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1.
Chem Commun (Camb) ; 60(46): 5956-5959, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38766982

ABSTRACT

Np(IV) Lewis base adducts were prepared by ligand substitution of NpCl4(DME)2. Using acetonitrile and pyridine, NpCl4(MeCN)4 (1) and NpCl4(pyr)4 (2) were isolated, respectively. Addition of t-butylbipyridine and triphenylphosphine oxide generated the respective Lewis base adducts, NpCl4(tBuBipy)2 (3) and NpCl4(OPPh3)2 (4). All species were fully characterized using spectroscopic and structural analyses.

2.
Orphanet J Rare Dis ; 19(1): 215, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38778404

ABSTRACT

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare neurodegenerative brain disease with rapid progression and currently limited treatment options. A comprehensive understanding of disease progression, management, and healthcare resource utilization is limited, and further research is challenging due to the small population of patients. To address these challenges in conducting PSP research, individuals with PSP were recruited using a multichannel approach tailored specifically to the PSP community. We performed a retrospective observational study using data abstracted from participant medical records collected from multiple patient care centers. RESULTS: Seventy-two individuals with PSP were eligible for inclusion. On average, 144 medical documents per participant were collected from an average of 2.9 healthcare centers per participant, with a mean study period of 7.9 years. Among participants with a date of symptom onset documented in the medical records, the median time for the onset of the first fall was 2.0 years (IQR 3.2) before diagnosis, the median onset of unsteady gait or gait impairment was 1.2 years (IQR 1.8) before diagnosis, and the median onset of mobility problems was 0.8 years (IQR 1.8) before diagnosis. The most widely utilized healthcare resources, with at least 85% of participants using each of these resources at some point during the disease course, were medications (100%), imaging (99%), assistive devices (90%), supportive care (86%), and surgeries and procedures (85%). CONCLUSIONS: This retrospective study adds to the current understanding of PSP symptoms, comorbidities, and healthcare resource utilization (HRU) across the disease journey. By involving individuals with PSP and their caregivers or legally authorized representatives in the research process, this study was unique in its approach to participant recruitment and enabled individuals to participate in research without the need for travel. We collected medical documents from multiple healthcare centers, allowing for broad data collection covering the entire disease journey. This approach to the collection of real-world data may be used to generate valuable insights into many aspects of disease progression and management in PSP and many other rare diseases.


Subject(s)
Disease Progression , Supranuclear Palsy, Progressive , Humans , Supranuclear Palsy, Progressive/therapy , Retrospective Studies , Female , Male , Aged , Canada , Middle Aged , United States , Patient Acceptance of Health Care/statistics & numerical data , Aged, 80 and over
3.
Inorg Chem ; 63(21): 9418-9426, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38097382

ABSTRACT

The synthesis and characterization of two cerium complexes of redox-active amine/amido-phenolate-type ligands are reported. A tripodal framework comprising the tris(2-(3',5'-di-tert-butyl-2'-hydroxyphenyl)amino-phenyl) amine (H6Clamp) proligand was synthesized for comparison of its cerium complex with a potassium-cerium heterobimetallic complex of the 4,6-di-tert-butyl-2-[(2,6-diisopropylphenyl)imino]quinone (dippap) proligand. Structural studies indicate differences in the cerium(III) cation coordination spheres, where CeIII(CH3CN)1.5(H3Clamp) (1-Ce(H3Clamp)) exhibits shorter Ce-O distances and longer Ce-N bond distances compared to the analogous distances in K3(THF)3CeIII(dippap)3 (2-Ce(ap)), due to the gross structural differences between the systems. Differences are also evident in the temperature-dependent magnetic properties, where smaller χT products were observed for 2-Ce(ap) compared to 1-Ce(H3Clamp). Solution electrochemical studies for the complexes were interpreted based on ligand- and metal-based oxidation events, and the cerium(III) oxidation of 2-Ce(ap) was observed to be more facile than that of 1-Ce(H3Clamp), behavior that was cautiously attributed to the rigidity of the encrypted 1-Ce(H3Clamp) complex compared to the heterobimetallic framework of 2-Ce(ap). These results contribute to the understanding of how ligand designs can promote facile redox cycling for cerium complexes of redox-active ligands, given the large contraction of cerium-ligand bonds upon oxidation.

