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Introduction: Impostor phenomenon (IP), grit, and other factors impact job satisfaction for faculty, particularly female faculty., Methods: The Impostor Phenomenon Research Collaborative (IPRC) evaluated IP, grit, and job satisfaction in pharmacy faculty. A cross-sectional study was conducted with a convenience sample of faculty using a survey, which included demographic questions and validated instruments: Clance Impostor Phenomenon (CIPS), Short GRIT Scale, and Overall Job Satisfaction Questionnaire. Differences between groups, relationships, and prediction were evaluated using independent t-tests, ANOVA, Pearson correlation, and regression analyses., Results: A total of 436 participants completed the survey; 380 self-identified as pharmacy faculty. Two hundred and one (54%) reported intense or frequent feelings of IP. The mean CIPS score was above 60, indicating a risk of negative outcomes related to IP. There were no differences in the prevalence of IP or job satisfaction levels when female and male faculty were compared. Female faculty had higher GRIT-S scores. Faculty reporting more IP had lower grit and lower job satisfaction. Job satisfaction in faculty was predicted by IP and grit; however, grit did not provide a unique prediction when combined with IP for male faculty., Conclusion: IP was not more prevalent in female faculty. Female faculty were grittier than male faculty. Higher grit was associated with less IP and higher job satisfaction. IP and grit predicted job satisfaction for female and male pharmacy faculty. Our findings suggest that improving grit may help mitigate IP and impact job satisfaction. Further research on evidence-based IP interventions is needed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Significant teratogenic effects have been demonstrated for ribavirin in animal studies. Ribavirin is prescribed for chronic hepatitis C and is contraindicated in pregnant women and their male sexual partners. Both are advised to avoid pregnancy for 6 months after exposure. The registry monitored pregnancy exposures to oral formulations of ribavirin for hepatitis C for signals of possible human teratogenicity from 2004 to 2020., Methods: Pregnant women were voluntarily enrolled following direct exposure (ribavirin use during pregnancy or the 6 months prior) or indirect exposure (through sexual contact during pregnancy or 6 months prior, with a man who has taken ribavirin within 6 months). Women were followed until the end of pregnancy. Infants were followed until 1 year of age. Birth defect rates were compared with the published rate of 2.67 per 100 live births from the Metropolitan Atlanta Congenital Defects Program (MACDP)., Results: The registry enrolled 280 pregnancies resulting in 186 live births: eight birth defect cases among 88 directly exposed [9.09% (8/88, 95% CI: 4.01, 17.13)], and six birth defect cases among 98 indirectly exposed [6.12% (6/98, 95% CI: 2.28, 12.85)]. The 95% CI around the birth defect rate among directly exposed pregnancies exceeds the MACDP rate; however, no patterns suggestive of a teratogenic mechanism or safety signal were detected., Conclusion: Based on the patterns of birth defects reported, the final results from this registry do not suggest a clear signal of human teratogenicity for ribavirin. The registry did not meet sample size requirements; therefore, caution should be exercised when interpreting the results., (© 2022 Wiley Periodicals LLC.)

Introduction: Primary Sjögren's syndrome (pSS) is a complex, heterogenous autoimmune disease; no immunomodulatory drug has demonstrated efficacy, and no current treatments target the underlying cause. This study aimed to explore the disease and treatment experiences of patients with pSS., Methods: This qualitative study (208399) comprised moderated online forum discussions and online one-to-one questions conducted in the USA over a 2-week period. Participants were self-reported patients with pSS; physician confirmation of diagnosis was sought. Participants described disease and symptom severity and satisfaction with current pSS treatments. Qualitative data analysis was performed using inductive coding analysis via open coding., Results: Fifty-two participants entered the study, of whom 48 provided analysable data. Symptoms were described as highly unpredictable and variable, with fatigue rated as the most severe and burdensome. Participants discussed how their pSS symptoms and the frequent need for regular treatment impacted their daily activities, social life, career and finances. Many participants perceived a poor understanding of pSS amongst physicians, leading to emotional distress and difficulties obtaining a diagnosis. All participants stated that an ideal medication would address the cause of pSS and not just treat symptoms., Conclusion: New insights into patients' perspectives of pSS were generated from online discussion forums, revealing the additional impact of unpredictable symptoms and multiple symptomatic treatments to the high disease burden. Improving physician education of pSS may help to alleviate frustrations and delays associated with diagnosis; the advent of novel effective treatments would be welcomed by patients with pSS.

