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1.
Urol Case Rep ; 54: 102733, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38655151

RESUMO

Metanephric adenoma presents as a rare benign tumor in children with differentiated diagnoses: Wilms tumor or renal cell carcinoma. When confronted with small renal tumors, whether they fall into one of these three diagnostic categories, tumor resection surgery with laparoscopic partial nephrectomy is considered a viable and effective operative approach. Herein, we report the case of an 11-year-old female patient initially diagnosed with stage T1a renal cell carcinoma with postoperative pathology results confirming metanephric adenoma. Successfully treated with laparoscopic partial nephrectomy, the patient showed no signs of recurrence or metastasis during follow-up.

2.
Int J Surg Case Rep ; 116: 109450, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38428051

RESUMO

INTRODUCTION: Renal cell carcinoma poses significant challenges in kidney diseases, particularly in the context of the T3 stage, where treatment strategies remain controversial. The utilization of laparoscopic partial nephrectomy, particularly in developing countries, has been restricted for such patients, primarily due to limited infrastructure and concerns about recurrence risk and long-term pathologic outcomes. PRESENTATION OF CASE: In this report, we present a case of a 64-year-old male diagnosed with T3aN0M0 renal cell carcinoma (RCC). Abdominal computed tomography revealed a 5.2 × 5.2 × 5.1 cm mass on the right upper part of the kidney with a possible thrombus in the superior renal polar vein. The patient underwent successful treatment with retroperitoneal laparoscopic partial nephrectomy (LPN), leading to the preservation of kidney function with <4 mL/min/1.73 m2 GFR reduced after one year postoperative (estimated GFR from 85 mL/min/1.73 m2 to 81.79 mL/min/1.73 m2). The patient was discharged after three days; no recurrence was observed during the follow-up. DISCUSSION: For stage T3a RCC, studies show that LPN induces comparable long-term outcomes to radical nephrectomy, with advantages such as preserved kidney function, reduced operative time, blood loss, and shorter hospital stays. However, due to infrastructure constraints and limited access to robotic-assisted surgery in our country, coupled with concerns about tumor recurrence, laparoscopic radical nephrectomy is predominantly employed for similar patients. Our case represents one of the very first cases in which we successfully treated a patient diagnosed with T3a RCC using retroperitoneal laparoscopic partial nephrectomy. CONCLUSION: Laparoscopic partial nephrectomy is a reliable choice for T3aN0M0 RCC with good long-term outcomes and preserved renal function, especially by the hands of an experienced laparoscopic surgeon.

3.
BMC Neurol ; 24(1): 103, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521933

RESUMO

BACKGROUND: MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT gene by promoter methylation is associated with greater overall and progression free survival with alkylating agent regimens. To date, there is marked heterogeneity in how MGMT promoter methylation is tested and which CpG sites are interrogated. METHODS: To further elucidate which MGMT promoter CpG sites are of greatest interest, we performed comprehensive searches in PubMed, Web of Science, and Embase and reviewed 2,925 article abstracts. We followed the GRADE scoring system to assess risk of bias and the quality of the studies we included. RESULTS: We included articles on adult glioblastoma that examined significant sites or regions within MGMT promoter for the outcomes: overall survival, progression free survival, and/or MGMT expression. We excluded systemic reviews and articles on lower grade glioma. fifteen articles met inclusion criteria with variable overlap in laboratory and statistical methods employed, as well as CpG sites interrogated. Pyrosequencing or BeadChip arrays were the most popular methods utilized, and CpG sites between CpG's 70-90 were most frequently investigated. Overall, there was moderate concordance between the CpG sites that the studies reported to be highly predictive of prognosis. Combinations or means of sites between CpG's 73-89 were associated with improved OS and PFS. Six studies identified CpG sites associated with prognosis that were closer to the transcription start site: CpG's 8, 19, 22, 25, 27, 32,38, and CpG sites 21-37, as well as low methylation level of the enhancer regions. CONCLUSION: The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Neoplasias Encefálicas/genética , Metilação de DNA/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Glioblastoma/genética , Glioma/genética , Prognóstico , Proteínas Supressoras de Tumor/genética
4.
RSC Adv ; 14(7): 4904-4916, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38323020

