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1.
Genome Res ; 32(4): 616-628, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34702734

RESUMO

We developed a method to tag telomeres and measure telomere length by nanopore sequencing in the yeast S. cerevisiae Nanopore allows long-read sequencing through the telomere, through the subtelomere, and into unique chromosomal sequence, enabling assignment of telomere length to a specific chromosome end. We observed chromosome end-specific telomere lengths that were stable over 120 cell divisions. These stable chromosome-specific telomere lengths may be explained by slow clonal variation or may represent a new biological mechanism that maintains equilibrium unique to each chromosome end. We examined the role of RIF1 and TEL1 in telomere length regulation and found that TEL1 is epistatic to RIF1 at most telomeres, consistent with the literature. However, at telomeres that lack subtelomeric Y' sequences, tel1Δ rif1Δ double mutants had a very small, but significant, increase in telomere length compared with the tel1Δ single mutant, suggesting an influence of Y' elements on telomere length regulation. We sequenced telomeres in a telomerase-null mutant (est2Δ) and found the minimal telomere length to be ∼75 bp. In these est2Δ mutants, there were apparent telomere recombination events at individual telomeres before the generation of survivors, and these events were significantly reduced in est2Δ rad52Δ double mutants. The rate of telomere shortening in the absence of telomerase was similar across all chromosome ends at ∼5 bp per generation. This new method gives quantitative, high-resolution telomere length measurement at each individual chromosome end and suggests possible new biological mechanisms regulating telomere length.


Assuntos
Sequenciamento por Nanoporos , Proteínas de Saccharomyces cerevisiae , Telomerase , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Serina-Treonina Quinases , Proteínas Repressoras/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Telomerase/genética , Telomerase/metabolismo , Telômero/genética , Telômero/metabolismo , Proteínas de Ligação a Telômeros/genética , Proteínas de Ligação a Telômeros/metabolismo
2.
Ann Surg ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38881439

RESUMO

OBJECTIVE: The goal of this study was to characterize the microRNA (miRNA) expression signatures in patients with PHPT and identify miRNA biomarkers of bone homeostasis. SUMMARY BACKGROUND DATA: Primary hyperparathyroidism (PHPT) is associated with increased bone turnover and decreased bone mass. miRNA are markers of bone remodeling. METHODS: We performed a prospective case-control study of post-menopausal females with PHPT and control subjects matched for race, age, and BMD. We collected clinical and biochemical data, assessed BMD by dual-energy X-ray absorptiometry, and measured 27 serum miRNAs related to bone remodeling. We used linear regression to assess the correlation between miRNA levels, conventional biochemical markers and BMD. RESULTS: A total of 135 subjects were evaluated, including 49 with PHPT (discovery group), 47 control patients without PHPT, and an independent validation cohort of 39 PHPT patients. Of 27 miRNAs evaluated, nine (miR-335-5p, miR-130b-3p, miR-125b-5p, miR-23a-3p, miR-152-3p, miR-582-5p, miR-144-5p, miR-320a and miR-19b-3p) were differentially expressed in PHPT compared to matched control subjects. All nine differentially expressed miRNAs significantly correlated with levels of serum parathyroid hormone (PTH), and eight of the nine correlated with calcium levels. No differentially expressed miRNAs were consistently correlated with markers of BMD. Subjects with PHPT segregate from controls based on the signature of these nine miRNAs on principle component analysis. CONCLUSIONS: These data suggest that PHPT is characterized by a unique miRNA signature that is distinct from postmenopausal and idiopathic osteoporosis. Levels of specific miRNAs significantly correlate with PTH, suggesting that bone remodeling in PHPT may be mediated in part by PTH-induced changes in miRNA.

3.
Opt Express ; 32(12): 20491-20502, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38859430

RESUMO

The Line Height Absorption (LHA) method uses absorption of light to estimate chlorophyll-a. While most users consider regional variability and apply corrections, the effect of temporal variability is typically not explored. The Northern Gulf of Alaska (NGA) was selected for this study because there was no published regional value and its large swings in temporal productivity would make it a good candidate to evaluate the effect of temporal variability on the relationship. The mean NGA value of 0.0114 obtained here should be treated with caution, as variation in the slope of the relationship (aLH*), and thus chlorophyll-a estimates, in the NGA region varied by ∼25% between spring (aLH* = 0.0109) and summer (aLH* = 0.0137). Results suggest that this change is driven by a shift in pigment packaging and cell size associated with changes in mixed layer depth and stratification. Consideration of how temporal variability may affect the accuracy of the LHA method in other regions is thus recommended.

