Modeling Lysosomal Storage Disorders in an Innovative Way: Establishment and Characterization of Stem Cell Lines from Human Exfoliated Deciduous Teeth of Mucopolysaccharidosis Type II Patients.

Among the many lysosomal storage disorders (LSDs) that would benefit from the establishment of novel cell models, either patient-derived or genetically engineered, is mucopolysaccharidosis type II (MPS II). Here, we present our results on the establishment and characterization of two MPS II patient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population has been isolated from LSD patient samples obtained from the dental pulp. Taking into account our results on the molecular and biochemical characterization of those cells and the fact that they exhibit visible and measurable disease phenotypes, we consider these cells may qualify as a valuable disease model, which may be useful for both pathophysiological assessments and in vitro screenings. Ultimately, we believe that patient-derived dental pulp stem cells (DPSCs), particularly those isolated from human exfoliated deciduous teeth (SHEDs), may represent a feasible alternative to induced pluripotent stem cells (iPSCs) in many labs with standard cell culture conditions and limited (human and economic) resources.

mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis.

BACKGROUND: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L-1·min-1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown. METHODS: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141). RESULTS: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P=0.036), indexed left atrial volume (OR per SD, 2.15; P=0.001), E/e' at rest (OR per SD, 1.61; P=0.012), mPAP/CO slope (OR per SD, 2.01; P=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P=0.219). Peak Vo2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (P<0.001). These results were confirmed in the validation cohort. CONCLUSIONS: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo2 and mPAP/CO slope cumulatively improved risk stratification.

The European Portuguese Version of the Brief Negative Symptom Scale.

Negative symptoms reflect a currently much-untreated loss of normal functioning and are frequently found in psychotic disorders. We present the first translation of the Brief Negative Symptom Scale (BNSS) to European Portuguese and evaluate its validity in a sample of Portuguese male patients with a psychotic spectrum disorder. The Portuguese BNSS showed excellent internal consistency, high convergent validity (i.e., strong correlation with the PANSS negative factor), and high discriminant validity (i.e., a lack of association with the PANSS positive factor). In sum, the present European Portuguese BNSS has shown to be reliable, thus extending this instrument's clinical availability worldwide.

Use of homologous platelet gel to manage refractory diabetic lower extremity ulcers: additional experience at a tertiary hospital.

BACKGROUND: DLEUs are a major cause of morbidity. Appropriate treatment is essential, and newer methods to achieve ulcer healing have been described, including application of PG. OBJECTIVE: This study evaluated the effectiveness and safety of homologous PG in patients with chronic noninfected DLEU refractory to standard treatment as well as possible correlations between patient comorbidities and response to treatment. MATERIALS AND METHODS: Data from patients with chronic refractory DLEU managed with homologous PG between January 2014 and October 2022 were evaluated (comorbidities, wound characteristics, number and time of treatment, outcome). Outcome was classified as complete response (complete ulcer healing with reepithelialization), partial response (≥50% reduction in area and/or improvement of pain), or absence of response. The chi-square test was used to compare groups, with alpha level set at less than .05. RESULTS: A total of 81 patients (63 male, 18 female; median age, 65 years; median HbA1c, 7.6%; median ulcer area, 2.9 cm2) were proposed for PG application. A total of 62 patients had 3 or more comorbidities. Outcome was evaluated in 69 patients, with response observed in 49% (complete, 32%; partial, 17%). Worse outcomes occurred in patients with polyneuropathy (chi-square statistic: 4.183; P = .041). CONCLUSION: Homologous PG is a safe and possibly effective therapeutic alternative for DLEU that is unresponsive to standard therapies.

Sex-dimorphic neuroprotective effect of CD163 in an α-synuclein mouse model of Parkinson's disease.

