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1.
BMC Public Health ; 24(1): 1258, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720248

ABSTRACT

BACKGROUND: The approval of long-acting pre-exposure prophylaxis PrEP (LA-PrEP) in the United States brings opportunities to overcome barriers of oral PrEP, particularly among sexual and gender minority communities who bear a higher HIV burden. Little is known about real-time decision-making among potential PrEP users of LA-PrEP post-licensure. METHODS: We held focus group discussions with people assigned male at birth who have sex with men in Baltimore, Maryland to explore decision-making, values, and priorities surrounding PrEP usage. A sexual and gender minority-affirming health center that provides PrEP services supported recruitment. Discussions included a pile-sorting activity and were audio-recorded. Recordings were transcribed and analyzed iteratively, combining an inductive and deductive approach. RESULTS: We held five focus groups from Jan-June 2023 with 23 participants (21 cisgender men who have sex with men, two transgender women who have sex with men; mean age 37). Among participants, 21 were on oral PrEP, one was on injectable PrEP, and one had never taken PrEP. Most had never heard about LA-PrEP. When making decisions about PrEP, participants particularly valued efficacy in preventing HIV, side effects, feeling a sense of security, and ease of use. Perceptions varied between whether oral or injectable PrEP was more convenient, but participants valued the new opportunity for a choice in modality. Factors influencing PrEP access included cost, individual awareness, provider awareness, and level of comfort in a healthcare environment. Participants emphasized how few providers are informed about PrEP, placing the burden of being informed about PrEP on them. Comfort and trust in a provider superseded proximity as considerations for if and where to access PrEP. CONCLUSIONS: There is still low awareness about LA-PrEP among sexual and gender minority communities; thus, healthcare providers have a critical role in influencing access to LA-PrEP. Despite this, providers are still vastly underinformed about PrEP and underprepared to support clients in contextualized ways. Clients are more likely to engage in care with affirming providers who offer non-judgmental conversations about sex and life experiences. Provider education in the United States is urgently needed to better support clients in choosing a PrEP modality that is right for them and supporting adherence for effective HIV prevention.


Subject(s)
Focus Groups , HIV Infections , Pre-Exposure Prophylaxis , Humans , Male , Baltimore , Adult , HIV Infections/prevention & control , Female , Health Services Accessibility , Sexual and Gender Minorities/psychology , Middle Aged , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/administration & dosage , Decision Making , Homosexuality, Male/psychology , Homosexuality, Male/statistics & numerical data , Transgender Persons/psychology , Transgender Persons/statistics & numerical data
2.
Psychol Assess ; 35(11): 938-948, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37902663

ABSTRACT

Face masks are recommended to minimize the spread of COVID-19 and are required in many health care settings. Although masks have documented health advantages, they also negatively impact communication, an essential element of clinical neuropsychological assessment. Using a large clinical data set from a major academic medical center, we investigated the effect of mask wearing on neuropsychological test performance. Specifically, we examined performance on eight standard, widely used neuropsychological tests between a prepandemic (unmasked) and postpandemic (masked) group, composed of 754 and 837 adult patients, respectively. We compared performance on verbally mediated versus visually mediated tests, hypothesizing that the postpandemic group, compared to the prepandemic group, would perform significantly lower on the verbally mediated tests but not on the visually mediated tests. In partial support of the hypothesis, we found that the postpandemic group performed significantly worse on the Auditory Verbal Learning Test (AVLT; p = .001). Secondary analyses showed that age moderated the mask-related effect (p = .038), whereby patients 65 and older had significantly worse performance on Digit Span (p = .0027) and the AVLT (p = .0002) with masks on, while patients younger than 65 showed no significant differences. There were no significant differences on any visually mediated tests. These findings suggest that mask wearing during neuropsychological assessment compromises performance on verbally mediated tests in older patients. These findings are particularly relevant for neuropsychologists practicing in geriatric settings. Neuropsychologists performing assessments with masks should be aware that masks may artificially deflate patient scores for reasons unrelated to cognition or clinical condition. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Subject(s)
Awareness , COVID-19 , Adult , Humans , Aged , Cognition , Communication , Neuropsychological Tests
3.
Anim Cogn ; 25(5): 1109-1131, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36018473