4.
Opt Express ; 32(12): 20459-20470, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38859427

RESUMO

When a hollow core fiber is drawn, the core and cladding holes within the internal cane geometry are pressurized with an inert gas to enable precise control over the internal microstructure of the fiber and counteract surface tension forces. Primarily by considering the temperature drop as the fiber passes through the furnace and the geometrical transformation of the internal microstructure from preform-to-fiber, we recently established that the gas pressure within the final 'as-drawn' fiber is substantially below atmospheric pressure. We have also established that slight changes in the gas refractive index within the core and surrounding cladding holes induced by changes in gas pressure are sufficient to significantly affect both the modality and loss of the fiber. Here we demonstrate, through both simulations and experimental measurements, that the combination of these effects leads to transient changes in the fiber's attenuation when the fibers are opened to atmosphere post-fabrication. It is important to account for this phenomenon for accurate fiber characterization, particularly when long lengths of fiber are drawn where it could take many weeks for every part of the internal microstructure to reach atmospheric pressure.

5.
Mol Psychiatry ; 28(9): 3930-3942, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37845497

RESUMO

Chronic cocaine exposure induces enduring neuroadaptations that facilitate motivated drug taking. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are known to modulate neuronal firing and pacemaker activity in ventral tegmental area (VTA) dopamine neurons. However, it remained unknown whether cocaine self-administration affects HCN channel function and whether HCN channel activity modulates motivated drug taking. We report that rat VTA dopamine neurons predominantly express Hcn3-4 mRNA, while VTA GABA neurons express Hcn1-4 mRNA. Both neuronal types display similar hyperpolarization-activated currents (Ih), which are facilitated by acute increases in cAMP. Acute cocaine application decreases voltage-dependent activation of Ih in VTA dopamine neurons, but not in GABA neurons. Unexpectedly, chronic cocaine self-administration results in enhanced Ih selectively in VTA dopamine neurons. This differential modulation of Ih currents is likely mediated by a D2 autoreceptor-induced decrease in cAMP as D2 (Drd2) mRNA is predominantly expressed in dopamine neurons, whereas D1 (Drd1) mRNA is barely detectable in the VTA. Moreover, chronically decreased cAMP via Gi-DREADD stimulation leads to an increase in Ih in VTA dopamine neurons and enhanced binding of HCN3/HCN4 with tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b), an auxiliary subunit that is known to facilitate HCN channel surface trafficking. Finally, we show that systemic injection and intra-VTA infusion of the HCN blocker ivabradine reduces cocaine self-administration under a progressive ratio schedule and produces a downward shift of the cocaine dose-response curve. Our results suggest that cocaine self-administration induces an upregulation of Ih in VTA dopamine neurons, while HCN inhibition reduces the motivation for cocaine intake.


Assuntos
Cocaína , Neurônios Dopaminérgicos , Ratos , Animais , Neurônios Dopaminérgicos/metabolismo , Área Tegmentar Ventral/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Regulação para Cima , Cocaína/farmacologia , RNA Mensageiro
6.
J Opt Soc Am A Opt Image Sci Vis ; 41(6): B85-B94, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38856414

RESUMO

The experimental study of optical turbulence proves difficult due to challenges in generating controllable conditions in a laboratory environment. Confined water tanks that produce Rayleigh-Bénard (RB) convection are one method to generate optical turbulence using a controllable temperature gradient. It is of utmost concern to quantify the properties of the optical turbulence generated for characterization of other optical applications such as imaging, sensing, or communications. In this experimental study a Gaussian beam is propagated through a RB water tank where two intensity measurements are made at the receiver's pupil and focal plane. The pupil and focal plane results include quantification of the intensity fluctuation distribution, scintillation distribution, and refractive index structure constant at various values of the temperature gradient. The angle of arrival fluctuations is also calculated at the focal plane to obtain a second estimate of C n2. The pupil plane estimate for C n2 using scintillation index and focal plane angle of arrival fluctuations is compared to preliminary predictions of C n2 as a function of RB temperature gradient showing C n2âˆ¼Δ T 4/3. The outcomes of the study confirm that the RB process produces intensity fluctuations that follow gamma-gamma and log-normal probability density functions. Estimates of the refractive index structure constant C n2 produce the same trends with different magnitudes when measured from the pupil and focal plane.

