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1.
BMC Musculoskelet Disord ; 25(1): 248, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561717

RESUMO

BACKGROUND: Obesity represents an epidemic of rising numbers worldwide year after year. In the Orthopedic field, obesity is one of the major causes leading to osteoarthritis needing Total Joint Arthroplasty (TJA). Still, contextually, it represents one of the most significant risk factors for joint replacement complications and failures. So, bariatric Surgery (BS) is becoming a valuable option for weight control and mitigating obesity-related risk factors. This review of the literature and meta-analysis aims to evaluate periprosthetic joint infections (PJI) and surgical site infections (SSI) rates in patients who underwent TKA after BS compared to obese patients without BS. METHODS: Systematic review was performed according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines up to October 2023. We included longitudinal studies comparing obese patients who underwent total knee arthroplasty after bariatric surgery (study group) and obese patients who underwent TKA (control group). The surgical site infection and Periprosthetic joint infection rate were compared among groups using a meta-analytical approach. RESULTS: The online database and references investigation identified one hundred and twenty-five studies. PJI rate differed significantly among groups, (z = -21.8928, p < 0.0001), with a lower risk in the BS group (z = -10.3114, p < 0.0001), for SSI, instead, not statistically significance were recorded (z = -0.6784, p = 0.4975). CONCLUSIONS: The current Literature suggests that Bariatric Surgery can reduce infectious complications in TKA, leading to better outcomes and less related costs treating of knee osteoarthritis in obese patients.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Artroplastia do Joelho , Cirurgia Bariátrica , Osteoartrite do Joelho , Infecções Relacionadas à Prótese , Humanos , Artroplastia do Joelho/efeitos adversos , Infecção da Ferida Cirúrgica/etiologia , Cirurgia Bariátrica/efeitos adversos , Obesidade/complicações , Obesidade/cirurgia , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/complicações , Artrite Infecciosa/etiologia , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/prevenção & controle , Estudos Retrospectivos , Artroplastia de Quadril/efeitos adversos
2.
Ther Adv Med Oncol ; 15: 17588359231186041, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37529158

RESUMO

Background: Nearly 30% of neuroendocrine tumors (NETs) have evidence of immunohistochemical (IHC) expression of estrogen (ER) and/or progesterone (PR) receptors. Therefore, targeting ER/PR may offer an effective NET-directed treatment to select patients. Methods: We conducted a multicenter Simon two-stage single-arm phase II trial of tamoxifen in patients with metastatic, progressive NETs. Eligible patients had positive IHC expression of ER and/or PR ⩾ 1%. Prior therapy with somatostatin analogs was required for progressing/functioning cases. Main exclusion criterion was aggressive disease requiring cytotoxic therapy. The primary end point was disease control rate (DCR) at week 24 by Response Evaluation Criteria in Solid Tumors version 1.1. We planned to enroll 23 patients in the first stage, to reach a DCR at week 24 of 70% (versus 50%); if ⩾12 patients reached the primary end point, a total of 37 would be included. Results: From February 2019 to February 2022, 23 out of 59 patients were eligible and enrolled: 15 (65%) were females; the most common sites were pancreas (11; 48%) and small bowel (6; 26%). In all, 13 patients (56.5%) had G2 NETs. At a median follow-up of 27 months, 13 patients (56.5%) had stable disease at week 24 and median progression-free survival (PFS) was 7.9 months [interquartile range (IQR): 3.7-12.1]. The best response was stable disease in 13 patients, with most patients experiencing minor tumor growth. Median PFS times were not significantly different according to ER/PR < or ⩾30% (p = 0.49) or ER versus PR expression (p = 0.19). One patient experienced grade 2 constipation. Conclusion: Tamoxifen for ER-/PR-positive NETs patients is safe but offers modest antitumor effects. Trial registry name: Study of Tamoxifen in Well Differentiated Neuroendocrine Tumors and Hormone Receptor Positive Expression (HORMONET). URL: https://clinicaltrials.gov/ct2/show/NCT03870399?term=03870399&draw=2&rank=1. Registration number: NCT03870399.

