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2.
Surg Obes Relat Dis ; 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39304459

RESUMEN

BACKGROUND: Most patients undergoing bariatric surgery demonstrate elements of the metabolic syndrome (MetS) and can therefore be diagnosed with metabolically unhealthy obesity (MUO). Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) as hepatic manifestations of the MetS occur in many patients with obesity, but their leverage on postoperative improvement to Metabolic Health (MH), defined as absence of any metabolic comorbidity, remains unclear. OBJECTIVES: The aim of this study was to assess the influence of liver health status, operative procedure, and sex on postoperative switch from a MUO to an MH phenotype. Secondary objective was weight loss to MH. SETTING: University Hospital, Germany. METHODS: Patients who underwent either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at our obesity surgery center were included in this retrospective study. Liver biopsy was taken and evaluated for presence of NAFLD/NASH. For diagnosis of MH, blood pressure and laboratory values referring to the MetS were assessed preoperatively and at 3, 6, 12, and 24 months' postoperatively. RESULTS: One hundred thirty-three patients (73% female) with a mean body mass index of 52.0 kg/m2 and mean age of 43 years were included in this study. A total of 55.6% underwent RYGB and 44.4% underwent SG. NAFLD was found in 51.1% of patients and NASH in 33.8%. All patients were diagnosed MUO at baseline. Postoperatively, 38.3% patients (n = 51) switched to a MH condition. Mean time to MH was 321 days and mean excess body mass index loss to MH was 63.8%. There were no differences regarding liver health status, operative procedure, or sex. CONCLUSIONS: Bariatric surgery can resolve MUO independent of liver health status, operative procedure, and sex. However, patients should be closely monitored to ensure sustainable long-term outcomes following the switch to the MH condition.

3.
NPJ Vaccines ; 9(1): 160, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39232020

RESUMEN

While first-generation, spike (S)-based COVID-19 vaccines were effective against early SARS-CoV-2 strains, the rapid evolution of novel Omicron subvariants have substantially reduced vaccine efficacy. As such, broadly protective vaccines against SARS-CoV-2 are needed to prevent future viral emergence. In addition, it remains less clear whether peripheral immunization, especially with mRNA vaccines, elicits effective respiratory immunity. Our group has developed a nucleoside-modified mRNA vaccine expressing the nucleocapsid (N) protein of the ancestral SARS-CoV-2 virus and has tested its use in combination with the S-based mRNA vaccine (mRNA-S). In this study, we examined efficacy of mRNA-N alone or in combination with mRNA-S (mRNA-S+N) against more immune evasive Omicron variants in hamsters. Our data show that mRNA-N alone induces a modest but significant protection against BA.5 and that dual mRNA-S+N vaccination confers complete protection against both BA.5 and BQ.1, preventing detection of virus in the hamster lungs. Analysis of respiratory immune response in mice shows that intramuscular mRNA-S+N immunization effectively induces respiratory S- and N-specific T cell responses in the lungs and in bronchoalveolar lavage (BAL), as well as antigen-specific binding IgG in BAL. Together, our data further support mRNA-S+N as a potential pan-COVID-19 vaccine for broad protection against current and emerging SARS-CoV-2 variants.

