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1.
J Wound Care ; 33(1): 66-71, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38197282

ABSTRACT

Foot ulceration and infection is associated with a substantial increase in morbidity and mortality in patients with diabetes. We present a clinical case of recurrent diabetic foot infection with an atypical clinical evolution. A 58-year-old male patient with type 1 diabetes and a history of bilateral Charcot foot neuroarthropathy was followed at our Diabetic Foot Clinic for an unhealed plantar foot ulcer for >1.5 years with recurrent episodes of infection. He was admitted to hospital due to foot ulcer reinfection with sepsis and ipsilateral lower limb cellulitis. The foot infection was found to be associated with an underlying abscess in the anterior compartment of the leg, with a cutaneous fistulous course with extensive alterations of an inflammatory nature. Exudate from the lesion was drained and tissue biopsied, revealing Serratia marcescens and Klebsiella oxytoca with dystrophic calcification (DC). Surgical excision of dystrophic tissue with debridement of the fistulous tracts was performed. The excised material corroborated the presence of fibroadipose connective tissue with marked DC, as well as areas of mixed inflammation compatible with a chronic infectious aetiology. Targeted long-term antibiotic therapy was implemented, for a total of six weeks, with a favourable clinical evolution and complete closure of the lesion at the final follow-up. DC results from calcium deposition in degenerated tissues without evidence of systemic mineral imbalance and is a potential cause of non-healing ulcers. Few cases of DC have been reported in diabetic foot patients and its treatment remains challenging and controversial. A longer follow-up period is necessary to verify the effectiveness of our approach.


Subject(s)
Calcinosis , Diabetes Mellitus , Diabetic Foot , Sepsis , Skin Diseases , Male , Humans , Middle Aged , Diabetic Foot/complications , Leg , Abscess , Calcinosis/complications
2.
Sensors (Basel) ; 23(20)2023 Oct 18.
Article in English | MEDLINE | ID: mdl-37896659

ABSTRACT

This study investigated the use of distributed optical fiber sensing to measure temperature and strain during thermomechanical processes in printed circuit board (PCB) manufacturing. An optical fiber (OF) was bonded to a PCB for simultaneous measurement of temperature and strain. Optical frequency-domain reflectometry was used to interrogate the fiber optic sensor. As the optical fiber is sensitive to both temperature and strain, a demodulation technique is required to separate both effects. Several demodulation techniques were compared to find the best one, highlighting their main limitations. The importance of good estimations of the temperature sensitivity coefficient of the OF and the coefficient of thermal expansion of the PCB was highlighted for accurate results. Furthermore, the temperature sensitivity of the bonded OF should not be neglected for accurate estimations of strains. The two-sensor combination model provided the best results, with a 2.3% error of temperature values and expected strain values. Based on this decoupling model, a methodology for measuring strain and temperature variations in PCB thermomechanical processes using a single and simple OF was developed and tested, and then applied to a trial in an industrial environment using a dynamic oven with similar characteristics to those of a reflow oven. This approach allows the measurement of the temperature profile on the PCB during oven travel and its strain state (warpage).

3.
Genet Med ; 24(5): 1120-1129, 2022 05.
Article in English | MEDLINE | ID: mdl-35125311

ABSTRACT

PURPOSE: The aim of this study was to determine how attitudes toward the return of genomic research results vary internationally. METHODS: We analyzed the "Your DNA, Your Say" online survey of public perspectives on genomic data sharing including responses from 36,268 individuals across 22 low-, middle-, and high-income countries, and these were gathered in 15 languages. We analyzed how participants responded when asked whether return of results (RoR) would motivate their decision to donate DNA or health data. We examined variation across the study countries and compared the responses of participants from other countries with those from the United States, which has been the subject of the majority of research on return of genomic results to date. RESULTS: There was substantial variation in the extent to which respondents reported being influenced by RoR. However, only respondents from Russia were more influenced than those from the United States, and respondents from 20 countries had lower odds of being partially or wholly influenced than those from the United States. CONCLUSION: There is substantial international variation in the extent to which the RoR may motivate people's intent to donate DNA or health data. The United States may not be a clear indicator of global attitudes. Participants' preferences for return of genomic results globally should be considered.


