Review of \u3cem\u3eEmpowering Vulnerable Populations: Cognitive-Behavioral Interventions.\u3c/em\u3e Mary Keegan Eamon. Reviewed Maria Y. Hernandez.

Book review of Mary Keegan Eamon, Empowering Vulnerable Populations: Cognitive Behavioral Interventions. Chicago, IL: Lyceum Press, 2008. $59.95 papercover

Bilingual Comics on the Border as Graphic Medicine: Journaling and Doodling for Dementia Caregiving during the COVID-19 Pandemic

The use of comics can be a powerful tool to expand educational outreach efforts for improving the health and well-being of people everywhere. Dr. Ian Williams coined the term graphic medicine to denote the use of comics in medical education and patient care ( Graphic Medicine ). Alzheimer\u27s disease affects approximately five million Americans and is expected to triple to 13.8 million by 2050. Hispanics and Blacks are disproportionately affected at a higher rate than other groups ( Facts and Figures ). There is a lack of culturally relevant educational materials available for these populations. To address this disparity, an interdisciplinary community engaged collaboration was initiated with the Alzheimer\u27s Association West Texas Chapter, The University of Texas at El Paso (UTEP), and Dukes Comics to produce a series of virtual workshops entitled, Journaling and Doodling for Stress Reduction and Relaxation for caregivers of people living with Alzheimer\u27s and other dementias. These sessions were live-streamed and began during the COVID-19 pandemic. Spanish sessions have also been provided to the public. Health information about the disease process and common caregiver challenges are provided in each session. A guided journaling and doodling activity are also included. Journaling has been shown to be an effective and easy tool to use for stress management (Scott). The impetus behind this project was to address the dire need for increasing access to Alzheimer\u27s disease education and resources in El Paso, Texas, a border community that is also home to Fort Bliss Army base. Hispanics comprise approximately 82% of the population and include a large Spanish-speaking segment. Language is often a barrier to health care access and education. To meet the aim of increasing accessibility, the workshops and comics are available in both English and Spanish and soon in-person. This project received a 2022 joint seed grant from Texas Tech University Health Sciences Center El Paso and UTEP to conduct research and examine data from these workshops that will be provided in-person in marginalized and multilingual Latina communities surrounding El Paso starting in the fall

A Mathematical Model to Optimize the Neoadjuvant Chemotherapy Treatment Sequence for Triple-Negative Locally Advanced Breast Cancer

Background: Triple-negative locally advanced breast cancer is an aggressive tumor type. Currently, the standard sequence treatment is applied, administering anthracyclines first and then a taxane plus platinum. Clinical studies for all possible treatment combinations are not practical or affordable, but mathematical modeling of the active mitotic cell population is possible. Our study aims to show the regions with the tumor’s most substantial cellular population variation by utilizing all possible values of the parameters () that define the annihilatory drug capacity according to the proposed treatment. Method: A piecewise linear mathematical model was used to analyze the cell population growth by applying four treatments: standard sequences of 21 days (SS21) and 14 days (SS14), administering anthracyclines first, followed by a taxane plus platinum, and inverted sequences of 21 days (IS21) and 14 days (IS14), administering a taxane plus platinum first then anthracyclines. Results: The simulation showed a higher effect of IS14 over SS14 when the rate of drug resistance was larger in the cell population during DNA synthesis (G1 and S) compared to cells in mitosis (G2 and M). However, if the proportion of resistant cells in both populations was equivalent, then treatments did not differ. Conclusions: When resistance is considerable, IS14 is more efficient than SS14, reducing the tumor population to a minimum

Bitter tastants and artificial sweeteners activate a subset of epithelial cells in acute tissue slices of the rat trachea

