"I'm worth saving"- A Qualitative Study of People with Alzheimer's Disease Considering Lecanemab Treatment.

Importance: People with Alzheimer's disease (AD) now have access to disease-modifying treatment with anti-amyloid monoclonal antibodies (mAbs). Their perception of risks and benefits and approach to treatment decisions remain unknown. Objective: To understand how people with early AD consider benefits and costs of anti-amyloid mAbs and make decisions about treatment. Design: Qualitative semi-structured interviews. Setting: Memory care clinics at two academic medical centers. Participants: People with biomarker or imaging-confirmed early AD referred for evaluation for treatment with anti-amyloid mAbs. Main Outcomes and Measures: Themes identified through content analysis. Results: Among 22 participants, mean age was 70 years, 8 (36%) were women, 22 (100%) were White, 8 (36%) had less than a college degree, 11 (50%) had annual income less than $100,000, and 6 (27%) lived in a rural area. The analysis revealed 3 major themes and associated subthemes: 1) People with AD sought and obtained information from different sources-advocacy organizations, the Internet, and clinicians; 2) hopes, expected benefits, and the existential threat of dementia drove willingness and readiness to start lecanemab-hopes included more time feeling like themselves and doing enjoyable activities; expected benefits included stalling progression, reversing cognitive decline or cure; 3) individual traits and preferences, family factors, and degree of trust in expertise influenced how people balanced risks and benefits- some would accept treatment at any cost; others carefully weighed risks and burdens carefully, but were motivated to pursue treatment by supportive families, insurance coverage, and trust in expertise; for a few, costs decidedly outweighed their personal benefits. People with AD desired more individualized information on risks and benefits and wanted to hear more from patients who took the medication. Conclusions and Relevance: Results from this qualitative analysis inform clinician, health system and policy efforts to promote individualized treatment decisions for anti-amyloid mAb treatment through multimodal education and outreach, evidence-based communication skills, and adaptation of similar care models. Key Points: Question: How do people with Alzheimer's disease (AD) decide on treatment with newly available anti-amyloid monoclonal antibodies?Findings: In this qualitative analysis, people with AD considering treatment relied on multiple information sources; were motivated by hope to delay cognitive decline and preserve independence; and worried side effects would impair quality of life. Personality traits, family support, and trust in expertise determined how they balanced these tradeoffs. People with AD wanted more personalized information and to hear from others who had taken the medications.Meaning: As access to treatment expands, these findings inform how clinicians can help people with AD make individualized treatment decisions.

Early Childhood Adversity Predicts Risk of Family Caregiver Suicidal Ideation:Roles of Neuroticism and Self-Compassion.

Background: Despite high rates of family caregiver suicidal ideation (SI), little is known about its relationship with childhood adversity. Those with a history of adverse childhood experiences (ACEs) have been shown to have higher neuroticism, lower self-compassion, and higher rates of late life mental health disorders. Caregiving for a family member with dementia may pose a particular challenge for those with ACEs. Methods: In a secondary analysis of 81 family caregivers of people living with dementia enrolled in clinical trials, we undertook a cross-sectional baseline analysis of the association between childhood adversity, measured with the ACE questionnaire, and self-reported suicidal ideation (SI). We further assessed whether the relationship between ACE and SI was mediated by neuroticism and self-compassion. Results: 18 caregivers self-reported SI (22%). 89% of caregivers with SI reported childhood adversity (ACE > 0), versus 63% of those without SI (p=.04). The relative risk of SI was 3.6x higher in those with childhood adversity than in those without (p=.04), and for those with a specific history childhood abuse, the relative risk of SI was 3.4x higher (p=.005). Neuroticism and self-compassion mediated the relationship between ACE and SI (p<.05), with neuroticism strengthening the association and self-compassion weakening it. Conclusions: The association of SI with history of childhood adversity is high in family caregivers. Whereas elevated neuroticism might be one mechanism linking ACEs and SI, training self-compassion is a promising target for reducing SI. The phenotypic relationship between childhood adversity and SI in family caregivers should be further explored in larger samples, and could represent a new treatment target to improve the efficacy of therapies on caregiver emotional symptoms.

Physical Activity and Neurocognitive Symptoms in Older Adults During COVID-19 Pandemic.

