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1.
Conserv Physiol ; 12(1): coae004, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38343722

RESUMO

Upper thermal limits in many fish species are limited, in part, by the heart's ability to meet increased oxygen demand during high temperatures. Cardiac plasticity induced by developmental temperatures can therefore influence thermal tolerance. Here, we determined how incubation temperatures during the embryonic stage influence cardiac performance across temperatures during the sensitive larval stage of the imperiled longfin smelt. We transposed a cardiac assay for larger fish to newly hatched larvae that were incubated at 9°C, 12°C or 15°C. We measured heart rate over increases in temperature to identify the Arrhenius breakpoint temperature (TAB), a proxy for thermal optimum and two upper thermal limit metrics: temperature when heart rate is maximized (Tpeak) and when cardiac arrhythmia occurs (TArr). Higher incubation temperatures increased TAB, Tpeak and TArr, but high individual variation in all three metrics resulted in great overlap of individuals at TAB, Tpeak and TArr across temperatures. We found that the temperatures at which 10% of individuals reached Tpeak or TArr and temperatures at which number of individuals at TAB relative to Tpeak (ΔN(TAB,Tpeak)) was maximal, correlated more closely with upper thermal limits and thermal optima inferred from previous studies, compared to the mean values of the three cardiac metrics of the present study. Higher incubation temperatures increased the 10% Tpeak and TArr thresholds but maximum ΔN(TAB,Tpeak) largely remained the same, suggesting that incubation temperatures modulate upper thermal limits but not Topt for a group of larvae. Overall, by measuring cardiac performance across temperatures, we defined upper thermal limits (10% thresholds; Tpeak, 14.4-17.5°C; TArr, 16.9-20.2°C) and optima (ΔN(TAB,Tpeak), 12.4-14.4°C) that can guide conservation strategies for longfin smelt and demonstrated the potential of this cardiac assay for informing conservation plans for the early life stages of fish.

2.
Am J Hematol ; 99(4): 745-750, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38264829

RESUMO

Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory and T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination of anti-Spike specific antibodies. Booster doses increased seroconversion rate and antibody titers in all patient categories, ultimately generating humoral responses similar to those observed in the postinfection cohort. In detail, humoral response with overscale median antibody titers arose in >80% of patients in watch and wait, off-therapy in remission, or under treatment with venetoclax single-agent. Anti-CD20 antibodies and active treatment with BTK inhibitors (BTKi) represent limiting factors of humoral response, still memory mounted in ~40% of cases following booster doses or infection. (Blue) Evaluation of SARS-CoV-2-specific T-cell responses. Number of T-cell functional activation markers documented in each patient. The vast majority of patients, including those seronegative, developed T-cell responses, qualitatively similar between treatment groups or between vaccination alone and infection cases. These data highlight the efficacy of booster doses in eliciting T-cell immunity independently of treatment status and support the use of additional vaccination boosters to stimulate humoral immunity in patients on active CLL-directed treatments.


Assuntos
COVID-19 , Leucemia Linfocítica Crônica de Células B , Humanos , SARS-CoV-2 , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Vacinas contra COVID-19 , Anticorpos , Subunidade alfa de Receptor de Interleucina-2 , Imunidade Celular , Anticorpos Antivirais , Vacinação
3.
Environ Sci Technol ; 57(26): 9580-9591, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37350451

