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1.
J Clin Psychopharmacol ; 44(1): 30-34, 2024.
Article in English | MEDLINE | ID: mdl-38011032

ABSTRACT

BACKGROUND: The cornerstone treatment of delirium is to assess and treat its underlying causes and prevent further complications. Drug therapy may be necessary to control agitation and behavioral symptoms associated with delirium. The aim of this pilot study was to evaluate the feasibility of a randomized placebo controlled trial to evaluate the efficacy and safety of risperidone in the treatment of delirium. METHODS: This was a randomized double-blinded placebo-controlled trial. Patients were enrolled in the study if they were hospitalized and 65 years or older and had a diagnosis of delirium. Delirium Rating Scale revised 98 was used to determine delirium and motor agitation. RESULTS: A total of 14 participants with 57% being men and having a mean age of 86 years were included. There were no statistically significant differences between the risperidone and placebo group for the Delirium Rating Scale revised 98 score. There were no severe adverse reactions reported in the study, and no patients discontinued the study for adverse reactions. CONCLUSIONS: Risperidone at low doses (1 mg daily or less) was well tolerated for the treatment of delirium. Future large-scale trials are needed to evaluate the safety and efficacy of risperidone in the treatment of delirium. This pilot study taught us that the phase 2 RIsperDone DELirium trial will need a multicenter design with more research personnel to increase the number of participants enrolled.


Subject(s)
Antipsychotic Agents , Delirium , Male , Humans , Aged, 80 and over , Female , Risperidone/adverse effects , Antipsychotic Agents/adverse effects , Pilot Projects , Delirium/drug therapy , Delirium/chemically induced , Treatment Outcome , Double-Blind Method
2.
J Am Pharm Assoc (2003) ; 63(4): 1197-1202, 2023.
Article in English | MEDLINE | ID: mdl-37164262

ABSTRACT

BACKGROUND: Health care deciders are aware of the inappropriate use of proton pump inhibitors (PPIs). To reduce inappropriate prescriptions, the Conseil du Médicament (CdM) issued a practice guideline and the Régie de l'Assurance Maladie du Quebec (RAMQ) asked prescribers to justify its use by writing a specific indication code for their patients to obtain drug coverage. OBJECTIVES: This study aimed to evaluate the effectiveness of the intervention by the RAMQ to reduce inappropriate PPI prescription. METHODS: A cross-sectional quasi-experimental prospective study was performed in an emergency department. Patients aged 18 years or older were included in 2016 to 2017 and 2019 to 2021 in the pre- and postintervention group, respectively. The proportion of patients on PPI without an appropriate indication were identified from patient interviews and chart review. RESULTS: A total of 871 and 1475 patients were recruited in the pre- and postintervention groups. According to the CdM guideline, the proportion of inappropriate PPI prescription was 30.7% (n = 267) in the preintervention group and 49.1% (n = 724) in the postintervention group (P < 0.001). According to the RAMQ criteria, the proportion of inappropriate PPI prescription was of 76.1% (n = 663) and 81.4% (n = 1200) in the pre- and postintervention group, respectively (P < 0.001). CONCLUSION: This study highlights the ineffectiveness of the codes for PPI prescriptions in reducing inappropriate prescriptions. It seems that the obligation to write a code does not lead to a reassessment of PPI indication.


Subject(s)
Inappropriate Prescribing , Proton Pump Inhibitors , Humans , Proton Pump Inhibitors/therapeutic use , Prospective Studies , Cross-Sectional Studies , Inappropriate Prescribing/prevention & control , Ambulatory Care
3.
Soc Psychiatry Psychiatr Epidemiol ; 57(3): 505-518, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34223935

ABSTRACT

PURPOSE: The epidemiology of late-life psychosis (LLP) remains unclear comparatively to early-onset psychosis. The study aims to estimate the prevalence and incidence of LLP over a 3-year period and examine the correlates of LLP in community-living older adults aged ≥ 65 years recruited in primary care. METHODS: Study sample included N = 1481 primary care older adults participating in the Étude sur la Santé des Aînés (ESA)-Services study. Diagnoses were obtained from health administrative and self-reported data in the 3 years prior and following baseline interview. The prevalence and incidence of LLP (number of cases) were identified in the 3-year period following interview. Participants with dementia or psychosis related to dementia were excluded. Logistic regressions were used to ascertain the correlates of LLP as function of various individual and health system factors. RESULTS: The 3-year prevalence and incidence of LLP was 4.7% (95% CI = 3.64-5.81) and 2.8% (95% CI = 1.99-3.68), respectively. Factors associated with both prevalent and incident LLP included functional status, number of physical diseases, hospitalizations, continuity of care and physical activity. Older age and the presence of suicidal ideation were associated with incident LLP, while higher education, a depressive disorder and a history of sexual assault were associated with persistent cases. CONCLUSIONS: Results highlight the importance of LLP in primary care older adult patients without dementia. Health system factors were consistent determinants of prevalent and incident LLP, suggesting the need for better continuity of care in at-risk primary care older adults.


