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1.
J Craniofac Surg ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38838366

ABSTRACT

INTRODUCTION: Somaliland is an autonomously run country that is not internationally recognized. As such, it has been largely excluded by global health development programs despite being the world's fourth poorest country. The purpose of this study was to provide the first known description of the pattern and clinical profile of patients with cleft lip and palate from this nation. METHODS: The authors performed a retrospective chart review on all patients who received cleft lip and palate repair by a single surgeon in 40 separate surgical camps at Edna Adan University Hospital in Hargeisa, Somaliland, between 2011 and 2024. Information regarding patient age, sex, cleft etiology, surgical management, and home location was retrieved. Descriptive statistical analysis was performed. RESULTS: A total of 767 patients (495 male, 64.5%) received 787 surgical procedures. The average age of primary surgery was 73.7 months. The most common chief complaint was left cleft lip with cleft palate (316, 41.2%). Males received primary surgery 19.2 months later than did females (73.7 and 54.6 mo, respectively, P<0.001). Patients residing in Hargeisa received their initial procedure an average of 17.8 months younger than those who lived elsewhere in Somaliland (62.9 and 80.7 mo, respectively, P=0.004). CONCLUSIONS: In this severely economically depressed region, patients received treatment at ages that lagged far beyond recommended guidelines. Our finding of earlier treatment for females than males is rare in the literature and likely relates to cultural sex expectations. Patients from rural locations were especially vulnerable to receiving delayed treatment. Further efforts to decrease the burden of craniofacial deformities in Somaliland should be pursued in earnest.

2.
J Craniofac Surg ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830020

ABSTRACT

INTRODUCTION: Most studies on the treatment of cleft lip and palate (CLP) in low-income and middle-income countries have reported on the experience of urban centers or surgical mission trips to rural locations. There is a paucity of literature on the experience of local teams providing orofacial cleft surgery in rural Sub-Saharan Africa. This study reports the efficacy and cost-effectiveness of cleft surgery performed by an all-local team in rural Kenya. METHODS: A retrospective chart review was performed on all patients who received CLP repair at Kapsowar Hospital between 2011 and 2023. Information regarding patient age, sex, cleft etiology, surgical management, and home location was retrieved. For the most recent year of study (2023), the authors performed a financial audit of all costs related to the performance of unilateral cleft lip surgery. Descriptive statistics were performed. RESULTS: The authors identified 381 CLP surgeries performed on 311 patients (197 male, 63.3%). The most common etiology of the cleft was left unilateral (28.3%). The average age of primary lip repair decreased from 46.3 months in 2008 to 2009 to 20.2 months in 2022 to 2023 (P<0.001). The average age of primary cleft palate repair decreased from 38.0 months in 2008 to 2009 to 25.3 months in 2022 to 2023 (P<0.001). Patients traveled from 23 districts to receive treatment. Age of treatment was not different when distinguished by sex, county poverty level, or travel time from the hospital. The total costs associated with cleft lip repair was $201.6. CONCLUSIONS: Adequately staffed hospitals in rural locations can meaningfully address a regional CLP backlog more cost-effectively than surgical mission trips.

3.
J Hosp Infect ; 150: 1-8, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38723903

ABSTRACT

BACKGROUND: Healthcare-associated infections (HAIs) remain a global health challenge, and have elevated rates in Sub-Saharan Africa. HAIs impact patients and their families by causing illness, prolonged hospital stay, potential disability, excess costs and, sometimes, death. The costs of HAIs are increasing due to spreading antimicrobial resistance. A major risk factor for HAIs is lack of water, sanitation and hygiene (WASH); environmental cleaning and healthcare waste management. In Sub-Saharan Africa, these services are lacking in at least 50% of healthcare facilities. AIM: To estimate the costs associated with HAIs at national level in 14 countries in Sub-Saharan Africa. METHODS: Economic methodologies were employed to estimate the medical costs, productivity losses and value of premature death from HAIs, drawing on national statistics and published studies to populate the economic model. RESULTS: In 2022, the number of HAIs was estimated at 4.8 million, resulting in 500,000 deaths. Health-related economic losses amounted to US$13 billion per year, equivalent to 1.14% of combined gross domestic product and US$15.7 per capita. Healthcare costs were US$500 per HAI, and represented 5.6% of total health expenditure. The costs of providing basic WASH were US$0.91 per capita, which, if they reduced HAIs by 50%, would result in benefit-cost ratios of 1.6 (financial healthcare savings alone) and 8.6 (all economic benefits). CONCLUSION: HAIs have a major health and economic burden on African societies, and a significant proportion can be prevented. It is critical that health policy makers and practitioners dedicate policy space, resources and training to address HAIs.