Alpha-synuclein (α-syn) aggregation and immune activation represent hallmark pathological events in Parkinson's disease (PD). The PD-associated immune response encompasses both brain and peripheral immune cells, although little is known about the immune proteins relevant for such a response. We propose that the upregulation of CD163 observed in blood monocytes and in the responsive microglia in PD patients is a protective mechanism in the disease. To investigate this, we used the PD model based on intrastriatal injections of murine α-syn pre-formed fibrils in CD163 knockout (KO) mice and wild-type littermates. CD163KO females revealed an impaired and differential early immune response to α-syn pathology as revealed by immunohistochemical and transcriptomic analysis. After 6 months, CD163KO females showed an exacerbated immune response and α-syn pathology, which ultimately led to dopaminergic neurodegeneration of greater magnitude. These findings support a sex-dimorphic neuroprotective role for CD163 during α-syn-induced neurodegeneration.

A Comparative Study between Onion Peel Extracts, Free and Complexed with ß-Cyclodextrin, as a Natural UV Filter to Cosmetic Formulations.

The growing concern regarding the adverse effects of synthetic UV filters found in sunscreens has spurred significant attention due to their potential harm to aquatic ecosystems and human health. To address this, the present study aimed to extract and microencapsulate sensitive bioactive compounds derived from by-product onion peel (OP) by molecular inclusion using ß-cyclodextrin as the wall material. Identification and quantification of bioactive compounds within the extract were conducted through high-performance liquid chromatography (HPLC-DAD) analysis, revealing quercetin and resveratrol as the primary constituents. The photoprotection capacity, evaluated by the sun protection factor (SPF), revealed a protection factor comparable to the value for a synthetic UV filter. The produced microparticles presented high antioxidant capacity, significant photoprotection capacity, encapsulation efficiency of 91.8%, mean diameter of 31 µm, and polydispersity of 2.09. Furthermore, to comprehensively evaluate the performance of OP extract and its potential as a natural UV filter, five O/W emulsions were produced. Results demonstrated that microparticles displayed superior ability in maintaining SPF values over a five-week period. Photoprotection evaluation-skin reactivity tests revealed that both extract and microparticles absorb UV radiation in other regions of UV radiation, revealing their potential to be used as a natural UV filter to produce a sustainable and eco-friendly value-added sunscreen.

Exercise Pulmonary Hypertension by the mPAP/CO slope in Primary Mitral Regurgitation.

AIMS: Exercise-induced pulmonary hypertension (PH), defined by a mean pulmonary arterial pressure over cardiac output (mPAP/CO) slope >3 mmHg/L/min has important diagnostic and prognostic implications. The aim of this study is to investigate the value of the mPAP/CO slope in patients with more than moderate primary MR with preserved ejection fraction and no or discordant symptoms. METHODS AND RESULTS: A total of 128 consecutive patients were evaluated with exercise echocardiography and cardiopulmonary testing. Clinical outcome was defined as the composite of mitral valve intervention, new-onset atrial fibrillation, cardiovascular hospitalization, and all-cause mortality. Mean age was 63 years, 61% male, and mean LVEF 66 ± 6%. The mPAP/CO slope correlated with peak VO2 (r = -0.52, p < 0.001), while peak sPAP did not (r = -0.06, p = 0.584). Forty-six percent (n = 59) had peak exercise sPAP ≥60 mmHg, and 37% (n = 47) had mPAP/CO slope >3 mmHg/L/min. Event-free survival was 55% at 1-year and 46% at 2-years, with reduced survival in patients with mPAP/CO slope >3 mmHg/L/min (HR 4.9, 95%CI 2.9-8.2, p < 0.001). In 53 cases (41%), mPAP/CO slope and peak sPAP were discordant: Patients with slope >3 mmHg/L/mmHg and sPAP <60 mmHg (n = 21) had worse outcome versus peak sPAP ≥60 mmHg and normal slope (n = 32, log-rank p = 0.003). The mPAP/CO slope improved predictive models for outcome, incremental to resting and exercise sPAP, and peak VO2. CONCLUSIONS: Exercise PH defined by the mPAP/CO slope >3 mmHg/L/min is associated with decreased exercise capacity and higher risk of adverse events in significant primary MR and no or discordant symptoms. The slope provides a greater prognostic value than single sPAP measures and peak VO2.

Palliative Care in Children with Inherited Metabolic Diseases: Why does it matter?