Subject(s)
Dementia , Psychotic Disorders , Aged , Dementia/diagnosis , Dementia/epidemiology , Humans , Prevalence , Primary Health Care , Psychotic Disorders/diagnosis , Psychotic Disorders/epidemiology , Suicidal Ideation
4.
Age Ageing ; 50(2): 527-533, 2021 02 26.
Article in English | MEDLINE | ID: mdl-32931546

ABSTRACT

BACKGROUND: evidence is largely available indicating benefits to adding a pharmacist on acute care wards. The benefits of maintaining pharmacotherapeutic consultant services on a geriatric ward remain unexplored. OBJECTIVES: to determine the impact of the removal of a clinical pharmacist from an acute geriatric ward on patients' Medication Appropriateness Index (MAI) scores, admission-related outcomes and drug burdens. METHODS: researchers consulted the archives for records of patients admitted to the geriatric care unit before and after the pharmacist's withdrawal. The primary outcome of differential MAI scores and secondary outcomes of rehospitalisations, emergency department visits, durations of hospitalisation and differential drug count were compared pre- and post-intervention. An interrupted time series analysis regression model was used for the primary outcome. RESULTS: a total of 305 patients admitted before (n = 208) and after (n = 97) the pharmacist's withdrawal were included in the study. The intervention had a significant impact on the primary outcome, increasing the relative differential MAI score (adjusted mean) by 9.3 points (95% confidence interval 3.9-14.6). As for the secondary outcomes, differences in admission-related outcomes were non-significant but the mean differential drug count significantly increased post-intervention from 0.02 to 1.36 (P < 0.001). CONCLUSION: the removal of the pharmacist led to an increase in inappropriate drug prescription. Careful consideration should be given to decisions regarding the removal of the pharmacist from acute geriatric care teams.


Subject(s)
Pharmacists , Potentially Inappropriate Medication List , Aged , Drug Prescriptions , Hospitalization , Humans , Inappropriate Prescribing/prevention & control
5.
Chemphyschem ; 20(21): 2874-2880, 2019 11 05.
Article in English | MEDLINE | ID: mdl-31502391

ABSTRACT

The understanding of major zeolite applications is partially based on diffusion of molecules inside or outside microporous networks. However, it is still a challenge to measure such phenomena. The diffusion ordered nuclear magnetic resonance spectroscopy (DOSY) technique has been reported to measure a probe molecule's diffusion inside porous solids. Pulsed-field gradient (PFG)-NMR has been used herein to measure the self-diffusivity of different probe molecules, such as neopentane, benzene, toluene and 1-dodecene with increasing dynamic diameter, respectively, on a series of H-ZSM-5 zeolites. The latter materials exhibit different crystal sizes, Si/Al ratios and the presence (or absence) of crystalline defects. In addition, shaped zeolite bodies representing industrial catalysts were compared with the afore-mentioned samples.

6.
Anesth Analg ; 128(6): e104-e108, 2019 06.
Article in English | MEDLINE | ID: mdl-31094804

ABSTRACT

We tested the hypothesis that during a continuous popliteal-sciatic nerve block, postoperative analgesia is improved with the catheter insertion point "deep" to the paraneural sheath immediately distal to the bifurcation between the tibial and common peroneal branches, compared with the traditional approach "superficial" to the paraneural sheath proximal to the bifurcation. The needle tip location was determined to be accurately located with a fluid bolus visualized with ultrasound; however, catheters were subsequently inserted without a similar fluid injection and visualization protocol (visualized air injection was permitted and usually implemented, but not required per protocol). The average pain (0-10 scale) the morning after surgery for subjects with a catheter inserted at the proximal subparaneural location (n = 31) was a median (interquartile) of 1.5 (0.0-3.5) vs 1.5 (0.0-4.0) for subjects with a catheter inserted at the distal supraparaneural location (n = 32; P = .927). Secondary outcomes were similarly negative.


