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1.
Bioengineering (Basel) ; 11(3)2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38534483

ABSTRACT

Platelet-rich plasma (PRP) has emerged as a promising therapy in regenerative medicine. However, the lack of standardization in PRP preparation protocols presents a challenge in achieving reproducible and accurate results. This study aimed to optimize the PRP preparation protocol by investigating the impact of two different anticoagulants, sodium citrate (SC) and ethylenediaminetetraacetic acid (EDTA), and resuspension media, plasma versus sodium chloride (NaCl). Platelet recovery rates were calculated and compared between groups, in addition to platelet activity and vascular endothelial growth factor (VEGF) released into plasma after PRP activation. The platelet recovery rate was higher with EDTA in comparison to SC (51.04% vs. 29.85%, p = 0.005). Platelet activity was also higher, with a higher expression of two platelet antibodies, platelet surface P-Selectin (CD62p) and PAC-1, in the EDTA group. The concentration of VEGF was higher with SC in comparison to EDTA (628.73 vs. 265.44 pg/mL, p = 0.013). Platelet recovery rates and VEGF levels were higher in PRP resuspended in plasma when compared to NaCl (61.60% vs. 48.61%, p = 0.011 and 363.32 vs. 159.83 pg/mL, p = 0.005, respectively). Our study reinforces the superiority of EDTA (as anticoagulant) and plasma (for resuspension) in obtaining a higher platelet recovery and preserving platelet functionality during PRP preparation.

2.
J Biomech ; 161: 111860, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37948877

ABSTRACT

Machine learning (ML) and deep learning (DL) approaches can solve the same problems as the finite element method (FEM) with a high degree of accuracy in a fraction of the required time, by learning from previously presented data. In this work, the bone remodelling phenomenon was modelled using feed-forward neural networks (NN), by gathering a dataset of density distribution comprising several geometries and load cases. The model should output for some point in the domain the its apparent density, taking into consideration the geometric and loading parameters of the model . After training. the trabecular distribution obtained with the NN was similar to the FEM while the analysis was performed in a fraction of the time, having shown a reduction from 1020 s to 0.064 s. It is expected that the results can be extended to different structures if a different dataset is acquired. In summary, the ML approach allows for significant savings in computational time while presenting accurate results.


Subject(s)
Femur , Neural Networks, Computer , Lower Extremity , Finite Element Analysis
3.
Front Endocrinol (Lausanne) ; 14: 1250203, 2023.
Article in English | MEDLINE | ID: mdl-38034001

ABSTRACT

The rarity of lipodystrophies implies that they are not well-known, leading to delays in diagnosis/misdiagnosis. The aim of this study was to assess the natural course and comorbidities of generalised and partial lipodystrophy in Spain to contribute to their understanding. Thus, a total of 140 patients were evaluated (77.1% with partial lipodystrophy and 22.9% with generalised lipodystrophy). Clinical data were collected in a longitudinal setting with a median follow-up of 4.7 (0.5-17.6) years. Anthropometry and body composition studies were carried out and analytical parameters were also recorded. The estimated prevalence of all lipodystrophies in Spain, excluding Köbberling syndrome, was 2.78 cases/million. The onset of phenotype occurred during childhood in generalised lipodystrophy and during adolescence-adulthood in partial lipodystrophy, with the delay in diagnosis being considerable for both cohorts. There are specific clinical findings that should be highlighted as useful features to take into account when making the differential diagnosis of these disorders. Patients with generalised lipodystrophy were found to develop their first metabolic abnormalities sooner and a different lipid profile has also been observed. Mean time to death was 83.8 ± 2.5 years, being shorter among patients with generalised lipodystrophy. These results provide an initial point of comparison for ongoing prospective studies such as the ECLip Registry study.


