Socioeconomic Disparities in Anal Cancer: Effect on Treatment Delay and Survival.

BACKGROUND: Socioeconomic inequities have implications for access to health care and may be associated with disparities in treatment and survival. OBJECTIVE: To investigate the impact of socioeconomic inequities on time to treatment and survival of anal squamous-cell carcinoma. DESIGN: This is a retrospective study using a nationwide data set. SETTINGS: The patients were selected from the National Cancer Database and enrolled from 2004 to 2016. PATIENTS: We identified patients with stage I to III squamous-cell carcinoma of the anus who were treated with chemoradiation therapy. MAIN OUTCOMES MEASURES: Socioeconomic factors, including race, insurance status, median household income, and percentage of the population with no high school degrees, were included. The association of these factors with treatment delay and overall survival was investigated. RESULTS: A total of 24,143 patients who underwent treatment for grade I to III squamous-cell carcinoma of the anus were identified. The median age was 60 years, and 70% of patients were women. The median time to initiation of treatment was 33 days. Patients from zip codes with lower median income, patients with a higher percentage of no high school degree, and patients with other government insurance followed by Medicaid insurance had treatment initiated after 60 days from diagnosis. Kaplan-Meier survival analysis showed that the late-treatment group had worse overall survival compared to the early treatment group (98 vs 125 months; p < 0.001). LIMITATIONS: No detailed information is available about the chemoradiotherapy regimen, completion of treatment, recurrence, disease-free survival, and individual-level socioeconomic condition and risk factors. CONCLUSION: Patients from communities with lower median income, level of education, and enrolled in public insurance had longer time to treatment. Lower socioeconomic status was also associated with poorer overall survival. These results warrant further analysis and measures to improve access to care to address this disparity. See Video Abstract . DESIGUALDADES SOCIOECONMICAS EN CASOS DE CNCER ANAL EFECTOS EN EL RETRASO DEL TRATAMIENTO Y LA SOBREVIDA: ANTECEDENTES:Las desigualdades socio-económicas tienen implicaciones en el acceso a la atención médica y pueden estar asociadas con disparidades en el tratamiento y la sobrevida.OBJETIVO:Indagar el impacto de las desigualdades socio-económicas sobre el tiempo de retraso en el tratamiento y la sobrevida en casos de carcinoma a células escamosas del ano (CCEA).DISEÑO:Estudio retrospectivo utilizando un conjunto de datos a nivel nacional.AJUSTES:Todos aquellos pacientes inscritos entre 2004 a 2016 y que fueron seleccionados de la Base Nacional de Datos sobre el Cáncer.PACIENTES:Identificamos pacientes con CCEA en estadíos I-III y que fueron tratados con radio-quimioterápia.PRINCIPALES MEDIDAS DE RESULTADOS:Se incluyeron factores socio-económicos tales como la raza, el tipo de seguro de salud, el ingreso familiar medio y el porcentaje de personas sin bachillerato de secundaria (SBS). Se investigó la asociación entre estos factores con el retraso en iniciar el tratamiento y la sobrevida global.RESULTADOS:Se identificaron un total de 24.143 pacientes que recibieron tratamiento para CCEA estadíos I-III. La mediana de edad fue de 60 años donde 70% eran de sexo femenino. La mediana del tiempo transcurrido desde el diagnóstico hasta el inicio del tratamiento fue de 33 días. Los pacientes residentes en zonas de código postal con ingresos medios más bajos, con un mayor porcentaje de individuos SBS y los pacientes con otro tipo de seguro gubernamental de salud, seguidos del seguro tipo Medicaid iniciaron el tratamiento solamente después de 60 días al diagnóstico inicial de CCEA. El análisis de Kaplan-Meier de la sobrevida mostró que el grupo de tratamiento tardío tuvo una peor supervivencia general comparada con el grupo de tratamiento precoz o temprano (98 frente a 125 meses; p <0,001).LIMITACIONES:No se dispone de información detallada sobre el tipo de radio-quimioterapia utilizada, ni sobre la finalización del tratamiento o la recurrencia, tampoco acerca de la sobrevida libre de enfermedad ni sobre las condiciones socio-económicas o aquellos factores de riesgo a nivel individual.CONCLUSIÓN:Los pacientes de comunidades con ingresos medios más bajos, con un nivel de educación limitado e inscritos en un seguro público tardaron mucho más tiempo en recibir el tratamiento prescrito. El nivel socio-económico más bajo también se asoció con una sobrevida global más baja. Los presentes resultados justifican mayor análisis y medidas mas importantes para mejorar el acceso a la atención en salud y poder afrontar esta disparidad. (Traducción-Dr. Xavier Delgadillo ).

