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1.
Proc Natl Acad Sci U S A ; 118(45)2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34732568

RESUMO

Numerous diverse microorganisms reside in the cold desert soils of continental Antarctica, though we lack a holistic understanding of the metabolic processes that sustain them. Here, we profile the composition, capabilities, and activities of the microbial communities in 16 physicochemically diverse mountainous and glacial soils. We assembled 451 metagenome-assembled genomes from 18 microbial phyla and inferred through Bayesian divergence analysis that the dominant lineages present are likely native to Antarctica. In support of earlier findings, metagenomic analysis revealed that the most abundant and prevalent microorganisms are metabolically versatile aerobes that use atmospheric hydrogen to support aerobic respiration and sometimes carbon fixation. Surprisingly, however, hydrogen oxidation in this region was catalyzed primarily by a phylogenetically and structurally distinct enzyme, the group 1l [NiFe]-hydrogenase, encoded by nine bacterial phyla. Through gas chromatography, we provide evidence that both Antarctic soil communities and an axenic Bacteroidota isolate (Hymenobacter roseosalivarius) oxidize atmospheric hydrogen using this enzyme. Based on ex situ rates at environmentally representative temperatures, hydrogen oxidation is theoretically sufficient for soil communities to meet energy requirements and, through metabolic water production, sustain hydration. Diverse carbon monoxide oxidizers and abundant methanotrophs were also active in the soils. We also recovered genomes of microorganisms capable of oxidizing edaphic inorganic nitrogen, sulfur, and iron compounds and harvesting solar energy via microbial rhodopsins and conventional photosystems. Obligately symbiotic bacteria, including Patescibacteria, Chlamydiae, and predatory Bdellovibrionota, were also present. We conclude that microbial diversity in Antarctic soils reflects the coexistence of metabolically flexible mixotrophs with metabolically constrained specialists.


Assuntos
Clima Desértico , Gases/metabolismo , Camada de Gelo/microbiologia , Microbiota , Microbiologia do Solo , Regiões Antárticas , Processos Autotróficos , Biodiversidade , Hidrogenase/metabolismo , Metagenoma , Oxirredução , Processos Fototróficos
2.
Br J Cancer ; 128(9): 1765-1776, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36810910

RESUMO

BACKGROUND: Ovarian cancers are hallmarked by chromosomal instability. New therapies deliver improved patient outcomes in relevant phenotypes, however therapy resistance and poor long-term survival signal requirements for better patient preselection. An impaired DNA damage response (DDR) is a major chemosensitivity determinant. Comprising five pathways, DDR redundancy is complex and rarely studied alongside chemoresistance influence from mitochondrial dysfunction. We developed functional assays to monitor DDR and mitochondrial states and trialled this suite on patient explants. METHODS: We profiled DDR and mitochondrial signatures in cultures from 16 primary-setting ovarian cancer patients receiving platinum chemotherapy. Explant signature relationships to patient progression-free (PFS) and overall survival (OS) were assessed by multiple statistical and machine-learning methods. RESULTS: DR dysregulation was wide-ranging. Defective HR (HRD) and NHEJ were near-mutually exclusive. HRD patients (44%) had increased SSB abrogation. HR competence was associated with perturbed mitochondria (78% vs 57% HRD) while every relapse patient harboured dysfunctional mitochondria. DDR signatures classified explant platinum cytotoxicity and mitochondrial dysregulation. Importantly, explant signatures classified patient PFS and OS. CONCLUSIONS: Whilst individual pathway scores are mechanistically insufficient to describe resistance, holistic DDR and mitochondrial states accurately predict patient survival. Our assay suite demonstrates promise for translational chemosensitivity prediction.


Assuntos
Neoplasias Ovarianas , Platina , Humanos , Feminino , Platina/uso terapêutico , Dano ao DNA , Recidiva Local de Neoplasia , Carcinoma Epitelial do Ovário , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Aprendizado de Máquina
3.
J Surg Res ; 278: 93-99, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35594620