Subject(s)
Analgesia/methods , Catheterization/methods , Nerve Block , Pain Management/methods , Pain, Postoperative/drug therapy , Sciatic Nerve/drug effects , Adult , Aged , Anesthetics, Local , Catheters , Female , Humans , Injections , Lidocaine/administration & dosage , Male , Middle Aged , Needles , Pain Measurement , Postoperative Period , Prospective Studies
7.
Anesth Analg ; 127(1): 240-246, 2018 07.
Article in English | MEDLINE | ID: mdl-29750695

ABSTRACT

BACKGROUND: A continuous adductor canal block provides analgesia after surgical procedures of the knee. Recent neuroanatomic descriptions of the thigh and knee led us to speculate that local anesthetic deposited in the distal thigh close to the adductor hiatus would provide superior analgesia compared to a more proximal catheter location. We therefore tested the hypothesis that during a continuous adductor canal nerve block, postoperative analgesia would be improved by placing the perineural catheter tip 2-3 cm cephalad to where the femoral artery descends posteriorly to the adductor hiatus (distal location) compared to a more proximal location at the midpoint between the anterior superior iliac spine and the superior border of the patella (proximal location). METHODS: Preoperatively, subjects undergoing total knee arthroplasty received an ultrasound-guided perineural catheter inserted either in the proximal or distal location within the adductor canal in a randomized, subject-masked fashion. Subjects received a single injection of lidocaine 2% via the catheter preoperatively, followed by an infusion of ropivacaine 0.2% (8 mL/h basal, 4 mL bolus, 30 minutes lockout) for the study duration. After joint closure, the surgeon infiltrated the entire joint using 30 mL of ropivacaine (0.5%), ketorolac (30 mg), epinephrine (5 µg/mL), and tranexamic acid (2 g). The primary end point was the median level of pain as measured on a numeric rating scale (NRS) during the time period of 8:00 AM to 12:00 PM the day after surgery. RESULTS: For the primary end point, the NRS of subjects with a catheter inserted at the proximal location (n = 24) was a median (10th, 25th-75th, 90th quartiles) of 0.5 (0.0, 0.0-3.2, 5.0) vs 3.0 (0.0, 2.0-5.4, 7.8) for subjects with a catheter inserted in the distal location (n = 26; P = .011). Median and maximum NRSs were lower in the proximal group at all other time points, but these differences did not reach statistical significance. There were no clinically relevant or statistically significant differences between the treatment groups for any other secondary end point, including opioid consumption and ambulation distance. CONCLUSIONS: For continuous adductor canal blocks accompanied by intraoperative periarticular local anesthetic infiltration, analgesia the day after knee arthroplasty is improved with a catheter inserted at the level of the midpoint between the anterior superior iliac spine and the superior border of the patella compared with a more distal insertion closer to the adductor hiatus.


Subject(s)
Anesthetics, Local/administration & dosage , Arthroplasty, Replacement, Knee/adverse effects , Catheters, Indwelling , Lidocaine/administration & dosage , Nerve Block/instrumentation , Pain, Postoperative/prevention & control , Ropivacaine/administration & dosage , Aged , Anesthetics, Local/adverse effects , California , Equipment Design , Female , Humans , Lidocaine/adverse effects , Male , Middle Aged , Nerve Block/adverse effects , Nerve Block/methods , Pain Measurement , Pain, Postoperative/diagnosis , Pain, Postoperative/etiology , Ropivacaine/adverse effects , Time Factors , Treatment Outcome
8.
Int Psychogeriatr ; 30(4): 503-510, 2018 04.
Article in English | MEDLINE | ID: mdl-29208069

ABSTRACT

ABSTRACTBackground:The Delirium Drug Scale (DDS) is an evaluation scale developed to assess a patient's drug burden for delirium. The primary goal is to validate the association between the DDS score and the incidence of delirium. METHODS: This study was an observational retrospective cross-sectional chart review study in patients aged 75 years and older. It was carried out in three emergency departments of a tertiary care university health center. Patients were included if a medication list was available. Delirium present upon admission was assessed during the first five days of admission. RESULTS: A total of 1,205 subjects were included in the analysis. The mean age was of 83.4 years, and 62.4% were female. The prevalence of delirium was 19.1%. A total of 745 patients (62%) were exposed to DDS medication. The relative risk for the low (1-2) and high (>2) exposure group according to the DDS score was of 1.26 (CI: 0.95; 1.66) and 2.18 (CI: 1.61; 2.96) compared to a score of 0. In the multivariate analysis, dementia, anxiety, insomnia, history of delirium, infection, and acute kidney failure were significantly associated to delirium. When adjusted for confounding variables, the DDS score was associated with the incidence of delirium with an odd ratio (OR) of 1.29 (CI: 1.16; 1.44). CONCLUSIONS: This study found that DDS score was associated with delirium incidence. The association persisted in the multivariate analysis adjusted for 26 known risks and precipitating factors for delirium.


