History and Science behind the Eating Assessment Tool-10 (Eat-10): Lessons Learned.

INTRODUCTION: Oropharyngeal dysphagia (OD) is an underdiagnosed medical condition with a high prevalence in populations such as patients with frailty, neurological disease, or head and neck pathology. Potential barriers to its diagnosis include lack of (or low) awareness of the existence and severity of the condition, the hidden nature of the condition within the 'normal ageing' process, clinical limitations, and socioeconomic reasons. Consequently, an effective treatment is not systematically offered in a timely manner, and complications, such as dehydration and respiratory infections or aspiration pneumonia, can arise. To overcome this issue, the early use of screening questionnaires to identify people at risk of swallowing disorders represents the cornerstone of preventive medicine. Several screening tools have been created but few are widely used in clinical practice. The Eating Assessment Tool-10 (EAT-10) was developed as a quick, easy-to-understand, and self-administered screening tool for OD. METHODS: A literature review was conducted in five databases with no restrictions on the language, date of publication, or design of the study to identify aspects of the validation, applicability, and usefulness of EAT-10. RESULTS AND CONCLUSIONS: Transcultural adaptation and translation studies, as well as studies involving various types of patients with dysphagia in different settings have shown the validity and reliability of EAT-10 in relation to the gold standard and other validation tools. The use of this standardised screening tool could be used as a primary screening instrument of dysphagia in routine clinical practice across a wide range of diseases and settings and thereby increase the likelihood of early diagnosis and management of a condition that lead to serious complications and impaired quality of life.

Extended p_{3/2} Neutron Orbital and the N=32 Shell Closure in

The one-neutron knockout from ^{52}Ca in inverse kinematics onto a proton target was performed at ∼230 MeV/nucleon combined with prompt γ spectroscopy. Exclusive quasifree scattering cross sections to bound states in ^{51}Ca and the momentum distributions corresponding to the removal of 1f_{7/2} and 2p_{3/2} neutrons were measured. The cross sections, interpreted within the distorted-wave impulse approximation reaction framework, are consistent with a shell closure at the neutron number N=32, found as strong as at N=28 and N=34 in Ca isotopes from the same observables. The analysis of the momentum distributions leads to a difference of the root-mean-square radii of the neutron 1f_{7/2} and 2p_{3/2} orbitals of 0.61(23) fm, in agreement with the modified-shell-model prediction of 0.7 fm suggesting that the large root-mean-square radius of the 2p_{3/2} orbital in neutron-rich Ca isotopes is responsible for the unexpected linear increase of the charge radius with the neutron number.

Pairing Forces Govern Population of Doubly Magic

Direct proton-knockout reactions of ^{55}Sc at ∼220 MeV/nucleon were studied at the RIKEN Radioactive Isotope Beam Factory. Populated states of ^{54}Ca were investigated through γ-ray and invariant-mass spectroscopy. Level energies were calculated from the nuclear shell model employing a phenomenological internucleon interaction. Theoretical cross sections to states were calculated from distorted-wave impulse approximation estimates multiplied by the shell model spectroscopic factors, which describe the wave function overlap of the ^{55}Sc ground state with states in ^{54}Ca. Despite the calculations showing a significant amplitude of excited neutron configurations in the ground-state of ^{55}Sc, valence proton removals populated predominantly the ground state of ^{54}Ca. This counterintuitive result is attributed to pairing effects leading to a dominance of the ground-state spectroscopic factor. Owing to the ubiquity of the pairing interaction, this argument should be generally applicable to direct knockout reactions from odd-even to even-even nuclei.

The KSHV ORF20 Protein Interacts with the Viral Processivity Factor ORF59 and Promotes Viral Reactivation.