7.
Eur Spine J ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910169

RESUMO

PURPOSE: To establish the prevalence and agreement between reported and observed leg weakness in people with sciatica. To establish which factors mediate any identified difference between reported and observed leg weakness in people with sciatica. METHODS: 68 people with a clinical diagnosis of sciatica, records from spinal service, secondary care NHS Hospital, England, UK reviewed. Primary outcome measures were the sciatica bothersome index for reported leg weakness and the Medical Research Council scale for observed weakness. Agreement was established with Cohen's Kappa and intraclass correlation coefficient. Potential factors that may mediate a difference between reported and observed weakness included leg pain, sciatica bothersome index sensory subscale, age, hospital anxiety and depression subscale for anxiety. RESULTS: 85% of patients reported weakness but only 34% had observed weakness. Cohen's Kappa (0.066, 95% CI - 0.53, 0.186; p = 0.317)] and ICC 0.213 (95% CI - 0.26, 0.428, p = 0.040) both showed poor agreement between reported and observed weakness. The difference between reported and observed measures of weakness was mediated by the severity of leg pain (b = 0.281, p = 0.024) and age (b = 0.253, p = 0.042). CONCLUSION: There is a high prevalence of reported leg weakness in people with sciatica, which is not reflected in observed clinical measures of weakness. Differences between reported and observed weakness may be driven by the severity of leg pain and age. Further work needs to establish whether other objective measures can detect patient reported weakness.

8.
Pediatr Neurosurg ; 59(2-3): 78-86, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38688244

RESUMO

INTRODUCTION: Pediatric cavum cysts are a rare yet complicated pathology to manage. The literature is scarce, primarily consisting of case series, and lacking a consensus regarding clear management. In this scoping review, we aimed to compile existing information in the literature regarding the management of pediatric cavum cysts across the last 10 years. We also present our management of 19 patients, the largest case series to date, highlighting knowledge gaps surrounding the management of this salient pathology. METHODS: A literature search using PubMed and SCOPUS was conducted using the following search terms: (pediatric) AND (Cavum septum pellucidum) OR (cavum vergae) OR (cavum velum interpositum) AND (management). Eligibility criteria included peer-reviewed publication published in the last 10 years, pediatric population, cavum cyst, and English language. A retrospective search was conducted for all pediatric cavum cysts between 2013 and 2023 at our institution. Clinical and radiographic characteristics as well as intervention and outcome data were collected for both the scoping review and our cases. RESULTS: 330 total articles were populated using our search. 12 articles met our inclusion criteria. 41.7% (n = 5) of the articles were case series, 33.3% (n = 4) were case reports, 8.3% (n = 1) was a technical article, 8.3% (n = 1) was a systematic review, and 8.3% (n = 1) was a case questionnaire. Resolution of symptoms was noted in all articles of our scoping review, regardless of treatment modality. The average age in our case series was 9.84 years old and average age at diagnosis was 5.53 years old. 6 patients (31.6%) were female and 13 patients (68.4%) were male. 2 out of the 19 patients (10.5%) were surgically treated. CONCLUSION: There is no clear consensus on the management of cavum cysts. A prospective, multicenter study is needed to create standardized pediatric cyst management guidelines. The current thought is that surgical intervention should be saved for those patients with obstructive hydrocephalus and signs of intracranial hypertension.


Assuntos
Septo Pelúcido , Humanos , Criança , Feminino , Masculino , Pré-Escolar , Adolescente , Lactente , Septo Pelúcido/diagnóstico por imagem , Septo Pelúcido/cirurgia , Cistos do Sistema Nervoso Central/cirurgia , Cistos do Sistema Nervoso Central/diagnóstico por imagem , Estudos Retrospectivos
9.
Int J Mol Sci ; 25(2)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38255987

RESUMO

The complex interactions between cancer cells and their surrounding microenvironment are fundamental in determining tumor progression, response to therapy, and, ultimately, patient prognosis [...].


