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1.
BMC Public Health ; 24(1): 684, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38438977

ABSTRACT

BACKGROUND: The human-animal bond has been recognized as having positive effects on the health and well-being of both humans and pets. The present study aims to explore the influence of attachment on physical activity (PA), lifestyle, and health outcomes of dog owners (DO), highlighting the mutual benefits resulting from the relationship between DO and dogs. METHODS: Thirty-eight DO and their dogs participated in this study. Socio-demographic data, the Self-Rated Health (SRH), FANTASTICO Lifestyle Scale, and the Lexington Attachment Pet Scale (LAPS) were assessed. PA was measured in both the DO and the dogs, using an ActiGraph GT3X accelerometer in the context of daily routine. Descriptive statistics and Spearman rank correlation analyses were performed to examine the associations between LAPS, PA levels, socio-demographic variables, lifestyle behaviors, and SRH. RESULTS: Significant correlations were found between the dog owners' light-level PA and the pets' vigorous level of PA (rho = 0.445, p = 0.01). Furthermore, the importance of the pets' health (rho = -0.785, p = 0.02) and the LAPS subscales, namely proximity (rho = 0.358, p = 0.03), and attachment (rho = 0.392, p = 0.01), were related to taking the pet for a walk. Regarding lifestyle, DO with a healthier lifestyle had a better self-assessment of their health using the SRH (rho = 0.39, p = 0.02). Moreover, DO with better lifestyles also exhibited greater concern for their pet's health (rho = 0.398, p = 0.01). CONCLUSIONS: This study emphasizes that individuals who adopt healthier habits tend to perceive themselves as healthier and exhibit greater concern for their pets' health. The attachment between DO and dogs is important in promoting healthy lifestyle behaviors and engagement in PA. Our results highlight that the presence of a dog is associated with a higher level of PA in DO, depending on the strength of the human-animal bond.


Subject(s)
Life Style , Walking , Humans , Dogs , Animals , Health Status , Healthy Lifestyle , Human-Animal Bond
2.
Proc Natl Acad Sci U S A ; 118(14)2021 04 06.
Article in English | MEDLINE | ID: mdl-33795519

ABSTRACT

Vascular calcification predicts atherosclerotic plaque rupture and cardiovascular events. Retrospective studies of women taking bisphosphonates (BiPs), a proposed therapy for vascular calcification, showed that BiPs paradoxically increased morbidity in patients with prior acute cardiovascular events but decreased mortality in event-free patients. Calcifying extracellular vesicles (EVs), released by cells within atherosclerotic plaques, aggregate and nucleate calcification. We hypothesized that BiPs block EV aggregation and modify existing mineral growth, potentially altering microcalcification morphology and the risk of plaque rupture. Three-dimensional (3D) collagen hydrogels incubated with calcifying EVs were used to mimic fibrous cap calcification in vitro, while an ApoE-/- mouse was used as a model of atherosclerosis in vivo. EV aggregation and formation of stress-inducing microcalcifications was imaged via scanning electron microscopy (SEM) and atomic force microscopy (AFM). In both models, BiP (ibandronate) treatment resulted in time-dependent changes in microcalcification size and mineral morphology, dependent on whether BiP treatment was initiated before or after the expected onset of microcalcification formation. Following BiP treatment at any time, microcalcifications formed in vitro were predicted to have an associated threefold decrease in fibrous cap tensile stress compared to untreated controls, estimated using finite element analysis (FEA). These findings support our hypothesis that BiPs alter EV-driven calcification. The study also confirmed that our 3D hydrogel is a viable platform to study EV-mediated mineral nucleation and evaluate potential therapies for cardiovascular calcification.


Subject(s)
Calcinosis/chemically induced , Diphosphonates/adverse effects , Extracellular Vesicles/drug effects , Plaque, Atherosclerotic/complications , Vascular Calcification/chemically induced , Animals , Cells, Cultured , Finite Element Analysis , Humans , Hydrogels , In Vitro Techniques , Mice , Mice, Knockout, ApoE
3.
J Fish Biol ; 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622912