Objectives: Examine whether physical activity (PA) changes during the COVID-19 pandemic were related to subjective cognitive decline (SCD), depression, and anxiety in older adults and whether these varied by sociodemographic variables. Methods: 301 older adults completed an online survey between May and October 2020 and 3 months later, including self-report questionnaires of SCD, depression, and anxiety. PA changes were determined with a question. Results: 60% of participants reported decreased PA. Those who reduced their PA were more likely to be from low to middle income and younger. PA increase was related to less SCD and depressive symptoms compared to those who decreased it. Participants who maintained their PA had fewer SCD concerns, depressive, and anxiety symptoms than those who decreased it. Discussion: Reducing PA was associated with worse neuropsychiatric and cognitive symptoms. Encouraging older adults to increase PA may help mitigate some of the pandemic's adverse effects on psychological well-being.

APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer's Disease.

BACKGROUND: Variants in APOE and PSEN1 (encoding apolipoprotein E and presenilin 1, respectively) alter the risk of Alzheimer's disease. We previously reported a delay of cognitive impairment in a person with autosomal dominant Alzheimer's disease caused by the PSEN1 E280A variant who also had two copies of the apolipoprotein E3 Christchurch variant (APOE3 Ch). Heterozygosity for the APOE3 Ch variant may influence the age at which the onset of cognitive impairment occurs. We assessed this hypothesis in a population in which the PSEN1 E280A variant is prevalent. METHODS: We analyzed data from 27 participants with one copy of the APOE3 Ch variant among 1077 carriers of the PSEN1 E280A variant in a kindred from Antioquia, Colombia, to estimate the age at the onset of cognitive impairment and dementia in this group as compared with persons without the APOE3 Ch variant. Two participants underwent brain imaging, and autopsy was performed in four participants. RESULTS: Among carriers of PSEN1 E280A who were heterozygous for the APOE3 Ch variant, the median age at the onset of cognitive impairment was 52 years (95% confidence interval [CI], 51 to 58), in contrast to a matched group of PSEN1 E280A carriers without the APOE3 Ch variant, among whom the median age at the onset was 47 years (95% CI, 47 to 49). In two participants with the APOE3 Ch and PSEN1 E280A variants who underwent brain imaging, 18F-fluorodeoxyglucose positron-emission tomographic (PET) imaging showed relatively preserved metabolic activity in areas typically involved in Alzheimer's disease. In one of these participants, who underwent 18F-flortaucipir PET imaging, tau findings were limited as compared with persons with PSEN1 E280A in whom cognitive impairment occurred at the typical age in this kindred. Four studies of autopsy material obtained from persons with the APOE3 Ch and PSEN1 E280A variants showed fewer vascular amyloid pathologic features than were seen in material obtained from persons who had the PSEN1 E280A variant but not the APOE3 Ch variant. CONCLUSIONS: Clinical data supported a delayed onset of cognitive impairment in persons who were heterozygous for the APOE3 Ch variant in a kindred with a high prevalence of autosomal dominant Alzheimer's disease. (Funded by Good Ventures and others.).

Family dementia caregivers with suicidal ideation improve with mentalizing imagery therapy: Results from a pilot study.

Background: Family caregivers of persons living with dementia often experience increased depression and suicidal ideation (SI). However, the feasibility and impact of therapies on caregiver SI has remained largely unexplored. Mentalizing imagery therapy (MIT) helps reduce psychological symptoms through mindfulness and guided imagery. This pilot study examined the feasibility of participation by caregivers with SI in a randomized controlled trial (RCT) of MIT versus a psychosocial support group (SG), and the respective impact of group on SI, depression, and secondary outcomes. Methods: A secondary analysis of data from an RCT of 4-week MIT or SG for caregivers (n = 46) was performed, identifying SI (n = 23) and non-SI (n = 23) cohorts. Group attendance and home practice were compared between cohorts. In the SI cohort (total n = 23, MIT n = 11, SG n = 12), group differences in SI, depression, and secondary outcomes were evaluated post-group and at 4-month follow-up. Results: Attendance in both groups and home practice in MIT were similar between SI and non-SI cohorts. In the SI cohort, MIT evinced greater improvements relative to SG in SI (p=.02) and depression (p=.02) post-group, and other secondary outcomes at follow-up. Limitations: Limitations include small sample size and single-item assessments of SI from validated depression rating scales. Conclusions: Participation in an RCT was feasible for caregivers with SI. MIT resulted in important benefits for SI and depression, while SG showed no acute SI benefit. The role of MIT in improving SI should be confirmed with adequately powered trials, as effective therapies to address caregiver SI are critical.

Promoting Growth in Behavioral Neurology: A Path Forward.

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist's perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP-efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities.