RESUMO

INTRODUCTION: With increasing rates of obesity worldwide, a correlation between high body mass index (BMI) and postoperative morbidity after thyroid surgery remains unclear. Postoperative transient hypocalcemia is common after total thyroidectomy due to interruption of parathyroid function. This study examines the relationship between BMI and hypocalcemia after total thyroidectomy. MATERIALS AND METHODS: A retrospective review of prospectively collected data for 1135 patients who underwent total thyroidectomy for cancer, multinodular goiter (MNG), or Graves' disease between June 2009 and November 2020 at a single institution was performed. BMI groups followed the World Health Organization classification. Hypocalcemia was defined as serum calcium ≤8 mg/dL. Calcium levels measured on postoperative day 0 and the following morning were compared between the BMI groups. RESULTS: Of 1135 total thyroidectomy patients, 85% were women. The mean age and standard deviation of patients was 49 (± 13) y, with most of Hispanic origin (64%). Overall, 41.5% of patients had cancer, 45% nontoxic MNG, 5.8% toxic MNG, and 12% Graves' disease. Stratified by BMI, 27% of patients were normal, 34% overweight, and 39% obese. Overall, overweight and obese patients experienced less transient hypocalcemia at both time points compared to normal patients postoperatively (P = 0.01 and P = 0.009). Furthermore, overweight and obese patients with Graves' disease experienced less transient hypocalcemia at both time points (P = 0.04 and P = 0.05). There was no statistical difference in other groups. CONCLUSIONS: A protective role of higher BMI or "obesity paradox" for postoperative hypocalcemia may exist in those obese patients after total thyroidectomy.


Assuntos
Hipocalcemia , Complicações Pós-Operatórias , Tireoidectomia , Adulto , Cálcio , Feminino , Doença de Graves/cirurgia , Humanos , Hipocalcemia/epidemiologia , Hipocalcemia/etiologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/cirurgia , Sobrepeso/cirurgia , Hormônio Paratireóideo , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Tireoidectomia/efeitos adversos
4.
Sensors (Basel) ; 22(18)2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36146111

RESUMO

The proliferation of the internet of things (IoT) technology has led to numerous challenges in various life domains, such as healthcare, smart systems, and mission-critical applications. The most critical issue is the security of IoT nodes, networks, and infrastructures. IoT uses the routing protocol for low-power and lossy networks (RPL) for data communication among the devices. RPL comprises a lightweight core and thus does not support high computation and resource-consuming methods for security implementation. Therefore, both IoT and RPL are vulnerable to security attacks, which are broadly categorized into RPL-specific and sensor-network-inherited attacks. Among the most concerning protocol-specific attacks are rank attacks and wormhole attacks in sensor-network-inherited attack types. They target the RPL resources and components including control messages, repair mechanisms, routing topologies, and sensor network resources by consuming. This leads to the collapse of IoT infrastructure. In this paper, a lightweight multiclass classification-based RPL-specific and sensor-network-inherited attack detection model called MC-MLGBM is proposed. A novel dataset was generated through the construction of various network models to address the unavailability of the required dataset, optimal feature selection to improve model performance, and a light gradient boosting machine-based algorithm optimized for a multiclass classification-based attack detection. The results of extensive experiments are demonstrated through several metrics including confusion matrix, accuracy, precision, and recall. For further performance evaluation and to remove any bias, the multiclass-specific metrics were also used to evaluate the model, including cross-entropy, Cohn's kappa, and Matthews correlation coefficient, and then compared with benchmark research.


Assuntos
Internet das Coisas , Algoritmos , Entropia , Aprendizado de Máquina
5.
J Surg Res ; 268: 209-213, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34358733

RESUMO

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology has 6 diagnostic categories, each with an implied cancer risk of malignancy (ROM). Bethesda III, defined as atypia or follicular lesions of undetermined significance (AUS/FLUS) on fine needle aspiration (FNA), has an indeterminate ROM. This study investigates the utility of Afirma Gene Expression Classifier (GEC) and Thyroid Sequencing (ThyroSeq) molecular testing to predict malignancy in AUS/FLUS thyroid nodules. METHODS: A retrospective review of prospectively collected data of 1457 patients with index thyroid nodules who underwent FNA and thyroidectomy at a single academic institution was performed. Use of GEC or ThyroSeq for AUS/FLUS thyroid nodules was examined. GEC testing was reported benign or suspicious for malignancy whereas ThyroSeq testing was reported on a spectrum of low, intermediate or high ROM. Descriptive statistics were utilized to compare the ROM among AUS/FLUS thyroid nodules. RESULTS: Of 1457 patients with FNA thyroid cytology, 359 (25%) corresponded to AUS/FLUS results. There were 132 (37%) patients with GEC testing and 88 (24%) had ThyroSeq testing. ROM without GEC or ThyroSeq testing was 49%, whereas ROM with suspicious GEC was 55%. ROM with positive ThyroSeq was 73%. Among ThyroSeq patients, 43 had intermediate-risk mutations with 60% malignancy, and 23 had high-risk mutations with 96% malignancy (P < 0.01). CONCLUSION: Surgical patients with AUS/FLUS thyroid nodules have a high ROM. High-risk ThyroSeq testing may have some utility in predicting malignancy, but GEC and intermediate-risk TGC results have limited value. Surgeons should carefully consider the utility of molecular tests to determine surgical resection.