Human amniotic membrane (AM) has a long history of clinical use for wound treatment. AM serves as a wound protective barrier maintaining proper moisture. AM is anti-inflammatory, anti-microbial and antifibrotic, and supports angiogenesis, granulation tissue formation and wound re-epithelialization. These properties of AM are attributed to its native extracellular matrix, growth factors, and endogenous cells including mesenchymal stem cells. Advances in tissue preservation have helped to overcome the short shelf life of fresh AM and led to the development of AM products for clinical use. Viable cryopreserved amnion (VCAM), which retains all native components of fresh AM, has shown positive outcomes in clinical trials for wound management. However, cryopreservation requires ultra-low temperature storage and shipment that limits widespread use of VCAM. We have developed a lyopreservation technique to allow for ambient storage of living tissues. Here, we compared the structural, molecular, and functional properties of a viable lyopreserved human amniotic membrane (VLAM) with properties of VCAM using in vitro and in vivo wound models. We found that the structure, growth factors, and cell viability of VLAM is similar to that of VCAM and fresh AM. Both, VCAM and VLAM inhibited TNF-α secretion and upregulated VEGF expression in vitro under conditions designed to mimic inflammation and hypoxia in a wound microenvironment, and resulted in wound closure in a diabetic mouse chronic wound model. Taken together, these data demonstrate that VLAM structural and functional properties are equivalent to VCAM but without the constraints of ultra-low temperature storage., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: All authors are full time paid employees of Osiris Therapeutics Inc.

Introduction: Significant teratogenic effects have been demonstrated in all animal species exposed to ribavirin. Ribavirin is prescribed for chronic hepatitis C and is contraindicated in women who are pregnant and in the male sexual partners of women who are pregnant. Both sexes are advised to avoid pregnancy for 6 months after exposure. The Ribavirin Pregnancy Registry was established in 2003 to monitor pregnancy exposures to ribavirin for signals of possible human teratogenicity., Methods: This voluntary registry enrolls pregnant women with prenatal exposure to ribavirin. Exposure is classified as direct-women taking ribavirin during pregnancy or the 6 months prior to conception-or indirect-women exposed through sexual contact, 6 months prior to or during pregnancy, with a man who is taking or has taken ribavirin in the past 6 months. Women are followed until delivery and infants for 1 year. When enrollment is complete, birth defect rates will be compared with the Metropolitan Atlanta Congenital Defects Program's published rate of 2.67. Using data collected since inception in 2003 through February 2016, preliminary rates were calculated., Results: The registry has enrolled 272 pregnant women, with 180 live births: there were seven birth defect cases among 85 directly exposed women [7/85 (8.2%) (95% confidence interval (CI) 3.4-16.2)] and four birth defect cases among 95 indirectly exposed women [4/95 (4.2%) (95% CI 1.2-10.4)]. Of the 11 infants, nine had structural defects and two had chromosomal anomalies. Patterns suggesting a common etiology or relationship with ribavirin exposure are not seen., Conclusion: Based on the patterns of birth defects reported, preliminary findings do not suggest a clear signal of human teratogenicity for ribavirin. However, the current sample size is insufficient for definitive conclusions, and ribavirin exposure should be avoided during pregnancy and during the 6 months prior to pregnancy, in accordance with prescribing information., Clinical Trial Registration: ClinicalTrials.gov identifier: NCT00114712.