RESUMO

The Longfin Smelt (Spirinchus thaleichthys) population in the San Franscisco Bay/Sacramento-San Joaquin Delta (Bay-Delta) has declined to ∼1% of its pre-1980s abundance and, as a result, is listed as threatened under the California Endangered Species Act. The reasons for this decline are multiple and complex, including the impacts of contaminants. Because the spawning and rearing seasons of Longfin Smelt coincide with the rainy season, during which concentrations of contaminants increase due to runoff, we hypothesized that early life stages may be particularly affected by those contaminants. Bifenthrin, a pyrethroid insecticide commonly used in agricultural and urban sectors, is of concern. Concentrations measured in the Bay-Delta have been shown to disrupt the behavior, development, and endocrine system of other fish species. The objective of the present work was to assess the impact of bifenthrin on the early developmental stages of Longfin Smelt. For this, embryos were exposed to 2, 10, 100, and 500 ng/L bifenthrin from fertilization to hatch, and larvae were exposed to 2, 10, and 100 ng/L bifenthrin from one day before to 3 days post-hatch. We assessed effects on size at hatch, yolk sac volume, locomotory behavior, and upper thermal susceptibility (via cardiac endpoints). Exposure to these environmentally relevant concentrations of bifenthrin did not significantly affect the cardiac function of larval Longfin Smelt; however, exposures altered their behavior and resulted in smaller hatchlings with reduced yolk sac volumes. This study shows that bifenthrin affects the fitness-determinant traits of Longfin Smelt early life stages and could contribute to the observed population decline.


Assuntos
Osmeriformes , Piretrinas , Poluentes Químicos da Água , Animais , Piretrinas/toxicidade , Espécies em Perigo de Extinção
5.
J Fam Pract ; 71(8): E1-E8, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36508563

RESUMO

These unique agents may be the answer when other treatments fail or are intolerable for patients with asthma, atopic dermatitis, hyperlipidemia, osteoporosis, or migraine headaches.


Assuntos
Asma , Dermatite Atópica , Transtornos de Enxaqueca , Humanos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Dermatite Atópica/tratamento farmacológico , Asma/tratamento farmacológico , Transtornos de Enxaqueca/tratamento farmacológico
6.
Sci Rep ; 12(1): 20751, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36456583

RESUMO

Developmental abnormalities in otoliths can impact growth and survival in teleost fishes. Here, we quantified the frequency and severity of developmental anomalies in otoliths of delta smelt (Hypomesus transpacificus), a critically endangered estuarine fish that is endemic to the San Francisco Estuary. Left-right asymmetry and anomalous crystalline polymorphs (i.e., vaterite) were quantified and compared between wild and cultured populations using digital image analysis. Visual estimates of vaterite were validated using X-ray diffraction, Raman spectroscopy, laser ablation ICPMS, and electron probe microanalysis. Results indicated that cultured delta smelt were 80 times more likely to contain a vateritic otolith and 18 times more likely to contain relatively large (≥ 15%) amounts of vaterite. Similarly, cultured fish exhibited 30% greater asymmetry than wild fish. These results indicate that cultured delta smelt exhibit a significantly higher frequency of vestibular abnormalities which are known to reduce fitness and survival. Such hatchery effects on otolith development could have important implications for captive culture practices and the supplementation of wild fish populations with cultured individuals.


Assuntos
Osmeriformes , Membrana dos Otólitos , Animais , Carbonato de Cálcio , Microanálise por Sonda Eletrônica , Estuários
7.
Inorg Chem ; 61(46): 18640-18652, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36350227