ABSTRACT

Dolphins gain information through echolocation, a publicly accessible sensory system in which dolphins produce clicks and process returning echoes, thereby both investigating and contributing to auditory scenes. How their knowledge of these scenes contributes to their echoic information-seeking is unclear. Here, we investigate their top-down cognitive processes in an echoic matching-to-sample task in which targets and auditory scenes vary in their decipherability and shift from being completely unfamiliar to familiar. A blind-folded adult male dolphin investigated a target sample positioned in front of a hydrophone to allow recording of clicks, a measure of information-seeking and effort; the dolphin received fish for choosing an object identical to the sample from 3 alternatives. We presented 20 three-object sets, unfamiliar in the first five 18-trial sessions with each set. Performance accuracy and click counts varied widely across sets. Click counts of the four lowest-performance-accuracy/low-discriminability sets (X = 41%) and the four highest-performance-accuracy/high-discriminability sets (X = 91%) were similar at the first sessions' starts and then decreased for both kinds of scenes, although the decrease was substantially greater for low-discriminability sets. In four challenging-but-doable sets, number of clicks remained relatively steady across the 5 sessions. Reduced echoic effort with low-discriminability sets was not due to overall motivation: the differential relationship between click number and object-set discriminability was maintained when difficult and easy trials were interleaved and when objects from originally difficult scenes were grouped with more discriminable objects. These data suggest that dolphins calibrate their echoic information-seeking effort based on their knowledge and expectations of auditory scenes.


Subject(s)
Bottle-Nosed Dolphin , Dolphins , Echolocation , Male , Animals , Information Seeking Behavior
4.
Arch Phys Med Rehabil ; 103(11): 2105-2113, 2022 11.
Article in English | MEDLINE | ID: mdl-35905772

ABSTRACT

OBJECTIVE: Determine anxiety trajectories and predictors up to 10 years posttraumatic brain injury (TBI). DESIGN: Prospective longitudinal, observational study. SETTING: Inpatient rehabilitation centers. PARTICIPANTS: 2836 participants with moderate to severe TBI enrolled in the TBI Model Systems National Database who had ≥2 anxiety data collection points (N=2836). MAIN OUTCOME MEASURE: Generalized Anxiety Disorder-7 (GAD-7) at 1, 2, 5, and 10-year follow-ups. RESULTS: Linear mixed models showed higher GAD-7 scores were associated with Black race (P<.001), public insurance (P<.001), pre-injury mental health treatment (P<.001), 2 additional TBIs with loss of consciousness (P=.003), violent injury (P=.047), and more years post-TBI (P=.023). An interaction between follow-up year and age was also related to GAD-7 scores (P=.006). A latent class mixed model identified 3 anxiety trajectories: low-stable (n=2195), high-increasing (n=289), and high-decreasing (n=352). The high-increasing and high-decreasing groups had mild or higher GAD-7 scores up to 10 years. Compared to the low-stable group, the high-decreasing group was more likely to be Black (OR=2.25), have public insurance (OR=2.13), have had pre-injury mental health treatment (OR=1.77), and have had 2 prior TBIs (OR=3.16). CONCLUSIONS: A substantial minority of participants had anxiety symptoms that either increased (10%) or decreased (13%) over 10 years but never decreased below mild anxiety. Risk factors of anxiety included indicators of socioeconomic disadvantage (public insurance) and racial inequities (Black race) as well as having had pre-injury mental health treatment and 2 prior TBIs. Awareness of these risk factors may lead to identifying and proactively referring susceptible individuals to mental health services.


Subject(s)
Anxiety , Brain Injuries, Traumatic , Humans , Prospective Studies , Anxiety/epidemiology , Anxiety/psychology , Brain Injuries, Traumatic/rehabilitation , Anxiety Disorders/epidemiology , Rehabilitation Centers
5.
J Pediatr Pharmacol Ther ; 27(2): 164-171, 2022.
Article in English | MEDLINE | ID: mdl-35241989

