Feasibility of Electrodermal Activity and Photoplethysmography Data Acquisition at the Foot Using a Sock Form Factor.

Wearable devices have been shown to play an important role in disease prevention and health management, through the multimodal acquisition of peripheral biosignals. However, many of these wearables are exposed, limiting their long-term acceptability by some user groups. To overcome this, a wearable smart sock integrating a PPG sensor and an EDA sensor with textile electrodes was developed. Using the smart sock, EDA and PPG measurements at the foot/ankle were performed in test populations of 19 and 15 subjects, respectively. Both measurements were validated by simultaneously recording the same signals with a standard device at the hand. For the EDA measurements, Pearson correlations of up to 0.95 were obtained for the SCL component, and a mean consensus of 69% for peaks detected in the two locations was obtained. As for the PPG measurements, after fine-tuning the automatic detection of systolic peaks, the index finger and ankle, accuracies of 99.46% and 87.85% were obtained, respectively. Moreover, an HR estimation error of 17.40±14.80 Beats-Per-Minute (BPM) was obtained. Overall, the results support the feasibility of this wearable form factor for unobtrusive EDA and PPG monitoring.

Non-tuberculous mycobacteria: clinical and laboratory characterisation (2009 and 2019).

A cross-sectional and retrospective study of patients with Mycobacterium spp. in a Portuguese tertiary hospital, in 2009 and 2019, was performed to understand better the rise in isolations of nontuberculous mycobacteria (NTM). The number of patients with positive samples for Mycobacterium spp. grew from 56 in 2009 to 83 in 2019. The proportion of NTM rose from 39.3% to 49.4% (P = 0.240), with Mycobacterium avium complex being more frequent in 2009 and Mycobacterium gordonae in 2019, and Mycobacterium tuberculosis complex decreased from 60.7% to 50.6%. Higher age was associated with NTM in both years, and pulmonary disease and immunosuppression were associated with NTM in 2019 (P < 0.05), with weak to moderate correlation (V = 0.231-0.343). The overall rise of NTM, allied to their known capacity to resist antimicrobial therapy, alerts clinicians to the importance of recognising potential risk factors for infection and improving future prevention strategies.

In search of intangible connections: intellectual capital, performance and quality of life in higher education institutions.

This study explores the contributions of different dimensions of the intellectual capital of higher education institutions (ICHEIs) to their performance, incorporating the previously unexplored dimension of quality of life (QoL) as a performance measure, and correspondingly taking into account the connection between the Theory of Stakeholders and the Theory of Legitimacy. Applying a Structural Equation Model and the Partial Least Squares method, we present new empirical findings from a sample of 738 students and 587 lecturers/researchers from seven Portuguese public HEIs. The ICHEIs positively influence the institution's performance, through relational capital and structural capital; and QoL emerges as an important dimension of HEIs' performance standards, especially regarding students' perception of academic QoL. When HEIs understand and measure their IC, they will gain a better understanding of their core competencies, enabling a better allocation of resources and implementation of more effective strategic and operational actions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10734-020-00653-9.

Guillain-Barré syndrome as the first presentation of human immunodeficiency virus infection.

AIM: Antiretroviral therapy (ART) development has reduced the severity of neurological complications of the human immunodeficiency virus (HIV), but they remain prevalent and need prompt recognition. Acute inflammatory demyelinating polyneuropathy (AIDP) is a rare complication of human immunodeficiency virus (HIV) infection that may appear at any stage of the disease. In this case, AIDP represents a late presentation of HIV infection. METHODS: Descriptive study. Patient data were collected from their medical records and by health assessment interviews. RESULTS: We report a case of a 52-year-old male with acute lower limb weakness. Given the suggestive clinical presentation of AIDP and a positive HIV test, intravenous immunoglobulin (IVIG) was administered along with antiretroviral therapy. Progressive weakness to the upper limbs, autonomic dysfunction, and pain was observed. The second regimen of IVIG plus corticosteroids was administered. Muscle strength improved after three weeks. CONCLUSIONS: Screening for HIV in a patient with AIDP may provide a better outcome because of the early start of ART with good central nervous system penetration in HIV-infected patients.

Estrogen Metabolism-Associated CYP2D6 and IL6-174G/C Polymorphisms in Schistosoma haematobium Infection.