RESUMO

We report a comprehensive assessment of Lewis acidity for a series of carbone-stibenium and -bismuthenium ions using the Gutmann-Beckett (GB) method. These new antimony and bismuth cations have been synthesized by halide abstractions from (CDC)PnBr3 and [(pyCDC)PnBr2][Br] (CDC = carbodicarbene; Pn = Sb or Bi; py = pyridyl). The reaction of (CDC)SbBr3 (1) with one or two equivalents of AgNTf2 (NTf2 = bis(trifluoromethanesulfonyl)imide) or AgSbF6 gives stibaalkene mono- and dications of the form [(CDC)SbBr3-n][A]n (2-4; n = 1,2; A = NTf2 or SbF6). The stibaalkene trication [(CDC)2Sb][NTf2]3 (5) was also isolated and collectively these molecules fill the gap among the series of cationic pnictaalkenes. The Sb cations are compared to the related CDC-bismaalkene complexes 6-9. With the goal of preparing highly Lewis acidic compounds, a tridentate bis(pyridine)carbodicarbene (pyCDC) was used as a ligand to access [(pyCDC)PnBr2][Br] (10, 12) and trications [(pyCDC)Pn][NTf2]3 (Pn = Sb (11), Bi (13)), forgoing the need for a second CDC as used in the synthesis of 5. The bonding situation in these complexes is elucidated through electron density and energy decomposition analyses in combination with natural orbital for chemical valence theory. In each complex, there exists a CDC-Pn double bonding interaction, consisting of a strong σ-bond and a weaker π-bond, whereby the π-bond gradually strengthens with the increase in cationic charge in the complex. Notably, [(CDC)SbBr][NTf2]2 (4) has an acceptor number (AN) (84) that is comparable to quintessential Lewis acids such as BF3, and tricationic pnictaalkene complexes 11 and 13 exhibit strong Lewis acidity with ANs of 109 (Pn = Sb) and 84 (Pn = Bi), respectively, which are among the highest values reported for any antimony or bismuth cation. Moreover, the calculated fluoride ion affinities (FIAs) for 11 and 13 are 99.8 and 94.3 kcal/mol, respectively, which are larger than that of SbF5 (85.1 kcal/mol), which suggest that these cations are Lewis superacids.

8.
J Orthop Surg Res ; 17(1): 417, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104792

RESUMO

OBJECTIVE: Primary purpose of this study was to determine the validity and reliability of the OneStep smartphone application in healthy adults. Secondary purpose was to determine the feasibility of measuring gait dysfunction, limitation in spatiotemporal characteristics, longitudinally in patients following total hip or knee arthroplasty. METHODS: First objective, 20 healthy adults (mean age, 42.3 ± 19.7 years; 60% males; mean body mass index, 29.0 ± 5.2 kg/m2) underwent gait analysis under four gait conditions (self-selected gait speed, fixed gait speed at 0.8 m/s, fixed gait speed at 2.0 m/s and self-selected gait speed with dual task) for the validity and reliability of the smartphone to the motion laboratory. Reliability was determined by intraclass correlation coefficients. Validity was determined by Pearson correlations. Agreement was assessed by the Bland-Altman method. Second objective, 12 additional patients with total hip or knee arthroplasty (mean age, 58.7 ± 6.5 years; 58% males; mean body mass index, 28.9 ± 5.8 kg/m2) were measured at 2- and 10 weeks postoperatively. The smartphone application was used to evaluate change in gait dysfunction over time within the patients' own environment using paired t test. RESULTS: The smartphone application demonstrated moderate-to-excellent intraclass correlation coefficients for reliability between-system (ICC range, 0.56-0.99), -limb (ICC range, 0.62-0.99) and -device (ICC range, 0.61-0.96) for gait analysis of healthy adults. Pearson correlations were low-to-very high between methods (r range, 0.45-0.99). Bland-Altman analysis revealed relative underestimation of spatiotemporal variables by the smartphone application compared to the motion system. For patients following total hip or knee arthroplasty, gait analysis using the OneStep application demonstrated significant improvement (p < 0.001, Cohen's d > 0.95) in gait dysfunction between 2- and 10 weeks postoperatively. CONCLUSION: The smartphone application can be a valid, reliable and feasible alternative to motion laboratories in evaluating deficits in gait dysfunction in various environments and clinical settings.


Assuntos
Aplicativos Móveis , Smartphone , Adulto , Idoso , Estudos de Viabilidade , Feminino , Marcha , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem
9.
Adv Radiat Oncol ; 7(6): 101014, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060637