4.
Nat Methods ; 21(6): 983-993, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38724692

ABSTRACT

The inability to scalably and precisely measure the activity of developmental cis-regulatory elements (CREs) in multicellular systems is a bottleneck in genomics. Here we develop a dual RNA cassette that decouples the detection and quantification tasks inherent to multiplex single-cell reporter assays. The resulting measurement of reporter expression is accurate over multiple orders of magnitude, with a precision approaching the limit set by Poisson counting noise. Together with RNA barcode stabilization via circularization, these scalable single-cell quantitative expression reporters provide high-contrast readouts, analogous to classic in situ assays but entirely from sequencing. Screening >200 regions of accessible chromatin in a multicellular in vitro model of early mammalian development, we identify 13 (8 previously uncharacterized) autonomous and cell-type-specific developmental CREs. We further demonstrate that chimeric CRE pairs generate cognate two-cell-type activity profiles and assess gain- and loss-of-function multicellular expression phenotypes from CRE variants with perturbed transcription factor binding sites. Single-cell quantitative expression reporters can be applied in developmental and multicellular systems to quantitatively characterize native, perturbed and synthetic CREs at scale, with high sensitivity and at single-cell resolution.


Subject(s)
Gene Expression Regulation, Developmental , Single-Cell Analysis , Single-Cell Analysis/methods , Animals , Mice , Genes, Reporter , Regulatory Sequences, Nucleic Acid , Humans , Transcription Factors/genetics , Transcription Factors/metabolism , Chromatin/genetics , Chromatin/metabolism , Regulatory Elements, Transcriptional , Gene Expression Profiling/methods
5.
J Leukoc Biol ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38809773

ABSTRACT

Neutrophils release extracellular vesicles (EVs) and some subsets of neutrophil-derived EVs are procoagulant. In response to S. aureus, neutrophils produce EVs that associate electrostatically with neutrophil extracellular traps (NETs). DNA in NETs is procoagulant, but whether neutrophil EVs produced during bacterial challenge have similar activity is unknown. Given that EV activity is agonist- and cell-type dependent and coagulation contributes to sepsis, we hypothesized that sepsis-causing bacteria increase production of neutrophil-derived EVs, as well as EV-associated DNA, and intact EVs and DNA cause coagulation. We recovered EVs from neutrophils challenged with S. aureus (SA), S. epidermidis (SE), E. coli (EC), and P. aeruginosa (PA), and measured associated DNA and procoagulant activity. EVs from SA-challenged neutrophils (SA-EVs), which were previously characterized, displayed dose-dependent procoagulant activity as measured by thrombin generation (TG) in platelet-poor plasma. EV lysis and DNase treatment reduced TG by 90% and 37%, respectively. SE, EC, and PA also increased EV production and EV-associated extracellular DNA, and these EVs were also procoagulant. Compared to spontaneously released EVs, which demonstrated some ability to amplify Factor XII-dependent coagulation in the presence of an activator, only EVs produced in response to bacteria could initiate the pathway. SA-EVs and SE-EVs had more surface-associated DNA than EC-EVs and PA-EVs, and SA-EVs and SE-EVs contributed to initiation and amplification of TG in a DNA-dependent manner. However, DNA on EC- or PA-EVs played no role, suggesting that neutrophils release procoagulant EVs which can activate the coagulation cascade through both DNA-dependent and independent mechanisms.