Nearly 90% of women in the United States have taken medications during pregnancy. Medication exposures during pregnancy can result in adverse pregnancy and neonatal outcomes including birth defects, fetal loss, intrauterine growth restriction, prematurity, and longer-term neurodevelopmental outcomes. Advising pregnant women about the safety of medication use during pregnancy is complicated by a lack of data necessary to engage the woman in an informed discussion. Routinely, health care providers turn to the package insert, yet this information can be incomplete and can be based entirely on animal studies. Often, adequate safety data are not available. In a busy clinical setting, health care providers need to be able to quickly locate the most up-to-date information in order to counsel pregnant women concerned about medication exposure. Deciding where to locate the best available information is difficult, particularly when the needed information does not exist. Pregnancy registries are initiated to obtain more data about the safety of specific medication exposures during pregnancy; however, these studies are slow to produce meaningful information, and when they do, the information may not be readily available in a published form. Health care providers have valuable data in their everyday practice that can expand the knowledge base about medication safety during pregnancy. This review aims to discuss the limitations of the package insert regarding medication safety during pregnancy, highlight additional resources available to health care providers to inform practice, and communicate the importance of pregnancy registries for expanding knowledge about medication safety during pregnancy., (© 2016 by the American College of Nurse-Midwives.)

Post-traumatic arthritis (PTA) is a rapidly progressive form of arthritis that develops due to joint injury, including articular fracture. Current treatments are limited to surgical restoration and stabilization of the joint; however, evidence suggests that PTA progression is mediated by the upregulation of pro-inflammatory cytokines, such as interleukin-1 (IL-1) or tumor necrosis factor-α (TNF-α). Although these cytokines provide potential therapeutic targets for PTA, intra-articular injections of anti-cytokine therapies have proven difficult due to rapid clearance from the joint space. In this study, we examined the ability of a cross-linked elastin-like polypeptide (xELP) drug depot to provide sustained intra-articular delivery of IL-1 and TNF-α inhibitors as a beneficial therapy. Mice sustained a closed intra-articular tibial plateau fracture; treatment groups received a single intra-articular injection of drug encapsulated in xELP. Arthritic changes were assessed 4 and 8 weeks after fracture. Inhibition of IL-1 significantly reduced the severity of cartilage degeneration and synovitis. Inhibition of TNF-α alone or with IL-1 led to deleterious effects in bone morphology, articular cartilage degeneration, and synovitis. These findings suggest that IL-1 plays a critical role in the pathogenesis of PTA following articular fracture, and sustained intra-articular cytokine inhibition may provide a therapeutic approach for reducing or preventing joint degeneration following trauma.

Objectives: To monitor for a signal of major teratogenicity by determining the risk of all birth major defects following in utero exposure to sumatriptan, naratriptan, and the sumatriptan/naproxen sodium combination product (tablets marketed in the United States as Treximet [GlaxoSmithKline, Research Triangle Park, NC, USA]), and to monitor for unusual patterns of defects that might suggest teratogenicity., Background: The prevalence of migraine is highest in women of childbearing age. Coupled with the recurrent nature of migraine attacks and the high proportion of unplanned pregnancies, intentional and inadvertent exposure to anti-migraine drugs in pregnancy is likely. The Sumatriptan, Naratriptan, and Treximet Pregnancy Registry captured data on women exposed to those drugs during pregnancy to monitor for evidence of major teratogenicity., Methods: In this primarily prospective, observational study, health care professionals from anywhere in the world enrolled, on a voluntary basis, women exposed to sumatriptan, naratriptan, or the sumatriptan/naproxen sodium combination product during their pregnancies. Only pregnancies with unknown outcomes at the time of enrollment were included in the analysis. The proportion of infants or fetuses with major birth defects was calculated as the total number of infants/fetuses with major birth defects divided by the sum of the number of infants/fetuses with major birth defects + the number of live births without defects. The risk of major birth defects was further stratified by earliest trimester of pregnancy exposure., Results: The registry enrolled 680 evaluable exposed pregnant women, which resulted in 689 infants and fetuses (outcomes). Of these outcomes, 626 were exposed to sumatriptan, 57 were exposed to naratriptan (seven were exposed to both sumatriptan and naratriptan), and six were exposed to the sumatriptan/naproxen sodium combination product. Twenty outcomes with major birth defects were reported among 528 outcomes exposed in the first trimester to sumatriptan. The estimated risk of major birth defects following first-trimester sumatriptan exposure is 4.2% (20/478 [95% confidence interval [CI] 2.6%-6.5%]). Among 52 first-trimester exposures to naratriptan, major birth defects were reported in one outcome, an infant with exposure to both sumatriptan and naratriptan [birth defect risk of 2.2% (1/46 [95% CI 0.1%-13.0%]). No major defects were reported among the five outcomes with first-trimester exposure to the sumatriptan/naproxen sodium combination products., Conclusions: The Sumatriptan, Naratriptan, and Treximet Pregnancy Registry detected no signal of teratogenicity associated with major birth defects for sumatriptan. This finding is consistent with results from other observational studies using a variety of control groups. Enrollment in the registry was insufficient to permit definitive conclusions of the risks associated with naratriptan or sumatriptan/naproxen sodium tablets, or to assess the risk of individual birth defects in any of the products studied. Low enrollment and high rates of loss to follow up within the registry over an extended period of time led the registry's scientific advisory committee to conclude that continuation of the registry beyond its 16 years would offer little additional power to rule out more moderate increases in the risk of birth defects. Data from the other ongoing surveillance sources constitute an important element of post-marketing surveillance of these medications. The lack of a signal of major teratogenicity with sumatriptan across these several sources of data is encouraging., (© 2014 American Headache Society.)

