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1.
Sensors (Basel) ; 22(15)2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35957396

RESUMO

The usage of digital and intelligent healthcare applications on mobile devices has grown progressively. These applications are generally distributed and access remote healthcare services on the user's applications from different hospital sources. These applications are designed based on client-server architecture and different paradigms such as socket, remote procedure call, and remote method invocation (RMI). However, these existing paradigms do not offer a security mechanism for healthcare applications in distributed mobile-fog-cloud networks. This paper devises a blockchain-socket-RMI-based framework for fine-grained healthcare applications in the mobile-fog-cloud network. This study introduces a new open healthcare framework for applied research purposes and has blockchain-socket-RMI abstraction level classes for healthcare applications. The goal is to meet the security and deadline requirements of fine-grained healthcare tasks and minimize execution and data validation costs during processing applications in the system. This study introduces a partial proof of validation (PPoV) scheme that converts the workload into the hash and validates it among mobile, fog, and cloud nodes during offloading, execution, and storing data in the secure form. Simulation discussions illustrate that the proposed blockchain-socket-RMI minimizes the processing and blockchain costs and meets the security and deadline requirements of fine-grained healthcare tasks of applications as compared to existing frameworks in work.


Assuntos
Blockchain , Segurança Computacional , Computadores , Atenção à Saúde , Humanos , Projetos de Pesquisa
2.
Ann Hum Genet ; 79(5): 350-356, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26102279

RESUMO

Dystrophic epidermolysis bullosa (DEB) is an inherited skin disorder with variable severity and heterogeneous genetic involvement. Diagnostic approaches for this condition include clinical evaluations and electron microscopy of patients' skin biopsies, followed by Sanger sequencing (SS) of a large gene (118 exons) that encodes the alpha chain of type VII collagen (COL7A1) located on Chromosome 3p21.1. However, the use of SS may hinder diagnostic efficiency and lead to delays because it is costly and time-consuming. We evaluated a 5-generation consanguineous family with 3 affected individuals presenting the severe generalised DEB phenotype. Human whole-exome sequencing (WES) revealed 2 homozygous sequence variants: the previously reported variant p.Arg578* in exon 13 and a novel variant p.Arg2063Gln in exon 74 of the COL7A1 gene. Validation by SS, performed on all family members, confirmed the cosegregation of the 2 variants with the disease phenotype. To the best of our knowledge, 2 homozygous COL7A1 variants have never been simultaneously reported in DEB patients; however, the upstream protein truncation variant is more likely to be disease-causing than the novel missense variant. WES can be used as an efficient molecular diagnostic tool for evaluating autosomal recessive forms of DEB.

3.
Transfus Apher Sci ; 51(1): 39-41, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24929836

RESUMO

OBJECTIVE: Find the allele frequencies of Duffy blood group antigens in donor population from northern Pakistan. DESIGN: Cross sectional study. PLACE AND DURATION OF STUDY: Armed Forces Institute of Transfusion (AFIT), Rawalpindi in year 2012. PATIENTS AND METHODS: A total of 1000 healthy, adult blood donors were included in the study. Blood samples were collected in ethylenediamine tetra aceticacid (EDTA) tube and then tested with anti sera Fy(a) and Fy(b) by the tube method. RESULTS: The allele frequencies of Duffy blood group antigens were calculated. The most common phenotype was Fy(a+b+) which was present in 552 (55.2%) donors followed by the Fy(a+b-) phenotype in 228 (22.8%) donors, while 178 (17.8%) were Fy(a-b+) and the least prevalent phenotype was Fy(a-b-) which was present in 42 (4.2%) of donors. CONCLUSION: The majority of our population is heterozygous for Duffy antigens a and b.


