Retinal Function in Long-Term Type 1 Diabetes without Retinopathy: Insights from Pattern Electroretinogram and Pattern Visual Evoked Potentials Assessments.

BACKGROUND: To evaluate changes in pattern electroretinogram (pERG) and pattern visual evoked potentials (pVEP) in patients with long-lasting type 1 diabetes without diabetic retinopathy (DR). METHODS: Prospective study involving 92 eyes divided into two groups. The diabetic group included 46 eyes of 23 patients with type 1 diabetes (T1DM); the control group included 23 age-matched healthy subjects. pERG and pVEP were assessed using the RETI-port/scan21 recording software (version 1021.3.0.0). RESULTS: Mean age was 48 ± 9.77 years for the diabetic group and 51.7 ± 4.75 years for the control group. The mean duration of diabetes was 28.88 ± 8.04 years. The mean HbA1c value was 7.29 ± 0.89%. There were no differences in the age or sex distribution. Regarding the pERG, T1DM patients exhibited a significant decrease in the amplitude of the P50 and N95 waves compared to the control group (p = 0.018 and p = 0.035, respectively), with no differences in the peak time of each component. pVEP showed no significant changes in either peak time or amplitude of the different components. CONCLUSIONS: Long-term T1DM patients without DR showed changes in the amplitude of pERG waves with preserved peak times. We did not observe modifications in pVEP. pERG may serve as a subclinical marker of ganglion cell damage in long-term T1DM patients.

Yeast-Derived Nucleotides Enhance Fibroblast Migration and Proliferation and Provide Clinical Benefits in Atopic Dermatitis.

Nucleotides, glycosaminoglycans, and omega-3 essential fatty acids (O3s) could be used for improving skin health, although their modes of action, alone or in combination, are not yet fully understood. To gain some insight into these mechanisms, we performed two in vitro tests and one in vivo pilot trial. The effects on human dermal fibroblast proliferation and migration were evaluated with the following compounds and combinations: 0.156 mg/mL O3s, 0.0017 mg/mL hyaluronic acid (HA), 0.0004 mg/mL dermatan sulfate (DS), 0.0818 mg/mL nucleotides, and [O3s + HA + DS] and [O3s + HA + DS + nucleotides] at the same concentrations. In both in vitro assays, adding nucleotides to [O3s + HA + DS] provided significant improvements. The resulting combination [O3s + HA + DS + nucleotides] was then tested in vivo in dogs with atopic dermatitis by oral administration of a supplement providing a daily amount of 40 mg/kg nucleotides, 0.9 mg/kg HA, 0.18 mg/kg DS, 53.4 mg/kg EPA, and 7.6 mg/kg DHA. After 30 days, the pruritus visual analog scale (pVAS) score was significantly reduced, and no adverse effects were observed. In conclusion, the combination of nucleotides plus glycosaminoglycans and O3s could serve as a useful therapeutic alternative in skin health applications.

Transitional Care Navigation.

