Is There an Adequate Therapeutic Approach to Thyroid Pathology in Patients with Down Syndrome?

Thyroid dysfunction stands as the most prevalent endocrine disorder in individuals with Down syndrome, particularly showcasing both clinical and subclinical hypothyroidism. TSH and FT4 blood values serve as common diagnostic and treatment adjustment markers. In Down syndrome (DS), hormone values may deviate from those observed in the general population, which may lead to overdiagnosis and consequent iatrogenesis of subclinical hypothyroidism. The objective of this study was to analyze the appropriateness of the replacement therapeutic approach by identifying the TSH and FT4 values that can be considered normal in these patients. METHODS: A cross-sectional study was conducted in 503 subjects with DS of both sexes and without age limit drawn from the Health Program for individuals with DS in Valencia (Spain) from February 1993 to November 2021. The exclusion criteria included hyperthyroidism, nodules, tumors, or individuals under treatment with drugs influencing iodine metabolism. The normality of data distribution was assessed using the Shapiro-Wilk test. Outliers were detected using the Reed's criterion. Hormone values were estimated using quantile regression models for the 2.5th and 97.5th percentiles. RESULTS: The normal values identified were 0.88-11.25 mIU/L for TSH and 0.71-1.63 ng/dL for FT4. The Wald test indicated no significant differences in the reference intervals based on age or sex. CONCLUSION: The establishment of these values, which, in people with DS, can be considered unique, is of great importance, allowing a watchful waiting attitude to be maintained before starting replacement therapy that is unnecessarily or adjusting medication in diagnosed cases.

Neo-functionalization in Saccharomyces cerevisiae: a novel Nrg1-Rtg3 chimeric transcriptional modulator is essential to maintain mitochondrial DNA integrity.

In Saccharomyces cerevisiae, the transcriptional repressor Nrg1 (Negative Regulator of Glucose-repressed genes) and the ß-Zip transcription factor Rtg3 (ReTroGrade regulation) mediate glucose repression and signalling from the mitochondria to the nucleus, respectively. Here, we show a novel function of these two proteins, in which alanine promotes the formation of a chimeric Nrg1/Rtg3 regulator that represses the ALT2 gene (encoding an alanine transaminase paralog of unknown function). An NRG1/NRG2 paralogous pair, resulting from a post-wide genome small-scale duplication event, is present in the Saccharomyces genus. Neo-functionalization of only one paralog resulted in the ability of Nrg1 to interact with Rtg3. Both nrg1Δ and rtg3Δ single mutant strains were unable to use ethanol and showed a typical petite (small) phenotype on glucose. Neither of the wild-type genes complemented the petite phenotype, suggesting irreversible mitochondrial DNA damage in these mutants. Neither nrg1Δ nor rtg3Δ mutant strains expressed genes encoded by any of the five polycistronic units transcribed from mitochondrial DNA in S. cerevisiae. This, and the direct measurement of the mitochondrial DNA gene complement, confirmed that irreversible damage of the mitochondrial DNA occurred in both mutant strains, which is consistent with the essential role of the chimeric Nrg1/Rtg3 regulator in mitochondrial DNA maintenance.

Soil versus atmospheric drought: A test case of plant functional trait responses.

Climate change alters mean global surface temperatures, precipitation regimes, and atmospheric moisture. Resultant drought affects the composition and diversity of terrestrial ecosystems worldwide. To date, there have been no assessments of the combined impacts of reduced precipitation and atmospheric drying on functional trait distributions of any species in an outdoor experiment. Here, we examined whether soil and atmospheric drought affected the functional traits of a focal grass species (Poa secunda) growing in monoculture and eight-species grass communities in outdoor mesocosms. We focused on specific leaf area (SLA), leaf area, stomatal density, root:shoot ratio, and fine root:coarse root ratio responses. Leaf area and overall growth were reduced with soil drying. Root:shoot ratio only increased for P. secunda growing in monoculture under combined atmospheric and soil drought. Plant energy allocation strategy (measured using principal components) differed when P. secunda was grown in combined soil and atmospheric drought conditions compared with soil drought alone. Given a lack of outdoor manipulations of this kind, our results emphasize the importance of atmospheric drying on functional trait responses more broadly. We suggest that drought methods focused purely on soil water inputs may be imprecisely predicting drought effects on other terrestrial organisms as well (other plants, arthropods, and higher trophic levels).

Ecology of Yellow Dwarf Viruses in Crops and Grasslands: Interactions in the Context of Climate Change.