Subject(s)
Cholinergic Antagonists/adverse effects , Delirium/chemically induced , Dementia/drug therapy , Drug-Related Side Effects and Adverse Reactions/epidemiology , Emergency Service, Hospital/statistics & numerical data , Aged , Aged, 80 and over , Cross-Sectional Studies , Delirium/diagnosis , Delirium/epidemiology , Dementia/complications , Female , Humans , Incidence , Male , Retrospective Studies , Sensitivity and Specificity
9.
BMC Vet Res ; 13(1): 104, 2017 Apr 13.
Article in English | MEDLINE | ID: mdl-28407742

ABSTRACT

BACKGROUND: The risks during early growth on becoming overweight in adulthood are widely studied in humans. However, early-life predictive factors for canine adult overweight and obesity have not yet been studied. To identify factors that may help explain the development of overweight and obesity at adulthood in dogs, a longitudinal study of 2 years was conducted in 24 female Beagle dogs of the same age, sexual status, and raised under identical environmental conditions. By means of a hierarchical classification on principal components with the following quantitative values: fat-free mass (FFM), percentage fat mass and pelvic circumference at 2 years of age, three groups of dogs were established and were nominally named: ideal weight (IW, n = 9), slightly overweight (OW1, n = 6) and overweight (OW2, n = 9). With the aim of identifying predictive factors of development of obesity at adulthood parental characteristics, growth pattern, energy balance and plasma factors were analysed by logistic regression analysis. RESULTS: At 24 months, the group compositions were in line with the body condition scores (BCS 1-9) values of the IW (5 or 6/9), the OW1 (6/9) and the OW2 (7 or 8/9) groups. Logistic regression analysis permitted the identification of neonatal growth rate during the first 2 weeks of life (GR2W) and BCS at 7 months as predictors for the development of obesity at adulthood. Seventy percent of dogs with either GR2W >125% or with BCS > 6/9 at 7 months belonged to the OW2 group. Results from energy intake and expenditure, corrected for FFM, showed that there was a greater positive energy imbalance between 7 and 10 months for the OW2, compared to the IW group. CONCLUSION: This study expands the understanding of previously reported risk factors for being overweight or obese in dogs, establishing that (i) 15 out of 24 of the studied dogs became overweight and (ii) GR2W and BCS at 7 months of age could be used as predictive factors as overweight adult dogs in the OW2 group had higher values compared the other groups of dogs.


Subject(s)
Dog Diseases/etiology , Obesity/veterinary , Animals , Animals, Newborn , Dog Diseases/metabolism , Dogs , Energy Intake , Energy Metabolism , Female , Longitudinal Studies , Obesity/etiology , Obesity/metabolism , Physical Conditioning, Animal , Risk Factors
10.
J Arthroplasty ; 32(12): 3632-3636, 2017 12.
Article in English | MEDLINE | ID: mdl-28709756

ABSTRACT

BACKGROUND: There is sparse evidence on the benefit of neuraxial (NA) vs general anesthesia (GA) as the primary anesthetic in postoperative outcomes following bilateral total knee arthroplasty. We sought to elucidate differences in outcomes in this surgical population using a national database. METHODS: We used data from the National Surgical Quality Improvement Program from 2007 to 2013 and compared rates of various postoperative outcomes in propensity-matched cohorts (NA vs GA). RESULTS: After exclusion, there were 1957 patients included in the final analysis, of which 26% received NA as the primary anesthetic. Propensity-matched cohorts were generated to ensure no differences in various comorbidities (including bleeding disorders or inadequate cessation of anticoagulation therapy), case duration, and patient demographics between both cohorts. Among the matched cohorts, there were no differences in preoperative platelet count, hematocrit, or international normalized ratio. NA was associated with decreased blood transfusion requirement and decreased total number of units of blood products transfused (P < .0001 for both outcomes). However, there were no differences in other outcomes, including hospital length of stay, pulmonary embolism, deep vein thrombosis, or urinary tract infections. CONCLUSION: Our study demonstrates that in matched cohorts, NA is associated with decreased blood transfusion requirements in patients undergoing bilateral total knee arthroplasty when compared to GA as the primary anesthetic.