Assuntos
Neoplasias da Mama , Humanos , Feminino , Microambiente Tumoral
10.
J Cancer Educ ; 39(2): 111-117, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37957501

RESUMO

Arkansas has a high cancer burden, and a pressing need exists for more medical students to pursue oncology as a career. The Partnership in Cancer Research (PCAR) program provides a summer research experience at the University of Arkansas for Medical Sciences for 12 medical students who have completed their first year of medical training. A majority of participants spend time pursuing cancer research in basic science, clinical, or community-based research. Students report on their research progress in an interactive "Live from the Lab!" series and assemble a final poster presentation describing their findings. Other activities include participation in a moderated, cancer-patient support group online, lecture series on cancer topics, medical simulations, palliative care clinic visit, "Death Over Dinner" event, and an entrepreneurship competition. Students completed surveys over PCAR's first 2 years in operation to evaluate all aspects of the program. Surveys reveal that students enthusiastically embraced the program in its entirety. This was especially true of the medical simulations which received the highest evaluations. Most significantly, surveys revealed that the program increased cancer knowledge and participant confidence to perform cancer research.


Assuntos
Neoplasias , Estudantes de Medicina , Humanos , Currículo , Pesquisa , Oncologia/educação , Neoplasias/terapia , Avaliação de Programas e Projetos de Saúde
11.
Gastroenterology ; 162(3): 877-889.e7, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34861219

RESUMO

BACKGROUND & AIMS: Excessive shedding of apoptotic enterocytes into the intestinal lumen is observed in inflammatory bowel disease and is correlated with disease relapse. Based on their cytolytic capacity and surveillance behavior, we investigated whether intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) are actively involved in the shedding of enterocytes into the lumen. METHODS: Intravital microscopy was performed on GFP γδ T cell reporter mice treated with intraperitoneal lipopolysaccharide (10 mg/kg) for 90 minutes to induce tumor necrosis factor-mediated apoptosis. Cell shedding in various knockout or transgenic mice in the presence or absence of blocking antibody was quantified by immunostaining for ZO-1 funnels and cleaved caspase-3 (CC3). Granzyme A and granzyme B release from ex vivo-stimulated γδ IELs was quantified by enzyme-linked immunosorbent assay. Immunostaining for γδ T cell receptor and CC3 was performed on duodenal and ileal biopsies from controls and patients with Crohn's disease. RESULTS: Intravital microscopy of lipopolysaccharide-treated mice revealed that γδ IELs make extended contact with shedding enterocytes. These prolonged interactions require CD103 engagement by E-cadherin, and CD103 knockout or blockade significantly reduced lipopolysaccharide-induced shedding. Furthermore, we found that granzymes A and B, but not perforin, are required for cell shedding. These extracellular granzymes are released by γδ IELs both constitutively and after CD103/E-cadherin ligation. Moreover, we found that the frequency of γδ IEL localization to CC3-positive enterocytes is increased in Crohn's disease biopsies compared with healthy controls. CONCLUSIONS: Our results uncover a previously unrecognized role for γδ IELs in facilitating tumor necrosis factor-mediated shedding of apoptotic enterocytes via CD103-mediated extracellular granzyme release.


Assuntos
Antígenos CD/metabolismo , Doença de Crohn/metabolismo , Enterócitos/fisiologia , Granzimas/metabolismo , Cadeias alfa de Integrinas/metabolismo , Linfócitos Intraepiteliais/fisiologia , Adolescente , Adulto , Animais , Antígenos CD/genética , Apoptose , Caderinas/metabolismo , Caspase 3/metabolismo , Doença de Crohn/patologia , Duodeno/patologia , Enterócitos/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Íleo/patologia , Cadeias alfa de Integrinas/genética , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Linfócitos Intraepiteliais/enzimologia , Linfócitos Intraepiteliais/patologia , Microscopia Intravital , Jejuno/imunologia , Jejuno/patologia , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
12.
J Vasc Interv Radiol ; 34(11): 1915-1921, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37527770