ABSTRACT

The blue shark is a highly migratory species with a worldwide distribution, making it susceptible to multiple fishing fleets across the globe. In southern Brazil, it is an important target, comprising up to 40% of the total biomass landed by the commercial surface longline fleet. This study aims to contribute to a better understanding of how the species uses the region and to update its life-history information available for future assessments. Over five consecutive years (2018-2022) of landings and onboard monitoring, we gathered size data and vertebral samples to describe the species size composition in the region, as well as its seasonal and interannual variability and to update estimated life-history parameters. The results showed that southern Brazil is mainly inhabited by large juvenile males that arrive during winter (July-September) and stay until spring (October-December), when their frequency decreases. Small adult males are present throughout the year but in higher frequencies during summer. A small number of adult females are present with higher frequencies during spring and summer, which decreases during the austral autumn and winter. Some variability in the presence of each life stage was observed among years. The estimated life-history parameters were as follows: L∞: 255.02 cm fork length (FL), k: 0.20, L0:35.68 cm FL for males; L∞: 246.47 cm FL, k: 0.23, L0:36.77 cm FL for females; and L∞: 269.58 cm FL, k: 0.18, L0:36.19 cm FL for pooled sexes. However, the estimated values must be cautiously interpreted, as the obtained samples cannot be construed as representative of the entire harvested stock due to the lack of consistent presence of some life stages in the study region.

4.
J Struct Biol ; 213(2): 107708, 2021 06.
Article in English | MEDLINE | ID: mdl-33581284

ABSTRACT

Osteogenesis imperfecta (OI or brittle bone disease) is a group of genetic disorders of the connective tissues caused mainly by mutations in the genes encoding collagen type I. Clinical manifestations of OI include skeletal fragility, bone deformities, and severe functional disabilities, such as hearing loss. Progressive hearing loss, usually beginning in childhood, affects approximately 70% of people with OI with more than half of the cases involving the inner ear. There is no cure for OI nor a treatment to ameliorate its corresponding hearing loss, and very little is known about the properties of OI ears. In this study, we investigate the morphology of the otic capsule and the cochlea in the inner ear of the oim mouse model of OI. High-resolution 3D images of 8-week old oim and WT inner ears were acquired using synchrotron microtomography. Volumetric morphometric measurements were conducted for the otic capsule, its intracortical canal network and osteocyte lacunae, and for the cochlear spiral ducts. Our results show that the morphology of the cochlea is preserved in the oim ears at 8 weeks of age but the otic capsule has a greater cortical thickness and altered intracortical bone porosity, with a larger number and volume density of highly branched canals in the oim otic capsule. These results portray a state of compromised bone quality in the otic capsule of the oim mice that may contribute to their hearing loss.


Subject(s)
Ear, Inner/diagnostic imaging , Ear, Inner/physiopathology , Osteogenesis Imperfecta/physiopathology , Animals , Bone Density , Cochlea/diagnostic imaging , Cochlea/physiopathology , Disease Models, Animal , Electron Microscope Tomography/methods , Haversian System/diagnostic imaging , Haversian System/physiopathology , Male , Mice, Mutant Strains , Osteogenesis Imperfecta/etiology , Synchrotrons
5.
Emerg Infect Dis ; 27(6): 1737-1740, 2021.
Article in English | MEDLINE | ID: mdl-33871331

ABSTRACT

We documented 4 cases of severe acute respiratory syndrome coronavirus 2 reinfection by non-variant of concern strains among healthcare workers in Campinas, Brazil. We isolated infectious particles from nasopharyngeal secretions during both infection episodes. Improved and continued protection measures are necessary to mitigate the risk for reinfection among healthcare workers.


Subject(s)
COVID-19/diagnosis , Health Personnel , Reinfection/diagnosis , Reinfection/virology , SARS-CoV-2/isolation & purification , Virus Shedding , Adult , Brazil/epidemiology , COVID-19/epidemiology , Female , Humans , Middle Aged , Reinfection/therapy
6.
Arterioscler Thromb Vasc Biol ; 40(8): 1838-1853, 2020 08.
Article in English | MEDLINE | ID: mdl-32460581