ABSTRACT

OBJECTIVE: To determine the incidence of cytomegalovirus (CMV) DNAemia and disease, identify potential risk factors, and assess the safety and efficacy of weight-based valganciclovir dosing in pediatric post-renal transplant patients. METHODS: This single-center, retrospective study included patients ≤21 years who received a kidney transplant between January 1, 2011, and November 1, 2019, with 3 to 24 months of follow-up data. Demographics and clinical characteristics were collected to assess for potential risk factors. Descriptive statistics and logistic regressions were used to determine rates of CMV DNAemia considering clinical characteristics and chemoprophylaxis. RESULTS: Fifty-seven patients were included. The incidence of CMV DNAemia was 43.9%. Cytomegalovirus seropositive status was associated with increased risk of CMV DNAemia. Patients receiving valganciclovir for <150 days had 8.33 (95% CI, 1.68-41.29) greater odds of developing CMV DNAemia than patients receiving valganciclovir for 180 ± 30 days, p = 0.01. The median time to detectable CMV PCR after transplant was 140 days (range, 12-511 days). Cytomegalovirus DNAemia was not statistically different between those receiving weight-based vs FDA-approved valganciclovir dosing; however, patients receiving the FDA-approved dosing were more likely to develop neutropenia. Among the intermediate-risk group, the adjusted relative risk of CMV DNAemia was 0.62 (95% CI, 0.36-1.09) for those not receiving chemoprophylaxis compared with those who did. CONCLUSIONS: Risk of CMV DNAemia is higher among patients receiving valganciclovir for <150 days. Further exploration of weight-based valganciclovir dosing for CMV chemoprophylaxis in high- and intermediate-risk post-renal transplant patients is needed to minimize adverse drug effects while maintaining efficacy.

6.
Clin Infect Dis ; 73(9): e2807-e2809, 2021 11 02.
Article in English | MEDLINE | ID: mdl-33354704

ABSTRACT

Enteroviral meningitis is seasonal, typically exhibiting a rise in prevalence in late summer/early fall. Based on clinical microbiology laboratory testing data of cerebrospinal fluid, the expected August/September/October peak in enteroviral meningitis did not occur in 2020, possibly related to coronavirus disease 2019 (COVID-19) mitigation strategies.


Subject(s)
COVID-19 , Enterovirus Infections , Enterovirus , Meningitis, Viral , Enterovirus Infections/epidemiology , Enterovirus Infections/prevention & control , Humans , Infant , Meningitis, Viral/diagnosis , Meningitis, Viral/epidemiology , Meningitis, Viral/prevention & control , SARS-CoV-2
7.
Mayo Clin Proc ; 95(8): 1701-1703, 2020 08.
Article in English | MEDLINE | ID: mdl-32753142

ABSTRACT

The possibility of seasonality of COVID-19 is being discussed; we show clinical microbiology laboratory data illustrating seasonality of coronaviruses 229E, HKU1, NL63, and OC43. The data shown are specific to the 4 studied coronaviruses and may or may not generalize to COVID-19.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus/pathogenicity , Seasons , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/virology , Global Health , Humans , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2
8.
Arch Phys Med Rehabil ; 101(7): 1260-1264, 2020 07.
Article in English | MEDLINE | ID: mdl-32113971

ABSTRACT

OBJECTIVE: Characterize the temporal profile of recovery of communication after severe brain injury. DESIGN: Retrospective cohort study. SETTING: Inpatient rehabilitation hospital. PARTICIPANTS: Patients with severe acquired brain injury and no evidence of communication on the Coma Recovery Scale-Revised (CRS-R) (N=175). MAIN OUTCOME MEASURES: Time from injury to recovery of intentional communication (IC, inconsistent yes/no responses) and functional communication (FC, consistent and accurate yes/no responses) on the CRS-R Communication subscale. RESULTS: Patients (N=175) were included in the primary observation period of the first 8 weeks of inpatient rehabilitation (median [interquartile range, IQR]: 48 [27-61] years old, 105 men, 28 [21-38] days postinjury, 100 traumatic etiology). Fifty-four patients (31%) did not recover IC or FC. Thirty patients (17%) recovered IC only (median [IQR] days from injury to IC= 40 [34-54]), 72 patients (41%) recovered IC followed by FC (days from injury to FC=50 [42-61]), and 19 patients (11%) recovered FC without first recovering IC (43 [32-63]). The patients who recovered neither IC nor FC within 8 weeks of admission were admitted to rehabilitation later than those who recovered IC and/or FC (P<.01). Sixteen patients who did not recover communication within 8 weeks of admission to rehabilitation subsequently recovered FC prior to discharge. CONCLUSIONS: In patients with severe brain injury receiving inpatient rehabilitation, discernible yes-no responses emerged approximately 6 weeks postinjury and became reliable 1 week later. Approximately 1 in 3 patients did not demonstrate IC or FC within 8 weeks of admission to rehabilitation, although 33% of these individuals recovered communication prior to discharge. In total, 61% of patients recovered FC prior to discharge from rehabilitation.