RESUMO

PURPOSE: To evaluate the effectiveness and safety of prophylactic multivessel selective embolization (MVSE) compared to those of internal iliac artery occlusion balloon (IIABO) placement in patients undergoing cesarean hysterectomy for placenta accreta spectrum (PAS). MATERIALS AND METHODS: An institutional review board-approved retrospective series was conducted with consecutive patients with PAS at a single institution between 2010 and 2021. MVSE was performed in a hybrid operating room after cesarean section prior to hysterectomy. IIABO was performed with balloons placed into the bilateral internal iliac arteries, which were inflated during hysterectomy. Median blood loss, transfusion requirements, percentage of cases requiring transfusion, and adverse events were recorded. RESULTS: A total of 20 patients treated with embolization and 34 patients with balloon placement were included. Placenta percreta and previa were seen in 60% and 90% of patients, respectively. Median blood loss in the MVSE group was 713 mL (interquartile range [IQR], 475-1,000 mL) compared to 2,000 mL (IQR, 1,500-2,425 mL) in the IIABO group (P < .0001). The median total number of units of packed red blood cell transfusions (0 vs 2.5) and percentage of cases requiring a transfusion (20% vs 65%) were less in the MVSE group (P < .01). A median of 4 vessels (IQR, 3-9) were embolized during MVSE. No major adverse events or nontarget embolization consequences were observed. CONCLUSIONS: Prophylactic MVSE is a safe procedure that reduces operative blood loss and transfusion requirements compared to those of IIABO in patients undergoing cesarean hysterectomy for presumed higher-degree PAS.


Assuntos
Oclusão com Balão , Placenta Acreta , Gravidez , Humanos , Feminino , Cesárea/efeitos adversos , Placenta Acreta/diagnóstico por imagem , Placenta Acreta/cirurgia , Artéria Ilíaca/diagnóstico por imagem , Estudos Retrospectivos , Oclusão com Balão/efeitos adversos , Oclusão com Balão/métodos , Histerectomia/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle
13.
Int J Mol Sci ; 24(3)2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36768830

RESUMO

The anti-CSPG4 monoclonal antibodies (mAbs) have shown anti-tumor activity and therapeutic potential for treating breast cancer. In addition, CSPG4 is a dominant tumor-associated antigen that is also involved in normal-tissue development in humans. Therefore, the potential for off-tumor activity remains a serious concern when targeting CSPG4 therapeutically. Previous work suggested that glycans contribute to the binding of specific anti-CSPG4 antibodies to tumor cells, but the specificity and importance of this contribution are unknown. In this study, the reactivity of anti-CSPG4 mAbs was characterized with a peptide mimetic of carbohydrate antigens expressed in breast cancer. ELISA, flow cytometry, and microarray assays were used to screen mAbs for their ability to bind to carbohydrate-mimicking peptides (CMPs), cancer cells, and glycans. The mAb VT68.2 displayed a distinctly strong binding to a CMP (P10s) and bound to triple-negative breast cancer cells. In addition, VT68.2 showed a higher affinity for N-linked glycans that contain terminal fucose and fucosylated lactosamines. The functional assays demonstrated that VT68.2 inhibited cancer cell migration. These results define the glycoform reactivity of an anti-CSPG4 antibody and may lead to the development of less toxic therapeutic approaches that target tumor-specific glyco-peptides.


Assuntos
Proteoglicanas , Neoplasias de Mama Triplo Negativas , Humanos , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Anticorpos Monoclonais/farmacologia , Antígenos Glicosídicos Associados a Tumores , Proteínas de Membrana
14.
Opt Express ; 30(24): 43317-43329, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36523032

RESUMO

We demonstrate recent progress in the development of a Raman gas sensor using a single cladding ring anti-resonant hollow core micro-structured optical fiber (HC-ARF) and a low power pump source. The HC-ARF was designed specifically for low attenuation and wide bandwidth in the visible spectral region and provided low loss at both the pump wavelength (532 nm) and Stokes wavelengths up to a Raman shift of 5000 cm-1. A novel selective core pressurization scheme was also implemented to further reduce the confinement loss, improving the Raman signal enhancement by a factor of 1.9 compared to a standard fiber filling scheme. By exploiting longer lengths of fiber, direct detection of both methane and hydrogen at concentrations of 5 and 10 ppm respectively is demonstrated and a noise equivalent limit-of-detection of 0.15 ppm is calculated for methane.

