Exosomes in Vascular/Neurological Disorders and the Road Ahead.

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), stroke, and aneurysms, are characterized by the abnormal accumulation and aggregation of disease-causing proteins in the brain and spinal cord. Recent research suggests that proteins linked to these conditions can be secreted and transferred among cells using exosomes. The transmission of abnormal protein buildup and the gradual degeneration in the brains of impacted individuals might be supported by these exosomes. Furthermore, it has been reported that neuroprotective functions can also be attributed to exosomes in neurodegenerative diseases. The potential neuroprotective functions may play a role in preventing the formation of aggregates and abnormal accumulation of proteins associated with the disease. The present review summarizes the roles of exosomes in neurodegenerative diseases as well as elucidating their therapeutic potential in AD, PD, ALS, HD, stroke, and aneurysms. By elucidating these two aspects of exosomes, valuable insights into potential therapeutic targets for treating neurodegenerative diseases may be provided.

First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study.

BACKGROUND: Despite immunotherapy advancements for patients with advanced or metastatic non-small-cell lung cancer (NSCLC), pivotal first-line trials were limited to patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and a median age of 65 years or younger. We aimed to compare the efficacy and safety of first-line atezolizumab monotherapy with single-agent chemotherapy in patients ineligible for platinum-based chemotherapy. METHODS: This trial was a phase 3, open-label, randomised controlled study conducted at 91 sites in 23 countries across Asia, Europe, North America, and South America. Eligible patients had stage IIIB or IV NSCLC in whom platinum-doublet chemotherapy was deemed unsuitable by the investigator due to an ECOG PS 2 or 3, or alternatively, being 70 years or older with an ECOG PS 0-1 with substantial comorbidities or contraindications for platinum-doublet chemotherapy. Patients were randomised 2:1 by permuted-block randomisation (block size of six) to receive 1200 mg of atezolizumab given intravenously every 3 weeks or single-agent chemotherapy (vinorelbine [oral or intravenous] or gemcitabine [intravenous]; dosing per local label) at 3-weekly or 4-weekly cycles. The primary endpoint was overall survival assessed in the intention-to-treat population. Safety analyses were conducted in the safety-evaluable population, which included all randomised patients who received any amount of atezolizumab or chemotherapy. This trial is registered with ClinicalTrials.gov, NCT03191786. FINDINGS: Between Sept 11, 2017, and Sept 23, 2019, 453 patients were enrolled and randomised to receive atezolizumab (n=302) or chemotherapy (n=151). Atezolizumab improved overall survival compared with chemotherapy (median overall survival 10·3 months [95% CI 9·4-11·9] vs 9·2 months [5·9-11·2]; stratified hazard ratio 0·78 [0·63-0·97], p=0·028), with a 2-year survival rate of 24% (95% CI 19·3-29·4) with atezolizumab compared with 12% (6·7-18·0) with chemotherapy. Compared with chemotherapy, atezolizumab was associated with stabilisation or improvement of patient-reported health-related quality-of-life functioning scales and symptoms and fewer grade 3-4 treatment-related adverse events (49 [16%] of 300 vs 49 [33%] of 147) and treatment-related deaths (three [1%] vs four [3%]). INTERPRETATION: First-line treatment with atezolizumab monotherapy was associated with improved overall survival, a doubling of the 2-year survival rate, maintenance of quality of life, and a favourable safety profile compared with single-agent chemotherapy. These data support atezolizumab monotherapy as a potential first-line treatment option for patients with advanced NSCLC who are ineligible for platinum-based chemotherapy. FUNDING: F Hoffmann-La Roche and Genentech Inc, a member of the Roche group.

Efficacy and safety results by menopausal status in monarchE: adjuvant abemaciclib combined with endocrine therapy in patients with HR+, HER2-, node-positive, high-risk early breast cancer.

