Search

Abstract The aim of this paper is to develop foundations of umbral calculus on the space D ′ of distributions on R d , which leads to a general theory of Sheffer polynomial sequences on D ′. We define a sequence of monic polynomials on D ′ , a polynomial sequence of binomial type, and a Sheffer sequence. We present equivalent conditions for a sequence of monic polynomials on D ′ to be of binomial type or a Sheffer sequence, respectively. We also construct a lifting of a sequence of monic polynomials on R of binomial type to a polynomial sequence of binomial type on D ′ , and a lifting of a Sheffer sequence on R to a Sheffer sequence on D ′. Examples of lifted polynomial sequences include the falling and rising factorials on D ′ , Abel, Hermite, Charlier, and Laguerre polynomials on D ′. Some of these polynomials have already appeared in different branches of infinite dimensional (stochastic) analysis and played there a fundamental role. [ABSTRACT FROM AUTHOR]

Fetal goiter is a rare disorder not expected to be found during a healthy woman's pregnancy. It can be a prenatal manifestation of congenital hypothyroidism due to thyroid dyshormonogenesis and it can lead to serious perinatal complications. A vascularized fetal neck mass was detected at 29 weeks' gestation of a healthy primigravida. Magnetic resonance was suggestive of goiter causing airway deviation without polyhydramnios. Maternal thyroid function was normal and thyroid antibodies were negative. Two intra-amniotic levothyroxine infusions were performed at 32 and 33 weeks. Serial imaging control showed no progression of the mass. Elective caesarean section was performed at 38 weeks. The male newborn was admitted to the intensive care unit due to cardiorespiratory insufficiency with pulmonary hypertension. Hormonal assays revealed primary congenital hypothyroidism and ultrasonography confirmed diffuse goiter. Levothyroxine was started. Currently, he is 6 years old with adequate growth and normal psychomotor development. Genetic study found a heterozygous mutation in the TPO gene. [ABSTRACT FROM AUTHOR]

We define and study a spatial (infinite-dimensional) counterpart of Stirling numbers. In classical combinatorics, the Pochhammer symbol (m) n can be extended from a natural number m ∈ N to the falling factorials (z) n = z (z − 1) ⋯ (z − n + 1) of an argument z from F = R or C , and Stirling numbers of the first and second kinds are the coefficients of the expansions of (z) n through z k , k ≤ n and vice versa. When taking into account spatial positions of elements in a locally compact Polish space X , we replace N by the space of configurations—discrete Radon measures γ = ∑ i δ x i on X , where δ x i is the Dirac measure with mass at x i. The spatial falling factorials (γ) n : = ∑ i 1 ∑ i 2 ≠ i 1 ⋯ ∑ i n ≠ i 1 , ... , i n ≠ i n − 1 δ (x i 1 , x i 2 , ... , x i n ) can be naturally extended to mappings M (1) (X) ∋ ω ↦ (ω) n ∈ M (n) (X) , where M (n) (X) denotes the space of F -valued, symmetric (for n ≥ 2) Radon measures on X n. There is a natural duality between M (n) (X) and the space CF (n) (X) of F -valued, symmetric continuous functions on X n with compact support. The Stirling operators of the first and second kind, s (n , k) and S (n , k) , are linear operators, acting between spaces CF (n) (X) and CF (k) (X) such that their dual operators, acting from M (k) (X) into M (n) (X) , satisfy (ω) n = ∑ k = 1 n s (n , k) ⁎ ω ⊗ k and ω ⊗ n = ∑ k = 1 n S (n , k) ⁎ (ω) k , respectively. In the case where X has only a single point, the Stirling operators can be identified with Stirling numbers. We derive combinatorial properties of the Stirling operators, present their connections with a generalization of the Poisson point process and with the Wick ordering under the canonical commutation relations. [ABSTRACT FROM AUTHOR]