Schistosoma haematobium is a human blood fluke causing a chronic infection called urogenital schistosomiasis. Squamous cell carcinoma of the urinary bladder (SCC) constitutes chronic sequelae of this infection, and S. haematobium infection is accounted as a risk factor for this type of cancer. This infection is considered a neglected tropical disease and is endemic in numerous countries in Africa and the Middle East. Schistosome eggs produce catechol-estrogens. These estrogenic molecules are metabolized to active quinones that induce modifications in DNA. The cytochrome P450 (CYP) enzymes are a superfamily of mono-oxygenases involved in estrogen biosynthesis and metabolism, the generation of DNA damaging procarcinogens, and the response to anti-estrogen therapies. IL6 Interleukin-6 (IL-6) is a pleiotropic cytokine expressed in various tissues. This cytokine is largely expressed in the female urogenital tract as well as reproductive organs. Very high or very low levels of IL-6 are associated with estrogen metabolism imbalance. In the present study, we investigated the polymorphic variants in the CYP2D6 gene and the C-174G promoter polymorphism of the IL-6 gene on S. haematobium-infected children patients from Guine Bissau. CYP2D6 inactivated alleles (28.5%) and IL6G-174C (13.3%) variants were frequent in S. haematobium-infected patients when compared to previously studied healthy populations (4.5% and 0.05%, respectively). Here we discuss our recent findings on these polymorphisms and whether they can be predictive markers of schistosome infection and/or represent potential biomarkers for urogenital schistosomiasis associated bladder cancer and infertility.

Wound healing and cancer progression in Opisthorchis viverrini associated cholangiocarcinoma.

Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). It was shown previously that O. viverrini-secreted proteins accelerate wound resolution in human cholangiocytes. Recombinant Ov-GRN-1 (O. viverrini-derived gene encoding granulin-like growth factor) induced angiogenesis and accelerated mouse wound healing. Given the striking similarities of wound healing and cancer progression, here we discuss the major implications of this finding for an infection-induced cancer of major public health significance in the developing world.

Schistosoma haematobium in Guinea-Bissau: unacknowledged morbidity due to a particularly neglected parasite in a particularly neglected country.

Schistosomiasis is the major neglected tropical helminthic disease worldwide. Current knowledge on the epidemiology of schistosomiasis in Guinea-Bissau is scarce and regarding to the absence of Schistosoma haematobium (S.h.). Therefore, a pilot study was undertaken to assess the prevalence and morbidity due to S.h. infection in randomly selected 90 children and adolescents aged 6 to 15 years. Prevalence of S.h. infection was 20.00 % (18/90). Microhematuria was observed in 61.11 % (11/18) of S.h.-egg-excreting vs. 37.50 % (27/72) of non-S.h.-egg-excreting children p ≤ 0.01. Body mass index (BMI) was less than 15 kg/m(2) in 52/90 (57.78 %) of all children and adolescents, but this proportion increased to 66.67 % (12/18) in S.h.-infected children who were more frequently stunted and wasted than in non-infected children. The mean weight-for-age Z score (WAZ) was reduced in S.h. infected as compared to non-infected children (-1.48 ± 1.08 SD vs. -0.80 ± 1.11 SD; p ≤ 0.01). To our knowledge, this is the first epidemiologic report on S. haematobium infection in Guinea-Bissau since 22 years. Even in this relatively small study sample, it appears that S. haematobium, besides the well-known symptoms such as hematuria, leads to significant, albeit commonly unacknowledged morbidity such as stunting and wasting. These observations underscore the notion that this vulnerable but neglected population urgently needs to be targeted for implementation of measures for treatment and control.

Effect of Molecular Stacking on Exciton Diffusion in Crystalline Organic Semiconductors.

Exciton diffusion is at the heart of most organic optoelectronic devices' operation, and it is currently the most limiting factor to their achieving high efficiency. It is deeply related to molecular organization, as it depends on intermolecular distances and orbital overlap. However, there is no clear guideline for how to improve exciton diffusion with regard to molecular design and structure. Here, we use single-crystal charge-transfer interfaces to probe favorable exciton diffusion. Photoresponse measurements on interfaces between perylenediimides and rubrene show a higher photocurrent yield (+50%) and extended spectral coverage (+100 nm) when there is increased dimensionality of the percolation network and stronger orbital overlap. This is achieved by very short interstack distances in different directional axes, which favors exciton diffusion by a Dexter mechanism. Even if the core of the molecule shows strong deviation from planarity, the similar electrical resistance of the different systems, planar and nonplanar, shows that electronic transport is not compromised. These results highlight the impact of molecular organization in device performance and the necessity of optimizing it to take full advantage of the materials' properties.

