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IntroductionThe sodium/iodide symporter (NIS) mediates active iodide accumulation in the thyroid follicular cell. Biallelic loss-of-function variants in the NIS-coding SLC5A5 gene cause congenital dyshormonogenic hypothyroidism due to a defect in the accumulation of iodide, which is required for thyroid hormonogenesis.ObjectiveWe aimed to identify, and if so to functionally characterize, novel pathogenic SLC5A5 gene variants in a patient diagnosed with severe congenital dyshormonogenic hypothyroidism characterized by undetectable radioiodide accumulation in a eutopic thyroid gland, as well as in the salivary glands.MethodsThe coding region of the SLC5A5 gene was sequenced using whole-exome sequencing. In silico analysis and in vitro functional characterization of missense SLC5A5 gene variants were performed.ResultsProposita’s whole-exome sequencing revealed a novel pair of compound heterozygous missense variants in the SLC5A5 gene, c.1,627G>A (p.G543R) and c.1,684T>A (p.L562M). The parents were heterozygous carriers of the variants as determined by Sanger sequencing of the SLC5A5 gene. The p.G543R variant in the homozygous state has previously been associated with congenital hypothyroidism. The novel p.L562M variant was not reported in the Genome Aggregation Consortium dataset. In silico analysis of the pathogenic impact of the p.L562M variant yielded inconclusive results. Functional in vitro studies showed that the p.L562M variant reduces iodide accumulation due to defective expression of the mutant NIS protein at the plasma membrane. Notably, the aliphatic residue Leu at position 562 in the carboxy terminus of the protein, which is highly conserved in NIS orthologues, is required for NIS plasma membrane expression.ConclusionsWe report novel compound heterozygous missense SLC5A5 gene variants causing defective iodide accumulation, thus leading to congenital dyshormonogenic hypothyroidism.

Animal venoms are natural products that have served as a source of novel molecules that have inspired novel drugs for several diseases, including for metabolic diseases such as type-2 diabetes and obesity. From venoms, toxins such as exendin-4 (Heloderma suspectum) and crotamine (Crotalus durissus terrificus) have demonstrated their potential as treatments for obesity. Moreover, other toxins such as Phospholipases A2 and Disintegrins have shown their potential to modulate insulin secretion in vitro. This suggests an unexplored diversity of venom peptides with a potential anti-obesogenic in Mexican rattlesnake venoms. For that reason, this study explored the in vitro effect of Crotalus venom peptide-rich fractions on models for insulin resistance, adipocyte lipid accumulation, antioxidant activity, and inflammation process through nitric oxide production inhibition. Our results demonstrated that the peptide-rich fractions of C. aquilus, C. ravus, and C. scutulatus scutulatus were capable of reverting insulin resistance, enhancing glucose consumption to normal control; C. culminatus, C. molossus oaxacus, and C. polystictus diminished the lipid accumulation on adipocytes by 20%; C. aquilus, C. ravus, and C. s. salvini had the most significant cellular antioxidant activity, having nearly 80% of ROS inhibition. C. aquilus, C. pyrrhus, and C. s. salvini inhibited nitric oxide production by about 85%. We demonstrated the potential of these peptides from Crotalus venoms to develop novel drugs to treat type-2 diabetes and obesity. Moreover, we described for the first time that Crotalus venom peptide fractions have antioxidant and inflammatory properties in vitro models.

Reseña de: Güemes, C. y Cos Montiel, F. (2023) (Eds.). Cuidados y ecofeminismo. Consolidar avances y construir futuros igualitarios en Latinoamérica. Fundación Carolina, 117 pp.

Objetivo: analizar la percepción de las madres hermosillenses sobre las prácticas de riesgo sanitario en la alimentación de sus hijos, preescolares y escolares. Metodología: estudio transversal realizado entre 2021 y 2022 en el municipio de Hermosillo, Sonora, México, el cual incluyó entrevistas semiestructuradas. El análisis de los datos se realizó de manera cualitativa, utilizando el análisis de contenido temático. Resultados: las madres perciben que los preescolares tienen mayor vulnerabilidad que los escolares a padecer una infección intestinal. Sin embargo, estos son más enfermizos. Limitaciones: la recolección de los datos se llevó a cabo durante la pandemia de COVID-19, por lo que la interacción con las voluntarias fue virtual. Valor: el estudio aborda los cuidados sobre la salud y la alimentación de los hijos desde una perspectiva materna. Conclusiones: la vigilancia que realizan las madres se acentúa más en los hijos de edad preescolar, con variantes que se relacionan con factores socioculturales, como las creencias, las costumbres familiares, el conocimiento y las experiencias previas.