BACKGROUND: Inherited metabolic diseases (IMD) bring considerable burden on the child and family. Challenging areas for health care include the identification of distressing symptoms, prognostic uncertainty, and bereavement. Literature regarding the impact of paediatric palliative care (PPC) is scarce. OBJECTIVE: This study aims to evaluate children with IMD referred to a PPC team (PPCT) and to analyse its impact on home care, decision to limit treatment (DLT), use of hospital resources (emergency department admissions - EDA, hospital admissions - HA, intensive care admissions - ICA) and end of life support. METHODS: Retrospective cohort study of children with IMD referred to a specialized PPCT (2016-2022). We assessed clinical data: symptoms control, time of referral and length of the follow-up period, DLT, device dependency, use of hospital resources prior to and after referral, place of death and end-of-life support. RESULTS: Fifteen children with IMD were referred to PPCT (8% of total referrals), with median age of 7 years (4 months - 17 years); 53% female. All children were non or pre-verbal. Most prevalent symptoms were neurologic and motor impairment (100%), respiratory and gastrointestinal (75%). 80% had tube feeding, 90% had some respiratory device (non-invasive ventilation in 23%). All children had multidrug use, with a mean of 6 drugs per child (2-9). 73% had home PPC and 80% had DLT planned. Nine children died (78% in hospital), after a mean of 17 months of follow-up (2 months to 4 years), all with DLT planned. 67% had support from PPCT at the end of life. All these families received emotional support. Decrease in EDA (10 vs 2) was noticed before and after PPCT. No impact was seen in HA and ICA (6 vs 5 and 1 vs 1, respectively) and there was a longer mean of hospitalisation stay (15 vs 32 days). CONCLUSION: Our cohort includes a group of children with severe, complex and neurodegenerative IMD. They need multiple medications for symptoms control, are highly dependent on medical devices and consume significant healthcare resources. Communication impairment adds complexity being a major barrier to symptom assessment. PPCT referral allowed home support, anticipated care plans development with end of life and bereavement support, as well as a tendency towards a reduction in EDA. These findings reinforce the need for holistic approach to identify and address the PPC needs of children with IMD.

Help Comes from Unexpected Places: How a Tiny Fairy and a Tropical Fish may help us Model Mucopolysaccharidoses.

INTRODUCTION: When it comes to disease modeling, countless models are available for Lysosomal Storage Diseases (LSD). Historically, two major approaches are well-established: in vitro assessments are performed in patient fibroblasts, while in vivo pre-clinical studies are performed in mouse models. Still, both platforms have a series of drawbacks. Thus, we implemented two alternative and innovative protocols to mimic a particular sub-group of LSDs, the Mucopolysaccharidoses both in vitro and in vivo. METHODS: The first one relies on a non-invasive approach using dental pulp stem cells from deciduous teeth (SHEDs). SHEDs are multipotent neuronal precursors that can easily be collected. The second uses a state-of-the-art gene editing technology (CRISPR/Cas9) to generate zebrafish disease models. RESULTS: Even though this is an ongoing project, we have already established and characterized two MPS II and one MPS VI SHED cell models. These cells self-maintain through several passages and can give rise to a variety of cells including neurons. Furthermore, all MPS-associated sub-cellular phenotypes we have assessed so far are easily observable in these cells. Regarding our zebrafish models, we have successfully knocked down both naglu and hgsnat and the first results we got from the behavioral analysis are promising ones, as we can observe altered activity and sleep patterns in the genetically modified fish. For this particular approach we chose MPS III forms as our target disorders, since their neurological features (hyperactivity, seizures and motor impairment) and lifespan decrease would be easily recognizable in zebrafish. CONCLUSION: Now that these methods are well-established in our lab, their potential is immense. On one hand, the newly developed models will be of ultimate value to understand the mechanisms underlying MPS sub-cellular pathology, which have to be further elucidated. On the other hand, they will constitute an optimal platform for drug testing in house. Also noteworthy, our models will be published as lab resources and made available for the whole LSD community.