4.
Trials ; 25(1): 575, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223600

RESUMEN

BACKGROUND: The World Health Organization's (WHO) Mental Health Gap Action Programme (mhGAP) is a validated intervention that can be provided by non-specialised healthcare workers to individuals with unhealthy alcohol use. However, it typically requires several in-person sessions at a health facility, which may limit its feasibility and effectiveness in remote settings. This trial compares mhGAP-Standard, a 4 to 6 in-person session intervention, to mhGAP-Remote, a 1 in-person session intervention followed by 8 week of short message service (SMS) in Lesotho. We hypothesise that mhGAP-Remote is superior to mhGAP-Standard in reducing alcohol use (as detailed by the primary and secondary outcomes below). METHODS: This is a two-arm randomised open-label multicentre superiority trial. Participants allocated to mhGAP-Standard receive 4 in-person sessions using motivational interviewing, identifying triggers, and alternative behaviours, with the option of two additional booster sessions. Participants in the mhGAP-Remote arm receive 1 in-person session covering the same content, followed by standardised SMSs over 8 weeks that reinforce intervention content. Non-specialist providers deliver the intervention and receive weekly supervision. Adults (Nplanned = 248) attending participating health facilities for any reason and who meet criteria for unhealthy alcohol use based on the Alcohol Use Disorders Identification Test ([AUDIT] score ≥ 6 for women, ≥ 8 for men) are individually randomised to the two arms (1:1 allocation, stratified by participant sex and age (≥ 50 vs < 50 years old). Follow-up assessments occur at 8, 20, and 32 weeks post-randomisation. The primary outcome is change in self-reported alcohol use (continuous AUDIT score), from baseline to 8 weeks follow-up. Change in the AUDIT from baseline to 20 and 32 weeks follow-up is a secondary outcome. Change in the biomarker phosphatidylethanol (secondary), liver enzyme values in serum (exploratory), and HIV viral load (for people with HIV only; exploratory) are also evaluated from baseline throughout the entire follow-up period. A linear regression model will be conducted for the primary analysis, adjusted for the stratification factors. Three a priori sensitivity analyses for the primary outcome are planned based on per protocol treatment attendance, recovery from unhealthy alcohol use, and clinically significant and reliable change. DISCUSSION: This trial will provide insight into feasibility and effectiveness of a shortened and primarily SMS supported version of mhGAP, which is especially relevant for settings where regular clinic attendance is a major barrier. TRIAL REGISTRATION: clinicaltrials.gov NCT05925270 . Approved on June 29th, 2023.


Asunto(s)
Entrevista Motivacional , Envío de Mensajes de Texto , Humanos , Lesotho , Masculino , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/prevención & control , Femenino , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto , Estudios Multicéntricos como Asunto , Resultado del Tratamiento , Alcoholismo/terapia , Persona de Mediana Edad , Factores de Tiempo
5.
bioRxiv ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39229113

RESUMEN

Senescent cells (SnC) accumulate in aging tissues, impairing their ability to undergo repair and regeneration following injury. Previous research has demonstrated that targeting tissue senescence with senolytics can enhance tissue regeneration and repair by selectively eliminating SnCs in specific aged tissues. In this study, we focused on eliminating SnC skin cells in aged mice to assess the effects on subsequent wound healing. We applied ABT-263 directly to the skin of 24-month-old mice over a 5-day period. Following topical ABT-263, aged skin demonstrated decreased gene expression of senescent markers p16 and p21, accompanied by reductions in SA-ß-gal and p21-positive cells compared to DMSO controls. However, ABT-263 also triggered a temporary inflammatory response and macrophage infiltration in the skin. Bulk RNA sequencing of ABT-263-treated skin revealed prompt upregulation of genes associated with wound healing pathways, including hemostasis, inflammation, cell proliferation, angiogenesis, collagen synthesis, and extracellular matrix organization. Aged mice skin pre-treated with topical ABT-263 exhibited accelerated wound closure. In conclusion, topical ABT-263 effectively reduced several senescence markers in aged skin, thereby priming the skin for improved subsequent wound healing. This enhancement may be attributed to ABT-263-induced senolysis which in turn stimulates the expression of genes involved in extracellular matrix remodeling and wound repair pathways.