Our understanding of the ecological interactions between plant viruses, their insect vectors, and their host plants has increased rapidly over the past decade. The suite of viruses known collectively as the yellow dwarf viruses infect an extensive range of cultivated and noncultivated grasses worldwide and is one of the best-studied plant virus systems. The yellow dwarf viruses are ubiquitous in cereal crops, where they can significantly limit yields, and there is growing recognition that they are also ubiquitous in grassland ecosystems, where they can influence community dynamics. Here, we discuss recent research that has explored (a) the extent and impact of yellow dwarf viruses in a diversity of plant communities, (b) the role of vector behavior in virus transmission, and (c) the prospects for impacts of climate change-including rising temperatures, drought, and elevated CO2-on the epidemiology of yellow dwarf viruses.

Occupational Health Physiotherapy (OHP) Practice: A Comparison between Japan and Australia.

OBJECTIVE: This study aimed to adapt a pre-existing cross-country comparison (CCC) model to Occupational Health Physiotherapy (OHP) practice as a basis for locating and examining contextual factors that may influence OHP practice in Japan and Australia. METHOD: A secondary analysis was conducted of existing publicly-available data on OHP and related influential factors, following the five components of the CCC model: work-related legislation; labor market characteristics; culture; physiotherapy practice norms; and organization of OHP practice. RESULTS: Legislation in both countries promotes safe work and rehabilitation of work injured/ill workers. 2019 unemployment was lower in Japan with higher employment protection than Australia. Both countries have an ageing workforce and rising retirement age. Cultural differences relate to higher long-term orientation and uncertainty avoidance in Japan. Australia has higher individualism and physiotherapists are autonomous practitioners with direct access, which differs from Japan. Both countries have a national OHP subgroup, to date only Australia has OHP professional practice standards. DISCUSSION: This study is the first to compare OHP practice in Japan and Australia. Contextual similarities and differences observed may underpin OHP practitioner role and its enhancement in work-related musculoskeletal disorder prevention and management strategies, the return-to-work process, and development of this physiotherapy discipline nationally. CONCLUSION: Adapting the CCC model to OHP practice enabled a structured exploration of resources and data, from which to extract and compare contextual factors that may shape OHP practice in Japan and Australia. This in turn may provide a useful springboard for further discussion about OHP practice internationally.

Soldier Load Carriage, Injuries, Rehabilitation and Physical Conditioning: An International Approach.

Soldiers are often required to carry heavy loads that can exceed 45 kg. The physiological costs and biomechanical responses to these loads, whilst varying with the contexts in which they are carried, have led to soldier injuries. These injuries can range from musculoskeletal injuries (e.g., joint/ligamentous injuries and stress fractures) to neurological injuries (e.g., paresthesias), and impact on both the soldier and the army in which they serve. Following treatment to facilitate initial recovery from injuries, soldiers must be progressively reconditioned for load carriage. Optimal conditioning and reconditioning practices include load carriage sessions with a frequency of one session every 10-14 days in conjunction with a program of both resistance and aerobic training. Speed of march and grade and type of terrain covered are factors that can be adjusted to manipulate load carriage intensity, limiting the need to adjust load weight alone. Factors external to the load carriage program, such as other military duties, can also impart physical loading and must be considered as part of any load carriage conditioning/reconditioning program.

Different contribution of conserved amino acids to the global properties of triosephosphate isomerases.

It is generally assumed that the amino acids that exist in all homologous enzymes correspond to residues that participate in catalysis, or that are essential for folding and stability. Although this holds for catalytic residues, the function of conserved noncatalytic residues is not clear. It is not known if such residues are of equal importance and have the same role in different homologous enzymes. In humans, the E104D mutation in triosephosphate isomerase (TIM) is the most frequent mutation in the autosomal diseases named "TPI deficiencies." We explored if the E104D mutation has the same impact in TIMs from four different organisms (Homo sapiens, Giardia lamblia, Trypanosoma cruzi, and T. brucei). The catalytic properties were not significantly affected by the mutation, but it affected the rate and extent of formation of active dimers from unfolded monomers differently. Scanning calorimetry experiments indicated that the mutation was in all cases destabilizing, but the mutation effect on rates of irreversible denaturation and transition-state energetics were drastically dependent on the TIM background. For instance, the E104D mutation produce changes in activation energy ranging from 430 kJ mol(-1) in HsTIM to -78 kJ mol(-1) in TcTIM. Thus, in TIM the role of a conserved noncatalytic residue is drastically dependent on its molecular background. Accordingly, it would seem that because each protein has a particular sequence, and a distinctive set of amino acid interactions, it should be regarded as a unique entity that has evolved for function and stability in the organisms to which it belongs.