15.
J Nutr ; 152(9): 2048-2059, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-35665820

RESUMO

BACKGROUND: Deuterium oxide (D2O) dilution is the criterion method for total body water (TBW) measurement, but results may vary depending on the specimen type, analysis method, and analyzing laboratory. Bioelectrical impedance (BIA) estimates TBW, but results may vary by device make and model. OBJECTIVES: We investigated the accuracy and precision of TBW estimates and how measurement conditions affected the accuracy of body composition using multicompartment body composition models. METHODS: Eighty collegiate athletes received duplicate TBW measures acquired from 3 BIA devices (S10, SFB7, and SOZO) and from unique D2O combinations of specimen type (saliva, urine), analysis methodology [Fourier transform infrared spectrophotometry (FTIR), isotope-ratio mass spectrometry (IRMS)], and 3 different laboratories. TBW measures were substituted into 2-compartment (2C) and 5-compartment (5C) body composition models. Criterion measures were compared using Lin's concordance correlation coefficient cutoff of poor (<0.90), moderate (0.90-0.95), substantial (0.95-0.99), and almost perfect (>0.99). RESULTS: Fifty-one participants (26 female) completed the protocol. Using IRMS saliva as the criterion TBW, all other measures produced a substantial or almost perfect agreement, except for SFB7 (poor) and SOZO (moderate). The 2C body composition measures using D2O and BIA produced poor agreement except for moderate agreement for lab 3 FTIR saliva. The 5C body composition measures using D2O produced a substantial agreement, whereas the BIA device S10 and SOZO had a moderate agreement, while the SFB7 had a poor agreement to the criterion. Test-retest precision varied between techniques from 0.3% to 1.2% for TBW. CONCLUSIONS: Small differences in TBW measurement led to significant differences in 2C models. The 5C models partially mitigate differences seen in 2C models when different TBW measures are used. Interchanging TBW measures in multicompartment models can be problematic and should be performed with these considerations.


Assuntos
Composição Corporal , Água Corporal , Atletas , Deutério , Óxido de Deutério , Impedância Elétrica , Feminino , Humanos , Técnicas de Diluição do Indicador
16.
J Endovasc Ther ; 29(6): 962-965, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34986704

RESUMO

PURPOSE: The objective of this study is to report a case of a primary aortoenteric fistula successfully treated with endovascular repair without aortic explant. CASE REPORT: A 48-year-old man presented with a 24-hour history of hematemesis and malena. A computed tomography (CT) abdomen and pelvis demonstrated a 6 cm infrarenal aortic aneurysm with periaortic stranding and contrast enhancement within the lumen of the third part of the duodenum. The patient underwent emergency Endovascular Aortic Repair (EVAR). The patient was discharged on day 8 of his admission on oral antibiotics. He returned 7 weeks postindex procedure and underwent a laparotomy with omental patch repair of the aortic defect. Intraoperative cultures grew candida albicans, and the patient was discharged on lifelong oral Fluconazole and Amoxycillin-Clavulanic Acid. At 18 months postoperatively, the patient was clinically stable with improved appearances on CT aortogram. CONCLUSION: We discuss the use of EVAR without aortic explant as a possible treatment option in the management of patient with primary aortoenteric fistulae. This may potentially avoid the significant morbidity and mortality associated with aortic explant in suitable candidates without perioperative signs of sepsis.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Fístula Intestinal , Fístula Vascular , Masculino , Humanos , Pessoa de Meia-Idade , Aneurisma da Aorta Abdominal/cirurgia , Fístula Intestinal/diagnóstico por imagem , Fístula Intestinal/etiologia , Fístula Intestinal/cirurgia , Resultado do Tratamento , Remoção de Dispositivo , Fístula Vascular/diagnóstico por imagem , Fístula Vascular/cirurgia
17.
Proc Natl Acad Sci U S A ; 116(11): 4973-4982, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30718387

