Pilot Study on the Use of Untargeted Metabolomic Fingerprinting of Liquid-Cytology Fluids as a Diagnostic Tool of Malignancy for Thyroid Nodules.

Although it is the gold standard for assessing the malignancy of thyroid nodules (TNs) preoperatively, the cytological analysis of fine-needle aspiration cytology (FNAC) samples results in 20-30% of cases in indeterminate lesions (ITNs). As two-thirds of these lesions will appear benign after diagnostic surgery, improved preoperative diagnostic methods need to be developed. In this pilot study, we evaluate if the metabolomic profiles of liquid-based (CytoRich®) FNAC samples of benign and malignant nodules can allow the molecular diagnosis of TNs. We performed untargeted metabolomic analyses with CytoRich® FNAC in a monocentric retrospective study. The cohort was composed of cytologically benign TNs, histologically benign or papillary thyroid carcinomas (PTCs) cytologically ITNs, and suspicious/malignant TNs histologically confirmed as PTCs. The diagnostic performance of the identified metabolomic signature was assessed using several supervised classification methods. Seventy-eight patients were enrolled in the study. We identified 7690 peaks, of which 2697 ions were included for further analysis. We selected a metabolomic signature composed of the top 15 metabolites. Among all the supervised classification methods, the supervised autoencoder deep neural network exhibited the best performance, with an accuracy of 0.957 (0.842-1), an AUC of 0.945 (0.833-1), and an F1 score of 0.947 (0.842-1). Here, we report a promising new ancillary molecular technique to differentiate PTCs from benign TNs (including among ITNs) based on the metabolomic signature of FNAC sample fluids. Further studies with larger cohorts are now needed to identify a larger number of biomarkers and obtain more robust signatures.

Forgiveness Interventions for Older Adults: A Review.

A meta-analysis of the efficacy of forgiveness interventions in older adults was conducted. International databases (Medline, PsycINFO, Scopus, Web of Science) were searched for studies published from 1990 to 2020 that attempted to promote forgiveness in older adults. Most intervention studies are group treatments targeted towards community-dwelling older adults. Participants in these studies are mainly women. The intervention objectives and contents vary widely and often criteria are not well-defined. Participants that received forgiveness interventions reported significantly higher levels of forgiveness than participants that did not receive treatment. Additionally, forgiveness interventions resulted in more changes in depression, stress and anger than no intervention conditions. Forgiveness treatment also enhances positive states (satisfaction with life, subjective happiness, and psychological wellbeing). The reported effects are moderate. The specific treatment model (e.g., Enright's, Worthington's) and format (e.g., group-based interventions and individually delivered programs) do not differentially predict better outcomes. In conclusion, future intervention studies should include more male participants and utilize a broader range of follow-up periods. Caution must be exercised because of the limited number of studies developed to date; researchers must be cautious when generalizing the results.

The impact of COVID-19 in hemodialysis patients: Experience in a hospital dialysis unit.

INTRODUCTION: COVID-19 is a very high transmission disease with a variable prognosis in the general population. Patients in hemodialysis therapy are particularly vulnerable to developing an infectious disease, but the incidence and prognosis of hemodialysis patients with COVID-19 is still unclear. The main objective is to describe the experience of our dialysis unit in preventing and controlling the spread of SARS-CoV-2 infection. METHODS: Preventive structural and organizational changes were applied to all patients and health care personnel in order to limit the risk of local transmission of SARS-CoV-2 infection. FINDINGS: The Nephrology department at Sant Joan Despí Moises Broggi Hospital-Consorci Sanitari Integral is a reference for two satellite hemodialysis centers caring for 156 patients. We combine our own hemodialysis maintenance program for 87 patients with hospitalized patients from peripheral hemodialysis centers. In this area, the reported incident rate of COVID-19 in these peripherical hemodialysis centers was 9.5% to 19.9% and the death rate 25% to 30.5%. In our hemodialysis program, the incidence rate was 5.7%. Three out of five required hospitalization (60%) and nobody died. DISCUSSION: Although the risk of local transmission of the disease was very high due to the increase in hemodialysis patients from peripheral centers admitted to hospital, the incidence rate of COVID-19 was very low in our own hemodialysis patients. We believe that the structural and organizational changes adopted early on and the diagnosis algorithm played an important role in minimizing the spread of the disease.