Subject(s)
Attitude , Genomics , DNA , Genomics/methods , Humans , Intention , Surveys and Questionnaires , United States
4.
J Oral Pathol Med ; 51(2): 113-125, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35048431

ABSTRACT

BACKGROUND: E-cigarette sales in the United States (US) are projected to reach 16.5 billion by 2024 according to market analysis. Six deaths and 450 lung illnesses have been linked to e-cigarette use. To our knowledge, a systematic review of the adverse effects of e-cigarettes on head, neck, and oral cells does not exist. This review aimed to conduct a systematic review of current literature to determine whether e-cigarettes caused adverse effects on cells of the head, neck, and oral cavity. METHODS: Five databases including Medline, Dentistry and Oral Sciences, CINAHL, CAPLUS, Web of Science, and gray literature were searched for articles any time up to December 2020. Using Rayyan software, two-independent researchers screened 233 articles and extracted 41 for further investigation. Based on the inclusion criteria, 18 articles were eligible for this review. RESULTS: Aberrant morphology, cytotoxicity, oxidative stress, reduced viability, delayed fibroblast migration, and genotoxicity were statistically significant when the head, neck, and oral cells were exposed to e-cigarettes. Of note, most articles in this systematic review found cigarette smoke to be significantly more toxic to head, neck, and oral cells than e-cigarettes. CONCLUSIONS: E-cigarettes are implicated in adverse effects on head, neck, and oral cells, yet very few have been tested against these cells. More longitudinal studies using a wider variety of e-cigarettes are necessary before we can determine their total adverse effects. Future research must also investigate chronic e-cigarette use and if it leads to periodontal disease and/or head, neck, or oral cancer.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Electronic Nicotine Delivery Systems , Vaping , Humans , United States , Vaping/adverse effects
5.
J Med Ethics ; 48(9): 616-623, 2022 09.
Article in English | MEDLINE | ID: mdl-34172523

ABSTRACT

Drawing on the views of donors and recipients about anonymity in a country that is experiencing a transition towards non-anonymous gamete donation mandated by the Constitutional Court, we explore how the intersection between rights-based approaches and an empirical framework enhances recommendations for ethical policy and healthcare. Between July 2017 and April 2018, 69 donors and 147 recipients, recruited at the Portuguese Public Bank of Gametes, participated in this cross-sectional study. Position towards anonymity was assessed through an open-ended question in a self-report questionnaire, which was subject to content analysis. Preference for an anonymous donation regime was mentioned by 82.6% of donors and 89.8% of recipients; and all those with children. Instead of the rights-based reasoning used by the Constitutional Court, donors highlighted concerns over future relationships and recipients focused on socioethical values linked with the safeguard of safety, privacy and confidentiality. The remaining participants advocated the choice between anonymity or non-anonymity (double-track policy), invoking respect for their autonomy. The complex, diverse ethical views and reasoning of donors and recipients expand a traditionally dichotomous discussion. Their perspectives challenge the transition towards non-anonymity and international guidelines, raising awareness to the need for their involvement in the design of policies to enable choice according to their values and preferences, and of psychosocial counselling responsive to their socioethical concerns and sensitive to their parental status. Empirical frameworks complement rights-based approaches to uphold justice, fairness and equal respect, and to incorporate utility, beneficence and non-maleficence in policymaking and healthcare in the transition towards non-anonymity.