Assuntos
Adenocarcinoma Folicular , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Adenocarcinoma Folicular/patologia , Biópsia por Agulha Fina , Humanos , Técnicas de Diagnóstico Molecular , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/genética , Nódulo da Glândula Tireoide/cirurgia
6.
J Surg Res ; 235: 264-269, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30691805

RESUMO

BACKGROUND: Parathyroidectomy guided by intraoperative parathormone (ioPTH) monitoring for primary hyperparathyroidism (pHPT) confirms removal of all hyperfunctioning parathyroid glands. This study evaluates the utility of an additional 20-min ioPTH measurement in patients who fail to meet the >50% ioPTH drop criterion. METHODS: A retrospective review of prospectively collected data of 706 patients with pHPT who underwent parathyroidectomy guided by ioPTH monitoring was performed. When a >50% ioPTH decrease from the highest either preincision or preexcision level was achieved after 10 min, parathyroidectomy was completed. If this criterion was not met, further exploration was performed or an additional 20-min ioPTH measurement was obtained. RESULTS: Of 706 patients, 72 (10%) patients did not meet the >50% ioPTH drop criterion at 10 min. Of these patients, 67% (48/72) underwent immediate bilateral neck exploration (BNE). For the other 33% of patients (24/72), a 20-min parathormone (PTH) measurement was drawn. Of patients with an additional 20-min PTH measurement, 46% (11/24) had a >50% ioPTH decrease at 20 min where BNE was avoided and parathyroidectomy completed, whereas 54% (13/24) did not. Compared to patients with insufficient ioPTH drop at 10 min and subsequent BNE, there was a statistically significant 46% reduction of BNE in patients with a 20-min PTH level (P < 0.01). CONCLUSIONS: A 20-min ioPTH measurement is useful in preventing unnecessary BNE in some patients who undergo focused parathyroidectomy with a delayed >50% ioPTH drop.


Assuntos
Hiperparatireoidismo Primário/cirurgia , Monitorização Intraoperatória , Hormônio Paratireóideo/sangue , Adolescente , Adulto , Idoso , Feminino , Humanos , Hiperparatireoidismo Primário/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Procedimentos Desnecessários , Adulto Jovem
7.
J Surg Res ; 207: 22-26, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27979480

RESUMO

BACKGROUND: Primary hyperparathyroidism (pHPT) is commonly treated with targeted parathyroidectomy (PTX) guided by preoperative imaging and intraoperative parathormone monitoring. Despite advanced imaging techniques, failure of parathyroid localization still occurs. This study determines the anatomical distribution of single abnormal parathyroid glands, which may help direct the surgeon in PTX when preoperative localization is unsuccessful. METHODS: A retrospective review of prospectively collected data of 810 patients with pHPT who underwent initial PTX at a tertiary medical center was performed. All patients had biochemically confirmed pHPT and single-gland disease. Abnormal parathyroid gland localization was determined at time of operation, correlated with operative and pathology reports, and confirmed by operative success defined as eucalcemia for ≥6 mo after PTX. Patients with multiple endocrine neoplasia, secondary, tertiary, or familial hyperparathyroidism, multiglandular disease, parathyroid cancer, and ectopic glands were excluded. Data were analyzed by chi-square and Z-test analyses. RESULTS: Among 810 patients who underwent PTX for pHPT, single abnormal parathyroid glands were unequally distributed among the four eutopic locations (left superior, 15.7%; left inferior, 31.3%; right superior, 15.8%; right inferior, 37.2%; P < 0.01). Abnormal inferior parathyroid glands (68.5%) were significantly more common than abnormal superior glands (31.5%), respectively (P < 0.01). In men, the most common location for single abnormal parathyroid glands was the right inferior position (43.4%, P < 0.01). Overall, there was no significant difference in laterality. CONCLUSIONS: This large series of patients suggests that single eutopic abnormal parathyroid glands are more likely to be inferior. In men, moreover, if an abnormal parathyroid gland is not localized preoperatively, the right inferior location should be explored first. Nevertheless, successful PTX remains predicated on knowledge of parathyroid anatomy, experience, and judgment of the surgeon.