OBJECTIVES: This manuscript aims to provide an extensive review of the literature, synthesize findings, and present substantial insights on the current state of transitional care navigation. Additionally, the existing models of care, pertaining to the concept and approach to transitional care navigation, will be highlighted. METHODS: An extensive search was conducted though using multiple search engines, topic-specific key terminology, eligibility of studies, as well as a limitation to only literature of existing relevance. Integrity of the evidence was established through a literature review matrix source document. A synthesis of nursing literature from organizations and professional publications was used to generate a comparison among various sources of evidence for this manuscript. Primary evidence sources consisted of peer-reviewed journals and publications from professional organizations such as the AHRQ, Academic Search Premier, CINAHL Plus with Full Text, and the Talbot research library. RESULTS: A total of five systematic reviews (four with meta-analysis) published between 2016 and 2022 and conducted in several countries (Brazil, Korea, Singapore, and the US) were included in this review. A combined total of 105 studies were included in the systematic reviews with 53 studies included in meta-analyses. The review of the systematic reviews identified three overarching themes: care coordination, care transition, and patient navigation. Care coordination was associated with an increase in care quality rating, increased the health-related quality of life in newly diagnosed patients, reduced hospitalization rates, reduced emergency department visits, timeliness in care, and increased appropriateness of healthcare utilization. Transitional care interventions resulted to reduced average number of admissions in the intervention (I) group vs control (C) (I = 0.75, C = 1.02) 180 days after a 60-day intervention, reduced readmissions at 6 months, and reduced average number of visits 180 days after 60-day intervention (I = 2.79, C = 3.60). Nurse navigators significantly improved the timeliness of care from cancer screening to first-course treatment visit (MD = 20.42, CI = 8.74 to 32.10, P = .001). CONCLUSION: The care of the cancer patient entails treatments, therapies, and follow-up care outside of the hospital setting. These transitions can be challenging as they require coordination and collaboration among various health care sites. The attributes of transitional care navigation overlap with care coordination, care transition, and patient navigation. There is an opportunity to formally develop a transitional care navigation model to effectively addresses the challenges in care transitions for patient including barriers to health professional exchange of information or communication across care settings and the complexity of coordination between care settings. The transitional care navigation and clinic model developed at a free-standing NCI-designated comprehensive cancer center is a multidisciplinary approach created to close the gaps in care from hospital to home. IMPLICATIONS FOR NURSING PRACTICE: A transitional care navigation model aims to transform the existing perspectives and viewpoints of hospital discharge and transition of care to home or post-acute care settings as two solitary processes to that of a collective approach to care. The model supports provides an integrated continuum of quality, comprehensive care that supports patient compliance with treatment regimens, reinforces patient and caregiver education, and improves health outcomes.

EMDR therapy vs. supportive therapy as adjunctive treatment in trauma-exposed bipolar patients: A randomised controlled trial.

INTRODUCTION: Patients with bipolar disorder (BD) are frequently exposed to traumatic events which worsen disease course, but this study is the first multicentre randomised controlled trial to test the efficacy of a trauma-focused adjunctive psychotherapy in reducing BD affective relapse rates. MATERIALS AND METHODS: This multicentre randomised controlled trial included 77 patients with BD and current trauma-related symptoms. Participants were randomised to either 20 sessions of trauma-focused Eye Movement Desensitization and Reprocessing (EMDR) therapy for BD, or 20 sessions of supportive therapy (ST). The primary outcome was relapse rates over 24-months, and secondary outcomes were improvements in affective and trauma symptoms, general functioning, and cognitive impairment, assessed at baseline, post-treatment, and at 12- and 24-month follow-up. The trial was registered prior to starting enrolment in clinical trials (NCT02634372) and carried out in accordance with CONSORT guidelines. RESULTS: There was no significant difference between treatment conditions in terms of relapse rates either with or without hospitalisation. EMDR was significantly superior to ST at the 12-month follow up in terms of reducing depressive symptoms (p=0.0006, d=0.969), manic symptoms (p=0.027, d=0.513), and improving functioning (p=0.038, d=0.486). There was no significant difference in dropout between treatment arms. CONCLUSIONS: Although the primary efficacy criterion was not met in the current study, trauma-focused EMDR was superior to ST in reducing of affective symptoms and improvement of functioning, with benefits maintained at six months following the end of treatment. Both EMDR and ST reduced trauma symptoms as compared to baseline, possibly due to a shared benefit of psychotherapy. Importantly, focusing on traumatic events did not increase relapses or dropouts, suggesting psychological trauma can safely be addressed in a BD population using this protocol.

Predictive factors of the psychological impact of the COVID-19 pandemic on university students: a study in six Ibero-American countries / Factores predictivos del impacto psicológico de la pandemia de COVID-19 en estudiantes universitarios: un estudio en seis países iberoamericanos