Objective: Women with multiple sclerosis are often diagnosed and treated during their reproductive years. Limited data are available on the safety of treatment during pregnancy. The Betaseron Pregnancy Registry prospectively monitored women exposed to interferon β-1b (IFNβ-1b) during pregnancy to estimate the rates of birth defects, spontaneous abortions (SABs) and other negative outcomes in this population., Design: From 2006 to 2011, this observational registry enrolled women exposed prior to conception or during pregnancy (but prior to or without abnormalities on prenatal screening). Follow-up continued from enrolment through the 4-month paediatric visit., Setting: Patients in the USA who met these criteria were enrolled in the registry., Results: The registry enrolled 99 pregnant women; 3 were lost to follow-up. The earliest exposure to IFNβ-1b occurred during the first trimester for 95 pregnancies and in the third trimester for 1 pregnancy. There were 99 birth outcomes (3 twins), including 86 (86.9%) live births, 11 (11.1%) SABs and 2 (2%) stillbirths. Birth defects were reported in five (5.1%) cases. Rates of birth defects and SAB were not significantly different from population comparators. No developmental concerns were identified at the 4-month paediatric visit., Conclusions: The small sample size limits the ability to draw definitive conclusions; however, there was no pattern to suggest increased negative outcomes with IFNβ-1b., Clinical Trials Registration Number: NCT00317564.

We tested the hypothesis that the feeling of knowing (FOK) after a failed recall attempt is influenced by recalling aspects of the original encoding strategy. Individuals were instructed to use interactive imagery to encode unrelated word pairs. We manipulated item concreteness (abstract vs. concrete) and item repetitions at study (one vs. three). Participants orally described the mediator produced immediately after studying each item, if any. After a delay, they were given cued recall, made FOK ratings, and attempted to recall their original mediator. Concreteness and item repetition enhanced strategy recall, which had a large effect on FOKs. Controlling on strategy recall reduced the predictive validity of FOKs for recognition memory, indicating that access to the original aspects of encoding influenced FOK accuracy. Confidence judgments (CJs) for correctly recognized items covaried with FOKs, but FOKs did not fully track the strategy recall associations with CJs, suggesting emergent effects of strategy cues that were elicited by recognition tests but not accessed at the time of the FOK judgment. In summary, cue-generated access to aspects of the original encoding strategy strongly influenced episodic FOKs, although other influences were also implicated.