Subject(s)
Brain Injuries, Traumatic/diagnosis , Brain Injuries, Traumatic/rehabilitation , Communication , Consciousness Disorders/rehabilitation , Recovery of Function , Adult , Cohort Studies , Consciousness Disorders/etiology , Consciousness Disorders/physiopathology , Female , Follow-Up Studies , Glasgow Coma Scale , Humans , Injury Severity Score , Inpatients/statistics & numerical data , Length of Stay , Male , Middle Aged , Rehabilitation Centers , Retrospective Studies , Time Factors , Treatment Outcome
9.
J Pediatr Pharmacol Ther ; 25(2): 81-95, 2020.
Article in English | MEDLINE | ID: mdl-32071582

ABSTRACT

OBJECTIVES: To describe the antipsychotics, route of administration, dosage regimen, and outcomes reported to prevent or treat delirium in hospitalized children. METHODS: Medline, Embase, and International Pharmaceutical Abstracts were searched using the keywords "haloperidol," "olanzapine," "quetiapine," "risperidone," "ziprasidone," and "delirium." Articles evaluating the use of these agents to manage delirium in hospitalized children that were published between 1946 and August 2019 were included. Two authors independently screened each article for inclusion. Reports were excluded if they were published abstracts or included fewer than 3 patients in the report. RESULTS: Thirteen reports that included 370 children receiving haloperidol, quetiapine, olanzapine, and/or risperidone for delirium treatment were reviewed. Most children received haloperidol (n = 131) or olanzapine (n = 125). Significant variability in dosing was noted. A total of 23 patients (6.2%) had an adverse drug event, including 13 (56.5%) who experienced dystonia and 3 (13.0%) with a prolonged corrected QT interval. Most reports described improvement in delirium symptoms; however, only 5 reports used a validated screening tool for PICU delirium to evaluate antipsychotic response. CONCLUSIONS: Most reports noted efficacy with antipsychotics, but these reports were limited by sample size and lacked a validated PICU delirium tool. Future research is needed to determine the optimal agent and dosage regimen to treat PICU delirium.

10.
J Med Food ; 23(1): 56-64, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31436500

ABSTRACT

Bone is maintained by an intricate balance between bone formation and bone resorption. The presence of inflammation can contribute to an imbalance in bone homeostasis by enhancing differentiation and activity of osteoclasts, the cells that participate in the breakdown of bone. Polyphenols such as flavonoids found in plant-derived foods have been shown to have anti-inflammatory effects in various tissues. Tart cherries are a rich source of such polyphenolic compounds. Using mouse macrophage cells (RAW 264.7), we examined whether tart cherry polyphenols could dose dependently inhibit the proliferation and activity of receptor activator of nuclear factor kappa-B ligand (RANKL) differentiated osteoclasts under inflammatory conditions. Tartrate-resistant acid phosphatase (TRAP) activity and staining of TRAP-positive multinucleated cells, used as indicators of osteoclast differentiation and activity, tended to decrease with tart cherry polyphenols treatment. Osteoprotegerin expression by osteoclasts was decreased in a similar manner. A significant increase in nitrite concentration was observed with the lower doses of tart cherry polyphenols of 50 and 100 µg/mL (P < .05). However, higher doses of tart cherry polyphenols (200 and 300 µg/mL) reduced nitrite concentrations below that of the control that received no tart cherry polyphenols treatment (P < .05). Western blot analyses showed that protein expression of cyclooxygenase-2 (COX-2) followed a similar trend, although results were not statistically significant. On the other hand, tart cherry polyphenols treatments dose dependently increased inducible nitric oxide synthase protein expression, with statistical significance noted at doses of 200 and 300 µg/mL. Overall, our findings suggest that the polyphenols associated with tart cherries potentially inhibit osteoclast differentiation and activity, which may be beneficial to bone health.