Subject(s)
Anesthesia, Conduction/adverse effects , Anesthesia, General/adverse effects , Arthroplasty, Replacement, Knee/adverse effects , Blood Transfusion/statistics & numerical data , Postoperative Complications/etiology , Aged , Arthroplasty, Replacement, Knee/statistics & numerical data , Comorbidity , Databases, Factual , Female , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Period , Pulmonary Embolism/epidemiology , Quality Improvement , Retrospective Studies , United States/epidemiology , Venous Thrombosis/epidemiology
11.
Anal Biochem ; 500: 63-5, 2016 May 01.
Article in English | MEDLINE | ID: mdl-26898306

ABSTRACT

Gas chromatography-mass spectrometry (GC-MS) was compared with gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) for measurements of cholesterol (13)C enrichment after infusion of labeled precursor ([(13)C1,2]acetate). Paired results were significantly correlated, although GC-MS was less accurate than GC-C-IRMS for higher enrichments. Nevertheless, only GC-MS was able to provide information on isotopologue distribution, bringing new insights to lipid metabolism. Therefore, we assessed the isotopologue distribution of cholesterol in humans and dogs known to present contrasted cholesterol metabolic pathways. The labeled tracer incorporation was different in both species, highlighting the subsidiarity of GC-MS and GC-C-IRMS to analyze in vivo stable isotope studies.


Subject(s)
Cholesterol/analysis , Gas Chromatography-Mass Spectrometry/methods , Carbon Isotopes/analysis
12.
BMC Vet Res ; 12(1): 130, 2016 Jun 28.
Article in English | MEDLINE | ID: mdl-27353524

ABSTRACT

BACKGROUND: Research in cats has shown that increased fermentation-derived propionic acid and its metabolites can be used as alternative substrates for gluconeogenesis, thus sparing amino acids for other purposes. This amino acid sparing effect could be of particular interest in patients with kidney or liver disease, where this could reduce the kidneys'/liver's burden of N-waste removal. Since dogs are known to have a different metabolism than the obligatory carnivorous cat, the main objective of this study was to assess the possibility of altering amino acid metabolism through intestinal fermentation in healthy dogs. This was studied by supplementing a low-protein diet with fermentable fibres, hereby providing an initial model for future studies in dogs suffering from renal/liver disease. RESULTS: Eight healthy dogs were randomly assigned to one of two treatment groups: sugar beet pulp and guar gum mix (SF: soluble fibre, estimated to mainly stimulate propionic acid production) or cellulose (IF: insoluble fibre). Treatments were incorporated into a low-protein (17 %) extruded dry diet in amounts to obtain similar total dietary fibre (TDF) contents for both diets (9.4 % and 8.2 % for the SF and IF diet, respectively) and were tested in a 4-week crossover feeding trial. Apparent faecal nitrogen digestibility and post-prandial fermentation metabolites in faeces and plasma were evaluated. Dogs fed the SF diet showed significantly higher faecal excretion of acetic and propionic acid, resulting in a higher total SCFA excretion compared to IF. SF affected the three to six-hour postprandial plasma acylcarnitine profile by significantly increasing AUC of acetyl-, propionyl-, butyryl- + isobutyryl-, 3-OH-butyryl-, 3-OH-isovaleryl- and malonyl-L-carnitine. Moreover, the amino acid plasma profile at that time was modified as leucine + isoleucine concentrations were significantly increased by SF, and a similar trend for phenylalanine and tyrosine's AUC was found. CONCLUSION: These results indicate that guar gum and sugar beet pulp supplementation diminishes postprandial use of amino acids favoring instead the use of short-chain fatty acids as substrate for the tricarboxylic acid (TCA) cycle. Further research is warranted to investigate the amino acid sparing effect of fermentable fibres in dogs with kidney/liver disease.


Subject(s)
Diet/veterinary , Dietary Fiber/metabolism , Dogs/metabolism , Acetic Acid/analysis , Amino Acids/metabolism , Animals , Carnitine/analogs & derivatives , Carnitine/blood , Cross-Over Studies , Fatty Acids, Volatile/metabolism , Feces/chemistry , Propionates/analysis , Random Allocation
13.
BMC Vet Res ; 12(1): 162, 2016 Aug 03.
Article in English | MEDLINE | ID: mdl-27487916