6.
Sci Rep ; 14(1): 6388, 2024 03 16.
Article in English | MEDLINE | ID: mdl-38493209

ABSTRACT

The nuclear lamina serves important functions in the nucleus, providing structural support to the nuclear envelope and contributing to chromatin organization. The primary proteins that constitute the lamina are nuclear lamins whose functions are impacted by post-translational modifications, including phosphorylation by protein kinase C (PKC). While PKC-mediated lamin phosphorylation is important for nuclear envelope breakdown during mitosis, less is known about interphase roles for PKC in regulating nuclear structure. Here we show that overexpression of PKC ß, but not PKC α, increases the Lamin A/C mobile fraction in the nuclear envelope in HeLa cells without changing the overall structure of Lamin A/C and Lamin B1 within the nuclear lamina. Conversely, knockdown of PKC ß, but not PKC α, reduces the Lamin A/C mobile fraction. Thus, we demonstrate an isoform-specific role for PKC in regulating interphase Lamin A/C dynamics outside of mitosis.


Subject(s)
Lamin Type A , Nuclear Proteins , Humans , Lamin Type A/metabolism , HeLa Cells , Phosphorylation , Nuclear Proteins/metabolism , Lamin Type B/metabolism , Lamins/metabolism , Nuclear Envelope/metabolism , Protein Kinase C/metabolism , Protein Processing, Post-Translational
7.
J Environ Manage ; 345: 118878, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37659363

ABSTRACT

Light pollution is a global phenomenon where anthropogenic light sources continue to grow unabated, affecting both social and ecological systems. This is leaving parks and protected areas as some of the last vestiges of naturally dark environments for protecting views of the night sky. Yet, even parks and protected areas have outdoor lighting. Alternative lighting practices are needed to reduce or prevent light pollution from within parks. However, making parks darker may not be desirable for some visitors if they believe it will reduce navigability, safety, or restrict how they recreate (e.g., requiring the use of red-light flashlights after dark and before dawn). How visitors will respond to alternative lighting practices that park managers can implement is still unknown. We used an on-site intercept survey at nine state and national park units in Utah, U.S., to investigate nighttime visitors' support or opposition to management actions to protect night sky quality and their interest in learning about topics related to night skies. Further, this study also segmented visitors into two groups: those 'dependent' on the dark sky as a resource and those whose activities did not depend on a dark sky. Defining what a 'dark sky dependent' visitor is, which has yet to be done in the literature, is a fundamental step to furthering night sky research and management efforts. Across nine parks and protected areas, 62% of nighttime visitors participated in dark sky dependent activities. Findings indicate broad support for management actions designed to improve night sky quality, with between 74% and 89% of all visitors supporting seven different management actions. There was stronger support from dark sky dependent visitors for some elements of alternative lighting practices, but there was still strong support for those who do not participate in dark sky dependent outdoor recreation. Additionally, between 57% and 75% of visitors were interested in learning more about topics related to night skies. This research indicates most visitors would welcome actions to preserve the quality of the rapidly dwindling naturally dark experiences offered by parks and protected areas.


Subject(s)
Learning , Parks, Recreational , Dissent and Disputes , Ecosystem , Light
8.
Invest Ophthalmol Vis Sci ; 64(5): 17, 2023 05 01.
Article in English | MEDLINE | ID: mdl-37204785

ABSTRACT

Purpose: Plasmalogens (Plgs) are highly abundant lipids in the retina, and their deficiency leads to severe abnormalities during eye development. The first acylation step in the synthesis of Plgs is catalyzed by the enzyme glyceronephosphate O-acyltransferase (GNPAT), which is also known as dihydroxyacetone phosphate-acyltransferase (EC 2.3.1.42). GNPAT deficiency produces rhizomelic chondrodysplasia punctata type 2, a genetic disorder associated with developmental ocular defects. Despite the relevance of retinal Plgs, our knowledge of the mechanisms that regulate their synthesis, and the role of GNPAT during eye development is limited. Methods: Using the Xenopus laevis model organism, we characterized by in situ hybridization the expression pattern of gnpat and compared it to glycerol 3-phosphate acyltransferase mitochondrial (gpam or gpat1) during eye neurogenesis, lamination, and morphogenesis. The Xenopus Gnpat was biochemically characterized in a heterologous expression system in yeast. Results: During development, gnpat is expressed in proliferative cells of the retina and lens, and post-embryogenesis in proliferative cells of the ciliary marginal zone and lens epithelium. In contrast, gpam expression is mainly restricted to photoreceptors. Xenopus Gnpat expressed in yeast is present in both soluble and membrane fractions, but only the membrane-bound enzyme displays activity. The amino terminal of Gnpat, conserved in humans, shows lipid binding capacity that is enhanced by phosphatidic acid. Conclusions: Enzymes involved in the Plgs and glycerophospholipid biosynthetic pathways are differentially expressed during eye morphogenesis. The gnpat expression pattern and the molecular determinants regulating Gnpat activity advance our knowledge of this enzyme, contributing to our understanding of the retinal pathophysiology associated with GNPAT deficiency.