ABSTRACT

OBJECTIVE: Vascular calcification is a cardiovascular risk factor and accelerated in diabetes mellitus. Previous work has established a role for calcification-prone extracellular vesicles in promoting vascular calcification. However, the mechanisms by which diabetes mellitus provokes cardiovascular events remain incompletely understood. Our goal was to identify that increased S100A9 promotes the release of calcification-prone extracellular vesicles from human macrophages in diabetes mellitus. Approach and Results: Human primary macrophages exposed to high glucose (25 mmol/L) increased S100A9 secretion and the expression of receptor for advanced glycation end products (RAGE) protein. Recombinant S100A9 induced the expression of proinflammatory and osteogenic factors, as well as the number of extracellular vesicles with high calcific potential (alkaline phosphatase activity, P<0.001) in macrophages. Treatment with a RAGE antagonist or silencing with S100A9 siRNA in macrophages abolished these responses, suggesting that stimulation of the S100A9-RAGE axis by hyperglycemia favors a procalcific environment. We further showed that an imbalance between Nrf-2 (nuclear factor 2 erythroid related factor 2) and NF-κB (nuclear factor-κB) pathways contributes to macrophage activation and promotes a procalcific environment. In addition, streptozotocin-induced diabetic Apoe-/-S100a9-/- mice and mice treated with S100a9 siRNA encapsulated in macrophage-targeted lipid nanoparticles showed decreased inflammation and microcalcification in atherosclerotic plaques, as gauged by molecular imaging and comprehensive histological analysis. In human carotid plaques, comparative proteomics in patients with diabetes mellitus and histological analysis showed that the S100A9-RAGE axis associates with osteogenic activity and the formation of microcalcification. CONCLUSIONS: Under hyperglycemic conditions, macrophages release calcific extracellular vesicles through mechanisms involving the S100A9-RAGE axis, thus contributing to the formation of microcalcification within atherosclerotic plaques.


Subject(s)
Calgranulin B/physiology , Diabetes Complications/etiology , Extracellular Vesicles/physiology , Macrophages/physiology , Receptor for Advanced Glycation End Products/physiology , Vascular Calcification/etiology , Animals , Diabetes Mellitus, Experimental/complications , Humans , Macrophage Activation , Mice , Mice, Inbred C57BL , Plaque, Atherosclerotic/etiology
7.
BMC Vet Res ; 17(1): 21, 2021 Jan 07.
Article in English | MEDLINE | ID: mdl-33413330

ABSTRACT

BACKGROUND: The black stork (Ciconia nigra Linnaeus, 1758) is a recognized endangered species in Europe and most of the specimens from the Western Palearctic region breed in the Iberian Peninsula. Available works regarding parasites in black storks are scarce. This work reports the presence one ecto- and two endoparasite species from a black stork in Portugal. CASE PRESENTATION: A black stork was found in southern Portugal after colliding against electric cables. The specimen did not survive its sustained injuries and a post-mortem exam was performed. During the procedure, several ecto- and endoparasite specimens were found. The collected parasites were lice (Neophilopterus tricolor), nematodes (Desportesius sagittatus) and trematodes (Cathaemasia hians). CONCLUSIONS: Three different species of parasites are reported from a black stork in Portugal. Ecto- and endoparasites of C. nigra have not frequently been described in the literature, and this case report is a contribution to the field. Additional studies will be important to better understand the impact that parasites can have on C. nigra health and survival.


Subject(s)
Bird Diseases/parasitology , Lice Infestations/veterinary , Rhabditida Infections/veterinary , Trematode Infections/veterinary , Animals , Birds , Echinostomatidae/isolation & purification , Phthiraptera , Portugal , Rhabditida/isolation & purification
8.
J Biomech Eng ; 143(1)2021 01 01.
Article in English | MEDLINE | ID: mdl-32601701

ABSTRACT

Mesenchymal stem cells (MSCs) are multipotent cells that can replicate and differentiate to different lineages, potentiating their use as integral components in regenerated mesenchymal tissues. Our previous work and other studies have indicated that mild heat shock enhances osteogenesis. However, the influence of pro-inflammatory cytokines on osteogenic differentiation during mildly elevated temperature conditions remains to be fully explored. In this study, human MSCs (hMSCs) were cultured with tumor necrosis factor-alpha (TNF-α), an important mediator of the acute phase response, and interleukin-6 (IL-6) which plays a role in damaging chronic inflammation, then heat shocked at 39 °C in varying frequencies-1 h per week (low), 1 h every other day (mild), and 1 h intervals three times per day every other day (high). DNA data showed that periodic mild heating inhibited suppression of cell growth caused by cytokines and induced maximal proliferation of hMSCs while high heating had the opposite effect. Quantitative osteogenesis assays show significantly higher levels of alkaline phosphatase (ALP) activity and calcium precipitation in osteogenic cultures following mild heating compared to low heating or nonheated controls. These results demonstrate that periodic mild hyperthermia may be used to facilitate bone regeneration using hMSCs, and therefore may influence the design of heat-based therapies in vivo.