Subject(s)
Lipodystrophy, Congenital Generalized , Lipodystrophy , Adolescent , Humans , Adult , Lipodystrophy, Congenital Generalized/diagnosis , Lipodystrophy, Congenital Generalized/epidemiology , Spain/epidemiology , Prospective Studies , Lipodystrophy/diagnosis , Lipodystrophy/epidemiology , Lipodystrophy/genetics , Syndrome
4.
WIREs Mech Dis ; 15(6): e1624, 2023.
Article in English | MEDLINE | ID: mdl-37533299

ABSTRACT

Endometriosis is a disease with a heterogeneous pathogenesis, explained by multiple theories, and also with a polymorphic presentation. The purpose of this literature review is to systematize the genetic, inflammatory, and environmental factors related to the pathophysiology of endometriosis. Current evidence suggests that endometriosis is a complex inherited genetic condition, in which the genes that determine susceptibility to the disease interact with the environment to develop different phenotypes. Genetic variants associated with risk of endometriosis have been identified in several genome-wide association studies, in addition to a group of genes related to the pathophysiology of endometriosis, namely the estrogen, progesterone and androgen receptors and the cytochrome P450 gene, as well as the p53 gene. The role of inflammation is controversial; however, it is an essential process, both in the initiation and perpetuation of the disease, in and outside the pelvis. Alterations in reactive oxygen species pathways that consequently determine oxidative stress are typical in the inflammatory environment of endometriosis. The role of environmental factors is a relatively new and broad-spectrum topic, with inconsistent evidence. Multiple factors have been studied such as endocrine-disrupting chemicals, metals, intrauterine exposure to diethylstilbesterol and lifestyle risk factors. In conclusion, endometriosis remains a mysterious condition, with multifactorial factors involved in its pathophysiology. The progress that has been made in the genetic predisposition to endometriosis may allow the establishment of new therapeutic targets. On the other hand, understanding the role of the environment in this disease may allow preventive intervention, minimizing its incidence and/or severity. This article is categorized under: Reproductive System Diseases > Molecular and Cellular Physiology Reproductive System Diseases > Environmental Factors Reproductive System Diseases > Genetics/Genomics/Epigenetics.


Subject(s)
Endometriosis , Female , Humans , Endometriosis/genetics , Genome-Wide Association Study , Genetic Predisposition to Disease/genetics , Estrogens , Progesterone
5.
Bioengineering (Basel) ; 10(5)2023 Apr 25.
Article in English | MEDLINE | ID: mdl-37237585

ABSTRACT

Multiscale techniques, namely homogenization, result in significant computational time savings in the analysis of complex structures such as lattice structures, as in many cases it is inefficient to model a periodic structure in full detail in its entire domain. The elastic and plastic properties of two TPMS-based cellular structures, the gyroid, and the primitive surface are studied in this work through numerical homogenization. The study enabled the development of material laws for the homogenized Young's modulus and homogenized yield stress, which correlated well with experimental data from the literature. It is possible to use the developed material laws to run optimization analyses and develop optimized functionally graded structures for structural applications or reduced stress shielding in bio-applications. Thus, this work presents a study case of a functionally graded optimized femoral stem where it was shown that the porous femoral stem built with Ti-6Al-4V can minimize stress shielding while maintaining the necessary load-bearing capacity. It was shown that the stiffness of cementless femoral stem implant with a graded gyroid foam presents stiffness that is comparable to that of trabecular bone. Moreover, the maximum stress in the implant is lower than the maximum stress in trabecular bone.

6.
JBRA Assist Reprod ; 27(3): 414-421, 2023 09 12.
Article in English | MEDLINE | ID: mdl-37257074

ABSTRACT

OBJECTIVE: To evaluate the outcomes of a long GnRH agonist protocol with corifollitropin alfa followed by hMG in low responders. METHODS: Retrospective cohort study. Patients with a suboptimal previous ovarian response (<9 oocytes) and a normal ovarian reserve (Poseidon groups 1 and 2) were classified in 1) Group 1 (n=88), submitted to a second cycle with a GnRH antagonist protocol using rFSH/hMG; 2) Group 2 (n=66), submitted to a long GnRH agonist protocol with corifollitropin alfa followed by hMG (named as simplified long protocol). Clinical outcomes were compared between groups and between the first/second cycle of each group. RESULTS: Clinical outcomes were similar between groups. There were no differences in the number of oocytes [7(5-11.75) versus 7(5-10), p=0.802], clinical pregnancy (19.3% versus 18.2%, p=0.858) and live birth rates (18.2% versus 15.2%, p=0.619). However, baseline characteristics were different, decoding a poor prognosis among women in group 2. Both groups (1 and 2) had significantly higher number of oocytes, pregnancy, and live birth rates in the second cycle. In group 2, there was a higher rate of embryo transfer (56.1% versus 27.3%, p<0.001). In group 1, despite the similar rate of embryo transfer, there was a higher positive hCG (23.9% versus 8.0%, p=0.004). CONCLUSIONS: Both simplified long protocol and GnRH antagonist protocol are suitable for low responders. The best second cycle clinical outcomes experienced in a population with worse prognosis (group 2) suggests that the simplified long protocol may be a better option, although prospective well-conducted studies must explore this hypothesis.