RESUMO

Purpose: Our purpose was to develop a rodent model of brain radionecrosis using clinical linear accelerator based stereotactic radiosurgery. Methods and Materials: Single fraction maximum prescription points in the mouse's left hemisphere were irradiated using linear accelerator-based stereotactic radiosurgery with multiple arcs at 60 (n = 5), 100 (n = 5), and 140 (n = 5) Gy. Rats (n = 6) were similarly treated with 140 Gy. Gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) was used to track radiation injury in mice over weeks (100 and 140 Gy) or months (60 Gy). Target accuracy was measured by the distance from the prescription point to the center of the earliest Gd-MRI enhancement. Confirmation of necrosis via histology was performed at the subject endpoints. Results: Radiation injury as indicated by Gd-MRI was first identified at 2 weeks (140 Gy), 4 to 6 weeks (100 Gy), and 8 months (60 Gy). A volumetric time course showed rapid growth in the volume of Gd-MRI signal enhancement after the appearance of apparent necrosis. Histopathologic features were consistent with radionecrosis. Conclusions: The presented method uses a commonly available clinical linear accelerator to induce radiation necrosis in both mice and rats. The treatment is modeled after patient therapy for a more direct model of human tissue under a range of doses used in clinical neuro-ablation techniques. The short time to onset of apparent necrosis, accurate targeting of the prescription point, high incidence of necrosis, and similar pathologic features make this a suitable animal model for further research in radionecrosis.

10.
Anal Chem ; 94(34): 11723-11727, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35981215

RESUMO

Adeno-associated viral (AAV) vectors have emerged as gene therapy and vaccine delivery systems. Differential scanning fluorimetry or differential scanning calorimetry is commonly used to measure the thermal stability of AAVs, but these global methods are unable to distinguish the stabilities of different AAV subpopulations in the same sample. To address this challenge, we combined charge detection-mass spectrometry (CD-MS) with a variable temperature (VT) electrospray source that controls the temperature of the solution prior to electrospray. Using VT-CD-MS, we measured the thermal stabilities of empty and filled capsids. We found that filled AAVs ejected their cargo first and formed intermediate empty capsids before completely dissociating. Finally, we observed that pH stress caused a major decrease in thermal stability. This new approach better characterizes the thermal dissociation of AAVs, providing the simultaneous measurement of the stabilities and dissociation pathways of different subpopulations.


Assuntos
Capsídeo , Dependovirus , Capsídeo/química , Proteínas do Capsídeo/química , Dependovirus/química , Espectrometria de Massas , Temperatura
11.
Conserv Physiol ; 10(1): coac041, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795015

RESUMO

Longfin smelt (Spirinchus thaleichthys) is a threatened anadromous fish species that spawns in freshwater to moderately brackish (i.e. 5-10 ppt) reaches of the upper San Francisco Estuary and has declined to ~1% of its pre-1980s abundances. Despite 50+ years of population monitoring, the efficacy of 10+ years of conservation efforts for longfin smelt remain uncertain due to a limited understanding of how the species responds to environmental variation, such as salinity. For example, high mortality during larval stages has prevented culture efforts from closing the life cycle in captivity. Here, we investigated the effects of salinity on longfin smelt yolk-sac larvae. Newly hatched larvae from four single-pair crosses were acutely transferred to and reared at salinities of 0.4, 5, 10, 20 or 32 ppt. We compared whole-body water and sodium ion (Na+) content, notochord length and yolk-sac volume at 12, 24, 48, 72, and 96 hours post-transfer for each salinity treatment. We found that larvae maintained osmotic and ionic balance at 0.4-10 ppt, whereas salinities ˃10 ppt resulted in decreased water and increased whole-body Na+ content. We also found that larvae grew largest and survived the longest when reared at 5 and 10 ppt, respectively, and that yolk resorption stalled at 0.4 ppt. Finally, there were significant but small interclutch variations in responses to different salinities, with clutch accounting for <8% of the variance in our statistical models. Overall, our results indicate that longfin smelt yolk-sac larvae likely perform best at moderately brackish conditions, thus yielding a mechanism that explains their distribution in field surveys and providing key information for future conservation efforts.