Long-read genome sequencing identifies cryptic structural variants in congenital aniridia cases.

BACKGROUND: Haploinsufficiency of the transcription factor PAX6 is the main cause of congenital aniridia, a genetic disorder characterized by iris and foveal hypoplasia. 11p13 microdeletions altering PAX6 or its downstream regulatory region (DRR) are present in about 25% of patients; however, only a few complex rearrangements have been described to date. Here, we performed nanopore-based whole-genome sequencing to assess the presence of cryptic structural variants (SVs) on the only two unsolved "PAX6-negative" cases from a cohort of 110 patients with congenital aniridia after unsuccessfully short-read sequencing approaches. RESULTS: Long-read sequencing (LRS) unveiled balanced chromosomal rearrangements affecting the PAX6 locus at 11p13 in these two patients and allowed nucleotide-level breakpoint analysis. First, we identified a cryptic 4.9 Mb de novo inversion disrupting intron 7 of PAX6, further verified by targeted polymerase chain reaction amplification and sequencing and FISH-based cytogenetic analysis. Furthermore, LRS was decisive in correctly mapping a t(6;11) balanced translocation cytogenetically detected in a second proband with congenital aniridia and considered non-causal 15 years ago. LRS resolved that the breakpoint on chromosome 11 was indeed located at 11p13, disrupting the DNase I hypersensitive site 2 enhancer within the DRR of PAX6, 161 Kb from the causal gene. Patient-derived RNA expression analysis demonstrated PAX6 haploinsufficiency, thus supporting that the 11p13 breakpoint led to a positional effect by cleaving crucial enhancers for PAX6 transactivation. LRS analysis was also critical for mapping the exact breakpoint on chromosome 6 to the highly repetitive centromeric region at 6p11.1. CONCLUSIONS: In both cases, the LRS-based identified SVs have been deemed the hidden pathogenic cause of congenital aniridia. Our study underscores the limitations of traditional short-read sequencing in uncovering pathogenic SVs affecting low-complexity regions of the genome and the value of LRS in providing insight into hidden sources of variation in rare genetic diseases.

VIsoQLR: an interactive tool for the detection, quantification and fine-tuning of isoforms in selected genes using long-read sequencing.

DNA variants altering the pre-mRNA splicing process represent an underestimated cause of human genetic diseases. Their association with disease traits should be confirmed using functional assays from patient cell lines or alternative models to detect aberrant mRNAs. Long-read sequencing is a suitable technique to identify and quantify mRNA isoforms. Available isoform detection and/or quantification tools are generally designed for the whole transcriptome analysis. However experiments focusing on genes of interest need more precise data fine-tuning and visualization tools.Here we describe VIsoQLR, an interactive analyzer, viewer and editor for the semi-automated identification and quantification of known and novel isoforms using long-read sequencing data. VIsoQLR is tailored to thoroughly analyze mRNA expression in splicing assays of selected genes. Our tool takes sequences aligned to a reference, and for each gene, it defines consensus splice sites and quantifies isoforms. VIsoQLR introduces features to edit the splice sites through dynamic and interactive graphics and tables, allowing accurate manual curation. Known isoforms detected by other methods can also be imported as references for comparison. A benchmark against two other popular transcriptome-based tools shows VIsoQLR accurate performance on both detection and quantification of isoforms. Here, we present VIsoQLR principles and features and its applicability in a case study example using nanopore-based long-read sequencing. VIsoQLR is available at https://github.com/TBLabFJD/VIsoQLR .

Comparison of Perineal Closure Techniques after Abdominoperineal Resections for Carcinoma of the Anus.

BACKGROUND: Perineal reconstruction following salvage APR's for squamous cell carcinoma of the anus (SCCA) are scant with conflicting results from large and single center studies. We analyzed these techniques taking into account sociodemographic and oncologic variables. METHODS: This is a retrospective cohort study from 2016-2019 using a targeted ACS/NSQIP database stratified into primary closure (PC), abdominal myocutaneous (AM), lower extremity (LE), and omental pedicled (OP) flaps. We analyzed major and wound complications through univariate and multivariate regression analysis. RESULTS: A total of 766 patients were analyzed, 512 (67%) had PC, 196 (25%) AM, 36 (5%) OP and 22 (3%) LE. Rates of chemotherapy and radiation within 90 days were similar between the groups. Having 2 or more additional organs resected was more common for the AM group (AM 4.1%, PC 1.6%, OP 3.3%, LE 0%). Overall, major complication rate was 41% (n = 324). Primary closure had 35.0%, OP 47.2%, AM 52.6%, and LE 45.5%. Wound complication rate was highest in AM with 11.7%, followed by OP 8.3%, PC 5.9%, and LE 0%. The multivariate regression analysis demonstrated none of the closure techniques to be associated with increasing or decreasing the probability of having a major or wound complication. Morbidity probability was the sole predictor of major complication (OR 1.07, 95% CI 1.04-1.1). CONCLUSIONS: Myocutaneous and omental flaps are associated with comparable wound and major complications when taking into account the baseline, oncologic and perioperative variables that drive the clinical decision making when selecting a perineal reconstruction.