Subject(s)
Acyltransferases , Plasmalogens , Xenopus Proteins , Animals , Humans , Acyltransferases/genetics , Acyltransferases/metabolism , Plasmalogens/metabolism , Saccharomyces cerevisiae/metabolism , Xenopus laevis/metabolism , Xenopus Proteins/genetics , Xenopus Proteins/metabolism
9.
Mol Biol Cell ; 34(2): ar10, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36598800

ABSTRACT

The nuclear lamina serves important roles in chromatin organization and structural support, and lamina mutations can result in laminopathies. Less is known about how nuclear lamina structure changes during cellular differentiation-changes that may influence gene regulation. We examined the structure and dynamics of the nuclear lamina in human-induced pluripotent stem cells (iPSCs) and differentiated germ layer cells, focusing on lamin B1. We report that lamin B1 dynamics generally increase as iPSCs differentiate, especially in mesoderm and ectoderm, and that lamin B receptor (LBR) partially redistributes from the nucleus to cytoplasm in mesoderm. Knocking down LBR in iPSCs led to an increase in lamin B1 dynamics, a change that was not observed for ELYS, emerin, or lamin B2 knockdown. LBR knockdown also affected expression of differentiation markers. These data suggest that differentiation-dependent tethering of lamin B1 either directly by LBR or indirectly via LBR-chromatin associations impacts gene expression.


Subject(s)
Lamin Type A , Lamin Type B , Humans , Lamin Type A/metabolism , Lamin Type B/metabolism , Cell Nucleus/metabolism , Cell Differentiation , Nuclear Envelope/metabolism , Lamin B Receptor
10.
J Environ Manage ; 331: 117314, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-36689860

ABSTRACT

We present a collaboratively developed social-ecological model of the Kenai River Fishery. We developed the model through iterative interviews with stakeholders throughout the Kenai Peninsula using a novel participatory Fuzzy Cognitive Mapping process grounded in Ostrom's social-ecological systems framework. Individual social-ecological models, developed one-on-one with stakeholders, were combined into a single aggregated model representing the system's structure and function. We validated this aggregated model through subsequent interviews with stakeholders and focused literature reviews. The result is a model that can: 1) illustrate the breadth and interconnectedness of the Kenai River Fishery's social-ecological system; 2) be used to facilitate discussions around management of the fishery; and 3) be used to explore the components and interactions that move the system toward or away from sustainability. Using the model, we identify how the nature of salmon (migratory) and their habitat (large and unpredictable) leads to uncertainty about effective management strategies. This uncertainty, in addition to a large and diverse set of resource users, creates conflicting management goals that ultimately limit the governance system in making decisions that might increase the sustainability of the fishery.


Subject(s)
Fisheries , Rivers , Alaska , Conservation of Natural Resources , Ecosystem
11.
Global Spine J ; 13(7): 1909-1917, 2023 Sep.
Article in English | MEDLINE | ID: mdl-35156878