Subject(s)
Oocyte Donation , Tissue Donors , Child , Confidentiality , Cross-Sectional Studies , Ethics, Medical , Germ Cells , Humans , Tissue Donors/psychology
6.
BMC Med Imaging ; 22(1): 61, 2022 04 02.
Article in English | MEDLINE | ID: mdl-35366812

ABSTRACT

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


Subject(s)
Thyroid Nodule , Adolescent , Humans , Retrospective Studies , Risk Assessment , Thyroid Nodule/diagnostic imaging , Thyroid Nodule/pathology , Ultrasonography
7.
J Assist Reprod Genet ; 39(9): 2077-2087, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35986809

ABSTRACT

PURPOSE: Research using gametes and embryos donated by reproductive and third-party donors contributed to substantial, albeit contentious achievements. The views of gamete donors and recipients on donation for research and the underpinning role of attitudes towards research have been seldom explored and are yet to be incorporated into ethical, legal, and regulatory landscapes. From a cultural standpoint, this study adapts and explores psychometric properties of the Portuguese version of the Research Attitudes Questionnaire (RAQ), and analyzes the willingness of gamete donors and recipients to donate gametes and embryos for research and its association with sociodemographic, reproductive characteristics, and attitudes towards research. METHODS: Between July 2017 and June 2018, 71 donors and 165 recipients completed a self-administered questionnaire at the Portuguese Public Bank of Gametes. Willingness to donate and attitudes towards research were measured with a 5-point Likert scale. RAQ psychometric characteristics were explored. RESULTS: Two RAQ components were identified: "trustworthiness of research" and "critical perspective". Most participants were willing to donate gametes and embryos: donors more willing to donate gametes and male recipients more willing to donate gametes and embryos. Higher RAQ scores, indicating a more positive attitude towards research, were observed on the component "trustworthiness of research" among those willing to donate gametes and embryos and on the component "critical perspective" among those willing to donate embryos. CONCLUSION: These findings help foster inclusivity, diversity, and responsiveness of research and call for upstream engagement of male and female gamete donors and recipients, promoting a trustworthy, anticipatory, democratic, and people-centered approach to policies, regulations, and practices in human gamete and embryo research.


Subject(s)
Embryo Disposition , Embryo Research , Female , Germ Cells , Humans , Male , Oocyte Donation , Tissue Donors
8.
Public Health ; 207: 24-27, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35483164

ABSTRACT

OBJECTIVES: The aim of this study was to explore concerns and coping mechanisms during the first national COVID-19 lockdown in Portugal. The general population provided statements via an open comment box as part of an online prospective study. STUDY DESIGN: This was an Internet-based open cohort study. METHODS: Individuals aged ≥16 years were eligible to participate in this study. Inductive content analysis was performed on completed questionnaires submitted between 23 and 29 March 2020 and 27 April and 3 May 2020 (corresponding with the early and late phases of the first national lockdown, respectively). RESULTS: Data suggest the prominence of behavioural and emotional responses to COVID-19; namely, self-compliance with measures promoted by the government; adopting practices of self-care and supporting/protecting others; and enacting hope (both currently and for the future). Concerns were related to the perception of vulnerabilities for oneself, family and others and to challenging situations presenting in society (e.g. physical and mental health, academic/professional careers, income, social inequality, potential discrimination and stigmatisation, inconsistent information and negative approach to the news), coupled with criticism, scepticism or doubts about government policy and performance of the healthcare system. Expressions of fear and worry and non-compliance with mitigation measures by others (e.g. close relatives, employees and general population) emerged as additional concerns. CONCLUSIONS: Continuous assessment of behavioural and emotional responses to the COVID-19 pandemic is needed to support effective communication and public health policies that are sensitive to the concerns, motivations and expectations of the population. Awareness of changing public opinions enables governments to continue to effectively mobilise the population to take recommended actions to reduce the transmission of COVID-19.