Assuntos
Alelos , Doadores de Sangue , Sistema do Grupo Sanguíneo Duffy/genética , Frequência do Gene , Heterozigoto , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão
4.
Comput Biol Med ; 163: 107210, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37442008

RESUMO

Urinary disease is a complex healthcare issue that continues to grow in prevalence. Urine tests have proven valuable in identifying conditions such as kidney disease, urinary tract infections, and lower abdominal pain. While machine learning has made significant strides in automating urinary tract infection detection, the accuracy of existing methods is hindered by concerns surrounding data privacy and the time-intensive nature of training and testing with large datasets. Our proposed method aims to address these limitations and achieve highly accurate urinary tract infection detection across various healthcare laboratories, while simultaneously minimizing data security risks and processing delays. To tackle this challenge, we approach the problem as a combinatorial optimization task. We optimize the accuracy objective as a concave function and minimize computation delay as a convex function. Our work introduces a framework enabled by federated learning and reinforcement learning strategy (FLRLS), leveraging lab urine data. FLRLS employs deterministic agents to optimize the exploration and exploitation of urinary data, while the actual determination of urinary tract infections is performed at a centralized, aggregated node. Experimental results demonstrate that our proposed method improves accuracy by 5% and reduces total delay. By combining federated learning, reinforcement learning, and a combinatorial optimization approach, we achieve both high accuracy and minimal delay in urinary tract infection detection.


Assuntos
Instalações de Saúde , Aprendizado de Máquina
5.
J Laparoendosc Adv Surg Tech A ; 33(4): 309-319, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36577030

RESUMO

Background: Online surgical videos serve as useful adjuncts for surgical training. YouTube is a social media platform increasingly used for education. However, the educational qualities of these videos have not been proven. This study aims to review the topmost 30 viewed videos on laparoscopic distal pancreatectomy (LDP) on YouTube. Methods: A YouTube search was performed on August 1, 2020, using the term "laparoscopic distal pancreatectomy." Inclusion criteria were LDP with or without splenectomy. Exclusion criteria were open or robotic distal pancreatectomy and radical antegrade modular pancreatosplenectomy. To grade the videos, we used a modified version of the LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) 24 of the original 37 consensus statements were used in our study. Results: Twenty-nine of the top 30 most viewed videos were included (1 video was a duplicate). The overall mean view count and number of likes were 7195 (range 2322-39,927) and 17 (range 0-108), respectively. Thirteen videos (44.8%) were on LDP with splenic preservation. The mean conformity to the modified LAP-VEGaS was 9.3 (range 4-16) with a mean of 38.8% (range 16.7%-66.7%) of the criteria met. There was weak correlation between the number of views and the number of criteria met (ρ = 0.189, P < .05). Twelve videos (41.4%) described about staple line management, nine videos (31%) about tips and tricks to reduce postoperative pancreatic fistula, including drainage tube management, and three videos (10.3%) identified the common hepatic artery. Videos with no commentary had the lowest mean percentage of criteria met (24.6%). Conclusion: The topmost viewed LDP surgical videos have gaps in meeting the educational needs of a trainee. Video uploaders should be cognizant of the learning needs of surgical trainees.


Assuntos
Laparoscopia , Mídias Sociais , Humanos , Pancreatectomia , Laparoscopia/educação , Escolaridade , Pâncreas , Complicações Pós-Operatórias , Gravação em Vídeo
6.
World J Gastrointest Surg ; 15(9): 1841-1857, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37901741

RESUMO

Indocyanine green (ICG) is a water-soluble fluorescent dye that is minimally toxic and widely used in gastrointestinal surgery. ICG facilitates anatomical identification of structures (e.g., ureters), assessment of lymph nodes, biliary mapping, organ perfusion and anastomosis assessment, and aids in determining the adequacy of oncological margins. In addition, ICG can be conjugated to artificially created antibodies for tumour markers, such as carcinoembryonic antigen for colorectal, breast, lung, and gastric cancer, prostate-specific antigen for prostate cancer, and cancer antigen 125 for ovarian cancer. Although ICG has shown promising results, the optimization of patient factors, dye factors, equipment, and the method of assessing fluorescence intensity could further enhance its utility. This review summarizes the clinical application of ICG in gastrointestinal surgery and discusses the emergence of novel dyes such as ZW-800 and VM678 that have demonstrated appropriate pharmacokinetic properties and improved target-to-background ratios in animal studies. With the emergence of robotic technology and the increasing reporting of ICG utility, a comprehensive review of clinical application of ICG in gastrointestinal surgery is timely and this review serves that aim.