Minigene Splicing Assays and Long-Read Sequencing to Unravel Pathogenic Deep-Intronic Variants in PAX6 in Congenital Aniridia.

PAX6 haploinsufficiency causes aniridia, a congenital eye disorder that involves the iris, and foveal hypoplasia. Comprehensive screening of the PAX6 locus, including the non-coding regions, by next-generation sequencing revealed four deep-intronic variants with potential effects on pre-RNA splicing. Nevertheless, without a functional analysis, their pathogenicity could not be established. We aimed to decipher their impact on the canonical PAX6 splicing using in vitro minigene splicing assays and nanopore-based long-read sequencing. Two multi-exonic PAX6 constructs were generated, and minigene assays were carried out. An aberrant splicing pattern was observed for two variants in intron 6, c.357+136G>A and c.357+334G>A. In both cases, several exonization events, such as pseudoexon inclusions and partial intronic retention, were observed due to the creation or activation of new/cryptic non-canonical splicing sites, including a shared intronic donor site. In contrast, two variants identified in intron 11, c.1032+170A>T and c.1033-275A>C, seemed not to affect splicing processes. We confirmed the high complexity of alternative splicing of PAX6 exon 6, which also involves unreported cryptic intronic sites. Our study highlights the importance of integrating functional studies into diagnostic algorithms to decipher the potential implication of non-coding variants, usually classified as variants of unknown significance, thus allowing variant reclassification to achieve a conclusive genetic diagnosis.

Outcomes of perineal wound closure techniques after abdominoperineal resections in rectal cancer: an NSQIP propensity score matched study.

Perineal defects following abdominoperineal resections (APRs) for rectal cancer may require myocutaneous or omental flaps depending upon anatomic, clinical and oncologic variables. However, studies comparing their efficacy have shown contradictory results. We aim to compare postoperative complication rates of APR closure techniques in rectal cancer using propensity score-matching. The American College of Surgeons Proctectomy Targeted Data File was queried from 2016 to 2019. The study population was defined using CPT and ICD-10 codes for patients with rectal cancer undergoing APR, stratified by repair technique. Perioperative demographic and oncologic variables were controlled for by propensity-score matching. Multivariate logistic regression analysis was performed for wound and major complications (MCs). Of the 3291 patients included in the study, 85% underwent primary closure (PC), 8.3% rectus abdominis myocutaneous (RAM) flap, 4.9% pedicled omental flap with PC, and 1.9% lower extremity (LE) flap repair. Primary closure rates were significantly higher for patients with stage T1 and T2 tumors (p < 0.001). RAM and LE flaps were most used with multi-organ resections, 24% and 25%, respectively (p < 0.001). Similarly, cases with T4 tumors used these flaps more frequently, 30% and 40%, respectively (p < 0.001). After propensity score matching for comorbidities and oncologic variables, there was no significant difference in 30-day postoperative wound or MC rates between perineal closure techniques. The complication rates of the different closure techniques are comparable when tumor stage is considered. Therefore, tumor staging and concurrent procedures should guide clinical decision making regarding the appropriate use of each technique.

Anal Adenocarcinoma Arising From a Fistula-in-Ano: A Case Report.

Crohn's disease (CD) is an inflammatory disease that can affect any portion of the gastrointestinal tract (GIT). Although it can present with a number of complications, perianal fistulae are among the most common consequences in patients with CD. In very rare cases, these patients can develop fistula-associated anal adenocarcinoma (FAAA). In this case report, we discuss a 72-year-old man with a long-term history of CD complicated by perianal fistulae, which failed medical and surgical management, ultimately presenting with acute anal pain in the outpatient setting. The physical examination revealed a seton traversing through a fistula surrounded by circumferential granulation tissue suspicious for malignancy. A biopsy of the tissue confirmed grade 3 mucinous-type infiltrating adenocarcinoma of the perianal skin. The patient was diagnosed with an anal verge malignancy associated with a fistula in the context of long-standing CD, and MRI staging demonstrated a T3N1 lesion with potential left inguinal node involvement. He completed neoadjuvant chemo-radiotherapy using capecitabine for five weeks with minimal tumor response, and subsequently, an abdominoperineal resection (APR) was performed with patient discharge on the fifth post-procedure day. Post-operative chemotherapy with oxaliplatin/leucovorin/fluorouracil was administered with minimal complications. Although rare, this report demonstrates the importance of consistent follow-up and mitigation of risk factors in patients with CD, along with the significance of prompt multimodal treatment in the event of developing FAAA.