Subject(s)
COVID-19 , Adaptation, Psychological , Cohort Studies , Communicable Disease Control , Humans , Pandemics , Portugal/epidemiology , Prospective Studies , SARS-CoV-2
9.
Int J Mol Sci ; 23(10)2022 May 17.
Article in English | MEDLINE | ID: mdl-35628390

ABSTRACT

Periodontitis is a chronic inflammatory oral disease that affects approximately 42% of adults 30 years of age or older in the United States. In response to microbial dysbiosis within the periodontal pockets surrounding teeth, the host immune system generates an inflammatory environment in which soft tissue and alveolar bone destruction occur. The objective of this study was to identify diagnostic biomarkers and the mechanistic drivers of inflammation in periodontitis to identify drugs that may be repurposed to treat chronic inflammation. A meta-analysis comprised of two independent RNA-seq datasets was performed. RNA-seq analysis, signal pathway impact analysis, protein-protein interaction analysis, and drug target analysis were performed to identify the critical pathways and key players that initiate inflammation in periodontitis as well as to predict potential drug targets. Seventy-eight differentially expressed genes, 10 significantly impacted signaling pathways, and 10 hub proteins in periodontal gingival tissue were identified. The top 10 drugs that may be repurposed for treating periodontitis were then predicted from the gene expression and pathway data. The efficacy of these drugs in treating periodontitis has yet to be investigated. However, this analysis indicates that these drugs may serve as potential therapeutics to treat inflammation in gingival tissue affected by periodontitis.


Subject(s)
Periodontitis , Adult , Biomarkers , Chronic Disease , Gingiva , Humans , Inflammation , Periodontitis/diagnosis , Periodontitis/drug therapy , Periodontitis/genetics , RNA-Seq
10.
Medicina (Kaunas) ; 59(1)2022 Dec 27.
Article in English | MEDLINE | ID: mdl-36676680

ABSTRACT

The pharmacological treatment of systemic lupus erythematosus (SLE) aims to decrease disease activity, progression, systemic compromise, and mortality. Among the pharmacological alternatives, there are chemically synthesized drugs whose efficacy has been evaluated, but which have the potential to generate adverse events that may compromise adherence and response to treatment. Therapy selection and monitoring will depend on patient characteristics and the safety profile of each drug. The aim of this review is to provide a comprehensive understanding of the most important synthetic drugs used in the treatment of SLE, including the current treatment options (mycophenolate mofetil, azathioprine, and cyclophosphamide), review their mechanism of action, efficacy, safety, and, most importantly, provide monitoring parameters that should be considered while the patient is receiving the pharmacotherapy.


Subject(s)
Lupus Erythematosus, Systemic , Humans , Lupus Erythematosus, Systemic/drug therapy , Cyclophosphamide/adverse effects , Azathioprine/therapeutic use , Mycophenolic Acid/therapeutic use , Immunosuppressive Agents/adverse effects
11.
J Contemp Dent Pract ; 23(9): 866-871, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-37282991

ABSTRACT

AIM: This study was carefully designed to analyze the perceived psychological impact of the COVID-19 pandemic among Roseman dental students. Students assessed their perceived changes in stress, self-esteem, and lifestyle behavior changes based on the impact of the pandemic. MATERIALS AND METHODS: A self-designed, anonymous, 18-item questionnaire was administered to Roseman dental students after being approved by the Institutional Review Board. Independent samples t-test and one-way ANOVA were utilized for comparison of psychological factors toward gender, as well as year of study. Chi-square correlations between stress and self-esteem, as well as lifestyle behavior, were also reported. RESULTS: In total, 313 students with a mean age of 28.15 (SD:4.21) completed the survey. Statistically significant differences were shown between students based upon age and year of study, with regard to stress and lifestyle behavior changes. Cross-tabulations of stress with self-esteem and lifestyle behavior changes showed positive relationships, as students with higher levels of stress showed significant self-esteem problems and lifestyle behavior changes. The largest frequency of stress/anxiety and lifestyle behavioral changes was found in the age range of 25-34 years old, particularly in the Class of 2024 and 2025. CONCLUSION: The COVID-19 pandemic has imposed a significant psychological impact on dental students at Roseman. However, further studies are needed to assess the long-lasting impacts of the pandemic on University healthcare students as a whole. CLINICAL SIGNIFICANCE: The pandemic has not only affected the way in which dental students progress academically but also as healthcare providers now and into the future.