RESUMO

Each genomic locus in a eukaryotic cell has a distinct average time of replication during S phase that depends on the spatial and temporal pattern of replication initiation events. Replication timing can affect genomic integrity because late replication is associated with an increased mutation rate. For most eukaryotes, the features of the genome that specify the location and timing of initiation events are unknown. To investigate these features for the fission yeast, Schizosaccharomyces pombe, we developed an integrative model to analyze large single-molecule and global genomic datasets. The model provides an accurate description of the complex dynamics of S. pombe DNA replication at high resolution. We present evidence that there are many more potential initiation sites in the S. pombe genome than previously identified and that the distribution of these sites is primarily determined by two factors: the sequence preferences of the origin recognition complex (ORC), and the interference of transcription with the assembly or stability of prereplication complexes (pre-RCs). We suggest that in addition to directly interfering with initiation, transcription has driven the evolution of the binding properties of ORC in S. pombe and other eukaryotic species to target pre-RC assembly to regions of the genome that are less likely to be transcribed.


Assuntos
Replicação do DNA , Células Eucarióticas/metabolismo , Schizosaccharomyces/metabolismo , Sequência Rica em At , Cromossomos Fúngicos/genética , Simulação por Computador , Período de Replicação do DNA , RNA Polimerases Dirigidas por DNA/metabolismo , Células Eucarióticas/citologia , Genoma Fúngico , Modelos Biológicos , Complexo de Reconhecimento de Origem/genética , Probabilidade , Schizosaccharomyces/citologia , Proteínas de Schizosaccharomyces pombe/metabolismo , Transcrição Gênica
18.
Am J Obstet Gynecol ; 225(4): 442.e1-442.e10, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34245679

RESUMO

BACKGROUND: Multidisciplinary care of placenta accreta spectrum cases improves pregnancy outcomes, but the specific components of such a multidisciplinary collaboration varies between institutions. As experience with placenta accreta spectrum increases, it is crucial to assess new surgical techniques and protocols to help improve maternal outcomes and to advocate for hospital resources. OBJECTIVE: This study aimed to assess a novel multidisciplinary protocol for the treatment of placenta accreta spectrum that comprises cesarean delivery, multivessel uterine embolization, and hysterectomy in a single procedure within a hybrid operative suite. STUDY DESIGN: This was a matched prepost study of placenta accreta spectrum cases managed before (2010-2017) and after implementation of the Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization protocol (2018-2021) at a tertiary medical center. Historical cases were managed with internal iliac artery balloon placement in selected cases with the decision to inflate the balloons intraoperatively at the discretion of the primary surgeon. Intraoperative Embolization cases were compared with historical cases in a 1:2 ratio matched on the basis of placenta accreta spectrum severity and surgical urgency. The primary outcome was a requirement for transfusion with packed red blood cells. Secondary outcomes included estimated surgical blood loss, operative and postoperative complications, procedural time, length of stay, and neonatal outcomes. RESULTS: A total of 15 Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization cases and 30 matched historical cases were included in the analysis. There were no demographic differences noted between the groups. A median (interquartile range) of 0 units (0-2 units) of packed red blood cells were transfused in the Intraoperative Embolization group compared with 2 units (0-4.5 units) in the historical group (P=.045); 5 of 15 (33.3%) Intraoperative Embolization cases required blood transfusions compared with 19 of 30 (63.3%) cases in the historical group (P=.11). The estimated blood loss was significantly less in the Intraoperative Embolization group with a median (interquartile range) of 750 mL (450-1050 mL) compared with 1750 mL (1050-2500 mL) in the historical group (P=.003). There were no cases requiring massive transfusion (≥10 red blood cell units in 24 hours) in the Intraoperative Embolization group compared with 5 of 30 (16.7%) cases in the historical group (P=.15). There were no intraoperative deaths from hemorrhagic shock using the Intraoperative Embolization protocol, whereas this occurred in 2 of the historical cases. The mean duration of the interventional radiology procedure was longer in the Intraoperative Embolization group (67.8 vs 34.1 minutes; P=.002). Intensive care unit admission and postpartum length of stay were similar, and surgical and postoperative complications were not significantly different between the groups. The gestational age and neonatal birthweights were similar; however, the neonatal length of stay was longer in the Intraoperative Embolization group (median duration, 32 days vs 15 days; P=.02) with a trend toward low Apgar scores. Incidence of arterial umbilical cord blood pH <7.2 and respiratory distress syndrome and intubation rates were not statistically different between the groups. CONCLUSION: A multidisciplinary pathway including a single-surgery protocol with multivessel uterine embolization is associated with a decrease in blood transfusion requirements and estimated blood loss with no increase in operative complications. The Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization protocol provides a definitive surgical method that warrants consideration by other centers specializing in placenta accreta spectrum treatment.