Methylmalonyl Coenzyme A (CoA) Epimerase Deficiency, an Ultra-Rare Cause of Isolated Methylmalonic Aciduria With Predominant Neurological Features.

Methylmalonyl coenzyme A (CoA) epimerase (MCE) converts D-methylmalonyl-CoA into L-methylmalonyl CoA in the final common degradation pathway of valine, isoleucine, methionine, threonine, odd-chain fatty acids, and cholesterol side chains. Methylmalonyl-CoA epimerase deficiency is an ultra-rare autosomal recessive disorder where methylmalonic acid, methylcitrate, 3-hydroxypropionate, and propionylcarnitine are accumulated. We describe two novel pediatric patients and review the previously reported cases of MCE deficiency. Including our two novel patients, at least 24 cases of MCE deficiency have been described, with a broad clinical spectrum ranging from asymptomatic to severely neurologically impaired patients. Our patients are siblings of Arabic origin who presented with metabolic decompensation with coma and epilepsy during infancy. Methylmalonic aciduria was disclosed, L-methylmalonyl-CoA mutase deficiency was assumed, and they were treated accordingly. When first seen in our country, aged 10 and four years, respectively, both presented severe intellectual disability and spasticity. The younger had an ataxic gait, and the older was wheelchair-ridden. The study of the MMUT, MMAA, MMAB, and MMADHC genes was normal. Subsequently, the pathogenic variant c.139C>T (p.Arg47*) in the MCEE gene was identified in homozygosity in both patients, leading to the diagnosis of MCE deficiency (Online Mendelian Inheritance in Man (OMIM®) 251120, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, MD, USA). Most patients were homozygous for that variant (83% of the alleles). Correct diagnosis allowed treatment adequacy and genetic counseling. Methylmalonyl-CoA epimerase deficiency shares a similar biochemical profile with other rare genetic disorders. Patients present with overlapping clinical features with predominant neurological manifestations; genetic testing is indispensable for diagnosis. We found no association between genotype and biochemical and clinical phenotypes.

Impact of Percutaneous Endoscopic Gastrostomy Tube Feeding on Nutritional Status in Patients Undergoing Chemoradiotherapy for Oesophageal Cancer.

Introduction: Oesophageal cancer causes dysphagia and weight loss. Malnutrition further worsens with multimodal treatment. Aim: The aim of the study was to evaluate the impact of percutaneous endoscopic gastrostomy (PEG) placement in the nutritional status of patients with oesophageal cancer requiring chemoradiotherapy (CRT). Methods: A comparative study with a prospective arm and a historical cohort was conducted. Oesophageal cancer patients undergoing CRT with dysphagia grade >2 and/or weight loss >10% were submitted to PEG-tube placement (pull method) before CRT. Stoma seeding was evaluated through a swab obtained after placement and, in surgical patients, the resected stoma. A matched historical cohort without PEG placement was used as control (trial ACTRN12616000697482). Results: Twenty-nine patients (intervention group, IG) were compared to 30 patients (control group, CG). Main outcomes did not differ in the IG and CG: weight loss during CRT 8.1 ± 5.5 kg versus 9.1 ± 4.2 kg (p = 0.503); 6-month mortality after CRT or surgery 17.2% versus 26.7% (p = 0.383); perioperative complication rate 54.5% versus 55.6% (p = 1.000); unplanned hospital admissions 34.5% versus 40.0% (p = 0.661). In the CG, during CRT, 14 (46.7%) patients presented with dysphagia grade 3-4, of whom 12 required nasogastric tube feeding (n = 10), surgical gastrostomy (n = 1), and oesophageal dilation (n = 1). In the IG, 89.7% used the PEG tube during CRT, sometimes exclusively in 51.7%. Adverse events were mainly minor (n = 12, 41.4%), mostly late peristomal infections, 1 major complication (exploratory laparotomy due to suspected colonic interposition, not confirmed). There was no cytological or histological evidence of stomal tumour seeding. Conclusion: Weight loss, hospital admissions, surgical complications, and mortality were identical in oesophageal cancer patients referred for CRT, regardless of prophylactic PEG. However, half of the patients required exclusive enteral nutritional support, making PEG-tube placement an alternative to consider.