The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies.

Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue - GLA p.(Arg118Cys) -, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands' close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease. The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for "rare" condition.

Exploring the electrical robustness of conductive textile fasteners for wearable devices in different human motion conditions.

Conventional snap fasteners used in clothing are often used as electrical connectors in e-textile and wearable applications for signal transmission due to their wide availability and ease of use. Nonetheless, limited research exists on the validation of these fasteners, regarding the impact of contact-induced high-amplitude artefacts, especially under motion conditions. In this work, three types of fasteners were used as electromechanical connectors, establishing the interface between a regular sock and an acquisition device. The tested fasteners have different shapes and sizes, as well as have different mechanisms of attachment between the plug and receptacle counterparts. Experimental evaluation was performed under static conditions, slow walking, and rope jumping at a high cadence. The tests were also performed with a test mass of 140 g. Magnetic fasteners presented excellent electromechanical robustness under highly dynamic human movement with and without the additional mass. On the other hand, it was demonstrated that the Spring snap buttons (with a spring-based engaging mechanism) presented a sub-optimal performance under high motion and load conditions, followed by the Prong snap fasteners (without spring), which revealed a high susceptibility to artefacts. Overall, this work provides further evidence on the importance and reliability of clothing fasteners as electrical connectors in wearable systems.

A novel portable anechoic chamber using ultra-thin 2D microwave absorber for industrial 5.0.

In this paper, the authors, for the first time, have shown the use of 2D conformal microwave absorbing material (MAM) in the design and fabrication of a portable Anechoic chamber (AC). The MAM is fabricated on the transparent and conductive metal oxide layer named indium-tin-oxide (ITO) with Polyethylene terephthalate as the substrate and the ground plane for zero transmission having overall thickness of 0.012 λ where λ is calculated at 0.7 GHz. The MAM is characterized for 0.7 to 18 GHz for both TE- and TM-polarisation and oblique incidence. High sheet resistance, dipole-like resonance structure patterned on the ITO, and the air-spacing between the layers is optimized to achieve broadband absorption. The MAM is used to line the six sides of the rectangular anechoic chamber having inner dimensions of: (L × W × H: 850 × 650 × 720 mm3). The return loss (RL), gain, and radiation pattern of three antenna working at 1.56, 2.43, and 4.93 GHz are analyzed inside the AC. The measurement results for all frequencies very well match with the simulation studies, thus validating and opening the door for the future use of ultra-thin and planar MAM in the AC.

Protective effect of an ERAP1 haplotype in ankylosing spondylitis: investigating non-MHC genes in HLA-B27-positive individuals.

OBJECTIVE: The association of non-MHC genes with AS has been recently suggested. We aimed to investigate the association of the ERAP1, IL23R and TNFSF15 regions and the susceptibility to and protection from AS in HLA-B27-positive individuals. METHODS: A total of 200 unrelated AS patients and 559 healthy unrelated subjects, all HLA-B27 positive, were tested. Twenty single nucleotide polymorphisms (SNPs) were investigated in and near IL23R (nine SNPs), in ERAP1 (five SNPs) and in TNFSF15 (six SNPs). RESULTS: ERAP1 rs30187 [odds ratio (OR) = 1.5, P = 4.7 × 10(-3)] had the strongest association with AS susceptibility. A protective effect was found in three of the ERAP1 SNPs: rs17482078 (OR = 0.7, P = 2.8 × 10(-2)), rs10050860 (OR = 0.7, P = 2.3 × 10(-2)), rs2287987 (OR = 0.6, P = 1.3 × 10(-2)). The ERAP1 haplotype rs17482078/rs10050860/rs30187/rs2287987-CCTT showed an association with AS susceptibility (P = 6.8 × 10(-3)) and a protective effect was identified in rs17482078/rs10050860/rs30187/rs2287987-TTCC (P = 3.1 × 10(-2)). Significant association with AS susceptibility was found in one IL23R marker (rs1004819, P = 4.3 × 10(-2), OR = 1.3). No associations were observed in the TNFSF15 region. CONCLUSION: The identification of a new protection haplotype in ERAP1 and the lack of association of the TNFSF15 region can provide new insights into the understanding of the mechanisms underlying the susceptibility to and protection from AS.