6.
Clin Rheumatol ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39172292

RESUMEN

INTRODUCTION/OBJECTIVES: Among people with or without hand osteoarthritis, we aimed to identify characteristics of people (e.g., age and gender) with marginal erosions (MEs). We also examined changes in MEs during 48 months. We described radiographic severity and progression among joints with MEs, changes in MEs, or central erosions (CEs). DESIGN: We studied participants from the Osteoarthritis Initiative with baseline and 48-month hand radiographs. A radiologist and rheumatologist evaluated the radiographs for disease severity (Kellgren-Lawrence grades) and erosions (central or marginal), respectively. We used descriptive statistics to characterize participants and calculated frequencies at the joint level. RESULTS: Of the 3558 participants, 89 had a ME at baseline. People with MEs were more often male, older, and ever (former and current) smokers than those without a ME. There was no difference in inflammatory biomarkers or the presence of hand pain between individuals with and without a baseline ME. Almost all hands had only one ME (80%), whereas only 50% of individuals with CEs had only one CE at baseline. Compared to CEs, MEs appeared more frequently in joints without osteoarthritis (54% vs. < 1%). Approximately 18% of joints with an ME progressed in Kellgren-Lawrence grade versus 4% without ME. Among the joints with an ME at baseline, 10% resolved by 48 months. Less than 0.1% of joints developed a new ME. CONCLUSION: MEs appear to be distinct from CEs. MEs are predominantly present in males, isolated to one specific joint without osteoarthritis within a hand, and possibly predictive of radiographic progression. Key Points • Marginal erosions appear to be distinct from central erosions. • Most marginal erosions occur in joints without radiographic osteoarthritis. • Radiographic progression but not hand pain is more common in joints with a marginal erosion than without one.

7.
J Rheumatol ; 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39147419

RESUMEN

In this issue of The Journal of Rheumatology, the article by King et al describes a registry-based cohort study of the Good Life With Osteoarthritis in Denmark (GLA:D) 8-week education and exercise program.1 Rather than focusing on knee pain, the authors examined change in self-reported difficulty walking, a primary reason people with knee osteoarthritis (OA) seek care, and assessed patient factors associated with improvement in difficulty walking after the program.

8.
Biofilm ; 8: 100214, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39184815

RESUMEN

Biofilm growth facilitates the interaction of uropathogenic Escherichia coli (UPEC) with the host environment. The extracellular polymeric substances (EPS) of UPEC biofilms are composed prominently of curli amyloid fiber and cellulose polysaccharide. When the organism is propagated as a colony biofilm on agar media, these macromolecules can generate pronounced macroscopic structures. Moreover, curli/cellulose associate tightly with Congo red, generating a characteristic pink-to-red staining pattern when the media is supplemented with this dye. Among different clinical isolates of UPEC, changes in the abundance of curli/cellulose can lead to diverse colony biofilm phenotypes on a strain-by-strain basis. Nevertheless, for any given isolate, these phenotypes are classically homogenous throughout the colony biofilm. Here, we report that a subset of clinical UPEC isolates display heterogenous 'peppermint' colony biofilms, with distinct pale and red subpopulations. Through isolation of these subpopulations and whole genome sequencing, we demonstrate various emergent mutations associated with the phenomenon, including within the gene encoding the outer membrane lipoprotein nlpI. Deletion of nlpI within independent strain-backgrounds increased biofilm rugosity, while its overexpression induced the peppermint phenotype. Upregulation of EPS-associated proteins and transcripts was likewise observed in the absence of nlpI. Overall, these results demonstrate that EPS elaboration in UPEC is impacted by nlpI. More broadly, this phenomenon of intra-strain colony biofilm heterogeneity may be leveraged as a tool to identify additional members within the broad collection of genes that regulate or otherwise affect biofilm formation.