ABSTRACT

BACKGROUND: Grape and blueberry extracts are known to protect against age-related cognitive decline. However, beneficial effects achieved by mixing grape and blueberry extracts have yet to be evaluated in dogs, or their bioavailability assessed. Of concern to us were cases of acute renal failure in dogs, after their ingestion of grapes or raisins. The European Pet Food Industry Federation (2013) considers only the grape or raisin itself to be potentially dangerous; grape-seed extracts per-se, are not considered to be a threat. Our aim was therefore to evaluate the renal and hepatic safety, and measure plasma derivatives of a polyphenol-rich extract from grape and blueberry (PEGB; from the Neurophenols Consortium) in dogs. Polyphenol expression was analyzed by UHPLC-MS/MS over 8 hours, for dogs given PEGB at 4 mg/kg. Safety was evaluated using four groups of 6 dogs. These groups received capsules containing no PEGB (control), or PEGB at 4, 20, or 40 mg/kg BW/d, for 24 weeks. Blood and urine samples were taken the week prior to study commencement, then at the end of the 24-wk study period. Routine markers of renal and liver damage, including creatinine (Creat), blood urea nitrogen, albumin, minerals, alkaline phosphatase (ALP), and alanine transaminase (ALT) were measured. Biomarkers for early renal damage were also evaluated in plasma (cystatin C (CysC), and neutrophil gelatinase-associated lipocalin (NGAL)), and urine (CysC, clusterin (Clu), and NGAL). Ratios of urinary biomarkers to Creat were calculated, and compared with acceptable maximal values obtained for healthy dogs, as reported in the literature. RESULTS: While several PEGB-specific polyphenols and metabolites were detected in dog plasma, at the end of the PEGB consumption period, our biomarker analyses presented no evidence of either renal or liver damage (Creat, BUN, ionogram, albumin and ALT, ALP). Similarly, no indication of early renal damage could be detected. Plasma CysC, urinary CysC/Creat, Clu/Creat, and NGAL/Creat ratios were all beneath reported benchmarked maximums, with no evidence of PEGB toxicity. CONCLUSIONS: Long-term consumption of a pet specific blend of a polyphenol-rich extract from grape and blueberry (PEGB; from the Neurophenols Consortium), was not associated with renal or hepatic injury, and can therefore be considered safe.


Subject(s)
Blueberry Plants , Dietary Supplements/standards , Dogs , Fruit/chemistry , Plant Extracts/standards , Vitis , Animals , Biomarkers/blood , Biomarkers/urine , Kidney/drug effects , Liver/drug effects , Plant Extracts/toxicity , Polyphenols/blood , Polyphenols/toxicity , Polyphenols/urine
14.
Nat Commun ; 15(1): 5270, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902233

ABSTRACT

Regulation of codon optimality is an increasingly appreciated layer of cell- and tissue-specific protein expression control. Here, we use codon-modified reporters to show that differentiation of Drosophila neural stem cells into neurons enables protein expression from rare-codon-enriched genes. From a candidate screen, we identify the cytoplasmic polyadenylation element binding (CPEB) protein Orb2 as a positive regulator of rare-codon-dependent mRNA stability in neurons. Using RNA sequencing, we reveal that Orb2-upregulated mRNAs in the brain with abundant Orb2 binding sites have a rare-codon bias. From these Orb2-regulated mRNAs, we demonstrate that rare-codon enrichment is important for mRNA stability and social behavior function of the metabotropic glutamate receptor (mGluR). Our findings reveal a molecular mechanism by which neural stem cell differentiation shifts genetic code regulation to enable critical mRNA stability and protein expression.


Subject(s)
Cell Differentiation , Drosophila Proteins , Neural Stem Cells , Neurons , RNA Stability , RNA, Messenger , Animals , Drosophila Proteins/metabolism , Drosophila Proteins/genetics , Neurons/metabolism , Neurons/cytology , RNA, Messenger/metabolism , RNA, Messenger/genetics , Cell Differentiation/genetics , Neural Stem Cells/metabolism , Neural Stem Cells/cytology , Codon/genetics , Drosophila melanogaster/genetics , Drosophila melanogaster/cytology , Drosophila melanogaster/metabolism , Receptors, Metabotropic Glutamate/metabolism , Receptors, Metabotropic Glutamate/genetics , mRNA Cleavage and Polyadenylation Factors/metabolism , mRNA Cleavage and Polyadenylation Factors/genetics , Drosophila/genetics , Drosophila/metabolism , Brain/metabolism , Brain/cytology , Transcription Factors
15.
J Vet Intern Med ; 38(1): 285-299, 2024.
Article in English | MEDLINE | ID: mdl-38084870

ABSTRACT

BACKGROUND: High-salt diets promote urine dilution and decrease urolithiasis risk. OBJECTIVE: Prospectively evaluate the safety of chronic high dietary salt intake (randomized controlled trial). ANIMALS: Twenty research colony neutered, healthy aged cats (11.5 years [10.0-11.6], median [interquartile range]). METHODS: Healthy cats were randomized to control or high-salt dry diets (sodium: 1.02 ± 0.16 [mean, SD] and 3.26 ± 0.30 g/Mcal metabolizable energy [ME], respectively; chloride: 2.26 ± 0.33 and 5.71 ± 0.28 g/Mcal ME, respectively), fed for up to 60 months. Assessments included CBC, plasma biochemistry, urinalysis, glomerular filtration rate (GFR), blood pressure, renal and cardiac (conventional Doppler and 2-dimensional color tissue Doppler) imaging, annually. Cats that died or were euthanized underwent necropsy. Diet effects over time were evaluated with linear mixed models. RESULTS: Follow-up duration (median [Interquartile range]) was similar between the control (38.7 months [28.6-48.2]) and high-salt group (51.4 months [45.7-59.0]). Diet had no significant effect on changes in GFR, blood pressure, plasma creatinine concentration, end-diastolic left ventricular (LV) wall thicknesses, LV internal diameters, LV systolic function, left atrial size, or systolic and diastolic Doppler variables. One control cat developed hypertension. One high-salt group cat developed persistent azotemia. Serial plasma biochemistry and urine specific gravity suggested early chronic kidney disease in 4 nonazotemic cats (2 per group), consistent with necropsy findings. CONCLUSIONS AND CLINICAL IMPORTANCE: In healthy aged cats, a commercial veterinary diet containing 3.26 ± 0.30 g/Mcal ME sodium was safe with regard to renal and cardiac function for up to 5 years.