7.
Obes Res Clin Pract ; 17(3): 271-274, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37188620

RESUMO

Obesity is a global pandemic with increasing prevalence and long-term negative health outcomes. Bariatric metabolic surgery (BMS) is the most effective treatment option for achieving long-term weight loss. A systematic search was performed from 1990 to 2020 of BMS procedures using standardised groups. Data were collected on operation type reported, country and continent of publication. North America and Europe were the leading contributors to global publications in BMS, producing 41.3 % (n = 4931) and 37.1 % (n = 4436) of publications respectively, with increasing publications from Asia. Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG) were the most studied procedure types with number of publications continuing to increase over time. A plateau and downward trend was seen for Laparoscopic Adjustable Gastric Band (LAGB) publication from 2015 to 2019. An increase in emerging/experimental techniques over the past decade is observed.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Humanos , Cirurgia Bariátrica/tendências , Biomarcadores , Gastrectomia/métodos , Derivação Gástrica/métodos , Laparoscopia/métodos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Pesquisa Biomédica
8.
Obes Surg ; 32(8): 2764-2771, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35674980

RESUMO

Chyloperitoneum and chylothorax (ChP/ChT) are rare complications after bariatric surgery. This systematic review aims to evaluate the incidence, cause, treatment, and outcome of ChP and ChT after bariatric surgery. This review investigates published English language scientific literature systematically in an attempt to answer these questions. Our literature search revealed 66 studies, of which 23 were included. There were a total of 40 patients (38, ChP; 2, ChT). Eighteen of 40 (43.9%) patients were treated laparoscopically, and one patient (2.44%) underwent thoracoscopy and ligation of the thoracic duct. Both ChP and ChT are rare complications after bariatric surgery.


Assuntos
Cirurgia Bariátrica , Quilotórax , Ascite Quilosa , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Cirurgia Bariátrica/efeitos adversos , Quilotórax/etiologia , Quilotórax/cirurgia , Ascite Quilosa/complicações , Ascite Quilosa/terapia , Gastrectomia/efeitos adversos , Derivação Gástrica/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Ligadura/efeitos adversos , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
9.
Obes Surg ; 31(5): 2255-2267, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33595790

RESUMO

Obesity is commonly associated with non-alcoholic fatty liver disease and is a significant cause of chronic liver disease and cirrhosis. Some patients undergoing bariatric surgery suffer from cirrhosis of the liver. Currently, there is a lack of consensus on the management of these patients and the safety and efficacy of bariatric surgery in this group. This review aims to update our previously published systematic review on the same topic. A total of 21 studies reporting experience on patients with cirrhosis undergoing bariatric surgery were included. Sleeve gastrectomy was the most common surgery performed, followed by Roux-en-Y gastric bypass. The results show that bariatric surgery may be feasible in carefully selected patients with obesity and cirrhosis although they have slightly higher morbidity and mortality rates.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Obesidade Mórbida , Gastrectomia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Redução de Peso
10.
J Clin Med ; 10(17)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34501472

RESUMO

Portomesenteric vein thrombosis (PMVT) is a rare post-operative complication of bariatric procedures, occurring in between 0.3% and 1% of cases. A structured questionnaire consisting of 27 items was available online to members of the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) to investigate the occurrence of PMVT. A total of 89 bariatric surgeons from 61 countries participated. Twenty-six (29.21%) reported at least one case of PMVT (46.15% males; 53.84% females). The surgery most associated with PMVT occurrence was sleeve gastrectomy (84.6%), followed by Roux-en-Y gastric bypass (RYGB) (7.69%), and laparoscopic adjustable gastric banding (LAGB) (7.69%). The time gap between surgery and PMVT was 19.28 ± 8.72 days. The predominant symptom was abdominal pain in 96.15% of patients, followed by fever in 26.9%. Complete occlusion of the portal vein was reported in 34.6% of cases, with involvement of the portal system in 69%, extension to the superior mesenteric district in 23%, and extension to the splenic vein in two patients (7.7%). Our survey, which is the largest regarding PMVT to date, revealed a diffuse lack of standardization in the choice, duration, and dosing of prophylaxis regimens as well as treatment modalities, reflecting the literature gap on the topic.