RESUMO

Graphene-based sensors exhibit high sensitivity, fast response, and good selectivity towards toxic gases but have low mechanical stability. The combination of graphene and two-dimensional hexagonal boron nitride (h-BN) is expected to increase the mechanical stability and enhance the adsorption performance of these gas sensors. Using first-principles calculations, we demonstrate that two-dimensional graphene/h-BN double layers can be used as good substrates for gas sensors with a small lattice mismatch of only 1.78%. Moreover, the presence of a h-BN layer widens the band gap by about 38 meV and considerably increases the work function, thus positively affecting the gas adsorption performance. Although these graphene/h-BN heterostructures do not change the physical adsorption mechanism of these sensors concerning the graphene-based materials, these bilayers significantly enhance the sensitivity of these sensors for detecting CO2, CO, NO, and NO2 toxic gases. Particularly, compared to the pristine graphene-based materials, the gas adsorption energies of graphene/h-BN increased by up to 13.78% for the adsorption of NO, and the shortest distances between the graphene/h-BN substrates and adsorbed gas molecules decreased. We also show that the graphene/h-BN heterostructure is more selective towards NOx gases while more inert towards COx gases, based on the different amounts of charge transferred from the substrate to the adsorbed gas molecules. Using the non-equilibrium Green functions in the context of density functional theory, we quantitatively associated these charge transfers with the reduction of the current passing through these scattering regions. These results demonstrate that graphene/h-BN heterostructures can be exploited as highly sensitive and selective room-temperature gas sensors for detecting toxic gases.

5.
Curr Opin Urol ; 34(2): 91-97, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37889517

RESUMO

PURPOSE OF REVIEW: Kidney stone disease is recognized to negatively impact quality of life. This pertains to acute episodes, surgical interventions and even during asymptomatic periods. Over time there has been increased attention towards assessing this subjective parameter, including as a determinant of treatment success. Our aim was to evaluate the current status and emerging trends in this field. RECENT FINDINGS: Patient groups most affected appear to be recurrent stone formers, cystine stone formers, women, younger populations, non-Caucasians and low-income populations. Several stone specific patient reported outcome measures are now available of which, WISQol has been implemented the most in clinical research studies. More invasive interventions such as percutaneous nephrolithotomy impede quality of life to greater extent than alternatives such as shockwave lithotripsy. SUMMARY: There are certain patient groups who are more vulnerable to the negative impact of kidney stone disease on their quality of life. Urologists can improve patient care by recognizing these particular populations as well as by implemented patient reported outcome measures in their routine clinical practice and when performing research.


Assuntos
Cálculos Renais , Litotripsia , Nefrolitotomia Percutânea , Humanos , Feminino , Qualidade de Vida , Resultado do Tratamento
6.
J Cereb Blood Flow Metab ; 44(4): 542-555, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37933736

RESUMO

Mild traumatic brain injury (mTBI) involves damage to the cerebrovascular system. Vascular endothelial growth factor-A (VEGF-A) is an important modulator of vascular health and VEGF-A promotes the brain's ability to recover after more severe forms of brain injury; however, the role of VEGF-A in mTBI remains poorly understood. Bevacizumab (BEV) is a monoclonal antibody that binds to VEGF-A and neutralises its actions. To better understand the role of VEGF-A in mTBI recovery, this study examined how BEV treatment affected outcomes in rats given a mTBI. Adult Sprague-Dawley rats were assigned to sham-injury + vehicle treatment (VEH), sham-injury + BEV treatment, mTBI + VEH treatment, mTBI + BEV treatment groups. Treatment was administered intracerebroventricularly via a cannula beginning at the time of injury and continuing until the end of the study. Rats underwent behavioral testing after injury and were euthanized on day 11. In both females and males, BEV had a negative impact on cognitive function. mTBI and BEV treatment increased the expression of inflammatory markers in females. In males, BEV treatment altered markers related to hypoxia and vascular health. These novel findings of sex-specific responses to BEV and mTBI provide important insights into the role of VEGF-A in mTBI.