La amable figura de Don Francisco de Navarra ha sido ampliamente estudiada por el benemérito sacerdote D. Mariano Arigita en un libro que rebasa las 700 páginas, de las que buena parte recogen documentos inéditos. En su capitulo VII dedica un epigrafe de siete páginas a la amistad que medió entre él y su paisano Bartolomé de Carranza, donde acumula datos precisos y atinadas conjeturas. Muy cerca anduvo el erudito investigador de la pista que le podría haber proporcionado nuevas y definitivas noticias sobre el asunto, ya que adivinó que el arzobispo valentino hubo de intervenir en el proceso inquisitorial del dominico; pero en realidad parece inclinarse por la negativa, al suponer que Francisco de Navarra murió cuando se recibían las deposiciones de los testigos citados por Carranza, entre los que se encontraba.

Antecedentes: la ingeniería tisular permite obtener órganos como injertos a partir de tejios descelularizados, regenerados con células autólogas. Objetivo: descelularizar y regenerar tráqueas porcinas. Materiales y métodos: se descelularizaron tráqueas porcinas colocándolas cada una en el epiplón de cuatro cerdos Yorkshire para su regeneración in vivo. Una tráquea descelularizada con tritón (DT), descelularizada con desoxicolato (DD), descelularizada con desoxicolato y reforzada con un polímero, y células epiteliales (DDR) y una nativa criopreservada (NC). Después de 8 días, se obtuvieron la DD, NC y DDR; y al día 15, la DT. Se las evaluó mecánica e histológicamente, se realizó el análisis casuístico. Resultados: las tráqueas descelularizadas conservaron la integridad del cartílago, sin diferencias mecánicas, excepto la DDR con mayor rigidez. Las tráqueas regeneradas presentaron menor rigidez, excepto la DDR que además perdió el epitelio y la vascularidad. Las DT, DD mostraron epitelio no respiratorio, fibrosis y vasculogénesis con inflamación. Conclusiones: las matrices conservaron sus características mecánicas. La regeneración in vivo ofrece ventajas como la esterilidad, interacción celular, nutrientes; es sencillo, factible y económico, pero no hay control del crecimiento celular y vascularización, y los tejidos presentaron alteraciones mecánicas e histológicas. El polímero impidió la re-epitelialización y revascularización. Este estudio abre la posibilidad de mejorar las metodologías de ingeniería tisular aplicadas al tejido traqueal.

ABSTRACT: Controlled machinery traffic is a technique to increase the efficiency of machines and make better use of inputs. This study evaluated the pollutant gas emissions of an agricultural tractor towing a precision seeder-fertilizer with different plow configurations in an area with varying intensities of controlled machinery traffic. The study was carried out in a commercial agricultural area located in the municipality of Carazinho, Brazil. The experimental design was of randomized 3 x 3 blocks, with three traffic situations (tractor traffic; tractor + harvester traffic; and tractor + harvester + sprayer traffic), as well as three plow settings. The pollutant gases analyzed were: particulate material (PM), nitrogen oxides (NOx), carbon dioxide (CO2), and oxygen (O2). We concluded that greater controlled traffic intensity, compared to an area without traffic, yields a PM reduction of 43% using the double disk, and 67% using the double disk without a ridge plow. The absence of plows on the traffic lines reduces the PM, NOx, and CO2 emissions by, respectively, 73%, 12%, and 17% with tractor + harvester traffic; and 80%, 12%, and 15% with tractor + harvester + sprayer traffic, compared to cultivation using ridge plows.

Hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN) is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy with over 130 pathogenic variants identified in the TTR gene. Hereditary transthyretin amyloidosis with peripheral neuropathy is a disabling, progressive and life-threatening genetic condition that leads to death in ∼ 10 years if untreated. The prospects for ATTRv-PN have changed in the last decades, as it has become a treatable neuropathy. In addition to liver transplantation, initiated in 1990, there are now at least 3 drugs approved in many countries, including Brazil, and many more are being developed. The first Brazilian consensus on ATTRv-PN was held in the city of Fortaleza, Brazil, in June 2017. Given the new advances in the area over the last 5 years, the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology organized a second edition of the consensus. Each panelist was responsible for reviewing the literature and updating a section of the previous paper. Thereafter, the 18 panelists got together virtually after careful review of the draft, discussed each section of the text, and reached a consensus for the final version of the manuscript.

This study aimed to measure frailty using the Edmonton frail scale (EFS) and examine whether frailty is associated with presenting complaints or worse pelvic floor symptom severity in older urogynecology outpatients. We conducted a cross-sectional study of new urogynecology patients aged 50 and older at 2 urban academic centers between November 2018 and January 2020. Pelvic floor symptom severity was assessed using surveys [overactive bladder validated 8-question screener (OAB-V8), pelvic floor distress inventory, and 6-item female sexual function index]. Multivariable linear and logistic regression analyses were performed to compare chief complaint and questionnaire scores by EFS score, frailty status, and EFS component. A total of 138 women were recruited, with a mean age of 65 years (standard deviation 9.3). 11.6% met the criteria for frailty. Frail women had 6.2 greater adjusted odds of endorsing urinary incontinence symptoms as their presenting complaint, and women with higher EFS scores had worse OAB-V8 scores (adjusted ß=0.04, p=0.03). Depression/sadness were associated with worse urinary and prolapse symptoms. Frailty is common in older urogynecology outpatients, especially those presenting with urinary incontinence. Individual components of the EFS associated with symptomatic pelvic floor dysfunction included depressed mood, lack of reliable help, and incontinence.

Objectives: To evaluate neonatal autopsy rates at a tertiary hospital in southern Brazil ascertain the level of agreement between premortem and postmortem diagnosis. Methods: The authors reviewed all neonatal autopsies performed over a 10-year period and described the percentage of neonates who died and underwent autopsy. The authors tested for agreement between autopsy findings and the cause of death as defined by the neonatologist. Agreement between clinical diagnosis and autopsy findings was classified using the modified Goldman criteria. Additional findings at autopsy were grouped by organ system. Linear regression and multiple comparisons were used for statistical analyses. Results: During the study period, 382 neonates died at the Neonatal Intensive Care Unit (NICU). Consent to perform an autopsy was obtained for 73 (19.1%). The complete agreement between autopsy findings and the neonatologist's premortem diagnosis was found in 48 patients (65.8%). Additional findings were obtained at autopsy in 25 cases (34.2%). In 5 cases (6.9%), the autopsy findings contributed to subsequent genetic counseling. Seven autopsies (9.6%) revealed a diagnosis that would have changed patient management if established premortem. The autopsy rate increased by an average of 1.87% each year. Conclusion: Despite a high level of agreement between clinical diagnosis and pathological findings, autopsies provided relevant data regarding the cause of death, providing additional clinical information to neonatologists and allowing genetic counseling of family members.

Background The coexistence of amyotrophic lateral sclerosis (ALS) with clinical forms of Parkinson disease (PD), although uncommon, is found to a greater degree than one would expect by chance. The pathological mechanisms of ALS and PD are still not fully understood, and the coexistence of these two diseases suggests that they could share mechanisms in common.

Lo vegetal y lo fantástico. Presentación

Abstract Polymerase chain reaction (PCR) has proven to be the gold-standard for SARS-CoV-2 detection in clinical settings. The most common approaches rely on nasopharyngeal specimens obtained from swabs, followed by RNA extraction, reverse transcription and quantitative PCR. Although swab-based PCR is sensitive, swabbing is invasive and unpleasant to administer, reducing patient compliance for regular testing and resulting in an increased risk of improper sampling. To overcome these obstacles, we developed a non-invasive one-step RT-qPCR assay performed directly on saliva specimens. The University of Nottingham Asymptomatic Testing Service protocol simplifies sample collection and bypasses the need for RNA extraction, or additives, thus helping to encourage more regular testing and reducing processing time and costs. We have evaluated the assay against the performance criteria specified by the UK regulatory bodies and attained accreditation (BS EN ISO/IEC 17,025:2017) for SARS-CoV-2 diagnostic testing by the United Kingdom Accreditation Service. We observed a sensitivity of 1 viral copy per microlitre of saliva, and demonstrated a concordance of > 99.4% between our results and those of other accredited testing facilities. We concluded that saliva is a stable medium that allows for a highly precise, repeatable, and robust testing method.