Subject(s)
Mesenchymal Stem Cells , Cell Differentiation , Cell Proliferation , Humans , Osteogenesis
9.
J Fish Biol ; 98(2): 548-556, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33111352

ABSTRACT

Otolith shape analysis is a powerful method for fish stock identification. We compared the otolith shape of Pagrus pagrus (Linnaeus 1758) along with its distribution in four south-western Atlantic regions where it is commercially fished: Rio de Janeiro, Rio Grande do Sul in southern Brazil, the Argentine-Uruguayan Common Fishing Zone (UA) and the Argentinian Exclusive Fishing Zone (AR). Otolith shapes were compared by Elliptical Fourier and Wavelet coefficients among specimens in a size range with similar otoliths, morphometric parameters and ages. Four potential stocks were identified: one in the AR, a second along the UA which included specimens from southern Brazil with well-marked opaque bands in its otoliths (MRS), the third in southern Brazil with faint or absent opaque bands in its otoliths (FRS) and the fourth along Rio de Janeiro. The difference in the otolith shape among regions followed differences reported using other stock identification techniques. The similarity between otoliths from UA and MRS (ANOVA-like, P > 0.01) can be explained by seasonal short-range migrations. Otoliths shape differences between MRS and FRS (ANOVA-like, P < 0.01) suggest that P. pagrus does not form a homogeneous group in southern Brazil.


Subject(s)
Otolithic Membrane/anatomy & histology , Perciformes/anatomy & histology , Perciformes/classification , Animals , Atlantic Ocean , Brazil , Fisheries , Species Specificity
10.
Transfus Apher Sci ; 59(4): 102777, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32487512

ABSTRACT

Infection with the protozoan parasite Toxoplasma gondii is prevalent in animals and humans worldwide. The present study aimed to evaluate the prevalence of antibodies to T. gondii and associated risk factors among blood donors in Portugal. Serum samples were tested for the presence of anti-T. gondii immunoglobulin (Ig) G by a modified agglutination test (MAT). A written standardized questionnaire was used to collect sociodemographic and behavioural data from the blood donors. Out of 520 participants (median age: 39.5 years; interquartile range: 29.0-47.0), who attended blood collection sessions promoted by the Portuguese Institute for Blood and Transplantation (IPST), 198 (38.1%) were positive for anti-T. gondii IgG (95% confidence interval [CI]: 33.9-42.4%). Multiple logistic regression analysis revealed that ages of 46-55 years (odds ratio [OR] = 6.72; 95% CI = 3.40-13.28), and of 56-65 years (OR = 4.34; 95% CI = 1.73-10.86), having a lower education level (OR = 2.55; 95% CI = 1.45-4.49), living in the North (OR = 2.14; 95% CI = 1.25-3.65) and in the Centre regions (OR = 2.54; 95% CI = 1.36-4.76) of Portugal, and drinking water from untreated sources (OR = 2.46; 95% CI = 1.12-5.39) were risk factors for seropositivity to T. gondii. This study provides the first data on the seroprevalence of T. gondii in blood donors in Portugal, as well insights to sociodemographic and behavioural risk factors as the basis for future prevention programs.


Subject(s)
Blood Donors/statistics & numerical data , Toxoplasma/metabolism , Adult , Aged , Female , Humans , Male , Middle Aged , Portugal , Seroepidemiologic Studies
11.
Perspect Biol Med ; 63(4): 623-631, 2020.
Article in English | MEDLINE | ID: mdl-33416801

ABSTRACT

The COVID-19 pandemic has provided medical students around the globe with unique challenges and opportunities. With formal medical school education and training interrupted, medical students sought innovative ways to contribute to their health-care systems and communities. Their responses could be organized into three categories: clinical (remote clinical care and triage, helping in COVID testing or treatment centers, and contact tracing), nonclinical (PPE acquisition, COVID-related policy and research, and supporting vulnerable groups in the community), and educational (creating materials to educate peers, the community, or community health workers). We present examples of responses developed by students from five countries: Brazil, Nepal, the Philippines, Rwanda, and the United States. We discuss the challenges, outcomes, and recommendations for each case. One critical opportunity for growth is strengthening international collaborations. We hope that these examples provide a framework for medical students to plan coordinated and effective responses to the next pandemic, and further medical student engagement in international collaboration.