Assuntos
Concussão Encefálica , Masculino , Feminino , Ratos , Animais , Bevacizumab , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ratos Sprague-Dawley , Modelos Animais de Doenças
7.
PLoS Negl Trop Dis ; 17(11): e0011311, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37934746

RESUMO

BACKGROUND: Under the pressure of Human Adenovirus (HAdV)-associated acute respiratory infection (ARI) outbreak in children in Northern Vietnam in the end of 2022, this study was initiated to identify the HAdV subtype(s) and examine the associated clinical features and risk factors of more severe cases. METHODS: This study evaluated pediatric patients with ARI which had tested positive for HAdV between October and November 2022 using a multiplex real-time PCR panel. Nasopharyngeal aspirates or nasal swab samples were used for sequencing to identify HAdV subtypes. Clinical data were collected retrospectively. RESULTS: Among 97 successfully sequenced samples, the predominant subtypes were HAdV-B3 (83%), HAdV-B7 (16%) and HAdV-C2 (1%). Lower respiratory manifestations were found in 25% of the patients of which 5% were diagnosed with severe pneumonia. There was no significant association between HAdV subtype and clinical features except higher white blood cell and neutrophil counts in those detected with HAdV-B3 (p<0.001). Co-detection of HAdV with ≥1 other respiratory viruses was found in 13/24(54%) of those with lower respiratory manifestations and 4/5(80%) of those with severe pneumonia (odds ratio (95% confidence interval) vs. those without = 10.74 (2.83, 48.17) and 19.44 (2.12, 492.73) respectively after adjusting for age, sex, birth delivery method, day of disease). CONCLUSION: HAdV-B3 and HAdV-B7 were predominant in the outbreak. Co-detection of HAdV together with other respiratory viruses was a strong risk factor for lower respiratory tract illnesses and severe pneumonia. The findings advocate the advantages of multi-factor microbial panels for the diagnosis and prognosis of ARI in children.


Assuntos
Infecções por Adenoviridae , Infecções por Adenovirus Humanos , Adenovírus Humanos , Pneumonia , Infecções Respiratórias , Humanos , Criança , Lactente , Adenoviridae , Vietnã/epidemiologia , Estudos Retrospectivos , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/diagnóstico , Infecções Respiratórias/epidemiologia , Pneumonia/epidemiologia , Adenovírus Humanos/genética , Infecções por Adenoviridae/epidemiologia , Surtos de Doenças , Fatores de Risco , Filogenia
8.
Urol Case Rep ; 51: 102578, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37842266

RESUMO

Prostatic abscess (PA) prevalence has decreased in the era of antibiotics. This condition is associated with chronic conditions, including diabetes, immunodeficiency, liver disease, or even severe diseases such as prostate cancer. Concomitant prostatic abscess and prostate cancer are very challenging to treat because of the lack of specific guidelines, significant complications, and controversial treatment approaches. By reporting a case with prostate cancer in the setting of a prostatic abscess treated successfully by surgery, we propose a 2-steps approach including transurethral resection drainage followed by laparoscopic radical prostatectomy.

9.
Int J Surg Case Rep ; 110: 108693, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37625233

RESUMO

INTRODUCTION AND IMPORTANCE: Aortic aneurysm is an uncommon but life-threatening cause of hemoptysis. Treatments include surgery and/or endovascular intervention, each with its own advantages and disadvantages. Endovascular intervention is associated with good early and medium-term outcomes. CASE PRESENTATIONS: We report three cases of hemoptysis due to ruptured thoracic aortic aneurysm who underwent endovascular intervention. In all three cases, endovascular grafts were placed in the descending thoracic aorta, the number of grafts used was 1, the average time to stop hemoptysis was 4 to 5 days, and the length of hospital stay was between 6 and 8 days. No intravascular fistula, renal failure, prolonged mechanical ventilation and other major cardiovascular events were reported. CLINICAL DISCUSSION: Endovascular treatment for descending TAA has been demonstrated to be safe and effective, particularly in emergencies in which patients presented with life-threatening hemoptysis, due to its rapid access to the aorta. In our experience at a tertiary hospital in southern Vietnam, the procedural time for a thoracic endovascular aortic repair is relatively brief and can last between 15 and 30 min. Thus, endovascular treatment for ruptured TAA can substantially improve patient prognosis, reduce mortality and complications. CONCLUSION: The implementation of endovascular intervention can help improve prognosis, reduce mortality and complications in patients with hemoptysis due to ruptured thoracic aortic aneurysm.