Association study of the platelet collagen receptor glycoprotein VI gene with rheumatoid arthritis.

OBJECTIVES: Beyond their role in haemostasis, platelets can actively contribute to immunity. The activation of the platelet collagen receptor glycoprotein VI (GPVI) promotes the release of small extracellular vesicles called microparticles. These microparticles are found in the joint bathing fluid of patients with rheumatoid arthritis (RA) and are thought to amplify inflammation. The gene coding for GPVI is localised on chromosome 19q13.4 and contains different single nucleotide polymorphisms (SNPs). Five non-synonymous SNPs define the major and minor haplotypes of GPVI. The minor haplotype is associated with higher risk of cardiovascular incidents. In this study, we examined whether this minor haplotype is also associated with RA. METHODS: Allelic discrimination of the SNPs reported to define these haplotypes encoding SKTQH and PEALN protein isoforms, ie rs1613662, rs1654416, rs2304167, rs1654413 and rs1671152, was performed in 399 RA patients and their two parents, all of Western European ethnicity. Statistical analysis relied on the transmission disequilibrium test by the use of the FBAT programme. Haplotypes were also estimated by the FBAT programme. RESULTS: We observed no statistically significant transmission disequilibrium for the SNPs tested. The major haplotype TAAC, which encodes the SKTQH isoform, was identified in 78% of our cohort individuals, and the CGGA haplotype which encodes the PEALN isoform was identified in 8% of our individuals. We observed no association of these haplotypes of the GPVI gene with RA. CONCLUSIONS: This demonstrates that the SNPs tested within the GPVI gene are not associated with RA susceptibility and/or severity, suggesting that platelet GPVI may contribute to arthritis independently of its gene polymorphism.

Equity matrix for kidney transplant allocation.

There is a general agreement that the distribution of kidneys for transplantation should balance utility criteria with justice. Moreover, a kidney allocation system must be based on transparent policies and seen as an ongoing process. This study aims to present an allocation system grounded on an equity matrix that balances the criteria of utility and justice. Synthetic data for a waiting list with 2000 transplant candidates and a pool of 280 donors were generated. A color priority system, the Eurotransplant (ET) kidney allocation system, and the proposed Equity Matrix (EQM) allocation system were compared after 1000 iterations of kidney allocations. Distributions of variables like the age difference, Human Leukocyte Antigens (HLA) mismatches (mmHLA), recipients' time on dialysis, cPRA, and a transplant score obtained by different allocation models were compared graphically and with Cohen's d effect size. For the analyzed variables, when we compare only the selected recipients from ET with the selected recipients from the EQM neutral model, we can conclude that the former model selects more hypersensitized recipients, a higher number of 65+ years' old recipients with 65+ years' old donors and higher number of recipients with 0 mmHLA. While recipients from EQM neutral are slightly older, have a lower age difference with their donors, have a lower number of mmHLA, are less likely to have 6 mmHLA with their donors, and have more time on dialysis. The proposed EQM model attempts to provide a simple, transparent, and equitable response to a complex question with results that outperform established practices.

Children then, adults now: long-term outcomes-performance at 15, 20, and 25 years of cochlear implant use.