Introdução: A neoplasia do esófago associa-se a disfagia e perda ponderal, sendo a desnutrição agravada pelo tratamento multimodal. Objetivo: Avaliar o impacto da colocação de gastrostomia percutânea endoscópica (PEG) no estado nutricional de doentes com neoplasia do esófago propostos para quimiorradioterapia (QRT). Métodos: Estudo comparativo com braço prospetivo e controlo retrospetivo. Incluídos doentes com neoplasia do esófago propostos para QRT definitiva ou neoadjuvante, com disfagia grau >2 e/ou perda de peso <10%. Colocada PEG (método pull) antes do início de QRT. Avaliada sementeira tumoral por zaragatoa e histologia. Como controlo, utilizada coorte histórica de doentes sem PEG. Registo ACTRN12616000697482. Resultados: 29 doentes (grupo intervenção, GI) foram comparados com 30 controlos (GC). Sem diferença significativa nos principais outcomes: perda de peso durante a QRT 8.1 ± 5.5 kg versus 9.1 ± 4.2 kg (p = 0.503); mortalidade aos 6 meses após QRT ou cirurgia 17.2% versus 26.7% (p = 0.383); taxa de complicações perioperatórias 54.5% versus 55.6% (p = 1.000); admissões hospitalares não planeadas 34.5% versus 40.0% (p = 0.661). No GC, durante a QRT, 14 (46.7%) apresentaram disfagia graus 3­4, dos quais 12 necessitaram de nutrição por sonda nasogástrica (n = 10), gastrostomia cirúrgica (n = 1) ou dilatação esofágica (n = 1). No GI, 89.7% utilizaram a PEG durante QRT, em algum momento de forma exclusiva em 51.7%. Os eventos adversos foram sobretudo minor (n = 12; 41.4%), sobretudo infeções tardias peri-estoma; 1 complicação major (laparotomia exploradora por suspeita de interposição de cólon, não confirmada). Sem evidência citológica ou histológica de sementeira tumoral no estoma. Conclusão: Embora não se tenham observado diferenças na perda de peso, complicações cirúrgicas e mortalidade entre grupos, metade dos utentes necessitou de nutrição entérica exclusiva, tornando a colocação de PEG uma alternativa a considerar.

Citrullinemia and What Else?

INTRODUCTION: Citrullinemia type I (CTLN1) is a rare autosomal recessive metabolic disorder. Symptoms typically include vomiting, lethargy, seizures and coma. In neonatal presentation, death occurs in days if untreated. Survivors may evolve with neurocognitive dysfunction. RESULTS/CASE REPORT: Two 10 years old, non-identical, twin sisters (S1; S2) with CTLN1 were born after a 36W gestation: S1 by eutocic delivery and S2 by cesarean section with nuchal cord (Apgar score 5/10). On day four, S2 presented hyperammonemia with coma. S1 had no complications. Diagnosis followed that of S2. Neurocognitive development was monitored at 3 months - 4 years of age with Griffiths Scales: global development quotient kept within the average, but S2 had a deficit in language and eye and hand coordination. At 5 years, the neurocognitive abilities were evaluated using Wechsler Preschool and Primary Scale of Intelligence - Revised (WPPSI-R). S2 revealed difficulties in verbal area (vocabulary, comprehension and memorizing sentences), with a lower average verbal intelligence quotient (IQ). S1 had high average IQ. Due to learning difficulties, S2 was reassessment at 8 years old with Wechsler Intelligence Scale for Children - Third edition (WISC-III): full-scale IQ -"extremely low". CONCLUSION: These non-identical twin sisters share the same citrullinemia type 1 causing variants in the ASS1 gene. Nevertheless, their clinical presentation and neurocognitive evolution are diverse. Other factors, like the different genetic background and perinatal issues such as the type of delivery and its circumstances and the neonatal coma episode of S2 may explain the dissimilar evolution. Maximum ammonium levels (and its duration) are critical for the patients' neurodevelopment: 131 in S1 and 546 umol/l in S2.

