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1.
Proc Natl Acad Sci U S A ; 121(12): e2316878121, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38466851

RESUMEN

Deep sea cold seeps are sites where hydrogen sulfide, methane, and other hydrocarbon-rich fluids vent from the ocean floor. They are an important component of Earth's carbon cycle in which subsurface hydrocarbons form the energy source for highly diverse benthic micro- and macro-fauna in what is otherwise vast and spartan sea scape. Passive continental margin cold seeps are typically attributed to the migration of hydrocarbons generated from deeply buried source rocks. Many of these seeps occur over salt tectonic provinces, where the movement of salt generates complex fault systems that can enable fluid migration or create seals and traps associated with reservoir formation. The elevated advective heat transport of the salt also produces a chimney effect directly over these structures. Here, we provide geophysical and geochemical evidence that the salt chimney effect in conjunction with diapiric faulting drives a subsurface groundwater circulation system that brings dissolved inorganic carbon, nutrient-rich deep basinal fluids, and potentially overlying seawater onto the crests of deeply buried salt diapirs. The mobilized fluids fuel methanogenic archaea locally enhancing the deep biosphere. The resulting elevated biogenic methane production, alongside the upward heat-driven fluid transport, represents a previously unrecognized mechanism of cold seep formation and regulation.

2.
Clin Microbiol Rev ; 37(1): e0010322, 2024 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-38095438

RESUMEN

Wastewater-based surveillance (WBS) has undergone dramatic advancement in the context of the coronavirus disease 2019 (COVID-19) pandemic. The power and potential of this platform technology were rapidly realized when it became evident that not only did WBS-measured SARS-CoV-2 RNA correlate strongly with COVID-19 clinical disease within monitored populations but also, in fact, it functioned as a leading indicator. Teams from across the globe rapidly innovated novel approaches by which wastewater could be collected from diverse sewersheds ranging from wastewater treatment plants (enabling community-level surveillance) to more granular locations including individual neighborhoods and high-risk buildings such as long-term care facilities (LTCF). Efficient processes enabled SARS-CoV-2 RNA extraction and concentration from the highly dilute wastewater matrix. Molecular and genomic tools to identify, quantify, and characterize SARS-CoV-2 and its various variants were adapted from clinical programs and applied to these mixed environmental systems. Novel data-sharing tools allowed this information to be mobilized and made immediately available to public health and government decision-makers and even the public, enabling evidence-informed decision-making based on local disease dynamics. WBS has since been recognized as a tool of transformative potential, providing near-real-time cost-effective, objective, comprehensive, and inclusive data on the changing prevalence of measured analytes across space and time in populations. However, as a consequence of rapid innovation from hundreds of teams simultaneously, tremendous heterogeneity currently exists in the SARS-CoV-2 WBS literature. This manuscript provides a state-of-the-art review of WBS as established with SARS-CoV-2 and details the current work underway expanding its scope to other infectious disease targets.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiología , Monitoreo Epidemiológico Basado en Aguas Residuales , ARN Viral , Aguas Residuales
3.
Nat Mater ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38951650

RESUMEN

The voltage penalty driving water dissociation (WD) at high current density is a major obstacle in the commercialization of bipolar membrane (BPM) technology for energy devices. Here we show that three materials descriptors, that is, electrical conductivity, microscopic surface area and (nominal) surface-hydroxyl coverage, effectively control the kinetics of WD in BPMs. Using these descriptors and optimizing mass loading, we design new earth-abundant WD catalysts based on nanoparticle SnO2 synthesized at low temperature with high conductivity and hydroxyl coverage. These catalysts exhibit exceptional performance in a BPM electrolyser with low WD overvoltage (ηwd) of 100 ± 20 mV at 1.0 A cm-2. The new catalyst works equivalently well with hydrocarbon proton-exchange layers as it does with fluorocarbon-based Nafion, thus providing pathways to commercializing advanced BPMs for a broad array of electrolysis, fuel-cell and electrodialysis applications.

4.
Mol Psychiatry ; 28(9): 3930-3942, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37845497

RESUMEN

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.