Subject(s)
COVID-19 , Students, Medical , Brazil , COVID-19 Testing , Contact Tracing , Delivery of Health Care , Education, Medical/methods , Education, Medical/organization & administration , Humans , Information Dissemination , Nepal , Philippines , Remote Consultation , Rwanda , United States
12.
Parasitol Res ; 119(9): 3109-3112, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32643084

ABSTRACT

Recent studies have described Spirocerca lupi-like nematodes in the stomach of red foxes (Vulpes vulpes) in Europe. A phylogenetic analysis of those specimens using mitochondrial DNA and their morphological reexamination allowed their characterization as a different species, Spirocerca vulpis. Between the years of 2010 and 2017, roundworms were collected from seven red foxes of northeastern Portugal found at necropsy with nodular lesions on their stomach wall. Histopathological analysis of four foxes revealed granulomatous lesions of the gastric nodules. On morphological assessment, by light microscopy, nematodes revealed the presence of six triangular teeth-like buccal capsule structures, which are absent in S. lupi. Polymerase chain reaction was run to amplify a 551 bp partial fragment of the cytochrome c oxidase subunit 1 gene. Sequences were 99% similar to S. vulpis (85% coverage) of red foxes from Spain and Bosnia and Herzegovina, 99% similar (99% coverage) to sequences of Spirocerca sp. of red foxes from Denmark and 93% similar (99% coverage) to S. lupi from South Africa. This is the first report of S. vulpis in foxes or any other host from Portugal.


Subject(s)
Foxes/parasitology , Spirurida Infections/veterinary , Thelazioidea/isolation & purification , Animals , Phylogeny , Polymerase Chain Reaction , Portugal , Spain , Spirurida Infections/pathology , Stomach/parasitology , Stomach/pathology , Thelazioidea/classification , Thelazioidea/genetics
13.
Aesthet Surg J ; 40(9): 950-959, 2020 08 14.
Article in English | MEDLINE | ID: mdl-31996914

ABSTRACT

BACKGROUND: Hump resection often requires reorganization of the keystone area. OBJECTIVES: The authors sought to describe the importance of the point where the perpendicular plate of ethmoid joins the septal cartilage (SC) and the nasal bones (NB) (Ethmoidal point [E-point]) for hump resection surgical planning. METHODS: Measurements from mid-sagittal slices in nasal computed tomography scans taken in adult Caucasian patients between January 2015 and December 2018 were compared between patients seeking primary rhinoplasty due to a nasal hump and patients not seeking rhinoplasty (control group). Patients with previous nasal surgery or trauma, genetic or congenital facial disorders, and high septal deviation were excluded. The length of overlap between NB and SC was compared between the 2 groups. The location of the E-point in relation to the beginning of the nasal hump in the cephalocaudal direction was documented in the patients seeking rhinoplasty. RESULTS: The study population included 138 patients, 69 seeking and 69 not seeking rhinoplasty (96 females). The mean age was 32.9 years (range, 18-55 years). The length of overlap between NB and SC was similar between both groups (11.7 ±â€…3.3 vs 10.8 ±â€…3.3; P = 0.235). The E-point was located before the beginning of the nasal hump in 97% (67/69) of nasal hump patients, and it could be found a mean distance of 2.3 (±2.3) mm cephalic to the latter. CONCLUSIONS: As a rule, the perpendicular plate of the ethmoid does not contribute to the nasal hump; therefore, only in exceptional cases should this be addressed while performing dorsal reduction.


Subject(s)
Nose Deformities, Acquired , Rhinoplasty , Adolescent , Adult , Female , Humans , Middle Aged , Nasal Bone/surgery , Nasal Septum/diagnostic imaging , Nasal Septum/surgery , Nose Deformities, Acquired/diagnostic imaging , Nose Deformities, Acquired/etiology , Nose Deformities, Acquired/surgery , Radiography , Young Adult
14.
Emerg Infect Dis ; 25(12): 1-4, 2019 12.
Article in English | MEDLINE | ID: mdl-31742505

ABSTRACT

Dogs are the main reservoir of Leishmania infantum and in some countries have been regularly culled as part of government policy to control visceral leishmaniasis. At the 13th Symposium of the Companion Vector-Borne Diseases World Forum in Windsor, UK, March 19-22, 2018, we consolidated a consensus statement regarding the usefulness of dog culling as a means of controlling visceral leishmaniasis. The statement highlighted the futility of culling infected dogs, whether healthy or sick, as a measure to control the domestic reservoir of L. infantum and reduce the risk for visceral leishmaniasis.