Noise is an important environmental risk factor. Industrial environments are rich in high-intensity infrasound (hi-IFS), which we have found to induce myocardial and coronary perivascular fibrosis in rats. The effects of exposure to IFS on the ventricles have been studied, but not on the atria. We hypothesized that rats exposed to hi-IFS develop atrial remodeling involving fibrosis and connexin 43, which we sought to evaluate. Seventy-two Wistar rats, half exposed to hi-IFS (120 dB, <20 Hz) during a maximum period of 12 weeks and half age-matched controls, were studied. Atrial fibrosis was analyzed by Chromotrope-aniline blue staining. The immunohistochemical evaluation of Cx43 was performed using the polyclonal antibody connexin-43 m diluted 1:1000 at 4 °C overnight. Digitized images were obtained with an optical microscope using 400× magnifications. The measurements were performed using image J software. A two-way ANOVA model was used to compare the groups. The mean values of the ratio "atrial fibrosis / cardiomyocytes" increased to a maximum of 0.1095 ± 0,04 and 0.5408 ± 0,01, and of the ratio "CX43 / cardiomyocytes" decreased to 0.0834 ± 0,03 and 0.0966 ± 0,03, respectively in IFS-exposed rats and controls. IFS-exposed rats exhibited a significantly higher ratio of fibrosis (p <.001) and lower ratio of Cx43 (p =.009). High-intensity infrasound exposure leads to an increase in atrial interstitial fibrosis and a decrease in connexin 43 in rat hearts. This finding reinforces the need for further experimental and clinical studies concerning the effects of exposure to infrasound. Unlabelled Image • High-intensity infrasound exposure triggers atrial structural changes in rat hearts. • Infrasound-exposed rats exhibit increased atrial fibrosis and decreased connexin 43. • Furthermore, Cx43 concentration seems to decrease significantly with time. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative condition that increasingly impairs cognitive functions and daily activities. Given the incurable nature of AD and its profound impact on the elderly, early diagnosis (at the mild cognitive impairment (MCI) stage) and intervention are crucial, focusing on delaying disease progression and improving patients' quality of life., Methods: This work aimed to develop an automatic sMRI-based method to detect AD in three different stages, namely healthy controls (CN), mild cognitive impairment (MCI), and AD itself. For such a purpose, brain sMRI images from the ADNI database were pre-processed, and a set of 22 texture statistical features from the sMRI gray-level co-occurrence matrix (GLCM) were extracted from various slices within different anatomical planes. Different combinations of features and planes were used to feed classical machine learning (cML) algorithms to analyze their discrimination power between the groups., Results: The cML algorithms achieved the following classification accuracy : 85.2% for AD vs. CN , 98.5% for AD vs. MCI , 95.1% for CN vs. MCI , and 87.1% for all vs. all ., Conclusions: For the pair AD vs. MCI , the proposed model outperformed state-of-the-art imaging source studies by 0.1% and non-imaging source studies by 4.6%. These results are particularly significant in the field of AD classification, opening the door to more efficient early diagnosis in real-world settings since MCI is considered a precursor to AD.

Introduction: Renal colic is the most common non-obstetric cause of abdominal pain during pregnancy and is associated with a higher risk of complications in these women. When invasive treatment is required, options are temporary drainage with ureteral stent (JJ) or percutaneous nephrostomy (PCN), or immediate definitive treatment with ureteroscopy (URS). Our goal was to review the safety and efficacy of these procedures in treating urolithiasis during pregnancy., Methods: Adhering to the PRISMA checklist guidelines, we searched PubMed, Embase, and Scopus databases for articles on the efficacy and complications of the three procedures in pregnant women. The quality of evidence and risk of bias were evaluated using the Critical Appraisal Skills Programme and the Institute of Health Economics tools., Results: We included 45 articles, totaling 3424 interventions in pregnant women - 2188 URS, 719 JJ, and 517 PCN. URS was the most assessed procedure, with stone-free rates comparable to the non-pregnant patients. The most frequent complications were lower urinary symptoms and infections independently of the intervention. Obstetric complications for all interventions included 167 cases of preterm labor, resulting in 24 premature births. No statistically significant differences in post-operative complications were reported between the procedures in the few comparative studies., Conclusions: Despite the absence of high-quality studies, current evidence suggests that URS, JJ, and PCN are all safe and effective during pregnancy. As most patients submitted to temporary drainage require a second procedure post-delivery, primary URS appears more efficient. Therefore, it is the preferred option unless there are indications for temporary drainage.