Subject(s)
COVID-19 , Humans , Adult , COVID-19/epidemiology , Pandemics , Universities , Life Style , Students
12.
J Gen Virol ; 102(8)2021 08.
Article in English | MEDLINE | ID: mdl-34435944

ABSTRACT

Human pathogens belonging to the Alphavirus genus, in the Togaviridae family, are transmitted primarily by mosquitoes. The signs and symptoms associated with these viruses include fever and polyarthralgia, defined as joint pain and inflammation, as well as encephalitis. In the last decade, our understanding of the interactions between members of the alphavirus genus and the human host has increased due to the re-appearance of the chikungunya virus (CHIKV) in Asia and Europe, as well as its emergence in the Americas. Alphaviruses affect host immunity through cytokines and the interferon response. Understanding alphavirus interactions with both the innate immune system as well as the various cells in the adaptive immune systems is critical to developing effective therapeutics. In this review, we summarize the latest research on alphavirus-host cell interactions, underlying infection mechanisms, and possible treatments.


Subject(s)
Alphavirus Infections , Alphavirus , Alphavirus/immunology , Alphavirus/pathogenicity , Alphavirus Infections/epidemiology , Alphavirus Infections/prevention & control , Alphavirus Infections/virology , Animals , Humans , Viral Vaccines/immunology
13.
Trop Med Int Health ; 26(10): 1164-1176, 2021 10.
Article in English | MEDLINE | ID: mdl-34169612

ABSTRACT

OBJECTIVES: The involvement of individuals and communities in health decision-making is enshrined in WHO policies. However, migrant groups are under-represented in health decision-making processes. Our aim was to explore migrants' involvement in health policy, service development and research in the WHO European Region to identify levers for inclusive and meaningful practice. METHODS: We conducted a narrative review of grey literature and peer-reviewed research on migrants' involvement in health decision-making across the 53 countries in WHO Europe. We searched for articles published in English between 2010 and the present in two electronic databases (PubMed, Scopus), IOM MIPEX Health Strand country reports, the EU SOPHIE project and using a Google advanced search. Findings were analysed descriptively and using Normalisation Process Theory to investigate levers and barriers to implementation of policy into practice. RESULTS: Of 1,444 articles retrieved, 79 met the inclusion criteria. We identified 20 policies promoting migrants' involvement, but national-level policies were present in only two countries. We identified 59 examples of migrants' involvement in practice from half of the WHO Europe countries (n = 27). Our Normalisation Process Theory (NPT) analysis of 14 peer-reviewed empirical papers found that participatory research approaches are a lever to putting policy into practice in a meaningful way. CONCLUSIONS: Migrants' involvement in health decision-making requires explicit national policies that are implemented evenly across policymaking, service provider and research activities in all countries in the WHO European Region. Participatory approaches to involvement activities are encouraged because they are a lever to perceived barriers to migrants' involvement.


Subject(s)
Biomedical Research , Health Policy , Health Services , Transients and Migrants , World Health Organization , Europe , Humans
14.
Anticancer Drugs ; 32(5): 567-574, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33661189