Upon Kaposi's Sarcoma-associated herpesvirus (KSHV) lytic reactivation, rapid and widespread amplification of viral DNA (vDNA) triggers significant nuclear reorganization. As part of this striking shift in nuclear architecture, viral replication compartments are formed as sites of lytic vDNA production along with remarkable spatial remodeling and the relocalization of cellular and viral proteins. These viral replication compartments house several lytic gene products that coordinate viral gene expression, vDNA replication, and nucleocapsid assembly. The viral proteins and mechanisms that regulate this overhaul of the nuclear landscape during KSHV replication remain largely unknown. KSHV's ORF20 is a widely conserved lytic gene among all herpesviruses, suggesting it may have a fundamental contribution to the progression of herpesviral infection. Here, we utilized a promiscuous biotin ligase proximity labeling method to identify the proximal interactome of ORF20, which includes several replication-associated viral proteins, one of which is ORF59, the KSHV DNA processivity factor. Using coimmunoprecipitation and immunofluorescence assays, we confirmed the interaction between ORF20 and ORF59 and tracked the localization of both proteins to KSHV replication compartments. To further characterize the function of ORF20, we generated an ORF20-deficient KSHV and compared its replicative fitness to that of wild-type virus. Virion production was significantly diminished in the ORF20-deficient virus as observed by supernatant transfer assays. Additionally, we tied this defect in viable virion formation to a reduction in viral late gene expression. Lastly, we observed an overall reduction in vDNA replication in the ORF20-deficient virus, implying a key role for ORF20 in the regulation of lytic replication. Taken together, these results capture the essential role of KSHV ORF20 in progressing viral lytic infection by regulating vDNA replication alongside other crucial lytic proteins within KSHV replication compartments. IMPORTANCE Kaposi's Sarcoma-associated herpesvirus (KSHV) is a herpesvirus that induces lifelong infection, and as such, its lytic replication is carefully controlled to allow for efficient dissemination from its long-term reservoir and for the spread of the virus to new hosts. Viral DNA replication involves many host and viral proteins, coordinating both in time and space to successfully progress through the viral life cycle. Yet, this process is still not fully understood. We investigated the role of the poorly characterized viral protein ORF20, and through proximity labeling, we found that ORF20 interacts with ORF59 in replication compartments and affects DNA replication and subsequent steps of the late viral life cycle. Collectively, these results provide insights into the possible contribution of ORF20 to the complex lytic DNA replication process and suggest that this highly conserved protein may be an important modulator of this key viral mechanism.

Quasifree Neutron Knockout from

Exclusive cross sections and momentum distributions have been measured for quasifree one-neutron knockout reactions from a ^{54}Ca beam striking on a liquid hydrogen target at ∼200 MeV/u. A significantly larger cross section to the p_{3/2} state compared to the f_{5/2} state observed in the excitation of ^{53}Ca provides direct evidence for the nature of the N=34 shell closure. This finding corroborates the arising of a new shell closure in neutron-rich calcium isotopes. The distorted-wave impulse approximation reaction formalism with shell model calculations using the effective GXPF1Bs interaction and ab initio calculations concur our experimental findings. Obtained transverse and parallel momentum distributions demonstrate the sensitivity of quasifree one-neutron knockout in inverse kinematics on a thick liquid hydrogen target with the reaction vertex reconstructed to final state spin-parity assignments.

How Robust is the N=34 Subshell Closure? First Spectroscopy of

The first γ-ray spectroscopy of ^{52}Ar, with the neutron number N=34, was measured using the ^{53}K(p,2p) one-proton removal reaction at ∼210 MeV/u at the RIBF facility. The 2_{1}^{+} excitation energy is found at 1656(18) keV, the highest among the Ar isotopes with N>20. This result is the first experimental signature of the persistence of the N=34 subshell closure beyond ^{54}Ca, i.e., below the magic proton number Z=20. Shell-model calculations with phenomenological and chiral-effective-field-theory interactions both reproduce the measured 2_{1}^{+} systematics of neutron-rich Ar isotopes, and support a N=34 subshell closure in ^{52}Ar.

Reliable and developmentally appropriate study end points are needed to achieve drug development for treatment of pediatric pulmonary arterial hypertension.

OBJECTIVE: To identify suitable end points and surrogates for pediatric pulmonary arterial hypertension (PAH) as the lack of developmentally appropriate end point and clinical trials contribute to the unmet medical need. STUDY DESIGN: Reviewed the efficacy end points and surrogates for all trials (1995 to 2013) that were submitted to the Food and Drug Administration (FDA) to support the approval of PAH therapy and conducted literature search. RESULTS: An increase in the 6 min walking distance (6MWD) was used as a primary end point in 8/9 adult PAH trials. This end point is not suitable for infants and young children because of performance limitations and lack of control data. One adult PAH trial used time to the first morbidity or mortality event as a primary end point, which could potentially be used in pediatric PAH trials. In the sildenafil pediatric PAH trial, the change in pulmonary vascular resistance index or mean pulmonary artery pressure was used as a surrogate for the 6MWD to assess exercise capacity. However, two deaths and three severe adverse events during the catheterizations made this an unacceptably high-risk surrogate. The INOmax persistent pulmonary hypertension of the newborn trial used a reduction in initiation of extracorporeal membrane oxygenation treatment as a primary end point, which is not feasible for other pediatric PAH trials. A Literature review revealed none of the existing noninvasive markers are fully validated as surrogates to assess PAH efficacy and long-term safety. CONCLUSIONS: For pediatric PAH trials, clinical end points are acceptable, and novel validated surrogates would be helpful. FDA seeks collaboration with academia, industry and parents to develop other suitable and possibly more efficient efficacy end points to facilitate pediatric PAH drug development.