Assuntos
Cesárea/métodos , Transfusão de Eritrócitos/estatística & dados numéricos , Histerectomia/métodos , Artéria Ilíaca , Cuidados Intraoperatórios/métodos , Placenta Acreta/terapia , Embolização da Artéria Uterina/métodos , Hemorragia Uterina/prevenção & controle , Adulto , Índice de Apgar , Oclusão com Balão , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Terapia Combinada , Embolização Terapêutica/métodos , Feminino , Idade Gestacional , Estudo Historicamente Controlado , Humanos , Unidades de Terapia Intensiva Neonatal , Tempo de Internação/estatística & dados numéricos , Duração da Cirurgia , Gravidez , Radiografia Intervencionista , Choque Hemorrágico/epidemiologia , Choque Hemorrágico/mortalidade , Hemorragia Uterina/terapia
19.
Soft Matter ; 16(26): 6021-6031, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32555906

RESUMO

Despite the development of the brilliant flat-panel TVs and computer screens that we all use on a daily basis, liquid crystals are far from being exhausted as a topic of research. Novel effects, new, modern, self-organized materials, and a range of applications are being developed, which are on the borderline between nanotechnology and soft condensed matter, and which use liquid crystals as a vehicle to study fundamental physical questions, all the way to mimicking nature and life. In this perspective article we will introduce an illustrative example, which will draw on a range of non-display aspects in liquid crystal research which have increasingly gained interest over the past years, namely self-organization of liquid crystals, colloidal ordering of magnetic nanoparticles, topological defects, and biological structures.

20.
Neurocrit Care ; 33(1): 173-181, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31792700

RESUMO

INTRODUCTION: Point-of-care ultrasound of the optic nerve sheath diameter (ONSD) to diagnose increased intracranial pressure (ICP) is of great interest in various clinical scenarios. Yet, the lack of examination standardization has made clinical utility difficult. We compare three ultrasound ocular plane views (inferior, sagittal, and transverse), which are currently used in the literature to evaluate their consistency. Comparisons for each view to magnetic resonance imaging (MRI) measurements were also made. METHODS: Fifty-one patients with recent MRI of the brain, but without clinical or radiological signs of elevated ICP, were selected to undergo ocular sonography via three ultrasound planes (inferior, sagittal, and transverse). Optic nerve sheath was measured in each ultrasound view as well with MRI. Image quality scores were assigned for the ultrasound views in different orientations. The three ocular plane views were analyzed for correlation. In addition, correlation of the three ocular ultrasound views with MRI was also performed. RESULTS: Correlation analysis showed a wide variability in the correlation between different ultrasound views with magnitude range of 0.1 to 0.8 and directions being both positive and negative. There was a difference in image quality scores between the ultrasound views. The inferior and transverse orientations were superior to the sagittal orientation in achieving high image quality. Comparison to MRI measurements did not demonstrate a significant correlation. CONCLUSION: Our findings suggest that absolute measurements should not be compared across different ultrasound orientations given the wide variability in the correlation between the ultrasound views used to assess the optic nerve sheath. The inferior and transverse ultrasound views are the most likely to yield high-quality images, although the specific view, for the best image, in an individual patient can vary. We would caution against absolute values of ONSD to indicate increased ICP, as it may be view dependent.


Assuntos
Hipertensão Intracraniana/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Nervo Óptico/diagnóstico por imagem , Sistemas Automatizados de Assistência Junto ao Leito , Ultrassonografia/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nervo Óptico/patologia , Tamanho do Órgão , Estudos Prospectivos
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