10.
Cureus ; 16(5): e61361, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38947681

RESUMEN

Hodgkin's lymphoma (HL) is a form of cancer that involves abnormal lymphocyte proliferation which affects the lymphatic system. Patients with HIV are at increased risk of developing HL, despite the introduction of combination antiretroviral therapy. The most common presentation of HL is painless lymphadenopathy with classic constitutional symptoms in advanced disease. Here we discuss a 39-year-old female with a history of HIV on emtricitabine/tenofovir and dolutegravir who presented with four days of worsening diarrhea along with fevers and chills. She had a similar presentation at a nearby hospital four months prior. After initial concern for gastrointestinal infection, an extensive infectious workup was conducted and was negative. After complaints of sore throat and increased confusion during the hospital stay, a CT Chest and Neck revealed diffuse lymphadenopathy. Severely elevated ferritin levels raised concern for secondary hemophagocytic lymphohistiocytosis and prompted expedited ultrasound-guided cervical lymph node (LN) core biopsy and bone marrow biopsy. Ultrasound-guided core biopsy of the LN showed classical Hodgkin's lymphoma of mixed cellularity. The patient was started on doxorubicin, vinblastine, and dacarbazine + nivolumab. This is a case of a patient with HIV who presented with chronic diarrhea of unidentifiable origin and was ultimately diagnosed with classical Hodgkin's lymphoma during her hospitalization and highlights the importance of maintaining lymphoproliferative diseases on the differential in patients with HIV and gastrointestinal symptoms.

11.
Nurse Educ ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38968442

RESUMEN

BACKGROUND: The integration of generative artificial intelligence (AI) tools like OpenAI's ChatGPT into nursing education marks a transformative advance in personalized learning and interactive engagement. PROBLEM: Variability in faculty's experience with AI outputs highlights the need for well-crafted prompts that align with educational objectives, maximize learning outcomes, and ensure contextual relevance. Effective prompting is a key to eliciting accurate, relevant responses from AI, fostering a dynamic learning environment that bolsters student comprehension of complex topics. APPROACH: This article examines the critical role of prompt engineering in optimizing AI-generated content's effectiveness within academic settings. With a detailed guide and strategies specifically designed for nursing education, the article prepares faculty to proficiently use generative AI. CONCLUSIONS: By mastering prompt engineering, educators can leverage AI tools as powerful aids, potentially significantly enhancing teaching effectiveness, work efficiency, and student learning outcomes.

13.
Clin Cancer Res ; 30(17): 3904-3918, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-38848043

RESUMEN

PURPOSE: Uterine leiomyosarcoma (LMS) is an aggressive sarcoma and a subset of which exhibits DNA repair defects. Polo-like kinase 4 (PLK4) precisely modulates mitosis, and its inhibition causes chromosome missegregation and increased DNA damage. We hypothesize that PLK4 inhibition is an effective LMS treatment. EXPERIMENTAL DESIGN: Genomic profiling of clinical uterine LMS samples was performed, and homologous recombination (HR) deficiency scores were calculated. A PLK4 inhibitor (CFI-400945) with and without an ataxia telangiectasia mutated (ATM) inhibitor (AZD0156) was tested in vitro on gynecologic sarcoma cell lines SK-UT-1, SKN, and SK-LMS-1. Findings were validated in vivo using the SK-UT-1 xenograft model in the Balb/c nude mouse model. The effects of CFI-400945 were also evaluated in a BRCA2-knockout SK-UT-1 cell line. The mechanisms of DNA repair were analyzed using a DNA damage reporter assay. RESULTS: Uterine LMS had a high HR deficiency score, overexpressed PLK4 mRNA, and displayed mutations in genes responsible for DNA repair. CFI-400945 demonstrated effective antitumor activity in vitro and in vivo. The addition of AZD0156 resulted in drug synergism, largely due to a preference for nonhomologous end-joining DNA repair. Compared with wild-type cells, BRCA2 knockouts were more sensitive to PLK4 inhibition when both HR and nonhomologous end-joining repairs were impaired. CONCLUSIONS: Uterine LMS with DNA repair defects is sensitive to PLK4 inhibition because of the effects of chromosome missegregation and increased DNA damage. Loss-of-function BRCA2 alterations or pharmacologic inhibition of ATM enhanced the efficacy of the PLK4 inhibitor. Genomic profiling of an advanced-stage or recurrent uterine LMS may guide therapy.