11.
Obes Surg ; 31(3): 949-964, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33159293

RESUMO

BACKGROUND: One-anastomosis gastric bypass (OAGB) was established as a recognized bariatric procedure in the 2018 International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) position statement. This study evaluates the outcomes of revisional OAGB (rOAGB) after a restrictive index procedure, and to compare it to revisional RYGB (rRYGB). METHODS: A literature search was performed according to the PRISMA guidelines on papers published from inception till February 2020. Original studies involving patients who underwent rOAGB after a primary failed restrictive procedure were included. The primary outcome measured was postrOAGB weight loss. Secondary outcome measures include comorbidity resolution, operative duration, length of stay, morbidity, and mortality. RESULTS: A total of 21 studies with 1377 patients were included. Five studies compared rOAGB versus rRYGB. Majority of the patients (76%) were female, with mean age of 43.5 years old. Mean body mass index (BMI) before revisional surgery was 41.6 kg/m2. The most common biliopancreatic limb length was 200 cm. Percentage of excess weight loss after rOAGB increases to a maximum of 76.0% at 48 months postsurgery. rOAGB resulted in a pooled prevalence of diabetes, hypertension, hyperlipidemia, and obstructive sleep apnea resolution of 74.9%, 48.4%, 63.2%, and 75.7% respectively. When compared to rRYGB, rOAGB demonstrated greater weight loss, comparable metabolic syndrome resolution, but with a shorter operating time. Morbidity and mortality rates were low across all studies. CONCLUSIONS: rOAGB has potential as an alternative revisional surgery, with weight loss profiles and rates of metabolic syndrome resolution that are comparable to rRYGB.


Assuntos
Derivação Gástrica , Obesidade Mórbida , Adulto , Índice de Massa Corporal , Feminino , Humanos , Obesidade Mórbida/cirurgia , Reoperação , Estudos Retrospectivos , Resultado do Tratamento , Redução de Peso
12.
AAPS PharmSciTech ; 11(4): 1580-90, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21057905

RESUMO

The freeze-drying behavior of three model proteins, namely, lysozyme, BSA, and IgG, has been studied using a variety of techniques under two different primary drying conditions (shelf temperatures of -25°C and +25°C, respectively) in an amorphous formulation. Manometric temperature measurements were used to characterize product temperature (T (pr)), sublimation rates, and product resistance (R (p)) during primary drying. Biophysical techniques such as circular dichroism, fluorescence, and Fourier transform infrared spectroscopy were used to study protein conformation. Size exclusion chromatography was used to monitor the formation of high-molecular-weight species (HMWS) over time on storage, and cake morphology was studied using scanning electron microscopy. The differences in the freeze-drying behavior of the three proteins were more evident at higher protein concentrations, where the protein significantly influences the behavior of the formulation matrix. However, these differences were minimized in the aggressive mode and were insignificant at lower protein concentrations where excipients dominated the freeze-drying behavior. Differences in cake morphology were observed between the two drying conditions employed as well as between the three proteins studied. The stability and the protein structure, however, were equivalent for the protein cakes generated using the two different primary drying conditions.


Assuntos
Excipientes/química , Imunoglobulina G/química , Muramidase/química , Proteínas/química , Soroalbumina Bovina/química , Cromatografia em Gel , Dessecação , Formas de Dosagem , Liofilização , Microscopia Eletrônica de Varredura , Conformação Proteica , Estabilidade Proteica , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura
13.
BMJ Innov ; 6(4): 252-254, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37556278

RESUMO

The COVID-19 pandemic continues to spread rapidly and overwhelm health systems around the world. To cope with this unprecedented usage of healthcare resources, increasingly novel solutions are being brought into the fray. Telemedicine has been thrust into the spotlight in the fight against COVID-19 and is being employed in many different ways to better tackle the challenges. Telemedicine will likely have a more permanent place in traditional healthcare delivery long after COVID-19 is over as users and providers recognise its utility.