12.
Animals (Basel) ; 12(12)2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35739815

RESUMO

The rapid decline of longfin smelt Spirinchus thaleichthys, a threatened euryhaline forage fish in California, is a serious concern for scientists and resource managers. To recover and conserve this species, a captive culture program was initiated, focusing on the collection, captive rearing and breeding of wild broodstock, and the rearing of their offspring. Although progress has been made in the collection of broodstock and the production and culturing of larvae, no studies have evaluated the rearing of juvenile life stages in captivity. The present study examines methodological considerations for culturing F1 juvenile longfin smelt, specifically, the first efforts toward weaning juveniles to a dry commercial pellet feed. Cultured juvenile longfin smelt were fed live Artemia only or co-fed Artemia and dry feed for 62 days, and the effects of feed type on juvenile survival, growth, body condition, and fatty acid profiles were examined. No significant differences were observed between feeding treatments, despite an 80% reduction in Artemia in the co-feeding treatment. Furthermore, examination of fish stomach contents at the end of the trial confirmed the transition to dry feed. This is the first study to indicate successful feeding by longfin smelt on dry commercial pellets, and suggests that juvenile longfin smelt can be fully weaned onto dry feeds. Results of this study are critical for closing the lifecycle of longfin smelt in captivity and developing a successful conservation culture program for this imperiled species.

13.
G3 (Bethesda) ; 12(8)2022 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-35640553

RESUMO

Migration is a complex phenotypic trait with some species containing migratory and nonmigratory individuals. Such life history variation may be attributed in part to plasticity, epigenetics, or genetics. Although considered semianadromous, recent studies using otolith geochemistry have revealed life history variation within the critically endangered Delta Smelt. Broadly categorizable as migratory or freshwater residents, we examined Restriction site Associated DNA sequencing data to test for a relationship between genetic variation and migratory behaviors. As previously shown, we found no evidence for neutral population genetic structure within Delta Smelt; however, we found significant evidence for associations between genetic variants and life history phenotypes. Furthermore, discriminant analysis of principal components, hierarchical clustering, and machine learning resulted in accurate assignment of fish into the freshwater resident or migratory classes based on their genotypes. These results suggest the presence of adaptive genetic variants relating to life history variation within a panmictic population. Mechanisms that may lead to this observation are genotype dependent habitat choice and spatially variable selection, both of which could operate each generation and are not exclusive. Given that the population of cultured Delta Smelt are being used as a refugial population for conservation, as a supply for wild population supplementation, and currently represent the majority of all living individuals of this species, we recommend that the hatchery management strategy consider the frequencies of life history-associated alleles and how to maintain this important aspect of Delta Smelt biological variation while under captive propagation.


Assuntos
Espécies em Perigo de Extinção , Osmeriformes , Animais , Água Doce , Osmeriformes/genética , Fenótipo , Análise de Sequência de DNA
14.
PeerJ ; 9: e12280, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34820160

RESUMO

BACKGROUND: The application of otolith-based tools to inform the management and conservation of fishes first requires taxon- and stage-specific validation. The Delta Smelt (Hypomesus transpacificus), a critically endangered estuarine fish that is endemic to the upper San Francisco Estuary (SFE), California, United States, serves as a key indicator species in the SFE; thus, understanding this species' vital rates and population dynamics is valuable for assessing the overall health of the estuary. Otolith-based tools have been developed and applied across multiple life stages of Delta Smelt to reconstruct age structure, growth, phenology, and migration. However, key methodological assumptions have yet to be validated, thus limiting confidence in otolith-derived metrics that are important for informing major water management decisions in the SFE. METHODS: Using known-age cultured Delta Smelt and multiple independent otolith analysts, we examined otolith formation, otolith-somatic proportionality, aging accuracy and precision, left-right symmetry, and the effects of image magnification for larval, juvenile, and adult Delta Smelt. RESULTS: Overall, otolith size varied linearly with fish size (from 10-60 mm), explaining 99% of the variation in fish length, despite a unique slope for larvae < 10 mm. Otolith-somatic proportionality was similar among wild and cultured specimens. Aging precision among independent analysts was 98% and aging accuracy relative to known ages was 96%, with age estimates exhibiting negligible differences among left and right otoliths. Though error generally increased with age, percent error decreased from 0-30 days-post-hatch, with precision remaining relatively high (≥ 95%) thereafter. Increased magnification (400×) further improved aging accuracy for the oldest, slowest-growing individuals. Together, these results indicate that otolith-based techniques provide reliable age and growth reconstructions for larval, juvenile, and adult Delta Smelt. Such experimental assessments across multiple developmental stages are key steps toward assessing confidence in otolith-derived metrics that are often used to assess the dynamics of wild fish populations.