ABSTRACT

Immune checkpoint inhibitors were approved for advanced nonsmall cell lung cancer (NSCLC) treatment. Despite improved survival, not all patients benefit from these agents. Here, the prognostic impact of pretreatment modified Glasgow Prognostic Score (mGPS) and neutrophil-to-lymphocyte ratio (NLR) was assessed. From 77 patients included, 83.2% received at least one prior systemic therapy. Immune-related adverse events (irAE) occurred in 20 patients. A lower mGPS was associated with higher median overall survival (OS), and a lower Eastern Cooperative Oncology Group (ECOG), irAE and fewer metastatic sites with better survival. A trend towards greater OS and progression-free survival (PFS) was stated among patients with NLR <5. mGPS 0 was associated with better survival; ≥3 metastatic sites with worse PFS and OS; ECOG >2 with worse OS and irAE with better survival. Pretreatment mGPS seems to be useful for predicting survival among advanced NSCLC patients treated with anti-programmed cell death 1 drugs, with ECOG performance status, irAE occurrence, and number of metastatic sites acting as survival predictors.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Cigarette Smoking/epidemiology , Comorbidity , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Inflammation Mediators/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Lymphocytes/cytology , Male , Middle Aged , Neoplasm Metastasis , Neutrophils/cytology , Prognosis , Severity of Illness Index
15.
Pulm Pharmacol Ther ; 71: 102078, 2021 12.
Article in English | MEDLINE | ID: mdl-34571094

ABSTRACT

Actinomycosis is a rare chronic infection triggered by species of Actinomyces. Although thoracic involvement represents about 15% of human actinomycosis, its true incidence may be underestimated, not only because of its challenging diagnosis, but also because it can be treated unintentionally with antibiotics for other diseases. In this sense, this work aims at providing an up-to-date literature review on thoracic actinomycoses, with particular emphasis on presentation, diagnostic and therapeutic approaches, also paving upcoming clinical interventions from findings obtained of a presentation of a case series. Data discussed here clearly denote the rarity, non-specificity and heterogeneity of clinical presentations of the disease, reinforcing the need for individualized therapeutic approaches.


Subject(s)
Actinomycosis , Bronchiectasis , Lung Diseases , Actinomyces , Actinomycosis/diagnosis , Actinomycosis/drug therapy , Bronchiectasis/drug therapy , Humans , Lung Diseases/diagnosis , Lung Diseases/drug therapy , Persistent Infection
16.
Endocr Regul ; 55(3): 169-173, 2021 Sep 13.
Article in English | MEDLINE | ID: mdl-34523298

ABSTRACT

Objectives. Immune reconstitution therapies (IRT), which include antibody-based cell-depleting therapies targeting CD52+ (alemtuzumab) or CD20+ (rituximab, ocrelizumab) leukocytes, are approved for the treatment of multiple sclerosis. Thyroid autoimmunity is a common adverse effect of alemtuzumab treatment, Graves' disease (GD) being the most prevalent manifestation. To date, thyroid autoimmunity events have not been reported with CD20-targeting monoclonal antibodies. Case Report. A 59-year-old woman with primary progressive multiple sclerosis with no prior personal history of thyroid disease or autoimmunity, was diagnosed with GD 6 months following the first ocrelizumab infusion. She was asymptomatic and had no signs of ophthalmopathy. Due to the temporal association of GD diagnosis with ocrelizumab infusion, absence of symptoms and our experience with alemtuzumab-induced GD, we decided for an active surveillance strategy and antithyroid drugs were not started. She underwent spontaneous resolution of hyperthyroidism with thyroid-stimulating hormone (TSH) receptor antibodies (TRAb) negativity and a mild and transitory period of subclinical hypothyroidism, while she continued the biannually ocrelizumab administration schedule. To present date, she has maintained close clinical and biochemical surveillance with normal TSH, free thyroxine (fT4) and free triiodothyronine (fT3) levels and undetectable TRAb. Conclusions. This is the first case of GD reported after ocrelizumab administration. The timing, onset and course of this case is similar to alemtuzumab-induced GD, usually interpreted as an "immune reconstitution syndrome"; however, ocrelizumab cell count depletion is inferior in severity, cell population affected and duration of depletion. This case highlights the importance of pre-screening and follow-up with thyroid function tests in patients treated with ocrelizumab. As a novel therapeutic antibody, further investigation is required to unravel the causes of thyroid autoimmunity.