Bitter and sweet receptors (T2Rs and T1Rs) are expressed in many extra-oral tissues including upper and lower airways. To investigate if bitter tastants and artificial sweeteners could activate physiological responses in tracheal epithelial cells we performed confocal Ca2+ imaging recordings on acute tracheal slices. We stimulated the cells with denatonium benzoate, a T2R agonist, and with the artificial sweeteners sucralose, saccharin and acesulfame-K. To test cell viability we measured responses to ATP. We found that 39% of the epithelial cells responding to ATP also responded to bitter stimulation with denatonium benzoate. Moreover, artificial sweeteners activated different percentages of the cells, ranging from 5% for sucralose to 26% for saccharin, and 27% for acesulfame-K. By using carbenoxolone, a gap junction blocker, we excluded that responses were mainly mediated by Ca2+ waves through cell-to-cell junctions. Pharmacological experiments showed that both denatonium and artificial sweeteners induced a PLC-mediated release of Ca2+ from internal stores. In addition, bitter tastants and artificial sweeteners activated a partially overlapping subpopulation of tracheal epithelial cells. Our results provide new evidence that a subset of ATP-responsive tracheal epithelial cells from rat are activated by both bitter tastants and artificial sweeteners

Brain ApoA-I, ApoJ and ApoE Immunodetection in Cerebral Amyloid Angiopathy

ApoA-I; ApoE; Cerebral amyloid angiopathyApoA-I; ApoE; Angiopatía amiloide cerebralApoA-I; ApoE; Angiopatia amiloide cerebralCerebral amyloid angiopathy (CAA) is a common cause of lobar intracerebral hemorrhage (ICH) in elderly individuals and it is the result of the cerebrovascular deposition of beta-amyloid (Aβ) protein. CAA is frequently found in patients with Alzheimer's disease (AD), although it has an independent contribution to the cognitive deterioration associated with age. Specific apolipoproteins (Apo) have been associated with Aβ fibrillization and clearance from the brain. In this regard, in the present study, we analyzed the brain levels of ApoE, ApoA-I, and ApoJ/clusterin in autopsy brains from 20 post-mortem cases with CAA type I, CAA type II, with parenchymal Aβ deposits or without Aβ deposits. Our objective was to find a possible differential pattern of apolipoproteins distribution in the brain depending on the CAA pathological presentation. The protein expression levels were adjusted by the APOE genotype of the patients included in the study. We found that ApoE and ApoJ were abundantly present in meningeal, cortical, and capillary vessels of the brains with vascular Aβ accumulation. ApoE and ApoJ also deposited extracellularly in the parenchyma, especially in cases presenting Aβ diffuse and neuritic parenchymal deposits. In contrast, ApoA-I staining was only relevant in capillary walls in CAA type I cases. On the other hand, ICH was the principal cause of death among CAA patients in our cohort. We found that CAA patients with ICH more commonly had APOEε2 compared with CAA patients without ICH. In addition, patients who suffered an ICH presented higher vascular ApoE levels in brain. However, higher ApoE presence in cortical arteries was the only independent predictor of suffering an ICH in our cohort after adjusting by age and APOE genotype. In conclusion, while ApoE and ApoJ appear to be involved in both vascular and parenchymal Aβ pathology, ApoA-I seems to be mainly associated with CAA, especially in CAA type I pathology. We consider that our study helps to molecularly characterize the distribution subtypes of Aβ deposition within the brain

Validation of Cell-Free DNA Collection Tubes for Determination of EGFR Mutation Status in Liquid Biopsy from NSCLC Patients

Altres ajuts: Roche Farma S.A., Spain.Precision medicine has revolutionized the understanding and treatment of cancer by identifying subsets of patients who are amenable to specific treatments according to their molecular characteristics, as exemplified by epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC). Although tissue biopsy is the gold standard for determining molecular alterations in tumors, its limitations have prompted the development of new techniques for studying tumor biomarkers in liquid biopsies, such as mutation analysis in cell-free DNA (cfDNA). cfDNA analysis can accurately determine tumor progression and prognosis and more effectively identify appropriate targeted therapies. However, cfDNA is vulnerable, particularly during plasma sample shipping. We compared the cell- and DNA-stabilizing properties of cell-free DNA blood collection tubes (BCTs) with those of the traditional shipping method (frozen plasma) for EGFR mutation testing using the cobas ® EGFR Mutation Test v2 in a prospective cohort of 49 patients from three different Spanish hospitals. In total, 98 NSCLC samples, two from each patient, were studied; five of the 49 cases were considered invalid by cobas ® with one of the two shipping methods analyzed. After excluding these samples, we analyzed 88 samples from 44 patients. Considering the current methodology (frozen plasma) for sending samples as the gold standard, we evaluated the sensitivity and specificity of cfDNA BCT shipment. The global agreement between the two methods was 95.4%, with 100% sensitivity and 94.6% specificity for the cfDNA BCTs. cfDNA BCTs had a positive predictive value of 81.8% and negative predictive value of 100%. cfDNA BCTs have the same sensitivity for EGFR mutation analysis in liquid biopsy as the current methodology and very high specificity. They also have some additional advantages in terms of collection and further shipment. Therefore, cfDNA BCTs can be perfectly incorporated into the routine practice for EGFR mutation determination. Roche Farma S.A., Spain. The online version of this article (10.1007/s40487-019-00099-9) contains supplementary material, which is available to authorized users