Radiculopathy, a painful neuroinflammation that can accompany intervertebral disc herniation, is associated with locally increased levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). Systemic administration of TNF antagonists for radiculopathy in the clinic has shown mixed results, and there is growing interest in the local delivery of anti-inflammatory drugs to treat this pathology as well as similar inflammatory events of peripheral nerve injury. Curcumin, a known antagonist of TNFα in multiple cell types and tissues, was chemically modified and conjugated to a thermally responsive elastin-like polypeptide (ELP) to create an injectable depot for sustained, local delivery of curcumin to treat neuroinflammation. ELPs are biopolymers capable of thermally-triggered in situ depot formation that have been successfully employed as drug carriers and biomaterials in several applications. ELP-curcumin conjugates were shown to display high drug loading, rapidly release curcumin in vitro via degradable carbamate bonds, and retain in vitro bioactivity against TNFα-induced cytotoxicity and monocyte activation with IC50 only two-fold higher than curcumin. When injected proximal to the sciatic nerve in mice via intramuscular (i.m.) injection, ELP-curcumin conjugates underwent a thermally triggered soluble-insoluble phase transition, leading to in situ formation of a depot that released curcumin over 4days post-injection and decreased plasma AUC 7-fold., (© 2013.)

Introduction: Tumor necrosis factor-α (TNFα) has received significant attention as a mediator of lumbar radiculopathy, with interest in TNF antagonism to treat radiculopathy. Prior studies have demonstrated that TNF antagonists can attenuate heightened nociception resulting from lumbar radiculopathy in the preclinical model. Less is known about the potential impact of TNF antagonism on gait compensations, despite being of clinical relevance. In this study, we expand on previous descriptions of gait compensations resulting from lumbar radiculopathy in the rat and describe the ability of local TNF antagonism to prevent the development of gait compensations, altered weight bearing, and heightened nociception., Methods: Eighteen male Sprague-Dawley rats were investigated for mechanical sensitivity, weight-bearing, and gait pre- and post-operatively. For surgery, tail nucleus pulposus (NP) tissue was collected and the right L5 dorsal root ganglion (DRG) was exposed (Day 0). In sham animals, NP tissue was discarded (n = 6); for experimental animals, autologous NP was placed on the DRG with or without 20 μg of soluble TNF receptor type II (sTNFRII, n = 6 per group). Spatiotemporal gait characteristics (open arena) and mechanical sensitivity (von Frey filaments) were assessed on post-operative Day 5; gait dynamics (force plate arena) and weight-bearing (incapacitance meter) were assessed on post-operative Day 6., Results: High-speed gait characterization revealed animals with NP alone had a 5% decrease in stance time on their affected limbs on Day 5 (P ≤0.032). Ground reaction force analysis on Day 6 aligned with temporal changes observed on Day 5, with vertical impulse reduced in the affected limb of animals with NP alone (area under the vertical force-time curve, P <0.02). Concordant with gait, animals with NP alone also had some evidence of affected limb mechanical allodynia on Day 5 (P = 0.08) and reduced weight-bearing on the affected limb on Day 6 (P <0.05). Delivery of sTNFRII at the time of NP placement ameliorated signs of mechanical hypersensitivity, imbalanced weight distribution, and gait compensations (P <0.1)., Conclusions: Our data indicate gait characterization has value for describing early limb dysfunctions in pre-clinical models of lumbar radiculopathy. Furthermore, TNF antagonism prevented the development of gait compensations subsequent to lumbar radiculopathy in our model.

Study Design: The inflammatory responses of primary human intervertebral disc (IVD) cells to tumor necrosis factor α (TNF-α) and an antagonist were evaluated in vitro., Objective: To investigate an ability for soluble TNF receptor type II (sTNFRII) to antagonize TNF-α-induced inflammatory events in primary human IVD cells in vitro., Summary of Background Data: TNF-α is a known mediator of inflammation and pain associated with radiculopathy and IVD degeneration. sTNFRs and their analogues are of interest for the clinical treatment of these IVD pathologies, although information on the effects of sTNFR on human IVD cells remains unknown., Methods: IVD cells were isolated from surgical tissues procured from 15 patients and cultured with or without 1.4 nmol/L TNF-α (25 ng/mL). Treatment groups were coincubated with varying doses of sTNFRII (12.5-100 nmol/L). Nitric oxide (NO), prostaglandin E₂ (PGE₂), and interleukin-6 (IL6) levels in media were quantified to characterize the inflammatory phenotype of the IVD cells., Results: Across all patients, TNF-α induced large, statistically significant increases in NO, PGE₂, and IL6 secretion from IVD cells compared with controls (60-, 112-, and 4-fold increases, respectively; P < 0.0001). Coincubation of TNF-α with nanomolar doses of sTNFRII significantly attenuated the secretion of NO and PGE₂ in a dose-dependent manner, whereas IL6 levels were unchanged. Mean IC₅₀ values for NO and PGE₂ were found to be 35.1 and 20.5 nmol/L, respectively., Conclusion: Nanomolar concentrations of sTNFRII were able to significantly attenuate the effects of TNF-α on primary human IVD cells in vitro. These results suggest this sTNFR to be a potent TNF antagonist with potential to attenuate inflammation in IVD pathology.