Dilatación no neumática de anastomosis después de derivación o bypass gástrico, revisión de 23 casos / Non pneumatic dilatation of anastomosis following gastric bypass, review of 23 cases

Antecedentes. La derivación gástrica por laparoscopia en Y de Roux es uno de los procedimientos más comúnmente practicados para el manejo de la obesidad mórbida. Este procedimiento requiere de una pequeña anastomosis gastro-yeyuno que, en ocasiones, puede causar estenosis. Este estudio pretende evaluar la seguridad y eficacia del manejo de la estenosis de la anastomosis gastro-yeyuno utilizando dilatadores de Savary-Gilliard guiados por endoscopia. Métodos. Setecientos ocho pacientes se sometieron a derivación gástrica por laparoscopia en Y de Roux. La edad promedio fue de 41 años, y la media de su índice de masa corporal fue 43 kg/m². A los pacientes con sospecha de estenosis de la anastomosis gastro-yeyuno, se les practicó endoscopia de vías digestivas altas. Aquellos que presentaron estenosis se manejaron endoscópicamente con dilatadores de Savary-Gilliard. Resultados. La estenosis de la anastomosis gastro-yeyuno fue confirmada en 23 pacientes (3,24 %). Se practicaron 36 dilataciones en estos pacientes, resultando en una media de 1,5 dilataciones por paciente. Fue necesario hacer una dilatación para 20 pacientes (87 %), tres dilataciones para uno (4 %), y cuatro dilataciones o más para dos (9 %). La media de tiempo entre la cirugía de derivación gástrica por laparoscopia en Y de Roux y la dilatación de la estenosis de la anastomosis gastro-yeyuno, fue de 10 semanas. Todas las dilataciones se hicieron de manera ambulatoria. Conclusión. El manejo y tratamiento de la estenosis de la anastomosis gastro-yeyuno luego de la derivación gástrica por laparoscopia en Y de Roux puede hacerse de manera ambulatoria, utilizando dilatadores de Savary-Gilliard, con resultados efectivos y seguros.

Background: Laparoscopic Roux en -Y Gastric Bypass (LRYGB) is one of the most commonly performed procedures for the management of morbid obesity. The success of this procedure requires the creation of a small gastrojejunostomy, which sometimes can become stenotic. The treatment of choice for this complication is endoscopic balloon dilatation. This study aims to evaluate the safety and effectiveness of the management of gastrojejunal anastomotic stricture (GJAS) using Savary-Gilliard dilators guided by endoscopy. Methods: 708 patients underwent LRYGB. The average age was 41 years, and mean bodymass index was 43 kg/m². Patients with symptoms suggesting stenosis of the anastomosis underwent upper gastrointestinal endoscopy. When confirmed, those stenosis were managed endoscopically with Savary-Gilliard dilators. Results: GJAS was confirmed in 23 patients (3.24%). A total of 36 dilatations were performed in these patients, which resulted in an average of 1.5 sessions per patient. It was necessary to perform one dilatation to 20 patients (87%), three dilatations in one patient (4%), and four or more in 2 patients (9%). The average time between surgery and GJAS dilation was 10 weeks. All dilations were performed on an outpatient basis. Conclusion: The management and treatment of GJAS after LRYGB can be done as an outpatient procedure using Savary-Gilliard dilators, which are effective and safe.

A ribosomal misincorporation of Lys for Arg in human triosephosphate isomerase expressed in Escherichia coli gives rise to two protein populations.

We previously observed that human homodimeric triosephosphate isomerase (HsTIM) expressed in Escherichia coli and purified to apparent homogeneity exhibits two significantly different thermal transitions. A detailed exploration of the phenomenon showed that the preparations contain two proteins; one has the expected theoretical mass, while the mass of the other is 28 Da lower. The two proteins were separated by size exclusion chromatography in 3 M urea. Both proteins correspond to HsTIM as shown by Tandem Mass Spectrometry (LC/ESI-MS/MS). The two proteins were present in nearly equimolar amounts under certain growth conditions. They were catalytically active, but differed in molecular mass, thermostability, susceptibility to urea and proteinase K. An analysis of the nucleotides in the human TIM gene revealed the presence of six codons that are not commonly used in E. coli. We examined if they were related to the formation of the two proteins. We found that expression of the enzyme in a strain that contains extra copies of genes that encode for tRNAs that frequently limit translation of heterologous proteins (Arg, Ile, Leu), as well as silent mutations of two consecutive rare Arg codons (positions 98 and 99), led to the exclusive production of the more stable protein. Further analysis by LC/ESI-MS/MS showed that the 28 Da mass difference is due to the substitution of a Lys for an Arg residue at position 99. Overall, our work shows that two proteins with different biochemical and biophysical properties that coexist in the same cell environment are translated from the same nucleotide sequence frame.