15.
J Low Genit Tract Dis ; 25(3): 187-191, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34138787

RESUMO

ABSTRACT: The American Cancer Society (ACS) released updated cervical cancer screening guidelines in 2020 that endorse a shift in practice to primary human papillomavirus (HPV) screening in people with a cervix, beginning at ages of 25-65 years. When access to US Food and Drug Administration-approved primary HPV testing is not available, the ACS offers cotesting or cytology as acceptable alternative strategies but suggests that these testing modalities may be excluded from future iterations of the guidelines. The ASCCP recognizes the benefits and risks of primary HPV cervical cancer screening while acknowledging the barriers to widespread adoption, including implementation issues, the impact of limited HPV vaccination in the United States, and inclusion of populations who may not be well represented on primary HPV screening trials, such as underrepresented minorities. The ASCCP endorses the 2018 US Preventive Services Task Force Recommendation Statement and supports the ACS cervical cancer screening guidelines. Most importantly, the ASCCP endorses any cervical cancer screening for secondary prevention of cervical cancer and recommends interventions that improve screening for those who are underscreened or unscreened.


Assuntos
Guias como Assunto , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , American Cancer Society , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Estados Unidos , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal
17.
Inorg Chem ; 60(7): 4733-4743, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33689349

RESUMO

The synthesis and thermal redox chemistry of the first antimony (Sb)- and bismuth (Bi)-phosphaketene adducts are described. When diphenylpnictogen chloride [Ph2PnCl (Pn = Sb or Bi)] is reacted with sodium 2-phosphaethynolate [Na[OCP]·(dioxane)x], tetraphenyldipnictogen (Ph2Pn-PnPh2) compounds are produced, and an insoluble precipitate forms from solution. In contrast, when the N-heterocyclic carbene adduct (NHC)-PnPh2Cl is combined with [Na[OCP]·(dioxane)x], Sb- and Bi-phosphaketene complexes are isolated. Thus, NHC serves as an essential mediator for the reaction. Immediately after the formation of an intermediary pnictogen-phosphaketene NHC adduct [NHC-PnPh2(PCO)], the NHC ligand transfers from the Pn center to the phosphaketene carbon atom, forming NHC-C(O)P-PnPh2 [Pn = Sb (3) or Bi (4)]. In the solid state, 3 and 4 are dimeric with short intermolecular Pn-Pn interactions. When compounds 3 and 4 are heated in THF at 90 and 70 °C, respectively, the pnictogen center PnIII is thermally reduced to PnII to form tetraphenyldipnictines (Ph2Pn-PnPh2) and an unusual bis-carbene-supported OCP salt, [(NHC)2OCP][OCP] (5). The formation of compound 5 and Ph2Pn-PnPh2 from 3 or 4 is unique in comparison to the known thermal reactivity for group 14 carbene-phosphaketene complexes, further highlighting the diverse reactivity of [OCP]- with main-group elements. All new compounds have been fully characterized by single-crystal X-ray diffraction, multinuclear NMR spectroscopy (1H, 13C, and 31P), infrared spectroscopy, and elemental analysis (1, 2, and 5). The electronic structure of 5 and the mechanism of formation were investigated using density functional theory (DFT).