Assuntos
Hiperparatireoidismo Primário/cirurgia , Glândulas Paratireoides/anatomia & histologia , Paratireoidectomia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Seguimentos , Humanos , Hiperparatireoidismo Primário/patologia , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
8.
J Surg Res ; 219: 259-265, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29078892

RESUMO

BACKGROUND: Both functional (hormone hypersecreting) and nonfunctional (nonhypersecreting) adrenal tumors can have benign or malignant pathology. This study compares perioperative in-hospital outcomes after adrenalectomy in patients with benign versus malignant nonfunctional primary adrenal tumors. METHODS: A retrospective cross-sectional analysis was performed using the Nationwide Inpatient Sample database (2006-2011) to identify patients who underwent unilateral open or laparoscopic adrenalectomy for nonfunctional primary adrenal tumors. Patients were subdivided by benign and malignant final pathology. Demographics, comorbidities, and perioperative complications were compared between groups using bivariate and multivariate logistic regression. RESULTS: Of 23,297 patients, 89.7% (n = 20,897) had benign tumors, whereas 10.3% (n = 2400) had malignant tumors. Those with malignant tumors had higher Charlson Comorbidity Index scores and were more likely to undergo adrenalectomy at high volume centers. For both laparoscopic and open approach, patients with malignant nonfunctional tumors had higher rates of intraoperative complications including vascular and splenic injury (P < 0.01), as well as postoperative complications including hematoma, shock, acute kidney injury, venous thromboembolism, and pneumothorax (P < 0.01). In addition, the malignant group had higher rates of blood transfusions, longer hospital stay, and higher in-hospital mortality (P < 0.05) than benign counterparts. On risk-adjusted multivariate analysis, malignant nonfunctional primary adrenal tumors were independently associated with increased risk of complications following adrenalectomy. CONCLUSIONS: Patients with malignant nonfunctional primary adrenal tumors have higher perioperative morbidity and mortality compared to patients with benign nonfunctional adrenal tumors. Such patients should be medically optimized before adrenalectomy, and surgeons must remain vigilant in preventing perioperative complications.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/mortalidade , Neoplasias das Glândulas Suprarrenais/mortalidade , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Estudos Retrospectivos , Estados Unidos/epidemiologia
9.
Cell Mol Biol (Noisy-le-grand) ; 62(10): 80-4, 2016 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-27609479

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common cancer types with a high prevalence and itis the leading cause of cancer deaths worldwide. This study aimed to investigate the antiproliferative effect of aqueous and ethanol extracts of Origanum majorana leaf on human hepatocellular carcinoma (HepG2) cell line through incubation of various concentrations of origanum majorana extracts with HepG2 and at different time intervals. The effects of aqueous and ethanol extracts of O. majorana L. on HepG2 cell viability, nuclear factor kappa B (NF-kB) gene expression were examined. The results of the cell viability assays showed that aqueous and ethanol extracts exhibited a highly significant inhibitory effect on HepG2 cell proliferation which was evidenced by a reduction in viable cell count. The results were confirmed by microscopical examination of cell morphology. Furthermore, the O. majorana L. extracts suppressed the activity of NF-kB gene expression of HepG2 cells compared to the control.The conclusions from this study suggest that marjoram extracts exhibit anti-proliferative effect against HCC through suppressing the activity of NF-kB gene expression and high antioxidant activity.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , NF-kappa B/metabolismo , Origanum/química , Extratos Vegetais/farmacologia , Carcinoma Hepatocelular/genética , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Neoplasias Hepáticas/genética , NF-kappa B/genética , Fatores de Tempo
10.
J Virol ; 87(5): 2401-11, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23269796