Subject(s)
Graves Disease , Multiple Sclerosis, Chronic Progressive , Multiple Sclerosis , Antibodies, Monoclonal, Humanized , Female , Graves Disease/drug therapy , Humans , Middle Aged , Multiple Sclerosis/drug therapy , Multiple Sclerosis, Chronic Progressive/drug therapy
17.
Int J Mol Sci ; 19(5)2018 Apr 26.
Article in English | MEDLINE | ID: mdl-29701673

ABSTRACT

Calcium influx is critical for T cell effector function and fate. T cells are activated when T cell receptors (TCRs) engage peptides presented by antigen-presenting cells (APC), causing an increase of intracellular calcium (Ca2+) concentration. Co-receptors stabilize interactions between the TCR and its ligand, the peptide-major histocompatibility complex (pMHC), and enhance Ca2+ signaling and T cell activation. Conversely, some co-receptors can dampen Ca2+ signaling and inhibit T cell activation. Immune checkpoint therapies block inhibitory co-receptors, such as cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), to increase T cell Ca2+ signaling and promote T cell survival. Similar to CTLA-4 and PD-1, the co-receptor CD5 has been known to act as a negative regulator of T cell activation and to alter Ca2+ signaling and T cell function. Though much is known about the role of CD5 in B cells, recent research has expanded our understanding of CD5 function in T cells. Here we review these recent findings and discuss how our improved understanding of CD5 Ca2+ signaling regulation could be useful for basic and clinical research.


Subject(s)
CD5 Antigens/metabolism , Calcium Signaling , T-Lymphocytes/metabolism , Animals , CD5 Antigens/genetics , CTLA-4 Antigen/genetics , CTLA-4 Antigen/metabolism , Humans , Programmed Cell Death 1 Receptor/genetics , Programmed Cell Death 1 Receptor/metabolism
18.
Can J Respir Ther ; 55(1)2018 Dec.
Article in English | MEDLINE | ID: mdl-30745796

ABSTRACT

Pulmonary alveolar proteinosis (PAP) is a rare pathology characterized by accumulation of phospholipoproteinaceous material within the alveoli. The evolution of PAP is variable and treatment modalities are limited. Pharmacological therapeutic targets are being actively developed, but whole-lung lavage (WLL), first described in the 1960s, remains the cornerstone of therapy. The preferential treatment for PAP in our center is sequential WLL, where each lung is separately and sequentially perfused with warmed saline. However, some patients do not tolerate single lung ventilation (SLV), as there is a greater risk of severe hypoxemia with this method. Extracorporeal membrane oxygenation (ECMO), referring to an extracorporeal circuit that directly oxygenates and removes carbon dioxide from the blood, may be considered in highly selected patients with severe respiratory failure who otherwise would not be able to undergo WLL. In this context, veno-venous ECMO is most often utilized. We describe a case of a 44-year-old male diagnosed with silicosis five years earlier who presented with severe hypoxemic respiratory failure not amenable to WLL under general anesthesia with SLV, which was successfully managed with ECMO-assisted WLL.