Coping Strategies for Exposure to Trauma Situations in First Responders: A Systematic Review.

OBJECTIVE: The objective of the present work was to characterize the coping strategies used by first responders to emergencies in the face of exposure to traumatic events. METHODS: A systematic search was performed in the databases MEDLINE (Ovid), EMBASE, LILACS (Latin American and Caribbean Literature in Health Sciences), and the Cochrane Central Registry of Controlled Clinical Trials (CENTRAL) from their inception through February 2022. First responders to emergencies with training in the prehospital area and who used validated measurement instruments for coping strategies were included. RESULTS: First responders to emergencies frequently used nonadaptive coping strategies, with avoidance or disconnection being one of the main strategies, as a tool to avoid confronting difficult situations and to downplay the perceived stressful event. The nonadaptive coping strategies used by these personnel showed a strong relationship with posttraumatic stress disorder (PTSD) symptoms, burnout syndrome, psychiatric morbidity, and chronic stress. As part of the adaptive strategies, active coping was found, which includes acceptance, positive reinterpretation, focusing on the problem, self-efficacy, and emotional support, either social or instrumental, as protective strategies for these personnel. CONCLUSIONS: Developing adaptive coping strategies, whether focused on problems or seeking emotional support, can benefit emergency personnel in coping with stressful situations. These coping strategies should be strengthened to help prevent people from experiencing long-term negative effects that could arise from the traumatic events to which they are exposed. Active coping strategies instead of avoidance strategies should be promoted.

Disaster Risk Management Plans in Colombia: General Guidelines for Their Development.

Over the years, Colombia has faced disaster situations that have generated changes in risk management models. These situations have brought suffering, destruction, and loss of human life, but have also served as lessons to develop procedures aimed at minimizing the risks caused by the presence of hazards. The objective of this article is to provide general evidence-based guidelines for formulating disaster risk management plans for each of the 3 action processes: risk awareness, risk reduction, and disaster management in Colombia. These plans can be achieved by preparing responses to different emergencies, which arise from threats in each of the possible scenarios, and are adverse events that alter the normal functioning of entities and communities. The implementation of these prevention strategies will allow communities to respond effectively to emergencies and recover rapidly in the face of adversity.

Activation of cryptic donor splice sites by non-coding and coding PAX6 variants contributes to congenital aniridia.

BACKGROUND: The paired-domain transcription factor paired box gene 6 (PAX6) causes a wide spectrum of ocular developmental anomalies, including congenital aniridia, Peters anomaly and microphthalmia. Here, we aimed to functionally assess the involvement of seven potentially non-canonical splicing variants on missplicing of exon 6, which represents the main hotspot region for loss-of-function PAX6 variants. METHODS: By locus-specific analysis of PAX6 using Sanger and/or targeted next-generation sequencing, we screened a Spanish cohort of 106 patients with PAX6-related diseases. Functional splicing assays were performed by in vitro minigene approaches or directly in RNA from patient-derived lymphocytes cell line, when available. RESULTS: Five out seven variants, including three synonymous changes, one small exonic deletion and one non-canonical splice variant, showed anomalous splicing patterns yielding partial exon skipping and/or elongation. CONCLUSION: We describe new spliceogenic mechanisms for PAX6 variants mediated by creating or strengthening five different cryptic donor sites at exon 6. Our work revealed that the activation of cryptic PAX6 splicing sites seems to be a recurrent and underestimated cause of aniridia. Our findings pointed out the importance of functional assessment of apparently silent PAX6 variants to uncover hidden genetic alterations and to improve variant interpretation for genetic counselling in aniridia.

Fine Breakpoint Mapping by Genome Sequencing Reveals the First Large X Inversion Disrupting the NHS Gene in a Patient with Syndromic Cataracts.

Inversions are structural variants that are generally balanced. However, they could lead to gene disruptions or have positional effects leading to diseases. Mutations in the NHS gene cause Nance-Horan syndrome, an X-linked disorder characterised by congenital cataracts and dental anomalies. Here, we aimed to characterise a balanced pericentric inversion X(p22q27), maternally inherited, in a child with syndromic bilateral cataracts by breakpoint mapping using whole-genome sequencing (WGS). 30× Illumina paired-end WGS was performed in the proband, and breakpoints were confirmed by Sanger sequencing. EdU assays and FISH analysis were used to assess skewed X-inactivation patterns. RNA expression of involved genes in the breakpoint boundaries was evaluated by droplet-digital PCR. We defined the breakpoint position of the inversion at Xp22.13, with a 15 bp deletion, disrupting the unusually large intron 1 of the canonical NHS isoform, and also perturbing topologically-associated domains (TADs). Moreover, a microhomology region of 5 bp was found on both sides. RNA analysis confirmed null and reduced NHS expression in the proband and his unaffected mother, respectively. In conclusion, we report the first chromosomal inversion disrupting NHS, fine-mapped by WGS. Our data expand the clinical spectrum and the pathogenic mechanisms underlying the NHS defects.