Introduction: The sodium/iodide symporter (NIS) mediates active iodide accumulation in the thyroid follicular cell. Biallelic loss-of-function variants in the NIS-coding SLC5A5 gene cause congenital dyshormonogenic hypothyroidism due to a defect in the accumulation of iodide, which is required for thyroid hormonogenesis. Objective: We aimed to identify, and if so to functionally characterize, novel pathogenic SLC5A5 gene variants in a patient diagnosed with severe congenital dyshormonogenic hypothyroidism characterized by undetectable radioiodide accumulation in a eutopic thyroid gland, as well as in the salivary glands. Methods: The coding region of the SLC5A5 gene was sequenced using whole-exome sequencing. In silico analysis and in vitro functional characterization of missense SLC5A5 gene variants were performed. Results: Proposita's whole-exome sequencing revealed a novel pair of compound heterozygous missense variants in the SLC5A5 gene, c.1,627G>A (p.G543R) and c.1,684T>A (p.L562M). The parents were heterozygous carriers of the variants as determined by Sanger sequencing of the SLC5A5 gene. The p.G543R variant in the homozygous state has previously been associated with congenital hypothyroidism. The novel p.L562M variant was not reported in the Genome Aggregation Consortium dataset. In silico analysis of the pathogenic impact of the p.L562M variant yielded inconclusive results. Functional in vitro studies showed that the p.L562M variant reduces iodide accumulation due to defective expression of the mutant NIS protein at the plasma membrane. Notably, the aliphatic residue Leu at position 562 in the carboxy terminus of the protein, which is highly conserved in NIS orthologues, is required for NIS plasma membrane expression. Conclusions: We report novel compound heterozygous missense SLC5A5 gene variants causing defective iodide accumulation, thus leading to congenital dyshormonogenic hypothyroidism. [ABSTRACT FROM AUTHOR]

Abstract In acquired immune aplastic anemia (AA), pathogenic cytotoxic Th1 cells are activated and expanded, driving an immune response against the hematopoietic stem and progenitor cells (HSPCs) that provokes cell depletion and causes bone marrow failure. However, additional HSPC defects may contribute to hematopoietic failure, reflecting on disease outcomes and response to immunosuppression. Here we derived induced pluripotent stem cells (iPSCs) from peripheral blood (PB) erythroblasts obtained from patients diagnosed with immune AA using non-integrating plasmids to model the disease. Erythroblasts were harvested after hematologic response to immunosuppression was achieved. Patients were screened for germline pathogenic variants in bone marrow failure-related genes and no variant was identified. Reprogramming was equally successful for erythroblasts collected from the three immune AA patients and the three healthy subjects. However, the hematopoietic differentiation potential of AA-iPSCs was significantly reduced both quantitatively and qualitatively as compared to healthy-iPSCs, reliably recapitulating disease: differentiation appeared to be more severely affected in cells from the two patients with partial response as compared to the one patient with complete response. Telomere elongation and the telomerase machinery were preserved during reprogramming and differentiation in all AA-iPSCs. Our results indicate that iPSCs are a reliable platform to model immune AA and recapitulate clinical phenotypes. We propose that the immune attack may cause specific epigenetic changes in the HSPCs that limit adequate proliferation and differentiation.

Full traceability and transparency are important to establish trust in engineered cell lines. Here the authors argue that version control for cell engineering marks a significant step toward more open, reproducible, traceable and ultimately more trustworthy engineering biology.