3.
Foods ; 12(14)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37509768

RESUMO

The objective of this work was to molecularly and genotypically characterize and test the inhibitory activity of six colicinogenic Escherichia coli strains (ColEc) and their partially purified colicins against STEC O157:H7 isolated from clinical human cases. Inhibition tests demonstrated the activity of these strains and their colicins against STEC O157:H7. By PCR it was possible to detect colicins Ia, E7, and B and microcins M, H47, C7, and J25. By genome sequencing of two selected ColEc strains, it was possible to identify additional colicins such as E1 and Ib. No genes coding for stx1 and stx2 were detected after analyzing the genome sequence. The inhibitory activity of ColEc against STEC O157:H7 used as an indicator showed that colicins are potent growth inhibitors of E. coli O157:H7, being a potential alternative to reduce the presence of pathogens of public health relevance.

4.
Eur Rev Med Pharmacol Sci ; 27(8): 3457-3466, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37140295

RESUMO

OBJECTIVE: Traumatic pelvic ring fractures include several comorbidities due to the close anatomical relationship between the skeletal system, pelvic organs, and neurovascular structures. In this retrospective multicenter study, we evaluated patients complaining of sexual dysfunction following pelvic ring fractures, assessed through different neuro-physiological examinations. PATIENTS AND METHODS: Patients were enrolled one year after the injury according to their reported ASEX scores and evaluated on the basis of the Tile's type of pelvic fracture. Lower limb and sacral somatosensory evoked potentials, pelvic floor electromyography, bulbocavernosus reflex and pelvic floor motor evoked potentials were recorded, according to the neurophysiological indications. RESULTS: A total of 14 male patients (mean age 50.4; 8 subjects Tile-type B and 6 Tile-type C) were enrolled. The ages between the Tile B group and the Tile C group of patients were not significantly different (p=0.187), while the ASEX scores were significantly different (p=0.014). In 57% of patients (n=8), no alterations in nerve conduction and/or pelvic floor neuromuscular responses were found. In 6 patients, electromyographic signs of denervation were revealed (2 patients), and alterations of the sacral efferent nerve component were detected in 4 patients. CONCLUSIONS: Sexual dysfunctions after a traumatic pelvic ring fracture are more common in Tile-type B. Our preliminary data did not reveal a significant association with neurogenic aetiology. Other causes could explain the complaining impairments.


Assuntos
Fraturas Ósseas , Ossos Pélvicos , Disfunções Sexuais Fisiológicas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dados Preliminares , Fraturas Ósseas/complicações , Ossos Pélvicos/lesões , Pelve , Fixação Interna de Fraturas
5.
Ecancermedicalscience ; 17: 1523, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37113718

RESUMO

Background: Prognostic and predictive markers in metastatic pheochromocytoma and paraganglioma (mPPGL) are unknown. We aimed to evaluate epidemiology of mPPGL, and prognostic factors of overall survival (OS) and predictive markers of treatment duration with first-line chemotherapy (TD1L). Patients and methods: Retrospective multicentre study of adult patients with mPPGL treated in Latin American centres between 1982 and 2021. Results: Fifty-eight patients were included: 53.4% were female, median age at diagnosis of mPPGL was 36 years and 12.1% had a family history of PPGL. The primary site was adrenal, non-adrenal infradiaphragmatic and supradiaphragmatic in 37.9%, 34.5% and 27.6%, respectively. 65.5% had a functioning tumour and 62.1% had metachronous metastases. Positive uptakes were found in 32 (55.2%) 68Gallium positron emission tomography (PET/CT), 27 (46.6%) 2-deoxy-2-[fluorine-18]fluoro-D-glucose PET/CT and 37 (63.8%) of 131Iodine-metaiodobenzylguanidine (MIBG) tests. Twenty-three (40%) patients received first-line chemotherapy, with cyclophosphamide, vincristine and dacarbazine used in 12 (52%) of patients. At a median follow-up of 62.8 months, median TD1L was 12.8 months. Either functional exams, tumour functionality, pathological characteristics or primary tumour location were significantly associated with response or survival. Yet, negative MIBG, Ki67 ≥ 10%, infradiaphragmatic location and functional tumours were associated with numerically inferior OS. Conclusions: In patients with mPPGL, prognostic and predictive factors to chemotherapy are still unknown, but negative MIBG uptake, Ki67 ≥ 10%, infradiaphragmatic location and functional tumours were numerically linked to worse OS. Our results should be further validated in larger and independent cohorts.