Asunto(s)
Daño del ADN , Reparación del ADN , Leiomiosarcoma , Proteínas Serina-Treonina Quinasas , Neoplasias Uterinas , Ensayos Antitumor por Modelo de Xenoinjerto , Femenino , Humanos , Animales , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/genética , Leiomiosarcoma/genética , Leiomiosarcoma/tratamiento farmacológico , Leiomiosarcoma/patología , Neoplasias Uterinas/genética , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/patología , Ratones , Línea Celular Tumoral , Reparación del ADN/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Proteínas de la Ataxia Telangiectasia Mutada/antagonistas & inhibidores , Proteínas de la Ataxia Telangiectasia Mutada/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Morfolinas/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Indoles/farmacología , Indoles/uso terapéutico , Piridinas , Quinolinas
14.
Ethics Hum Res ; 46(4): 27-37, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38944884

RESUMEN

The use of patient-reported outcome measures (PROMs) is increasingly common in routine clinical practice. As tools to quantify symptoms and health status, PROMs play an important role in focusing health care on outcomes that matter to patients. The uses of PROM data are myriad, ranging from clinical care to survey-based research and quality improvement. Discerning the boundaries between these use cases can be challenging for institutional review boards (IRBs). In this article, we provide a framework for classifying the three primary PROM use cases (clinical care, human subjects research, and quality improvement) and discuss the level of IRB oversight (if any) necessary for each. One of the most important considerations for IRB staff is whether PROMs are being used primarily for clinical care and thus do not constitute human subjects research. We discuss characteristics of PROMs implemented primarily for clinical care, focusing on: data platform; survey location; questionnaire length; patient interface; and clinician interface. We also discuss IRB oversight of projects involving the secondary use of PROM data that were collected during the course of clinical care, which span human subjects research and quality improvement. This framework provides practical guidance for IRB staff as well as clinicians who use PROMs as communication aids in routine clinical practice.


Asunto(s)
Comités de Ética en Investigación , Medición de Resultados Informados por el Paciente , Mejoramiento de la Calidad , Humanos , Comités de Ética en Investigación/normas , Mejoramiento de la Calidad/normas , Encuestas y Cuestionarios/normas
16.
J Behav Med ; 47(5): 828-838, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38796664

RESUMEN

Sedentary behavior (SB) has been linked to risk factors of cardiometabolic disease, with inconsistent findings reported in the literature. We aimed to assess the associations of SB with multiple biomarkers of inflammation and insulin resistance in adults. Domain-specific SB, sitting time and moderate-to-vigorous physical activity (MVPA) were measured in 78 adults (mean ± SD 52.0 ± 10.8 y). Body fat percentage (BF%) was assessed using multi-frequency bioelectrical impedance. A blood draw assessed glucose, insulin, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), leptin, and adiponectin. Adiponectin-leptin ratio (ALR), homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-ß) were calculated. Multivariable linear regression analyses, controlling for age, sex, MVPA, and BF%, were used to assess associations. After adjustment for age, sex and MVPA, total SB (7.5 ± 2.5 h/day) was positively associated with leptin, insulin, HOMA-IR, HOMA-ß (Standardized Beta (ß) range 0.21-0.32) and negatively associated with ALR (ß = -0.24, p < 0.05 for all). Similarly, total sitting time (7.2 ± 2.9 h/day) was associated with TNF-α (ß = 0.22) and ALR (ß = -0.26). These associations were attenuated to non-significance after adjustment for BF%. Leisure screen time was detrimentally associated with IL-6 (ß = 0.24), leptin (ß = 0.21), insulin (ß = 0.37), HOMA-IR (ß = 0.37), and HOMA-ß (ß = 0.34), independent of age, sex and MVPA (p < 0.05 for all). Only the associations with insulin (ß = 0.26), HOMA-IR (ß = 0.26), and HOMA-ß (ß = 0.23) remained significant after further controlling BF% (p < 0.05). Self-reported SB is associated with biomarkers of inflammation and insulin resistance, independent of MVPA, and in some cases BF%.