On the importance of being structured: instantaneous coalescence rates and human evolution--lessons for ancestral population size inference?

Most species are structured and influenced by processes that either increased or reduced gene flow between populations. However, most population genetic inference methods assume panmixia and reconstruct a history characterized by population size changes. This is potentially problematic as population structure can generate spurious signals of population size change through time. Moreover, when the model assumed for demographic inference is misspecified, genomic data will likely increase the precision of misleading if not meaningless parameters. For instance, if data were generated under an n-island model (characterized by the number of islands and migrants exchanged) inference based on a model of population size change would produce precise estimates of a bottleneck that would be meaningless. In addition, archaeological or climatic events around the bottleneck's timing might provide a reasonable but potentially misleading scenario. In a context of model uncertainty (panmixia versus structure) genomic data may thus not necessarily lead to improved statistical inference. We consider two haploid genomes and develop a theory that explains why any demographic model with structure will necessarily be interpreted as a series of changes in population size by inference methods ignoring structure. We formalize a parameter, the inverse instantaneous coalescence rate, and show that it is equivalent to a population size only in panmictic models, and is mostly misleading for structured models. We argue that this issue affects all population genetics methods ignoring population structure which may thus infer population size changes that never took place. We apply our approach to human genomic data.

Stroop Color-Word Interference Test: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data on the Stroop Test across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the Stroop Test, as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained 14-36% of the variance in Stroop Word scores, 12-41% of the variance in the Stoop Color, 14-36% of the variance in the Stroop Word-Color scores, and 4-15% of variance in Stroop Interference scores. Although t-tests showed significant differences between men and women on the Stroop test, none of the countries had an effect size larger than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America to create norms for the Stoop Test in a Spanish-Speaking sample. This study will therefore have important implications for the future of neuropsychology research and practice throughout the region.

Standard form of the Boston Naming Test: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data on the Boston Naming Test (BNT) across 10 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,779 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the BNT as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained between 3-32% of the variance in BNT scores. Although t-tests showed significant differences between men and women for Mexico, Argentina, Chile, Cuba, Guatemala, and Bolivia on the BNT, none of the six countries had an effect size larger than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America to generate norms for the BNT; this study will have substantial repercussions for the practice of neuropsychology throughout the global region.

Symbol Digit Modalities Test: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data on the Symbol Digit Modalities Test (SDMT) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the SDMT as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained 29-56% of the variance in SDMT scores. Although there were gender differences on the SDMT in Mexico, Honduras, Paraguay, and Guatemala, none of the four countries had an effect size greater than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America to create norms for the SDMT; this study will have an impact on the future practice of neuropsychology throughout the global region.

Rey-Osterrieth Complex Figure - copy and immediate recall: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data on the Rey-Osterrieth Complex Figure Test (ROCF) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the ROCF as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained 7-34% of the variance in ROCF copy scores and 21-41% of the variance in immediate recall scores. Although t-tests showed significant differences between men and women on ROCF copy and immediate recall scores, none of the countries had an effect size larger than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: The present study is the first to create norms for the ROCF in Latin America. As a result, this study will have important implications for the formation and practice of neuropsychology in this region.

Verbal fluency tests: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data for the Verbal Fluency Tests across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the Verbal Fluency Test as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models for the letter F explained 8-30% of the variance, 7-32% for letter A, 8-32% for the letter S, and 16-43% for the animal category in Verbal Fluency Test scores. Although t-tests showed significant differences between men and women on the Verbal Fluency Test, they did not have an effect size larger than 0.3. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in Latin America aiming to create norms for the Verbal Fluency Test; this study will have important outcomes for the future of neuropsychology in the region.

Trail Making Test: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data on the Trail Making Test (TMT) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Mexico, Argentina, Peru, Paraguay, Honduras, Chile, Cuba, Puerto Rico, Guatemala, El Salvador, and Bolivia. Each subject was administered the TMT as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models for the TMT-A explained 23- 50% of the variance, and the final multiple linear models for the TMT-B explained 22- 49% of the variance. Although there were gender differences on the TMT in Mexico, Peru, Paraguay, and Honduras, only Honduras had an effect size greater than 0.3. As a result, gender-adjusted norms were generated for the Trail Making Test-A, but not B, in this country. CONCLUSIONS: The present study is the first to create norms for the TMT in Latin America. As a result, this study will have important implications for the practice of neuropsychology in the future.

