Skull Density Ratio as Arm-Allocation Parameter for a Controlled Focused Ultrasound Trial in Parkinson's Disease.

BACKGROUND: MR-guided focused ultrasound (FUS) thermoablation is an established therapy for movement disorders. FUS candidates must meet a predefined threshold of skull density ratio (SDR), a parameter that accounts for the efficiency in reaching ablative temperatures. Randomized sham-controlled trials to provide definitive therapeutic evidence employ pure randomization of subjects into active treatment or control arms. The latter design has several general limitations. OBJECTIVE: To demonstrate that SDR values are not associated with clinically and demographically relevant variables in patients with Parkinson's disease (PD). This in turn would allow using SDR as an arm-allocation parameter, separating patients who will receive active FUS treatment and best medical management treatment (BMT). METHODS: We studied a cohort of 215 PD patients who were candidates for FUS subthalamotomy to determine if the SDR was correlated with demographic or clinical variables that could introduce bias for group allocation in a controlled trial. RESULTS: SDR was unassociated with age, gender, and clinical motor features nor with levodopa daily dose in our cohort of PD patients. A negative association with age was found for the female subgroup. CONCLUSIONS: Our results show that in a PD population considered for FUS subthalamotomy treatment, the SDR may be a valid group-allocation parameter. This could be considered as the basis for a controlled study comparing FUS subthalamotomy vs BMT.

Staged Bilateral MRI-Guided Focused Ultrasound Subthalamotomy for Parkinson Disease.

Importance: Unilateral magnetic resonance imaging (MRI)-guided focused ultrasound subthalamotomy (FUS-STN) improves cardinal motor features among patients with asymmetrical Parkinson disease (PD). The feasibility of bilateral FUS-STN is as yet unexplored. Objective: To assess the safety and effectiveness of staged bilateral FUS-STN to treat PD. Design, Setting, and Participants: This prospective, open-label, case series study was conducted between June 18, 2019, and November 7, 2023, at HM-CINAC, Puerta del Sur University Hospital, Madrid, Spain, and included 6 patients with PD who had been treated with unilateral FUS-STN contralateral to their most affected body side and whose parkinsonism on the untreated side had progressed and was not optimally controlled with medication. Intervention: Staged bilateral FUS-STN. Main Outcomes and Measures: Primary outcomes were assessed 6 months after the second treatment and included safety (incidence and severity of adverse events after second treatment) and effectiveness in terms of motor change (measured with the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III [MDS-UPDRS III]) in the off-medication state (ie, after at least 12 hours of antiparkinsonian drug withdrawal) compared with baseline (ie, prior to the first side ablation). Secondary outcomes included motor change in patients in the on-medication state (ie, after usual antiparkinsonian medication intake), motor complications (measured with the MDS-UPDRS IV), daily living activities (measured with the MDS-UPDRS I-II), quality of life (measured with the 39-item Parkinson's Disease Questionnaire), change in dopaminergic treatment, patient's global impression of change (measured with the Global Impression of Change [PGI-C] scale), and long-term (24-month) follow-up. Results: Of 45 patients previously treated with unilateral FUS-STN, 7 were lost to follow-up, and 4 were excluded due to adverse events. Of the remaining 34 patients, 6 (median age at first FUS-STN, 52.6 years [IQR, 49.0-57.3 years]; 3 women [50%]) experienced progression of parkinsonism on the untreated body side and were included. At the time of the first FUS-STN, patients' median duration of disease was 5.7 years (IQR, 4.7-7.3 years). The median time between procedures was 3.2 years (IQR, 1.9-3.5 years). After the second FUS-STN, 4 patients presented with contralateral choreic dyskinesia, which resolved by 3 months. Four patients developed speech disturbances, which gradually improved but remained in a mild form for 2 patients at 6 months; 1 patient experienced mild imbalance and dysphagia during the first week after treatment, which subsided by 3 months. No behavioral or cognitive disturbances were found on neuropsychological testing. For patients in the off-medication state, MDS-UPDRS III scores improved by 52.6% between baseline and 6 months after the second FUS-STN (from 37.5 [IQR, 34.2-40.0] to 20.5 [IQR, 8.7-24.0]; median difference, 23.0 [95% CI, 7.0-33.7]; P = .03). The second treated side improved by 64.3% (MDS-UPDRS III score, 17.0 [IQR, 16.0-19.5] prior to the second treatment vs 5.5 [IQR, 3.0-10.2]; median difference, 9.5 [95% CI, 3.2-17.7]; P = .02). After the second procedure, all self-reported PGI-C scores were positive. Conclusions: Findings of this pilot study suggest that staged bilateral FUS-STN was safe and effective for the treatment of PD, although mild but persistent speech-related adverse events were observed among a small number of patients.