Asunto(s)
Biomarcadores , Proteína C-Reactiva , Inflamación , Resistencia a la Insulina , Leptina , Tiempo de Pantalla , Conducta Sedentaria , Humanos , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores/sangre , Inflamación/sangre , Leptina/sangre , Proteína C-Reactiva/análisis , Insulina/sangre , Adiponectina/sangre , Interleucina-6/sangre , Adulto , Ejercicio Físico , Factor de Necrosis Tumoral alfa/sangre , Glucemia
17.
JAMA Netw Open ; 7(5): e2412291, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38805228

RESUMEN

Importance: Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years. Objectives: To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD. Design, Setting, and Participants: This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children's hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks' gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024. Intervention: Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks' gestational age. Main Outcomes and Measures: The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment. Results: The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, -1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis (P for interaction = .03) and fetal sex (P for interaction = .04), but not genetic profile (P for interaction = .16) or maternal-fetal environment (P for interaction = .70). Conclusions and Relevance: In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex. Trial Registration: ClinicalTrials.gov Identifier: NCT02133573.


Asunto(s)
Cardiopatías Congénitas , Progesterona , Humanos , Progesterona/uso terapéutico , Femenino , Cardiopatías Congénitas/tratamiento farmacológico , Cardiopatías Congénitas/complicaciones , Masculino , Embarazo , Método Doble Ciego , Lactante , Adulto , Recién Nacido , Desarrollo Infantil/efectos de los fármacos , Progestinas/uso terapéutico , Trastornos del Neurodesarrollo
18.
Neuropharmacology ; 255: 110002, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38754577

RESUMEN

RATIONALE: Recent studies report that fentanyl analogs with relatively low pKa values produce antinociception in rodents without other mu opioid-typical side effects due to the restriction of their activity to injured tissue with relatively low pH values. However, it is unclear if and to what degree these compounds may produce mu opioid-typical side effects (respiratory depression, reinforcing effects) at doses higher than those required to produce antinociception. OBJECTIVES: The present study compared the inflammatory antinociceptive, respiratory-depressant, and reinforcing effects of fentanyl and two analogs of intermediate (FF3) and low (NFEPP) pKa values in terms of potency and efficacy in male and female Sprague-Dawley rats. METHODS: Nociception was produced by administration of Complete Freund's Adjuvant into the hind paw of subjects, and antinociception was measured using an electronic Von Frey test. Respiratory depression was measured using whole-body plethysmography. Reinforcing effects were measured in self-administration using a progressive-ratio schedule of reinforcement. The dose ranges tested for each drug encompassed no effect to maximal effects. RESULTS: All compounds produced full effects in all measures but varied in potency. FF3 and fentanyl were equipotent in antinociception and self-administration, but FF3 was less potent than fentanyl in respiratory depression. NFEPP was less potent than fentanyl in every measure. The magnitude of potency difference between antinociception and other effects was greater for FF3 than for NFEPP or fentanyl, indicating that FF3 had the widest margin of safety when relating antinociception to respiratory-depressant and reinforcing effects. CONCLUSIONS: Low pKa fentanyl analogs possess potential as safer analgesics, but determining the optimal degree of difference for pKa relative to fentanyl will require further study due to some differences between the current results and findings from prior work with these analogs.