The epidermal growth factor receptor (EGFR) signaling pathway is one of the main pathways responsible for propagating the luteinizing hormone (LH) signal throughout the cumulus cells and the oocyte. Recently, we have proposed the C-C motif chemokine receptor 2 (CCR2) and its main ligand (monocyte chemoattractant protein-1, MCP1) as novel mediators of the ovulatory cascade. Our previous results demonstrate that the gonadotropins (GNT), amphiregulin (AREG), and prostaglandin E2 (PGE2) stimulation of periovulatory gene mRNA levels occurs, at least in part, through the CCR2/MCP1 pathway, proposing the CCR2 receptor as a novel mediator of the ovulatory cascade in a feline model. For that purpose, feline cumulus-oocyte complexes (COCs) were cultured in the presence or absence of an EGFR inhibitor, recombinant chemokine MCP1, and gonadotropins [as an inducer of cumulus-oocyte expansion (C-OE), and oocyte maturation] to further assess the mRNA expression of periovulatory key genes, C-OE, oocyte nuclear maturation, and steroid hormone production. We observed that MCP1 was able to revert the inhibition of AREG mRNA expression by an EGFR inhibitor within the feline COC. In accordance, the confocal analysis showed that the GNT-stimulated hyaluronic acid (HA) synthesis, blocked by the EGFR inhibitor, was recovered by the addition of recombinant MCP1 in the C-OE culture media. Also, MCP1 was able to revert the inhibition of progesterone (P4) production by EGFR inhibitor in the C-OE culture media. Regarding oocyte nuclear maturation, recombinant MCP1 could also revert the inhibition triggered by the EGFR inhibitor, leading to a recovery in the percentage of metaphase II (MII)-stage oocytes. In conclusion, our results confirm the chemokine receptor CCR2 as a novel intermediate in the ovulatory cascade and demonstrate that the EGFR/AREG and the CCR2/MCP1 signaling pathways play critical roles in regulating feline C-OE and oocyte nuclear maturation, with CCR2/MCP1 signaling pathway being downstream EGFR/AREG pathway within the ovulatory cascade.

Advances in synthetic biology and genetic engineering are bringing into the spotlight a wide range of bio-based applications that demand better sensing and control of biological behaviours. Transcription factor (TF)-based biosensors are promising tools that can be used to detect several types of chemical compounds and elicit a response according to the desired application. However, the wider use of this type of device is still hindered by several challenges, which can be addressed by increasing the current metabolite-activated transcription factor knowledge base, developing better methods to identify new transcription factors, and improving the overall workflow for the design of novel biosensor circuits. These improvements are particularly important in the bioproduction field, where researchers need better biosensor-based approaches for screening production-strains and precise dynamic regulation strategies. In this work, we summarize what is currently known about transcription factor-based biosensors, discuss recent experimental and computational approaches targeted at their modification and improvement, and suggest possible future research directions based on two applications: bioproduction screening and dynamic regulation of genetic circuits.

BackgroundCancer survival has doubled and is likely to continue increasing in the near future. Cancer survivors experience long-term adverse effects, with associated psychological changes, and often they have needs that are yet to be met. Recognizing the lack of continuity-of-care initiatives for cancer survivors and caregivers, Osakidetza Basque Health Service has started to implement through primary care a peer-led active patient education program called "Looking after my health after cancer". This study explores how cancer survivors and their caregivers rate the experience of participating in the program, to what extent the program helps them understand and address their unmet felt needs, and helps them improve their activation for self-care and self-management.MethodsA qualitative exploratory phenomenological study was conducted using five focus groups: four with cancer survivors (n = 29) and caregivers (n = 2), and one with peer leaders (n = 7). Narrative content analysis was performed using the constant comparison method, facilitated by Atlas-ti software. Descriptive analysis of sociodemographic and clinical data was performed. The study was developed according to the Consolidated criteria for reporting qualitative research (COREQ) checklist.ResultsFive main themes emerged from the content analysis: 1) satisfaction with the program as a positive learning experience; 2) peer sharing and learning ("if they can, so can I"); 3) fears prior to attending the program; 4) becoming more aware of unmet felt needs and feeling understood in the "new normal"; and 5) a more positive view of their experience, helping them become active in self-care and empowered in the self-management of their condition.ConclusionsThe peer education program has shown to have a positive impact on cancer survivors and caregivers. It is necessary to design, implement and evaluate interventions of this type to address unmet felt needs during cancer survivorship and improve their quality of life.