Telemedicine-Based Cognitive Examinations During COVID-19 and Beyond: Perspective of the Massachusetts General Hospital Behavioral Neurology & Neuropsychiatry Group.

Telehealth and telemedicine have encountered explosive growth since the beginning of the COVID-19 pandemic, resulting in increased access to care for patients located far from medical centers and clinics. Subspecialty clinicians in behavioral neurology & neuropsychiatry (BNNP) have implemented the use of telemedicine platforms to perform cognitive examinations that were previously office based. In this perspective article, BNNP clinicians at Massachusetts General Hospital (MGH) describe their experience performing cognitive examinations via telemedicine. The article reviews the goals, prerequisites, advantages, and potential limitations of performing a video- or telephone-based telemedicine cognitive examination. The article shares the approaches used by MGH BNNP clinicians to examine cognitive and behavioral areas, such as orientation, attention and executive functions, language, verbal learning and memory, visual learning and memory, visuospatial function, praxis, and abstract abilities, as well as to survey for neuropsychiatric symptoms and assess activities of daily living. Limitations of telemedicine-based cognitive examinations include limited access to and familiarity with telecommunication technologies on the patient side, limitations of the technology itself on the clinician side, and the limited psychometric validation of virtual assessments. Therefore, an in-person examination with a BNNP clinician or a formal in-person neuropsychological examination with a neuropsychologist may be recommended. Overall, this article emphasizes the use of standardized cognitive and behavioral assessment instruments that are either in the public domain or, if copyrighted, are nonproprietary and do not require a fee to be used by the practicing BNNP clinician.

Sex differences in blood biomarkers and cognitive performance in individuals with autosomal dominant Alzheimer's disease.

INTRODUCTION: Plasma tau phosphorylated at threonine 217 (P-tau217) and neurofilament light (NfL) have emerged as markers of Alzheimer's disease (AD) pathology. Few studies have examined the role of sex in plasma biomarkers in sporadic AD, yielding mixed findings, and none in autosomal dominant AD. METHODS: We examined the effects of sex and age on plasma P-tau217 and NfL, and their association with cognitive performance in a cross-sectional study of 621 Presenilin-1 E280A mutation carriers (PSEN1) and non-carriers. RESULTS: As plasma P-tau217 levels increase, cognitively unimpaired female carriers showed better cognitive performance than cognitively unimpaired male carriers. Yet, as disease progresses, female carriers had a greater plasma NfL increase than male carriers. There were no sex differences in the association between age and plasma biomarkers among non-carriers. DISCUSSION: Our findings suggest that, among PSEN1 mutation carriers, females had a greater rate of neurodegeneration than males, yet it did not predict cognitive performance. HIGHLIGHTS: We examined sex differences in plasma P-tau217 and NfL in Presenilin-1 E280A (PSEN1) mutation carriers and non-carriers. Female carriers had a greater plasma NfL increase, but not P-tau217, than male carriers. As plasma P-tau217 levels increase, cognitively unimpaired female carriers showed better cognitive performance than cognitively unimpaired male carriers. The interaction effect of sex by plasma NfL levels did not predict cognition among carriers.

Resilience to autosomal dominant Alzheimer's disease in a Reelin-COLBOS heterozygous man.

We characterized the world's second case with ascertained extreme resilience to autosomal dominant Alzheimer's disease (ADAD). Side-by-side comparisons of this male case and the previously reported female case with ADAD homozygote for the APOE3 Christchurch (APOECh) variant allowed us to discern common features. The male remained cognitively intact until 67 years of age despite carrying a PSEN1-E280A mutation. Like the APOECh carrier, he had extremely elevated amyloid plaque burden and limited entorhinal Tau tangle burden. He did not carry the APOECh variant but was heterozygous for a rare variant in RELN (H3447R, termed COLBOS after the Colombia-Boston biomarker research study), a ligand that like apolipoprotein E binds to the VLDLr and APOEr2 receptors. RELN-COLBOS is a gain-of-function variant showing stronger ability to activate its canonical protein target Dab1 and reduce human Tau phosphorylation in a knockin mouse. A genetic variant in a case protected from ADAD suggests a role for RELN signaling in resilience to dementia.

Virtual mentalizing imagery therapy for Spanish language Latino family dementia caregivers: A feasibility and acceptability study.