Subject(s)
Gonadotropin-Releasing Hormone , Ovulation Induction , Pregnancy , Humans , Female , Prospective Studies , Retrospective Studies , Pregnancy Rate , Ovulation Induction/methods , Fertilization in Vitro/methods
8.
Genet Mol Biol ; 45(4): e20220038, 2022.
Article in English | MEDLINE | ID: mdl-36469480

ABSTRACT

Banana tree bacterial wilt is caused by the Ralstonia solanacearum Moko ecotype. These strains vary in their symptom progression in banana, and are classified as typical Moko variants (phylotype IIA and IIB strains from across Central and South America), Bugtok variant (Philippines), and Sergipe facies (the states of Sergipe and Alagoas, Brazil). This study used comparative genomic and phylogenomic approaches to identify a correlation between the symptom progression of the Moko ecotypes based on the analysis of 23 available genomes. Average nucleotide identity and in silico DNA-DNA hybridization revealed a high correlation (>96% and >78%, respectively) between the genomes of Moko variants. Pan-genome analysis identified 21.3% of inheritable regions between representatives of the typical Moko and Sergipe facies variants, which could be traced to an abundance of exclusive homolog clusters. Moko ecotype genomes shared 1,951 orthologous genes, but representatives with typical symptoms did not display unique orthologues. Moreover, Bugtok disease and Sergipe facies genomes did not share any unique genes, suggesting convergent evolution to a shared symptom progression. Overall, genomic and phylogenomic analyses were insufficient to differentiate the Moko variants based on symptom progression.

9.
Bioengineering (Basel) ; 9(8)2022 Jul 30.
Article in English | MEDLINE | ID: mdl-36004882

ABSTRACT

Ovarian tissue cryopreservation is a female fertility preservation technique that presents major challenges for the maintenance of follicular viability after transplantation. The aim of this study was to evaluate and compare the application of L-Mesitran Soft®, a product containing 40% medical grade honey (MGH), with other strategies to improve ovarian grafts' viability. For this purpose, bovine ovarian tissue was vitrified, warmed and randomly assigned to culture groups: (1) control, (2) MGH 0.2% in vitro, (3) MGH in vivo (direct application in the xenotransplantation), (4) vascular endothelial growth factor (VEGF 50 ng/mL) and (5) vitamin D (100 Nm), during a 48 h period. A sixth group (6) of fragments was thawed on transplantation day and was not cultured. The tissue was xenotransplanted into immunodeficient (Rowett nude homozygous) ovariectomized rats. Grafts were analyzed 48 h after culture, and 7 and 28 days after transplantation. The tissue was subjected to histological and immunohistochemical analysis. Treatments using MGH showed the highest angiogenic and cell proliferation stimulation, with cellular apoptosis, within a healthy cellular turnover pathway. In conclusion, MGH should be considered as a potentially effective and less expensive strategy to improve ovarian tissue transplantation.

10.
Nat Commun ; 13(1): 1160, 2022 03 04.
Article in English | MEDLINE | ID: mdl-35246567

ABSTRACT

Biological systems must adjust to changing external conditions, and their resilience depends on their control mechanisms. How is dynamic control implemented in noisy, decentralized systems? Army ants' self-assembled bridges are built on unstable features, like leaves, which frequently move. Using field experiments and simulations, we characterize the bridges' response as the gaps they span change in size, identify the control mechanism, and explore how this emerges from individuals' decisions. For a given gap size, bridges were larger after the gap increased rather than decreased. This hysteresis was best explained by an accumulator model, in which individual decisions to join or leave a bridge depend on the difference between its current and equilibrium state. This produces robust collective structures that adjust to lasting perturbations while ignoring small, momentary shifts. Our field data support separate joining and leaving cues; joining is prompted by high bridge performance and leaving by an excess of ants. This leads to stabilizing hysteresis, an important feature of many biological and engineered systems.