Motivation: Severe to profound sensorineural hearing loss interferes with a child's development at the cognitive, linguistic, academic, and social levels. Since the beginning of the pediatric auditory rehabilitation program through cochlear implantation in the Ear, Nose, and Throat (ENT) Service of the Coimbra Hospital and University Center (CHUC), Portugal, its mentors defended the early diagnosis of hearing loss followed by timely intervention, and this was considered the starting point to optimize (re)habilitation through this method. Three decades or so later, recently we conducted this study to evaluate the performance of patients implanted in the initial phase of the cochlear implantation program. Objectives: The study aimed to evaluate the performance of individuals with severe to profound congenital hearing loss who underwent pediatric cochlear implantation and have used the cochlear implant for at least 25 years, to analyze the beneficial effect of early intervention in improving performance results. Methods: The study sample is composed of 31 individuals with severe to profound congenital hearing loss and no other comorbidities, divided into two groups (Group 1: age at implantation was under 3 years; Group 2: age at implantation was over 3 years). All 31 subjects were evaluated at 15, 20, and 25 years of cochlear implant (CI) use with a comprehensive set of tests. In addition, data were collected regarding the academic level of each participant. The results of both groups were compared to find out if there is an effect of age at implantation on auditory performance, and if there is an improvement in the performance with CI over time (15, 20, and 25 years of use). Results: The results show that there is a positive effect, with statistical significance, of early implantation on auditory performance, and telephone use. In both groups, there is an increase in performance over time, but it tends to stabilize after 20 years of CI use. Discussion and conclusion: The results obtained in this work support the importance of early intervention in patients with severe to profound hearing loss who are cochlear implant users and show that CI is an effective and reliable method in the treatment of these patients, contributing to their improved socio-educational integration, and that the benefits last over time.

A high density SNP genotyping approach within the 19q13 chromosome region identifies an association of a CNOT3 polymorphism with ankylosing spondylitis.

OBJECTIVE: To identify genomic variants in the 19q13 chromosome region associated with ankylosing spondylitis (AS) in human leucocyte antigen (HLA)-B27-positive populations. METHODS: High-throughput genotyping of 1536 haplotype-tag single nucleotide polymorphisms (SNPs) was performed in 249 patients with AS and 302 healthy controls. Some of the identified associations were validated by genotyping four SNPs in two additional cohorts consisting of 412 cases/301 controls and 144 cases/203 controls. All individuals selected (both cases and controls) were HLA-B27-positive. RESULTS: Two markers in two different genes (CNOT3 and LAIR2) showed significant association (p<10(-3)) with AS. In addition, sliding windows analysis showed association of groups of adjacent SNPs in regions located around CNOT3 (Chr19: 59347459-59356564, p=2.43 × 10(-4) to 6.54 × 10(-4)). The associations were validated by genotyping four SNPs from regions located near LAIR2 and CNOT3 genes (rs1055234, rs8111398, rs2287828 and rs4591276) in two additional cohorts. The CNOT3 polymorphism (rs1055234) remained associated with AS (combined p=9.73 × 10(-6)). One SNP, located downstream of KIR3DL1, was detected which, tested in combination with HLA-Bw4I80, was associated with AS. CONCLUSION: A novel significant association was detected between SNP rs1055234 and AS susceptibility.

Kidney allocation rules simulator.

The greatest challenge of any kidney transplant program lies in finding enough organ donors (in number and quality) for all waitlisted transplant candidates. Unfortunately, we must resign ourselves to a manifestly insufficient supply of organs for the current demand. Furthermore we must be able to predict kidney transplant success at organ allocation if we want to minimize the number of patients who return to an already overcrowded waiting list for transplantation. Therefore, the definition of deceased donors' kidney allocation rules on transplantation must be supported by simulations that allow foreseeing, as much as possible, the consequences of these rules. Here we present the Kidney Allocation Rules Simulator (KARS) application that enables testing different kidney transplant allocation' systems with different donors and transplant candidates' datasets. In this application, it is possible to simulate allocation rules implemented in Portugal, in the United Kingdom, in countries within Eurtotransplant, and a previously suggested color priority system. As inputs, this application needs three data files: a file with transplant candidates' information, a file with candidates' anti-HLA antibodies, and a file with donors' information. As output, we will have a file with donor-recipient pairs selected according to the kidney allocation system simulated. When seeking waste reduction while ensuring a fair distribution of organs from deceased donors, the definition of rules selecting donor-recipient pairs in renal transplantation must be based on evidence supported by data. On the continuously changing process for a better distribution of an increasingly scarce resource must, we must be able to predict transplant outcomes when defining the best allocation rules.

Harvesting circuits for triboelectric nanogenerators for wearable applications.