18.
J Am Pharm Assoc (2003) ; 61(4): e218-e224, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33674205

RESUMO

Gabapentin is approved to treat postherpetic neuralgia and epilepsy with partial-onset seizures. The large majority of gabapentin prescribing is off label. Gabapentin may be abused for euphoria, potentiating the high from opiates, reduction of alcohol cravings, a cocaine-like high, as well as sedation or sleep. Individuals at the highest risk for abusing gabapentin include those with opioid abuse, mental illness, or previous history of prescription drug abuse. States are now taking action to track gabapentin use through prescription monitoring programs, and some states have reclassified it as a Schedule V controlled substance. This commentary summarizes gabapentin's abuse potential, identifies state-level actions regarding gabapentin monitoring, and discusses possible clinical implications and ways to enhance patient safety when prescribing gabapentin.


Assuntos
Ácidos Cicloexanocarboxílicos , Epilepsia , Transtornos Relacionados ao Uso de Substâncias , Aminas/efeitos adversos , Substâncias Controladas , Ácidos Cicloexanocarboxílicos/efeitos adversos , Gabapentina/uso terapêutico , Humanos , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle
19.
Angew Chem Int Ed Engl ; 60(12): 6682-6690, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33290596

RESUMO

We report a combined experimental and theoretical study on the first examples of carbodicarbene (CDC)-stabilized bismuth complexes, which feature low-coordinate cationic bismuth centers with C=Bi multiple-bond character. Monocations [(CDC)Bi(Ph)Cl][SbF6 ] (8) and [(CDC)BiBr2 (THF)2 ][SbF6 ] (11), dications [(CDC)Bi(Ph)][SbF6 ]2 (9) and [(CDC)BiBr(THF)3 ][NTf2 ]2 (12), and trication [(CDC)2 Bi][NTf2 ]3 (13) have been synthesized via sequential halide abstractions from (CDC)Bi(Ph)Cl2 (7) and (CDC)BiBr3 (10). Notably, the dications and trication exhibit C ⇉ Bi double dative bonds and thus represent unprecedented bismaalkene cations. The synthesis of these species highlights a unique non-reductive route to C-Bi π-bonding character. The CDC-[Bi] complexes (7-13) were compared with related NHC-[Bi] complexes (1, 3-6) and show substantially different structural properties. Indeed, the CDC ligand has a remarkable influence on the overall stability of the resulting low-coordinate Bi complexes, suggesting that CDC is a superior ligand to NHC in heavy pnictogen chemistry.

20.
Colorectal Dis ; 22(10): 1325-1335, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32397003

RESUMO

AIM: To describe the results of a feasibility phase and the expected results of a new approach to increase the participation rate in a Colorectal Cancer Organized Screening Program (CRCSP) through Facebook awareness messages. METHOD: This approach targets people aged 50-74 years, who reside in an urban deprived area and regularly connect to Facebook. The feasibility phase ran over 2 months (December 2018 and January 2019) in six municipalities (Seine-Saint-Denis, France). The full provisional campaign will run over a year. The approach consists of sending electronic awareness messages on the importance of screening for colorectal cancer using a specific Facebook module. Subjects who consent to screening complete a test-kit application form. The eligibility of each subject to participate in screening is determined by a doctor before the kit is sent out. RESULTS: A total of 39 900 people were reached by the feasibility phase campaign, and 9200 were able to watch at least one Facebook message/video. Of those, 4450 people logged to learn more about the CRCSP, 298 applied for a test kit, 160 test kit applicants were eligible to participate and the test completion rate was 41.9%. According to these feasibility results, 366 120 targeted people would connect regularly in the tested area, 141 541 of whom would be interested in a specific promotional message posted on Facebook. Requests could be made for 9770 kits, with 5246 people being eligible to participate in screening. The expected test-completion rate is estimated at 42%-89%. This would represent 5%-11% of the tests carried out in the area during the same period by 'classical' CRCSP. CONCLUSION: Implementation of the Facebook strategy would significantly improve the rate of participation in the CRCSP by mobilizing people with no previous participation, including younger subjects.


Assuntos
Neoplasias Colorretais , Mídias Sociais , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Estudos de Viabilidade , Humanos , Programas de Rastreamento , Rede Social
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