Implementation of an inpatient hyperglycemia management program incorporating a nurse consultant. / Implantación de un programa para el manejo de la hiperglucemia en la hospitalización con la incorporación de la enfermera consultora.

BACKGROUND AND AIMS: The efficacy and safety of inpatient hyperglycemia management protocols using basal-bolus regimens have been widely demonstrated, but their implementation is insufficient. The aim of the study was to assess implementation and to establish the efficacy and safety of inpatient hyperglycemia management protocol based on a basal-bolus regimen and the incorporation of a nurse consultant. MATERIAL AND METHODS: Evaluation was performed at 10 hospital units. Data were retrospectively reviewed during hospital stay and 90 days after discharge in 400 patients after protocol implementation and 200 patients before implementation. The degree of satisfaction of professionals was assessed using a questionnaire 12 months after implementation. RESULTS: The proportion of patients with basal-bolus regimens upon admission was higher in the postimplementation group (58% vs. 9%, P<0.001). Mean pre-prandial and bedtime blood glucose levels during admission were lower in the postimplementation group (164±41mg/L vs. 196±50mg/dL, P<0.001). After implementation, there were less patients with blood glucose levels >300mg/dL (36.3% vs. 50.5%, P<0.001) and more patients with values <70mg/dL (15% vs. 9%, P=0.040). Insulin addition and intensification was the main change in treatment at discharge, and a significant HbA1c reduction was seen three months after discharge in the postimplementation phase (P=0.04). The professionals assigned the protocol a score of 4.5 on a 1 to 5 scale. CONCLUSIONS: Incorporation of a nurse consultant expert in diabetes as key component of a hyperglycemia management program ensures that a majority of patients admitted to hospital for hyperglycemia receive treatment with a basal-bolus regimen and improves blood glucose control during hospital stay and after discharge.

Adherence to somatotropin treatment administered with an electronic device. / Adherencia al tratamiento con somatotropina administrada con dispositivo electrónico.

INTRODUCTION: Adherence to somatotropin treatment is associated with increased growth velocity and improved adult height. The purpose of this study is to determine the adherence of patients undergoing treatment with an electronic device and its relationship with different variables (age, gender, duration of treatment, diagnosis, height, and growth rate). MATERIAL AND METHODS: Descriptive, longitudinal and retrospective study of children less than 14 years of age undergoing treatment with somatotropin administered with the Easypod® electronic device in the Paediatric Endocrinology Outpatient Clinic of the General University Hospital of Ciudad Real, Spain. Adherence was monitored for 12 months and was defined according to the equation: (days administered at the prescribed dose / prescribed days)×100. The data analysis was performed using SPSS software. RESULTS: Data were collected from 30 patients, with a predominance of males (57%), a mean age of 6.09 years, with 51% of children less than 5 years old. The most common reasons for the treatment were: small for gestational age (55%) and growth hormone deficiency (38%). The mean duration of treatment was 4.3 years (3.6-5). A mean adherence of 92.3% (87.7-96.9) was observed, and there was a significant correlation with age (Pearson R = -0.384, P=.03), and duration of treatment (Pearson R = -0.537; P=.003). CONCLUSIONS: The adherence in our patients with electronic device is high (92.3%), and is inversely associated with age and duration. The use of electronic devices allows monitoring of therapeutic compliance, which affects the optimisation of treatment.

Inhibition of Fusarium Growth and Mycotoxin Production in Culture Medium and in Maize Kernels by Natural Phenolic Acids.