ABSTRACT

STUDY DESIGN: Retrospective Analysis. BACKGROUND: Venous thromboembolism (VTE) represents a significant cause of morbidity and mortality in major spine surgery. Placement of prophylactic inferior vena cava filters (IVCF) in patients undergoing major spine surgery was previously adopted at our institution. This study reports our experience and compares VTE rates between patients with and without preoperative IVCF placement. METHODS: A Retrospective comparative study was conducted on adult patients who underwent IVCF placement and those who did not prior to their spinal fusion procedure, between 2013 and 2016. Thoracolumbar fusions (anterior and/or posterior) of 7 or more levels, spinal osteotomies, and a minimum of a 3-month follow-up were included. Traumatic, oncologic, and cervical pathology were excluded. Primary outcomes measured included the incidence of overall VTE (DVT/PE), death, IVCF related complications, and IVCF retrieval. RESULTS: 386 patients who underwent major spine surgery, 258 met the eligibility criteria. Of those patients, 105 patients (40.7%) had prophylactic IVCF placement. All patients had postoperative SCDs and chemoprophylaxis. The presence of an IVCF was associated with an increased rate of overall VTE (14.3% vs 6.5%, P ≤ .05) and DVT episodes (8.6% vs 2.6%, P = .04). The rate of PE for the IVCF group and non-IVCF group was 8.6% and 4.6%, respectively, which was not statistically significant (P = .32). The all-cause mortality rate overall of 2.3% was statistically similar between both groups (P = 1.0). The IVCF group had higher rates of hematoma/seroma vs the non-IVCF group (12.4% vs 3.9%, P ≤ .05). 99 IVCFs were retrievable designs, and 85% were successfully retrieved. Overall IVCF-related complication rate was 11%. CONCLUSIONS: No statistical difference in PE or mortality rates existed between the IVCF and the control group. Patients with IVCF placement experienced approximately twice the rate of VTE and three times the rate of DVT compared to those without IVCF. The IVCF-related complication rate was 11%. Based on the results of this study, the authors recommend against the routine use of prophylactic IVCFs in adults undergoing major spine surgery. LEVEL OF EVIDENCE: III.

12.
J Radiol Case Rep ; 17(10): 14-20, 2023 Oct.
Article in English | MEDLINE | ID: mdl-38343882

ABSTRACT

Persistent craniopharyngeal canal (PCC) is a rare congenital anomaly that appears as a linear well-corticated canal running from the sella through the clivus and into the nasopharynx. Case reports of this anomaly have shown it is associated with a range of craniofacial defects, pituitary abnormalities, and meningoencephaloceles. It predisposes patients to bacterial meningitis. In this case a 46-year-old gentleman presenting for preoperative planning for surgical drainage of Potts Puffy tumor was found to have a PCC on CT and MRI. Imaging also demonstrated the presence of chronic inflammation and a fistula extending from the tract into the sphenoid sinus. This unusual presentation of a PCC with a sphenoid sinus fistula broadens the potential clinical presentations of PCC and further emphasizes the ability of this anomaly to serve as a conduit for CNS infection.


Subject(s)
Meningocele , Sphenoid Sinus , Male , Humans , Middle Aged , Sphenoid Sinus/diagnostic imaging , Sphenoid Sinus/surgery , Encephalocele/complications , Encephalocele/pathology , Encephalocele/surgery , Magnetic Resonance Imaging
13.
ACS Omega ; 7(49): 44825-44835, 2022 Dec 13.
Article in English | MEDLINE | ID: mdl-36530285

ABSTRACT

Biofilm formation is an adaptive resistance mechanism that pathogens employ to survive in the presence of antimicrobials. Pseudomonas aeruginosa is an infectious Gram-negative bacterium whose biofilm allows it to withstand antimicrobial attack and threaten human health. Chronic wound healing is often impeded by P. aeruginosa infections and the associated biofilms. Previous findings demonstrate that 600 Da branched polyethylenimine (BPEI) can restore ß-lactam potency against P. aeruginosa and disrupt its biofilms. Toxicity concerns of 600 Da BPEI are mitigated by covalent linkage with low-molecular-weight polyethylene glycol (PEG), and, in this study, PEGylated BPEI (PEG350-BPEI) was found exhibit superior antibiofilm activity against P. aeruginosa. The antibiofilm activity of both 600 Da BPEI and its PEG derivative was characterized with fluorescence studies and microscopy imaging. We also describe a variation of the colony biofilm model that was employed to evaluate the biofilm disruption activity of BPEI and PEG-BPEI.