Interleukin-17 (IL-17) is a cytokine recently shown to be elevated, along with interferon-γ (IFNγ) and tumor necrosis factor (TNFα), in degenerated and herniated intervertebral disc (IVD) tissues, suggesting a role for these cytokines in intervertebral disc disease. The objective of our study was to investigate the involvement of IL-17 and costimulants IFNγ and TNFα in intervertebral disc pathology. Cells were isolated from anulus fibrosus and nucleus pulposus tissues of patients undergoing surgery for intervertebral disc degeneration or scoliosis. The production of inflammatory mediators, nitric oxide (NOx), prostaglandin E2 (PGE2) and interleukin-6 (IL-6), as well as intercellular adhesion molecule (ICAM-1) expression, were quantified for cultured cells following exposure to IL-17, IFNγ, and TNFα. Intervertebral disc cells exposed to IL-17, IFNγ, or TNFα showed a remarkable increase in inflammatory mediator release and ICAM-1 expression (GLM and ANOVA, p < 0.05). Addition of IFNγ or TNFα to IL-17 demonstrated a synergistic increase in inflammatory mediator release, and a marked increase in ICAM-1 expression. These findings suggest that IVD cells not only respond with a catabolic phenotype to IL-17 and costimulants IFNγ and TNFα, but also express surface ligands with consequent potential to recruit additional lymphocytes and immune cells to the IVD microenvironment. IL-17 may be an important regulator of inflammation in the IVD pathologies., (Copyright © 2010 Orthopaedic Research Society.)

In recent studies, researchers have argued for adult age-related deficits in the resolution of episodic feeling of knowing (FOK) owing to a decline in inferential processes. In the present study, we introduce the memory constraint hypothesis, which argues that deficits are an outcome of differences in the level of learning. A repetition delay paradigm for a list of paired-associate items showed that repeated presentations at encoding increased memory performance and in turn increased FOK resolution for unrecalled items. Older adults who were given a 48-h delay between encoding and subsequent tests (and FOKs) had equivalent memory performance to younger adults who were given a 7-day delay. In this case, age equivalence arose in FOK resolution except at the lowest levels of recognition in the single-presentation condition. The use of effective strategies during encoding correlated with memory performance and FOKs, even for unrecalled pairs. These results are inconsistent with an inferential-deficit explanation of age deficits in FOK resolution; they point to the importance of original encoding quality as a potent contributor to FOK resolution, and they argue for equating age groups on memory performance when evaluating the episodic FOK resolution of age differences.

Researchers of metacognitive development in adulthood have exclusively used extreme-age-groups designs. We used a full cross-sectional sample (N = 285, age range: 18-80) to evaluate how associative relatedness and encoding strategies influence judgments of learning (JOLs) in adulthood. Participants studied related and unrelated word pairs and made JOLs. After a cued-recall test, retrospective item strategy reports were collected. Results revealed developmental patterns not available from previous studies (e.g., a linear age-related increase in aggregate JOL resolution across the life span). They also demonstrated the value of investigating multiple cues' influences on JOLs. Multilevel regression models showed that both relatedness and effective strategy use positively and independently influenced JOLs. Furthermore, effective strategy use was responsible for higher resolution of JOLs for unrelated items (relative to related items). The effects of relatedness and strategy use with JOLs did not interact with age. The monitoring of learning is spared by adult development despite age differences in learning itself.