The possible role of natural phenolic compounds in inhibiting fungal growth and toxin production has been of recent interest as an alternative strategy to the use of chemical fungicides for the maintenance of food safety. Fusarium is a worldwide fungal genus mainly associated with cereal crops. The most important Fusarium mycotoxins are trichothecenes, zearalenone, and fumonisins. This study was conducted to evaluate the potential of four natural phenolic acids (caffeic, ferulic, p-coumaric, and chlorogenic) for the control of mycelial growth and mycotoxin production by six toxigenic species of Fusarium . The addition of phenolic acids to corn meal agar had a marked inhibitory effect on the radial growth of all Fusarium species at levels of 2.5 to 10 mM in a dose-response pattern, causing total inhibition (100%) in all species except F. sporotrichioides and F. langsethiae . However, the effects of phenolic acids on mycotoxin production in maize kernels were less evident than the effects on growth. The fungal species differed in their responses to the phenolic acid treatments, and significant reductions in toxin concentrations were observed only for T-2 and HT-2 (90% reduction) and zearalenone (48 to 77% reduction). These results provide data that could be used for developing pre- and postharvest strategies for controlling Fusarium infection and subsequent toxin production in cereal grains.

Effects of bread making and wheat germ addition on the natural deoxynivalenol content in bread.

Deoxynivalenol (DON, vomitoxin) is a type-B trichothecene mycotoxin produced by several field fungi such as Fusarium graminearum and Fusarium culmorum and known to have various toxic effects. This study investigated the effect of the bread making process on the stability of DON in common bread and wheat germ-enriched bread using naturally contaminated ingredients at the level of 560 µg/kg. The concentration of DON and its evolution during bread making were determined by immunoaffinity column cleanup followed by liquid chromatography with diode array detection (HPLC-DAD). During the bread making process, DON was reduced by 2.1% after fermentation and dropped by 7.1% after baking, reaching a maximum reduction of 19.8% in the crust as compared with a decrease of 5.6% in the crumb. The addition of 15% wheat germ to the dough did not affect DON stability during bread making, showing an apparent increase of 3.5% after fermentation and a reduction by 10.2% after baking.

Occurrence and exposure assessment of Fusarium mycotoxins in maize germ, refined corn oil and margarine.

Analytical methods were validated for the analysis of fumonisins (FB1 and FB2), deoxynivalenol (DON) and zearalenone (ZEA) in maize germ, corn oil and margarine. A survey of 74 samples consisting of 12 wet-milled maize germ, 12 dry-milled maize germ, 25 refined corn oil, and 25 corn oil margarine was conducted. Results revealed that 100% and 87.5% of maize germ samples presented FB1 and FB2, respectively, attaining concentrations for the sum of both toxins of 1302±541 µg kg(-1) in wet-milled and 820±831 µg kg(-1) in dry-milled maize germ. The lower incidence of FB1, FB2 and DON in edible oil and margarine (4-8%) may be related with the industrial processes for their obtaining besides the high water-solubility of these mycotoxins. In contrast, 25% of maize germ samples were positive for ZEA as well as 32% of corn oil and 24% of margarine, which may be related with its lipophilic nature. A number of samples exceeded the maximum limits indicating that strict control is needed, though estimated dietary exposure was less than 0.2% tolerable daily intakes in all cases.

Toxicidad en peces de herbicidas formulados con glifosato / Toxicity in fishes of herbicides formulated with glyphosate

En nuestro país existe una gran extensión de hectáreas cultivadas con soja transgénica, la misma ha sido modificada genéticamente para soportar la acción de un herbicida denominado glifosato. Debido a la gran cantidad de formulaciones comerciales que incluyen glifosato es de importancia analizar el impacto ambiental producido por éstas. La evaluacion de la toxicidad aguda de dos herbicidas comerciales formulados con glifosato y de una solución del mismo; frente a peces de la especie Poecilia reticulata "lebistes" acusa que una de las soluciones produce mortalidad del 100 % de los especimenes a 100 μl/l (equivalente a 48 mg/l de principio activo); la otra a 50 μl/l (equivalente a 24 mg/l de principio activo) y la solución formulada con glifosato puro no produce mortalidad aún a concentraciones de 400 mg/l. Utilizando dosis sub letales en función de los datos obtenidos en el ensayo de toxicidad aguda se determinó que a largo plazo especimenes de Cyprinus carpio haematopterus "carpa koi", manifestaron severas alteraciones hematológicas principalmente frente a una de las formulaciones evaluadas.

