and periocular inflammatory manifestations in the pediatric population.