Leigh Syndrome Spectrum: A Portuguese Population Cohort in an Evolutionary Genetic Era.

Mitochondrial diseases are the most common inherited inborn error of metabolism resulting in deficient ATP generation, due to failure in homeostasis and proper bioenergetics. The most frequent mitochondrial disease manifestation in children is Leigh syndrome (LS), encompassing clinical, neuroradiological, biochemical, and molecular features. It typically affects infants but occurs anytime in life. Considering recent updates, LS clinical presentation has been stretched, and is now named LS spectrum (LSS), including classical LS and Leigh-like presentations. Apart from clinical diagnosis challenges, the molecular characterization also progressed from Sanger techniques to NGS (next-generation sequencing), encompassing analysis of nuclear (nDNA) and mitochondrial DNA (mtDNA). This upgrade resumed steps and favored diagnosis. Hereby, our paper presents molecular and clinical data on a Portuguese cohort of 40 positive cases of LSS. A total of 28 patients presented mutation in mtDNA and 12 in nDNA, with novel mutations identified in a heterogeneous group of genes. The present results contribute to the better knowledge of the molecular basis of LS and expand the clinical spectrum associated with this syndrome.

Predictors of cancer in patients with acute pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (PE) can occur as a manifestation of an underlying cancer and be of paraneoplastic aetiology. A previously unknown cancer is sometimes diagnosed after the acute PE diagnosis. The identification of a group of patients with elevated probability of having an occult cancer underlying PE was never performed. We aimed to determine predictors of occult cancer in acute PE. Our hypothesis was that the D-dimer levels would be a predictor of cancer. PATIENTS AND METHODS: We retrospectively analysed a cohort of patients hospitalized with acute PE. EXCLUSION CRITERIA: <18 years, venous embolism only of veins other than pulmonary territory or when the embolism was considered chronic, and no image confirmation of acute PE. Patients were grouped according to the timing of cancer diagnosis: 1) known concomitant active cancer, 2) cancer diagnosed during acute PE admission or in the following 2 years and, 3) no known cancer during the 2-year follow-up since PE diagnosis. Predictors of concomitant cancer were determined using a logistic regression analysis. Multivariate models were built. RESULTS: We studied 562 patients; median age was 72 years and 219 (39.0 %) were men. In 223 (39.7 %) of the patients the PE was of central arteries and 61.4 % presented with bilateral PE. PE was considered unprovoked at time of discharge in 47.7 %. Median (interquartile range) D-dimer level was 7.98 (3.30-14.99) µg/mL. A total of 126 (22.4 %) patients were in group 1, 47 in group 2 (cancer diagnosed after the diagnosis of acute PE and up to 2 years) and 389 patients were in group 3. Elevated D-dimer levels were independently associated with already known cancer. D-dimer were independent predictors of future cancer diagnosis: OR = 1.07 ((95 % CI: 1.01-1.14) per each 5 ng/mL increase; for patients with D-dimer >15.0 µg/mL the OR of future cancer was 2.10 (1.05-4.18). If only patients with unprovoked PE upon admission (n = 307) were to be considered results were similar considering D-dimer; anaemia also predicted unknown cancer [OR = 2.13 (1.08-4.16)]. CONCLUSIONS: Patients with D-dimer >15 µg/mL presented a >2-fold higher risk of being diagnosed with a cancer condition in the upcoming 2 years. D-dimer may help clinicians in identifying which patients are at higher risk of occult cancer.

A Giant Parathyroid Adenoma Presenting With Parathyroid Crisis.

Giant parathyroid adenomas (GPA) are a benign cause of primary hyperparathyroidism (PHPT) that might present similarly to parathyroid carcinomas (PC). Rarely, PHPT can present with a parathyroid crisis, a life-threatening decompensation with severe hypercalcemia.  A 77-year-old woman presented with lethargy and muscle weakness. Investigation revealed parathyroid hormone-dependent hypercalcemia and an enlarged parathyroid measuring 31x24 mm. The patient was submitted for parathyroidectomy. Histology showed no evidence of malignancy, confirming a GPA.  We report a GPA presenting with a parathyroid crisis. The clinical picture mimicked that of a PC. There are no clinical, analytical, or imagiological features pathognomonic of PC.