Asunto(s)
Cocaína , Neuronas Dopaminérgicas , Ratas , Animales , Neuronas Dopaminérgicas/metabolismo , Área Tegmental Ventral/metabolismo , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/genética , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/metabolismo , Regulación hacia Arriba , Cocaína/farmacología , ARN Mensajero
5.
Stat Med ; 43(6): 1153-1169, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38221776

RESUMEN

Wastewater-based surveillance has become an important tool for research groups and public health agencies investigating and monitoring the COVID-19 pandemic and other public health emergencies including other pathogens and drug abuse. While there is an emerging body of evidence exploring the possibility of predicting COVID-19 infections from wastewater signals, there remain significant challenges for statistical modeling. Longitudinal observations of viral copies in municipal wastewater can be influenced by noisy datasets and missing values with irregular and sparse samplings. We propose an integrative Bayesian framework to predict daily positive cases from weekly wastewater observations with missing values via functional data analysis techniques. In a unified procedure, the proposed analysis models severe acute respiratory syndrome coronavirus-2 RNA wastewater signals as a realization of a smooth process with error and combines the smooth process with COVID-19 cases to evaluate the prediction of positive cases. We demonstrate that the proposed framework can achieve these objectives with high predictive accuracies through simulated and observed real data.


Asunto(s)
COVID-19 , Humanos , Teorema de Bayes , COVID-19/epidemiología , Pandemias , ARN Viral/genética , SARS-CoV-2/genética , Aguas Residuales
6.
Surg Endosc ; 38(2): 931-941, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37910247

RESUMEN

BACKGROUND: Laparoscopic cholecystectomy with common bile duct exploration (LCBDE) is equivalent in safety and efficacy to endoscopic retrograde cholangiopancreatography (ERCP) plus laparoscopic cholecystectomy (LC) while decreasing number of procedures and length of stay (LOS). Despite these advantages LCBDE is infrequently utilized. We hypothesized that formal, simulation-based training in LCBDE would result in increased utilization and improve patient outcomes across participating institutions. METHODS: Data was obtained from an on-going multi-center study in which simulator-based transcystic LCBDE training curricula were instituted for attending surgeons and residents. A 2-year retrospective review of LCBDE utilization prior to LCBDE training was compared to utilization up to 2 years after initiation of training. Patient outcomes were analyzed between LCBDE strategy and ERCP strategy groups using χ2, t tests, and Wilcoxon rank tests. RESULTS: A total of 50 attendings and 70 residents trained in LCBDE since November 2020. Initial LCBDE utilization rate ranged from 0.74 to 4.5%, and increased among all institutions after training, ranging from 9.3 to 41.4% of cases. There were 393 choledocholithiasis patients analyzed using LCBDE (N = 129) and ERCP (N = 264) strategies. The LCBDE group had shorter median LOS (3 days vs. 4 days, p < 0.0001). No significant differences in readmission rates between LCBDE and ERCP groups (4.7% vs. 7.2%, p = 0.33), or in post-procedure pancreatitis (0.8% v 0.8%, p > 0.98). In comparison to LCBDE, the ERCP group had higher rates of bile duct injury (0% v 3.8%, p = 0.034) and fluid collections requiring intervention (0.8% v 6.8%, p < 0.009) secondary to cholecystectomy complications. Laparoscopic antegrade balloon sphincteroplasty had the highest technical success rate (87%), followed by choledochoscopic techniques (64%). CONCLUSION: Simulator-based training in LCBDE results in higher utilization rates, shorter LOS, and comparable safety to ERCP plus cholecystectomy. Therefore, implementation of LCBDE training is strongly recommended to optimize healthcare utilization and management of patients with choledocholithiasis.


Asunto(s)
Colecistectomía Laparoscópica , Coledocolitiasis , Laparoscopía , Humanos , Coledocolitiasis/cirugía , Conducto Colédoco/cirugía , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colecistectomía Laparoscópica/métodos , Estudios Retrospectivos , Tiempo de Internación
7.
Pediatr Dermatol ; 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38621697

RESUMEN

Several dermatologic concerns are known to disproportionally affect transgender and gender-diverse (TGD) adults, but little is known about dermatologic conditions in TGD youth. This study assesses the prevalence of acne, androgenic alopecia, scarring from gender-affirming procedures, and eczema in pediatric TGD patients seen at Boston Children's Hospital between April 2021 and April 2022. The results demonstrate that, for TGD youth, the studied dermatologic concerns are common, referral rates to dermatology are low, and acne is significantly associated with testosterone use. Future studies should examine additional dermatologic concerns and barriers to accessing dermatologic care for this historically underserved population.