Subject(s)
Cell Differentiation/drug effects , Fruit/chemistry , Osteoclasts/cytology , Osteoclasts/drug effects , Polyphenols/pharmacology , Prunus avium/chemistry , Animals , Cyclooxygenase 2/metabolism , Mice , Nitric Oxide Synthase Type II/metabolism , Nitrites/analysis , Osteoprotegerin/metabolism , Plant Extracts/pharmacology , RANK Ligand/metabolism , RAW 264.7 Cells , Tartrate-Resistant Acid Phosphatase/metabolism
11.
Sci Transl Med ; 10(472)2018 12 19.
Article in English | MEDLINE | ID: mdl-30545964

ABSTRACT

Schizophrenia and bipolar disorder are complex psychiatric diseases with risks contributed by multiple genes. Dysregulation of gene expression has been implicated in these disorders, but little is known about such dysregulation in the human brain. We analyzed three transcriptome datasets from 394 postmortem brain tissue samples from patients with schizophrenia or bipolar disorder or from healthy control individuals without a known history of psychiatric disease. We built genome-wide coexpression networks that included microRNAs (miRNAs). We identified a coexpression network module that was differentially expressed in the brain tissue from patients compared to healthy control individuals. This module contained genes that were principally involved in glial and neural cell genesis and glial cell differentiation, and included schizophrenia risk genes carrying rare variants. This module included five miRNAs and 545 mRNAs, with six transcription factors serving as hub genes in this module. We found that the most connected transcription factor gene POU3F2, also identified on a genome-wide association study for bipolar disorder, could regulate the miRNA hsa-miR-320e and other putative target mRNAs. These regulatory relationships were replicated using PsychENCODE/BrainGVEX datasets and validated by knockdown and overexpression experiments in SH-SY5Y cells and human neural progenitor cells in vitro. Thus, we identified a brain gene expression module that was enriched for rare coding variants in genes associated with schizophrenia and that contained the putative bipolar disorder risk gene POU3F2 The transcription factor POU3F2 may be a key regulator of gene expression in this disease-associated gene coexpression module.


Subject(s)
Brain/metabolism , Gene Regulatory Networks , Homeodomain Proteins/metabolism , Mental Disorders/genetics , POU Domain Factors/metabolism , Cell Differentiation/genetics , Cell Proliferation/genetics , Databases, Genetic , Gene Expression Regulation , Genetic Predisposition to Disease , Genetic Variation , Genome-Wide Association Study , Homeodomain Proteins/genetics , Humans , Neural Stem Cells/metabolism , POU Domain Factors/genetics , Postmortem Changes , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reproducibility of Results
12.
Sci Transl Med ; 10(472)2018 12 19.
Article in English | MEDLINE | ID: mdl-30545965

ABSTRACT

A number of studies indicate that rare copy number variations (CNVs) contribute to the risk of schizophrenia (SCZ). Most of these studies have focused on protein-coding genes residing in the CNVs. Here, we investigated long noncoding RNAs (lncRNAs) within 10 SCZ risk-associated CNV deletion regions (CNV-lncRNAs) and examined their potential contribution to SCZ risk. We used RNA sequencing transcriptome data derived from postmortem brain tissue from control individuals without psychiatric disease as part of the PsychENCODE BrainGVEX and Developmental Capstone projects. We carried out weighted gene coexpression network analysis to identify protein-coding genes coexpressed with CNV-lncRNAs in the human brain. We identified one neuronal function-related coexpression module shared by both datasets. This module contained a lncRNA called DGCR5 within the 22q11.2 CNV region, which was identified as a hub gene. Protein-coding genes associated with SCZ genome-wide association study signals, de novo mutations, or differential expression were also contained in this neuronal module. Using DGCR5 knockdown and overexpression experiments in human neural progenitor cells derived from human induced pluripotent stem cells, we identified a potential role for DGCR5 in regulating certain SCZ-related genes.