Spanish speaking family caregivers of people living with dementia have limited supportive resources in Spanish. There are few validated, culturally acceptable virtual interventions for reducing these caregivers' psychological distress. We investigated the feasibility of a Spanish language adaptation of a virtual Mentalizing Imagery Therapy (MIT) program, which provides guided imagery and mindfulness training to reduce depression, increase mentalizing, and promote well-being. 12 Spanish-speaking family dementia caregivers received a 4-week virtual MIT program. Follow-up was obtained post group and at 4 months post baseline assessment. Feasibility, acceptability, and satisfaction with MIT were assessed. The primary psychological outcome was depressive symptoms; secondary outcomes included caregiver burden, dispositional mindfulness, perceived stress, well-being, interpersonal support, and neurological quality of life. Statistical analysis was performed with mixed linear models. Caregivers were 52 ± 8 (mean ± SD) years of age. 60% had a high school education or less. Participation in weekly group meetings was 100%. Home practice was performed on average 4 ± 1 times per week [range 2-5]. Satisfaction with MIT reached 19 ± 2 of a possible 20 points. Reduction in depression from baseline was observed by week three (p = 0.01) and maintained at 4 month follow-up (p = 0.05). There were significant improvements in mindfulness post-group, and in caregiver burden and well-being at 4 months. MIT was successfully adapted for Latino Spanish language family dementia caregivers within a virtual group environment. MIT is feasible and acceptable and may help reduce depressive symptoms and improve subjective well-being. Larger, randomized controlled trials of MIT should determine durability of effects and validate efficacy in this population.

Associations Among Loneliness, Purpose in Life and Subjective Cognitive Decline in Ethnoracially Diverse Older Adults Living in the United States.

Subjective cognitive decline (SCD), which precedes Mild Cognitive Impairment and dementia, may be affected by purpose in life (PiL) and loneliness in older adults. We investigated associations among PiL, loneliness, and SCD in US Latino (n = 126), Black (n = 74), Asian (n = 33), and White (n = 637) adults. Higher PiL predicted lower SCD in all groups (p-values < .012), except Black participants. Lower loneliness predicted lower SCD in Latino and White groups (p-values < .05), and PiL moderated this association in White adults. PiL and loneliness may play important roles in cognitive decline. Differential predictors of SCD suggest differential targets for preventing cognitive decline and dementia across ethnoracial groups.

Waning locus coeruleus integrity precedes cortical tau accrual in preclinical autosomal dominant Alzheimer's disease.

INTRODUCTION: Autopsy studies recognize the locus coeruleus (LC) as one of the first sites accumulating tau in Alzheimer's disease (AD). Recent AD work related in vivo LC magnetic resonance imaging (MRI) integrity to tau and cognitive decline; however, relationships of LC integrity to age, tau, and cognition in autosomal dominant AD (ADAD) remain unexplored. METHODS: We associated LC integrity (3T-MRI) with estimated years of onset, cortical amyloid beta, regional tau (positron emission tomography [PET]) and memory (Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word-List-Learning) among 27 carriers and 27 non-carriers of the presenilin-1 (PSEN1) E280A mutation. Longitudinal changes between LC integrity and tau were evaluated in 10 carriers. RESULTS: LC integrity started to decline at age 32 in carriers, 12 years before clinical onset, and 20 years earlier than in sporadic AD. LC integrity was negatively associated with cortical tau, independent of amyloid beta, and predicted precuneus tau increases. LC integrity was positively associated with memory. DISCUSSION: These findings support LC integrity as marker of disease progression in preclinical ADAD.

Real-world effectiveness and safety of insulin glargine 300 U/ml in insulin-naïve people with type 2 diabetes in the Latin America region: A subgroup analysis of the ATOS.

AIM: To evaluate the real-world effectiveness and safety of insulin glargine 300 U/ml (Gla-300) in achieving glycaemic goals in insulin-naïve people with type 2 diabetes (T2D) in Mexico, Colombia and Peru (Latin America region) in the A Toujeo Observational Study (ATOS). MATERIALS AND METHODS: ATOS was a multicentre, prospective, 12-month observational study, which included 4422 insulin-naïve adults (age ≥ 18 years) with T2D uncontrolled (HbA1c > 7% and ≤11%) on at least one oral antidiabetic drug (OAD) who initiated Gla-300 treatment as per routine practice. The primary endpoint was the percentage of participants achieving their predefined individualized HbA1c goal at month 6. Key secondary endpoints included change from baseline in HbA1c, fasting plasma glucose (FPG), fasting self-monitored blood glucose (SMBG), body weight and incidence of hypoglycaemia. RESULTS: In this subgroup analysis, a total of 314 participants with T2D received Gla-300. At baseline, mean ± SD age was 56.0 ± 11.6 years, duration of diabetes was 9.7 ± 6.6 years and 65.9% of participants were on at least two OADs. The individualized HbA1c target was achieved by 25.8% of participants (95% confidence interval [CI]: 20.3-31.9) at month 6 and by 35.3% (95% CI: 28.5-42.5) at month 12. Gla-300 treatment improved glycaemic control with meaningful reductions in mean HbA1c, FPG and fasting SMBG. The incidence of hypoglycaemia reported was low and body weight remained stable. CONCLUSIONS: In a real-world setting in the Latin America region, the initiation of Gla-300 in people with T2D uncontrolled on OADs resulted in improved glycaemic control with a low incidence of hypoglycaemia and no change in body weight.