Long-term surveillance of the feline leukemia virus in the endangered Iberian lynx (Lynx pardinus) in Andalusia, Spain (2008-2021).

Feline leukemia virus (FeLV) infection is considered one of the most serious disease threats for the endangered Iberian lynx (Lynx pardinus) Over 14 years (2008-2021), we investigated FeLV infection using point-of-care antigen test and quantitative real-time TaqMan qPCR for provirus detection in blood and tissues in lynxes from Andalusia (Southern Spain). A total of 776 samples from 586 individuals were included in this study. The overall prevalence for FeLV antigen in blood/serum samples was 1.4% (5/360) (95% CI: 0.2-2.6), FeLV proviral DNA prevalence in blood samples was 6.2% (31/503) (95% CI: 4.1-8.6), and FeLV proviral DNA in tissues samples was 10.2% (34/333) (95% CI: 7-13.5). From a subset of 129 longitudinally sampled individuals, 9.3% (12/129) PCR-converted during the study period. Our results suggest that FeLV infection in the Andalusian population is enzootic, with circulation of the virus at low levels in almost all the sampling years. Moreover, since only one viremic individual succumbed to the infection, this study suggests that lynxes may therefore control the infection decreasing the possibility of developing a more aggressive outcome. Although our results indicate that the FeLV infection in the Iberian lynx from Andalusia tends to stay within the regressive stage, continuous FeLV surveillance is paramount to predict potential outbreaks and ensure the survival of this population.

Energy imbalance gap was associated with body mass index and sex in Latin American adolescents-results from the ELANS study.

Introduction: Energy imbalance gap (EIG) is defined as the average daily difference between energy intake (EI) and energy expenditure (EE). This study aimed to examine the associations between EIG and sociodemographic and anthropometric variables in the adolescent population of eight Latin America countries. Methods: A total of 680 adolescents aged 15 to 18 were included in this study. The estimation of EI was based on two non-consecutive 24-h dietary recalls. EE was predicted from Schofield equations using physical activity level obtained through the long version of the International Physical Activity Questionnaire. Sociodemographic data and anthropometric measurements were also obtained. A descriptive analysis and multilevel linear regression models were used to examine associations between variables. Results: The mean EI, EE, and EIG were 2091.3 kcal, 2067.8 kcal, and 23.5 kcal, respectively. Argentina had the highest EI and EIG, whereas Chile had the lowest EI and EIG. Males had a higher EI (2262.4 kcal) and EE (2172.2 kcal) than females (1930.1 kcal and 2084.5 kcal), respectively (p < 0.05). Overweight subjects had a lower EIG than did underweight and normal-weight subjects (p < 0.05). Subjects with low socioeconomic status (SES) had a lower EE (2047.0 kcal) than those with a high SES (2164.2 kcal) (p < 0.05). Conclusion: Sex and BMI were associated with EIG in adolescents from Latin America.

Cognitive Reserve in Parkinson's Disease without Dementia: ß-Amyloid and Metabolic Assessment.

BACKGROUND: Cognitive reserve (CR) is the mismatch between preserved cognition and neuropathological damage. Amyloidopathy in Parkinson's disease (PD) could be associated with faster progression to dementia, but the putative protective effect of CR is unknown. OBJECTIVES: To evaluate the effect of CR on ß-amyloid burden and brain metabolism in non-demented PD subjects. METHODS: Participants with PD (n = 53) underwent a clinical evaluation, [18 F]-fluorodeoxyglucose and [18 F]-flutemetamol positron emission tomography magnetic resonances, and were classified according to CR. The metabolic pattern of 16 controls was compared to PD subjects. RESULTS: The PD subjects showed hypometabolism mainly in the bilateral posterior cortex. Superior-CR subjects (n = 22) exhibited better cognitive performance, increased amyloid burden, and higher metabolism in several right hemisphere areas compared to low-medium-CR subjects (n = 31). CONCLUSIONS: Higher CR in non-demented PD is associated with better cognitive performance, which might reduce vulnerability to the effect of ß-amyloid. Whether superior CR leads to protection against metabolic deterioration, and predominantly right hemisphere involvement, deserves further exploration.