6.
Eur Rev Med Pharmacol Sci ; 27(6): 2624-2633, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37013780

RESUMO

OBJECTIVE: Robotic-assisted arthroplasty is a relatively modern concept, quickly arising in its use. The aim of this systematic review is to assess, according to the existing literature, which are the functional and clinical outcomes and component positioning and implant survivorship of unicompartmental knee arthroplasty surgery performed using an image-free hand-held robotic system. Moreover, we analyzed whether there are significant differences and advantages compared to conventional surgery. MATERIALS AND METHODS: A systematic review has been performed on studies published between 2004 and 2021, on the electronic library databases, according to the Preferred Reporting Items of Systematic Reviews and Meta-analysis (PRISMA) statement. The inclusion criteria were all studies described as unicompartmental knee arthroplasty performed with the Navio robotic system. RESULTS: Fifteen studies were included, and 1,262 unicondylar knee arthroplasties were analyzed. These studies showed a satisfactory recovery of joint function, with a good range of motion (extension <5° and flexion which ranged from 105° to 130.3°) in patients of the NAVIO group. The revision rate was <2% while the infection rate <1%; no postoperative transfusion was needed in all UKA implanted. CONCLUSIONS: The use of a robotic tool for unicompartmental knee arthroplasty (UKA) could lead to a better implant positioning and joint alignment than conventional surgery. There is still limited evidence to support that the use of this robot in unicompartmental knee arthroplasty is a greater survivorship than other systems or conventional techniques; therefore, a long-term follow-up is needed.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Procedimentos Cirúrgicos Robóticos , Humanos , Artroplastia do Joelho/métodos , Articulação do Joelho , Osteoartrite do Joelho/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
7.
Reumatismo ; 74(4)2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36942981

RESUMO

Rheumatic musculoskeletal diseases or RMD [rheumatoid arthritis (RA) and spondyloarthritis (SpA)] are systemic inflammatory diseases for which there are no biomarkers capable of predicting treatments with a higher likelihood of response in naive patients. In addition, the expiration of the anti-TNF blocking drugs' patents has resulted in the availability of anti-TNF biosimilar drugs with the same efficacy and safety than originators but at significantly reduced prices. To guarantee a personalized therapeutic approach to RMD treatment, a board of rheumatologists and stakeholders from the Campania region, Italy, developed a clinically applicable arthritis therapeutic algorithm to guide rheumatologists (DATA project). The general methodology relied on a Delphi technique forecast to produce a set of statements that summarized the experts' consensus. Selected clinical scenarios were discussed in light of the available evidence, and there were two rounds of voting on the therapeutic approaches. Separate discussions were held regarding rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. The decision-making factors for each disease were clinical presentation, demographics, and comorbidities. In this paper, we describe a virtuous process between rheumatologists and healthcare system stakeholders that resulted in the development of a shared therapeutic algorithm for RMD patients naive to bDMARDs.


Assuntos
Antirreumáticos , Artrite Psoriásica , Artrite Reumatoide , Espondilartrite , Espondilite Anquilosante , Humanos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Atenção à Saúde , Algoritmos , Antirreumáticos/uso terapêutico
8.
Ther Adv Med Oncol ; 15: 17588359231156218, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36950274

RESUMO

Background: Gastroenteropancreatic (GEP) neuroendocrine neoplasms with Ki-67 > 20% were subdivided in the most recent 2019 World Health Organization histopathological classification into grade 3 (G3) neuroendocrine tumors (NETs), described as well-differentiated tumors, and neuroendocrine carcinomas, which are described as poorly differentiated tumors. This classification met the demand noted for different prognoses between these subgroups, prompting the need for treatment recommendations for well-differentiated G3 tumors. Methods: We systematically searched medical literature databases and oncology conferences for studies on G3 GEP NET to describe epidemiology, diagnosis, molecular features, and treatments used. We excluded studies that did not discriminate G3 NET data. Data were tabulated and described, and a quality analysis of the reports was performed. Results: We found 23 published studies and six abstracts; 89.7% of studies were retrospective, six were composed exclusively of G3 NETs. Among 761 patients, the median number of patients per study was 15, most were male and older than 60 years, and functional imaging tests were positive in more than 80% of cases. Overall, the scientific evidence supporting the treatment of G3 GEP NETs is limited. For localized disease, resection remains the standard treatment but there is no evidence to support neoadjuvant or adjuvant therapy. For advanced disease, capecitabine and temozolomide seems to be the most effective option, with a response rate, median progression-free survival, and median overall survival up to 37.9%, 20.6 months, and 41.2 months, respectively. Conclusion: The latest available data on the epidemiology, diagnosis, molecular changes, and treatment of G3 GEP NET are described. Yet, the level of evidence for treatment recommendations is low, as most studies are retrospective. A treatment algorithm for G3 GEP NET is proposed.