8.
J Acoust Soc Am ; 155(6): 3983-3994, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38934563

RESUMEN

Advancing age is associated with decreased sensitivity to temporal cues in word segments, particularly when target words follow non-informative carrier sentences or are spectrally degraded (e.g., vocoded to simulate cochlear-implant stimulation). This study investigated whether age, carrier sentences, and spectral degradation interacted to cause undue difficulty in processing speech temporal cues. Younger and older adults with normal hearing performed phonemic categorization tasks on two continua: a Buy/Pie contrast with voice onset time changes for the word-initial stop and a Dish/Ditch contrast with silent interval changes preceding the word-final fricative. Target words were presented in isolation or after non-informative carrier sentences, and were unprocessed or degraded via sinewave vocoding (2, 4, and 8 channels). Older listeners exhibited reduced sensitivity to both temporal cues compared to younger listeners. For the Buy/Pie contrast, age, carrier sentence, and spectral degradation interacted such that the largest age effects were seen for unprocessed words in the carrier sentence condition. This pattern differed from the Dish/Ditch contrast, where reducing spectral resolution exaggerated age effects, but introducing carrier sentences largely left the patterns unchanged. These results suggest that certain temporal cues are particularly susceptible to aging when placed in sentences, likely contributing to the difficulties of older cochlear-implant users in everyday environments.


Asunto(s)
Estimulación Acústica , Envejecimiento , Señales (Psicología) , Percepción del Habla , Humanos , Percepción del Habla/fisiología , Anciano , Adulto Joven , Adulto , Factores de Edad , Envejecimiento/psicología , Envejecimiento/fisiología , Persona de Mediana Edad , Factores de Tiempo , Femenino , Masculino , Acústica del Lenguaje , Fonética , Audiometría del Habla , Anciano de 80 o más Años , Adolescente , Inteligibilidad del Habla
9.
J Am Pharm Assoc (2003) ; 64(1): 301-306, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37844734

RESUMEN

BACKGROUND AND OBJECTIVE: Unintended pregnancies occur more frequently in college students and negatively affect health outcomes and educational attainment. This study examined access to on-campus contraceptives at all 4-year colleges and universities in North Carolina (NC). METHODS: This institutional review board-exempt study evaluated availability of on-campus contraceptives including condoms; hormonal contraceptives including pills, patches, and vaginal rings; medroxyprogesterone injections; implants; intrauterine devices; and emergency contraception via website review. Institutions were stratified by characteristics including size, location, type (e.g., public, private, religious affiliation, historically black colleges and universities, women's colleges), and presence of a student health pharmacy. Comparisons were made using chi-square test or Fisher's exact test. RESULTS: Fifty-four 4-year colleges and universities were identified. A plurality or the majority of schools were considered small (41%) and urban (48%) and had a religious affiliation (61%). Thirty-three percent of colleges and universities had an on-campus pharmacy. The most frequent contraceptives offered were condoms (43%), oral contraceptives (33%), and medroxyprogesterone injections (22%). Emergency contraception was available at approximately one-third of colleges and universities. Six percent of institutions provided a full range of contraceptive methods. Contraceptives were offered more frequently at large, public, urban institutions, whereas religious institutions and smaller institutions were less likely to offer contraceptives. CONCLUSION: Access to on-campus contraception for college students in NC is lacking, and the vast majority of institutions did not provide a full range of contraceptives. Policy measures, such as enhancing reproductive health services at student health centers or increasing contraception availability directly through pharmacies, are needed to improve access for college students.


Asunto(s)
Anticoncepción , Anticonceptivos , Embarazo , Humanos , Femenino , Universidades , North Carolina , Anticoncepción/métodos , Medroxiprogesterona
10.
J Gerontol Nurs ; 50(3): 13-17, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38417077

RESUMEN

PURPOSE: Research demonstrates that aging in place is the goal of most adults aged >50 years. Unfortunately, multiple barriers to aging in place continue to exist, especially for vulnerable populations. Achieving this goal will require innovative nurse-led models of care and new policies for RN reimbursement. The current article describes a nurse-led clinic implemented in one community. METHOD: Using an evidence-based nurse-led model of care, a team of university faculty, students, and a family nurse practitioner designed and implemented a nurse-led clinic for a religious community in the Pacific Northwest. RESULTS: Today, the nurse-led clinic offers care coordination and primary care to support aging in place and is one example of a nurse-led model well-positioned to address the aging in place needs of vulnerable populations. CONCLUSION: Replication and sustainability of this nurse-led model requires sweeping policy change, including consideration of requiring all nurses to attain a National Provider Identification number to expand RN reimbursement and ultimately increase access to care. [Journal of Gerontological Nursing, 50(3), 13-17.].