Exploring Differences in Dietary Diversity and Micronutrient Adequacy between Costa Rican and Mexican Adolescents.

Diet diversity becomes especially relevant during adolescence to satisfy the adequate micronutrient intake. Diet diversity (DD) and micronutrient probability of adequacy (PA) were studied in 818 Costa Rican (CR) and 1202 Mexican (MX) adolescents aged 13-18 years. DD was compared using the Minimum Dietary Diversity (MDD) score. Receiver-operating characteristic (ROC) curves were employed to identify the optimal MDD for each sample from the respective countries. The mean MDD for the overall CR sample was 4.17 ± 1.43 points, and for the MX sample, the mean MDD was 4.68 ± 1.48 points. The proportion of adolescents with a DD was significantly higher in Costa Rica than in Mexico (66.5% vs. 55.6%; p < 0.0001). Also, DD was higher in rural Costa Rican adolescents, while no difference was found in the MX adolescents by area of residence. CR adolescents reported significantly higher PA than MX participants for 6 of the 11 micronutrients assessed. The calcium PA in MX adolescents was significantly higher than in the CR sample (MX: 0.84 vs. CR: 0.03; p < 0.0001), while low PA was obtained for iron in both countries (CR: 0.01 vs. MX: 0.07; p < 0.0001). In Costa Rica and Mexico, nutritional interventions and assessing the compliance of food-fortifying programs are needed to improve the PA of diverse micronutrients.

Unilateral focused ultrasound subthalamotomy in early Parkinson's disease: a pilot study.

BACKGROUND: Unilateral focused ultrasound subthalamotomy (FUS-STN) improves motor features of Parkinson's disease (PD) in moderately advanced patients. The less invasive nature of FUS makes its early application in PD feasible. We aim to assess the safety and efficacy of unilateral FUS-STN in patients with PD of less than 5 years from diagnosis (early PD). METHODS: Prospective, open-label study. Eligible patients with early PD had highly asymmetrical cardinal features. The primary outcome was safety, defined as treatment-related adverse events at 6 months. Secondary outcomes included efficacy, assessed as motor improvement in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), motor fluctuations, non-motor symptoms, daily living activities, quality of life, medication and patients' impression of change. RESULTS: Twelve patients with PD (median age 52.0 (IQR 49.8-55.3) years, median time from diagnosis 3.0 (2.1-3.9) years) underwent unilateral FUS-STN. Within 2 weeks after treatment, five patients developed dyskinesia on the treated side, all resolved after levodopa dose adjustment. One patient developed mild contralateral motor weakness which fully resolved in 4 weeks. One patient developed dystonic foot and another hand and foot dystonia. The latter impaired gait and became functionally disabling initially. Both cases were well controlled with botulinum toxin injections. The off-medication motor MDS-UPDRS score for the treated side improved at 12 months by 68.7% (from 14.5 to 4.0, p=0.002), and the total motor MDS-UPDRS improved by 49.0% (from 26.5 to 13.0, p=0.002). Eleven patients (92%) reported global improvement 12 months after treatment. CONCLUSION: Unilateral FUS-STN may be safe and effective to treat motor manifestations in patients with early PD. A larger confirmatory trial is warranted. TRIAL REGISTRATION NUMBER: NCT04692116.

Reducing dietary intake of added sugars could affect the nutritional adequacy of vitamin A in adolescents: the Costa Rica case.

BACKGROUND: In countries where sugar fortification with vitamin A is mandatory, strategies to reduce the prevalence of overweight/obesity in adolescents that involve lowering added sugar intake could lead to vitamin A inadequate intakes, since vitamin A-fortified sugar for home consumption contributes to a high proportion of this vitamin intake in the adolescent diet. METHODS: The study employed a hierarchical linear model to perform a mediation analysis on a cross-sectional sample of adolescents (13-18 years old) in the province of San José, Costa Rica. RESULTS: Lowering the total energy intake derived from added sugars to less than 10% significantly increases the prevalence of vitamin A inadequate intake in adolescents by 12.1% (from 29.6% to 41.7%). This is explained by the mediation model in which, the reduced adequacy of vitamin A intake is mediated by a reduction in total energy intake derived from added sugars fortified with vitamin A. CONCLUSIONS: The vitamin A fortification of sugar for household consumption should be reassessed according to the current epidemiological profile in Costa Rica to promote strategies that reduce the prevalence of overweight/obesity in adolescents by lowering the consumption of added sugars without affecting vitamin A intake.