4.
Emerg Microbes Infect ; 12(2): 2270071, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37869789

ABSTRACT

The emergence of SARS-CoV-2 recombinants is of particular concern as they can result in a sudden increase in immune evasion due to antigenic shift. Recent recombinants XBB and XBB.1.5 have higher transmissibility than previous recombinants such as "Deltacron." We hypothesized that immunity to a SARS-CoV-2 recombinant depends on prior exposure to its parental strains. To test this hypothesis, we examined whether Delta or Omicron (BA.1 or BA.2) immunity conferred through infection, vaccination, or breakthrough infection could neutralize Deltacron and XBB/XBB.1.5 recombinants. We found that Delta, BA.1, or BA.2 breakthrough infections provided better immune protection against Deltacron and its parental strains than did the vaccine booster. None of the sera were effective at neutralizing the XBB lineage or its parent BA.2.75.2, except for the sera from the BA.2 breakthrough group. These results support our hypothesis. In turn, our findings underscore the importance of multivalent vaccines that correspond to the antigenic profile of circulating variants of concern and of variant-specific diagnostics that may guide public health and individual decisions in response to emerging SARS-CoV-2 recombinants.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/prevention & control , Vaccination , Antigenic Drift and Shift , Breakthrough Infections , Antibodies, Neutralizing , Antibodies, Viral
5.
JCI Insight ; 8(20)2023 Oct 23.
Article in English | MEDLINE | ID: mdl-37698919

ABSTRACT

Retinoic acid receptor (RAR) signaling is essential for mammalian kidney development but, in the adult kidney, is restricted to occasional collecting duct epithelial cells. We now show that there is widespread reactivation of RAR signaling in proximal tubular epithelial cells (PTECs) in human sepsis-associated acute kidney injury (AKI) and in mouse models of AKI. Genetic inhibition of RAR signaling in PTECs protected against experimental AKI but was unexpectedly associated with increased expression of the PTEC injury marker Kim1. However, the protective effects of inhibiting PTEC RAR signaling were associated with increased Kim1-dependent apoptotic cell clearance, or efferocytosis, and this was associated with dedifferentiation, proliferation, and metabolic reprogramming of PTECs. These data demonstrate the functional role that reactivation of RAR signaling plays in regulating PTEC differentiation and function in human and experimental AKI.


Subject(s)
Acute Kidney Injury , Kidney Tubules, Proximal , Mice , Animals , Humans , Kidney Tubules, Proximal/metabolism , Tretinoin/pharmacology , Tretinoin/metabolism , Kidney/metabolism , Acute Kidney Injury/metabolism , Epithelial Cells/metabolism , Mammals
6.
Inorg Chem ; 62(39): 15819-15823, 2023 Oct 02.
Article in English | MEDLINE | ID: mdl-37713645

ABSTRACT

A family of thorium complexes featuring the redox-noninnocent pyridinediimine ligand MesPDIMe was synthesized, including (MesPDIMe)ThCl4 (1-Th), (MesPDIMe)ThCl3(THF) (2-Th), (MesPDIMe)ThCl2(THF)2 (3-Th) and [(MesPDIMe)Th(THF)]2 (5-Th) Full characterization of these species shows that these complexes feature MesPDIMe in four different oxidation states. The electronic structures of these complexes have been explored using 1H NMR and electronic absorption spectroscopies, X-ray crystallography, and SQUID magnetometry where appropriate.