Background/Objective: During Covid-19, high prevalences of anxiety and depression were reported among university students, suggesting that they may be at higher risk than the general population of developing psychological disorders in lockdown situations. This study aimed to analyze how sociocultural factors and individual differences contributed to explaining the psychological impact of the pandemic among Ibero-American university students from Argentina, Colombia, Ecuador, Spain, Mexico, and Uruguay. Method: The study was carried out on 7601 university students (72% women). Data were collected through an online questionnaire that measured anxiety (GAD-2), depression (PHQ-2), somatic symptoms (SSQ-5), post-traumatic growth (PTGI), loneliness (UCLS), personality (NEO-FFI), Resilience (CD-RISC-2), Perceived Competences (PCS) and sociodemographic data. Descriptive statistics and multiple linear regression model were performed. Results: Analysis indicated a high prevalence (46.15%) of distress among university students, regardless of country and significantly higher than in the general population (28.27%). Greater feelings of loneliness and greater neuroticism were significantly associated with anxiety, depression, and somatization. Likewise, male gender and higher levels of resilience were found to be protective factors, while post-traumatic growth was also higher in men and was associated with higher levels of resilience, perceived competence, and responsibility. Conclusions: The results suggest the need to consider individual risk factors such as being a woman, presenting higher levels of neuroticism and loneliness in understanding the psychological impact of the pandemic on university students. It is concluded that universities should offer specific interventions to address mental health problems and manage the added complications of crisis events on the health of students.(AU)

Antecedentes/Objetivo: Durante el Covid-19, se informaron altas prevalencias de ansiedad y depresión entre estudiantes universitarios, lo que sugiere que pueden tener un mayor riesgo que la población general de desarrollar trastornos psicológicos en situaciones de encierro. Este estudio tuvo como objetivo analizar cómo los factores socioculturales y las diferencias individuales contribuyeron a explicar el impacto psicológico de la pandemia entre estudiantes universitarios iberoamericanos de Argentina, Colombia, Ecuador, España, México y Uruguay. Método: El estudio se realizó en 7601 estudiantes universitarios (72% mujeres). Los datos fueron recolectados a través de un cuestionario en línea que midió ansiedad (GAD-2), depresión (PHQ-2), síntomas somáticos (SSQ-5), crecimiento postraumático (PTGI), soledad (UCLS), personalidad (NEO-FFI), Resiliencia (CD-RISC-2), Competencia Percibida (PCS) y datos sociodemográficos. Se realizó estadística descriptiva y modelo de regresión lineal múltiple. Resultados: Los análisis indicaron una alta prevalencia (46,15%) de angustia entre los estudiantes universitarios, independientemente del país y significativamente mayor que en la población general (28,27%). Mayores sentimientos de soledad y mayor neuroticismo se asociaron significativamente con ansiedad, depresión y somatización. Asimismo, el género masculino y mayores niveles de resiliencia resultaron ser factores protectores, mientras que el crecimiento postraumático también fue mayor en los hombres y se asoció con mayores niveles de resiliencia, competencia percibida y responsabilidad. Conclusiones: Los resultados sugieren la necesidad de considerar factores de riesgo individuales como ser mujer, presentar mayores niveles de neuroticismo y soledad en la comprensión del impacto psicológico de la pandemia en estudiantes universitarios. Se concluye que las universidades deben ofrecer intervenciones específicas para abordar los problemas de salud mental y manejar las complicaciones añadidas de los eventos de crisis sobre la salud de los estudiantes.(AU)

Impact of the lipid phase composition and state on the in vitro digestibility and chlorophyllin bioaccessibility of W1/O/W2 emulsions into whole milk.

Water-in-oil-in-water (W1/O/W2) emulsions offer the potential to deliver hydrophilic bioactive compounds into foods, yet their application remains limited due to their instability. Thus, the impact of lipid phase composition and state on the colloidal stability, in vitro lipid digestibility and chlorophyllin (CHL) bioaccessibility of W1/O/W2 emulsions before and after incorporation into whole milk was studied. Medium-chain triglyceride oil (MCT) was used as a liquid lipid phase and MCT with glyceryl stearate (GS) or pure hydrogenated palm oil (HPO) as gelled lipid phases. The lipid phase composition was crucial to forming W1/O/W2 emulsions. MCT or MCT+GS allowed the successful formation of W1/O/W2 emulsions, being more stable upon gastric conditions those formulated with MCT+GS than pure MCT. In contrast, the use of HPO led to phase separation, which was maintained after the gastric conditions. Regarding their lipid digestibility, W1/O/W2 emulsions formulated with MCT or MCT+GS were fully digested, whereas only 40% of the lipid was digested using HPO. In accordance, the CHL bioaccessibility was higher using MCT or MCT+GS than HPO. When co-digested with whole milk, the colloidal stability and lipid digestibility of the W1/O/W2 emulsions with MCT or MCT+GS were not altered, whereas the W1/O/W2 emulsion-HPO showed enhanced colloidal stability and lipid digestibility (57.71 ± 3.06%), due to the surface-active properties of milk protein. The present study provides useful information to develop stable functional foods enriched with hydrophilic bioactive compounds by using W1/O/W2 emulsions.