A Landscape of Micronutrient Dietary Intake by 15- to 65-Years-Old Urban Population in 8 Latin American Countries: Results From the Latin American Study of Health and Nutrition.

BACKGROUND: Latin American countries have shifted from traditional diets rich in micronutrients to a Westernized diet rich in high energy-dense foods and low in micronutrients. OBJECTIVE: This study aimed to determine the prevalence of adequate micronutrient intakes in urban populations of 8 Latin American countries. METHOD: Micronutrient dietary intake data were collected from September 2014 to August 2015 from 9216 men and women aged 15.0 to 65.0 years living in urban populations of 8 Latin American countries. Dietary intake was collected using two 24-hour recalls on nonconsecutive days. Micronutrient adequacy of intake was calculated using the Estimated Average Requirement cut-off method. RESULTS: In general terms, the prevalence of inadequate intake of thiamine, riboflavin, niacin, folate, cobalamin, iron, phosphorus, copper, and selenium ranged from 0.4% to 9.9%. In contrast, the prevalence of inadequacy of pyridoxine, zinc, vitamin C, and vitamin A ranged from 15.7% to 51.5%. The nutrients with a critical prevalence of inadequacy were magnesium (80.5%), calcium (85.7%), and vitamin D (98.2%). The highest prevalence of inadequate intakes was observed in the low educational level, participants with overweight/obesity, in men, and varies according to socioeconomic status. CONCLUSIONS: There is an urgent need to define direct regional actions and strategies in Latin America aimed at improving micronutrient adequacy, either through staple food fortification programs, agronomic biofortification, or food policies that facilitate economic access to micronutrient-rich foods.

Plain language titleDescription of the Vitamin and Mineral Consumption Status in Urban Cities of Latin America: Results of the Latin American Health and Nutrition Study.Plain language summaryVitamins and minerals are essential for maintaining good health. However, traditional Latin American diets are changing to include foods that have a lot of sugar and fat but fewer vitamins and minerals. This study was designed to analyze the consumption of these nutrients in urban cities of 8 Latin American countries. We collected food consumption information from September 2014 to August 2015 from 9216 men and women between 15 and 65 years old using a method called 24-hour recall. To find out if participants were consuming the necessary daily amounts of vitamins and minerals, intakes were compared with the daily recommended amounts suggested by the Institutes of Medicine of the United States. We found that Latin American urban populations consume fewer vitamins and minerals than recommended. In some cases, few people do not consume the required amounts of vitamins and minerals, but in other cases, many do not. For example, few do not consume enough thiamine, riboflavin, niacin, folate, cobalamin, iron, phosphorus, copper, and selenium. However an intermediate number of people do not consume enough pyridoxine and zinc, a high number consume little vitamin C and vitamin A, and many people consume very little magnesium, calcium, and vitamin D. We found that the people who consume fewer vitamins and minerals are mostly males, overweight/obese, have lower education and varies according to their financial resources. A deficient intake of vitamins and minerals showed up in most age groups, from adolescence to adulthood. To improve vitamins and minerals intake, it is important that some foods that are frequently eaten are fortified or that the price of foods that are high in vitamins and minerals is lowered.

Brain hypometabolism in non-demented microtubule-associated protein tau H1 carriers with Parkinson's disease.

BACKGROUND AND PURPOSE: The microtubule-associated protein tau (MAPT) H1 homozygosity (H1/H1 haplotype) is a genetic risk factor for neurodegenerative diseases, such as Parkinson's disease (PD). MAPT H1 homozygosity has been associated with conversion to PD; however, results are conflicting since some studies did not find a strong influence. Cortical hypometabolism is associated with cognitive impairment in PD. In this study, we aimed to evaluate the metabolic pattern in nondemented PD patients MAPT H1/H1 carriers in comparison with MAPT H1/H2 haplotype. In addition, we evaluated domain-specific cognitive differences according to MAPT haplotype. METHODS: We compared a group of 26 H1/H1 and 20 H1/H2 carriers with late-onset PD. Participants underwent a comprehensive neuropsychological cognitive evaluation and a [18F]-Fluorodeoxyglucose PET-MR scan. RESULTS: MAPT H1/H1 carriers showed worse performance in the digit span forward test of attention compared to MAPT H1/H2 carriers. In the [18F]-Fluorodeoxyglucose PET comparisons, MAPT H1/H1 displayed hypometabolism in the frontal cortex, parahippocampal, and cingulate gyrus, as well as in the caudate and globus pallidus. CONCLUSION: PD patients MAPT H1/H1 carriers without dementia exhibit relative hypometabolism in several cortical areas as well as in the basal ganglia, and worse performance in attention than MAPT H1/H2 carriers. Longitudinal studies should assess if lower scores in attention and dysfunction in these areas are predictors of dementia in MAPT H1/H1 homozygotes.