14.
Surg Laparosc Endosc Percutan Tech ; 29(5): 393-398, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31498269

RESUMO

Laparoscopic resection of gastrointestinal stromal tumor (GIST) has increased popularity with studies showing good outcomes for patients with tumors <5 cm, with a shorter hospital stay, lower blood loss, and morbidity. Our study aims to audit the clinical profile and surgical outcomes of GISTs, with an evaluation of laparoscopic versus open surgery and the prognostic role of positive R1 margins. In our retrospective study, 62 GIST patients who underwent surgery were included and further analysis was made for the 48 gastric GISTs patients. In total, 33 patients underwent laparoscopic gastric GIST resection, whereas the rest underwent open resection. There was no difference in operative duration but the blood loss was lesser and length of stay shorter in the laparoscopic group. The laparoscopic group had a higher incidence of R1 resection but none developed recurrence or metastasis during follow-up. Laparoscopic resection in the management of gastric GISTs resulted in higher R1 resection rates but this did not affect recurrence rates or overall survival.


Assuntos
Tumores do Estroma Gastrointestinal/cirurgia , Laparoscopia/métodos , Neoplasias Retais/cirurgia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Prognóstico , Neoplasias Retais/patologia , Neoplasias Gástricas/patologia , Resultado do Tratamento
15.
Obes Surg ; 29(1): 114-126, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30196357

RESUMO

BACKGROUND: Obesity and type 2 diabetes mellitus (T2DM) are now increasingly epidemic in Asia. As obesity and T2DM have different disease patterns in Asians compared to Westerners, outcomes after metabolic surgery may differ. The aim of this meta-analysis was to gather the current available evidence on the outcomes after metabolic surgery in Asians. METHODS: A literature search was conducted in September 2017. Four outcome measures were examined: (1) % excess weight loss (EWL), (2) post-intervention body mass index (BMI), (3) T2DM resolution or improvement, and (4) hypertension resolution. RESULTS: Thirteen publications with a total of 1052 patients were analyzed, of which nine were randomized controlled trials, and four were case-matched studies. All the studies had a minimum follow-up duration of at least 1 year. % EWL was significantly higher in those who have undergone Roux-en-Y gastric bypass (RYGB) (SMD 0.53, 95% CI 0.12 to 0.94) versus sleeve gastrectomy (SG). T2DM resolution/improvement was favorable in those who have undergone RYGB (pooled OR 1.39, 95% CI 0.53 to 3.67) versus SG, although not statistically significant. Hypertension resolution was not significantly different between patients who have undergone SG versus RYGB (pooled OR 0.96, 95% CI 0.44 to 2.11). CONCLUSION: RYGB results in better weight loss compared to SG in Asians, but the rate of T2DM resolution/improvement and improvement of hypertension appears to be similar. In Asian patients without symptoms of gastro-esophageal reflux disease in whom metabolic surgery is performed mainly for T2DM and metabolic syndrome, SG may be the surgery of choice.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Obesidade Mórbida , Ásia/epidemiologia , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/estatística & dados numéricos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/cirurgia , Humanos , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/metabolismo , Obesidade Mórbida/cirurgia , Resultado do Tratamento
16.
Sci Rep ; 8(1): 2053, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29391579