7.
Am J Physiol Renal Physiol ; 324(5): F472-F482, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36995924

ABSTRACT

Acute kidney injury (AKI) is common in surgical and critically ill patients. This study examined whether pretreatment with a novel Toll-like receptor 4 agonist attenuated ischemia-reperfusion injury (IRI)-induced AKI (IRI-AKI). We performed a blinded, randomized-controlled study in mice pretreated with 3-deacyl 6-acyl phosphorylated hexaacyl disaccharide (PHAD), a synthetic Toll-like receptor 4 agonist. Two cohorts of male BALB/c mice received intravenous vehicle or PHAD (2, 20, or 200 µg) at 48 and 24 h before unilateral renal pedicle clamping and simultaneous contralateral nephrectomy. A separate cohort of mice received intravenous vehicle or 200 µg PHAD followed by bilateral IRI-AKI. Mice were monitored for evidence of kidney injury for 3 days postreperfusion. Kidney function was assessed by serum blood urea nitrogen and creatinine measurements. Kidney tubular injury was assessed by semiquantitative analysis of tubular morphology on periodic acid-Schiff (PAS)-stained kidney sections and by kidney mRNA quantification of injury [neutrophil gelatinase-associated lipocalin (Ngal), kidney injury molecule-1 (Kim-1), and heme oxygenase-1 (Ho-1)] and inflammation [interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (Tnf-α)] using quantitative RT-PCR. Immunohistochemistry was used to quantify proximal tubular cell injury and renal macrophages by quantifying the areas stained with Kim-1 and F4/80 antibodies, respectively, and TUNEL staining to detect the apoptotic nuclei. PHAD pretreatment yielded dose-dependent kidney function preservation after unilateral IRI-AKI. Histological injury, apoptosis, Kim-1 staining, and Ngal mRNA were lower in PHAD-treated mice and IL-1ß mRNA was higher in PHAD-treated mice. Similar pretreatment protection was noted with 200 mg PHAD after bilateral IRI-AKI, with significantly reduced Kim-1 immunostaining in the outer medulla of mice treated with PHAD after bilateral IRI-AKI. In conclusion, PHAD pretreatment leads to dose-dependent protection from renal injury after unilateral and bilateral IRI-AKI in mice.NEW & NOTEWORTHY Pretreatment with 3-deacyl 6-acyl phosphorylated hexaacyl disaccharide; a novel synthetic Toll-like receptor 4 agonist, preserves kidney function during ischemia-reperfusion injury-induced acute kidney injury.


Subject(s)
Acute Kidney Injury , Reperfusion Injury , Toll-Like Receptor 4 , Animals , Male , Mice , Acute Kidney Injury/etiology , Acute Kidney Injury/pathology , Acute Kidney Injury/prevention & control , Kidney/pathology , Lipocalin-2 , Mice, Inbred C57BL , Reperfusion Injury/complications , Reperfusion Injury/drug therapy , Reperfusion Injury/pathology , RNA, Messenger , Toll-Like Receptor 4/agonists
8.
J Am Acad Orthop Surg ; 30(20): e1327-e1336, 2022 Oct 15.
Article in English | MEDLINE | ID: mdl-36200821

ABSTRACT

INTRODUCTION: Antimicrobial stewardship has been cited as a crucial component of orthopaedic surgical care; however, limited high-quality data exist to guide antibiotic use across the total joint arthroplasty continuum. Antimicrobial stewardship program (ASP) implementation and evaluation is needed in this space. METHODS: We pursued a prospective, sequential cohort study of an interprofessional ASP for total joint arthroplasty (TJA) formed in late 2017 at the study institution. Twelve total evidence-based recommendations for protocol change were issued, with 11 accepted and implemented across three project phases spanning March 2018 to December 2019. The primary study outcome was the rate of optimal preoperative intravenous antibiotic selection as assessed for Baseline versus Postintervention time periods. Secondary outcomes included individual antibiotic utilization rates. Descriptive statistics were pursued for institutional surgical site infection (SSI) and postoperative acute kidney injury (AKI) rates across the affected time frame. A cost-benefit analysis of the ASP was estimated from the institutional perspective. RESULTS: The rate of optimal preoperative antibiotic selection increased from 64.9% in the Baseline Period (February 2018, n = 57) to 95.4% in the Postimplementation period (June 2018 to December 2019, n = 1,220) (P < 0.001). The rates of second-line preoperative antibiotics and total perioperative antibiotic exposures decreased. Total SSI and AKI rates in primary elective TJA seemed to decrease from calendar year 2018 to 2019 (deep SSI 1.00% to 0.22%, superficial SSI 0.66% to 0.00%, and AKI 1.97% to 1.03%). The institution realized an estimated $197,050 cost savings per 1000 TJA procedures. DISCUSSION: A comprehensive ASP for TJA was associated with an increased use of optimal preoperative antibiotic selection, decreased total antibiotic exposures, and cost savings, without apparent detriment to SSI or AKI rates.