High Rate of Inappropriate Antibiotics in Patients with Hematologic Malignancies and Pseudomonas aeruginosa Bacteremia following International Guideline Recommendations.

Optimal coverage of Pseudomonas aeruginosa is challenging in febrile neutropenic patients due to a progressive increase in antibiotic resistance worldwide. We aimed to detail current rates of resistance to antibiotics recommended by international guidelines for P. aeruginosa isolated from bloodstream infections (BSI) in patients with hematologic malignancies. Secondarily, we aimed to describe how many patients received inappropriate empirical antibiotic treatment (IEAT) and its impact on mortality. We conducted a retrospective, multicenter cohort study of the last 20 BSI episodes caused by P. aeruginosa in patients with hematologic malignancies from across 14 university hospitals in Spain. Of the 280 patients with hematologic malignancies and BSI caused by P. aeruginosa, 101 (36%) had strains resistant to at least one of the ß-lactam antibiotics recommended in international guidelines, namely, cefepime, piperacillin-tazobactam, and meropenem. Additionally, 21.1% and 11.4% of the strains met criteria for MDR and XDR P. aeruginosa, respectively. Even if international guidelines were followed in most cases, 47 (16.8%) patients received IEAT and 66 (23.6%) received inappropriate ß-lactam empirical antibiotic treatment. Thirty-day mortality was 27.1%. In the multivariate analysis, pulmonary source (OR 2.22, 95% CI 1.14 to 4.34) and IEAT (OR 2.67, 95% CI 1.37 to 5.23) were factors independently associated with increased mortality. We concluded that P. aeruginosa-causing BSI in patients with hematologic malignancies is commonly resistant to antibiotics recommended in international guidelines, which is associated with frequent IEAT and higher mortality. New therapeutic strategies are needed. IMPORTANCE Bloodstream infection (BSI) caused by P. aeruginosa is related with an elevated morbidity and mortality in neutropenic patients. For this reason, optimal antipseudomonal coverage has been the basis of all historical recommendations in the empirical treatment of febrile neutropenia. However, in recent years the emergence of multiple types of antibiotic resistances has posed a challenge in treating infections caused by this microorganism. In our study we postulated that P. aeruginosa-causing BSI in patients with hematologic malignancies is commonly resistant to antibiotics recommended in international guidelines. This observation is associated with frequent IEAT and increased mortality. Consequently, there is a need for a new therapeutic strategy.

Exploratory Analysis of Social Networks Linked to the Provision of Beverages in Costa Rican Schools.

Sugar-sweetened beverages (SSBs) are implicated in weight gain and adverse cardiometabolic heath. Social networks of stakeholders involved in providing potable water and sugar-sweetened beverages (SSBs) in high schools in Costa Rica were studied using social analysis network. In public and private schools, the interactions between the stakeholders in charge of providing beverages are fragmented and their role in preventing the availability of SSBs is weak. School canteen owners ultimately decide what beverages are available at school, which may cause students to choose beverages that increase the risk of overweight/obesity. It is therefore urgently necessary to improve the capacity for two-way interactions between the stakeholders to enhance their roles in the provision of beverages. Hence, it is essential to reinforce the stakeholders' leadership, and set up innovative ways to exert it in order to develop a shared vision of the types of drinks that should be available in the school environment.

BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging.

Intracerebral vector delivery in nonhuman primates has been a major challenge. We report successful blood-brain barrier opening and focal delivery of adeno-associated virus serotype 9 vectors into brain regions involved in Parkinson's disease using low-intensity focus ultrasound in adult macaque monkeys. Openings were well tolerated with generally no associated abnormal magnetic resonance imaging signals. Neuronal green fluorescent protein expression was observed specifically in regions with confirmed blood-brain barrier opening. Similar blood-brain barrier openings were safely demonstrated in three patients with Parkinson's disease. In these patients and in one monkey, blood-brain barrier opening was followed by 18F-Choline uptake in the putamen and midbrain regions based on positron emission tomography. This indicates focal and cellular binding of molecules that otherwise would not enter the brain parenchyma. The less-invasive nature of this methodology could facilitate focal viral vector delivery for gene therapy and might allow early and repeated interventions to treat neurodegenerative disorders.