9.
Eur Rev Med Pharmacol Sci ; 26(1 Suppl): 60-65, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36448857

RESUMO

OBJECTIVE: Muscular flaps may represent a valid treatment option for prosthetic infection after knee arthroplasty. PATIENTS AND METHODS: We present the results of 20 consecutive patients treated with the use of medial gastrocnemius flap for the management of different types of injuries or integumentary defects after total knee arthroplasty. Tissue necrosis or dehiscence occurred within 1 and 2 months after arthroplasty. The mean follow-up was 23.4 (12-60) months. Clinical outcome was evaluated according to the infection control rate and post-operative Knee Society Score (KSS). RESULTS: Prosthesis salvage and complete restoration of skin coverage were achieved in all patients. Functional assessment was performed using the KSS score. The final knee KSS score was classified as excellent (score: 80-100) in 0 patients, good (score: 70-79) in 17 patients, fair (score: 60-69) in 2 patients, and poor (score: 60) in 1 patient. Residual Extension Deficit: 0-20°; Very Satisfactory in 17 patients. 30-70° Satisfactory in 2 patients, 80-90° Unsatisfactory in 1 patient. Patients who successfully underwent flap treatment experienced a much greater increase in both components of the KSS score. CONCLUSIONS: The results highlight the effectiveness of medial gastrocnemius muscular flap for the treatment of prosthetic knee infection, in terms of function, limb salvage, cost-effectiveness and post-surgery quality of life. Further larger studies may consolidate these findings.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Humanos , Prótese do Joelho/efeitos adversos , Qualidade de Vida , Retalhos Cirúrgicos , Artroplastia do Joelho/efeitos adversos , Articulação do Joelho/cirurgia
10.
Eur Rev Med Pharmacol Sci ; 26(1 Suppl): 113-118, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36448863

RESUMO

OBJECTIVE: Proximal periprosthetic femoral fractures (PPFFs) are gradually increasing and surgical management is often associated with high risk of complications, due to elderly population and associated comorbidities. PATIENTS AND METHODS: We retrospectively assessed 39 patients at least at 2-years follow-up. We identified two study groups, similar for demographic data. Group A included patients surgically treated without involving prosthetic implants, whereas Group B included patients in which an implant revision was performed. RESULTS: Data were recorded from January 2017 to February 2020, and 39 patients were included: 30 females (76.9%) and 9 males (23.1%), with a confirmed diagnosis of periprosthetic fracture of the proximal femur. 23 (58.9%) patients were treated with Open Reduction and Internal Fixation (ORIF), 12 (30.7%) with revision surgery and 4 (10.3%) were treated by modular megaprosthesis. CONCLUSIONS: The treatment options considered in the study, revision arthroplasty and internal fixation had shown no significant differences as a matter of clinical outcomes and postoperative complications.


Assuntos
Artroplastia de Quadril , Fraturas do Fêmur , Fraturas Periprotéticas , Feminino , Masculino , Humanos , Idoso , Fraturas Periprotéticas/cirurgia , Artroplastia de Quadril/efeitos adversos , Estudos Retrospectivos , Fêmur , Fraturas do Fêmur/cirurgia
11.
Diseases ; 10(4)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36278566

RESUMO

Facial hemiplegia happens when the seventh cranial nerve is inflamed, causing a dysfunction of the facial nerve in specific regions. This case report brings a complex case of facial hemiplegia, a non-temporary lesion caused by a traumatic accident, which had a more conservative approach, treating the patient with botulinum toxin. After explanation of treatment outcomes, the patient favored treatment on a unilateral side with botulinum toxin applied locally to the muscles. It was applied on her left side, in order to change the muscles tonus and improve the esthetic. The patient adhered to immediate and short-term instructions following the procedure, including movement limitation and skin exposure avoidance. At 2 weeks, the patient returned to follow-up, and the result was checked. After around 6-month follow-up, the patient was reassessed, and a new application was done. The patient tried to contract the procerus and corrugator muscles which were treated, and periorbicular region that was corrected. After contracting the frontal muscle, a satisfactory result was also seen in the frontal area. While limited to a single case presentation, botulinum toxin may be an effective short-term tool for treatment of facial hemiplegia to establish an effective esthetic result.