Subject(s)
Arachis , Sodium Chloride, Dietary , Cats , Animals , Sodium Chloride, Dietary/adverse effects , Prospective Studies , Kidney , Sodium
16.
bioRxiv ; 2023 Jul 27.
Article in English | MEDLINE | ID: mdl-37546801

ABSTRACT

Regulation of codon optimality is an increasingly appreciated layer of cell- and tissue-specific protein expression control. Here, we use codon-modified reporters to show that differentiation of Drosophila neural stem cells into neurons enables protein expression from rare-codon-enriched genes. From a candidate screen, we identify the cytoplasmic polyadenylation element binding (CPEB) protein Orb2 as a positive regulator of rare-codon-dependent expression in neurons. Using RNA sequencing, we reveal that Orb2-upregulated mRNAs in the brain with abundant Orb2 binding sites have a rare-codon bias. From these Orb2-regulated mRNAs, we demonstrate that rare-codon enrichment is important for expression control and social behavior function of the metabotropic glutamate receptor (mGluR). Our findings reveal a molecular mechanism by which neural stem cell differentiation shifts genetic code regulation to enable critical mRNA and protein expression.

17.
Br J Nutr ; 107(9): 1305-15, 2012 May.
Article in English | MEDLINE | ID: mdl-21920060

ABSTRACT

Glucose intolerance and dyslipidaemia are independent risk factors for endothelium dysfunction and CVD. The aim of the present study was to analyse the preventive effect of n-3 PUFA (EPA and DHA) on lipid and carbohydrate disturbances and endothelial dysfunction. Three groups of adult hamsters were studied for 20 weeks: (1) control diet (Control); (2) high-fat diet (HF); (3) high-fat diet enriched with n-3 PUFA (HFn-3) groups. The increase in body weight and fat mass in the HF compared to the Control group (P < 0.05) was not found in the HFn-3 group. Muscle TAG content was similar in the Control and HF groups, but significantly lower in the HFn-3 group (P = 0.008). Glucose tolerance was impaired in the HF compared to the Control group, but this impairment was prevented by n-3 PUFA in the HFn-3 group (P < 0.001). Plasma TAG and cholesterol were higher in the HF group compared to the Control group (P < 0.001), but lower in the HFn-3 group compared to the HF group (P < 0.001). HDL-cholesterol was lower in the HFn-3 group compared to the Control and HF groups (P < 0.0005). Hepatic secretion of TAG was lower in the HFn-3 group compared to the HF group (P < 0.005), but did not differ from the Control group. Hepatic gene expression of sterol regulatory element-binding protein-1c, diacylglycerol O-acyltransferase 2 and stearyl CoA desaturase 1 was lower in the HFn-3 group, whereas carnitine palmitoyl transferase 1 and scavenger receptor class B type 1 expression was higher (P < 0.05). In adipocytes and adipose macrophages, PPARγ and TNFα expression was higher in the HF and HFn-3 groups compared to the Control group. Endothelium relaxation was higher in the HFn-3 (P < 0.001) than in the HF and Control groups, and was correlated with glucose intolerance (P = 0.03) and cholesterol (P = 0.0003). In conclusion, n-3 PUFA prevent some metabolic disturbances induced by high-fat diet and improve endothelial function in hamsters.