Riesgos del personal que labora en atención prehospitalaria: Reto para los servicios de emergencia / Risks of the staff working in Pre-Hospital care: A challenge for the emergency services

RESUMEN La atención prehospitalaria o la respuesta a una emergencia en el escenario prehospitalario, definido en un contexto internacional, comprende todas las intervenciones médicas y de transporte realizadas a pacientes que presentan eventos médicos o traumáticos en diferentes escenarios fuera del ámbito hospitalario. Quienes realizan la labor prehospitalaria deben enfrentarse a situaciones y escenarios variados, complejos y no controlados; todas estas situaciones implican estar expuestos a una variabilidad de riesgos que pueden ser prevenibles si se toman las medidas necesarias para mitigarlos. Los riesgos biológicos, biomecánicos, psicosociales, físicos, asociados a la violencia física y verbal, entre otros, exponen a este personal al desarrollo de accidentes de trabajo y enfermedades laborales en muchas ocasiones de magnitudes severas y con graves consecuencias. Caracterizar la labor prehospitalaria plantea muchos desafíos, la atención del paciente varía con cada llamada, y esta, a su vez, presenta retos únicos dependiendo del estado clínico, la necesidad de cada paciente y el escenario donde se está presentando el evento. Conocer con más detalle los riesgos laborales de esta profesión que diariamente se expone a situaciones diversas y diseñar estrategias para mejorar la salud y el bienestar de los trabajadores de esta área, se traduce en una atención médica de emergencia más efectiva y eficiente, contribuyendo a mejorar la calidad y a fortalecer los sistemas de salud en el ámbito prehospitalario.

ABSTRACT In an international context, the Prehospital care or response to an emergency in the prehospital setting includes all medical and transport interventions performed on patients who have suffered medical or traumatic events in different scenarios outside the hospital setting. Those who perform prehospital work must face varied, complex, and uncontrolled situations and scenarios which involve the exposure to variability of risks that may be prevented if mitigation measures are taken in advance. The biological, biomechanical, psychosocial, and physical risks associated with physical and verbal violence, among others, expose these personnel to severe work accidents and occupational diseases, which represent serious consequences. Characterizing the prehospital work poses many challenges. Patient care, for example, varies with each call, and this in turn presents unique challenges depending on the clinical status, the need of each patient, and the setting where the event is taking place. Knowing in more detail the occupational risks of the staff working in prehospital care who, in fact, expose themselves to diverse situations, and designing strategies to improve their health and well-being, translates into more effective and efficient emergency medical care which contributes to improve quality and strengthen health systems in the prehospital setting.

Patterns of Use of Smartphone-Based Interventions Among Latina Breast Cancer Survivors: Secondary Analysis of a Pilot Randomized Controlled Trial.

BACKGROUND: Latina breast cancer survivors experience poorer health-related quality of life (HRQoL), greater symptom burden, and more psychosocial needs compared to non-Latina breast cancer survivors. eHealth platforms such as smartphone apps are increasingly being used to deliver psychosocial interventions to cancer survivors. However, few psychosocial eHealth interventions have been developed specifically for Latina breast cancer survivors. Further, little is known about how Latinas, in general, engage with eHealth interventions and whether specific participant characteristics are associated with app use in this population. We evaluated the use of 2 culturally informed, evidence-based smartphone apps for Latina breast cancer survivors-one that was designed to improve HRQoL and reduce symptom burden (My Guide) and the other to promote healthy lifestyle behaviors (My Health). OBJECTIVE: The objectives of our study were to explore the patterns of use of the My Guide intervention app and My Health attention-control app among Latina breast cancer survivors. METHODS: Eighty Latina breast cancer survivors were randomized to use the My Guide or My Health app for 6 weeks. Assessments were collected at baseline (T1), immediately after the 6-week intervention (T2), and 2 weeks after T2 (T3). Specific study outcomes included subdomains of HRQoL, symptom burden, cancer-specific distress, cancer-relevant self-efficacy, and breast cancer knowledge. RESULTS: On average, participants used their assigned app for more than 1 hour per week. Sociodemographic or psychological characteristics were not significantly associated with app use, except for employment status in the My Health group. Content related to common physical and emotional symptoms of breast cancer survivors as well as recommendations for nutrition and physical activity were most frequently accessed by My Guide and My Health participants, respectively. Lastly, clinically meaningful improvements were demonstrated in breast cancer well-being among low app users (ie, <60 minutes of use/week) of My Guide and social well-being among high app users (ie, ≥60 minutes of use/week) of My Health. CONCLUSIONS: The favorable rates of participant use across both apps suggest that Latina breast cancer survivors are interested in the content delivered across both My Guide and My Health. Furthermore, since sociodemographic variables, excluding employment status, and baseline HRQoL (psychological variable) were not related to app use, My Guide and My Health may be accessible to diverse Latina breast cancer survivors. TRIAL REGISTRATION: ClinicalTrials.gov NCT03645005; https://clinicaltrials.gov/ct2/show/NCT03645005.