Prospective Long-term Follow-up of Focused Ultrasound Unilateral Subthalamotomy for Parkinson Disease.

BACKGROUND AND OBJECTIVES: Unilateral magnetic resonance-guided focused ultrasound subthalamotomy (FUS-STN) has been shown to improve the cardinal motor features of Parkinson disease (PD). Whether this effect is sustained is not known. This study aims to report the long-term outcome of patients with PD treated with unilateral FUS-STN. METHODS: We conducted a prospective open-label study of patients with asymmetrical PD who underwent unilateral FUS-STN. All patients were evaluated up to 36 months after treatment. The primary outcome was the difference from baseline to 36 months after FUS-STN in the score of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor part (III) for the treated hemibody in the off-medication state. The safety outcome included all adverse events occurring during follow-up. Secondary outcomes were the change in the MDS-UPDRS III score on-medication; subscores of rigidity, bradykinesia, tremor, and axial features; total MDS-UPDRS III; and the MDS-UPDRS part IV. Functional disability and quality of life were assessed using the MDS-UPDRS II and the PDQ39, respectively. Patient impression of change and satisfaction with the treatment were self-assessed. The Wilcoxon signed-rank test with subsequent Bonferroni's correction was used for data analysis. RESULTS: Thirty-two patients with PD were evaluated at 36 months after treatment. The mean (±SD) age at baseline was 56.0 ± 10.1 years, with a mean disease duration of 6.8 ± 2.8 years. The MDS-UPDRS III score for the treated hemibody off-medication was improved by 52.3% from baseline to 3 years (score reduction from 19.0 ± 3.2 to 8.9 ± 3.3, 95% CI 8.7 to 11.6, p < 0.001), and all specific motor features were improved from baseline. No disabling or delayed adverse events were reported. The total MDS-UPDRS III off-medication score was 22.9% lower at 3 years than before treatment (36.8 ± 7.4 vs 27.4 ± 6.2, 95% CI 6.0 to 11.5, p < 0.001). The MDS-UPDRS II, IV, and PDQ39 scores and levodopa dose were equivalent to those at baseline. DISCUSSION: The benefit of unilateral FUS-STN on PD motor features is sustained in the long term. FUS-STN contributes to better clinical control over several years of evolution. NCT02912871/03454425. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence on the utility of focused ultrasound unilateral subthalamotomy in the treatment of people with Parkinson disease.

Standard deviations of MR signal intensities show a consistent trend during imaging follow-ups for glioblastoma patients when corrected for non-biological heterogeneity due to hardware and software variation.

INTRODUCTION: Glioblastoma multiforme (GBM) has a poor prognosis in spite of advanced MRI guided treatments today. Routine MRI using conventional T1 or advanced permeability based MRI of GBM often does not adequately represent changing tumor phases or overall survival. In this work, region of interest (ROI) based tissue MR standard deviation (SD) is demonstrated as an important MRI variable that could be a potential biomarker of GBM heterogeneity and radioresistance. MATERIALS AND METHODS: MRI characterization is often qualitative and lacks reproducibility. Using standardized MRI phantoms we have normalized retrospective records of 12 radioresistant GBM patients that underwent radiation therapy (RT) with concomitant and adjuvant temozolomide (TMZ) chemotherapy followed by serial MR imaging with gadolinium contrast. RESULTS AND DISCUSSION: We have identified key variables like hardware, software and protocol variation and have standardized those using test phantoms at five MR systems. We suggest GBM growth during the treatment period can be linked to normalized MRI signal and its fluctuations from session to session and from magnet to magnet by using an ROI derived standard deviation that corresponds to heterogeneity of the tumor MRI signal and changes in magnetic susceptibility. The time period observed in our patient group for peak standard deviations is approximately halfway through the tumor course and may correspond to a growth of more aggressive MES subtype of cells. To model the GBM heterogeneity we performed in vitro T1 weighted inversion recovery MRI experiments at 3 T for porous media of silicate particles in 1% aq solution of Gadavist and linked SD with particle size and local gadolinium volume within porous media. Such in vitro models mimic the increased SD in radioresistant GBM and as a novel contribution suggest that finer texture with high surface area might arise approximately halfway through the overall survival duration in GBM. CONCLUSION: Standard deviation as a measure of magnetic susceptibility may be collectively linked to the changes in texture, cell fractions (biological) and trapped contrast media (vascular as well as artifactual consequences) and should be evaluated as a potential biomarker of GBM aggressiveness than the overall MRI signal intensity from a GBM.