Background. Molluscum contagiosum (MC) is a common viral skin infection primarily affecting children which is difficult to treat using available therapeutic approaches. The sulfated polysaccharide named calcium spirulan (Ca-SP) has demonstrated antiviral effects against herpes simplex virus in keratinocytes in vitro, and a cream containing 1.5% Ca-SP and 1% of a defined microalgae extract (Spiralin®) effectively prevented herpes labialis in a trial with susceptible individuals. This observational study aimed to show antiviral effects of a similar formulation (Spirularin® VS) against MC in children. Methods. Children with active MC lesions were treated with Spirularin® VS cream twice daily on affected skin over several months and asked to return for follow-up visits after 1 to 3 months. Clinical status of MC infection was documented at baseline and follow-up visits. Results. Of the 31 children enrolled in the study, 26 completed treatment and returned for control visits. Spirularin® VS cream was applied twice daily over a period of 1 to 9 months (mean treatment duration 3.9 months). 19/26 (73.1%) children achieved complete clearance of MC lesions with no clinical evidence of bacterial skin infection during treatment. No irritative skin reactions or unpleasant symptoms were observed or reported. Conclusion. This open-label observational study suggests that a cream formulation containing 1.5% Ca-SP and 1% Spiralin® may be an effective and safe treatment option for children with active MC lesions. The high rate of complete clearance of MC lesions and lack of adverse reactions warrant further investigation in larger, controlled trials.

A 41-year-old woman presented with a violaceous papule on the dorsum of the hand, large ipsilateral axillary lymphadenopathy, and tender, erythematous, subcutaneous nodules on the legs. Accompanying signs included fever, ankle swelling, and bilateral red eye. She recalled having a previous exposure to kittens one month before and had a positive family history for sarcoidosis. Histological examination of the hand lesion showed sarcoidal granulomas with positive Bartonella henselae DNA, whereas a biopsy done on the leg nodules was compatible with erythema nodosum. Cat scratch disease (CSD) typically presents as a tender regional lymphadenopathy preceded by an inoculation papule with spontaneous resolution occurring between 8-16 weeks. Cutaneous manifestations of CSD are rare, with erythema nodosum accompanying only 0.6% of cases. Although speculative, the background of a positive family history for sarcoidosis may explain the atypical presentation of this case, with red eye, persistent arthralgia, and associated sarcoidal granulomas.

Patch testing (PT) has been used to evaluate the culprit drug and cross-reactive chemicals in non-immediate cutaneous adverse drug reactions (CADR), but histopathology of patch tests is seldom performed. With the objective of characterizing the patterns of positive drugs patch tests in correlation with the acute skin reaction, we performed skin biopsies in 16 patients with different CADR, five cases of acute generalized exanthematous pustulosis (AGEP), six cases of maculopapular exanthema (MPE), four cases of drug reaction with eosinophilia and systemic symptoms (DRESS) and one case of toxic epidermal necrolysis (TEN). Particular macroscopic features of drug patch tests included pustules, particularly in AGEP, and epidermal necrosis in TEN and on histopathology, we highlight the occurrence of subcorneal spongiform pustules in AGEP, full-thickness epidermal necrolysis in the case of TEN and vacuolization of basal cells, lymphocyte exocytosis with occasional necrotic keratinocytes and a perivascular and interstitial lymphocyte infiltrate both in DRESS and MPE, although less intense in the latter. Similarities between the acute eruption and the patch test suggest the patch test can be considered a form of localized drug provocation test that can be used to further investigate the pathophysiology of CADR.

ABSTRACT: This research determined the engine warm-up time and the number of tests that must be carried out to obtain the performance parameters of a Diesel cycle engine. To this end, an agricultural tractor coupled to an eddy current dynamometer via a power take-off was used. Pure biodiesel (B100) was used as the fuel, and the hourly consumption was determined by means of a flowmeter. Data regarding torque, power, and hourly and specific fuel consumption was collected and analyzed at three engine warm-up times (20, 60, and 100 min). To determine the number of tests, 18 dynamometric tests were carried out to verify which of those presented the smallest experimental error, through the smallest coefficient of variation. No difference was observed in relation to the warm-up time for the analyzed variables, with a time of 20 min being enough to start the engine performance evaluations. In total, four trials were sufficient to assess engine performance and reduce experimental error.