Subject(s)
Acute Kidney Injury , Antimicrobial Stewardship , Acute Kidney Injury/drug therapy , Anti-Bacterial Agents/therapeutic use , Arthroplasty , Cohort Studies , Humans , Prospective Studies , Retrospective Studies , Surgical Wound Infection/drug therapy , Surgical Wound Infection/prevention & control
9.
Sci Rep ; 12(1): 17046, 2022 10 11.
Article in English | MEDLINE | ID: mdl-36221029

ABSTRACT

Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to persist due to mutations resulting in newer, more infectious variants of concern. We aimed to leverage an ongoing private SARS-CoV-2 testing laboratory's infrastructure to monitor SARS-CoV-2 variants in two large California counties. Study enrollment was offered to adults aged 18 years or older in Los Angeles County and Riverside County who recently tested positive for SARS-CoV-2 with a polymerase chain reaction (PCR) assay. A cycle threshold value less than or equal to 30 cycles was considered a positive test for sequencing purposes. Within 5 days of study enrollment, clinician-monitored, self-collected oral fluid and anterior nares swab specimens were obtained from participants. Specimens were transported and stored at 8 °C or cooler. Samples underwent ribonucleic acid extraction, library preparation, and sequencing. SARS-CoV-2 lineages were identified using sequencing data. Participant and genomic data were analyzed using statistical tools and visualized with toolkits. The study was approved by Advarra Institutional Review Board (Pro00053729). From May 27, 2021 to September 9, 2021, 503 individuals were enrolled and underwent specimen collection. Of the 503 participants, 238 (47.3%) participants were women, 329 (63.6%) participants were vaccinated, and 221 (43.9%) participants were of Hispanic or Spanish origin. Of the cohort, 496 (98.6%) participants had symptoms at the time of collection. Among the 503 samples, 443 (88.1%) nasal specimens and 353 (70.2%) oral specimens yielded positive sequencing results. Over our study period, the prevalence of the Alpha variant of SARS-CoV-2 decreased (initially 23.1% [95% confidence interval (95% CI): 0-0.49%] to 0% [95% CI 0.0-0.0%]) as the prevalence of the Delta variant of SARS-CoV-2 increased (initially 33.3% [95% CI 0.0-100.0%] to 100.0% [95% CI 100.0-100.0%]). A strain that carried mutations of both Delta and Mu was identified. We found that outpatient SARS-CoV-2 variant surveillance could be conducted in a timely and accurate manner. The prevalence of different variants changed over time. A higher proportion of nasal specimens yielded results versus oral specimens. Timely and regional outpatient SARS-CoV-2 variant surveillance could be used for public health efforts to identify changes in SARS-CoV-2 strain epidemiology.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Testing , Female , Humans , Male , RNA , SARS-CoV-2/genetics
10.
Proc Natl Acad Sci U S A ; 119(31): e2200592119, 2022 08 02.
Article in English | MEDLINE | ID: mdl-35858386

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant contains extensive sequence changes relative to the earlier-arising B.1, B.1.1, and Delta SARS-CoV-2 variants that have unknown effects on viral infectivity and response to existing vaccines. Using SARS-CoV-2 virus-like particles (VLPs), we examined mutations in all four structural proteins and found that Omicron and Delta showed 4.6-fold higher luciferase delivery overall relative to the ancestral B.1 lineage, a property conferred mostly by enhancements in the S and N proteins, while mutations in M and E were mostly detrimental to assembly. Thirty-eight antisera samples from individuals vaccinated with Pfizer/BioNTech, Moderna, or Johnson & Johnson vaccines and convalescent sera from unvaccinated COVID-19 survivors had 15-fold lower efficacy to prevent cell transduction by VLPs containing the Omicron mutations relative to the ancestral B.1 spike protein. A third dose of Pfizer vaccine elicited substantially higher neutralization titers against Omicron, resulting in detectable neutralizing antibodies in eight out of eight subjects compared to one out of eight preboosting. Furthermore, the monoclonal antibody therapeutics casirivimab and imdevimab had robust neutralization activity against B.1 and Delta VLPs but no detectable neutralization of Omicron VLPs, while newly authorized bebtelovimab maintained robust neutralization across variants. Our results suggest that Omicron has similar assembly efficiency and cell entry compared to Delta and that its rapid spread is due mostly to reduced neutralization in sera from previously vaccinated subjects. In addition, most currently available monoclonal antibodies will not be useful in treating Omicron-infected patients with the exception of bebtelovimab.