Background: Abemaciclib is the first and only cyclin-dependent kinases 4 and 6 inhibitor approved for adjuvant treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, and high-risk early breast cancer (EBC), with indications varying by geography. Premenopausal patients with HR+, HER2- tumors may have different tumor biology and treatment response compared to postmenopausal patients. Objectives: We describe the efficacy and safety of abemaciclib plus endocrine therapy (ET) for the large subgroup of premenopausal patients with HR+, HER2- EBC in monarchE. Design: Randomized patients (1:1) received adjuvant ET with or without abemaciclib for 2 years plus at least 3 additional years of ET as clinically indicated. Methods: Patients were stratified by menopausal status (premenopausal versus postmenopausal) at diagnosis. Standard ET (tamoxifen or aromatase inhibitor) with or without gonadotropin-releasing hormone agonist was determined by physician's choice. Invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) by menopausal status were assessed at data cutoff on 1 April 2021 (median follow-up of 27 months). Results: Among randomized patients, 2451 (43.5%) were premenopausal and 3181 (56.4%) were postmenopausal. The choice of ET for premenopausal patients varied considerably between countries. Treatment benefit was consistent across menopausal status, with a numerically greater effect size in premenopausal patients. For premenopausal patients, abemaciclib with ET resulted in a 42.2% and 40.3% reduction in the risk of developing IDFS and DRFS events, respectively. Absolute improvement at 3 years was 5.7% for IDFS and 4.4% for DRFS rates. Safety profile for premenopausal patients was consistent with the overall safety population. Conclusion: Abemaciclib with ET demonstrated clinically meaningful treatment benefit for IDFS and DRFS versus ET alone regardless of menopausal status and first ET, with a numerically greater benefit in the premenopausal compared to the postmenopausal population. Safety data in premenopausal patients are consistent with the overall safety profile of abemaciclib.

Miranda Warning Comprehension: The Influence of Verbal Aptitude and Hearing Status.

The Miranda warning was drafted in order to inform people of their rights upon arrest in an easy to understand manner. However, to understand the warning a person needs a high school level reading comprehension (which is above the level of most offenders). Among these offenders, deaf and hard-of-hearing (DHH) individuals are particularly prone to misinterpreting the Miranda warning due to language barriers with law enforcement and below average English literacy compared to hearing individuals. Two studies were performed. The first compared Miranda warning comprehension between hearing and DHH participants, and it was found that DHH participants showed overall lower comprehension. The second study, consisting only of DHH participants, compared the effectiveness of four different presentations of the Miranda warning: signed in American Sign Language (ASL), signed in Signed Exact English (SEE), oral presentation, and written presentation. The written presentation demonstrated the lowest comprehension scores while the other three methods showed no significant difference in comprehension. The results suggest that the Miranda warning is best administered to DHH individuals with the assistance of a certified sign language interpreter. Limitations of the sample and directions for future research are discussed.

Making virtual health care accessible to the deaf community: Findings from the telehealth survey.

INTRODUCTION: To reduce COVID-19 exposure risk, virtual visits became widely adopted as a common form of healthcare delivery for the general population. It is unknown how this affected the deaf population, a sociolinguistic minority group that continues to face communication and healthcare barriers. The survey's objective was to describe the deaf participants' experiences with telehealth visits. METHODS: A 28-item online survey, available in American Sign Language and English, was developed and disseminated between November 2020 and January 2021. Ninety-nine deaf participants responded. Descriptive statistics were performed to assess the participant's virtual health care use, experiences, and communication approaches. RESULTS: Seventy-five percent of respondents used telehealth at least once in the past 12 months (n = 74; age = 37.6 ± 14.5 years). Of those who used telehealth, nearly two-thirds experienced communication challenges (65.3%; n = 49). Half of the participants reported having to connect via a video relay service that employs interpreters who maintain general certification instead of a remote interpreter with specialized health care interpreting certifications for video visits with their health care providers (n = 37) and a third of participants reported needing to use their residual hearing to communicate with their providers (n = 25). CONCLUSION: Standard protocols for health care systems and providers are needed to minimize the burden of access on deaf patients and ensure virtual visits are equitable. It is recommended these visits be offered on Health Insurance Portability and Accountability Act-compliant platforms and include multi-way video to allow for the inclusion of remote medical interpreters and/or real-time captionists to ensure effective communication between the provider and the deaf patient occurs.