Cancer-Relevant Self-Efficacy Is Related to Better Health-Related Quality of Life and Lower Cancer-Specific Distress and Symptom Burden Among Latina Breast Cancer Survivors.

BACKGROUND: Latina breast cancer survivors (BCS) often report poorer health-related quality of life (HRQOL), higher symptom burden, and greater psychosocial needs compared to non-Latina BCS. However, Latinas are underrepresented in cancer survivorship research and more work is needed to examine the factors contributing to these psychosocial disparities. This study aimed to evaluate potentially modifiable patient characteristics associated with HRQOL, breast cancer concerns, and cancer-specific distress among Latina BCS. METHODS: Baseline data was evaluated in 95 Latina BCS who participated in a smartphone-based psychosocial intervention designed to improve HRQOL. Hierarchical linear regression analyses were conducted to evaluate the associations between modifiable factors that have been shown to favorably impact outcomes in cancer populations (i.e., cancer-relevant self-efficacy, breast cancer knowledge) with overall and domain-specific HRQOL, breast cancer symptom burden, and cancer-specific distress, after controlling for sociodemographic and cancer-related characteristics. RESULTS: Greater cancer-relevant self-efficacy was related to better overall HRQOL as well as better social, emotional, and functional well-being domains. Greater cancer-relevant self-efficacy was also related to less breast cancer symptom burden and less cancer-specific distress. Breast cancer knowledge was not associated with any of the study outcomes. CONCLUSIONS: Results demonstrate that cancer-relevant self-efficacy is a significant correlate of general and domain-specific HRQOL, breast cancer symptom burden, and cancer-specific distress among Latina BCS. Future interventions in this population should target cancer-relevant self-efficacy as a possible mechanism to improve HRQOL outcomes and survivorship experiences for Latina BCS.

CPAMD8 loss-of-function underlies non-dominant congenital glaucoma with variable anterior segment dysgenesis and abnormal extracellular matrix.

Abnormal development of the ocular anterior segment may lead to a spectrum of clinical phenotypes ranging from primary congenital glaucoma (PCG) to variable anterior segment dysgenesis (ASD). The main objective of this study was to identify the genetic alterations underlying recessive congenital glaucoma with ASD (CG-ASD). Next-generation DNA sequencing identified rare biallelic CPAMD8 variants in four patients with CG-ASD and in one case with PCG. CPAMD8 is a gene of unknown function and recently associated with ASD. Bioinformatic and in vitro functional evaluation of the variants using quantitative reverse transcription PCR and minigene analysis supported a loss-of-function pathogenic mechanism. Optical and electron microscopy of the trabeculectomy specimen from one of the CG-ASD cases revealed an abnormal anterior chamber angle, with altered extracellular matrix, and apoptotic trabecular meshwork cells. The CPAMD8 protein was immunodetected in adult human ocular fluids and anterior segment tissues involved in glaucoma and ASD (i.e., aqueous humor, non-pigmented ciliary epithelium, and iris muscles), as well as in periocular mesenchyme-like cells of zebrafish embryos. CRISPR/Cas9 disruption of this gene in F0 zebrafish embryos (96 hpf) resulted in varying degrees of gross developmental abnormalities, including microphthalmia, pharyngeal maldevelopment, and pericardial and periocular edemas. Optical and electron microscopy examination of these embryos showed iridocorneal angle hypoplasia (characterized by altered iris stroma cells, reduced anterior chamber, and collagen disorganized corneal stroma extracellular matrix), recapitulating some patients' features. Our data support the notion that CPAMD8 loss-of-function underlies a spectrum of recessive CG-ASD phenotypes associated with extracellular matrix disorganization and provide new insights into the normal and disease roles of this gene.