12.
Rev. Hosp. Ital. B. Aires (2004) ; 42(3): 121-128, sept. 2022. graf, tab
Artigo em Espanhol | LILACS, UNISALUD, BINACIS | ID: biblio-1396175

RESUMO

Introducción: debido a la pandemia desarrollada por COVID-19, el Gobierno argentino, adoptó ­a partir del 20 de marzo de 2020­ medidas excepcionales de aislamiento social, preventivo y obligatorio (ASPO) o cuarentena, con el fin de proteger la salud pública. En esta etapa se manifestó un mayor uso de pantallas que, en exceso, constituye un factor de riesgo de enfermedades cardiovasculares y alteración en la calidad del sueño. El objetivo de estudio fue estimar el cambio de las horas de sueño y de uso de pantallas antes del inicio del ASPO, en comparación con la tercera y octava semana de cuarentena en personas de 13 a 80 años de la provincia del Neuquén y el Alto Valle Río Negro-Neuquén. Métodos: se realizaron dos Encuestas, en la tercera y octava semana de cuarentena, sobre conductas y hábitos de vida en personas entre 13-80 años. Fueron autoadministradas y enviadas por redes sociales. El muestreo fue aleatorio. Los datos se analizaron usando el paquete estadístico SPSS®. Las encuestas fueron anónimas y confidenciales. Resultados: se obtuvieron 3386 respuestas. De ellas se infirió que la cantidad de horas diarias frente a pantallas y las horas de sueño y el inicio del sueño fueron diferentes por grupos en los períodos precuarentena, y tercera y octava semana de la cuarentena. El grupo de adolescentes mostró mayores diferencias en todas las variables respecto del período precuarentena. La correlación entre las horas de pantalla y las horas de sueño fue baja, en las 3 etapas de la cuarentena. Conclusión: este estudio estimó el cambio de hábitos durante la cuarentena. En ese período se observó mayor cantidad de horas de sueño, un retraso en el tiempo de inicio del sueño y más horas frente a las pantallas; estas diferencias fueron significativas respecto del período precuarentena, y las mayores diferencias se registraron entre los adolescentes. (AU)


Introduction: due to the pandemic developed by COVID 19, the Argentine Government adopted, as of March 20, 2020, exceptional measures of social, preventive and mandatory isolation (ASPO) or quarantine in order to protect public health. In this stage, there was a greater use of screens that in excess, constitutes a risk factor for cardiovascular diseases and alteration in the quality of sleep. Methods: two Surveys were conducted, in the third and eighth week of quarantine, on behaviors and life habits in people between 13-80 years of age. They were self-administered and sent through social networks. The sampling was random. The data were analyzed using the SPSS® statistical package. The surveys were anonymous and confidential. Results: 3386 responses were obtained. It was obtained that the amount of daily hours in front of screens and the hours of sleep and the onset of sleep were different by groups of pre, third and eighth week of quarantine. The adolescent groups howed greater differences in all variables with respect to the pre-quarantine period. The correlation between the hours of screen and the hours of sleep was low, in the 3 stages of quarantine. Conclusion: this study estimated the change in habits during quarantine. In quarantine, longer hours of sleep, a delay in the time of onset of sleep and more hours in front of screens were observed, these differences being significant with respect to the pre-quarantine period, with the greatest differences being established in adolescents. (AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Sono , Isolamento Social , Quarentena , Tempo de Tela , COVID-19/complicações , Qualidade do Sono , Argentina , Estudos Transversais , Inquéritos e Questionários , Comportamento do Adolescente , Comportamento Sedentário , Análise de Dados
13.
Arthritis Res Ther ; 24(1): 163, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35794662