Efectividad del Heberferon en el tratamiento del carcinoma basocelular

El Carcinoma basocelular es el cáncer de piel más frecuente en el ser humano, representa aproximadamente entre un 70 y un 80 % de los cánceres cutáneos no melanoma en la población de color de piel blanca, este es un tumor maligno de estirpe epitelial y es el más frecuente en la consulta dermatológica, soliendo afectar a individuos mayores de 50 años con máxima incidencia entre la sexta y octava década de la vida. Se realizó un estudio postcomercialización, observacional, de serie de casos, de vigilancia temprana del medicamento en condiciones de práctica médica habitual. La investigación se ejecutó con los pacientes con diagnóstico de carcinoma basocelular, atendidos en la consulta en la consulta de oncodermatología, que tiene su sede Hospital ‟Carlos Manuel de Céspedes" de Bayamo, durante el período comprendido entre enero 2018 a diciembre 2019.El universo estuvo constituido por 120 pacientes y la muestra por 92 pacientes mayores de 18 años, a los que se les administró HeberFERON, resultando ser efectivo en el tratamiento de carcinoma basocelular de cualquier localización, tipo y tamaño. Se confirmó la efectividad en condiciones de práctica médica habitual, en las variables: respuesta clínica al tratamiento, utilizando para ello, los criterios RECIST, además mostró un perfil de seguridad adecuado. Los eventos adversos reportados fueron en su mayoría grado 1 y grado 2, según la clasificación del CTCAE, versión 5 y por su gravedad, se clasificaron no grave.

Basal cell carcinoma is the most frequent skin cancer in humans, representing approximately between 70 and 80% of non-melanoma skin cancers in the white-skinned population, this is a malignant tumor of epithelial lineage and is the most frequent in dermatological consultation, usually affecting individuals over 50 years of age with maximum incidence between the sixth and eighth decade of life. A post-marketing study was conducted, observational, case series, of early surveillance of the drug under conditions of routine medical practice. The research was carried out with patients diagnosed with basal cell carcinoma, attended in the consultation in the oncodermatology consultation, which has its headquarters Hospital ‟Carlos Manuel de Céspedes" of Bayamo, during the period from January 2018 to December 2019. The universe consisted of 120 patients and the sample was 92 patients over 18 years of age, who were administered HeberFERON, proving to be effective in the treatment of basal cell carcinoma of any location, type and size. The effectiveness in conditions of usual medical practice was confirmed, in the variables: clinical response to treatment, using the RECIST criteria, in addition to showing an adequate safety profile. The adverse events reported were mostly grade 1 and grade 2, according to the classification of the CTCAE, version 5 and due to their severity, they were classified as non-serious.

O carcinoma basocelular é o câncer de pele mais frequente em humanos, representando aproximadamente entre 70 e 80% dos cânceres de pele não melanoma na população de pele branca, sendo este um tumor maligno de linhagem epitelial e o mais frequente na consulta dermatológica, acometendo geralmente indivíduos com mais de 50 anos de idade com incidência máxima entre a sexta e a oitava década de vida. Foi realizado um estudo pós-comercialização, observacional, série de casos, de vigilância precoce da droga sobcondições de prática médica de rotina.A pesquisa foi realizada com pacientes diagnosticados com carcinoma basocelular, atendidos na consulta na consulta de oncodermatologia, que temsua sede no Hospital Carlos Manuel de Céspedes, de Bayamo, no período de janeiro de 2018 a dezembro de 2019. O universo foi composto por 120 pacientes e a amostra foi de 92 pacientes com mais de 18 anos de idade, aos quais foi administrado HeberFERON, mostrando-se eficaz no tratamento do carcinoma basocelular de qualquer localização, tipo e tamanho. A efetividade nas condições de prática médica habitual foi confirmada, nas variáveis: resposta clínica ao tratamento, utilizando-se os critérios RECIST, além de apresentarum perfil de segurança adequado. Os eventos adversos relatados foram, em sua maioria, grau 1 e grau 2, de acordo com a classificação do CTCAE, versão 5 e, devido à sua gravidade, foram classificados como não graves.