Nowadays, transgenic soya, modified in order to withstand the impact of the herbicide glyphosate, in one of the main crops grown in Argentina. Due to the large number of commercial formulations that include this drug, is important to analyze both, the acute and chronic environmental impact that they cause. Here the acute toxicity of two commercial herbicides glyphosatebased toward the fish Poecilia reticulate "guppy" was evaluated and compared with pure glyphosate solutions. Interestingly, while commercial herbicides formulations induce a 100% of mortality at concentration ranged between 50 and 100 μl/l, the pure glyphosathe does not present mortality even at doses higher than 400 mg/l. When some long term effects toward Cyprinus carpio haematopterus "koi" were determined by using the sub-lethal doses already calculated it was demonstrated that one of the commercial herbicides induces severe haematological alterations.

Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome.

BACKGROUND AND OBJECTIVES: The increasing number of podocyte-expressed genes implicated in steroid-resistant nephrotic syndrome (SRNS), the phenotypic variability, and the uncharacterized relative frequency of mutations in these genes in pediatric and adult patients with SRNS complicate their routine genetic analysis. Our aim was to compile the clinical and genetic data of eight podocyte genes analyzed in 110 cases (125 patients) with SRNS (ranging from congenital to adult onset) to provide a genetic testing approach. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Mutation analysis was performed by sequencing the NPHS1, NPHS2, TRPC6, CD2AP, PLCE1, INF2, WT1 (exons 8 and 9), and ACTN4 (exons 1 to 10) genes. RESULTS: We identified causing mutations in 34% (37/110) of SRNS patients, representing 67% (16/24) familial and 25% (21/86) sporadic cases. Mutations were detected in 100% of congenital-onset, 57% of infantile-onset, 24 and 36% of early and late childhood-onset, 25% of adolescent-onset, and 14% of adult-onset patients. The most frequently mutated gene was NPHS1 in congenital onset and NPHS2 in the other groups. A partial remission was observed in 7 of 26 mutation carriers treated with immunosuppressive agents and/or angiotensin-converting enzyme inhibitors. Patients with NPHS1 mutations showed a faster progression to ESRD than patients with NPHS2 mutations. None of these mutation carriers relapsed after kidney transplantation. CONCLUSIONS: We propose a genetic testing algorithm for SRNS based on the age at onset and the familial/sporadic status. Mutation analysis of specific podocyte-genes has a clinical value in all age groups, especially in children.

Clinical value of NPHS2 analysis in early- and adult-onset steroid-resistant nephrotic syndrome.

BACKGROUND AND OBJECTIVES: To date, very few cases with adult-onset focal segmental glomerulosclerosis (FSGS) carrying NPHS2 variants have been described, all of them being compound heterozygous for the p.R229Q variant and one pathogenic mutation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Mutation analysis was performed in 148 unrelated Spanish patients, of whom 50 presented with FSGS after 18 years of age. Pathogenicity of amino acid substitutions was evaluated through an in silico scoring system. Haplotype analysis was carried out using NPHS2 single nucleotide polymorphism and microsatellite markers. RESULTS: Compound heterozygous or homozygous NPHS2 pathogenic mutations were identified in seven childhood-onset steroid-resistant nephrotic syndrome (SRNS) cases. Six additional cases with late childhood- and adult-onset SRNS were compound heterozygotes for p.R229Q and one pathogenic mutation, mostly p.A284V. p.R229Q was more frequent among SRNS cases relative to controls (odds ratio=2.65; P=0.02). Significantly higher age at onset of the disease and slower progression to ESRD were found in patients with one pathogenic mutation plus the p.R229Q variant in respect to patients with two NPHS2 pathogenic mutations. CONCLUSIONS: NPHS2 analysis has a clinical value in both childhood- and adult-onset SRNS patients. For adult-onset patients, the first step should be screening for p.R229Q and, if positive, for p.A284V. These alleles are present in conserved haplotypes, suggesting a common origin for these substitutions. Patients carrying this specific NPHS2 allele combination did not respond to corticoids or immunosuppressors and showed FSGS, average 8-year progression to ESRD, and low risk for recurrence of FSGS after kidney transplant.