Subject(s)
Gene Expression Regulation , RNA, Long Noncoding/metabolism , Schizophrenia/genetics , Adult , Brain/pathology , DNA Copy Number Variations/genetics , Humans , Molecular Sequence Annotation , Open Reading Frames/genetics , RNA, Long Noncoding/genetics , Risk Factors
13.
Oncotarget ; 9(40): 25826-25832, 2018 May 25.
Article in English | MEDLINE | ID: mdl-29899824

ABSTRACT

We have developed a clinically validated NGS assay that includes tumor, germline and RNA sequencing. We apply this assay to clinical specimens and cell lines, and we demonstrate a clinical sensitivity of 98.4% and positive predictive value of 100% for the clinically actionable variants measured by the assay. We also demonstrate highly accurate copy number measurements and gene rearrangement identification.

14.
J Pediatr Pharmacol Ther ; 23(2): 72-83, 2018.
Article in English | MEDLINE | ID: mdl-29720907

ABSTRACT

OBJECTIVES: To describe the method of delivery, dosage regimens, and outcomes of sedatives and analgesics administered via the extravascular route for laceration repair in children. METHODS: Medline, Embase, and International Pharmaceutical Abstracts were searched using the keywords "child," "midazolam," "ketamine," dexmedetomidine," "fentanyl," "nitrous oxide" (N2O), and "laceration repair." Articles evaluating the use of extravascular sedation in children for laceration repair published in the English language between 1946 and June 2017 were included. Two authors independently screened each article for inclusion. Reports were excluded if they did not contain sufficient details on dosage regimen and outcomes. RESULTS: A total of 16 reports representing 953 children receiving sedatives and analgesics via the extravascular route were included for analyses. A statistical analysis was not performed because of heterogeneity in dosing and types of analyses conducted. Midazolam and N2O were the most common agents, with oral (PO) midazolam being the most common agent. Other agents that have supporting data were intranasal (IN) dexmedetomidine, IN ketamine, IN midazolam, PO diazepam, PO ketamine, transmucosal (TM) midazolam, and TM fentanyl. CONCLUSIONS: Most of the agents administered through the extravascular route were efficacious. Selection of the agents should be based on perceived need for analgesia versus sedation, patient accessibility, and adverse drug events. Future research is needed to determine the optimal agent and route for laceration repair.

15.
Am J Health Syst Pharm ; 74(15): 1174-1183, 2017 Aug 01.
Article in English | MEDLINE | ID: mdl-28588011

ABSTRACT

PURPOSE: The relationship between initial fentanyl infusion dosage and time to goal sedation in nonobese and obese critically ill children was examined. METHODS: A retrospective cohort study of 75 fentanyl infusions initiated in mechanically ventilated children age 2-17 years with an inpatient admission between January 1, 2012, and May 31, 2014, who subsequently received a fentanyl infusion was conducted. The primary outcomes of the study included the time to goal sedation and fentanyl dosage characteristics (i.e., underdosage, optimal dosage, or overdosage). Sedation scores were assessed by the State Behavioral Scale, a validated instrument to assess sedation in children. Key independent (predictor) variables were collected, including baseline demographics and admission diagnoses. Multivariable regression models were used to examine the association between initial fentanyl infusion dosage and time to goal sedation or dosing characteristics while controlling for obesity status and other modifying or confounding factors. RESULTS: A total of 75 infusions met the study's inclusion criteria, representing 74 patients. The majority of patients (52%) were boys, and the median age was 8.1 years. Eighteen children (24%) were obese. The median time to goal sedation was 10.9 hours. Among nonobese children, every 10-µg/hr increase in initial fentanyl dosage was associated with a 19% lower probability of achieving goal sedation at any point in time. Initial fentanyl dosage was not associated with time to goal sedation in obese children. CONCLUSION: Fentanyl infusion rates in obese and nonobese children varied widely in the time needed to achieve goal sedation. At any given time, initial fentanyl infusion rates were less likely to result in goal sedation in nonobese than in obese children.