Use of a Water Filter at Home Reduces Sugary Drink Consumption among Parents and Infants/Toddlers in a Predominantly Hispanic Community: Results from the Water Up!@ Home Intervention Trial.

BACKGROUND: Water is recommended as an alternative for sugar-sweetened beverages (SSBs). Low-income, minority groups in the United States continue to exhibit high SSB and low water consumption, and are more likely to exceed 100% fruit juice recommendations. OBJECTIVE: To test the effects of a home-based intervention designed to replace SSBs with tap water and reduce excess juice consumption among parents and their infants/toddlers. DESIGN: Randomized controlled trial. PARTICIPANTS: Parents (n = 92) of infants/toddlers who participated in three Early Head Start home-visiting programs that serve predominantly Hispanic, low-income communities during 2019-2021. INTERVENTION: The 12-week intervention (Water Up!@Home) simultaneously addressed physical barriers to tap water consumption (via a water filter) and sociocultural barriers to replacing SSBs and juice with water (via a curriculum). Comparison group received a water filter only. We hypothesized that the intervention would lead to a reduction of 6 fl oz/d in SSB and juice consumption. MAIN OUTCOMES: Parent-reported self and infant/toddler SSBs, water (filtered, tap, or bottled), and 100% fruit juice consumption. STATISTICAL ANALYSES: Analysis of covariance to compare changes in consumption between experimental groups was performed. We also conducted t tests to assess changes within groups. RESULTS: Participants in both groups reported significant reductions in SSBs from baseline (parents: intervention [-11.2 fl oz/d; P < 0.01]; comparison [-8.0 fl oz/d; P < 0.01]; children: intervention [-1.50 fl oz/d; P = 0.03]; comparison [-1.56 fl oz/d; P = 0.02]), increased water consumption (parents in both groups [+5.6 fl oz/d]; children: intervention [+3.61 fl oz/d; P = 0.01], comparison [+2.24 fl oz/d; P = 0.05]), mostly from filtered tap water. Differences between groups were not statistically significant. Intervention participants reported significant reductions in 100% fruit juice vs comparison (parents: -3.6 fl oz/d vs -1.0 fl oz/d; P < 0.01; children: -0.73 fl oz/d vs +0.48 fl oz/d; P = .03). CONCLUSIONS: The intervention effectively reduced 100% fruit juice consumption. Water security should be examined as a contributor to SSB consumption in this population.

Association between Fathers' and Mothers' Parenting Styles and the Risk of Overweight/Obesity among Adolescents in San José Province, Costa Rica.

Parenting styles are a risk factor for adolescents overweight/obesity worldwide, but this association is not well understood in the context of Latin America. This study examines the association between the parenting styles of mothers and fathers and the risk of overweight/obesity among Costa Rican adolescents. Data are cross-sectional from a sample of adolescents (13-18 years old) enrolled in ten urban and eight rural schools (n = 18) in the province of San José, Costa Rica, in 2017. Hierarchical logistic regression analyses were performed to assess the likelihood of adolescents being overweight according to the mothers' and fathers' parenting styles. A significant association was found between the risk of adolescent overweight/obesity and the paternal authoritarian style only in rural areas (B = 0.622, SE = 0.317, Wald = 3.864, ExpB = 1.863, p = 0.04), and between said risk and the paternal permissive style only in male adolescents (B = 0.901, SE = 0.435, Wald = 4.286, ExpB = 2.461, p = 0.038). For maternal parenting styles, no associations reached significant levels once logistic regression models were adjusted for the fathers' parenting styles. These findings underscore the importance of further studying the role of fathers' paternal parenting styles on Latin American adolescent weight outcomes. Expanding our understanding of the parenting styles of fathers has important implications for the design and implementation of culturally- and gender-appropriate family interventions.

Hard-sphere jamming through the lens of linear optimization.