Subject(s)
Ants , Animals , Ants/physiology , Humans , Noise
11.
Hum Fertil (Camb) ; : 1-10, 2022 Feb 21.
Article in English | MEDLINE | ID: mdl-35184644

ABSTRACT

The incidence of haematological malignancies is increasing in women of childbearing age. Survival rates accompany this increase, making it essential to assess the impact of treatments on their future quality of life, evaluate the impact of each treatment on ovarian reserve and define the fertility preservation techniques used by women with haematologic malignancies. A retrospective study was conducted after data collection from 61 women diagnosed with haematological malignancies and followed-up in a fertility preservation centre between January 2008 and June 2019. Cancer treatments caused a decrease in ovarian reserve, demonstrated by an increase in FSH levels and a decrease in AMH levels. When assessing which treatments have the greatest impact on AMH levels, we found that the BEACOPP regimen, and the agents vincristine, etoposide, procarbazine, prednisone and the haematopoietic stem cell transplantation were mainly responsible. Regarding pregnancy after oncological treatments, of the eleven women who became pregnant, ten did so spontaneously. This study reinforces the importance of referring patients to a fertility preservation consultation before starting oncological treatment, as most of them opt to preserve fertility. This work also helps to clarify the impact of each chemotherapeutic agent on the ovarian reserve.

12.
J Ovarian Res ; 14(1): 147, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34724957

ABSTRACT

BACKGROUND: Cryopreservation of ovarian tissue is a powerful technique for preserving female fertility, as it can restore fertility and endocrine function. To increase the longevity of the transplant and decrease the risk of reimplantation of neoplastic cells, several studies have been carried out with culture of ovarian tissue. The aim of this study was to compare a conventional (2D) culture with an alginate matrix three-dimensional (3D) model for ovarian tissue culture. RESULTS: The ovarian tissue culture within the alginate matrix (3D) was similar to 2D culture, regarding follicular density and cell apoptosis in follicles and stroma. The proliferation rate remained stable in both models for follicles, but for stromal cell proliferation it decreased only in 3D culture (p = 0.001). At 24 h of culture, cytotoxicity was lower in the 3D model (p = 0.006). As culture time increased, cytotoxicity seemed similar. Degradation of the tissue was suggested by the histological score analysis of tissue morphology after 72 h of culture. Tissue injury was greater (p = 0.01) in 3D culture due to higher interstitial oedema (p = 0.017) and tissue necrosis (p = 0.035). CONCLUSION: According to our results, 3D culture of ovarian tissue has no advantage over 2Dculture; it is more time consuming and difficult to perform and has worse reproducibility.


Subject(s)
Cryopreservation/methods , Fertility Preservation/methods , Ovarian Follicle/diagnostic imaging , Tissue Culture Techniques/methods , Female , Humans
13.
J Clin Med ; 10(7)2021 Apr 03.
Article in English | MEDLINE | ID: mdl-33916827

ABSTRACT

Type 2 familial partial lipodystrophy, or Dunnigan disease, is a metabolic disorder characterized by abnormal subcutaneous adipose tissue distribution. This rare condition results from variants principally affecting exons 8 and 11 of the LMNA gene. In this study, five FPLD2-diagnosed patients carrying the c.1583C>T, p.(Thr528Met) variant in exon 9 of the LMNA gene and with obvious clinical heterogeneity were evaluated. Specific polymorphisms in LMNA and in PPARG were also detected. Exhaustive clinical course, physical examination, biochemical features and family history were recorded, along with the assessment of anthropometric features and body composition by dual-energy X-ray absorptiometry. Preadipocytes obtained from a T528M patient were treated with the classic adipose differentiation medium with pioglitazone. Various adipogenes were evaluated by real-time PCR, and immunofluorescence was used to study intracellular localization of emerin, lamin A and its precursors. As demonstrated with Oil red O staining, the preadipocytes of the T528M patient failed to differentiate, the expression of various adipogenic genes was reduced in the lipodystrophic patient and immunofluorescence studies showed an accumulation of farnesylated prelamin A in T528M cells. We conclude that the T528M variant in LMNA could lead to FPLD2, as the adipogenic machinery is compromised.