19.
BMC Health Serv Res ; 17(1): 682, 2017 Sep 26.
Article in English | MEDLINE | ID: mdl-28950866

ABSTRACT

BACKGROUND: Public and patient involvement in the design of people-centred care and research is vital for communities whose needs are underserved, as are people with rare diseases. Innovations devised collectively by patients, caregivers, professionals and other members of the public can foster transformative change toward more responsive services and research. However, attempts to involve lay and professional stakeholders in devising community-framed strategies to address the unmet needs of rare diseases are lacking. In this study, we engaged with the community of Congenital Disorders of Glycosylation (CDG) to assess its needs and elicit social innovations to promote people-centred care and research. METHODS: Drawing on a qualitative study, we conducted three think tanks in France with a total of 48 participants, including patients/family members (n = 18), health care professionals (n = 7), researchers (n = 7) and people combining several of these roles (n = 16). Participants came from 20 countries across five continents. They were selected from the registry of the Second World Conference on CDG through heterogeneity and simple random sampling. Inductive and deductive approaches were employed to conduct interpretational analysis using open, axial and selective coding, and the constant-comparison method to facilitate the emergence of categories and core themes. RESULTS: The CDG community has unmet needs for information, quality health care, psychosocial support and representation in decision-making concerned with care and research. According to participants, these needs can be addressed through a range of social innovations, including peer-support communities, web-based information resources and a CDG expertise platform. CONCLUSION: This is one of the few studies to engage lay and professional experts in needs assessment and innovation for CDG at a global level. Implementing the innovations proposed by the CDG community is likely to have ethical, legal and social implications associated with the potential donation of patients' clinical and biological material that need to be assessed and regulated with involvement from all stakeholders. To promote people-centred care for the CDG community, and increase its participation in the governance of care and research, it is necessary to create participatory spaces in which the views of people affected by CDG can be fully expressed.


Subject(s)
Congenital Disorders of Glycosylation , Needs Assessment , Patient Participation , Congenital Disorders of Glycosylation/therapy , Decision Making , Family , Female , France , Health Personnel , Home Nursing , Humans , Male , Qualitative Research , Research Personnel , Self-Help Groups
20.
Anesth Analg ; 122(4): 943-52, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26991612

ABSTRACT

BACKGROUND: It is unclear whether maintaining pulmonary perfusion and ventilation during cardiopulmonary bypass (CPB) reduces pulmonary inflammatory tissue injury compared with standard CPB where the lungs are not ventilated and are minimally perfused. In this study, we tested the hypothesis that maintenance of lung perfusion and ventilation during CPB decreases regional lung inflammation, which may result in less pulmonary structural damage. METHODS: Twenty-seven pigs were randomly allocated into a control group only submitted to sternotomy (n = 8), a standard CPB group (n = 9), or a lung perfusion group (n = 10), in which lung perfusion and ventilation were maintained during CPB. Hemodynamics, gas exchanges, respiratory mechanics, and systemic interleukins (ILs) were determined at baseline (T0), at the end of 90 minutes of CPB (T90), and 180 minutes after CPB (T180). Bronchoalveolar lavage (BAL) ILs were obtained at T0 and T180. Dorsal and ventral left lung tissue samples were examined for optical and electron microscopy. RESULTS: At T90, there was a transient reduction in PaO2/FIO2 in CPB (126 ± 64 mm Hg) compared with the control and lung perfusion groups (296 ± 46 and 244 ± 57 mm Hg; P < 0.001), returning to baseline at T180. Serum ILs were not different among the groups throughout the study, whereas there were significant increases in BAL IL-6 (P < 0.001), IL-8 (P < 0.001), and IL-10 (P < 0.001) in both CPB and lung perfusion groups compared with the control group. Polymorphonuclear counts within the lung tissue were smaller in the lung perfusion group than in the CPB group (P = 0.006). Electron microscopy demonstrated extrusion of surfactant vesicles into the alveolar spaces and thickening of the alveolar septa in the CPB group, whereas alveolar and capillary histoarchitecture was better preserved in the lung perfusion group. CONCLUSIONS: Maintenance of lung perfusion and ventilation during CPB attenuated early histologic signs of pulmonary inflammation and injury compared with standard CPB. Although increased compared with control animals, there were no differences in serum or BAL IL in animals receiving lung ventilation and perfusion during CPB compared with standard CPB.


Subject(s)
Cardiopulmonary Bypass/adverse effects , Lung/pathology , Perfusion/methods , Pneumonia/pathology , Pneumonia/prevention & control , Respiration, Artificial/methods , Animals , Cardiopulmonary Bypass/trends , Male , Perfusion/trends , Respiration, Artificial/trends , Swine
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