Asunto(s)
Enfermería Geriátrica , Enfermeras y Enfermeros , Humanos , Anciano , Vida Independiente , Rol de la Enfermera , Estudiantes
11.
J Neurosci ; 42(47): 8870-8880, 2022 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-36257687

RESUMEN

Aging is the greatest risk factor for the development of neurodegenerative diseases, yet we still do not understand how the aging process leads to pathologic vulnerability. The research community has relied heavily on mouse models, but the considerable anatomic, physiological, and cognitive differences between mice and humans limit their translational relevance. Ultimately, these barriers necessitate the development of novel aging models. As a nonhuman primate (NHP), the common marmoset (Callithrix jacchus) shares many features in common with humans and yet has a significantly shorter lifespan (10 years) than other primates, making it ideally suited to longitudinal studies of aging. Our objective was to evaluate the marmoset as a model of age-related cognitive impairment. To do this, we used the Delayed Recognition Span Task (DRST) to characterize age-related changes in working memory capacity in a cohort of sixteen marmosets, of both sexes, varying in age from young adult to geriatric. These monkeys performed thousands of trials over periods of time ranging up to 50% of their adult lifespan. To our knowledge, this represents the most thorough cognitive profiling of any marmoset aging study conducted to date. By analyzing individual learning curves, we found that aged animals exhibited delayed onset of learning, slowed learning rate after onset, and decreased asymptotic working memory performance. These findings are not accounted for by age-related impairments in motor speed and motivation. This work firmly establishes the marmoset as a model of age-related cognitive impairment.SIGNIFICANCE STATEMENT Understanding the normal aging process is fundamental to identifying therapeutics for neurodegenerative diseases for which aging is the biggest risk factor. Historically, the aging field has relied on animal models that differ markedly from humans, constraining translatability. Here, we firmly establish a short-lived nonhuman primate (NHP), the common marmoset, as a key model of age-related cognitive impairment. We demonstrate, through continuous testing over a substantial portion of the adult marmoset lifespan, that aging is associated with both impaired learning and working memory capacity, unaccounted for by age-related changes in motor speed and motivation. Characterizing individual cognitive aging trajectories reveals inherent heterogeneity, which could lead to earlier identification of the onset of impairment, and extended timelines during which therapeutics are effective.


Asunto(s)
Callithrix , Enfermedades Neurodegenerativas , Humanos , Masculino , Femenino , Ratones , Animales , Anciano , Callithrix/fisiología , Memoria a Corto Plazo , Trastornos de la Memoria , Modelos Animales de Enfermedad
12.
Crit Care Med ; 51(12): 1706-1715, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37607081

RESUMEN

OBJECTIVES: Impaired nitric oxide (NO) bioavailability may contribute to microvascular dysfunction in sepsis. Excessive plasma NO consumption has been attributed to scavenging by circulating cell-free hemoglobin. This may be a mechanism for NO deficiency in sepsis and critical illness. We hypothesized that plasma NO consumption is high in critically ill patients, particularly those with sepsis, acute respiratory distress syndrome (ARDS), shock, and in hospital nonsurvivors. We further hypothesized that plasma NO consumption is correlated with plasma cell-free hemoglobin concentration. DESIGN: Retrospective cohort study. SETTING: Adult ICUs of an academic medical center. PATIENTS AND SUBJECTS: Three hundred sixty-two critically ill patients and 46 healthy control subjects. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma NO consumption was measured using reductive chemiluminescence and cell-free hemoglobin was measured with a colorimetric assay. Mean (95% CI) plasma NO consumption (µM) was higher in critically ill patients versus healthy control subjects (3.9 [3.7-4.1] vs 2.1 [1.8-2.5]), septic versus nonseptic patients (4.1 [3.8-4.3] vs 3.6 [3.3-3.8]), ARDS versus non-ARDS patients (4.4 [4.0-4.9] vs 3.7 [3.6-3.9]), shock vs nonshock patients (4.4 [4.0-4.8] vs 3.6 [3.4-3.8]), and hospital nonsurvivors versus survivors (5.3 [4.4-6.4] vs 3.7 [3.6-3.9]). These relationships remained significant in multivariable analyses. Plasma cell-free hemoglobin was weakly correlated with plasma NO consumption. CONCLUSIONS: Plasma NO consumption is elevated in critically ill patients and independently associated with sepsis, ARDS, shock, and hospital death. These data suggest that excessive intravascular NO scavenging characterizes sepsis and adverse outcomes of critical illness.