14.
Cureus ; 14(9): e29547, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36312640

ABSTRACT

We describe a 60-year-old female patient who suffered an apparently intentional overdose of lacosamide and who developed status epilepticus secondary to its toxicity, complicated by refractory ventricular arrhythmia necessitating advanced cardiac life support and percutaneous stellate ganglion blockade. Extracorporeal membrane oxygenation was considered, and arterial and venous small-bore sheaths were placed in order to allow for extracorporeal cardiopulmonary resuscitation if cardiac arrest recurred, but they were not ultimately used. She suffered an embolic left middle cerebral artery stroke but otherwise recovered from the episode. This eventful clinical course highlights the dangers of lacosamide in high doses.

15.
Nature ; 608(7921): 98-107, 2022 08.
Article in English | MEDLINE | ID: mdl-35794474

ABSTRACT

DNA is naturally well suited to serve as a digital medium for in vivo molecular recording. However, contemporary DNA-based memory devices are constrained in terms of the number of distinct 'symbols' that can be concurrently recorded and/or by a failure to capture the order in which events occur1. Here we describe DNA Typewriter, a general system for in vivo molecular recording that overcomes these and other limitations. For DNA Typewriter, the blank recording medium ('DNA Tape') consists of a tandem array of partial CRISPR-Cas9 target sites, with all but the first site truncated at their 5' ends and therefore inactive. Short insertional edits serve as symbols that record the identity of the prime editing guide RNA2 mediating the edit while also shifting the position of the 'type guide' by one unit along the DNA Tape, that is, sequential genome editing. In this proof of concept of DNA Typewriter, we demonstrate recording and decoding of thousands of symbols, complex event histories and short text messages; evaluate the performance of dozens of orthogonal tapes; and construct 'long tape' potentially capable of recording as many as 20 serial events. Finally, we leverage DNA Typewriter in conjunction with single-cell RNA-seq to reconstruct a monophyletic lineage of 3,257 cells and find that the Poisson-like accumulation of sequential edits to multicopy DNA tape can be maintained across at least 20 generations and 25 days of in vitro clonal expansion.


Subject(s)
DNA , Gene Editing , Genome , CRISPR-Cas Systems/genetics , DNA/genetics , Gene Editing/methods , Genome/genetics , RNA, Guide, Kinetoplastida/genetics , RNA-Seq , Single-Cell Analysis , Time Factors
16.
Am J Lifestyle Med ; 16(4): 462-468, 2022.
Article in English | MEDLINE | ID: mdl-35860365

ABSTRACT

Physician burnout is a public health crisis. Although recent studies underscore its prevalence, there are few rigorous studies examining its prevention, especially among medical students and residents. Prior interventions have centered on mindfulness techniques and flexible workload scheduling, yielding limited success. However, interventions that combine fitness with philanthropy and community building may be more effective. The purpose of this report is 2-fold: first, to provide a review of physician burnout and potential prevention mechanisms and, second, to present a case study of how Medicine in Motion (MiM) addresses these issues. MiM facilitates various athletic workouts, competitions, and other events for students and professionals in medicine, dentistry, nursing, and physical therapy to support wellness and charitable initiatives. This analysis identifies 4 barriers to physicians and those in the health care profession from participating in wellness activities: (1) insufficient awareness, (2) logistical challenges, (3) lack of purpose, and (4) absence of perceived support. To overcome these barriers, MiM provides a model toolkit for starting a grassroots movement against physician burnout that other health care institutions may emulate. Institutions should provide financial support for these wellness programs. Future research is needed to evaluate these combined exercise, philanthropic, and community building efforts.

18.
Nat Commun ; 13(1): 2448, 2022 05 04.
Article in English | MEDLINE | ID: mdl-35508497

ABSTRACT

The ecological and oceanographic processes that drive the response of pelagic ocean microbiomes to environmental changes remain poorly understood, particularly in coastal upwelling ecosystems. Here we show that seasonal and interannual variability in coastal upwelling predicts pelagic ocean microbiome diversity and community structure in the Southern California Current region. Ribosomal RNA gene sequencing, targeting prokaryotic and eukaryotic microbes, from samples collected seasonally during 2014-2020 indicate that nitracline depth is the most robust predictor of spatial microbial community structure and biodiversity in this region. Striking ecological changes occurred due to the transition from a warm anomaly during 2014-2016, characterized by intense stratification, to cooler conditions in 2017-2018, representative of more typical upwelling conditions, with photosynthetic eukaryotes, especially diatoms, changing most strongly. The regional slope of nitracline depth exerts strong control on the relative proportion of highly diverse offshore communities and low biodiversity, but highly productive nearshore communities.