Subject(s)
Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , COVID-19/therapy , COVID-19/virology , Humans , Mutation , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics
11.
Nature ; 607(7918): 351-355, 2022 07.
Article in English | MEDLINE | ID: mdl-35584773

ABSTRACT

SARS-CoV-2 Delta and Omicron are globally relevant variants of concern. Although individuals infected with Delta are at risk of developing severe lung disease, infection with Omicron often causes milder symptoms, especially in vaccinated individuals1,2. The question arises of whether widespread Omicron infections could lead to future cross-variant protection, accelerating the end of the pandemic. Here we show that without vaccination, infection with Omicron induces a limited humoral immune response in mice and humans. Sera from mice overexpressing the human ACE2 receptor and infected with Omicron neutralize only Omicron, but not other variants of concern, whereas broader cross-variant neutralization was observed after WA1 and Delta infections. Unlike WA1 and Delta, Omicron replicates to low levels in the lungs and brains of infected animals, leading to mild disease with reduced expression of pro-inflammatory cytokines and diminished activation of lung-resident T cells. Sera from individuals who were unvaccinated and infected with Omicron show the same limited neutralization of only Omicron itself. By contrast, Omicron breakthrough infections induce overall higher neutralization titres against all variants of concern. Our results demonstrate that Omicron infection enhances pre-existing immunity elicited by vaccines but, on its own, may not confer broad protection against non-Omicron variants in unvaccinated individuals.


Subject(s)
COVID-19 , Cross Protection , SARS-CoV-2 , Vaccination , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/administration & dosage , Cross Protection/immunology , Cytokines , Humans , Mice , SARS-CoV-2/classification , SARS-CoV-2/immunology , Vaccination/statistics & numerical data
12.
Inorg Chem ; 61(16): 6182-6192, 2022 Apr 25.
Article in English | MEDLINE | ID: mdl-35420825

ABSTRACT

The first actinide complexes of the pyridine dipyrrolide (PDP) ligand class, (MesPDPPh)UO2(THF) and (Cl2PhPDPPh)UO2(THF), are reported as the UVI uranyl adducts of the bulky aryl substituted pincers (MesPDPPh)2- and (Cl2PhPDPPh)2- (derived from 2,6-bis(5-(2,4,6-trimethylphenyl)-3-phenyl-1H-pyrrol-2-yl)pyridine (H2MesPDPPh, Mes = 2,4,6-trimethylphenyl), and 2,6-bis(5-(2,6-dichlorophenyl)-3-phenyl-1H-pyrrol-2-yl)pyridine (H2Cl2PhPDPPh, Cl2Ph = 2,6-dichlorophenyl), respectively). Following the in situ deprotonation of the proligand with lithium hexamethyldisilazide to generate the corresponding dilithium salts (e.g., Li2ArPDPPh, Ar = Mes of Cl2Ph), salt metathesis with [UO2Cl2(THF)2]2 afforded both compounds in moderate yields. The characterization of each species has been undertaken by a combination of solid- and solution-state methods, including combustion analysis, infrared, electronic absorption, and NMR spectroscopies. In both complexes, single-crystal X-ray diffraction has revealed a distorted octahedral geometry in the solid state, enforced by the bite angle of the rigid meridional (ArPDPPh)2- pincer ligand. The electrochemical analysis of both compounds by cyclic voltammetry in tetrahydrofuran (THF) reveals rich redox profiles, including events assigned as UVI/UV redox couples. A time-dependent density functional theory study has been performed on (MesPDPPh)UO2(THF) and provides insight into the nature of the transitions that comprise its electronic absorption spectrum.

13.
medRxiv ; 2022 Jan 02.
Article in English | MEDLINE | ID: mdl-34981067

ABSTRACT

The Omicron SARS-CoV-2 virus contains extensive sequence changes relative to the earlier arising B.1, B.1.1 and Delta SARS-CoV-2 variants that have unknown effects on viral infectivity and response to existing vaccines. Using SARS-CoV-2 virus-like particles (SC2-VLPs), we examined mutations in all four structural proteins and found that Omicron showed increased infectivity relative to B.1, B.1.1 and similar to Delta, a property conferred by S and N protein mutations. Thirty-eight antisera samples from individuals vaccinated with tozinameran (Pfizer/BioNTech), elasomeran (Moderna), Johnson & Johnson vaccines and convalescent sera from unvaccinated COVID-19 survivors had moderately to dramatically reduced efficacy to prevent cell transduction by VLPs containing the Omicron mutations. The Pfizer/BioNTech and Moderna vaccine antisera showed strong neutralizing activity against VLPs possessing the ancestral spike protein (B.1, B.1.1), with 3-fold reduced efficacy against Delta and 15-fold lower neutralization against Omicron VLPs. Johnson & Johnson antisera showed minimal neutralization of any of the VLPs tested. Furthermore, the monoclonal antibody therapeutics Casirivimab and Imdevimab had robust neutralization activity against B.1, B.1.1 or Delta VLPs but no detectable neutralization of Omicron VLPs. Our results suggest that Omicron is at least as efficient at assembly and cell entry as Delta, and the antibody response triggered by existing vaccines or previous infection, at least prior to boost, will have limited ability to neutralize Omicron. In addition, some currently available monoclonal antibodies will not be useful in treating Omicron-infected patients.