RESUMO

BACKGROUND: Multiple studies have confirmed dysbiosis in ankylosing spondylitis (AS) and inflammatory bowel disease (IBD); however, due to methodological differences across studies, it has not been possible to determine if these diseases have similar or different gut microbiomes. RESULTS: In this study, faecal and intestinal biopsies were obtained from 33 Australian AS patients (including 5 with concomitant IBD, 'AS-IBD'), 59 IBD patients and 105 healthy controls. Stool samples were also obtained from 16 Italian AS patients and 136 Swedish AS patients. Focusing on the Australian cohort, AS, AS-IBD and IBD patients differed from one another and from healthy controls in both alpha and beta diversity. AS patients with and without clinical IBD could be distinguished from one another with moderate accuracy using stool microbiome (AUC=0.754). Stool microbiome also accurately distinguished IBD patients from healthy controls (AUC=0.757). Microbiome composition was correlated with disease activity measured by BASDAI and faecal calprotectin (FCP) levels. Enrichment of potentially pathogenic Streptococcus was noted in AS, AS-IBD and IBD patients. Furthermore, enrichment of another potentially pathogenic genus, Haemophilus, was observed in AS, AS-IBD, IBD, AS patients with increased BASDAI, and IBD patients with faecal calprotectin >100 µg/mg. Apart from these genera, no other taxa were shared between AS and IBD patients. CONCLUSIONS: In conclusion, the distinct gut microbiome of AS and AS-IBD patients compared to IBD patients and healthy controls is consistent with immunological and genetic evidence suggesting that the gut plays a different role in driving AS compared with IBD. However, enrichment of two potentially pathogenic genera in both diseases suggests that the presence of a shared/common microbial trigger of disease cannot be discounted.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Espondilite Anquilosante , Austrália , Doença Crônica , Microbioma Gastrointestinal/genética , Humanos , Complexo Antígeno L1 Leucocitário
14.
Commun Biol ; 4(1): 1301, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795391

RESUMO

Inflammatory liver disease increases the risk of developing primary liver cancer. The mechanism through which liver disease induces tumorigenesis remains unclear, but is thought to occur via increased mutagenesis. Here, we performed whole-genome sequencing on clonally expanded single liver stem cells cultured as intrahepatic cholangiocyte organoids (ICOs) from patients with alcoholic cirrhosis, non-alcoholic steatohepatitis (NASH), and primary sclerosing cholangitis (PSC). Surprisingly, we find that these precancerous liver disease conditions do not result in a detectable increased accumulation of mutations, nor altered mutation types in individual liver stem cells. This finding contrasts with the mutational load and typical mutational signatures reported for liver tumors, and argues against the hypothesis that liver disease drives tumorigenesis via a direct mechanism of induced mutagenesis. Disease conditions in the liver may thus act through indirect mechanisms to drive the transition from healthy to cancerous cells, such as changes to the microenvironment that favor the outgrowth of precancerous cells.


Assuntos
Colangite Esclerosante/genética , Cirrose Hepática Alcoólica/genética , Hepatopatias/genética , Mutagênese , Hepatopatia Gordurosa não Alcoólica/genética , Lesões Pré-Cancerosas/genética , Células-Tronco/metabolismo , Humanos , Fígado/fisiologia , Organoides/metabolismo
15.
Front Digit Health ; 3: 630273, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34713102

RESUMO

The challenges presented by the Coronavirus disease 2019 (COVID-19) pandemic to the National Health Service (NHS) in the United Kingdom (UK) led to a rapid adaptation of infection disease protocols in-hospital. In this paper we report on the optimisation of our wearable ambulatory monitoring system (AMS) to monitor COVID-19 patients on isolation wards. A wearable chest patch (VitalPatch®, VitalConnect, United States of America, USA) and finger-worn pulse oximeter (WristOx2® 3150, Nonin, USA) were used to estimate and transmit continuous Heart Rate (HR), Respiratory Rate (RR), and peripheral blood Oxygen Saturation (SpO2) data from ambulatory patients on these isolation wards to nurse bays remote from these patients, with a view to minimising the risk of infection for nursing staff. Our virtual High-Dependency Unit (vHDU) system used a secure web-based architecture and protocols (HTTPS and encrypted WebSockets) to transmit the vital-sign data in real time from wireless Android tablet devices, operating as patient data collection devices by the bedside in the isolation rooms, into the clinician dashboard interface available remotely via any modern web-browser. Fault-tolerant software strategies were used to reconnect the wearables automatically, avoiding the need for nurses to enter the isolation ward to re-set the patient monitoring equipment. The remote dashboard also displayed the vital-sign observations recorded by the nurses, using a separate electronic observation system, allowing them to review both sources of vital-sign data in one integrated chart. System usage was found to follow the trend of the number of local COVID-19 infections during the first wave of the pandemic in the UK (March to June 2020), with almost half of the patients on the isolation ward monitored with wearables during the peak of hospital admissions in the local area. Patients were monitored for a median of 31.5 [8.8, 75.4] hours, representing 88.1 [62.5, 94.5]% of the median time they were registered in the system. This indicates the system was being used in the isolation ward during this period. An updated version of the system has now also been used throughout the second and third waves of the pandemic in the UK.