RESUMO

Infection by HIV-1 most often results from the successful transmission and propagation of a single virus variant, termed the transmitted/founder (T/F) virus. Here, we compared the attachment and entry properties of envelope (Env) glycoproteins from T/F and chronic control (CC) viruses. Using a panel of 40 T/F and 47 CC Envs, all derived by single genome amplification, we found that 52% of clade C and B CC Envs exhibited partial resistance to the CCR5 antagonist maraviroc (MVC) on cells expressing high levels of CCR5, while only 15% of T/F Envs exhibited this same property. Moreover, subtle differences in the magnitude with which MVC inhibited infection on cells expressing low levels of CCR5, including primary CD4(+) T cells, were highly predictive of MVC resistance when CCR5 expression levels were high. These results are consistent with previous observations showing a greater sensitivity of T/F Envs to MVC inhibition on cells expressing very high levels of CCR5 and indicate that CC Envs are often capable of recognizing MVC-bound CCR5, albeit inefficiently on cells expressing physiologic levels of CCR5. When CCR5 expression levels are high, this phenotype becomes readily detectable. The utilization of drug-bound CCR5 conformations by many CC Envs was seen with other CCR5 antagonists, with replication-competent viruses, and did not obviously correlate with other phenotypic traits. The striking ability of clade C and B CC Envs to use MVC-bound CCR5 relative to T/F Envs argues that the more promiscuous use of CCR5 by these Env proteins is selected against at the level of virus transmission and is selected for during chronic infection.


Assuntos
Cicloexanos/farmacologia , HIV-1/fisiologia , Receptores CCR5/metabolismo , Triazóis/farmacologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo , Antagonistas dos Receptores CCR5 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Linhagem Celular , Células HEK293 , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , Infecções por HIV/virologia , Humanos , Maraviroc , Ligação Viral , Internalização do Vírus
11.
Geochem Trans ; 15: 7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24959098

RESUMO

BACKGROUND: The paper presents a quantification of main (hydrogen sulfide and sulfate), as well as of intermediate sulfur species (zero-valent sulfur (ZVS), thiosulfate, sulfite, thiocyanate) in the Yellowstone National Park (YNP) hydrothermal springs and pools. We combined these measurements with the measurements of quadruple sulfur isotope composition of sulfate, hydrogen sulfide and zero-valent sulfur. The main goal of this research is to understand multiple sulfur isotope fractionation in the system, which is dominated by complex, mostly abiotic, sulfur cycling. RESULTS: Water samples from six springs and pools in the Yellowstone National Park were characterized by pH, chloride to sulfate ratios, sulfide and intermediate sulfur species concentrations. Concentrations of sulfate in pools indicate either oxidation of sulfide by mixing of deep parent water with shallow oxic water, or surface oxidation of sulfide with atmospheric oxygen. Thiosulfate concentrations are low (<6 µmol L(-1)) in the pools with low pH due to fast disproportionation of thiosulfate. In the pools with higher pH, the concentration of thiosulfate varies, depending on different geochemical pathways of thiosulfate formation. The δ(34)S values of sulfate in four systems were close to those calculated using a mixing line of the model based on dilution and boiling of a deep hot parent water body. In two pools δ(34)S values of sulfate varied significantly from the values calculated from this model. Sulfur isotope fractionation between ZVS and hydrogen sulfide was close to zero at pH < 4. At higher pH zero-valent sulfur is slightly heavier than hydrogen sulfide due to equilibration in the rhombic sulfur-polysulfide - hydrogen sulfide system. Triple sulfur isotope ((32)S, (33)S, (34)S) fractionation patterns in waters of hydrothermal pools are more consistent with redox processes involving intermediate sulfur species than with bacterial sulfate reduction. Small but resolved differences in ∆(33)S among species and between pools are observed. CONCLUSIONS: The variation of sulfate isotopic composition, the origin of differences in isotopic composition of sulfide and zero-valent sulfur, as well as differences in ∆(33)S of sulfide and sulfate are likely due to a complex network of abiotic redox reactions, including disproportionation pathways.

12.
J Med Entomol ; 51(1): 220-5, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24605472

RESUMO

There is a threat for dengue virus (DENV) reemergence in many regions of the world, particularly in areas where the DENV vectors, Aedes aegypti (L.) and Aedes albopictus (Skuse), are readily available. However, there are currently no accurate and reliable diagnostic methods to provide critical, real-time information for early detection of DENV within the vector populations to implement appropriate vector control and personal protective measures. In this article, we report the ability of an immuno-chromatographic assay developed by VecTOR Test Systems Inc. to detect DENV in a pool of female Aedes mosquitoes infected with any of the four viral serotypes. The DENV dipstick assay was simple to use, did not require a cold chain, and provided clear results within 30 min. It was highly specific and did not cross-react with samples spiked with West Nile, yellow fever, Japanese encephalitis, Rift Valley fever, chikungunya, Venezuelan equine encephalomyelitis, Ross River, LaCrosse, or Caraparu viruses. The DENV assay can provide real-time critical information on the presence of DENV in mosquitoes to public health personnel. Results from this assay will allow a rapid threat assessment and the focusing of vector control measures in high-risk areas.