The influence of middle-aged male driver profile on driving performance and the effects of three perceptual countermeasures: A simulator study.

The human-environment-vehicle triad and how it relates to crashes has long been a topic of discussion, in which the human factor is consistently seen as the leading cause. Recently, more sophisticated approaches to Road Safety have advocated for a road-driver interaction view, in which human characteristics influence road perception and road environment affects driver behavior. This study focuses on road-driver interaction by using a driving simulator. The objective is to investigate how the driver profile influences driving performance and the effects of three countermeasures (peripheral transverse lines before and after the beginning of the curves and roadside poles in the curves). Fifty-six middle-aged male participants drove a non-challenging rural highway simulated scenario based on a real road where many single-vehicle crashes occurred. The drivers' profiles were assessed through their behavioral history measured by a validated version of the Driver Behavior Questionnaire (DBQ) comprising three dimensions: Errors (E), Ordinary Violations (OV), and Aggressive Violations (AV). The relationship between speed and trajectory measures and drivers' profiles was investigated using random-parameter models with heterogeneity in the means. The models' results showed that the DBQ subscale scores in OV explained a considerable part of the heterogeneity found in drivers' performance. Furthermore, the heterogeneity in the means caused by the DBQ subscale scores in OV and E in the presence of peripheral transverse lines indicates a difference in how drivers react to the countermeasures. The peripheral lines were more efficient than roadside poles to moderate speed but did not positively influence all drivers' trajectories. Although the peripheral lines could be seen as an alternative to change driver behavior in a non-challenging or monotonous road environment, the design used in this study should be reviewed.

Abordagem à pessoa nos Serviço de Urgência e Unidade de Cuidados Intensivos após a pandemia COVID-19: scoping review / Approach to the person in emergency and intensive care after the pandemic covid-19: scoping review

Objetivo: Perceber quais as alterações que ocorreram na abordagem à pessoa em situação crítica no Serviço de Urgência e Unidade de Cuidados Intensivos após início da pandemia COVID-19. Método: A estratégia de pesquisa para a scopingreview foi realizada nas bases de dados Medline via PubMed, EBSCO Host, BioMed Central, ScienceDirect, BVS e Scielo através da utilização de descritores MeSH e DeCS, artigos com fulltext gratuito, publicados em língua portuguesa, inglesa e espanhola, com datas de publicação entre 2019 e 2021, implementados critérios de inclusão e exclusão.Resultados: Foram identificados 4 estudos elegíveis para análise, publicados em 2020, nenhum dos estudos em Português. Conclusão: As principais alterações estão relacionadas com a utilização de equipamento de proteção individual, colocando o enfoque na segurança dos profissionais de saúde.(AU)

Aim: To understand the changes that occurred in the approach to critically ill patients in the Emergency Department and Intensive Care Unit after the beginning of the COVID-19 pandemic. Method: The search strategy for the scoping review was conducted in Medline databases via PubMed, EBSCO Host, BioMed Central, ScienceDirect, BVS and Scielo by using MeSH and DeCS descriptors, articles with free full text, published in Portuguese, English and Spanish language, with publication dates between 2019 and 2021, implemented inclusion and exclusion criteria.Results: Four eligible studies were identified for analysis, published in 2020, and none of the studies was in Portuguese. Conclusion: The main changes are related to the use of personal protective equipment, focusing on the safety of health professionals.(AU)

Objetivo: Conocer qué cambios se han producido en el abordaje a los pacientes críticos en el Servicio de Urgencia y enUnidades de Cuidados Intensivos tras el inicio de la pandemia COVID-19.Método: La estrategia de búsqueda para la revisión se realizó en las bases de datos Medline e PubMed, EBSCO Host, BioMed Central, ScienceDirect, BVS y Scielo con el uso de descriptores MeSH y DeCS, artículos con libre acceso a texto completo, publicados en portugués, inglés y español, entre el 2019 y 2021, usando criterios de inclusión y exclusión.Resultados: Identificamos 4 estudios elegibles para el análisis, todos publicados en 2020, e ninguno en portugués.Conclusión: Los principales cambios están relacionados con el uso de equipamientos de protección personal, conel enfoque en la seguridad de los profesionales de salud.(AU)

Immune checkpoint inhibitor-induced hypophysitis: clinical and biochemical features.