Efectividad del Heberferon en pacientes con queratosis actínica asociada a carcinoma basocelular

Las queratosis actínicas son neoformaciones dermatológicas planas oexofísticas, presentes mayormente en zonas fotoexpuestas, de evolución crónica y generalmente asintomáticas, siendo la expresión más temprana del carcinoma espinocelular, producidas por la exposición solar crónica en personas fundamentalmente de piel clara. Se realizó un estudio longitudinal prospectivo de intervención terapéutica. El universo estuvo constituido por 130 pacientes y la muestra por 116 pacientes diagnosticados con queratosis actínica que concomitaron con carcinoma basocelular que asistieron a la consulta de oncodermatología del Hospital Provincial Docente "Carlos Manuel de Céspedes" de Bayamo, en el período comprendido de enero 2019 a diciembre 2020; con el objetivo de evaluar la efectividad del tratamiento con HeberFERON® en la queratosis actínica asociada a carcinoma basocelular. Para valorar la asociación entre las variables se empleó el test de Chi Cuadrado de Mantel. Fue frecuente en el estudio el sexo masculino, las edades comprendidas entre 61 y 80 años, el fototipo cutáneo II de la clasificación de Fitzpatrick, que presentaron más de 20 lesiones de queratosis actínica, de localización frecuente en los antebrazos. El HeberFERON fue efectivo y se logró respuesta favorable al tratamiento desde el punto de vista clínico y por dermatoscopia. Los efectos adversos frecuentes tras la administración del HeberFERON® fueron la fiebre, seguido de malestar general y el dolor en el sitio de la inyección.

Actinic keratoses are flat dermatological neoformations or oexofistic, present mostly in photoexposed areas, of chronic evolution and generally asymptomatic, being the earliest expression of squamous cell carcinoma, produced by chronic sun exposure in people mainly fair-skinned. A prospective longitudinal study of therapeutic intervention was conducted. The universe consisted of 130 patients and the sample consisted of 116 patients diagnosed with actinic con queratosis who concomitated with basal cell carcinoma who attended the oncodermatology consultation of the "Carlos Manuel de Céspedes" Provincial Teaching Hospital of Bayamo, in the period from January 2019 to December 2020; with the objective of evaluating the effectiveness of treatment with HeberFERON® in actinic keratosis associated with basal cell carcinoma. To assess the association between the variables, the Mantel Chi-Square test was used. The male sex, ages between 61 and 80 years, cutaneous phototype II of the Fitzpatrick classification, which presented more than 20 lesions of actinic keratosis, of frequent location in the forearms, were frequent in the study. HeberFERON was effective and a favorable response to treatment was achieved from the clinical point of view and by dermoscopy. Common side effects following administration of HeberFERON® were fever, followed by malaise and pain at the injection site.

As ceratoses actínicas são neoformações dermatológicas planas ou oexofísticas, presentes principalmente em áreas fotoexpostas, de evolução crônica e geralmente assintomáticas, sendo a expressão mais precoce do carcinoma espinocelular, produzido pela exposição solar crônica em pessoas principalmente de pele clara. Foi realizado um estudo longitudinal prospectivo de intervenção terapêutica. O universo foi composto por 130 pacientes e a amostra por 116 pacientes diagnosticados com conqueratose actínica que se concomitaram com carcinoma basocelular e que compareceram à consulta de oncodermatologia do Hospital Universitário Provincial "Carlos Manuel de Céspedes" de Bayamo, no período de janeiro de 2019 a dezembro de 2020; com o objetivo de avaliar a eficácia do tratamento com HeberFERON® na queratose actínica associada ao carcinoma basocelular. Para avaliar a associação entre as variáveis, foi utilizado o teste Qui-Quadrado de Mantel. O sexo masculino, com idades entre 61 e 80 anos, o fototipo cutâneo II da classificação de Fitzpatrick, que apresentou mais de 20 lesões de queratose actínica, de localização frequente nos antebraços, foram frequentes no estudo. O HeberFERON foi eficaz e uma resposta favorável ao tratamento foi alcançada do ponto de vista clínico e por dermatoscopia. Os efeitos secundários frequentes após a administração de HeberFERON® foram febre, seguida de mal-estar e dor no local da injeção.