Study Question: What is the contribution of genetic defects in Portuguese patients with congenital hypogonadotropic hypogonadism (CHH)?, Summary Answer: Approximately one-third of patients with CHH were found to have a genetic cause for their disorder, with causal pathogenic and likely pathogenic germline variants distributed among 10 different genes; cases of oligogenic inheritance were also included., What Is Known Already: CHH is a rare and genetically heterogeneous disorder characterized by deficient production, secretion, or action of GnRH, LH, and FSH, resulting in delayed or absent puberty, and infertility., Study Design Size Duration: Genetic screening was performed on a cohort of 81 Portuguese patients with CHH (36 with Kallmann syndrome and 45 with normosmic hypogonadotropic hypogonadism) and 263 unaffected controls., Participants/materials Setting Methods: The genetic analysis was performed by whole-exome sequencing followed by the analysis of a virtual panel of 169 CHH-associated genes. The main outcome measures were non-synonymous rare sequence variants (population allele frequency <0.01) classified as pathogenic, likely pathogenic, and variants of uncertain significance (VUS)., Main Results and the Role of Chance: A genetic cause was identified in 29.6% of patients. Causal pathogenic and likely pathogenic variants were distributed among 10 of the analysed genes. The most frequently implicated genes were GNRHR , FGFR1 , ANOS1 , and CHD7 . Oligogenicity for pathogenic and likely pathogenic variants was observed in 6.2% of patients. VUS and oligogenicity for VUS variants were observed in 85.2% and 54.3% of patients, respectively, but were not significantly different from that observed in controls., Large Scale Data: N/A., Limitations Reasons for Caution: The identification of a large number of VUS presents challenges in interpretation and these may require reclassification as more evidence becomes available. Non-coding and copy number variants were not studied. Functional studies of the variants were not undertaken., Wider Implications of the Findings: This study highlights the genetic heterogeneity of CHH and identified several novel variants that expand the mutational spectrum of the disorder. A significant proportion of patients remained without a genetic diagnosis, suggesting the involvement of additional genetic, epigenetic, or environmental factors. The high frequency of VUS underscores the importance of cautious variant interpretation. These findings contribute to the understanding of the genetic architecture of CHH and emphasize the need for further studies to elucidate the underlying mechanisms and identify additional causes of CHH., Study Funding/competing Interests: This research was funded by the Portuguese Foundation for Science and Technology (grant numbers PTDC/SAU-GMG/098419/2008, UIDB/00709/2020, CEECINST/00016/2021/CP2828/CT0002, and 2020.04924.BD) and by Sidra Medicine-a member of the Qatar Foundation (grant number SDR400038). The authors declare no competing interests., Competing Interests: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Summary: We report a 61-year-old male patient without personal history of thyroid carcinoma or radiation exposure. In 2011, he presented with a cervical mass whose biopsy diagnosed a papillary thyroid carcinoma (PTC) in a lymph node metastasis (LNM). Total thyroidectomy with lymphadenectomy of central and ipsilateral compartment was performed. Histopathology identified a 2 mm follicular variant of PTC and LNM in 25/25 lymph nodes. The patient was treated with 150 mCi of radioactive iodine (RAI), followed by levothyroxine suppressive therapy. In 2016, a retrotracheal mass was diagnosed, suggesting local recurrence; patient was submitted to surgical excision and RAI therapy (120 mCi). Due to seizures, in 2019, a brain CT was performed that diagnosed brain metastases. The patient underwent debulking of the main lesion. Histopathology analysis confirmed a metastatic lesion with variated morphology: classical PTC and follicular pattern and hobnail and tall cell features. Molecular analysis revealed BRAFV600E in LNM at presentation and BRAFV600E and TERT promoter (TERTp) mutations in the recurrent LNM and brain metastasis. Based upon this experience we review the reported cases of subcentimetric PTC with brain metastases and discuss the molecular progression of the present case., Learning Points: Papillary microcarcinoma (PMCs) usually have very good prognosis with low impact on patient survival. PMCs presenting in elderly patients with LNM at diagnosis may carry a guarded outcome. Brain metastasis although rare indicate aggressive phenotypic features. Patient risk stratification of PMCs based on histopathological analysis and genetic testing may have a significant impact on prognosis providing therapeutic markers, that may predict disease progression and overall outcome.

Introduction: Men born with pathogenic/likely pathogenic variants in genes associated with the Hereditary Breast and Ovarian Cancer Syndrome have a higher risk to develop breast cancer and other cancers (such as prostate cancer) and should undergo adequate surveillance protocols in highly specialized Centers., Methods: A retrospective study was conducted to assess these genetic variants' epidemiological and phenotypical manifestations in male carriers, as well as the efficacy of the surveillance protocol and compliance toward it through a survey. During follow-up, a genetic panel for testing was implemented, the starting age for surveillance was delayed, and the six-month screening interval was extended to annual., Results: A total of 104 men from a tertiary hospital's High-Risk Consultation were included, 102 with positive genetic testing for BRCA1 (n = 31), BRCA2 (n = 55), both BRCA2 and another gene (n = 5), CDH1 (n = 2), CHEK2 (n = 4), NF1 (n = 1), RAD51C (n = 4), and an additional two men with no actionable genetic variant identified. The follow-up period ranged from 1 to 13 years, and only one man developed cancer. Survey responses from 48 men in active surveillance showed that more than half recognizes their carrier status and consequent surveillance impact on their life, including the risk of transmission to offspring, fear of future cancer, meaningful distress, and feeling of injustice. Biannual surveillance was not actively detecting more cancer disease cases, confirming the adequacy of the currently implemented protocol CONCLUSION: With support of Genetics to fulfill the current gaps in high-risk management, the proposed redefinition of surveillance protocol would adapt it to the population needs and concerns., (© 2023. The Author(s).)

Early and accurate detection of infection by pathogenic microorganisms, such as Plasmodium, the causative agent of malaria, is critical for clinical diagnosis and ultimately determines the patient's outcome. We have combined a polystyrene-based microfluidic device with an immunoassay which utilises Surface-Enhanced Raman Spectroscopy (SERS) to detect malaria. The method can be easily translated to a point-of-care testing format and shows excellent sensitivity and specificity, when compared to the gold standard for laboratorial detection of Plasmodium infections. The device can be fabricated in less than 30 min by direct patterning on shrinkable polystyrene sheets of adaptable three-dimensional microfluidic chips. To validate the microfluidic system, samples of P. falciparum -infected red blood cell cultures were used. The SERS-based immunoassay enabled the detection of 0.0012 ± 0.0001% parasitaemia in a P. falciparum -infected red blood cell culture supernatant, an ∼7-fold higher sensitivity than that attained by most rapid diagnostic tests. Our approach successfully overcomes the main challenges of the current Plasmodium detection methods, including increased reproducibility, sensitivity, and specificity. Furthermore, our system can be easily adapted for detection of other pathogens and has excellent properties for early diagnosis of infectious diseases, a decisive step towards lowering their high burden on healthcare systems worldwide.