14.
medRxiv ; 2022 Feb 09.
Article in English | MEDLINE | ID: mdl-35075459

ABSTRACT

SARS-CoV-2 Delta and Omicron strains are the most globally relevant variants of concern (VOCs). While individuals infected with Delta are at risk to develop severe lung disease 1 , Omicron infection causes less severe disease, mostly upper respiratory symptoms 2,3 . The question arises whether rampant spread of Omicron could lead to mass immunization, accelerating the end of the pandemic. Here we show that infection with Delta, but not Omicron, induces broad immunity in mice. While sera from Omicron-infected mice only neutralize Omicron, sera from Delta-infected mice are broadly effective against Delta and other VOCs, including Omicron. This is not observed with the WA1 ancestral strain, although both WA1 and Delta elicited a highly pro-inflammatory cytokine response and replicated to similar titers in the respiratory tracts and lungs of infected mice as well as in human airway organoids. Pulmonary viral replication, pro-inflammatory cytokine expression, and overall disease progression are markedly reduced with Omicron infection. Analysis of human sera from Omicron and Delta breakthrough cases reveals effective cross-variant neutralization induced by both viruses in vaccinated individuals. Together, our results indicate that Omicron infection enhances preexisting immunity elicited by vaccines, but on its own may not induce broad, cross-neutralizing humoral immunity in unvaccinated individuals.

15.
Pediatr Nephrol ; 37(11): 2583-2597, 2022 11.
Article in English | MEDLINE | ID: mdl-34913986

ABSTRACT

Diabetic kidney disease (DKD), previously encountered predominantly in adult patients, is rapidly gaining center stage as a childhood morbidity and one that pediatric nephrologists are likely to encounter with increasing frequency. This is in large part due to the obesity epidemic and the consequent rise in type 2 diabetes in children and adolescents, as well as the more aggressive diabetes phenotype in today's youth with more rapid ß-cell decline and faster development and progression of diabetes-related complications along with lower responsiveness to the treatments used in adults. DKD, an end-organ complication of diabetes, is at the very least a marker of, and more likely a predisposing factor for, the development of adverse cardiovascular outcomes and premature mortality in children with diabetes. On an optimistic note, several new therapeutic approaches are now available for the management of diabetes in adults, such as GLP1 receptor agonists, SGLT2 inhibitors, and DPP4 inhibitors, that have also been shown to have a favorable impact on cardiorenal outcomes. Also promising is the success of very low-energy diets in inducing remission of diabetes in adults. However, the addition of these pharmacological and dietary approaches to the management toolbox of diabetes and DKD in children and adolescents awaits thorough assessment of their safety and efficacy in this population. This review outlines the scope of diabetes and DKD, and new developments that may favorably impact the management of children and young adults with diabetes and DKD.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Dipeptidyl-Peptidase IV Inhibitors , Sodium-Glucose Transporter 2 Inhibitors , Biomarkers , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/therapy , Diabetic Nephropathies/epidemiology , Diabetic Nephropathies/etiology , Diabetic Nephropathies/therapy , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
16.
Sci Rep ; 11(1): 24448, 2021 12 27.
Article in English | MEDLINE | ID: mdl-34961780