The jamming transition is ubiquitous. It is present in granular matter, foams, colloids, structural glasses, and many other systems. Yet, it defines a critical point whose properties still need to be fully understood. Recently, a major breakthrough came about when the replica formalism was extended to build a mean-field theory that provides an exact description of the jamming transition of spherical particles in the infinite-dimensional limit. While such theory explains the jamming critical behavior of both soft and hard spheres, investigating the transition in finite-dimensional systems poses very difficult and different problems, in particular from the numerical point of view. Soft particles are modeled by continuous potentials; thus, their jamming point can be reached through efficient energy minimization algorithms. In contrast, the latter methods are inapplicable to hard-sphere (HS) systems since the interaction energy among the particles is always zero by construction. To overcome these difficulties, here we recast the jamming of hard spheres as a constrained optimization problem and introduce the CALiPPSO algorithm, capable of readily producing jammed HS packings without including any effective potential. This algorithm brings a HS configuration of arbitrary dimensions to its jamming point by solving a chain of linear optimization problems. We show that there is a strict correspondence between the force balance conditions of jammed packings and the properties of the optimal solutions of CALiPPSO, whence we prove analytically that our packings are always isostatic and in mechanical equilibrium. Furthermore, using extensive numerical simulations, we show that our algorithm is able to probe the complex structure of the free-energy landscape, finding qualitative agreement with mean-field predictions. We also characterize the algorithmic complexity of CALiPPSO and provide an open-source implementation of it.

Role of Residence Area on Diet Diversity and Micronutrient Intake Adequacy in Urban and Rural Costa Rican Adolescents.

Dietary diversity might be essential to meet nutritional demands during adolescence. Diet diversity among 818 urban and rural Costa Rican adolescents aged 13−18 years was studied using the Minimum Dietary Diversity Score for Women. The Nutrient Adequacy Ratio (NAR) was calculated for 11 nutrients to estimate the nutrient adequacy of the diet. A NAR < 0.7 was considered inadequate for micronutrient intake. The optimal Diet Diversity Score (DDS) cut-off point for this study was 4, established using receiver-operating characteristic curves. The mean DDS for the overall sample was 4.17 ± 1.43, although DDS was significantly higher in adolescents from rural vs. urban areas (4.33 ± 1.43 vs. 4.00 ± 1.42, p-value = 0.001). The odds of having a diverse diet were 62% higher in rural vs. urban adolescents. Overall, 80−95% of adolescents reached a NAR ≥ 0.70 for 8 nutrients except for calcium, zinc, and vitamin A. The residence area plays a key role in adolescent dietary diversity. Although overall DDS was low, foods that make up the rural adolescent diet were nutritionally dense enough to satisfy the EAR for most micronutrients. A high DDS is not necessarily required for the diet to meet most micronutrient demands in adolescence. Improved dietary adequacy of vitamin A, zinc, and calcium is required due to the importance of these micronutrients in maintaining optimal health.

How providing a low-cost water filter pitcher led Latino parents to reduce sugar-sweetened beverages and increase their water intake: explanatory qualitative results from the Water Up!@Home intervention trial.

OBJECTIVE: This study sought to explain results of the Water Up!@Home randomised controlled trial where low-income parents were randomised to receive an educational intervention +a low-cost water filter pitcher or only the filter. Parents in both groups had reported statistically significant reductions in sugar-sweetened beverages (SSB) and increases in water intake post-intervention. DESIGN: Qualitative explanatory in-depth interviews analysed thematically and deductively. SETTING: Washington, DC metropolitan area, USA. PARTICIPANTS: Low-income Latino parents of infants/toddlers who had participated in the Water Up! @Home randomised controlled trial. RESULTS: The filter-stimulated water consumption in both groups by (1) increasing parents' perception of water safety; (2) acting as a cue to action to drink water; (3) improving the flavour of water (which was linked to perceptions of safety) and (4) increasing the perception that this option was more economical than purchasing bottled water. Safe and palatable drinking water was more accessible and freely available in their homes; participants felt they did not need to ration their water consumption as before. Only intervention participants were able to describe a reduction in SSB intake and described strategies, skills and knowledge gained to reduce SSB intake. Among the comparison group, there was no thematic consensus about changes in SSB or any strategies or skills to reduce SSB intake. CONCLUSIONS: A low-cost water filter facilitated water consumption, which actively (or passively for comparison group) displaced SSB consumption. The findings have implications for understanding and addressing the role of water security on SSB consumption.