10.
J Clin Invest ; 133(10)2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-36976651

RESUMO

BackgroundLung infections are among the most consequential manifestations of cystic fibrosis (CF) and are associated with reduced lung function and shortened survival. Drugs called CF transmembrane conductance regulator (CFTR) modulators improve activity of dysfunctional CFTR channels, which is the physiological defect causing CF. However, it is unclear how improved CFTR activity affects CF lung infections.MethodsWe performed a prospective, multicenter, observational study to measure the effect of the newest and most effective CFTR modulator, elexacaftor/tezacaftor/ivacaftor (ETI), on CF lung infections. We studied sputum from 236 people with CF during their first 6 months of ETI using bacterial cultures, PCR, and sequencing.ResultsMean sputum densities of Staphylococcus aureus, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Achromobacter spp., and Burkholderia spp. decreased by 2-3 log10 CFU/mL after 1 month of ETI. However, most participants remained culture positive for the pathogens cultured from their sputum before starting ETI. In those becoming culture negative after ETI, the pathogens present before treatment were often still detectable by PCR months after sputum converted to culture negative. Sequence-based analyses confirmed large reductions in CF pathogen genera, but other bacteria detected in sputum were largely unchanged. ETI treatment increased average sputum bacterial diversity and produced consistent shifts in sputum bacterial composition. However, these changes were caused by ETI-mediated decreases in CF pathogen abundance rather than changes in other bacteria.ConclusionsTreatment with the most effective CFTR modulator currently available produced large and rapid reductions in traditional CF pathogens in sputum, but most participants remain infected with the pathogens present before modulator treatment.Trial RegistrationClinicalTrials.gov NCT04038047.FundingThe Cystic Fibrosis Foundation and the NIH.


Assuntos
Fibrose Cística , Pneumonia , Humanos , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Fibrose Cística/complicações , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Escarro/microbiologia , Estudos Prospectivos , Bactérias , Benzodioxóis/farmacologia , Benzodioxóis/uso terapêutico , Pulmão , Mutação
11.
J Telemed Telecare ; 29(3): 165-176, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33377820

RESUMO

INTRODUCTION: Telepharmacy has the potential to enhance pharmacy services in oncology care, especially in remote areas. This scoping review explored the range, critical benefits and barriers of using telepharmacy services in oncology care. METHODS: The scoping review followed the Arksey and O'Malley's five-stage framework to identify available evidence. PubMed, CINAHL, Embase, PsycINFO, Ovid MEDLINE and Scopus databases were searched for original research published between 2010 and 2020. The five dimensions of the Alberta Quality Matrix for Health were used to analyse reported outcomes. RESULTS: Eligible articles (n = 21) were analysed. Telepharmacy in oncology care was used for follow-up, monitoring and counselling, intravenous chemotherapy and sterile compounding, expanding availability of pharmacy services, and remote education. Telepharmacy obtained high acceptability among cancer patients (n = 5) and healthcare professionals (n = 5), and increased accessibility of pharmaceutical services to underserved cancer populations (n = 2). Commonly cited effectiveness and safety outcomes were improved patient adherence (n = 5), increased pharmacy services (n = 3) and early identification of medication-related problems (n = 5). Telepharmacy improved efficiency in staffing and workload (n = 3), and increased cost savings (n = 3). A shortage of resources (n = 5), technical problems (n = 4) and prolonged turnaround time (n = 4), safety concerns (n = 2) and patient willingness to pay (n = 1) were identified barriers to implementing telepharmacy in oncology care. DISCUSSION: Despite evidence pointing to the advantages and opportunities for expanding oncology pharmacy services through telepharmacy, certain challenges remain. Further research is needed to investigate safety concerns and patient willingness to pay for telepharmacy services.