ABSTRACT

COVID-19 mRNA vaccines are highly effective at preventing COVID-19. Prior studies have found detectable SARS-CoV-2 IgG antibodies in oral mucosal specimens of participants with history of COVID-19. To assess the development of oral SARS-CoV-2 IgG antibodies among people who received either the Moderna or Pfizer/BioNTech COVID-19 vaccination series, we developed a novel SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) to quantify the concentrations of oral and nasal mucosal SARS-CoV-2 IgG levels. We enrolled 52 participants who received the Moderna vaccine and 80 participants who received the Pfizer/BioNTech vaccine. Oral mucosal specimens were self-collected by participants prior to or on the day of vaccination, and on days 5, 10, 15, and 20 following each vaccination dose and 30, 60, and 90 days following the second vaccination dose. A subset of the cohort provided additional nasal mucosal specimens at every time point. All participants developed detectable oral mucosal SARS-CoV-2 IgG antibodies by 15 days after the first vaccination dose. There were no significant differences in oral mucosal antibody concentrations once participants were fully vaccinated in the Moderna and Pfizer/BioNTech vaccines. Oral or nasal mucosal antibody testing could be an inexpensive and less invasive alternative to serum antibody testing. Further research is needed to understand the duration of detectable oral or nasal mucosal antibodies and how antibody concentrations change with time.


Subject(s)
Antibodies, Viral/analysis , Immunoglobulin G/analysis , Mouth Mucosa/metabolism , Respiratory System/metabolism , mRNA Vaccines/immunology , Adult , Aged , COVID-19/prevention & control , COVID-19/virology , Female , Health Personnel , Humans , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Time Factors , Vaccination , Young Adult , mRNA Vaccines/administration & dosage
17.
Front Immunol ; 12: 777858, 2021.
Article in English | MEDLINE | ID: mdl-34956206

ABSTRACT

Background: Developing an understanding of the antibody response, seroprevalence, and seroconversion from natural infection and vaccination against SARS-CoV-2 will give way to a critical epidemiological tool to predict reinfection rates, identify vulnerable communities, and manage future viral outbreaks. To monitor the antibody response on a larger scale, we need an inexpensive, less invasive, and high throughput method. Methods: Here we investigate the use of oral mucosal fluids from individuals recovered from SARS-CoV-2 infection to monitor antibody response and persistence over a 12-month period. For this cohort study, enzyme-linked immunosorbent assays (ELISAs) were used to quantify anti-Spike(S) protein IgG antibodies in participants who had prior SARS-CoV-2 infection and regularly (every 2-4 weeks) provided both serum and oral fluid mucosal fluid samples for longitudinal antibody titer analysis. Results: In our study cohort (n=42) with 17 males and 25 females with an average age of 45.6 +/- 19.3 years, we observed no significant change in oral mucosal fluid IgG levels across the time course of antibody monitoring. In oral mucosal fluids, all the participants who initially had detectable antibodies continued to have detectable antibodies throughout the study. Conclusions: Based on the results presented here, we have shown that oral mucosal fluid-based assays are an effective, less invasive tool for monitoring seroprevalence and seroconversion, which offers an alternative to serum-based assays for understanding the protective ability conferred by the adaptive immune response from viral infection and vaccination against future reinfections.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin G/immunology , Saliva/immunology , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Longitudinal Studies , Male , Middle Aged , Mouth Mucosa/immunology , SARS-CoV-2 , Seroconversion , Spike Glycoprotein, Coronavirus/immunology
18.
Rev. habanera cienc. méd ; 20(5): e3660, 2021. tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1352080

ABSTRACT

Introducción: El método de Moyers se utiliza en Cuba para predecir el tamaño de caninos y bicúspides no erupcionados. Objetivo: Determinar la precisión del método de Moyers para predecir tamaño de dientes no erupcionados en pacientes de Centro Habana. Material y métodos: Investigación de desarrollo en el Policlínico Luis Galván Soca de marzo 2019 a mayo de 2020. Universo formado por individuos de 12 a 24 años. Muestra de 100 personas seleccionadas por muestreo aleatorio simple. Se analizó la tabla de Moyers por sexos para todos los percentiles. Resultados: En el sexo femenino para la arcada superior e inferior el error cuadrático medio menor correspondió al percentil 50: 0,476 y 0,464 respectivamente; único donde las diferencias entre el valor estimado y el real no fueron significativas. Por tanto, el percentil elegible para féminas en ambas arcadas sería el 50 por ciento. En masculinos para la arcada superior el error cuadrático medio menor (0,576) para el percentil 65 con diferencias entre el valor estimado y el real no significativas(p=0,269); mientras en la arcada inferior fue de 0,592 para el percentil 75. Por tanto, el percentil elegible para hombres en la arcada superior fue el 65 y en la inferior el 75; la fuerza de esta correspondencia es intensa para ambas arcadas. Conclusiones: En la población que se estudia el método de Moyers, para predecir el tamaño de dientes no erupcionados es preciso en el sexo femenino, pero no en el masculino(AU)