14.
Ginekol Pol ; 92(3): 220-225, 2021.
Article in English | MEDLINE | ID: mdl-33751518

ABSTRACT

Endometriosis-associated malignancy in an episiotomy scar is rare. The predictive factors are poorly understood as are the mechanisms and pathways associated with implantation and malignant transformation. In this study we describe the cases reported in the literature of malignancies arising in endometriosis foci of an episiotomy scar. We identified 5 cases described between 1990 and 2016. These cases represent recurrence of endometriotic lesions in an episiotomy scar after previous diagnosis of endometriosis, 3 to 25 months before. Histology revealed clear cell tumours in 4 cases and a serous papillary carcinoma. The approach encompassed surgical removal for diagnosis and as part of the therapeutic strategy. Adjuvant treatment was performed depending on classical prognostic factors. Mechanisms of endometriosis implantation in scars include the influence of estrogens in the healing process and activation of COX-2, aromatase and matrix metalloproteinases. Nevertheless, for malignant transformation, other pathways seem to play a role, namely inflammation, immune response and oxidative stress, induced by iron deposits due to haemorrhage. Further studies are needed to allow the establishment of a predictive model for malignant transformation of endometriosis in episiotomy scars.


Subject(s)
Endometriosis , Episiotomy , Cell Transformation, Neoplastic , Cicatrix/complications , Endometriosis/complications , Endometriosis/surgery , Episiotomy/adverse effects , Female , Humans , Pregnancy
15.
J Clin Med ; 10(3)2021 Jan 22.
Article in English | MEDLINE | ID: mdl-33499120

ABSTRACT

Ovarian endometrioma are found in up to 40% of women with endometriosis and 50% of infertile women. The best surgical approach for endometrioma and its impact on pregnancy rates is still controversial. Therefore, we conducted a literature review on surgical management of ovarian endometrioma and its impact on pregnancy rates and ovarian reserve, assessed by anti-Müllerian hormone (AMH) serum levels. Ovarian cystectomy is the preferred technique, as it is associated with lower recurrence and higher spontaneous pregnancy rate. However, ablative approaches and combined techniques are becoming more popular as ovarian reserve is less affected and there are slightly higher pregnancy rates. Preoperative AMH level might be useful to predict the occurrence of pregnancy. In conclusion, AMH should be included in the preoperative evaluation of reproductive aged women with endometriosis. The surgical options for ovarian endometrioma should be individualized. The endometrioma ablation procedure seems to be the most promising treatment.

16.
Gynecol Endocrinol ; 37(6): 483-489, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33501866

ABSTRACT

Ovarian cancer is more frequent in post-menopausal women, however it can also occur in young premenopausal women. After diagnosis and cancer staging, health care providers should address the possibility of infertility and might offer fertility preservation options. Chemotherapy, frequently used when treating ovarian cancer, has proven to cause extensive ovarian damage. Standard surgery may be aggressive and the recurrence risk may not be relevant enough to opt for these approaches. Fertility sparing surgery has been progressively accepted and many alternative surgical approaches have proven to be successful in both cancer treatment, fertility preservation and low recurrence rates. Though there are several techniques available for fertility preservation in cancer patients, when dealing with ovarian cancer patients, oocyte and embryo cryopreservation are the only suitable. Ovarian tissue cryopreservation has been largely studied, but no data on ovarian cancer patients exist, due to the risk of reimplanting cancer cells.


Subject(s)
Carcinoma, Ovarian Epithelial/therapy , Fertility Preservation/methods , Ovarian Neoplasms/therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Ovarian Epithelial/pathology , Cryopreservation/methods , Embryo, Mammalian , Female , Humans , Infertility, Female/chemically induced , Infertility, Female/prevention & control , Neoplasm Recurrence, Local/prevention & control , Oocytes , Ovarian Neoplasms/pathology , Ovary
17.
Genet Mol Biol ; 44(1): e20200172, 2021.
Article in English | MEDLINE | ID: mdl-33458736