The Deaf Community's Experiences Navigating COVID-19 Pandemic Information.

BACKGROUND: Users of American Sign Language (ASL) who are deaf often face barriers receiving health information, contributing to significant gaps in health knowledge and health literacy. To reduce the spread of coronavirus disease 2019 (COVID-19) and its risk to the public, the government and health care providers have encouraged social distancing, use of face masks, hand hygiene, and quarantines. Unfortunately, COVID-19 information has rarely been available in ASL, which puts the deaf community at a disadvantage for accessing reliable COVID-19 information. OBJECTIVE: This study's primary objective was to compare COVID-19-related information access between participants who are deaf and participants who are hearing. METHODS: The study included 104 adults who are deaf and 74 adults who are hearing who had participated in a prior health literacy study. Surveys were conducted between April and July 2020 via video conference, smartphone apps, or phone calls. COVID-19 data were linked with preexisting data on demographic and health literacy data as measured by the Newest Vital Sign (NVS) and the ASL-NVS. KEY RESULTS: Neither group of participants differed in their ability to identify COVID-19 symptoms. Adults who are deaf were 4.7 times more likely to report difficulty accessing COVID-19 information (p = .011), yet reported using more preventive strategies overall. Simultaneously, adults who are deaf had 60% lower odds of staying home and calling their doctor versus seeking health care immediately or doing something else compared with participants who are hearing if they suspected that they had COVID-19 (p = .020). CONCLUSIONS: Additional education on recommended COVID-19 management and guidance on accessible health care navigation strategies are needed for the deaf community and health care providers. Public health officials should ensure that public service announcements are accessible to all audiences and should connect with trusted agents within the deaf community to help disseminate health information online in ASL through their social media channels. [HLRP: Health Literacy Research and Practice. 2021;5(2):e162-e170.] Plain Language Summary: Compared to participants who are hearing, a higher portion of participants who are deaf reported challenges with accessing, understanding, and trusting COVID-19 information. Although respondents who are deaf had similar knowledge of symptoms compared to participants who are hearing, they used more prevention strategies and were more likely to plan immediate care for suspected symptoms. Improved guidance on COVID-19 management and health care navigation accessible to the deaf community is needed.

Juntos: A Model for Language Congruent Care to Better Serve Spanish-Speaking Patients with COVID-19.

Coronavirus disease 2019 (COVID-19) exacerbated pre-existing health disparities and disproportionately affected the Latino community. Clinicians identified communication barriers as a major challenge in care for COVID-19 Latino patients with limited English proficiency (LEP). To address these challenges, Juntos (Together) consult service was established to promote language-congruent care with cultural sensitivity, identify barriers to safe discharge, and facilitate referral to appropriate resources. Spanish speaking volunteer health care providers worked synergistically with medical teams caring for LEP Latino patients. Volunteers were trained on consultant responsibilities and discharge planning resources. The program was evaluated by a satisfaction survey distributed to providers who requested a Juntos consult and Juntos volunteers. Between May 5 and July 30, 2020, 19 individuals volunteered time to the Juntos consult service, 12 (63%) Latinos, 14 (74%) physicians, and 5 (26%) staff. The service supported 127 patients, 76 (60%) males, mean age 42 (±16), 83 (65%) uninsured, and 91 (72%) without primary care. The most common referral sources were medical units (52, 41%) and intensive care units (47, 37%). The most common services offered were family engagement (55, 43%), goals of care (35, 28%), and mental status assessment (26, 20%). The majority of providers who consulted Juntos were very satisfied (48/59, 81%) with the care delivered. The Juntos service offered critical support tailored to the patients' and primary teams' needs. The experience reinforced the need for cultural-based communication to provide optimal care to LEP patients. The Juntos consult service could be a model for providing language-congruent care even beyond COVID-19, but to do so will require institutional investment and rigorous outcomes evaluation.