Aims: To characterize a cohort of T1D patients and to compare diabetes control between patients using different regimen of insulin therapy and glucose monitoring., Methods: Were included all T1D patients followed at the Pediatric Endocrinology Unit, between April 1st and June 30th, 2021. Several clinical and demographic variables were analyzed., Results: Our sample included 208 patients, 56.7 % males, mean age of 12.7 ± 4.6 years. The median HbA1c was 7.3 %. Most patients, 78.8% were treated with continuous subcutaneous insulin infusion (CSII) and 81.3 % used continuous glucose monitoring (CGM). CSII had a lower HbAc compared with multiple daily injections (MDI) users (7.1vs 8.1 %, p < 0.01). In the CSII group, those who used CGM had a lower HbAc (7.1 vs 7.5 %,p = 0.02). Analyzing the data of the ambulatory glucose report, the CSII users had a lower glucose management indicator, (7.2 % vs 7.6 %, p < 0.01), more time in range (58.0 % vs 52.4 %;p < 0.01) and less time above range > 250 mg/dL (12.4 % vs 20.5 %;p < 0.01) than MDI users., Conclusions: The median HbA1c was 7.3% very close to the recommended target. In Portugal, pediatric patients can access a CSII provided by the national health service and a CGM system due to an elevated reimbursement of their cost. This healthy policy allows us to achieve better goals without the risk of hypoglycemia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background and objective Pediatric thyroid disease requiring surgery is rare. Thyroid nodules are a frequent indication for surgery and are mostly benign. However, up to 25% of cases can be malignant. In this study, we aimed to describe our center's experience with regard to pediatric thyroid surgery. Methods This was a retrospective transverse study involving pediatric patients who underwent thyroid surgery at a tertiary hospital between January 2010 and December 2021. Results A total of 14 patients underwent 15 surgeries. The main reason for referral to pediatric endocrinology was thyroid nodules (n=10). Thirteen fine needle aspirations (FNAs) were performed, with follicular tumor (n=6) being the most common finding. The median age of patients at surgery was 15.9 years [interquartile range (IQR): 14.0-16.8]. The most common surgical indications were the presence of a follicular tumor on FNA (n=5) and thyroid nodule size causing symptoms (n=5). There was one case of prophylactic thyroidectomy due to the identification of a multiple endocrine neoplasia type 2A (MEN2A) mutation. The most frequently described histopathology results were follicular adenoma (n=6) and colloid nodular goiter (n=6). Three postoperative complications were observed in three different patients: bilateral lesion of the recurrent laryngeal nerve, cervical hematoma, and transient hypoparathyroidism with hypocalcemia. Conclusion In our study, the most frequent surgical indication was a follicular tumor. A good correlation was found between FNA cytology and final histopathology results, which is in accordance with previous studies. This reinforces the importance of FNA in diagnosis and surgical planning. The rate of complications in our study is comparable to that in larger single-center series in the literature., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Vieira et al.)

Introduction: MODY probability calculator (MPC) represents an easy-to-use tool developed by Exeter University to help clinicians prioritize which individuals should be oriented to genetic testing. We aimed to assess the utility of MPC in a Portuguese cohort with early-onset monogenic diabetes., Methods: This single-centre retrospective study enrolled 132 participants submitted to genetic testing between 2015 and 2020. Automatic sequencing and, in case of initial negative results, generation sequencing were performed. MODY probability was calculated using the probability calculator available online. Positive and negative predictive values (PPV and NPV, respectively), accuracy, sensitivity and specificity of the calculator were determined for this cohort., Results: Seventy-three individuals were included according to inclusion criteria: 20 glucokinase (GCK-MODY); 16 hepatocyte nuclear factor 1A (HNF1A-MODY); 2 hepatocyte nuclear factor 4A (HNF4A-MODY) and 35 DM individuals with no monogenic mutations found. The median probability score of MODY was significantly higher in monogenic diabetes-positive subgroup (75.5% vs. 24.2%, p < .001). The discriminative accuracy of the calculator, as expressed by area under the curve, was 75% (95% CI: 64%-85%). In our cohort, the best cut-off value for the MODY calculator was found to be 36%, with a PPV of 74.4%, NPV of 73.5% and corresponding sensitivity and specificity of 76.2% and 71.4%, respectively., Conclusions: In a highly pre-selected group of probands qualified for genetic testing, the Exeter MODY probability calculator provided a useful tool in individuals' selection for genetic testing, with good discrimination ability under an optimal probability cut-off of 36%. Further geographical and population adjustments are warranted for general use., (© 2022 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background: Thyroid nodules are a challenge in clinical practice and thyroid ultrasonography is essential for assessing the risk of malignancy. The use of ultrasound-based malignancy risk classification systems has been recommended by several scientific societies but radiologist's adherence to these guidelines may vary. The authors aimed to analyze the quality of the information provided by the thyroid ultrasound report, to assess the malignancy risk of thyroid nodules, in Portugal., Methods: Multicenter and retrospective study, conducted in three of the five Portuguese NUTS2 corresponding to about 88.3% of the mainland population. We included 344 consecutive unselected participants aged ≥ 18 years who underwent thyroid ultrasonography in 2019. The description of six features of the dominant thyroid nodule was analyzed: maximum size, shape, margins, composition, echogenicity and echogenic foci. A utility score, including these six features, was used as an indicator of the report's quality. A score of 4 was considered as a minimum value., Results: Maximum diameter was reported for all nodules. Shape, margins, composition, echogenicity and echogenic foci were reported in 8.1%, 25.0%, 76.5%, 53.2% and 20.9%, respectively. Only 21.8% of the nodules had a score ≥ 4. At least one of four suspicious features, including marked hypoechogenicity, microcalcifications, irregular margins and non-oval shape, was identified in 8.7% of the nodules. Cervical lymph nodes' status was reported in 93% of the exams. The risk category was only reported in 7.8% of the participants., Conclusion: The adherence of Portuguese radiologists to a standardized reporting model and to an ultrasound-based malignancy risk stratification system is still low and has implications for the correct characterization of the malignancy risk of nodules and the decision to perform fine-needle aspiration biopsy., (© 2022. The Author(s).)