Neuropsychiatric comorbidities and cognition in epilepsy with eyelid myoclonia: A retrospective pediatric case series.

OBJECTIVE: Epilepsy with eyelid myoclonia (EEM) is a rare epileptic syndrome classified within the Genetic Generalized Epilepsies of childhood. It is characterized by a high drug resistance, and little is known about prognostic factors and neurodevelopmental comorbidities. The aim of this study was to describe the clinical features, cognitive profile, and prognostic factors in a series of children with EEM. METHODS: This is a retrospective observational study of patients diagnosed with EEM from 2012 to 2022 in a tertiary pediatric hospital. RESULTS: Seventeen patients were analyzed (mean age at symptom onset 5.8 years). Neuropsychiatric comorbidities were present in 76.4% (attention deficit hyperactivity disorder 58.8%, behavioral disorder 11.8%, autism spectrum disorder 11.8%, and psychotic outbreaks 11.8%). Neurocognitive assessment was performed in 75%, revealing cognitive impairment in 66.6% (62.5% with borderline intellectual function and 37.5% with -IQ <70-), with predominant difficulties in executive functions, comprehensive language, and motor skills. Cognitive deterioration was observed in one patient in parallel onset with psychotic symptoms. High refractoriness to antiseizure medication (ASM) was observed, with only 23.5% of the patients being seizure-free after a mean follow-up of 7 years. The most effective ASM was valproic acid, and two of them received ketogenic diet with good response. Regarding prognostic factors, psychotic symptoms were associated with a greater number of antiseizure medication (p < .05) implying a more drug-resistant epilepsy. SIGNIFICANCE: In our study, we found a high rate of cognitive and psychiatric comorbidities and high refractoriness. These data support the concept of EEM as an intermediate entity between idiopathic generalized epilepsy and epileptic and/or neurodevelopmental encephalopathy. Making a proper diagnosis and management of these comorbidities is necessary to improve prognosis and quality of life in EEM.

H7N9 influenza A virus transmission in a multispecies barnyard model.

Influenza A viruses are a diverse group of pathogens that have been responsible for millions of human and avian deaths throughout history. Here, we illustrate the transmission potential of H7N9 influenza A virus between Coturnix quail (Coturnix sp.), domestic ducks (Anas platyrhynchos domesticus), chickens (Gallus gallus domesticus), and house sparrows (Passer domesticus) co-housed in an artificial barnyard setting. In each of four replicates, individuals from a single species were infected with the virus. Quail shed virus orally and were a source of infection for both chickens and ducks. Infected chickens transmitted the virus to quail but not to ducks or house sparrows. Infected ducks transmitted to chickens, resulting in seroconversion without viral shedding. House sparrows did not shed virus sufficiently to transmit to other species. These results demonstrate that onward transmission varies by index species, and that gallinaceous birds are more likely to maintain H7N9 than ducks or passerines.

Circulating tumor DNA reveals complex biological features with clinical relevance in metastatic breast cancer.

Liquid biopsy has proven valuable in identifying individual genetic alterations; however, the ability of plasma ctDNA to capture complex tumor phenotypes with clinical value is unknown. To address this question, we have performed 0.5X shallow whole-genome sequencing in plasma from 459 patients with metastatic breast cancer, including 245 patients treated with endocrine therapy and a CDK4/6 inhibitor (ET + CDK4/6i) from 2 independent cohorts. We demonstrate that machine learning multi-gene signatures, obtained from ctDNA, identify complex biological features, including measures of tumor proliferation and estrogen receptor signaling, similar to what is accomplished using direct tumor tissue DNA or RNA profiling. More importantly, 4 DNA-based subtypes, and a ctDNA-based genomic signature tracking retinoblastoma loss-of-heterozygosity, are significantly associated with poor response and survival outcome following ET + CDK4/6i, independently of plasma tumor fraction. Our approach opens opportunities for the discovery of additional multi-feature genomic predictors coming from ctDNA in breast cancer and other cancer-types.