Elucidating the Distribution of Plant Metabolites from Native Tissues with Laser Desorption Low-Temperature Plasma Mass Spectrometry Imaging.

Secondary metabolites of plants have important biological functions, which often depend on their localization in tissues. Ideally, a fresh untreated material should be directly analyzed to obtain a realistic view of the true sample chemistry. Therefore, there is a large interest for ambient mass-spectrometry-based imaging (MSI) methods. Our aim was to simplify this technology and to find an optimal combination of desorption/ionization principles for a fast ambient MSI of macroscopic plant samples. We coupled a 405 nm continuous wave (CW) ultraviolet (UV) diode laser to a three-dimensionally (3D) printed low-temperature plasma (LTP) probe. By moving the sample with a RepRap-based sampling stage, we could perform imaging of samples up to 16 × 16 cm2. We demonstrate the system performance by mapping mescaline in a San Pedro cactus ( Echinopsis pachanoi) cross section, tropane alkaloids in jimsonweed ( Datura stramonium) fruits and seeds, and nicotine in tobacco ( Nicotiana tabacum) seedlings. In all cases, the anatomical regions of enriched compound concentrations were correctly depicted. The modular design of the laser desorption (LD)-LTP MSI platform, which is mainly assembled from commercial and 3D-printed components, facilitates its adoption by other research groups. The use of the CW-UV laser for desorption enables fast imaging measurements. A complete tobacco seedling with an image size of 9.2 × 15.0 mm2 was analyzed at a pixel size of 100 × 100 µm2 (14 043 mass scans), in less than 2 h. Natural products can be measured directly from native tissues, which inspires a broad use of LD-LTP MSI in plant chemistry studies.

Testimonios, A Mental Health Support Group for Latino Immigrants in an Emergent Latino Community.

Latino immigrants face many stressors before, during, and after migration to the U.S., but there are few mental health services available to help them cope with this transition. We established free group sessions moderated by bilingual therapists to address the unmet mental health needs of Latino immigrants.

American Sign Language Comprehension Test: A Tool for Sign Language Researchers.

The American Sign Language Comprehension Test (ASL-CT) is a 30-item multiple-choice test that measures ASL receptive skills and is administered through a website. This article describes the development and psychometric properties of the test based on a sample of 80 college students including deaf native signers, hearing native signers, deaf non-native signers, and hearing ASL students. The results revealed that the ASL-CT has good internal reliability (α = 0.834). Discriminant validity was established by demonstrating that deaf native signers performed significantly better than deaf non-native signers and hearing native signers. Concurrent validity was established by demonstrating that test results positively correlated with another measure of ASL ability (r = .715) and that hearing ASL students' performance positively correlated with the level of ASL courses they were taking (r = .726). Researchers can use the ASL-CT to characterize an individual's ASL comprehension skills, to establish a minimal skill level as an inclusion criterion for a study, to group study participants by ASL skill (e.g., proficient vs. nonproficient), or to provide a measure of ASL skill as a dependent variable.

Nivel cognitivo y habilidad procedimental de la delimitación de las líneas oclusales en prótesis completa en estudiantes de odontología / Cognitive level and procedural skill of the delimitation of the occlusal lines in full denture in dental students

Conocer el nivel de relación entre los aspectos cognitivos y procedimentales en el diseño y delimitación de las líneas para la confección del rodete de oclusión y contorno en prótesis completa, en estudiantes de odontología. Materiales y métodos. La muestra estuvo conformada por 134 estudiantes, de los cuales 51 fueron del sexo masculino. Se evaluó el aspecto cognitivo mediante un examen escrito, el cual fue calificado de 0 a 20 para luego subdividirlo en cinco grupos. El mismo sistema de evaluación se aplicó sobre los trabajos de diseño y graficación realizado sobre los modelos de trabajo y placas bases. Resultados. En aprestamiento procedimental no se encontró asociación significativa con el grado de conocimiento, sin embargo, un mayor número de alumnos obtuvieron un buen grado de conocimientos y la mayoría obtuvo un buen nivel de aprestamiento procedimental. En el grado de conocimiento con relación al nivel de aprestamiento procedimental no se encontró una asociación estadísticamente significativa por sexo. Al evaluar grado de conocimiento según edad se encontraron diferencias significativas, en el grupo de 19-24 años se observó un mayor grado de conocimientos. En la evaluación del nivel de aprestamiento procedimental para el grupo de teoría, no se encontró asociación estadísticamente significativa al igual que en edad y sexo. Conclusiones. Es importante reforzar el conocimiento teórico de la confección de las líneas para la realización del rodete de oclusión y contorno, ya que este es un procedimiento básico para la correcta preparación de una prótesis completa...