A new avenue has opened up for applications of surface-enhanced Raman spectroscopy (SERS) in the biomedical field, mainly due to the striking advantages offered by SERS tags. SERS tags provide indirect identification of analytes with rich and highly specific spectral fingerprint information, high sensitivity, and outstanding multiplexing potential, making them very useful in in vitro and in vivo assays. The recent and innovative advances in nanomaterial science, novel Raman reporters, and emerging bioconjugation protocols have helped develop ultra-bright SERS tags as powerful tools for multiplex SERS-based detection and diagnosis applications. Nevertheless, to translate SERS platforms to real-world problems, some challenges, especially for clinical applications, must be addressed. This review presents the current understanding of the factors influencing the quality of SERS tags and the strategies commonly employed to improve not only spectral quality but the specificity and reproducibility of the interaction of the analyte with the target ligand. It further explores some of the most common approaches which have emerged for coupling SERS with microfluidic technologies, for biomedical applications. The importance of understanding microfluidic production and characterisation to yield excellent device quality while ensuring high throughput production are emphasised and explored, after which, the challenges and approaches developed to fulfil the potential that SERS-based microfluidics have to offer are described., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)

Not required for Clinical Vignette.

Introduction: Urban noise pollution has been associated with an increased risk of developing metabolic syndrome. Nevertheless, existing observational studies relating to noise exposure and metabolic syndrome are based on non-generalizable cohorts. Lisbon remains a noisy city where this association has not been evaluated, and for this reason, we studied the relationship between exposure to urban noise and the prevalence of type 2 diabetes mellitus, obesity, and hypertension., Methods: Diurnal, evening and nocturnal noise emission levels were obtained for each street in the city from the Lisbon noise map. After allocation of all roads to the respective parish of Lisbon, the noise emission for each parish was averaged for each day period. The number of adult patients with type 2 diabetes mellitus, obesity and hypertension in 2014, 2015 and 2016 in each parish of Lisbon was obtained from the Regional Health Administration of Lisbon and Tagus Valley. Prevalence as a percentage of the population was determined using the number of residents in each parish determined in the 2011 population census. Spearman's non-parametric correlation coefficient was used due to the non-normal distribution of the variables, at the 5% significance level (α = 0.05)., Results: No correlations were found between daytime, afternoon or night-time noise exposure and the prevalence of type 2 diabetes mellitus, obesity or hypertension, although correlations were found between the cardiometabolic variables. Nevertheless, noise levels in Lisbon were above the legally established limit and the World Health Organization guidelines for environmental noise exposure in the European region., Conclusion: Our results do not agree with previous studies and should be faced as preliminary due to a strong biological plausibility for an association between noise exposure and cardiometabolic diseases and to encourage further studies, with longitudinal cohorts., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by The Author(s). Published by S. Karger AG, Basel on behalf of NOVA National School of Public Health.)

The development of robust and sensitive point-of-care testing platforms is necessary to improve patient care and outcomes. Surface-enhanced Raman scattering (SERS)-based immunosensors are especially suited for this purpose. Here, we present a highly sensitive and selective SERS immunoassay, demonstrating for example the detection of horseradish peroxidase (HRP), in a sandwich format. The strength of our biosensor lies in merging: (i) SERS-immunotags based on gold nanostars, allowing exceptional intense SERS from attached Raman probes, covalent attachment of anti-HRP antibodies by a simple chemical method providing exceptional antigen binding activity; (ii) the ease of preparation of the capture platform from a regenerated cellulose-based hydrogel, a transparent material, ideal for microfluidics applications, with low background fluorescence and Raman signal, particularly suited for preserving high activity of the covalently bound anti-HRP antibodies. The sandwich complexes formed were characterised by atomic force microscopy, and by scanning electron microscopy coupled with electron diffraction spectroscopy; and (iii) the robustness of the simple Classical Least Squares method for SERS data analysis, resulting in superior discrimination of SERS signals from the background and much better data fitting, compared to the commonly used peak integral method. Our SERS immunoassay greatly improves the detection limits of traditional enzyme-linked immunosorbent assay approaches, and its performance is better or comparable to those of existing SERS-based immunosensors. Our approach successfully overcomes the main challenges of application at point-of-care, including increasing reproducibility, sensitivity, and specificity, associated with an environmentally friendly and robust design. Also, the proposed design withstands several cycles of regeneration, a feature absent in paper-SERS immunoassays and this opens the way for sensitive multiplexing applications on a microfluidic platform.