Validación del “inventario de razones para vivir” (RFL) en sujetos con conducta suicida de Colombia / Validation of the Reasons for Living Inventory (Rfl) in subjects with suicidal behavior in Colombia

Objetivo: Evaluar la estructura factorial, la confiabilidad y la validez de contenido y constructo de una versión en español para Colombia del Inventario de Razones para Vivir (Rfl) en una muestra clínica de sujetos con intento de suicidio. Método: Se hicieron dos traducciones al español y dos traducciones en sentido inverso de cada uno de los ítems. Se examinó la validez del contenido y del constructo, la consistencia interna y la reproducibilidad prueba-reprueba. Resultados: La estructura factorial tiene seis dominios que explican el 63,5% de la varianza: “Creencia en la vida y capacidad de afrontamiento”, “Miedo a la muerte y a la desaprobación social”, “Responsabilidad con la familia”, “Preocupación por los hijos”, “Percepción de incapacidad para el suicidio” y “Objeciones morales”. La consistencia interna fue alta (Alfa de Cronbach=0,96), así como la reproducibilidad prueba-reprueba (CCI=0,89, IC95%: 0,78-0,94). Cuando se evaluó la validez del constructo encontramos diferencias significativas en las puntuaciones del Rflentre individuos con riesgo de suicidio alto y bajo, definido clínicamente. Conclusiones: La versión colombiana del Rflmuestra buenas propiedades psicométricas en una población clínica con comportamiento suicida.

Objective: To evaluate the factor structure, reliability, and construct and content validity of the Colombian Spanish version of the Reasons for Living Inventory (Rfl) in a clinical sample of subjects who attempted suicide. Method: Two translations into Spanish and two back-translations for each of the items were done. We assessed content and construct validity as well as internal consistency and test-retest reproducibility. Results: The factor structure has six domains which explain 63.5% of the variance: “survival and coping beliefs”, “fear of death and social disapproval”, “responsibility to family”, “child-related concerns”, “perception of incapacity for suicide” and “moral objections”. The internal consistency was high (Cronbach’s alpha=0.96), as was test-retest reproducibility (ICC=0.89, IC95%: 0.78-0.94). When assessing construct validity, we found significant differences between individuals with clinically defined high and low suicide risk in Rflscores. Conclusions: The Rflversion for Colombia shows good psychometric properties in clinical population with suicidal behavior.

[Validation of the Diagnostic Interview for Genetic Studies (DIGS) in Colombia]. / Validación de la entrevista diagnóstica para estudios genéticos (DIGS) en Colombia.

An interview tool, Diagnostic Interview for Genetic Studies (DIGS 3.0), was translated into Spanish for application in studies of psychiatric disorders in Colombia. Two Spanish translations of the original English version of DIGS were prepared and back-translated into English. A review committee verified the linguistic and cultural equivalence of the translations. The evaluator and test-retest reliability were assessed calculating Cohen's kappa for samples of 65 and 91 patients respectively. DIGS proved valid in both appearance and content. The confidence interval (C.I.) was excellent for schizophrenia (kappa = 0.81, C.I. 95% = 0.68-0.93), bipolar disorder (kappa = 0.87, C.I. 95% = 0.75-0.99), major depressive disorder (kappa = 0.86, C.I. 95% = 0.70-1.00), and for a normal diagnosis (kappa = 0.65, C.I. 95% = 0.41-0.89); it was good for other psychiatric diagnosis (kappa = 0.65, C.I. 95% = 0.41-0.89) and poor for schizoaffective disorder (kappa = 0.37, C.I. 95% = -0.02-0.76). Test-retest reliability was excellent for all diagnoses (kappa > 0.8), except for "other psychiatric diagnoses" (kappa = 0.64, C.I. 95% = 0.31-0.96). The Spanish translation of the DIGS was comprehensible, with face and content validity, and good test-retest and evaluator reliability. This translation will be a useful tool for genetic studies of psychiatric disorders in Latin America, particularly where schizophrenia and affective disorders are involved.