Subject(s)
Dog Diseases/epidemiology , Dog Diseases/prevention & control , Leishmaniasis/veterinary , Animals , Disease Reservoirs/veterinary , Dog Diseases/parasitology , Dog Diseases/transmission , Dogs , Leishmaniasis, Visceral/veterinary
15.
Adv Exp Med Biol ; 1097: 129-155, 2018.
Article in English | MEDLINE | ID: mdl-30315543

ABSTRACT

For many decades, cardiovascular calcification has been considered as a passive process, accompanying atheroma progression, correlated with plaque burden, and apparently without a major role on plaque vulnerability. Clinical and pathological analyses have previously focused on the total amount of calcification (calcified area in a whole atheroma cross section) and whether more calcification means higher risk of plaque rupture or not. However, this paradigm has been changing in the last decade or so. Recent research has focused on the presence of microcalcifications (µCalcs) in the atheroma and more importantly on whether clusters of µCalcs are located in the cap of the atheroma. While the vast majority of µCalcs are found in the lipid pool or necrotic core, they are inconsequential to vulnerable plaque. Nevertheless, it has been shown that µCalcs located within the fibrous cap could be numerous and that they behave as an intensifier of the background circumferential stress in the cap. It is now known that such intensifying effect depends on the size and shape of the µCalc as well as the proximity between two or more µCalcs. If µCalcs are located in caps with very low background stress, the increase in stress concentration may not be sufficient to reach the rupture threshold. However, the presence of µCalc(s) in the cap with a background stress of about one fifth to one half the rupture threshold (a stable plaque) will produce a significant increase in local stress, which may exceed the cap rupture threshold and thus transform a non-vulnerable plaque into a vulnerable one. Also, the classic view that treats cardiovascular calcification as a passive process has been challenged, and emerging data suggest that cardiovascular calcification may encompass both passive and active processes. The passive calcification process comprises biochemical factors, specifically circulating nucleating complexes, which would lead to calcification of the atheroma. The active mechanism of atherosclerotic calcification is a cell-mediated process via cell death of macrophages and smooth muscle cells (SMCs) and/or the release of matrix vesicles by SMCs.


Subject(s)
Atherosclerosis/pathology , Calcinosis/pathology , Plaque, Atherosclerotic/pathology , Fibrosis , Humans , Necrosis
16.
Hum Mutat ; 38(12): 1621-1648, 2017 12.
Article in English | MEDLINE | ID: mdl-28881068

ABSTRACT

Parathyroid carcinoma (PC) may occur as part of a complex hereditary syndrome or an isolated (i.e., non-syndromic) non-hereditary (i.e., sporadic) endocrinopathy. Studies of hereditary and syndromic forms of PC, which include the hyperparathyroidism-jaw tumor syndrome (HPT-JT), multiple endocrine neoplasia types 1 and 2 (MEN1 and MEN2), and familial isolated primary hyperparathyroidism (FIHP), have revealed some genetic mechanisms underlying PC. Thus, cell division cycle 73 (CDC73) germline mutations cause HPT-JT, and CDC73 mutations occur in 70% of sporadic PC, but in only ∼2% of parathyroid adenomas. Moreover, CDC73 germline mutations occur in 20%-40% of patients with sporadic PC and may reveal unrecognized HPT-JT. This indicates that CDC73 mutations are major driver mutations in the etiology of PCs. However, there is no genotype-phenotype correlation and some CDC73 mutations (e.g., c.679_680insAG) have been reported in patients with sporadic PC, HPT-JT, or FIHP. Other genes involved in sporadic PC include germline MEN1 and rearranged during transfection (RET) mutations and somatic alterations of the retinoblastoma 1 (RB1) and tumor protein P53 (TP53) genes, as well as epigenetic modifications including DNA methylation and histone modifications, and microRNA misregulation. This review summarizes the genetics and epigenetics of the familial syndromic and non-syndromic (sporadic) forms of PC.