Assuntos
Aedes/virologia , Vírus da Dengue/isolamento & purificação , Insetos Vetores/virologia , Animais , Cromatografia , Feminino , Técnicas Imunológicas , Sensibilidade e Especificidade
13.
Exp Neurol ; 374: 114714, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38325653

RESUMO

Traumatic brain injury (TBI) is a leading cause of disability and increases the risk of developing neurodegenerative diseases. The mechanisms linking TBI to neurodegeneration remain to be defined. It has been proposed that the induction of cellular senescence after injury could amplify neuroinflammation and induce long-term tissue changes. The induction of a senescence response post-injury in the immature brain has yet to be characterised. We carried out two types of brain injury in juvenile CD1 mice: invasive TBI using controlled cortical impact (CCI) and repetitive mild TBI (rmTBI) using weight drop injury. The analysis of senescence-related signals showed an increase in γH2AX-53BP1 nuclear foci, p53, p19ARF, and p16INK4a expression in the CCI group, 5 days post-injury (dpi). At 35 days, the difference was no longer statistically significant. Gene expression showed the activation of different senescence pathways in the ipsilateral and contralateral hemispheres in the injured mice. CCI-injured mice showed a neuroinflammatory early phase after injury (increased Iba1 and GFAP expression), which persisted for GFAP. After CCI, there was an increase at 5 days in p16INK4, whereas in rmTBI, a significant increase was seen at 35 dpi. Both injuries caused a decrease in p21 at 35 dpi. In rmTBI, other markers showed no significant change. The PCR array data predicted the activation of pathways connected to senescence after rmTBI. These results indicate the induction of a complex cellular senescence and glial reaction in the immature mouse brain, with clear differences between an invasive brain injury and a repetitive mild injury.


Assuntos
Concussão Encefálica , Lesões Encefálicas Traumáticas , Lesões Encefálicas , Camundongos , Animais , Concussão Encefálica/complicações , Doenças Neuroinflamatórias , Lesões Encefálicas Traumáticas/complicações , Senescência Celular , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
14.
Emerg Microbes Infect ; 13(1): 2294859, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38088796

RESUMO

Identification of the diverse animal hosts responsible for spill-over events from animals to humans is crucial for comprehending the transmission patterns of emerging infectious diseases, which pose significant public health risks. To better characterize potential animal hosts of Lassa virus (LASV), we assessed domestic and non-domestic animals from 2021-2022 in four locations in southern Nigeria with reported cases of Lassa fever (LF). Birds, lizards, and domestic mammals (dogs, pigs, cattle and goats) were screened using RT-qPCR, and whole genome sequencing was performed for lineage identification on selected LASV positive samples. Animals were also screened for exposure to LASV by enzyme-linked immunosorbent assay (ELISA). Among these animals, lizards had the highest positivity rate by PCR. Genomic sequencing of samples in most infected animals showed sub-lineage 2 g of LASV. Seropositivity was highest among cattle and lowest in pigs. Though the specific impact these additional hosts may have in the broader virus-host context are still unknown - specifically relating to pathogen diversity, evolution, and transmission - the detection of LASV in non-rodent hosts living in proximity to confirmed human LF cases suggests their involvement during transmission as potential reservoirs. Additional epidemiological data comparing viral genomes from humans and animals, as well as those circulating within the environment will be critical in understanding LASV transmission dynamics and will ultimately guide the development of countermeasures for this zoonotic health threat.


Assuntos
Febre Lassa , Vírus Lassa , Humanos , Animais , Bovinos , Cães , Suínos , Vírus Lassa/genética , Febre Lassa/epidemiologia , Febre Lassa/veterinária , Febre Lassa/genética , Nigéria/epidemiologia , Genoma Viral , Saúde Pública , Mamíferos
15.
Microb Biotechnol ; 16(8): 1623-1628, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37354042