Exploring circumstellar effects on the lithium and calcium abundances in massive Galactic O-rich AGB stars

Context. We previously explored the circumstellar effects on Rb and Zr abundances in a sample (21) of massive Galactic O-rich asymptotic giant branch (AGB) stars. Here we are interested in clarifying the role of the extended atmosphere in the case of Li and Ca. Li is an important indicator of hot bottom burning while the total Ca abundances in these stars could be affected by neutron captures.Aims. We report new Li and Ca abundances in a larger sample (30) of massive Galactic O-rich AGB stars by using more-realistic extended model atmospheres. Li abundances had previously studied with hydrostatic models, while the Ca abundances have been determined here for the first time.Methods. We used a modified version of the spectral synthesis code Turbospectrum and consider the presence of a gaseous circumstellar envelope and radial wind in the modelling of the spectra of these massive AGB stars. The Li and Ca abundances were obtained from the 6708 angstrom Li I and 6463 angstrom Ca I resonance lines, respectively. In addition, we studied the sensitivity of the pseudo-dynamical models to variations of the stellar and wind parameters.Results. The Li abundances derived with the pseudo-dynamical models are very similar to those obtained from hydrostatic models (the average difference is 0.18 dex, sigma(2) = 0.02), with no difference for Ca. This indicates that the Li and Ca content in these stars is only slightly affected by the presence of a circumstellar envelope. We also found that the Li I and Ca I line profiles are not very sensitive to variations of the model wind parameters.Conclusions. The new Li abundances confirm the Li-rich (and super Li-rich, in some cases) nature of the sample stars, supporting the activation of hot bottom burning in massive Galactic AGB stars. This is in good agreement with the theoretical predictions for solar metallicity AGB models from ATON, Monash, and NuGrid/MESA but is at odds with the FRUITY database, which predicts no hot bottom burning leading to the production of Li. Most (20) sample stars display nearly solar (within the estimated errors and considering possible non-local thermodynamic equilibrium effects) Ca abundances that are consistent with the available s-process nucleosynthesis models for solar metallicity massive AGB stars, which predict overproduction of Ca-46 relatively to the other Ca isotope and the creation of the radioactive isotope Ca-41 (half life of 0.1 Myr) but no change in the total Ca abundance. A minority (five) of the sample stars seem to show a significant Ca depletion (by up to 1.0 dex). Possible explanations are offered to explain their apparent and unexpected Ca depletion

Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer’s disease

Alzheimer; CD2AP; Enfermedad de PickAlzheimer's disease; CD2AP; Pick's diseaseAlzheimer; CD2AP; Malaltia de PickGenome-wide association studies have described several genes as genetic susceptibility loci for Alzheimer's disease (AD). Among them, CD2AP encodes CD2-associated protein, a scaffold protein implicated in dynamic actin remodeling and membrane trafficking during endocytosis and cytokinesis. Although a clear link between CD2AP defects and glomerular pathology has been described, little is known about the function of CD2AP in the brain. The aim of this study was to analyze the distribution of CD2AP in the AD brain and its potential associations with tau aggregation and β-amyloid (Aβ) deposition. First, we performed immunohistochemical analysis of CD2AP expression in brain tissue from AD patients and controls (N = 60). Our results showed granular CD2AP immunoreactivity in the human brain endothelium in all samples. In AD cases, no CD2AP was found to be associated with Aβ deposits in vessels or parenchymal plaques. CD2AP neuronal inclusions similar to neurofibrillary tangles (NFT) and neuropil thread-like deposits were found only in AD samples. Moreover, immunofluorescence analysis revealed that CD2AP colocalized with pTau. Regarding CD2AP neuronal distribution, a hierarchical progression from the entorhinal to the temporal and occipital cortex was detected. We found that CD2AP immunodetection in neurons was strongly and positively associated with Braak neurofibrillary stage, independent of age and other pathological hallmarks. To further investigate the association between pTau and CD2AP, we included samples from cases of primary tauopathies (corticobasal degeneration [CBD], progressive supranuclear palsy [PSP], and Pick's disease [PiD]) in our study. Among these cases, CD2AP positivity was only found in PiD samples as neurofibrillary tangle-like and Pick body-like deposits, whereas no neuronal CD2AP deposits were detected in PSP or CBD samples, which suggested an association of CD2AP neuronal expression with 3R-Tau-diseases. In conclusion, our findings open a new road to investigate the complex cellular mechanism underlying the tangle conformation and tau pathology in the brain.This work was funded by Instituto de Salud Carlos III (ISCIII) (PI17/00275, PI20/00465), cofinanced by the European Regional Development Fund (FEDER). The Neurovascular Research Laboratory is part of the INVICTUS+ network, ISCIII, Spain (RD16/0019/0021). M.H.-G. is supported by the Miguel Servet Programme, ISCIII, Spain (CPII17/00010

Reference values for areal bone mineral density among a healthy Mexican population

Objective. Compare the influence of ethnicity in the prevalence of osteopenia and osteoporosis in various Mexican populations using two normal dual X-ray absorptiometry (DXA) reference databases: manufacturer¿s incorporating US Hispanic population and a normal mestizo Mexican population. Material and Methods. MMP included 9 946 subjects participating in an ongoing long-term cohort study focusing on lifestyle and chronic diseases, of which 6 487 MMP males and females aged 7 to 80 years were the normal subjects used to determine bone density T- and Z-scores, following WHO criteria, and peak bone mass values. Abnormal bone mass density values estimated by the manufacturer's and peak bone mass reference values were compared. Results and Conclusions. Our results show that by using the manufacturer´s T-score values in the mestizo Mexican population we are underestimating the number of abnormal bone mass BMD populations

Causes of variation in BCG vaccine efficacy: examining evidence from the BCG REVAC cluster randomized trial to explore the masking and the blocking hypotheses.

BCG protection varies and in some places (nearest the equator) is low or absent. Understanding this variation can inform the efforts to develop new vaccines against tuberculosis. Two main hypotheses are used to explain this variation: under masking, new vaccines are unlikely to increase protection; under blocking new vaccines have a greater potential to be effective when BCG is not. We conducted a cluster randomized trial to explored the masking and blocking hypotheses by studying BCG vaccine efficacy of neonatal vaccination and when administered for the first or a second (revaccination) time at school age in two sites (Manaus close and Salvador further south from the equator). Seven hundred and sixty three state schools were matched on socio economic characteristics of the neighborhood and 239,934 children were randomized to vaccine (BCG vaccination at school age) or control group. Protection by first BCG vaccination at school age was high in Salvador (34%, 95% CI 7-53%, p=0.017) but low in Manaus (8%, 95% CI t0 39-40%, p=0.686). For revaccination at school age, protection was modest in Salvador (19%, 95% CI 3-33%, p=0.022) and absent in Manaus (1%, 95% CI to 27-23%, p=0.932). Vaccine efficacy for neonatal vaccination was similar in Salvador (40%, 95% CI 22-54%, p<0.001) and Manaus (36%, 95% CI 11-53%, p=0.008). Variation in BCG efficacy was marked when vaccine was given at school age but absent at birth, which points towards blocking as the dominant mechanism. New tuberculosis vaccines that overcome or by pass this blocking effect could confer protection in situations where BCG is not protective