Asunto(s)
Síndrome de Dificultad Respiratoria , Sepsis , Adulto , Humanos , Enfermedad Crítica , Óxido Nítrico , Estudios Retrospectivos , Hemoglobinas
13.
J Med Virol ; 95(2): e28442, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36579780

RESUMEN

Wastewater-based SARS-CoV-2 surveillance enables unbiased and comprehensive monitoring of defined sewersheds. We performed real-time monitoring of hospital wastewater that differentiated Delta and Omicron variants within total SARS-CoV-2-RNA, enabling correlation to COVID-19 cases from three tertiary-care facilities with >2100 inpatient beds in Calgary, Canada. RNA was extracted from hospital wastewater between August/2021 and January/2022, and SARS-CoV-2 quantified using RT-qPCR. Assays targeting R203M and R203K/G204R established the proportional abundance of Delta and Omicron, respectively. Total and variant-specific SARS-CoV-2 in wastewater was compared to data for variant specific COVID-19 hospitalizations, hospital-acquired infections, and outbreaks. Ninety-six percent (188/196) of wastewater samples were SARS-CoV-2 positive. Total SARS-CoV-2 RNA levels in wastewater increased in tandem with total prevalent cases (Delta plus Omicron). Variant-specific assessments showed this increase to be mainly driven by Omicron. Hospital-acquired cases of COVID-19 were associated with large spikes in wastewater SARS-CoV-2 and levels were significantly increased during outbreaks relative to nonoutbreak periods for total SARS-CoV2, Delta and Omicron. SARS-CoV-2 in hospital wastewater was significantly higher during the Omicron-wave irrespective of outbreaks. Wastewater-based monitoring of SARS-CoV-2 and its variants represents a novel tool for passive COVID-19 infection surveillance, case identification, containment, and potentially to mitigate viral spread in hospitals.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , ARN Viral , Aguas Residuales , Centros de Atención Terciaria , Brotes de Enfermedades
14.
Mol Psychiatry ; 27(1): 640-651, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34145393

RESUMEN

The neurobiology of addiction has been an intense topic of investigation for more than 50 years. Over this time, technological innovation in methods for studying brain function rapidly progressed, leading to increasingly sophisticated experimental approaches. To understand how specific brain regions, cell types, and circuits are affected by drugs of abuse and drive behaviors characteristic of addiction, it is necessary both to observe and manipulate neural activity in addiction-related behavioral paradigms. In pursuit of this goal, there have been several key technological advancements in in vivo imaging and neural circuit modulation in recent years, which have shed light on the cellular and circuit mechanisms of addiction. Here we discuss some of these key technologies, including circuit modulation with optogenetics, in vivo imaging with miniaturized single-photon microscopy (miniscope) and fiber photometry, and how the application of these technologies has garnered novel insights into the neurobiology of addiction.


Asunto(s)
Neurobiología , Optogenética , Encéfalo , Optogenética/métodos
15.
Clin Transplant ; 37(4): e14893, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36571802