Internet of Things (IoT) and recently Internet of Nano Things (IoNT) bear the promise of new devices able to communicate and assist our daily lives toward wearable technologies which demand a versatile integration such as in wireless body networks (WBN), sensing, and health monitorization. These must comply with stringent constraints on energy usage. Dimensions and complexity intensify the need for small and maintenance-free power sources. Environment energy harvesting and storage is an important approach to sustain operation for a long time. Triboelectric nanogenerators (TENGs) arise as a strong and promising solution to power the new field of outcoming self-sustainable devices, implantable, and wearable devices. They can transform mechanical energy in different modes, have simple structures, and use vulgar and sustainable materials. This paper makes a review about TENGs technology, construction, materials, operation, and focus on strategies for harvesting circuits. Main challenges like efficiency, reliability, energy storage, and sustainability are discussed.

Glycaemic control during the COVID-19 pandemic: A catastrophe or a sign of hope for the person with type 1 Diabetes Mellitus?

INTRODUCTION: In a person with type 1 diabetes, any change concerning daily routine may lead to changes in glycaemic control. This study aimed to evaluate the impact of work and lockdown on glycaemic control in adults with type 1 diabetes. MATERIAL AND METHODS: A retrospective cohort was stratified into three activity groups (g1-students/telework/laid-off; g2-unemployed/retired; g3-work without lockdown). Continuous and categorical variations (reductions≥0.4%) in glycated haemoglobin were obtained in 2020 (t3:December/2019-March/2020; t4:April/2020-July/2020) and in homologous periods of 2019. Intragroup comparisons between years and intergroups in the same year were made. Regression models were developed to predict the variation of glycated haemoglobin in 2020. RESULTS: 241 participants were included, with a significant reduction between t4 and t3 (vs. t2 and t1) in g1 (p<0.001) and g2 (p=0.025) and in 2020 in g1 (vs. g2, p<0.001; vs. g3, p<0.001). Only g1 presented superiority in the reduction ≥0.4% in glycated haemoglobin in 2020 (vs. 2019, p<0.001; vs. g2, p<0.001; vs. g3, p<0.001). The insulin regimens were comparable and the development of hypoglycaemia was found to be superimposed between t3 and t4, except for g1, which was higher at t3 (p=0.029). G1 correlated with continuous reductions (vs. g2, p=0.001; vs. g3, p<0.001) and ≥0.4% in glycated haemoglobin in 2020 (vs. g2, OR 3.6, p<0.001; vs. g3, OR 12.7, p<0.001), regardless of the age and duration of type 1 diabetes. CONCLUSIONS: A more stable and better glycaemic control was observed in participants who transitioned from face-to-face work to total lockdown.

Impact of pharmacological treatment of gestational diabetes on the mode of delivery and birth weight: a nationwide population-based study on a subset of singleton pregnant Portuguese women.

AIMS: To access the impact of increasing use of metformin on cesarean section and large for gestational age rates, when compared to insulin. METHODS: A retrospective observational study was developed using data from the Portuguese National Registry, between 2011 and 2019, of 5038 Portuguese women with single pregnancies and gestational diabetes treated with metformin and/or insulin. Three groups were defined according to the therapeutic regimen adopted: g1-insulin in monotherapy (n = 3027[60.1%]); g2-metformin in monotherapy (n = 1366[27.1%]); g3-metformin and insulin (n = 645[12.8%]). Multivariate analysis was adjusted for statistically significant covariates. RESULTS: The cesarean section rate in g1 was similar to g2 (g1:36.9% vs. g2:37%, p = 0.982), although g3 was associated with cesarean delivery (g3:43.6% vs. g1:36.9%, p = 0.005; g3:43.6% vs. g1:37.0%, p = 0.002), with no differences reported in the multivariate analysis adjusted for year of delivery and pregestational body mass index. A delivery of a large for gestational age newborn was less frequently observed in g2 than in g1 (g2:4.1% vs. g1:5.4%, p = 0.044) and in g3 (g2:4.1% vs. g3:9.1%, p < 0.001), and in g1, when compared to g3 (g1:5.4% vs. g3:9.1%, p < 0.001). In the multivariate analysis, g2 showed lower odds of delivering a large for gestational age newborn, compared to g1 (ß = -0.511, OR = 0.596, CI95% = 0.428-0.832, p < 0.001). CONCLUSIONS: The use of metformin was not associated with higher cesarean section rates, compared to insulin. Instead, it was suggested a protective role of metformin on large gestational age rates. The concomitant use of dual therapy suggests more complex pregnancies, requiring closer surveillance that mitigate serious perinatal and obstetrical outcomes.