Nephrin mutations cause childhood- and adult-onset focal segmental glomerulosclerosis.

Mutations in the NPHS1 gene cause congenital nephrotic syndrome of the Finnish type presenting before the first 3 months of life. Recently, NPHS1 mutations have also been identified in childhood-onset steroid-resistant nephrotic syndrome and milder courses of disease, but their role in adults with focal segmental glomerulosclerosis remains unknown. Here we developed an in silico scoring matrix to evaluate the pathogenicity of amino-acid substitutions using the biophysical and biochemical difference between wild-type and mutant amino acid, the evolutionary conservation of the amino-acid residue in orthologs, and defined domains, with the addition of contextual information. Mutation analysis was performed in 97 patients from 89 unrelated families, of which 52 presented with steroid-resistant nephrotic syndrome after 18 years of age. Compound heterozygous or homozygous NPHS1 mutations were identified in five familial and seven sporadic cases, including one patient 27 years old at onset of the disease. Substitutions were classified as 'severe' or 'mild' using this in silico approach. Our results suggest an earlier onset of the disease in patients with two 'severe' mutations compared to patients with at least one 'mild' mutation. The finding of mutations in a patient with adult-onset focal segmental glomerulosclerosis indicates that NPHS1 analysis could be considered in patients with later onset of the disease.

TRPC6 mutational analysis in a large cohort of patients with focal segmental glomerulosclerosis.

BACKGROUND: Mutations in the TRPC6 gene have been reported in six families with adult-onset (17-57 years) autosomal dominant focal segmental glomerulosclerosis (FSGS). Electrophysiology studies confirmed augmented calcium influx only in three of these six TRPC6 mutations. To date, the role of TRPC6 in childhood and adulthood non-familial forms is unknown. METHODS: TRPC6 mutation analysis was performed by direct sequencing in 130 Spanish patients from 115 unrelated families with FSGS. An in silico scoring matrix was developed to evaluate the pathogenicity of amino acid substitutions, by using the bio-physical and bio-chemical differences between wild-type and mutant amino acid, the evolutionary conservation of the amino acid residue in orthologues, homologues and defined domains, with the addition of contextual information. RESULTS: Three new missense substitutions were identified in two clinically non-familial cases and in one familial case. The analysis by means of this scoring system allowed us to classify these variants as likely pathogenic mutations. One of them was detected in a female patient with unusual clinical features: mesangial proliferative FSGS in childhood (7 years) and partial response to immunosupressive therapy (CsA + MMF). Asymptomatic carriers of this likely mutation were found within her family. CONCLUSIONS: We describe for the first time TRPC6 mutations in children and adults with non-familial FSGS. It seems that TRPC6 is a gene with a very variable penetrance that may contribute to glomerular diseases in a multi-hit setting.

Incidencia de la ß-talasemia en San Luis, Argentina: índices hematimétricos en la diferenciación entre ß-talasemia y anemia ferropénica / The frecuency of ß-thalassemia in San Luis, Argentina: hematimetric indexs in the differentiation between ß-thelassemia and ferropenic anemia

A fin de determinar la incidencia de la ß-talasemia en la provincia de San Luis, se analizaron 4400 muestras de pacientes que asistieron a hospitales públicos de toda la provincia. Se detectaron 390 anemias microcíticas (8.86 por ciento) de las cuales 7 resultaron ß-talasemia (0.16 por ciento del total) las que presentaron Hb A2 mayor de 3.5 por ciento. Para determinar las diferencias entre pacientes ferropénicos y ß-talasémicos se analizaron los datos de índices hematimétricos, hierro sérico, ferritina, transferrina, protoporfirina libre eritrocitaria, reticulocitos y HbA2. En pacientes talasémicos se observó que no hubo diferencias significativas en el valor de los índices hematimétricos respecto de los controles y ferropénicos, excepto que incrementó significativamente el contenido de reticulocitos y de HbA2. En pacientes ferropénicos se observó un incremento significativo de los valores de RDW y de protoporfirinas libres eritrocitarias respecto de los talasémicos y los controles. La incidencia de la ß-talasemia en la provincia de San Luis es de 1,6 por cada 1000 habitantes, la cual resulta inferior a la observada en otras provincias, probablemente por las corrientes migratorias que habitaron la región