Nature provides a remarkable database of possible adaptation strategies that can be implemented in biomimetic design of shading systems. However, at this moment, successful design methods are conditioned to a limited knowledge and ability to emulate nature's strategies to meet corresponding functional needs. The implementation of biomimetic processes has some major challenges: (1) the search and selection among several databases of appropriate strategies adopted by nature; (2) difficulties in reading, interpreting and translating at different scales; (3) connection problems between concepts and material premises. The selection of nature models is a very common situation among architectural projects. Proof of Concept (PoC) 1.0 was the first experience of application of the Bioshading System Design Method (BSDM). BSDM is a problem-based method that guides its users since the initial architectural challenge definition, improving users' capabilities to interpret and translate nature strategies into architecture design, until its final state of creation, it's physical condition. This experience enabled us to validate and evolve initial decisions, based on users experience and evaluation. At the end, PoC 1.0 revealed to be a fundamental step into the final version of BSDM.

Background: To investigate if self-perceived xerostomia and stress are significant variables on the Oral-Health Related Quality of Life (OHRQoL) of elderly patients, considering the periodontal status, oral hygiene habits and sociodemographic characteristics simultaneously., Methods: The study cohort included 592 participants (320 females/272 Males), aged 65 years or older, representing the elder inhabitants of the Study of Periodontal Health in Almada-Seixal (SoPHiAS). Patients answered a socio-demographic and oral hygiene habits questionnaire. The Oral Health Impact Profile-14 (OHIP-14), Summated Xerostomia Inventory-5 (SXI-5) and Perceived Stress Scale-10 (PSS-10) were used. Full-mouth circumferential periodontal inspection was carried out. Multivariable regression analyses were used considering the level of periodontitis, clinical characteristics, the number of teeth, SXI, PSS-10, age, gender and oral hygiene habits., Results: Self-perceived xerostomia and stress showed a positive significant correlation with OHRQoL and each of its domains. Multiple linear regression analysis demonstrated the significant impact of SXI-5 (B = 1.20, p <  0.001) and PSS-10 (B = 0.35, p <  0.001) on the OHRQoL. SXI-5 (Odds Ratio (OR) = 1.28, p <  0.001) and PSS-10 (OR = 1.03, p = 0.022) were associated with a more frequently affected OHRQoL. The number of missing teeth, being male, mean probing depth and mean clinical attachment loss were also significant towards a frequently affected OHRQoL. Conversely, age was negatively associated with a lower OHRQoL., Conclusion: Self-perceived xerostomia and stress are significant variables towards OHRQoL in elderly patients. Future studies should consider these self-perceived xerostomia and stress when investigating the impact of periodontitis and missing teeth on quality of life of older adults.

Previous experimental studies show that exposure to noise with high and audible frequencies causes multiple metabolic alterations, such as increased liver glycogen and triglycerides. However, the effect of exposure to sound with lower frequencies, such as high-intensity infrasound (frequency <20 Hz and sound pressure level >90 dB), on the liver lipid content is still unclear. As such, we aimed to study the effect of exposure to high-intensity infrasound of both normal and glucose intolerant rats on the liver lipid content. For this study, 79 wild-type male Wistar rats were randomly divided into two groups: G1, no treatment, and G2, induced glucose intolerance. Each of these two groups was randomly divided in two subgroups: s (animals kept in silence) and i (animals continuously exposed to high-intensity infrasound noise). At three noise-exposure time-points (1, 6 and 12 weeks) the rats were sacrificed, the liver was excised and hepatic lipids extracted. Data analysis was performed using a two-way ANOVA (p = 0.05). No significant effects due to interactions between the several factors exist on the liver lipid content (p=0.077). Moreover, no significant effects due to infrasound exposure (p=0.407) or glucose tolerance status (p=0.938) were observed. Our study shows that continuous exposure to high-intensity infrasound has no influence on the lipid content of the liver of both normal and glucose intolerant animals. This finding reinforces the need for further experimental studies on the physiological effects of infrasound due to its possible hazardous effects on human health., (© 2020 The Author(s).)