Asunto(s)
Analgésicos Opioides , Fentanilo , Ratas Sprague-Dawley , Animales , Fentanilo/farmacología , Fentanilo/análogos & derivados , Masculino , Femenino , Analgésicos Opioides/farmacología , Ratas , Refuerzo en Psicología , Relación Dosis-Respuesta a Droga , Autoadministración , Insuficiencia Respiratoria/inducido químicamente , Dimensión del Dolor/efectos de los fármacos , Dimensión del Dolor/métodos
19.
J Adolesc ; 96(6): 1388-1396, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38752304

RESUMEN

INTRODUCTION: Patterns of biethnic adolescents' perceived biethnic acceptance across families, peers, and school contexts were examined during the transition from elementary to middle school in South Korea. We also examined how the transition patterns were related to their psychological outcomes during this period. METHODS: Utilizing 2-wave data (2017 and 2019) from the Panel Survey of Korean Multicultural Youth Adjustment, a latent transition analysis was conducted. Participants were biethnic adolescents who were in 5th or 6th grade at Wave 1 (N = 245; 51.02% female; Mage = 11.38). Their fathers were Korean, and mothers were immigrants from neighboring countries. Familial ethnic socialization, peer discrimination, and school multicultural climate scores were used as indicators of biethnic acceptance. Outcomes of self-esteem, depression, and biethnic affirmation were also examined. RESULTS: Latent profile and transition analyses yielded two groups (i.e., high acceptance and low acceptance) at each wave and four transition patterns (i.e., high-high, low-high, low-low, and high-low). Compared to high-high group, which was the most prevalent group, low-low and high-low groups reported lower self-esteem and ethnic affirmation, and greater depression at Wave 3. CONCLUSIONS: While for the majority of participants, their daily settings continued to be high in biethnic acceptance across the transition period, most at risk were those who perceived a decrease in biethnic acceptance in their daily settings. Results shed light on the need for support to maintain the context of high biethnic acceptance surrounding biethnic adolescents for their psychological well-being in school transitions.


Asunto(s)
Autoimagen , Humanos , Masculino , Femenino , República de Corea/etnología , Adolescente , Niño , Instituciones Académicas , Depresión/etnología , Depresión/psicología , Etnicidad/psicología , Grupo Paritario , Psicología del Adolescente , Bienestar Psicológico
20.
Am J Hematol ; 99(8): 1492-1499, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38695834

RESUMEN

Iron deficiency anemia (IDA) and non-anemic iron deficiency (NAID) are highly prevalent among non-pregnant females of reproductive age. Canada has no national screening guidelines for this population. Screening, when performed, is often with a complete blood count alone without ferritin or iron indices. The primary objective was to determine the prevalence of screening for NAID and IDA over a 3-year period in non-pregnant females of reproductive age who had tests performed at outpatient laboratories in Ontario, Canada. Retrospective cohort study of non-pregnant females ages 15-54 in Ontario, from 2017 to 2019. NAID was defined as ferritin <30 µg/L, anemia as hemoglobin <120 g/L, and IDA as ferritin <30 µg/L and hemoglobin <120 g/L. Annual household income was estimated using patient postal codes. A total of 784 132 non-pregnant females were included. The 82.1% were screened for iron deficiency, 38.3% had NAID and 13.1% had IDA; 55.6% with IDA had normal mean corpuscular volumes. The median household income was $89454.80 compared with a provincial median of $65285.00. Patients in the lowest income quintile had the highest odds of being anemic, and the lowest odds of having a ferritin checked. A large proportion of non-pregnant females of reproductive age in this cohort were screened for iron deficiency. In this relatively privileged cohort, NAID affected nearly 40%, and IDA 13%. Most patients with IDA did not have microcytosis. Low household income was associated with the greatest odds of anemia and the lowest odds of being screened, highlighting inequitable access to screening for IDA in Ontario, Canada.


Asunto(s)
Anemia Ferropénica , Disparidades Socioeconómicas en Salud , Adolescente , Adulto , Femenino , Humanos , Persona de Mediana Edad , Adulto Joven , Anemia Ferropénica/epidemiología , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/sangre , Ferritinas/sangre , Deficiencias de Hierro , Tamizaje Masivo , Ontario/epidemiología , Prevalencia , Estudios Retrospectivos
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