Seroprotección para virus de hepatitis B en estudiantes universitarios de atención prehospitalaria en Cali, Colombia / Seroprotection for hepatitis B virus in university students of prehospital care in Cali, Colombia

Introducción: El personal de salud se encuentra expuesto a contraer enfermedades infecto contagiosas en el ejercicio de su labor, una de ellas es la hepatitis B. Los estudiantes de atención prehospitalaria no se encuentran exentos de sufrir esta enfermedad, sobre todo por el contexto de las emergencias y desastres donde se desenvuelven. Objetivo: Determinar la prevalencia de seroprotección para el virus de hepatitis B en estudiantes de atención prehospitalaria en una universidad en Colombia. Métodos: Estudio descriptivo de corte transversal realizado a estudiantes de atención prehospitalaria en el periodo febrero-junio de 2017. No se utilizó ninguna técnica de muestreo porque se incluyó la totalidad de los estudiantes en práctica. Se aplicó un cuestionario con preguntas de datos sociodemográficos, registro del esquema de vacunación para hepatitis B y el resultado de los anticuerpos (Anti-HBs). Para el análisis estadístico se utilizó Microsoft Excel 2010, se construyeron estadísticas descriptivas. Las variables numéricas se describieron con base en medidas de tendencia central y variabilidad, las variables categóricas se describieron con base en prevalencias y distribuciones porcentuales. Resultados: En la caracterización de los 103 estudiantes evaluados se encontró que el 98 por ciento obtuvo títulos de anticuerpos (Anti-HBs) mayores a 10 UI/ml, considerándose como reactivos a las dosis de las vacunas, alcanzando títulos protectores. Sin embargo, el 93 por ciento no cumplió con el esquema de vacunación establecido. Conclusiones: Los resultados obtenidos evidencian la efectividad de las dosis aplicadas de vacuna para el virus de hepatitis B para obtener los títulos de anticuerpos a estudiantes de atención prehospitalaria en una universidad en Colombia. Pero existen incumplimientos en los tiempos recomendados para la aplicación de cada una de las dosis y en el tiempo de toma de los títulos(AU)

Introduction: Health personnel are at risk of infectious diseases when doing their job. One of them is hepatitis B. Prehospital care students are not free from suffering this disease, especially due to the emergencies and disasters context in which they work. Objective: To determine the prevalence of seroprotection for the hepatitis B virus in prehospital care students at a university in Colombia. Methods: Descriptive cross-sectional study carried out on prehospital care students during the period February-June 2017. No sampling technique was used because all the students in practice were included. A questionnaire was applied with questions of social-demographic data, registration of the vaccination schedule for hepatitis B and result of (Anti-HBs) antibodies. For statistical analysis, Microsoft Excel 2010 was used and descriptive statistics were designed. Numerical variables were described based on measures of central tendency and variability, categorical variables were described based on prevalence and percentage distributions. Results: In the depiction of the 103 students who were evaluated, it was found that 98 percent obtained antibody titers (Anti-HBs) bigger than 10 IU / ml, being considered as reactive to the doses of the vaccines and getting protective titles. However, 93 percent did not fill the established vaccination schedule. Conclusions: It can be concluded that the results obtained show the effectiveness of the applied doses of vaccine for the hepatitis B virus to obtain antibody titers to prehospital care students at a university in Colombia. But there are breaches in the recommended times for the application of each of the doses and in the time of taking the antibody titers(AU)

Seroprotección para virus de hepatitis B en estudiantes universitarios de atención prehospitalaria en Cali, Colombia / Seroprotection for hepatitis B virus in university students of prehospital care in Cali, Colombia

RESUMEN Introducción: El personal de salud se encuentra expuesto a contraer enfermedades infecto contagiosas en el ejercicio de su labor, una de ellas es la hepatitis B. Los estudiantes de atención prehospitalaria no se encuentran exentos de sufrir esta enfermedad, sobre todo por el contexto de las emergencias y desastres donde se desenvuelven. Objetivo: Determinar la prevalencia de seroprotección para el virus de hepatitis B en estudiantes de atención prehospitalaria en una universidad en Colombia. Métodos: Estudio descriptivo de corte transversal realizado a estudiantes de atención prehospitalaria en el periodo febrero-junio de 2017. No se utilizó ninguna técnica de muestreo porque se incluyó la totalidad de los estudiantes en práctica. Se aplicó un cuestionario con preguntas de datos sociodemográficos, registro del esquema de vacunación para hepatitis B y el resultado de los anticuerpos (Anti-HBs). Para el análisis estadístico se utilizó Microsoft Excel 2010, se construyeron estadísticas descriptivas. Las variables numéricas se describieron con base en medidas de tendencia central y variabilidad, las variables categóricas se describieron con base en prevalencias y distribuciones porcentuales. Resultados: En la caracterización de los 103 estudiantes evaluados se encontró que el 98 % obtuvo títulos de anticuerpos (Anti-HBs) mayores a 10 UI/ml, considerándose como reactivos a las dosis de las vacunas, alcanzando títulos protectores. Sin embargo, el 93 % no cumplió con el esquema de vacunación establecido. Conclusiones: Los resultados obtenidos evidencian la efectividad de las dosis aplicadas de vacuna para el virus de hepatitis B para obtener los títulos de anticuerpos a estudiantes de atención prehospitalaria en una universidad en Colombia. Pero existen incumplimientos en los tiempos recomendados para la aplicación de cada una de las dosis y en el tiempo de toma de los títulos.