Primary and Community Care Transformation in Post-COVID Era: Nationwide General Practitioner Survey.

Introduction: The health emergency caused by COVID-19 has led to substantial changes in the usual working system of primary healthcare centers and in relations with users. The Catalan Society of Family and Community Medicine designed a survey that aimed to collect the opinions and facilitate the participation of its partners on what the future work model of general practitioners (GPs) should look like post-COVID-19. Methodology: Online survey of Family and Community Medicine members consisting of filiation data, 22 Likert-type multiple-choice questions grouped in five thematic axes, and a free text question. Results: The number of respondents to the questionnaire was 1051 (22.6% of all members): 83.2% said they spent excessive time on bureaucratic tasks; 91.8% were against call center systems; 66% believed that home care is the responsibility of every family doctor; 77.5% supported continuity of care as a fundamental value of patient-centered care; and >90% defended the contracting of complementary tests and first hospital visits from primary healthcare (PHC). Conclusions: The survey responses describe a strong consensus on the identity and competencies of the GP and on the needs of and the threats to the PHC system. The demand for an increase in health resources, greater professional leadership, elimination of bureaucracy, an increase in the number of health professionals, and greater management autonomy, are the axes towards which a new era in PHC should be directed.

Clinical and Sonographic Classification of Neurofibromas in Children with Neurofibromatosis Type 1 - A Cluster Analysis.

PURPOSE: High-frequency ultrasound allows the accurate identification of neurofibromas in neurofibromatosis type 1 (NF1). This study aimed to analyze the ultrasound features of neurofibromas in children with NF1, to establish a classification based on the clinical and sonographic patterns of the different types of neurofibromas, and to evaluate the interobserver correlation coefficient (κ) of this classification. MATERIALS AND METHODS: In this prospective, single referral center observational study, clinical and ultrasound findings of neurofibromas in children diagnosed with NF 1 were analyzed. To identify the ultrasound patterns, a cluster analysis allowing the inclusion of both clinical and ultrasound data was designed. The κ coefficient was calculated using 9 external evaluators. RESULTS: 265 ultrasound scans were performed on a total of 242 neurofibromas from 108 children diagnosed with NF1. Cluster analysis allowed the identification of 9 patterns (Snedecor's F, P < 0.001) classified as "classic" cutaneous neurofibroma, blue-red neurofibroma, pseudoatrophic neurofibroma, nodular subcutaneous neurofibroma, diffuse subcutaneous neurofibroma, congenital cutaneous neurofibroma, congenital plexiform neurofibroma, congenital diffuse and plexiform neurofibroma, and subfascial neurofibroma. The κ coefficient of the interobserver ratings was 0.82. CONCLUSION: Patterns identified in the cluster analysis allow neurofibromas to be classified with a very high interobserver correlation.

High incidence of PTSD diagnosis and trauma-related symptoms in a trauma exposed bipolar I and II sample.