Subject(s)
Anesthetics, Intravenous/administration & dosage , Critical Illness/therapy , Fentanyl/administration & dosage , Hypnotics and Sedatives/administration & dosage , Obesity/drug therapy , Adolescent , Child , Child, Preschool , Cohort Studies , Female , Humans , Infusions, Intravenous , Male , Obesity/surgery , Retrospective Studies , Time Factors
16.
Genome Res ; 27(3): 385-392, 2017 03.
Article in English | MEDLINE | ID: mdl-28052920

ABSTRACT

Phenotypic differences within populations and between closely related species are often driven by variation and evolution of gene expression. However, most analyses have focused on the effects of genomic variation at cis-regulatory elements such as promoters and enhancers that control transcriptional activity, and little is understood about the influence of post-transcriptional processes on transcript evolution. Post-transcriptional modification of RNA by N6-methyladenosine (m6A) has been shown to be widespread throughout the transcriptome, and this reversible mark can affect transcript stability and translation dynamics. Here we analyze m6A mRNA modifications in lymphoblastoid cell lines (LCLs) from human, chimpanzee and rhesus, and we identify patterns of m6A evolution among species. We find that m6A evolution occurs in parallel with evolution of consensus RNA sequence motifs known to be associated with the enzymatic complexes that regulate m6A dynamics, and expression evolution of m6A-modified genes occurs in parallel with m6A evolution.


Subject(s)
Adenosine/analogs & derivatives , Evolution, Molecular , RNA Processing, Post-Transcriptional , RNA, Messenger/metabolism , Adenosine/metabolism , Animals , Cells, Cultured , Consensus Sequence , Humans , Macaca mulatta/genetics , Nucleotide Motifs , Pan troglodytes/genetics , RNA, Messenger/genetics
17.
PeerJ ; 4: e2035, 2016.
Article in English | MEDLINE | ID: mdl-27231657

ABSTRACT

Cuttlefish are known for their ability to quickly alter their total appearance, or body pattern, to camouflage or to communicate with predators, prey and conspecifics. The body patterns of some species have been extensively documented to gain a better understanding of their behaviors. However, the flamboyant cuttlefish (Metasepia pfefferi) is largely unstudied. Recently, aquarists have been able to breed, house and display M. pfefferi, giving researchers ample opportunities to study their behavior under those conditions. This study aimed to identify the dorsally-visible components of the body patterns used by 5 sexually-mature, freely-behaving, F5 generation M. pfefferi in their home aquarium at The Seas in Epcot at Walt Disney World Resorts(®), Lake Buena Vista, FL, USA. Furthermore, we aimed to determine the most probable patterns used by this population of animals and to create a database of components that can be used in future behavioral studies. We found that this population of M. pfefferi use a combination of 7 textural, 14 postural, 7 locomotor and between 42 and 75 chromatic components in their home aquarium. Using maximum likelihood analysis and AutoClass@IJM software, we found that these components combine to generate 11 distinct body patterns. The software was able to sort 98% of the live animal observations into one of the 11 patterns with 90% confidence and 88% of observations with 99% confidence. Unusually for cuttlefish, 8 of the 11 identified patterns contained at least one "traveling" component (i.e., traveling waves or blinking spots) in which the colors on the skin appeared to travel on the animal's mantle. In other species, these components are generally seen during hunting or aggression, but this population of M. pfefferi uses them frequently during a variety of contexts in their home aquarium. With few published data on the behavior of M. pfefferi in their natural environment, we cannot compare the behavior of the tank-raised individuals in this study to animals in the wild. However, this study provides the groundwork necessary for future studies of M. pfefferi body patterning and behavior.