Interpretable Classification of Tauopathies with a Convolutional Neural Network Pipeline Using Transfer Learning and Validation against Post-Mortem Clinical Cases of Alzheimer's Disease and Progressive Supranuclear Palsy.

Neurodegenerative diseases, tauopathies, constitute a serious global health problem. The etiology of these diseases is unclear and an increase in their incidence has been projected in the next 30 years. Therefore, the study of the molecular mechanisms that might stop these neurodegenerative processes is very relevant. Classification of neurodegenerative diseases using Machine and Deep Learning algorithms has been widely studied for medical imaging such as Magnetic Resonance Imaging. However, post-mortem immunofluorescence imaging studies of the brains of patients have not yet been used for this purpose. These studies may represent a valuable tool for monitoring aberrant chemical changes or pathological post-translational modifications of the Tau polypeptide. We propose a Convolutional Neural Network pipeline for the classification of Tau pathology of Alzheimer's disease and Progressive Supranuclear Palsy by analyzing post-mortem immunofluorescence images with different Tau biomarkers performed with models generated with the architecture ResNet-IFT using Transfer Learning. These models' outputs were interpreted with interpretability algorithms such as Guided Grad-CAM and Occlusion Analysis. To determine the best classifier, four different architectures were tested. We demonstrated that our design was able to classify diseases with an accuracy of 98.41% on average whilst providing an interpretation concerning the proper classification involving different structural patterns in the immunoreactivity of the Tau protein in NFTs present in the brains of patients with Progressive Supranuclear Palsy and Alzheimer's disease.

Bacillus mycoides y ácidos húmicos como bioestimulantes de fríjol caupí bajo estrés por salinidad

Los bioestimulantes tienen gran potencial en la agricultura, no solo por aumentar el crecimiento de las plantas, sino porque también promueven la tolerancia frente a diferentes tipos de estrés. En este estudio, se evaluó el efecto de dos bioestimulantes Bacillus mycoides, inmovilizado en perlas de alginato y ácidos húmicos (AH), en plantas de fríjol caupí, cultivadas en un suelo salino, bajo los siguientes tratamientos: 1) solución de AH, mediante aspersión foliar, 2) suspensión de B. mycoides, inmovilizado en perlas aplicado en la rizósfera y 3) solución de AH + suspensión de B. mycoides inmovilizado; el tratamiento control fueron plantas sin aplicación de bioestimulantes. Se determinó el contenido hídrico relativo, el índice de contenido de clorofila, además del contenido de prolina y polifenoles, como indicadores de tolerancia al estrés. El tratamiento 3 generó un aumento de 11,27 % en el contenido hídrico relativo, mientras que con el tratamiento 2, se observó un incremento significativo del 48,33 %, en el índice de contenido de clorofila y del 49,07 %, en el contenido de prolina, lo cual, se sugiere la estimulación de mecanismos de tolerancia frente al estrés salino. La activación de estos mecanismos, observada con tratamientos que incluyen la inmovilización de B. mycoides, sugiere que esta forma de aplicación de la bacteria puede contribuir a mejorar las condiciones de crecimiento de plantas de fríjol caupí sometidas a estrés salino y puede ser probada en otras plantas de interés agrícola, en regiones afectadas por la salinidad.

Biostimulants have great potential in agriculture enhancing plant growth as well as stimulating tolerance to different types of stress. In this study, the effect of two biostimulants, Bacillus mycoides immobilized in alginate beads and humic acids (HA), was evaluated in cowpea plants grown in saline soil, following treatments were evaluated: 1) HA solution applied through foliar spray, 2) suspension of immobilized B. mycoides in beads applied around in the rhizosphere and 3) HA solution + immobilized B. mycoides suspension. Plants without biostimulant application were considered as control treatment. Relative water content (RWC), chlorophyll content index (CCI), proline, and polyphenol content were determined as indicators of stress tolerance mechanisms expression. Treatment 3 generated an increase of 11.27 % in RWC, while with treatment 2 a significant increase of 48.33 % in CCI and 49.07 % in proline content was observed; these results suggest the stimulation of tolerance mechanisms against salt stress. Effects exhibited after the treatments with immobilized B. mycoides suggest that this way of application of the bacteria can contribute to improving the growth and adaption of cowpea plants subjected to salt stress and can be tested in other plants of agricultural interest over saline stress affection.