16.
Sci Rep ; 11(1): 7767, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33833396

RESUMO

The electro-mechanical and electro-thermal properties of high-performance Restacked-Rod-Process (RRP) Nb3Sn wires are key factors in the realization of compact magnets above 15 T for the future particle physics experiments. Combining X-ray micro-tomography with unsupervised machine learning algorithm, we provide a new tool capable to study the internal features of RRP wires and unlock different approaches to enhance their performances. Such tool is ideal to characterize the distribution and morphology of the voids that are generated during the heat treatment necessary to form the Nb3Sn superconducting phase. Two different types of voids can be detected in this type of wires: one inside the copper matrix and the other inside the Nb3Sn sub-elements. The former type can be related to Sn leaking from sub-elements to the copper matrix which leads to poor electro-thermal stability of the whole wire. The second type is detrimental for the electro-mechanical performance of the wires as superconducting wires experience large electromagnetic stresses in high field and high current conditions. We analyze these aspects thoroughly and discuss the potential of the X-ray tomography analysis tool to help modeling and predicting electro-mechanical and electro-thermal behavior of RRP wires and optimize their design.

17.
Crit Rev Food Sci Nutr ; 61(12): 2078-2089, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32496815

RESUMO

From 2012, the preservation of food products under pressure has been increasingly studied and the knowledge acquired has enlarged since several food products have been studied at different storage conditions. This new food preservation methodology concept called Hyperbaric Storage (HS) has gain relevance due to its potential as a replacement or an improvement to the conventional cold storage processes, such as the traditional refrigeration (RF), or even frosting, from the energetic savings to the reduction of the carbon foot-print. Briefly, HS is capable to inhibit the microbial proliferation or its inactivation which results in the extension of the shelf-life of several food products when compared to RF. Moreover, the overall quality parameters seem not to be affected by HS, being the differences detected on samples over storage similar to lower when compared to the ones stored at RF. This review paper aims to gather data from all studies carried out so far regarding HS performance, mainly at room temperature on fruit juices, meat and fisheries, as well on dairy products and ready-to-eat meals. The HS advantages as a new food preservation methodology are presented and explained, being also discussed the industrial viability and environmental impact of this methodology, as well its limitations.


Assuntos
Armazenamento de Alimentos , Refrigeração , Microbiologia de Alimentos , Conservação de Alimentos , Carne/análise , Temperatura
19.
Mol Psychiatry ; 26(4): 1272-1285, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-31492942

RESUMO

The dopamine D2 and D3 receptors are implicated in schizophrenia and its pharmacological treatments. These receptors undergo intracellular trafficking processes that are modulated by dysbindin-1 (Dys). Indeed, Dys variants alter cognitive responses to antipsychotic drugs through D2-mediated mechanisms. However, the mechanism by which Dys might selectively interfere with the D3 receptor subtype is unknown. Here, we revealed an interaction between functional genetic variants altering Dys and D3. Specifically, both in patients with schizophrenia and in genetically modified mice, concomitant reduction in D3 and Dys functionality was associated with improved executive and working memory abilities. This D3/Dys interaction produced a D2/D3 imbalance favoring increased D2 signaling in the prefrontal cortex (PFC) but not in the striatum. No epistatic effects on the clinical positive and negative syndrome scale (PANSS) scores were evident, while only marginal effects on sensorimotor gating, locomotor functions, and social behavior were observed in mice. This genetic interaction between D3 and Dys suggests the D2/D3 imbalance in the PFC as a target for patient stratification and procognitive treatments in schizophrenia.


Assuntos
Disbindina , Receptores de Dopamina D3 , Esquizofrenia , Animais , Cognição , Humanos , Camundongos , Receptores de Dopamina D2/genética , Receptores de Dopamina D3/genética , Esquizofrenia/genética
20.
Nat Commun ; 11(1): 3932, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32753580

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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