Triagem das hemoglobinopatias por isoeletrofocalizaçäo / Screening of hemoglobinopathies by isoelectric focusing

Com o propósito de verificar a aplicabilidade da isoeletrofocalizaçäo (IEF) na triagem populacional das hemoglobinopatias, analisamos dois grupos de amostras constituídos por 1.537 pacientes laboratoriais na faixa etária entre quatro meses e 71 anos e 303 amostras de sangue de recém-nascidos. Todos foram classificados pela cor da pele em caucasóides e negróides, e triados por métodos radicionais de identificaçäo de fenótipos das hemoglobinas, bem como por eletroforese com focalizaçäo isoelétrica. Os resultados, expressos pela soma das observaçöes nos dois procedimentos, evidenciaram que 3,9 por cento dos pacientes laboratorias (61 indivíduos) eram portadores de hemoglobinopatias, sendo o fenótipo prevalente o traço falciforme (2,8 por cento), seguido do traço da hemoglobina C (0,5 por cento) e da talassemia beta-heterozigota (0,4 por cento). Neste grupo, os negróides apresentaram 9,8 por cento de hemoglobinas anormais e os caucasóides, 2,5 por cento. Entre os recém-nascidos, 11,9 por cento (36 indivíduos) apresentaram hemoglobinopatias, com expressiva percentagem de fenótipo compatível com talassemia alfa (6,3 por cento), seguida da talassemia beta-heterozigota (3 por cento) e do traço falciforme (1,6 por cento). Neste grupo, os negróides apresentaram 35,3 por cento de hemoglobinas anormais e os caucasóides 7,1 por cento. A IEF evidenciou, para ambos 35,3 por cento de hemoglobinas anormais e os caucasóides, 7,1 por cento. A IEF evidenciou, para ambos os grupos, quatro indivíduos portadores de talassemia beta-heterozigota e 19 fenótipos compatíveis com talassemia alfa, sendo que, por isso, mostrou-se válida na visualizaçäo de fraçöes que säo pouco nítidas em outros sistemas eletroforéticos

Evaluación químico-nutricional de Sorghum saccharatum var. sugar drip: estudio de complementación con proteína de lactosuero / Chemical-nutritional evaluation of Sorghum saccharatum var. sugar drip: a supplementation study with lactoserum proteins

Se determinó la composición química y algunos índices de calidad biológica de la harina integral, sin lavar, de sorgo (Sorghum saccharatum, var. sugar drip), cuyo cultivo y selección fue ensayado en la Estación Experimental "San Roque". Dirección de Agricultura. Subsecretaria de Asuntos Agrarios. San Luis, República Argentina. El valor del contenido proteico de la harina obtenida por nosotros fue de 7.5 por ciento (N x 6.25). Los valores de utilización proteica neta (NPU), digestibilidad verdadera (tD), razón proteínica neta (NPR) y razón proteínica neta relativa (RNPR), fueron: 12.4+0.6, 22.0+0.2, 0.8+0.1 y 24 por ciento respectivamente. El deficiente aprovechamiento nitrogenado limita el uso de sorgo. Dada la abundancia de este cereal y su bajo costo, este puede ser una fuente alimenticia aprovechable si es convenientemente complementado, sin aumentar costos. Se realizaron estudios de harina de sorgo complementada con proteína recuperada de suero de ricota (50:50), residuo industrial, tendiente a mejorar el déficit de lisina y treonina del cereal. En la mezcla ensayada se obtuvo un valor de RNPR de 85.7 por ciento. Esto nos permite inferir que un cereal de escaso valor biológico es aprovechable mediante adecuada complementación, con potencial utilización como alimento para aves.