Introduction: In Cuba, the Moyers method is used to predict the size of non-erupted canines and bicuspids. Objective: To determine the precision of the Moyers method to predict the size of non-erupted teeth in patients from Centro Habana municipality. Material and Methods: A development research was conducted in Luis Galván Soca Polyclinic from March 2019 to May 2020. The universe consisted of individuals aged 12-24 years. The sample was composed of 100 people who were selected by simple random sampling. Moyers table was analyzed by sex for all percentiles. Results: In the female sex, the lower mean square error for the upper and lower arches corresponded to the 50th percentile: 0.476 and 0.464 respectively, the only one in which the difference between the estimated and the real values was not significant. Therefore, for females, the eligible percentile in both arches would be 50 percent. In males, in the upper arches, the lower mean square error (0.576) for the 65th percentile showed no significant differences between the estimated and the real values (p = 0,269); however, in the lower arch it was 0,592 for the 75th percentile. Therefore, in the upper arch, the eligible percentile for males was 65 while, in the lower arch, it was 75; the strength of this correspondence is intense for both arches. Conclusions: In the population studied, the Moyers method was found to be accurate in predicting the size of non-erupted teeth in females, but not in males(AU)


Subject(s)
Humans , Male , Female , Child , Adolescent , Health Centers , Cuspid , Bicuspid , Simple Random Sampling , Cuba
19.
J Undergrad Neurosci Educ ; 18(2): A75-A85, 2020.
Article in English | MEDLINE | ID: mdl-32848515

ABSTRACT

UCNeuro, a University of California, Riverside student-run organization, developed, implemented, and tested a school-based supplemental science intervention. The purpose of this intervention was to improve students' neuroscience knowledge and education attitudes and meet, in part, California's new elementary science education standards. The intervention consisted of interactive, hands-on neuroscience workshops on the structure of a neuron, neuron-to-neuron communication, brain structure and function, autonomic nervous system function, and drug effects on the brain. Under the supervision of a faculty neuroscientist, undergraduate students implemented the intervention with 77 sixth-grade students in one school in Riverside County, California. Pre- and post-test results showed increases in students' neuroscience knowledge, confidence in achieving their goals, likeliness to go to college, and desire to attend school. Excitement about learning science material and school learning opportunities did not change after the workshops. We hope that the UCNeuro workshops can be employed and adapted to the existing curriculum to improve knowledge in the life sciences while California's new elementary science standards are being operationalized.

20.
Am J Health Syst Pharm ; 76(Supplement_2): S41-S48, 2019 May 17.
Article in English | MEDLINE | ID: mdl-30854546

ABSTRACT

PURPOSE: The results and methods of a pharmacist-driven multifaceted educational intervention on the appropriate management of asymptomatic bacteriuria (ABU) within an emergency department (ED) are reported. METHODS: A retrospective, single-center cohort study was conducted to evaluate the effects of an educational intervention aimed at reducing the rates of mismanaged ABU within an ED at a Level 1 trauma center. The education involved a multifaceted approach directed by pharmacists and involved a handout and algorithm communicated through in-person discussions, emails, and general distribution. In order to evaluate the effectiveness of this education the preintervention and postintervention rates of inappropriate treatments were determined through a retrospective chart review. The primary outcome was the difference in the frequency of inappropriately treated ABU between the preintervention and postintervention periods. RESULTS: A total of 268 patients were included in the study for review (134 in each group). There was a 16.5% reduction in the frequency of patients that had ABU inappropriately treated as a urinary tract infection in the postintervention period compared with the preintervention period (31 [23.1%] versus 53 [39.6%], p = 0.004). CONCLUSION: Pharmacist-driven education was effecitive in reducing the rates of inappropriately used antibiotics for ABU within an ED.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antimicrobial Stewardship/organization & administration , Asymptomatic Infections/therapy , Bacteriuria/drug therapy , Pharmacists/organization & administration , Adult , Aged , Asymptomatic Infections/epidemiology , Bacteriuria/diagnosis , Bacteriuria/epidemiology , Education, Continuing/organization & administration , Female , Hospitals, Teaching/organization & administration , Humans , Inappropriate Prescribing/prevention & control , Male , Middle Aged , Nurses , Physicians , Prevalence , Professional Role , Program Evaluation , Retrospective Studies , Trauma Centers/organization & administration
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