RESUMO

Childhood onset clinical syndromes involving intellectual disability and dysmorphic features, such as polydactyly, suggest common developmental pathways link seemingly unrelated phenotypes. We identified a consanguineous family of Saudi origin with varying complex features including intellectual disability, speech delay, facial dysmorphism and polydactyly. Combining, microarray based comparative genomic hybridisation (CGH) to identify regions of homozygosity, with exome sequencing, led to the identification of homozygous mutations in five candidate genes (RSPH6A, ANKK1, AMOTL1, ALKBH8, TRAPPC6A), all of which appear to be pathogenic as predicted by Proven, SIFT and PolyPhen2 and segregate perfectly with the disease phenotype. We therefore looked for differences in expression levels of each protein in HEK293 cells, expressing either the wild-type or mutant full-length cDNA construct. Unexpectedly, wild-type TRAPPC6A appeared to be unstable, but addition of the proteasome inhibitor MG132 stabilised its expression. Mutations have previously been reported in several members of the TRAPP complex of proteins, including TRAPPC2, TRAPPC9 and TRAPPC11, resulting in disorders involving skeletal abnormalities, intellectual disability, speech impairment and developmental delay. TRAPPC6A joins a growing list of proteins belonging to the TRAPP complex, implicated in clinical syndromes with neurodevelopmental abnormalities.


Assuntos
Deficiências do Desenvolvimento/genética , Mutação de Sentido Incorreto , Polidactilia/genética , Proteínas de Transporte Vesicular/genética , Criança , Deficiências do Desenvolvimento/patologia , Feminino , Células HEK293 , Humanos , Masculino , Polidactilia/patologia , Estabilidade Proteica , Síndrome
17.
Int J Surg Case Rep ; 38: 176-179, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28768231

RESUMO

INTRODUCTION: Splenic abscess (SA) is a rare potentially fatal condition in the paediatric population. It is difficult to diagnose given its non-specific presentation. There are no current guidelines for management of SA in this population but splenic preservation is advantageous given the vital role the spleen plays in immunity. PRESENTATION OF CASE: We present a case of a 15-year-old boy with a large splenic abscess. He underwent successful partial splenectomy with resolution of his symptoms thereafter. DISCUSSION: Standard surgical treatment for splenic abscess is antibiotics and drainage. Spleen-preserving options include percutaneous drainage, partial splenectomy, subtotal splenectomy and splenic auto-transplantation. Spleen-preserving techniques should be used where possible to achieve best outcome in clearing infection and to ensure the immunologic role of the spleen is not compromised. CONCLUSION: Splenic abscess is rare conditions seen in paediatric practice with high mortality and partial splenectomy can be a useful spleen-preserving technique in treating this condition.

18.
Nat Genet ; 49(4): 537-549, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28191891

RESUMO

To ensure efficient genome duplication, cells have evolved numerous factors that promote unperturbed DNA replication and protect, repair and restart damaged forks. Here we identify downstream neighbor of SON (DONSON) as a novel fork protection factor and report biallelic DONSON mutations in 29 individuals with microcephalic dwarfism. We demonstrate that DONSON is a replisome component that stabilizes forks during genome replication. Loss of DONSON leads to severe replication-associated DNA damage arising from nucleolytic cleavage of stalled replication forks. Furthermore, ATM- and Rad3-related (ATR)-dependent signaling in response to replication stress is impaired in DONSON-deficient cells, resulting in decreased checkpoint activity and the potentiation of chromosomal instability. Hypomorphic mutations in DONSON substantially reduce DONSON protein levels and impair fork stability in cells from patients, consistent with defective DNA replication underlying the disease phenotype. In summary, we have identified mutations in DONSON as a common cause of microcephalic dwarfism and established DONSON as a critical replication fork protein required for mammalian DNA replication and genome stability.


Assuntos
Replicação do DNA/genética , Proteínas de Ligação a DNA/genética , Nanismo/genética , Instabilidade Genômica/genética , Microcefalia/genética , Mutação/genética , Linhagem Celular , Dano ao DNA/genética , Feminino , Humanos , Masculino
20.
HPB Surg ; 2016: 6120143, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27143815

RESUMO

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Majority of patients with HCC are diagnosed in the advanced stages of disease and hence they are only suitable for palliative therapy. TACE (transarterial chemoembolization) is the most commonly used treatment for unresectable HCC. It is however unclear if TACE improves the quality of life (QoL) in patients with HCC. The aim of this review is to evaluate the impact of TACE on QoL of HCC patients.

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