Subject(s)
Adenoma/genetics , Epigenomics , Fibroma/genetics , Hyperparathyroidism, Primary/genetics , Hyperparathyroidism/genetics , Jaw Neoplasms/genetics , MicroRNAs/genetics , Parathyroid Neoplasms/genetics , Tumor Suppressor Proteins/genetics , DNA Methylation , Germ-Line Mutation , Humans , Proto-Oncogene Proteins/genetics , Retinoblastoma Binding Proteins/genetics , Tumor Suppressor Protein p53/genetics , Ubiquitin-Protein Ligases/genetics
17.
Clin Endocrinol (Oxf) ; 86(3): 347-353, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27588366

ABSTRACT

CONTEXT: Insulin-binding antibodies may produce severe dysglycaemia in insulin-naïve patients ('insulin autoimmune syndrome' (IAS) or Hirata disease), while rendering routine insulin assays unreliable. OBJECTIVE: To assess the performance of clinically used insulin assays and an optimal analytical approach in the context of IAS. DESIGN: Observational biochemical study of selected patients with hyperinsulinaemic hypoglycaemia. PATIENTS: Three patients without diabetes with recurrent spontaneous hyperinsulinaemic hypoglycaemia and 'positive' insulin antibodies. MEASUREMENTS: A panel of clinically used insulin assays (Siemens ADVIA® Centaur, Siemens Immulite® 2000, DiaSorin LIAISON® XL, PE AutoDELFIA® and the Beckman Coulter Access® 2) were used before and after plasma dilution or polyethylene glycol (PEG) precipitation. Anti-insulin IgG antibodies were measured by Isletest™ -IAA ELISA. Gel filtration chromatography (GFC) was undertaken with and without preincubation of plasma with exogenous insulin. RESULTS: Dilution of IAS plasma with assay-specific buffer increased insulin recovery, supporting negative immunoassay interference by antibodies. PEG precipitation of IAS plasma decreased insulin recovery using all assays except the Immulite® 2000. GFC discriminated high molecular weight and monomeric insulin, while ex vivo addition of exogenous insulin to plasma increased insulin bound to antibody, thereby improving the sensitivity of detection of insulin immunocomplexes. CONCLUSIONS: Immunoprecipitation with PEG must be used with caution in screening for insulin-antibody complexes as results are assay dependent. GFC with addition of exogenous insulin can identify significant insulin immunocomplexes with enhanced sensitivity, with attendant greater clinical utility and avoidance of radiolabelled reagents.


Subject(s)
Autoimmune Diseases/diagnosis , Chemical Precipitation , Chromatography, Gel/methods , Immunoassay/methods , Insulin Antibodies/analysis , Adult , Congenital Hyperinsulinism , Female , Humans , Insulin/immunology , Middle Aged , Polyethylene Glycols/chemistry
18.
FASEB J ; 30(2): 635-52, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26481310

ABSTRACT

Bone minerals are acquired during growth and are key determinants of adult skeletal health. During puberty, the serum levels of growth hormone (GH) and its downstream effector IGF-1 increase and play critical roles in bone acquisition. The goal of the current study was to determine how bone cells integrate signals from the GH/IGF-1 to enhance skeletal mineralization and strength during pubertal growth. Osteocytes, the most abundant bone cells, were shown to orchestrate bone modeling during growth. We used dentin matrix protein (Dmp)-1-mediated Ghr knockout (DMP-GHRKO) mice to address the role of the GH/IGF axis in osteocytes. We found that DMP-GHRKO did not affect linear growth but compromised overall bone accrual. DMP-GHRKO mice exhibited reduced serum inorganic phosphate and parathyroid hormone (PTH) levels and decreased bone formation indices and were associated with an impaired response to intermittent PTH treatment. Using an osteocyte-like cell line along with in vivo studies, we found that PTH sensitized the response of bone to GH by increasing Janus kinase-2 and IGF-1R protein levels. We concluded that endogenously secreted PTH and GHR signaling in bone are necessary to establish radial bone growth and optimize mineral acquisition during growth.


Subject(s)
Bone Development/physiology , Carrier Proteins/metabolism , Extracellular Matrix Proteins/metabolism , Parathyroid Hormone/metabolism , Animals , Bone Density/genetics , Bone Density/physiology , Bone Development/genetics , Carrier Proteins/genetics , Cell Line , Extracellular Matrix Proteins/genetics , Female , Fibroblast Growth Factor-23 , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Gene Expression Regulation/physiology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Parathyroid Hormone/genetics , Phosphorus/blood
19.
Diabetes Obes Metab ; 19(9): 1223-1232, 2017 09.
Article in English | MEDLINE | ID: mdl-28244626