RESUMEN

Kidney transplant recipients carrying the CYP3A5*1 allele have lower tacrolimus troughs, and higher dose requirements compared to those with the CYP3A5*3/*3 genotype. However, data on the effect of CYP3A5 alleles on post-transplant tacrolimus management are lacking. The effect of CYP3A5 metabolism phenotypes on the number of tacrolimus dose adjustments and troughs in the first 6 months post-transplant was evaluated in 78 recipients (64% Caucasians). Time to first therapeutic concentration, percentage of time in therapeutic range (TTR), and estimated glomerular filtration rate (eGFR) were also evaluated. Fifty-five kidney transplant recipients were CYP3A5 poor metabolizers (PM), 17 were intermediate metabolizers (IM), and 6 were extensive metabolizers (EM). Compared to PMs, EMs/IMs had significantly more dose adjustments (6.1 vs. 8.1, p = .015). Overall, 33.82% of trough measurements resulted in a dose change. There was no difference in the number of tacrolimus trough measurements between PMs and EM/IMs. The total daily tacrolimus dose requirements were higher in EMs and IMs compared to PMs (<.001). TTR was ∼50% in the PMs and EMs/IMs groups. CYP3A5 EM/IM metabolizers have more tacrolimus dose changes and higher dose requirements which increases clinical management complexity. Larger studies are needed to assess the cost and benefits of including genotyping data to improve clinical management.


Asunto(s)
Trasplante de Riñón , Tacrolimus , Humanos , Tacrolimus/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Riñón/métodos , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Genotipo , Receptores de Trasplantes , Polimorfismo de Nucleótido Simple
16.
Proc Natl Acad Sci U S A ; 117(20): 11029-11037, 2020 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-32354993

RESUMEN

Marine cold seeps transmit fluids between the subseafloor and seafloor biospheres through upward migration of hydrocarbons that originate in deep sediment layers. It remains unclear how geofluids influence the composition of the seabed microbiome and if they transport deep subsurface life up to the surface. Here we analyzed 172 marine surficial sediments from the deep-water Eastern Gulf of Mexico to assess whether hydrocarbon fluid migration is a mechanism for upward microbial dispersal. While 132 of these sediments contained migrated liquid hydrocarbons, evidence of continuous advective transport of thermogenic alkane gases was observed in 11 sediments. Gas seeps harbored distinct microbial communities featuring bacteria and archaea that are well-known inhabitants of deep biosphere sediments. Specifically, 25 distinct sequence variants within the uncultivated bacterial phyla Atribacteria and Aminicenantes and the archaeal order Thermoprofundales occurred in significantly greater relative sequence abundance along with well-known seep-colonizing members of the bacterial genus Sulfurovum, in the gas-positive sediments. Metabolic predictions guided by metagenome-assembled genomes suggested these organisms are anaerobic heterotrophs capable of nonrespiratory breakdown of organic matter, likely enabling them to inhabit energy-limited deep subseafloor ecosystems. These results point to petroleum geofluids as a vector for the advection-assisted upward dispersal of deep biosphere microbes from subsurface to surface environments, shaping the microbiome of cold seep sediments and providing a general mechanism for the maintenance of microbial diversity in the deep sea.


Asunto(s)
Sedimentos Geológicos/microbiología , Hidrocarburos/metabolismo , Microbiota/fisiología , Agua de Mar/microbiología , Alcanos/metabolismo , Archaea/clasificación , Archaea/metabolismo , Bacterias/clasificación , Bacterias/metabolismo , Biodiversidad , Sedimentos Geológicos/química , Golfo de México , Metagenoma , Metagenómica , Petróleo/metabolismo , Filogenia , ARN Ribosómico 16S/genética , Agua de Mar/química
17.
J Am Soc Nephrol ; 33(8): 1546-1567, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35906089

RESUMEN

BACKGROUND: Maintenance of the kidney filtration barrier requires coordinated interactions between podocytes and the underlying glomerular basement membrane (GBM). GBM ligands bind podocyte integrins, which triggers actin-based signaling events critical for adhesion. Nck1/2 adaptors have emerged as essential regulators of podocyte cytoskeletal dynamics. However, the precise signaling mechanisms mediated by Nck1/2 adaptors in podocytes remain to be fully elucidated. METHODS: We generated podocytes deficient in Nck1 and Nck2 and used transcriptomic approaches to profile expression differences. Proteomic techniques identified specific binding partners for Nck1 and Nck2 in podocytes. We used cultured podocytes and mice deficient in Nck1 and/or Nck2, along with podocyte injury models, to comprehensively verify our findings. RESULTS: Compound loss of Nck1/2 altered expression of genes involved in actin binding, cell adhesion, and extracellular matrix composition. Accordingly, Nck1/2-deficient podocytes showed defects in actin organization and cell adhesion in vitro, with podocyte detachment and altered GBM morphology present in vivo. We identified distinct interactomes for Nck1 and Nck2 and uncovered a mechanism by which Nck1 and Nck2 cooperate to regulate actin bundling at focal adhesions via α actinin-4. Furthermore, loss of Nck1 or Nck2 resulted in increased matrix deposition in vivo, with more prominent defects in Nck2-deficient mice, consistent with enhanced susceptibility to podocyte injury. CONCLUSION: These findings reveal distinct, yet complementary, roles for Nck proteins in regulating podocyte adhesion, controlling GBM composition, and sustaining filtration barrier integrity.