Immune checkpoint inhibitors are a very promising novel class of immune response-regulating drugs for cancer treatment. Hypophysitis is one of their most common immune-related adverse events, occurring in a significant proportion of patients. Since this is a potentially severe entity, regular hormone monitoring is recommended during treatment to allow for a timely diagnosis and adequate treatment. Identification of clinical signs and symptoms, such as headaches, fatigue, weakness, nausea and dizziness, can also be key for its recognition. Compressive symptoms, such as visual disturbances, are uncommon, as is diabetes insipidus. Imaging findings are usually mild and transient and can easily go unnoticed. However, the presence of pituitary abnormalities in imaging studies should prompt closer monitoring, as these can precede clinical manifestations. The clinical importance of this entity relates mainly to the risk of hormone deficiency, especially ACTH, which occurs in the majority of patients and is rarely reversible, requiring lifelong glucocorticoid replacement therapy.

A Novel Approach in Skin Care: By-Product Extracts as Natural UV Filters and an Alternative to Synthetic Ones.

The cosmetic industry has been focusing on replacing synthetic ingredients with natural ones, taking advantage of their bioactive compounds. This work assessed the biological properties of onion peel (OP) and passion fruit peel (PFP) extracts in topical formulations as an alternative to synthetic antioxidants and UV filters. The extracts were characterized regarding their antioxidant capacity, antibacterial capacity and sun protection factor (SPF) value. Results revealed that the OP extract exhibited better results, which can result from the high concentrations of quercetin, as identified and quantified in HPLC analysis. Afterward, nine formulations of O/W creams were produced with minor changes in the quantity of additives: OP and PFP extract (natural antioxidants and UV filters), BHT (synthetic antioxidant) and oxybenzone (synthetic UV filter). The stability of the formulations was determined for 28 days; it was verified that they remained stable throughout the study period. The assays of the formulations' antioxidant capacity and SPF value revealed that OP and PFP extracts have some photoprotective properties and are excellent sources of antioxidants. As a result, they can be incorporated in daily moisturizers with SPF and sunscreens replacing and/or diminishing the quantities of synthetic ingredients, reducing their negative effects on human health and the environment.

The proof is in the poo: Non-invasive method to detect endoparasitic infection.

Almost every animal trait is strongly associated with parasitic infection or the potential exposure to parasites. Despite this importance, one of the greatest challenges that researchers still face is to accurately determine the status and severity of the endoparasitic infection without killing and dissecting the host. Thus, the precise detection of infection with minimal handling of the individual will improve experimental designs in live animal research. Here, we quantified extracellular DNA from two species of endoparasitic worm that grow within the host body cavity, hairworms (phylum Nematomorpha) and mermithids (phylum Nematoda), from the frass of their insect host, a cave weta (Orthoptera: Rhaphidophoridae) and an earwig (Dermaptera: Forficulidae), respectively. Frass collection was done at two successive time periods, to test if parasitic growth correlated with relative DNA quantity in the frass. We developed and optimized two highly specific TaqMan assays, one for each parasite-specific DNA amplification. We were able to detect infection prevalence with 100% accuracy in individuals identified as infected through post-study dissections. An additional infection in earwigs was detected with the TaqMan assay alone, probably because some worms were either too small or degraded to observe during dissection. No difference in DNA quantity was detected between sampling periods, although future protocols could be refined to support such a trend. This study demonstrates that a noninvasive and minimally stressful method can be used to detect endoparasitic infection with greater accuracy than dissection alone, helping improve protocols for live animal studies.