Background: Post-traumatic stress disorder (PTSD) is an established comorbidity in Bipolar Disorder (BD), but little is known about the characteristics of psychological trauma beyond a PTSD diagnosis and differences in trauma symptoms between BD-I and BD-II. Objective: (1) To present characteristics of a trauma-exposed BD sample; (2) to investigate prevalence and trauma symptom profile across BD-I and BD-II; (3) to assess the impact of a lifetime PTSD diagnosis vs. a history of trauma on BD course; and (4) to research the impacts of sexual and physical abuse. Methods: This multi-center study comprised 79 adult participants with BD with a history of psychological trauma and reports baseline data from a trial registered in Clinical Trials (https://clinicaltrials.gov; ref: NCT02634372). Clinical variables were gathered through clinical interview, validated scales and a review of case notes. Results: The majority (80.8%) of our sample had experienced a relevant stressful life event prior to onset of BD, over half of our sample 51.9% had a lifetime diagnosis of PTSD according to the Clinician Administered PTSD scale. The mean Impact of Event Scale-Revised scores indicated high levels of trauma-related distress across the sample, including clinical symptoms in the PTSD group and subsyndromal symptoms in the non-PTSD group. Levels of dissociation were not higher than normative values for BD. A PTSD diagnosis (vs. a history of trauma) was associated with psychotic symptoms [2(1) = 5.404, p = 0.02] but not with other indicators of BD clinical severity. There was no significant difference between BD-I and BD-II in terms of lifetime PTSD diagnosis or trauma symptom profile. Sexual abuse significantly predicted rapid cycling [2(1) = 4.15, p = 0.042], while physical abuse was not significantly associated with any clinical indicator of severity. Conclusion: Trauma load in BD is marked with a lack of difference in trauma profile between BD-I and BD-II. Although PTSD and sexual abuse may have a negative impact on BD course, in many indicators of BD severity there is no significant difference between PTSD and subsyndromal trauma symptoms. Our results support further research to clarify the role of subsyndromic PTSD symptoms, and highlight the importance of screening for trauma in BD patients.

Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias.

Our clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs. First, NBIA genes were analysed by Sanger sequencing and 59 patients achieved a diagnosis, including the detection of the founder mutation PANK2 p.T528M in Romani people. Then, we used a custom panel MovDisord and/or exome sequencing; 29 cases were solved with a great genetic heterogeneity (34 different mutations in 23 genes). Three patients presented brain iron deposits with Fe-sensitive MRI sequences and mutations in FBXO7, GLB1, and KIF1A, suggesting an NBIA-like phenotype. Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in ITPR1, KIF1A, SPTBN2, PLA2G6, PMPCA, and PRDX3. The novel variants were investigated by structural modelling, luciferase analysis, transcript/minigenes studies, or immunofluorescence assays. Our findings expand the phenotypes and the genetics of MDs and ataxias with early-onset CA and cortical hyperintensities and highlight that the abnormal brain iron accumulation or early cerebellar gliosis may resembling an NBIA phenotype.

Manipulation of pantothenate kinase in Anopheles stephensi suppresses pantothenate levels with minimal impacts on mosquito fitness.

Pantothenate (Pan) is an essential nutrient required by both the mosquito vector and malaria parasite. We previously demonstrated that increasing pantothenate kinase (PanK) activity and co-enzyme A (CoA) biosynthesis led to significantly decreased parasite infection prevalence and intensity in the malaria mosquito Anopheles stephensi. In this study, we demonstrate that Pan stores in A. stephensi are a limited resource and that manipulation of PanK levels or activity, via small molecule modulators of PanK or transgenic mosquitoes, leads to the conversion of Pan to CoA and an overall reduction in Pan levels with minimal to no effects on mosquito fitness. Transgenic A. stephensi lines with repressed insulin signaling due to PTEN overexpression or repressed c-Jun N-terminal kinase (JNK) signaling due to MAPK phosphatase 4 (MKP4) overexpression exhibited enhanced PanK levels and significant reductions in Pan relative to non-transgenic controls, with the PTEN line also exhibiting significantly increased CoA levels. Provisioning of the PTEN line with the small molecule PanK modulator PZ-2891 increased CoA levels while provisioning Compound 7 decreased CoA levels, affirming chemical manipulation of mosquito PanK. We assessed effects of these small molecules on A. stephensi lifespan, reproduction and metabolism under optimized laboratory conditions. PZ-2891 and Compound 7 had no impact on A. stephensi survival when delivered via bloodmeal throughout mosquito lifespan. Further, PZ-2891 provisioning had no impact on egg production over the first two reproductive cycles. Finally, PanK manipulation with small molecules was associated with minimal impacts on nutritional stores in A. stephensi mosquitoes under optimized rearing conditions. Together with our previous data demonstrating that PanK activation was associated with significantly increased A. stephensi resistance to Plasmodium falciparum infection, the studies herein demonstrate a lack of fitness costs of mosquito Pan depletion as a basis for a feasible, novel strategy to control parasite infection of anopheline mosquitoes.