ABSTRACT

AIMS: The objective of this study was to investigate short- (≤ 30 days) and long-term (≥ 2 years) all-cause mortality after bariatric surgery among adult patients with obesity. MATERIALS AND METHODS: For short-term mortality, eligible studies comprised randomized controlled trials (RCTs) reporting perioperative mortality. For long-term mortality, eligible studies comprised RCTs and observational studies comparing mortality between obese patients after bariatric surgery and non-operated controls. Random-effects models using a Bayesian or frequentist approach were used to pool effect estimates of short- and long-term mortality, respectively. RESULTS: Short-term all-cause mortality based on 38 RCTs involving 4030 patients was 0.18% (95% CI, 0.04%-0.38%) and was higher for open surgeries (0.31%; 95% CI, 0.03%-0.97%) and similar in mixed surgeries (0.17%; 95% CI, 0.03%-0.43%) and restrictive surgeries (0.17%; 95% CI, 0.03%-0.45%). For long-term mortality, 12 observational studies involving 27 258 operated patients and 97 154 non-operated obese controls were included. Of these, 8 studies were eligible for the meta-analysis, which showed a reduction of 41% in all-cause mortality (hazard ratio, 0.59; 95% CI, 0.52-0.67; P < .001). Additionally, operated patients were 0.42 times as likely (95% CI, 0.25-0.72, P < .001) and 0.47 times as likely (95% CI, 0.36-0.63, P < .001) as non-operated obese controls to die from cardiovascular diseases and cancer, respectively. CONCLUSIONS: Bariatric surgery is associated with low short-term mortality and may be associated with long-term reductions in all-cause, cardiovascular and cancer-related mortality.


Subject(s)
Bariatric Surgery/adverse effects , Evidence-Based Medicine , Obesity, Morbid/surgery , Bariatric Surgery/mortality , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/mortality , Comorbidity , Humans , Middle Aged , Mortality , Neoplasms/epidemiology , Neoplasms/mortality , Obesity, Morbid/epidemiology , Obesity, Morbid/mortality , Observational Studies as Topic , Postoperative Complications/mortality , Postoperative Complications/prevention & control , Randomized Controlled Trials as Topic
20.
Parasitology ; 144(10): 1384-1393, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28534448

ABSTRACT

Canine leishmaniosis (CanL) is a major veterinary concern and a public health issue. Serological data are essential for disease management. Several antigens used in serological assays have specificity related problems preventing relevant seropositivity values establishment. Herein we report significant seropositivity level disparity in a study cohort with 384 dogs from eight countries, for antigens traditionally used in CanL - soluble promastigote Leishmania antigens (SPLA) and K39 recombinant protein (rK39): 43·8 and 2·9% for SPLA and rK39, respectively. To better understand the reasons for this disparity, CanL-associated serological response was characterized using, for complement serological evaluation, a ubiquitous antigen - soluble Escherichia coli antigens (SECAs). Using cohorts of CanL dogs and dogs without clinical evidences of CanL from non-endemic regions of Portugal, the serological response of CanL animals followed specific trend of seropositivity rK39 > SPLA > SECA absent in non-diseased animals. Using receiver operating characteristic curve analysis, these characteristic trends were converted in ratios, SPLA/SECA, rK39/SECA and rK39/SPLA, that presented high predictive for discriminating the CanL cohort that was potentiated when applied in a scoring system involving positivity to four out of five predictors (rK39, SPLA, SPLA/SECA, rK39/SECA and rK39/SPLA). In fact, this approach discriminated CanL with similar sensitivity/specificity as reference antigens, diminishing seropositivity in European cohort to 1·8%. Ultimately, non-related antigens like SECA and seropositivity ratios between antigens enable different perspectives into serological data focusing on the search of characteristic serological signatures and not simple absolute serology values contributing to comprehensive serological status characterization.


Subject(s)
Adenosine Triphosphatases/blood , Antigens, Bacterial/blood , Antigens, Protozoan/blood , Bacterial Proteins/blood , Dog Diseases/diagnosis , Escherichia coli/immunology , Leishmania infantum/isolation & purification , Leishmaniasis, Visceral/veterinary , SEC Translocation Channels/blood , Animals , Dog Diseases/immunology , Dogs , Enzyme-Linked Immunosorbent Assay/veterinary , Leishmaniasis, Visceral/diagnosis , Leishmaniasis, Visceral/immunology , Portugal , Protozoan Proteins/blood , Recombinant Proteins/blood , SecA Proteins , Sensitivity and Specificity
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