Objective The aim of this study was to evaluate the impact of pre-pregnancy body mass index (BMI) on pregnancy outcomes in women with gestational diabetes (GD). Subjects and methods Retrospective multicenter study using data from the Portuguese National Register. We included women with GD with a singleton pregnancy. GD diagnosis was according to the International Association of the Diabetes and Pregnancy Study Group criteria. Women were divided into groups according to their pre-pregnancy BMI: < 18.5 kg/m2 (underweight), ≥ 18.5 and < 25.0 kg/m2 (normal weight), ≥ 25 and < 30 kg/m2 (overweight) and ≥ 30 kg/m2 (obese). Results We included 3,103 pregnant women with GD, 29.6% (n = 918) were overweight and 27.3% (n = 846) were obese. Compared to normal weight, the overweight and obese groups had a higher percentage of gestational hypertension (4.0% and 8.5% vs. 2.1%), cesarean delivery (32.8% and 41.3% vs. 27.9%), macrosomia (3.9% and 6.7% vs. 2.4%), and large for gestational age (LGA) newborns (8.3% and 13.5% vs. 6.0%). Obesity increased the risk of gestational hypertension (OR 4.5, p < 0.001), preeclampsia (OR 1.9, p = 0.034), cesarean delivery (OR 2.0, p < 0.001), macrosomia (OR 3.1, p < 0.001) and LGA (OR 2.3, p < 0.001). Conclusion In pregnant women with GD, pregnancy complications increase with pre-pregnancy BMI. In obese women, appropriate diet and counseling prior to gestation and more aggressive medical intervention during pregnancy are needed in order to prevent macrosomic and LGA newborns and to reduce maternal complications.

Cancer immunotherapy has been used in several malignancies with clinical benefit. Despite the clinical success, immune-related adverse events are frequent and endocrinopathies can be particularly severe. We report a 55-year-old male patient with stage IV pulmonary carcinoma treated with nivolumab who presented with thyroid dysfunction after the sixth administration of the drug. One year after thyroid dysfunction, the patient complained of severe fatigue, asthenia and weight loss. Laboratory testing showed low morning cortisol with undetected adrenocorticotropic hormone; other pituitary hormones were normal and MRI showed homogeneous enhancement of the pituitary gland and no space-occupying lesions. The diagnosis of nivolumab-induced hypophysitis was made and replacement treatment with hydrocortisone was started with clinical improvement. This case demonstrates that patients under immunotherapy are at risk for a large spectrum of endocrine dysfunctions that may worsen their prognosis. Close monitoring of these patients is warranted., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Fetal goitrous hypothyroidism is a rare entity and is caused mainly by maternal treatment of Graves' disease (GD). We report a case of a 22-year-old woman referred at 12 weeks of gestation due to hyperthyroidism subsequent to recently diagnosed GD. She started treatment with propylthiouracil and, at 21 weeks of gestation, fetal goitre was detected. A cordocentesis confirmed the diagnosis of fetal goitrous hypothyroidism, and intra-amniotic administration of levothyroxine (LT4) was performed and repeated through the pregnancy due to maintenance of fetal goitre. The pregnancy proceeded without further complications and a healthy female infant was born at 37 weeks of gestation, with visible goitre and thyroid function within the normal range at birth. Although there is no consensus on the optimal dose, the number of injections and the interval between them, intra-amniotic LT4 administration is recommended once fetal goitrous hypothyroidism is suspected, in order to prevent long-term complications of fetal hypothyroidism., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Critically ill patients are at risk of developing stress ulcers in the upper digestive tract. Agents that suppress gastric acid are commonly prescribed to reduce the incidence of clinically important stress ulcer-related gastrointestinal bleeding. However, the indiscriminate use of stress ulcer prophylaxis in all patients admitted to the intensive care unit is not warranted and can have potential adverse clinical effects and cost implications. The present guidelines from the Sociedade Portuguesa de Cuidados Intensivos summarizes the current evidence and gives six clinical statements and an algorithm aiming to provide a standardized prescribing policy for the use of stress ulcer prophylaxis in the intensive care unit.