Subject(s)
Diet, High-Fat , Endothelium, Vascular/drug effects , Fatty Acids, Omega-3/metabolism , Obesity/metabolism , Adipocytes/cytology , Adipose Tissue/metabolism , Animal Feed , Animals , Aorta/pathology , Body Composition , Body Weight , CD36 Antigens/metabolism , Carbohydrate Metabolism , Cricetinae , Dyslipidemias/metabolism , Endothelium, Vascular/metabolism , Glucose/metabolism , Glucose Intolerance , Lipid Metabolism , Lipids/blood , Lipoproteins, VLDL/metabolism , Liver/metabolism , Macrophages/cytology , Male , Mesocricetus , Muscles/metabolism , Obesity/physiopathology
18.
Sr Care Pharm ; 37(4): 157-162, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-35337430

ABSTRACT

Objective To describe the use of clonidine in hospitalized older people for acute management of hypertension. Methods This was an observational retrospective cross-sectional chart review study. Older people hospitalized between November 2017 and November 2018, with a one-time or as-needed clonidine order were eligible, and a random sample of these patients were included. Hospitalized patients could be admitted for hypertensive urgency or emergency, or for other reasons. Results During the 12-month study period, 546 charts were identified as having at least one clonidine prescription, 248 were screened and 205 were included. The mean age was 75 years of age ± 8 years of age and men made up 53% (n = 109) of the group. One hundred fifty-one patients (74%) received at least one dose of clonidine and the remaining patients has a clonidine prescription but did not reach the blood pressure threshold for clonidine administration. The mean number of doses per patient was 1.8 ± 2.0. Twenty-nine percent of clonidine doses were given when systolic and diastolic blood pressure was below 180 mmHg and 120 mmHg respectively. A total of 25 patients (17%) had a potential adverse reaction following clonidine administration. One patient had a stroke and two patients fell. Sixty-eight patients had evidence of target organ dysfunction related to hypertension prior to clonidine administration. Conclusions Clonidine remains widely prescribed in hospitalized older people. It is possibly due to its rapid onset and little need for dosing adjustment. Clinical interventions should be designed and implanted to reduce its prescription.


Subject(s)
Clonidine , Hypertension , Aged , Blood Pressure , Clonidine/adverse effects , Cross-Sectional Studies , Female , Humans , Hypertension/chemically induced , Hypertension/drug therapy , Hypertension/epidemiology , Male , Retrospective Studies
19.
Surg Clin North Am ; 102(5): 797-808, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36209746

ABSTRACT

Perforated appendicitis continues to be a significant cause of morbidity for children. In most centers, ultrasound has replaced computed tomography as the initial imaging modality for this condition. Controversies surrounding optimal medical and surgical management of appendicitis are discussed. Management of intussusception begins with clinical assessment and ultrasound, followed by image-guided air or saline reduction enema. When surgery is required, laparoscopy is typically utilized unless bowel resection is required. The differential diagnosis for pediatric gastrointestinal bleeding is broad but often made with age, history, and physical examination. Endoscopy or laparoscopy is sometimes needed to confirm a diagnosis or for treatment.


Subject(s)
Appendicitis , Intussusception , Laparoscopy , Acute Disease , Appendicitis/complications , Appendicitis/diagnosis , Appendicitis/surgery , Child , Enema/methods , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/therapy , Humans , Infant , Intussusception/diagnosis , Intussusception/etiology , Intussusception/surgery
20.
J Feline Med Surg ; 24(12): 1203-1211, 2022 12.
Article in English | MEDLINE | ID: mdl-35142590

ABSTRACT

OBJECTIVES: From the authors' experience, the consumption of a balanced prescription home-prepared diet that includes zucchini (courgette) benefits cats with recurrent urolithiasis, but there is no published evidence to support this. The aim was to study the effects on urinary parameters of (1) a balanced prescription home-prepared diet containing zucchini, and (2) the addition of zucchini to a dry food, compared with two commercial therapeutic diets. METHODS: Eight healthy cats were included in a Latin-square designed protocol. Five diets were evaluated: two commercial diets, designed for cats with urinary disorders, one high-moisture (U-WET) and one high-sodium dry (U-DRY); one home-prepared diet (HOME); one commercial dry food for adult maintenance (DRY); and DRY given together with 10 g of zucchini per kg body weight (DRY-Zuc). After a 7-day adaptation period, urine was collected and daily food and water intakes were assessed for 12 days. Urinary parameters, and relative supersaturation (RSS) for calcium oxalate (CaOx) and struvite, were determined. Data underwent repeated measures ANOVA analysis. RESULTS: The digestibility of energy, dry matter, protein and fat was highest with the HOME diet. CaOx RSS was lowest in cats eating the HOME diet, but not significantly different from the U-WET or U-DRY diets. CaOx RSS was lower in cats eating the DRY-Zuc diet than in cats eating the DRY diet. Struvite RSS did not differ significantly among groups. CONCLUSIONS AND RELEVANCE: This study shows that a balanced prescription home-prepared diet was safe and allowed a very low urinary CaOx RSS. It also showed that adding zucchini to dry food lowered the urine CaOx RSS.


Subject(s)
Calcium Oxalate , Oxalates , Cats , Animals , Calcium , Diet/veterinary , Prescriptions
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