Feasibility and Acceptability of Personalized Breast Cancer Screening (DECIDO Study): A Single-Arm Proof-of-Concept Trial.

The aim of this study was to assess the acceptability and feasibility of offering risk-based breast cancer screening and its integration into regular clinical practice. A single-arm proof-of-concept trial was conducted with a sample of 387 women aged 40-50 years residing in the city of Lleida (Spain). The study intervention consisted of breast cancer risk estimation, risk communication and screening recommendations, and a follow-up. A polygenic risk score with 83 single nucleotide polymorphisms was used to update the Breast Cancer Surveillance Consortium risk model and estimate the 5-year absolute risk of breast cancer. The women expressed a positive attitude towards varying the frequency of breast screening according to individual risk and, especially, more frequently inviting women at higher-than-average risk. A lower intensity screening for women at lower risk was not as welcome, although half of the participants would accept it. Knowledge of the benefits and harms of breast screening was low, especially with regard to false positives and overdiagnosis. The women expressed a high understanding of individual risk and screening recommendations. The participants' intention to participate in risk-based screening and satisfaction at 1-year were very high.

Guillain-Barré Syndrome in Mexico: An Updated Review Amid the Coronavirus Disease 2019 Era

ABSTRACT Guillain-Barré syndrome (GBS) is the most frequent cause of acute flaccid paralysis and if not diagnosed and treated timely, a significant cause of long-term disability. Incidence in Latin America ranges from 0.71 to 7.63 cases/100,000 person-years. Historically, GBS has been linked to infections (mainly gastrointestinal by Campylobacter jejuni) and vaccines (including those against severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]); however, a trigger cannot be detected in most cases. Regarding SARS-CoV-2, epidemiological studies have found no association with its development. Acute motor axonal neuropathy is the most common electrophysiological variant in Mexico and Asian countries. Intravenous immunoglobulin or plasma exchanges are still the treatment cornerstones. Mortality in Mexico can be as high as 12%. Advances in understanding the drivers of nerve injury in GBS that may provide the basis for developing targeted therapies have been made during the past decade; despite them, accurate criteria for selecting patients requiring acute treatment, prognostic biomarkers, and novel therapies are still needed. The newly-developed vaccines against SARS-CoV-2 have raised concerns regarding the potential risk for developing GBS. In the midst of coronavirus disease 2019 and vaccination campaigns against SARS-CoV-2, this review discusses the epidemiology, clinical presentation, management, and outcomes of GBS in Mexico.

Avances hacia el cribado personalizado del cáncer de mama: el papel de la Atención Primaria / Moving toward personalized breast cancer screening: The role of Primary Care

El cáncer de mama es la primera causa de muerte en el mundo entre las mujeres. El Sistema Nacional de Salud (SNS) introdujo el cribado poblacional de cáncer de mama en 1990. Como en la mayoría de los programas europeos, el riesgo se identifica con base en la edad y se ofrece una mamografía cada dos años a mujeres de 50 a 69 años. La evidencia científica está avanzando hacia un cribado personalizado, basado en el riesgo individual. En este artículo se presentan los ensayos clínicos que evaluarán la eficacia del cribado personalizado y algunos estudios realizados en nuestro entorno sobre el efecto de informar a las mujeres de los beneficios y efectos adversos del cribado o la aceptabilidad y viabilidad de ofrecer cribado personalizado, que incluya la toma de decisiones compartidas. El Programa de Actividades Preventivas y Promoción de la Salud puede ayudar a transformar el cribado en nuestro SNS.(AU)

Breast cancer is the leading cause of death in the world among women. The Spanish National Health System (SNHS) introduced population-based breast cancer screening in 1990. As in most European programs, risk is identified on the basis of age and a mammogram is offered every two years to women aged 50–69 years. Scientific evidence is moving toward personalized screening, based on individual risk. This article presents the clinical trials that will evaluate the efficacy of personalized screening and some studies carried out in our environment on the effect of informing women of the benefits and adverse effects of screening or the acceptability and feasibility of offering personalized screening, in the Shared Decision Making context. The Preventive Activities and Health Promotion Program can help transform screening in our SNHS.(AU)

[Moving toward personalized breast cancer screening: The role of Primary Care]. / Avances hacia el cribado personalizado del cáncer de mama: el papel de la Atención Primaria.