Distinct tau neuropathology and cellular profiles of an APOE3 Christchurch homozygote protected against autosomal dominant Alzheimer's dementia.

We describe in vivo follow-up PET imaging and postmortem findings from an autosomal dominant Alzheimer's disease (ADAD) PSEN1 E280A carrier who was also homozygous for the APOE3 Christchurch (APOE3ch) variant and was protected against Alzheimer's symptoms for almost three decades beyond the expected age of onset. We identified a distinct anatomical pattern of tau pathology with atypical accumulation in vivo and unusual postmortem regional distribution characterized by sparing in the frontal cortex and severe pathology in the occipital cortex. The frontal cortex and the hippocampus, less affected than the occipital cortex by tau pathology, contained Related Orphan Receptor B (RORB) positive neurons, homeostatic astrocytes and higher APOE expression. The occipital cortex, the only cortical region showing cerebral amyloid angiopathy (CAA), exhibited a distinctive chronic inflammatory microglial profile and lower APOE expression. Thus, the Christchurch variant may impact the distribution of tau pathology, modulate age at onset, severity, progression, and clinical presentation of ADAD, suggesting possible therapeutic strategies.

Olfactory Function and Markers of Brain Pathology in Non-Demented Individuals with Autosomal Dominant Alzheimer's Disease.

BACKGROUND: Olfactory dysfunction is one of the earliest signs of Alzheimer's disease (AD), highlighting its potential use as a biomarker for early detection. It has also been linked to progression from mild cognitive impairment (MCI) to dementia. OBJECTIVE: To study olfactory function and its associations with markers of AD brain pathology in non-demented mutation carriers of an autosomal dominant AD (ADAD) mutation and non-carrier family members. METHODS: We analyzed cross-sectional data from 16 non-demented carriers of the Presenilin1 E280A ADAD mutation (mean age [SD]: 40.1 [5.3], and 19 non-carrier family members (mean age [SD]: 36.0 [5.5]) from Colombia, who completed olfactory and cognitive testing and underwent amyloid and tau positron emission tomography (PET) imaging. RESULTS: Worse olfactory identification performance was associated with greater age in mutation carriers (r = -0.52 p = 0.037). In carriers, worse olfactory identification performance was related to worse MMSE scores (r = 0.55, p = 0.024) and CERAD delayed recall (r = 0.63, p = 0.007) and greater cortical amyloid-ß (r = -0.53, p = 0.042) and tau pathology burden (entorhinal: r = -0.59, p = 0.016; inferior temporal: r = -0.52, p = 0.038). CONCLUSION: Worse performance on olfactory identification tasks was associated with greater age, a proxy for disease progression in this genetically vulnerable ADAD cohort. In addition, this is the first study to report olfactory dysfunction in ADAD mutation carriers with diagnosis of MCI and its correlation with abnormal accumulation of tau pathology in the entorhinal region. Taken together, our findings suggest that olfactory dysfunction has promise as an early marker of brain pathology and future risk for dementia.

Mentalizing imagery therapy to augment skills training for dementia caregivers: Protocol for a randomized, controlled trial of a mobile application and digital phenotyping.

More than 50 million people worldwide live with a dementia, and most are cared for by family members. Family caregivers often experience chronic stress and insomnia, resulting in decreased mental and physical health. Accessibility of in-person stress reduction therapy is limited due to caregiver time constraints and distance from therapy sites. Mentalizing imagery therapy (MIT) provides mindfulness and guided imagery tools to reduce stress, promote self and other understanding, and increase feelings of interconnectedness. Combining MIT with caregiver skills training might enable caregivers to both reduce stress and better utilize newly learned caregiving skills, but this has never been studied. Delivering MIT through a smartphone application (App) has the potential to overcome difficulties with scalability and dissemination and offers caregivers an easy-to-use format. Harnessing passive smartphone data provides an important opportunity to study behavioral changes continuously and with higher granularity than routine clinical assessments. This protocol describes a randomized, controlled, superiority trial in which 120 family dementia caregivers, aged 60 years or older, will be assigned to smartphone App delivery of caregiver skills with MIT (experimental condition) or without MIT (control condition). The primary objectives of the trial are to assess whether the experimental condition is superior to control on reducing family caregiver stress, insomnia and related outcomes and to demonstrate the feasibility of developing behavioral markers from passive smartphone data that predict health outcomes in older adults. Trial outcomes may inform the suitability of our intervention for caregivers and provide new methods for assessment of older adults.