RESUMO

Hydrogen-oxidising bacteria play a key role in maintaining the composition of gases within the atmosphere and are ubiquitous in agricultural soils. While studies have shown that hydrogen accumulates in soil surrounding legume nodules and the soil surface, soils as a whole act as a net sink for hydrogen, raising questions about how hydrogen is internally recycled by soils. Can the energy derived from hydrogen oxidation be directly funnelled into plants to promote their growth or does it only act as a booster for other plant-growth promoting bacteria? Moreover, while the fertilisation effect of hydrogen on plants has previously been shown to be beneficial, questions remain about the upper limit of hydrogen uptake by plants before it becomes detrimental. Agricultural practices such as fertilisation may impact the balance of hydrogen-oxidisers and hydrogen-producers in these ecosystems, potentially having detrimental effects on not only agricultural land but also global biogeochemical cycles. In this perspectives piece, we highlight the importance of understanding the contribution of hydrogen to agricultural soils and the effects of agricultural practices on the ability for bacteria to cycle hydrogen in agricultural soils. We propose a framework to gain better insights into microbial hydrogen cycling within agroecosystems, which could contribute to the development of new agricultural biotechnologies.


Assuntos
Ecossistema , Hidrogênio , Microbiologia do Solo , Agricultura , Plantas , Solo/química , Bactérias/genética
16.
J Acquir Immune Defic Syndr ; 93(2): 171-180, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36881816

RESUMO

BACKGROUND: Food and water insecurity are associated with poor health outcomes that may be exacerbated by social marginalization and barriers to health care experienced by sexual and gender minorities (SGM) in resource-limited settings. We explored factors associated with food and water insecurity in SGM with HIV. SETTING: A longitudinal study of 357 men who have sex with men, transgender women, and other gender-identifying people in Lagos, Nigeria. METHODS: Laboratory testing, interviews, food and water assessments, and anthropometry were performed quarterly. Robust Poisson regression with generalized estimating equations was used to evaluate factors potentially associated with food and water insecurity. RESULTS: From 2014 to 2018, 357 SGM with HIV completed either the food or water assessments. At baseline, participants identified as cisgender men who have sex with men 265 (74.2%), transgender women 63 (17.7%), or as nonbinary/other gender 29 (8.1%). Food insecurity and water insecurity were reported by 63/344(18.3%) and 113/357(31.7%), respectively, at any visit. Food and water insecurity each decreased with ongoing study participation. Food insecurity was associated with nonpartnered relationship status, CD4 count <500 cells/mm 3 , and lack of access to piped water. Water insecurity was associated with age 25 years or older, living with a man, transactional sex, and food insecurity. CONCLUSIONS: Food and water insecurity were common among SGM in Nigeria and decreased with continued study participation, suggesting amenability to intervention when SGM are successfully engaged in care. Targeted interventions to support food and water security may improve HIV-related outcomes, such as CD4 count.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Masculino , Humanos , Feminino , Adulto , Estudos Longitudinais , Homossexualidade Masculina , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Nigéria/epidemiologia , Insegurança Hídrica , Abastecimento de Alimentos
17.
Nat Microbiol ; 8(4): 581-595, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36747116

RESUMO

Molecular hydrogen (H2) is an abundant and readily accessible energy source in marine systems, but it remains unknown whether marine microbial communities consume this gas. Here we use a suite of approaches to show that marine bacteria consume H2 to support growth. Genes for H2-uptake hydrogenases are prevalent in global ocean metagenomes, highly expressed in metatranscriptomes and found across eight bacterial phyla. Capacity for H2 oxidation increases with depth and decreases with oxygen concentration, suggesting that H2 is important in environments with low primary production. Biogeochemical measurements of tropical, temperate and subantarctic waters, and axenic cultures show that marine microbes consume H2 supplied at environmentally relevant concentrations, yielding enough cell-specific power to support growth in bacteria with low energy requirements. Conversely, our results indicate that oxidation of carbon monoxide (CO) primarily supports survival. Altogether, H2 is a notable energy source for marine bacteria and may influence oceanic ecology and biogeochemistry.


Assuntos
Bactérias , Água do Mar , Bactérias/genética , Água do Mar/microbiologia , Hidrogênio , Oxirredução , Oceanos e Mares
18.
Trends Microbiol ; 30(4): 330-337, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34462186

RESUMO

Molecular hydrogen (H2) is available in trace amounts in most ecosystems through atmospheric, biological, geochemical, and anthropogenic sources. Aerobic bacteria use this energy-dense gas, including at atmospheric concentrations, to support respiration and carbon fixation. While it was thought that aerobic H2 consumers are rare community members, here we summarize evidence suggesting that they are dominant throughout soils and other aerated ecosystems. Bacterial cultures from at least eight major phyla can consume atmospheric H2. At the ecosystem scale, H2 consumers are abundant, diverse, and active across diverse soils and are key primary producers in extreme environments such as hyper-arid deserts. On this basis, we propose that H2 is a universally available energy source for the survival of aerobic bacteria.