To know the level of relationship between cognitive and procedural aspects in the design and delimitation of the lines for the confection of the occlusion rim and the contour in full denture, in dental students. Materials and methods. The sample was formed by 134 students, of which 51 were male. The cognitive aspect was evaluated by means of a written examination which was qualified from 0 to 20, and then it was subdivided into five groups. The same evaluation system was applied for the design work and charting on the models of work and base plaques. Results. In procedural readiness not significant association was found with the degree of knowledge, however, a greater number of students obtained a good degree of knowledge and most of them obtained a good level of procedural readiness. On the degree of knowledge in relation to the level of procedural readiness there was not a statisticallysignificant association by sex; however women provided a good level of knowledge and a level of readiness in comparison with men. In assessing the degree of knowledge according to age it was a significant higher prevalence of students from 19-24 years of age with a good degree of knowledge. In the assessment of the level of procedural for the theory group readiness, no significant association was found just that in age and sex. Conclusions. It is important to strengthen the theoretical knowledge of making lines for the confection of the occlusion rim and contour, since this is a basic procedure for the correct preparation of a full denture...

Associative Hebbian synaptic plasticity in primate visual cortex.

In primates, the functional connectivity of adult primary visual cortex is susceptible to be modified by sensory training during perceptual learning. It is widely held that this type of neural plasticity might involve mechanisms like long-term potentiation (LTP) and long-term depression (LTD). NMDAR-dependent forms of LTP and LTD are particularly attractive because in rodents they can be induced in a Hebbian manner by near coincidental presynaptic and postsynaptic firing, in a paradigm termed spike timing-dependent plasticity (STDP). These fundamental properties of LTP and LTD, Hebbian induction and NMDAR dependence, have not been examined in primate cortex. Here we demonstrate these properties in the primary visual cortex of the rhesus macaque (Macaca mulatta), and also show that, like in rodents, STDP is gated by neuromodulators. These findings indicate that the cellular principles governing cortical plasticity are conserved across mammalian species, further validating the use of rodents as a model system.

Frequency and clinical and dermatoscopic features of volar and ungual pigmented melanocytic lesions: a study in schoolchildren of Manizales, Colombia.

In Latin American populations, acral lentiginous melanoma is the prevailing type of melanoma. Its relationship to preexistent benign volar melanocytic lesions has not been established; however, it is common practice to remove these lesions from children in spite of the fact that childhood acral lentiginous melanoma is extremely rare. To determine the frequency and the clinical and dermatoscopic characteristics of acrally located pigmented melanocytic lesions in schoolchildren of Manizales, Colombia, we undertook an exploratory, descriptive study of 1106 schoolchildren in search of pigmented volar and ungual lesions. In the study group there were 680 males and 426 females, ranging in age from 6 to 23 years (median age 13 years). At least one acral pigmented lesion was found in 464 individuals (42%). Their distribution over the volar surface was rather regular. Increasing age and darkness of the skin correlated with an increased number of lesions. Dermatoscopic patterns were consistent and suggestive of union nevus and simple lentigo as the predominant types of melanocytic proliferation. Typical pigmented melanocytic volar skin lesions are very common in our schoolchildren. Removal of these lesions is not routinely recommended since a relationship with acral lentiginous melanoma has not been established.