Background: Chronic exposure to industrial noise is known to affect biological systems, namely, by inducing fibrosis in the absence of inflammatory cells. In rat hearts exposed to this environmental hazard, we have previously found myocardial and perivascular fibrosis. The acoustic spectrum of industrial environments is particularly rich in high-intensity infrasound (<20 Hz), whose effects on the heart are unknown. We evaluated the morphological changes induced by IFS in rat coronaries in the presence and absence of dexamethasone., Methods: Adult Wistar rats were divided into three groups: group A (GA)-IFS (<20 Hz, 120 dB)-exposed rats for 28 days treated with dexamethasone; group B (GB)-IFS-exposed rats; group C (GC)-age-matched controls. The midventricle was prepared for observation with an optical microscope using 100× magnification. Thirty-one arterial vessels were selected (GA 8, GB 10, GC 13). The vessel caliber, thickness of the wall, and perivascular dimensions were quantified using image J software. Mann-Whitney and Kruskal-Wallis tests were used to compare the groups for lumen-to-vessel wall (L/W) and vessel wall-to-perivascular tissue (W/P) ratios., Results: IFS-exposed rats exhibited a prominent perivascular tissue. The median L/W and median W/P ratios were 0.54 and 0.48, 0.66 and 0.49, and 0.71 and 0.68, respectively, in GA, GB, and GC. The W/P ratio was significantly higher in GC compared with IFS-exposed animals (P=.001). The difference was significant between GC and GB (P=.008) but not between GC and GA., Conclusion: IFS induces coronary perivascular fibrosis that differs under treatment with corticosteroid., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Neuromuscular diseases (NMD) are a group of rare heterogeneous disorders that may be accompanied by respiratory muscle weakness. The simplest measurements of respiratory muscle strength are maximum inspiratory pressure (P Imax ) and maximum expiratory pressure (P Emax ) of the mouth. Inspiratory muscle weakness can also be evaluated by the sniff test (sniff nasal inspiratory pressure method). This study tested the agreements in P Imax and P Emax (measured by using a plethysmograph and portable equipment) as well as the correlations of P Imax and P Emax by using the sniff nasal inspiratory pressure method, lung function, and arterial blood gas parameters in subjects with NMD., Methods: This prospective, noninterventional study measured respiratory parameters in all the subjects with NMD who underwent measurement of maximum respiratory pressures., Results: A total of 55 subjects with NMD were included. There were no statistically significant differences in P Imax and P Emax measured by using a plethysmograph and portable equipment. Moreover, P Imax showed a good correlation with the sniff nasal inspiratory pressure method., Conclusions: Measurements of P Imax and P Emax by using portable equipment were equivalent to those performed by using the accepted standard, plethysmography, in the subjects with NMD. Noninvasive evaluation of the sniff test with the portable equipment correlates with P Imax , which makes this approach a good method for measuring the maximum strength of inspiratory muscles in patients with NMD., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2018 by Daedalus Enterprises.)

Introduction: Graves' disease (GD) is an autoimmune thyroid disease, common in adults but rare in children. The best therapeutic approach remains controversial., Objectives: To ascertain the current treatment of pediatric GD in Portugal and to assess the clinical and biochemical factors that determine definitive/long-term remission after treatment with antithyroid drugs (ATDs)., Patients and Methods: A retrospective analysis of data about pediatric GD treatment collected from a nationwide survey conducted by the Portuguese Society of Pediatric Endocrinology and Diabetology from May to August 2013. Population was categorized based on sex, age, use of ATDs, dosage, treatment duration, adverse reactions, thyrotropin receptor-stimulating antibody (TRAB) titer, remission and remission/relapse rates, and definitive treatment, and divided into group A (with ongoing treatment) and group B (with treatment stopped). Group B was subdivided into 'Remission', 'Remission+relapse' and 'No remission' subgroups based on the course of disease. The same parameters were compared between both groups., Results: Survey response rate was 77%; 152 subjects, 116 female, mean age at diagnosis 11.23±3.46 years. They all started treatment with ATDs, 70.4% with thiamazole, with a mean treatment duration of 32.38±28.29 months, and 5.9% had adverse effects. Remission rate was 32.6%. Lower age at diagnosis correlated with higher remission rates. Treatment duration was longer when propylthiouracil was used. Initial TRAB titer was significantly higher in the 'No remission' group. Surgery and radioiodine were used as second-line treatments., Conclusion: Our study results were similar to those reported in the literature. Age and TRAB titer were identified as potential clinical and laboratory determinants of remission. Based on risk/benefit analysis, it was concluded that treatment should be individualized based on age, accessibility to treatments, and physician's experience., (Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Alpha-1-antitrypsin deficiency (AATD) is a genetic condition caused by SERPINA1 mutations, which culminates into lower protease inhibitor activity in the serum and predisposes affected individuals to emphysema. Clinical manifestations of AATD are often associated to ZZ (p.Glu342Lys) and SZ (p.Glu264Val) genotypes and less frequently to rare deficiency or null alleles in heterozygous and homozygous states., Methods: We sequenced SERPINA1 (approximately 8 kb) and genotyped two microsatellites located upstream and downstream of the gene (195 and 5.6 kb, respectively) in a cohort of 51 AATD patients found to carry different rare alleles. A meta-analysis of SERPINA1 mutation spectrum was also performed., Results: We detected a total of 14 rare alleles including 3 defined by novel mutations (p.Glu162Gly, p.Arg281Lysfs*17 and p.Met374Leufs*19) and 11 characterized by previously described variants (c.-5+2dupT, p.Arg39Cys, p.Phe52del, p.Thr68Ile, p.Asp256Val, p.Leu263Pro, p.Glu264Val, p.Leu353Phefs*24, p.Pro369Ser and p.Pro369Leu) but in several instances differing in their molecular backgrounds. So far, SERPINA1 has 132 low-frequency variants (<1%), where AATD mutations are not evenly distributed across the three-dimensional structure and tend to cluster in functional domains like the gate or the shutter., Conclusion: The contribution of rare SERPINA1 alleles into AATD should not be neglected in the diagnosis practice given there is a wide spectrum of variants originated by mutation and sometimes shuffled between chromosomes by recombination. Even though many of the rare variants are likely to be recent and population specific others seems to be as old as the Z allele and dispersed across European populations., (Copyright © 2016 Elsevier Ltd. All rights reserved.)