ABSTRACT

Banana vascular wilt or Moko is a disease caused by Ralstonia solanacearum. This study aimed to sequence, assemble, annotate, and compare the genomes of R. solanacearum Moko ecotypes of different sequevar strains from Brazil. Average nucleotide identity analyses demonstrated a high correlation (> 96%) between the genome sequences of strains CCRMRs277 (sequevar IIA-24), CCRMRs287 (IIB-4), CCRMRs304 (IIA-24), and CCRMRsB7 (IIB-25), which were grouped into phylotypes IIA and IIB. The number of coding sequences present in chromosomes and megaplasmids varied from 3,070 to 3,521 and 1,669 to 1,750, respectively. Pangenome analysis identified 3,378 clusters in the chromosomes, of which 2,604 were shared by all four analyzed genomes and 2,580 were single copies. In megaplasmids, 1,834 clusters were identified, of which 1,005 were shared by all four genomes and 992 were identified as single copies. Strains CCRMRsB7 and CCRMRs287 differed from the others by having unique clusters in both their chromosomes and megaplasmids, and CCRMRsB7 possessed the largest genome among all Moko ecotype strains sequenced to date. Therefore, the genomic information obtained in this study provides a theoretical basis for the identification, characterization, and phylogenetic analysis of R. solanacearum Moko ecotypes.

18.
Acta Med Port ; 34(9): 580-585, 2021 Aug 31.
Article in English | MEDLINE | ID: mdl-33118925

ABSTRACT

INTRODUCTION: Chromosome abnormalities contribute to about 10% of cases of premature ovarian insufficiency. Most are associated with X chromosome. Fragile mental retardation 1 (FMR1) gene premutation has an estimated prevalence of 1% - 7% in sporadic cases and up to 13% in familial cases. Our aim was to describe the clinical characteristics, cytogenetic and FMR1 testing of a Portuguese population with premature ovarian insufficiency. MATERIAL AND METHODS: Women diagnosed with premature ovarian insufficiency in a Portuguese tertiary centre were retrospectivelyanalysed. Data were retrieved from electronic medical records including clinical characteristics, cytogenetic and FMR1 testing. The main outcome measures were the prevalence of chromosome abnormalities and FMR1 premutation in a Portuguese population with premature ovarian insufficiency. RESULTS: Ninety-four patients were included, with a median age at menopause of 36 years. The prevalence of chromosome abnormalities was 16.5% (14/85) and most were X chromosome related (78.6%). The prevalence of FMR1 premutation was 6.7% (6/90). The prevalence of karyotypic abnormalities or FMR1 premutation did not differ significantly between familial and sporadic cases. Neither chromosome abnormalities nor FMR1 premutation influenced age at menopause or follicle stimulating hormone levels at diagnosis in premature ovarian insufficiency patients. DISCUSSION: This is the first study describing the clinical characteristics and both cytogenetic and FMR1 testing in a Portuguese population with premature ovarian insufficiency. The rate of chromosome abnormalities in our sample was higher than in other populations, while the prevalence of FMR1 premutation was similar to previous reports. CONCLUSION: Our results underline the importance of genetic screening in premature ovarian insufficiency patients in both etiological study and genetic counselling.


Introdução: As anomalias cromossómicas contribuem para 10% dos casos de insuficiência ovárica prematura estando maioritariamente associadas ao cromossoma X. A pré-mutação do gene fragile mental retardation 1 (FMR1) tem uma prevalência estimada de 1% - 7% nos casos esporádicos e até 13% nos casos familiares. O nosso objetivo foi descrever as características clínicas e a análise citogenética e do gene FMR1 de uma população Portuguesa com insuficiência ovárica prematura. Material e Métodos: Análise retrospetiva das mulheres com o diagnóstico de insuficiência ovárica prematura vigiadas num hospital terciário Português. Recolha de dados através do processo médico eletrónico incluindo características clínicas, análise citogenética e análise do gene FMR1. Os desfechos principais foram a prevalência de anomalias cromossómicas e da pré-mutação FMR1 numa população Portuguesa com insuficiência ovárica prematura. Resultados: Foram incluídas 94 doentes, com uma mediana de idade de menopausa de 36 anos. A prevalência de anomalias cromossómicas foi 16,5% (14/85) e a maioria estavam relacionadas com o cromossoma X (78,6%, n = 11). A prevalência da pré-mutação FMR1 foi de 6,7% (6/90). A prevalência de anomalias cromossómicas ou pré-mutação FMR1 não diferiu entre casos esporádicos e familiares. Nem as anomalias cromossómicas nem a pré-mutação FMR1 influenciaram a idade de menopausa ou os níveis da hormona estimulante dos folículos capilares aquando do diagnóstico na população com insuficiência ovárica prematura. Discussão: Este é o primeiro estudo a descrever as características clínicas e a análise citogenética e do gene FMR1 numa população Portuguesa com insuficiência ovárica prematura. A prevalência de anomalias cromossómicas na nossa amostra foi superior à descrita para outras populações, enquanto a prevalência da pré-mutação FMR1 foi semelhante à descrita em estudos anteriores. Conclusão: Os nossos resultados sublinham a importância do rastreio genético em doentes com insuficiência ovárica prematura, quer no estudo etiológico, quer no aconselhamento genético.