Assuntos
Oncologia , Neoplasias , Telemedicina , Humanos , Telemedicina/métodos , Oncologia/métodos , Neoplasias/terapia
12.
Scand J Clin Lab Invest ; 83(1): 3-7, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36476017

RESUMO

Myeloproliferative neoplasms are hematological disorders characterized by increased production in one or more myeloid cell lines, associated with driver mutations in JAK2-, MPL- and CALR-genes. The aims of this study were to investigate the prevalence of these driver mutations in a Norwegian patient cohort with myeloproliferative neoplasms, and to assess whether the different mutations were associated with different clinical presentation and natural history.Results from 820 patients in whom analysis for JAK2V617F-, CALR- and MPL had been performed at Haukeland University Hospital in the period 2014-2019 were retrieved and analyzed together with clinical variables related to diagnosis, hematological blood parameters and complications, obtained from patient records.We identified 182 cases of myeloproliferative neoplasms: 78 with JAK2V617F, 28 with CALR-mutations, two with MPL-mutations and 23 cases without a driver mutation. There was a lower prevalence of JAK2V617F mutation than expected in the polycythemia vera group, likely related to overdiagnosis. In patients with essential thrombocytosis, we found significantly higher levels of hemoglobin and erythrocyte volume fraction for JAK2V617F-mutated disease, and significantly higher levels of platelets and lactate dehydrogenase for CALR-mutated disease. Patients with JAK2V617F-mutated primary myelofibrosis had significantly higher levels of hemoglobin, and there was an increased number of smokers or former smokers in this group compared to patients with CALR-mutations.Except for a lower prevalence of JAK2V617F-mutation in polycythemia vera, the mutational distribution in our patient cohort was similar to previous findings in other populations. The novel finding of a higher prevalence of smokers in JAK2V617F-mutated primary myelofibrosis warrants further investigation.


Assuntos
Calreticulina , Janus Quinase 2 , Transtornos Mieloproliferativos , Receptores de Trombopoetina , Humanos , Hemoglobinas , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Mutação , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Policitemia Vera/genética , Mielofibrose Primária/genética , Receptores de Trombopoetina/genética , Receptores de Trombopoetina/metabolismo , Calreticulina/metabolismo
13.
Acta Inform Med ; 32(1): 76-81, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38585604

RESUMO

Background: Prostate cancer (PCa) is the second most common cancer and the sixth leading cause of cancer-related mortality in men. In 2000, Abbou performed the first robot-assisted radical prostatectomy, and radical prostatectomy has developed rapidly. Robot-assisted radical prostatectomy (RARP) is a valuable therapeutic option for the management of localized Pca. Objective: To present the functional outcome of robot-assisted laparoscopic radical prostatectomy using traditional and modified endopelvic fascia preservation methods in a single center in Vietnam. Methods: We prospectively analyzed a series of 65 patients diagnosed with prostate cancer from 2020 to 2023. All of those were operated by DaVinci Si system robot-assisted laparoscopic prostatectomy. Twenties patients were applied with a modified nerve-sparing technique, intrafascial dissection, and lateral prostatic fascia preservation, leaving the lateral tissue, including the neurovascular bundle, untouched and covered. We used the traditional approach, intrafascial nerve-sparing with open endopelvic fascia and lateral prostatic fascia in 45 cases. Patients were followed up to 12 months to assess the continence and erectile function by using IIEF-5 and EPIC questionnaires. Results: The study sample included 65 cases; the mean patient age was 64.21 ± 6.68, erection rate after surgery at six months in bilateral NS was 36.58% (15/41) in the traditional group, and 68.42% (13/19) in the modified group (p=0.028). The patient did not recover erectile ability in the group of elderly patients (>65 years old) and unilateral nerve-sparing group. The continence rate six months after surgery was 86.66 % in the conventional group and 85% in the modified group, with no significant difference between the two groups. In the potency group, the IIEF-5 score was 13 ± 4.9, and the EPIC-26 score was 62.20 ± 10.04. Erectile ability in the modified group was better than the traditional group at six months after surgery. Conclusion: Our results showed better potency recovery in the modified group. These results should be tested in future research with randomized studies.