Asunto(s)
Podocitos , Actinina/metabolismo , Actinas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Membrana Basal Glomerular/metabolismo , Ratones , Proteínas Oncogénicas/metabolismo , Podocitos/metabolismo , Proteómica
18.
J Gerontol Nurs ; 49(12): 11-16, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38015146

RESUMEN

An increase in demand for health care services for older adults is being negatively impacted by lack of a sufficient nursing workforce with competence in home- and community-based services (HCBS). The current article examines the unique challenges and opportunities in caring for older adults in HCBS settings, outlines the core competencies nurses must possess to provide this care, and proposes strategies to leverage legislative and regulatory initiatives to incorporate these competencies into nursing education and practice. Examining the American Association of Colleges of Nursing's Essentials Competencies through the HCBS lens, it is an ideal time to create a roadmap for nurses in practice, policy, and education to shape the health care workforce to meet the needs of a diverse and vulnerable population: older adults who depend on home- and community-based care for maintaining or improving their health outcomes and overall quality of life. [Journal of Gerontological Nursing, 49(12), 11-16.].


Asunto(s)
Enfermería Geriátrica , Personal de Enfermería , Humanos , Anciano , Servicios de Salud Comunitaria , Calidad de Vida , Personal de Salud
19.
Angew Chem Int Ed Engl ; 62(18): e202218854, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-36877590

RESUMEN

Although many porous materials, including metal-organic frameworks (MOFs), have been reported to selectively adsorb C2 H2 in C2 H2 /CO2 separation processes, CO2 -selective sorbents are much less common. Here, we report the remarkable performance of MFU-4 (Zn5 Cl4 (bbta)3 , bbta=benzo-1,2,4,5-bistriazolate) toward inverse CO2 /C2 H2 separation. The MOF facilitates kinetic separation of CO2 from C2 H2 , enabling the generation of high purity C2 H2 (>98 %) with good productivity in dynamic breakthrough experiments. Adsorption kinetics measurements and computational studies show C2 H2 is excluded from MFU-4 by narrow pore windows formed by Zn-Cl groups. Postsynthetic F- /Cl- ligand exchange was used to synthesize an analogue (MFU-4-F) with expanded pore apertures, resulting in equilibrium C2 H2 /CO2 separation with reversed selectivity compared to MFU-4. MFU-4-F also exhibits a remarkably high C2 H2 adsorption capacity (6.7 mmol g-1 ), allowing fuel grade C2 H2 (98 % purity) to be harvested from C2 H2 /CO2 mixtures by room temperature desorption.

20.
Emerg Infect Dis ; 28(9): 1770-1776, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35867051

RESUMEN

Wastewater monitoring of SARS-CoV-2 enables early detection and monitoring of the COVID-19 disease burden in communities and can track specific variants of concern. We determined proportions of the Omicron and Delta variants across 30 municipalities covering >75% of the province of Alberta (population 4.5 million), Canada, during November 2021-January 2022. Larger cities Calgary and Edmonton exhibited more rapid emergence of Omicron than did smaller and more remote municipalities. Notable exceptions were Banff, a small international resort town, and Fort McMurray, a medium-sized northern community that has many workers who fly in and out regularly. The integrated wastewater signal revealed that the Omicron variant represented close to 100% of SARS-CoV-2 burden by late December, before the peak in newly diagnosed clinical cases throughout Alberta in mid-January. These findings demonstrate that wastewater monitoring offers early and reliable population-level results for establishing the extent and spread of SARS-CoV-2 variants.


Asunto(s)
COVID-19 , SARS-CoV-2 , Alberta/epidemiología , COVID-19/epidemiología , Humanos , SARS-CoV-2/genética , Aguas Residuales
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