ABSTRACT Introduction: Health personnel are at risk of infectious diseases when doing their job. One of them is hepatitis B. Prehospital care students are not free from suffering this disease, especially due to the emergencies and disasters context in which they work. Objective: To determine the prevalence of seroprotection for the hepatitis B virus in prehospital care students at a university in Colombia. Methods: Descriptive cross-sectional study carried out on prehospital care students during the period February-June 2017. No sampling technique was used because all the students in practice were included. A questionnaire was applied with questions of social-demographic data, registration of the vaccination schedule for hepatitis B and result of (Anti-HBs) antibodies. For statistical analysis, Microsoft Excel 2010 was used and descriptive statistics were designed. Numerical variables were described based on measures of central tendency and variability, categorical variables were described based on prevalence and percentage distributions. Results: In the depiction of the 103 students who were evaluated, it was found that 98% obtained antibody titers (Anti-HBs) bigger than 10 IU / ml, being considered as reactive to the doses of the vaccines and getting protective titles. However, 93% did not fill the established vaccination schedule. Conclusions: It can be concluded that the results obtained show the effectiveness of the applied doses of vaccine for the hepatitis B virus to obtain antibody titers to prehospital care students at a university in Colombia. But there are breaches in the recommended times for the application of each of the doses and in the time of taking the antibody titers.

My health smartphone intervention decreases daily fat sources among Latina breast cancer survivors.

Breast cancer is the most common cancer among Latina women, and Latina women are at higher risk for breast cancer mortality than white women. Lifestyle factors, such as consuming a nutritious diet and engaging in regular physical activity, promote health and are protective against heart disease, type 2 diabetes, and breast cancer recurrence. Previous studies have developed and tested interventions for Latina breast cancer survivors to improve diet and increase physical activity, however, no studies to date have developed a smartphone delivered intervention. The purpose of the current study was to compare two Smartphone delivered interventions, My Health, which focused on diet and physical activity, and My Guide, which focused on psychosocial functioning, on dietary and physical activity outcomes, post-intervention, and at a 2-week follow-up assessment. Overall, participants receiving the My Health intervention reported a greater reduction in daily fat sources than the My Guide group over time. However, daily sources of fat did not differ between conditions. Walking, measured by estimated weekly metabolic equivalents, increased across time points in both groups. These preliminary findings suggest that eHealth interventions aimed at improving lifestyle factors may favorably impact nutritional intake and physical activity. Future research should utilize more comprehensive and objective measures of diet and physical activity, and incorporate more behavioral lifestyle components into the intervention in larger samples with a longer follow-up period.

Brief culturally informed smartphone interventions decrease breast cancer symptom burden among Latina breast cancer survivors.

OBJECTIVE: Latina breast cancer survivors (BCS) report more symptom burden and poorer health-related quality of life than non-Latina BCS. However, there are few evidence-based and culturally informed resources that are easily accessible to this population. This study aimed to establish the feasibility and preliminary efficacy of the My Guide and My Health smartphone applications among Latina BCS. Both applications are culturally informed and contain evidence-based information for reducing symptom burden and improving health-related quality of life (My Guide) or healthy lifestyle promotion (My Health). METHODS: Participants (N = 80) were randomized to use the My Guide or My Health smartphone applications for 6 weeks. Assessments occurred at baseline (T1) after the 6-week intervention (T2) and 2-week post-T2 (T3). Outcomes were participant recruitment and retention rates, patient-reported satisfaction, and validated measures of symptom burden and health-related quality of life. RESULTS: Recruitment was acceptable (79%), retention was excellent (>90%), and over 90% of participants were satisfied with their application. On average, participants in both conditions used the applications for more than 1 hour per week. Symptom burden declined from T1 to T2 across both conditions, but this decline was not maintained at T3. Breast cancer well-being improved from T1 to T2 across both conditions and was maintained at T3. CONCLUSIONS: Latina BCS who used the My Guide and My Health applications reported temporary decreases in symptom burden and improved breast cancer well-being over time, though there were no differential effects between conditions. Findings suggest that technology may facilitate Latina BCS engagement in care after breast cancer treatment.