Validación de la entrevista diagnóstica para estudios genéticos (DIGS) en Colombia / Validation of the Diagnostic Interview for Genetic Studies (DIGS) in Colombia

Objetivo: validar la entrevista diagnóstica para estudios genéticos (DIGS 3.0) en Colombia. Métodos: se hicieron dos traducciones del inglés al español del DIGS y se hizo traducción en sentido inverso (al inglés) de cada una. Un comité de revisión verificó la equivalencia translingüística y transcultural. Se evaluó la confiabilidad examen-reexamen e interevaluador del DIGS 3.0 en 65 y 91 pacientes, respectivamente, mediante el cálculo de kappa de Cohen. Resultados: el DIGS 3.0 mostró ser comprensible, con validez de apariencia y de contenido. La confiabilidad interevaluador fue excelente para esquizofrenia (kapa=0,81, IC95%: 0,68-0,93), trastorno bipolar (kapa=0,87, IC95%: 0,75-0,99), trastorno depresivo mayor (kapa=0,86, IC95%: 0,7- 1) y ausencia de trastorno psiquiátrico (kapa=0,88, IC95%: 0,71-1); fue buena para otro diagnóstico psiquiátrico (kapa=0,65, IC95%: 0,41-0,89) y pobre para trastorno esquizoafectivo (kapa=0,37, IC95%: -0,02-0,76). La confiabilidad examen-reexamen fue excelente para todos los diagnósticos (kapa>0,8), excepto para otro diagnóstico psiquiátrico (kapa=0,64, IC95%: 0,31-0,96), donde fue buena. Conclusiones: la versión en español del DIGS para Colombia mostró comprensibilidad, validez de apariencia y de contenido, y confiabilidad examen-reexamen e interevaluador. Es una herramienta útil para estudios genéticos en esquizofrenia y en trastornos afectivos.

An interview tool, Diagnostic Interview for Genetic Studies (DIGS 3.0), was translated into Spanish for application in studies of psychiatric disorders in Colombia. Two Spanish translations of the original English version of DIGS were prepared and backtranslated into English. A review committee verified the linguistic and cultural equivalence of the translations. The evaluator and test-retest reliability were assessed calculating Cohen’s kappa for samples of 65 and 91 patients respectively. DIGS proved valid in both appearance and content. The confidence interval (C.I.) was excellent for schizophrenia (kappa=0.81, C.I. 95% = 0.68-0.93), bipolar disorder (kappa=0.87, C.I. 95% = 0.75-0.99), major depressive disorder (kappa=0.86, C.I. 95% = 0.70-1.00), and for a normal diagnosis (kappa=0.65, C.I. 95% = 0.41-0.89); it was good for other psychiatric diagnosis (kappa=0.65, C.I. 95% = 0.41-0.89) and poor for schizoaffective disorder (kappa=0.37, C.I. 95% = -0.02-0.76). Test-retest reliability was excellent for all diagnoses (kappa>0.8), except for "other psychiatric diagnoses" (kappa=0.64, C.I. 95% = 0.31-0.96). The Spanish translation of the DIGS was comprehensible, with face and content validity, and good test-retest and evaluator reliability. This translation will be a useful tool for genetic studies of psychiatric disorders in Latin America, particularly where schizophrenia and affective disorders are involved.

Aspectos do funcionamento da clínica de grupos e sua especificidade na terapia ocupacional / Aspects of the functioning of clinic of groups and its specialism in occupational therapy

As autoras se propöem a reflexöes sobre a clínica grupal e sua multiplicaçäo na Terapia Ocupacional a partir de pressupostos teóricos e experiência clínica no Hospital Dia "A CASA"

Dipropionato de beclometasona en altas dosis en el tratamiento del asma severo del niño: aspectos clínicos, funcionales y evaluación de sus efectos sistémicos / High dosage Beclometasone diproprionate in the treatment of severe asthma in children: clinical and functional aspects and evaluation of systemic effects

Se evaluaron los aspectos clínicos, funcionales y efectos secundarios del dipropionato de beclometasona (DPBM) inhalado en altas dosis, en el tratamiento de 10 niños asmáticos severos, corticoideo dependientes (inhalados, sistémicos o ambos). Se trataron durante un período de 8 meses, con dosis entre 800 y 1500 µg/kg/día). Se comprobó mejoría clínica significativa, y de los registros de pico de flujo espiratorio (PEFR) diarios, con aumento de 22 por ciento y estabilización de sus valores. El cambio a DPBM en altas dosis permitió suspender la corticoterapia sistémica en todos los pacientes. No hubo evidencias de efectos secundarios locales, ni inhibición de la función del eje hipotálamo-hipófiso-suprarrenal, valorado a través de los aspectos clínicos, cortisol plasmático, cortisol libre urinario y prueba de estimulación con ACTH