Subject(s)
Intellectual Disability , Primary Ovarian Insufficiency , Chromosome Aberrations , Female , Fragile X Mental Retardation Protein/genetics , Humans , Portugal/epidemiology , Prevalence , Primary Ovarian Insufficiency/genetics
19.
J Oncol Pharm Pract ; 27(6): 1432-1438, 2021 Sep.
Article in English | MEDLINE | ID: mdl-32936721

ABSTRACT

PURPOSE: The aim of this study was to assess the safety profiles of two biosimilar medicines (rituximab and trastuzumab) in the treatment of cancer patients within a Portuguese oncology hospital. METHODS: This hospital-based prospective observational study followed a cohort event monitoring approach focused on signalling suspected adverse drug reactions (ADRs). Patients undergoing treatment with rituximab biosimilar CT-P10 (Truxima®) or trastuzumab biosimilar CT-P6 (Herzuma®) were recruited over an 11-month and a 6-month period, respectively. Clinicians identified eligible patients and used paper-based forms to report all ADRs associated with biosimilar medicines. ADR case reports were assessed for seriousness, expectedness and causality in the Pharmacovigilance Unit of Coimbra. RESULTS: Ninety-four patients received biosimilar medicines (rituximab, n = 35; trastuzumab, n = 59). Of those, 4 patients (11.4%) experienced 16 ADRs with rituximab and 1 patient (1.7%) experienced 5 ADRs with trastuzumab. All case reports contained serious and expected ADRs that were at least probably related with biosimilar medicines under study. Based on the MedDRA PT coding, the most reported ADR for rituximab CT-P10 was chest discomfort (n = 4; 19.1%), followed by odynophagia (n = 2; 9.5%). Trastuzumab CT-P6 was associated with back pain, headache, pain in extremity, tachypnoea and tremor (each, n = 1; 4.8%). CONCLUSION: The results of this study suggest that using biosimilar rituximab and biosimilar trastuzumab to treat cancer patients in the real-world clinical setting is associated with acceptable safety profiles. No new safety problems were identified.


Subject(s)
Biosimilar Pharmaceuticals , Biosimilar Pharmaceuticals/adverse effects , Hospitals , Humans , Portugal , Rituximab/adverse effects , Trastuzumab/adverse effects
20.
Genet Mol Biol ; 43(4): e20200155, 2020.
Article in English | MEDLINE | ID: mdl-33156891

ABSTRACT

Ralstonia solanacearum is the causal agent of Moko disease in bananas, which in the state of Sergipe in northeastern Brazil causes "Sergipe facies". This disease induces atypical symptoms similar to those of Bugtok disease in the Philippines. This study was conducted to sequence, assemble, and annotate the genomes of the Sergipe facies-causing isolates SFC and IBSBF2570 (sequevar IIA-53) and compare their genomes with two representative isolates causing Bugtok disease. The genomes were sequenced and assembled, resulting in lengths of 5.58 Mb (SFC) and 5.46 Mb (IBSBF2570) in 185 and 174 contigs, respectively. The isolates of Sergipe facies and Bugtok disease showed similarities in their gene contents. We identified 5,668 information clusters, 3,752 of which were shared by all genomes (core genes). Moreover, 3,585 single-copy genes were identified. Isolates causing Bugtok disease exclusively shared 266 more information clusters than the isolates causing Sergipe facies. These results suggest that Sergipe facies and Bugtok disease isolates show high genomic similarity. However, the similarity is even greater between the Bugtok disease isolates. This may be because of their longer period of interaction compared to Sergipe facies isolates.

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