Modified Wisconsin Card Sorting Test (M-WCST): Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data on the Modified Card Sorting Test (M-WCST) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico. Each subject was administered the M-WCST as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained between 2-33% of the variance in M-WCST scores. Although t-tests showed significant differences between men and women from seven different countries on the M-WCST, the effect sizes were small. As a result, gender-adjusted norms were not generated. CONCLUSIONS: This is the first normative multicenter study conducted in in Latin America aiming to create norms for the M-WCST; this study will have important implications for the future of neuropsychology in the region.

Hopkins Verbal Learning Test- Revised: Normative data for the Latin American Spanish speaking adult population.

OBJECTIVE: To generate normative data on the Hopkins Verbal Learning Test- Revised (HVLT-R) across 11 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 3,977 healthy adults who were recruited from Argentina, Bolivia, Chile, Cuba, El Salvador, Guatemala, Honduras, Mexico, Paraguay, Peru, and, Puerto Rico. Each subject was administered the HVLT-R as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: The final multiple linear regression models explained 17- 45% of the variance in HVLT-R scores. Although t-tests showed significant differences between men and women in Guatemala on the HVLT-R, it was a small effect size. As a result, gender-adjusted norms were not generated. CONCLUSIONS: The results from this study will have a substantial impact on the practice of neuropsychology in Latin America, as this is the first normative multicenter study to develop norms for the HVLT-R in this region.

Test of Memory Malingering (TOMM): Normative data for the Latin American Spanish speaking adult population.

BACKGROUND: The Test of Memory Malingering (TOMM) is an instrument used to assess purposeful embellishment or fabrication of memory difficulties for personal gain. Although the TOMM can be use in non-English speaking cultures, it has not been validated in Spanish-speaking Central and South American contexts. OBJECTIVE: To generate normative data on TOMM across 7 countries in Latin America, with country-specific adjustments for gender, age, and education, where appropriate. METHOD: The sample consisted of 2,266 healthy adults who were recruited from Argentina, Bolivia, Chile, Mexico, Paraguay, Peru, and Puerto Rico. Each subject was administered the TOMM as part of a larger neuropsychological battery. A standardized five-step statistical procedure was used to generate the norms. RESULTS: t-tests did not show significant differences in TOMM performance between men and women in any countries of the TOMM Trial 1 or 2. As a result, gender-adjusted norms were not generated. CONCLUSIONS: The results from this study will have a large impact on the practice of neuropsychology in Latin America, as this is the first normative multicenter study to create norms for the TOMM in this global region.

Infant formula and neurocognitive outcomes: impact of study end-point selection.

OBJECTIVES: Assessing validity and reliability of end points used in docosahexanoic and arachidonic acids (DHA and ARA) infant formula supplementation trials as an example for addressing the impact of end-point selection and critical need for well-defined, reliable and validated clinical outcome assessments for neurocognitive assessment in neonates and infants. STUDY DESIGN: We searched eight electronic databases and reviewed all randomized, controlled human trials using DHA/ARA supplements with neurodevelopment clinical outcomes. We systematically evaluated the validity and reliability of end-point measures based on the criteria for studying nutritional additives recommended by the Institute of Medicine, criteria described in the Food and Drug Administration guidance for clinical outcome assessment, development and literature review. RESULTS: We identified 29 articles that met the selection criteria. The end points that were used for neurodevelopment measures in 23 out of 29 original short-term studies included the Bayley Scale of Infant Development (BSID)-I and -II (n=12), Brunet-Lezine test (n=2), videotape infant's movements (n=1), record time to milestones including sitting, crawling, standing and walking (n=1), problem-solving test (n=2), brainstem auditory-evoked potential (n=1), Touwen examination (n=1), Fagan test of infant intelligence (n=2) and visual habituation protocol (n=1). None of these end points have a long-term predictive property for neurocognitive assessment. Compared with standard infant formula, the beneficial effects of DHA/ARA supplementation on neurodevelopment were reported in 2 out of 12 studies using BSID vs 8 out of 11 studies using other end-point measures. In addition, 6 out of 29 long-term follow-up studies used the end points including Stanford-Binet IQ test (n=1), Wechsler Preschool and Primary Scale of Intelligence (n=4) and Bracken Basic Concept Scale (n=1), which are generally scales of intellectual ability and typically do not change substantively in the short term. None of these long-term follow-up studies demonstrated beneficial effects of DHA/ARA supplementation on neurodevelopment. CONCLUSION: The choice of end-point measures affects the outcomes of DHA/ARA-supplemented infant formula trials. Available data are currently inadequate to conclude that DHA/ARA supplementation has a clinically meaningful beneficial effect upon neurological development. Although BSID is validated to assess early developmental delays, it is not designed to predict long-term neurocognitive outcome. A well-defined, valid and reliable clinical outcome assessment that measures neurocognitive function in neonates and infants is essential to provide the scientific evidence required for future clinical trials.

El retorno del nevus / Nevus returns

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