14.
Sensors (Basel) ; 22(20)2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36298184

RESUMO

In this paper, the problem of an APPTMC for manipulators is investigated. During the robot's operation, the error states should be kept within an outlined range to ensure a steady-state and dynamic attitude. Firstly, we propose the modified PPFs. Afterward, a series of transformed errors is used to convert "constrained" systems into equivalent "unconstrained" ones, to facilitate control design. The modified PPFs ensure position tracking errors are managed in a pre-designed performance domain. Especially, the SSE boundaries will be symmetrical to zero, so when the transformed error is zero, the tracking error will be as well. Secondly, a modified NISMS based on the transformed errors allows for determining the highest acceptable range of the tracking errors in the steady-state, finite-time convergence index, and singularity elimination. Thirdly, a fixed-time USOSMO is proposed to directly estimate the lumped uncertainty. Fourthly, an ASTwCL is applied to deal with observer output errors and chattering. Finally, an observer-based-control solution is synthesized from the above techniques to achieve PCP in the sense of finite-time Lyapunov stability. In addition, the precision, robustness, as well as harmful chattering reduction of the proposed APPTMC are improved significantly. The Lyapunov theory is used to analyze the stability of closed-loop systems. Throughout simulations, the proposed PPTMC has been shown to perform well and be effective.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Robótica/métodos , Movimento (Física) , Incerteza
15.
mBio ; 13(5): e0142422, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36121157

RESUMO

Within-host evolution produces genetic diversity in bacterial strains that cause chronic human infections. However, the lack of facile methods to measure bacterial allelic variation in clinical samples has limited understanding of intrastrain diversity's effects on disease. Here, we report a new method termed genome capture sequencing (GenCap-Seq) in which users inexpensively make hybridization probes from genomic DNA or PCR amplicons to selectively enrich and sequence targeted bacterial DNA from clinical samples containing abundant human or nontarget bacterial DNA. GenCap-Seq enables accurate measurement of allele frequencies over targeted regions and is scalable from specific genes to entire genomes, including the strain-specific accessory genome. The method is effective with samples in which target DNA is rare and inhibitory and DNA-degrading substances are abundant, including human sputum and feces. In proof-of-principle experiments, we used GenCap-Seq to investigate the responses of diversified Pseudomonas aeruginosa populations chronically infecting the lungs of people with cystic fibrosis to in vivo antibiotic exposure, and we found that treatment consistently reduced intrastrain genomic diversity. In addition, analysis of gene-level allele frequency changes suggested that some genes without conventional resistance functions may be important for bacterial fitness during in vivo antibiotic exposure. GenCap-Seq's ability to scalably enrich targeted bacterial DNA from complex samples will enable studies on the effects of intrastrain and intraspecies diversity in human infectious disease. IMPORTANCE Genetic diversity evolves in bacterial strains during human infections and could affect disease manifestations and treatment resistance. However, the extent of diversity present in vivo and its changes over time are difficult to measure by conventional methods. We developed a novel approach, GenCap-Seq, to enrich microbial DNA from complex human samples like sputum and feces for genome-wide measurements of bacterial allelic diversity. The approach is inexpensive, scalable to encompass entire targeted genomes, and works in the presence of abundant untargeted nucleic acids and inhibiting substances. We used GenCap-Seq to investigate in vivo responses of diversified bacterial strains to antibiotic treatment. This method will enable new ideas about the effects of intrastrain diversity on human infections to be tested.


Assuntos
Fibrose Cística , Infecções por Pseudomonas , Humanos , DNA Bacteriano/genética , Pseudomonas aeruginosa/genética , Fibrose Cística/microbiologia , Genoma Bacteriano , Análise de Sequência de DNA , Antibacterianos/farmacologia , Variação Genética , Infecções por Pseudomonas/microbiologia
16.
Cytotherapy ; 24(12): 1190-1194, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36151003

RESUMO

BACKGROUND AIMS: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for patients with hematological malignancies; however, allo-HSCT does not come without the cost of treatment-related morbidity and mortality. Early detection of risk factors could be helpful in identifying patients who could benefit from early interventions. Many patients gain weight during the allo-HSCT treatment, although little is known about the impact of weight gain. METHODS: Weight gain in 146 consecutively enrolled adult patients undergoing allo-HSCT was explored. RESULTS: In total, 141 patients (97%) gained weight along the course of allo-HSCT. Median weight increase was 4.8 kg (range 0.0-16.1 kg), with median increase in body weight 6.5% (range 0.0%-30.8%). Maximum weight increase was observed at day +7 (range day -8, +44). Weight gain was associated with increased incidence of acute graft-versus-host disease. Patients with weight gain >10% had a significantly greater 5-year mortality compared with those with lower weight gain (P = 0.031, rank sum test). CONCLUSIONS: Weight gain is a simple variable with the ability to provide prognostic information for patients undergoing allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Adulto , Transplante Homólogo/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/complicações , Resultado do Tratamento , Aumento de Peso , Estudos Retrospectivos
18.
Sensors (Basel) ; 22(7)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35408229