Assuntos
Ecossistema , Hidrogênio , Bactérias Aeróbias , Oxirredução , Microbiologia do Solo
19.
Surgery ; 172(5): 1373-1378, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36031445

RESUMO

BACKGROUND: Surgical excision of substernal thyroid goiters is usually achieved through a conventional transcervical approach, and transthoracic excision is rarely necessary. Currently, there are no clear guidelines for substernal thyroid goiters that may require a transthoracic approach. This study examined what preoperative factors were significantly associated with transthoracic surgical excision for substernal thyroid goiters. METHODS: A retrospective review of prospectively collected data of 109 patients with substernal thyroid goiters from a single institution was performed. The patients were stratified by transcervical and transthoracic approaches for substernal thyroid goiters. The factors possibly predictive of a transthoracic approach, including substernal extension beyond the thoracic inlet, patient-reported symptoms, tracheal deviation, and malignancy, were analyzed. Demographics including age, sex, and race, among others, were also studied. RESULTS: Of 1,080 patients who underwent surgical resection for multinodular goiter, there were 109 (10%) patients with substernal thyroid goiters. Of the substernal thyroid goiter group, 11 (10%) patients underwent partial sternotomy, whereas 6 (5.5%) underwent total sternotomy. On logistic regression, only substernal component of the thyroid goiter extending beyond the sternal notch into the mediastinum was statistically significant in predicting sternotomy (odds ratio 3.43, confidence interval 1.65-6.41, P < .001). Substernal thyroid goiters with mediastinal extension of ≥5 cm beyond the sternal notch showed a sensitivity of 94% and specificity of 86.5% to predict need of sternotomy. CONCLUSION: Patients with substernal thyroid goiters who exhibit progressive enlargement and/or compressive symptoms should undergo surgical excision. Although most are removed through the conventional transcervical approach, substernal thyroid goiters with a depth of mediastinal extension ≥5 cm have a high likelihood of requiring sternotomy.


Assuntos
Bócio Subesternal , Esternotomia , Bócio Subesternal/diagnóstico , Bócio Subesternal/patologia , Bócio Subesternal/cirurgia , Humanos , Mediastino/patologia , Estudos Retrospectivos , Tireoidectomia
20.
J Am Coll Surg ; 232(4): 545-550, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33421566

RESUMO

BACKGROUND: Papillary thyroid carcinoma (PTC) comprises the majority of thyroid malignancy, but it is associated with excellent long-term survival. Highly prevalent, with increasing incidence, the optimal operative management for patients with 1- to 4-cm PTC remains unclear. This study determined factors that affect clinical outcomes, including survival, in this patient population. STUDY DESIGN: Patients with 1- to 4-cm PTC, who underwent thyroidectomy between 2004 and 2016, were identified in the National Cancer Database (NCDB). Factors affecting survival, including margin status, extent of resection, operative volume, and institution type, were studied. Outcomes were estimated by Kaplan-Meier and log rank tests. Cox proportional hazard and binary logistic regression analyses identified factors affecting survival as well as margin positivity. RESULTS: Of 14,471 patients with 1- to 4-cm PTC, 2,269 (15.7%) exhibited lymphovascular invasion, 6,925 (47.9%) had multifocality, 14,235 (98.3%) underwent total thyroidectomy, and 2,212 (15.3%) had microscopic margin positivity, which conferred lower survival (hazard ratio [HR] 1.464, p < 0.05), with 30-day and 90-day mortality of 0.1% and 0.2%, respectively. Operative volume (odds ratio [OR] 0.979, p < 0.01) and thyroid surgery at an academic center (OR 0.623, p < 0.001) were associated with lower odds of margin positivity. CONCLUSIONS: In patients with 1- to 4-cm PTC, margin positivity confers lower survival. Factors associated with lower rate of margin positivity are higher operative volume and referral for treatment at academic center. Because margin positivity is a modifiable risk factor, referral of patients with aggressive features of PTC to high volume academic centers may improve survival.


Assuntos
Câncer Papilífero da Tireoide/mortalidade , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/mortalidade , Tireoidectomia/estatística & dados numéricos , Centros Médicos Acadêmicos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Hospitais com Baixo Volume de Atendimentos/estatística & dados numéricos , Humanos , Estimativa de Kaplan-Meier , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Estados Unidos/epidemiologia , Adulto Jovem
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