Breast cancer is the leading cause of death in the world among women. The Spanish National Health System (SNHS) introduced population-based breast cancer screening in 1990. As in most European programs, risk is identified on the basis of age and a mammogram is offered every two years to women aged 50-69 years. Scientific evidence is moving toward personalized screening, based on individual risk. This article presents the clinical trials that will evaluate the efficacy of personalized screening and some studies carried out in our environment on the effect of informing women of the benefits and adverse effects of screening or the acceptability and feasibility of offering personalized screening, in the Shared Decision Making context. The Preventive Activities and Health Promotion Program can help transform screening in our SNHS.

The LINCE Project: A Pathway for Diagnosing NCL2 Disease.

Introduction: Neuronal Ceroid Lipofuscinosis (NCL) comprises a clinically and genetically heterogeneous group of 13 neurodegenerative lysosomal storage disorders. Neuronal Ceroid lipofuscinosis type 2 disease (NCL2), caused by the deficient lysosomal enzyme tripeptidyl peptidase 1 (TPP1), is the only one with an approved enzyme replacement treatment (ERT). Early initiation of ERT appears to modify significantly the natural history of the disease. We aimed to shorten the time to diagnosis of NCL2. Methods: In March 2017, we started per first time in Spain a selective screening program, the LINCE project, in pediatric patients with clinical symptoms compatible with NCL2 disease. The program covered the whole country. We distributed kits to pediatricians with the necessary material to assess patients. All samples in this study were received within one week of collection. Enzymatic activity determined on dried blood spots was the main method used to screen for TPP1 and palmitoyl protein thioesterase 1 (PPT1) for the differential diagnosis with neuronal ceroid lipofuscinosis type 1 (NCL1). Results: Over a period of three years, we received 71 samples. The analysis was minimally invasive, relatively cheap and fast-executing. Three cases identified as a direct result of the selective screening strategy were confirmed by genetic study of NCL2 disease with a median age of 4.5 years. Our screening method has a specificity of 100%, and, with the absence to date of false negatives. We did not detect any NCL1-positive cases. Conclusions: LINCE proved to be a simple, useful, and reliable tool for the diagnosis of NCL2, enabling clinicians to diagnose NCL2 faster. The presence of NCL2-positive cases in our population and availability of treatment may facilitate the inclusion of NCL2 in neonatal screening programs for early diagnosis.

Guillain-Barré Syndrome in Mexico: An Updated Review Amid the Coronavirus Disease 2019 ERA.

Guillain-Barré syndrome (GBS) is the most frequent cause of acute flaccid paralysis and if not diagnosed and treated timely, a significant cause of long-term disability. Incidence in Latin America ranges from 0.71 to 7.63 cases/100,000 person-years. Historically, GBS has been linked to infections (mainly gastrointestinal by Campylobacter jejuni) and vaccines (including those against severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]); however, a trigger cannot be detected in most cases. Regarding SARS-CoV-2, epidemiological studies have found no association with its development. Acute motor axonal neuropathy is the most common electrophysiological variant in Mexico and Asian countries. Intravenous immunoglobulin or plasma exchanges are still the treatment cornerstones. Mortality in Mexico can be as high as 12%. Avances in understanding the drivers of nerve injury in GBS that may provide the basis for developing targeted therapies have been made during the past decade; despite them, accurate criteria for selecting patients requiring acute treatment, prognostic biomarkers, and novel therapies are still needed. The newly-developed vaccines against SARS-CoV-2 have raised concerns regarding the potential risk for developing GBS. In the midst of coronavirus disease 2019 and vaccination campaigns against SARS-CoV-2, this review discusses the epidemiology, clinical presentation, management, and outcomes of GBS in Mexico.