Subject(s)
Microbiota , Plankton , Biodiversity , Ecosystem , Microbiota/genetics , Nutrients , Plankton/genetics , Seawater
19.
Neuropharmacology ; 209: 109001, 2022 05 15.
Article in English | MEDLINE | ID: mdl-35189132

ABSTRACT

The ability to decide adaptively between immediate vs. delayed gratification (intertemporal choice) is critical for well-being and is associated with a range of factors that influence quality of life. In contrast to young adults, many older adults show enhanced preference for delayed gratification; however, the neural mechanisms underlying this age difference in intertemporal choice are largely un-studied. Changes in signaling through GABAB receptors (GABABRs) mediate several age-associated differences in cognitive processes linked to intertemporal choice. The current study used a rat model to determine how GABABRs in two brain regions known to regulate intertemporal choice (prelimbic cortex; PrL and basolateral amygdala; BLA) contribute to age differences in this form of decision making in male rats. As in humans, aged rats showed enhanced preference for large, delayed over small, immediate rewards during performance in an intertemporal choice task in operant test chambers. Activation of PrL GABABRs via microinfusion of the agonist baclofen increased choice of large, delayed rewards in young adult rats but did not influence choice in aged rats. Conversely, infusion of baclofen into the BLA strongly reduced choice of large, delayed rewards in both young adult and aged rats. Aged rats further showed a significant reduction in expression of GABABR1 subunit isoforms in the prefrontal cortex, a discovery that is consonant with the null effect of intra-PrL baclofen on intertemporal choice in aged rats. In contrast, expression of GABABR subunits was generally conserved with age in the BLA. Jointly, these findings elucidate a role for GABABRs in intertemporal choice and identify fundamental features of brain maturation and aging that mediate an improved ability to delay gratification.


Subject(s)
Basolateral Nuclear Complex , Delay Discounting , Animals , Baclofen/pharmacology , Basolateral Nuclear Complex/physiology , Choice Behavior/physiology , Decision Making/physiology , Delay Discounting/physiology , Male , Quality of Life , Rats , Receptors, GABA-B , Reward
20.
Urology ; 161: 42-49, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34986408

ABSTRACT

OBJECTIVE: To evaluate the reporting quality of systematic reviews (SRs) underpinning the American Urologic Association (AUA) clinical practice guidelines (CPGs). METHODS: We searched the AUA for CPGs from 2015-2021. We extracted all SRs from the reference sections and two independent investigators evaluated eligible SR/meta-analysis using the PRISMA (Preferred Reporting Instrument for Systematic Reviews and Meta-Analyses) and AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews 2) instruments. We compared SRs conducted by the Cochrane group to non-Cochrane SRs using a Mann-Whitney test. A multivariate regression was used to compare study characteristics. RESULTS: Eighteen CPG's met inclusion criteria. We extracted 120 unique SRs, which accounted for 5.1% (n = 120/2346) of all citations. Mean percent adherence to PRISMA and AMSTAR-2 was 65.4% -d 55.2% respectively. SRs conducted by the Cochrane Collaboration scored higher on AMSTAR-2 compared to non-Cochrane (z = -4.41, P <.01) and a positive correlation between PRISMA and AMSTAR-2 scores (r = 0.56, P <.001) was determined. CONCLUSION: Our study indicated the quality of SRs used to develop AUA CPGs across both PRISMA and AMSTAR-2 was variable. Despite higher evaluations, Cochrane SRs accounted for less than 15% of SRs underpinning CPG recommendations. Given the importance placed on CPGs within clinical practice, we recommended a synergistic relationship between the AUA and the Cochrane Collaboration to increase the number of quality urologic SRs.


Subject(s)
Research Design , Urology , Humans , Practice Guidelines as Topic , Systematic Reviews as Topic , United States
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