18.
PeerJ ; 4: e1857, 2016.
Article in English | MEDLINE | ID: mdl-27069797

ABSTRACT

Praziquantel (PZQ) is a drug commonly utilized to treat both human schistosomiasis and some parasitic infections and infestations in animals. In the aquarium industry, PZQ can be administered in a "bath" to treat the presence of ectoparasites on both the gills and skin of fish and elasmobranchs. In order to fully treat an infestation, the bath treatment has to maintain therapeutic levels of PZQ over a period of days or weeks. It has long been assumed that, once administered, PZQ is stable in a marine environment throughout the treatment interval and must be mechanically removed, but no controlled experiments have been conducted to validate that claim. This study aimed to determine if PZQ would break down naturally within a marine aquarium below its 2 ppm therapeutic level during a typical 30-day treatment: and if so, does the presence of fish or the elimination of all living biological material impact the degradation of PZQ? Three 650 L marine aquarium systems, each containing 12 fish (French grunts: Haemulon flavolineatum), and three 650 L marine aquariums each containing no fish were treated with PZQ (2 ppm) and concentrations were measured daily for 30 days. After one round of treatment, the PZQ was no longer detectable in any system after 8 (±1) days. The subsequent two PZQ treatments yielded even faster PZQ breakdown (non-detectable after 2 days and 2 ± 1 day, respectively) with slight variations between systems. Linear mixed effects models of the data indicate that day and trial most impact PZQ degradation, while the presence of fish was not a factor in the best-fit models. In a completely sterilized marine system (0.5 L) PZQ concentration remained unchanged over 15 days, suggesting that PZQ may be stable in a marine system during this time period. The degradation observed in non-sterile marine systems in this study may be microbial in nature. This work should be taken into consideration when providing PZQ bath treatments to marine animals to ensure maximum drug administration.

19.
PLoS One ; 10(6): e0128930, 2015.
Article in English | MEDLINE | ID: mdl-26061662

ABSTRACT

Harbor seal (Phoca vitulina) pups begin diving within hours of birth, stimulating the development of the blood oxygen (O2) stores necessary to sustain underwater aerobic metabolism. Since harbor seals experience a brief nursing period, the early-life development of these blood O2 stores is necessary for successful post-weaning foraging. If mothers and pups become prematurely separated, the pup may be transported to a wildlife rehabilitation center for care. Previous studies suggest that the shallow pools and lack of diving in rehabilitation facilities may lead to under-developed blood O2 stores, but diving behavior during rehabilitation has not been investigated. This study aimed to simultaneously study the diving behaviors and blood O2 store development of rehabilitating harbor seal pups. Standard hematology measurements (Hct, Hb, RBC, MCV, MCH, MCHC) were taken to investigate O2 storage capacity and pups were equipped with time-depth recorders to investigate natural diving behavior while in rehabilitation. Linear mixed models of the data indicate that all measured blood parameters changed with age; however, when compared to literature values for wild harbor seal pups, rehabilitating pups have smaller red blood cells (RBCs) that can store less hemoglobin (Hb) and subsequently, less O2, potentially limiting their diving capabilities. Wild pups completed longer dives at younger ages (maximum reported <25 days of age: 9 min) in previous studies than the captive pups in this study (maximum <25 days of age: 2.86 min). However, captivity may only affect the rate of development, as long duration dives were observed (maximum during rehabilitation: 13.6 min at 89 days of age). Further, this study suggests that there may be a positive relationship between RBC size and the frequency of long duration dives. Thus, rehabilitating harbor seal pups should be encouraged to make frequent, long duration dives to prepare themselves for post-release foraging.


Subject(s)
Diving , Oxygen/blood , Phoca/physiology , Animals , Phoca/blood
20.
J Pediatr Pharmacol Ther ; 20(6): 418-30, 2015.
Article in English | MEDLINE | ID: mdl-26766932

ABSTRACT

OBJECTIVES: The purpose of this study was to describe the method of delivery, dosage regimens, and outcomes of sedatives administered by extravascular route for imaging procedures in children. METHODS: Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Database of Systematic Reviews were searched using keywords "child", "midazolam", "ketamine", dexmedetomidine", "fentanyl", "nitrous oxide", and "imaging." Articles evaluating the use of extravascular sedation in children for imaging procedures published in English between 1946 and March 2015 were included. Two authors independently screened each article for inclusion. Reports were excluded if they did not contain sufficient details on dosage regimens and outcomes. RESULTS: Twenty reports representing 1,412 patients ranging in age from 0.33 to 19 years of age were included for analysis. Due to discrepancies in doses and types of analyses, statistical analyses were not performed. Oral midazolam was the most common agent evaluated; other agents included intranasal (IN) ketamine, IN midazolam, IN fentanyl, IN and transmucosal dexmedetomidine, and N2O. Most agents were considered efficacious compared with placebo. CONCLUSIONS: Most agents showed efficacy for sedation during imaging when delivered through an extra-vascular route. Selection of agents should be based on onset time, duration, patient acceptability, recovery time, and adverse events. More robust studies are necessary to determine the optimal agent and route to utilize for imaging procedures when sedation is needed.

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