RESUMO

Through this article, we present an advanced prescribed performance-tracking control system with finite-time convergence stability for uncertain robotic manipulators. It is therefore necessary to define a suitable performance function and error transformation to guarantee a prescribed performance within a finite time. Following the definitions mentioned, a modified integral nonlinear sliding-mode hyperplane is constructed from the transformed errors. By using the designed nonlinear sliding-mode surface and the super-twisting reaching control law, an advanced approach to the prescribed performance control was formed for the trajectory tracking control of uncertain robotic manipulators. The proposed controller exhibits improved properties, including estimated convergence speed and a predefined upper and lower limit for maximum overshoot during transient responses. Furthermore, the maximum allowable size of the control errors at the steady-state can be predefined and these errors will inevitably converge to zero within a finite time, while the proposed controller can provide a smooth control torque without the loss of its robustness. It is shown that the proposed control system is globally stable and convergent over a finite time. A comprehensive analysis of the effectiveness of the proposed control algorithm was already conducted via the simulation of an industrial robot manipulator.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Algoritmos , Simulação por Computador , Incerteza
19.
Blood Adv ; 6(18): 5295-5306, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-35443023

RESUMO

Chronic graft-versus-host disease (cGVHD) is the most common long-term complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). During the last decade, the interest of micro RNAs (miRNAs) in the pathophysiological process of cGVHD has increased. The objectives of this study were to investigate a wide range of serum miRNAs in allografted patients and identify associations between miRNAs and cGVHD. The study included 79 allotransplanted adults, where serum samples were obtained 1 year after the allo-HSCT, and miRNA profiling analysis in serum was performed. Fifty of the 79 patients (63%) had signs of cGVHD at the 1-year post-allo-HSCT control. miRNA sequencing analysis revealed 1380 different miRNAs detected for at least 1 patient, whereas 233 miRNAs (17%) were detected in >70 patients. We identified 10 miRNAs that differed significantly between patients with and without cGVHD (P < .005; false discovery rate <0.1), and all of these miRNAs were detected for >75 of the patients. Furthermore, 5 distinct miRNAs, miR-365-3p, miR-148-3p, miR-122-5p, miR-378-3p, and miR-192-5p, were found to be particularly associated with cGVHD in our analysis and were validated by receiver operating characteristics analysis. Based on only 3 miRNAs, miR-365-3p, miR-148-3p, and miR-378-3p, we developed a miRNA signature that, by bioinformatic approaches and linear regression model, utterly improved our potential diagnostic biomarker model for cGVHD. We conclude that miRNAs are differently expressed among patients with and without cGVHD, although further and larger studies are needed to validate our present findings.


Assuntos
Doença Enxerto-Hospedeiro , MicroRNAs , Adulto , Biomarcadores , Biologia Computacional , Perfilação da Expressão Gênica , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Humanos , MicroRNAs/genética
20.
Epilepsy Behav Rep ; 18: 100526, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35198955

RESUMO

Compared to high grade gliomas, low grade gliomas such as oligodendrogliomas are often more epileptogenic. Epilepsy develops in 70-90% of patients with oligodendrogliomas and 40% of these are resistant to anti-seizure medications and surgery [3]. IDH1/2 mutation is one defining feature of oligodendrogliomas and confers improved prognosis when found in astrocytomas [7]. One possible etiology of the high rate of epileptogenicity in oligodendrogliomas is D-2-Hydroxyglutarate (D2HG), an oncometabolite seen in IDH mutation [8]. D2HG can mimic the effect of glutamate at the NMDA receptor and increase the seizure risk [11]. In this case report, we present a patient with drug resistant focal epilepsy from IDH1 mutant oligodendroglioma with markedly improved seizure frequency after starting Ivosidenib, an IDH1 inhibitor, in the absence of any changes to traditional anti-seizure medications. Our case suggests the possibility that IDH1 inhibitors may help reduce seizure burden in patients with difficult to control epilepsy from IDH1 mutant oligodendrogliomas. This is significant because we show that a targeted cancer therapy is able to improve seizure frequency through a unique pathway, and suggests that research into similar targeted, precision medicine therapies in brain lesions associated with epilepsy may be beneficial.

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