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JAMA Network Open Jul 2024Discrimination, bullying, and harassment in medicine have been reported internationally, but exposures for Indigenous medical students and physicians, and for racism...
IMPORTANCE
Discrimination, bullying, and harassment in medicine have been reported internationally, but exposures for Indigenous medical students and physicians, and for racism specifically, remain less examined.
OBJECTIVE
To examine the prevalence of racism, discrimination, bullying, and harassment for Māori medical students and physicians in New Zealand and associations with demographic and clinical characteristics.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study used data from an anonymous national survey of Māori medical students and physicians in New Zealand in late 2021 and early 2022. Data were analyzed from March 2022 to April 2024.
EXPOSURES
Age, gender, marginalized status (ie, in addition to being Māori, belonging to other groups traditionally marginalized or underrepresented in medicine), year of medical school, year of graduation, and main work role.
MAIN OUTCOMES AND MEASURES
Direct and witnessed racism, discrimination, bullying, and harassment were measured as any experience in the last year and ever. Any exposure to negative comments about social groups and witnessing discriminatory treatment toward Māori patients or whānau (extended family). Considering leaving medicine, including because of mistreatment, was measured.
RESULTS
Overall, 205 Māori medical students (median [IQR] age, 23.1 [21.6-24.3] years; 137 [67.2%] women) and 200 physicians (median [IQR] age, 36.6 [30.1-45.3] years; 123 [62.8%] women) responded. Direct and witnessed exposure to racism (184 students [91.5%]; 176 physicians [90.7%]) and discrimination (176 students [85.9%]; 179 physicians [89.5%]) ever in medical education, training, or work environments was common. Ever exposure to witnessed and direct bullying (123 students [66.5%]; 150 physicians [89.3%]) and harassment (73 students [39.5%]; 112 physicians [66.7%]) was also common. Most respondents reported witnessing Māori patients or their whānau being treated badly in clinical settings, in direct interactions (67 students [57.8%]; 112 physicians [58.9%]) or behind their backs (87 students [75.0%]; 138 physicians [72.6%]). One-quarter of Māori medical students (45 students), and 37.0% of physicians (61 physicians) had considered leaving or taken a break from medicine because of these experiences. Additional marginalized statuses were significantly associated with any direct experience of mistreatment in the last year for students and physicians. Exposure to some forms of mistreatment were also significantly associated with higher likelihood of thinking about leaving or taking a break from medicine for physicians.
CONCLUSIONS AND RELEVANCE
In this study, Māori medical students and physicians reported high exposure to multiple forms of racism, discrimination, bullying, and harassment in medical education, training, and work environments, requiring an urgent response from medical institutions.
Topics: Humans; Students, Medical; Racism; Male; Bullying; Female; New Zealand; Cross-Sectional Studies; Adult; Physicians; Native Hawaiian or Other Pacific Islander; Young Adult; Surveys and Questionnaires; Middle Aged; Maori People
PubMed: 38949810
DOI: 10.1001/jamanetworkopen.2024.19373 -
Journal of Counseling Psychology Jul 2024Mental health researchers have focused on promoting culturally sensitive clinical care (Herman et al., 2007; Whaley & Davis, 2007), emphasizing the need to understand...
Mental health researchers have focused on promoting culturally sensitive clinical care (Herman et al., 2007; Whaley & Davis, 2007), emphasizing the need to understand how biases may impact client well-being. Clients report that their therapists commit racial microaggressions-subtle, sometimes unintentional, racial slights-during treatment (Owen et al., 2014). Yet, existing studies often rely on retrospective evaluations of clients and cannot establish the causal impact of varying ambiguity of microaggressions on clients. This study uses an experimental analogue design to examine offensiveness, emotional reactions, and evaluations of the interaction across three distinct levels of microaggression statements: subtle, moderate, and overt. We recruited 158 adult African American participants and randomly assigned them to watch a brief counseling vignette. We found significant differences between the control and three microaggression statements on all outcome variables. We did not find significant differences between the microaggression conditions. This study, in conjunction with previous correlational research, highlights the detrimental impact of microaggressions within psychotherapy, regardless of racially explicit content. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Topics: Humans; Adult; Male; Black or African American; Female; Aggression; Psychotherapy; Professional-Patient Relations; Racism; Middle Aged; Young Adult
PubMed: 38949778
DOI: 10.1037/cou0000742 -
Annals of Dyslexia Jun 2024Reading proficiency is important because it has life-long consequences and influences success in other academic areas. Many students with behavior problems are poor...
Reading proficiency is important because it has life-long consequences and influences success in other academic areas. Many students with behavior problems are poor readers and many students with learning disabilities have more behavior problems than their typical peers. We conducted a correlational meta-analysis to examine the association between reading and externalizing behavior in students ages 5-12. We identified 33 studies that reported 88 effect sizes. Using a random-effects linear regression model with robust variance estimation, we found a significant, negative correlation (r= -0.1698, SE = 0.01, p < 0.0001) between reading and externalizing behavior. We tested several moderators related to measurement and sample characteristics. We found that rater type, behavior dimension (e.g., aggression), time between longitudinal measurement points, age of the sample, and percentage male of the sample moderated the relation between reading and behavior. Whether the reading assessment measured comprehension or word reading and socioeconomic status of the sample did not moderate the relation. Understanding the association between reading and externalizing behavior has implications for disability identification and intervention practices for children in elementary school. Future research should examine shared cognitive factors and environmental influences that explain the relation between the constructs.
PubMed: 38949745
DOI: 10.1007/s11881-024-00307-w -
Biology of the Cell Jul 2024One of the confounding factors in pancreatic cancer (PC) pathogenesis is hyperglycemia. The molecular mechanism by which high glucose (HG) influences PC severity is...
BACKGROUND INFORMATION
One of the confounding factors in pancreatic cancer (PC) pathogenesis is hyperglycemia. The molecular mechanism by which high glucose (HG) influences PC severity is poorly understood. Our investigation delved into the impact of lncRNA highly upregulated in liver cancer (HULC) and its interaction with yes-associated protein (YAP) in regulating the fate of pancreatic ductal adenocarcinoma cells (PDAC) under HG-induced conditions. PDAC cells were cultured under normal or HG conditions. We thereafter measured the effect of HG on the viability of PDAC cells, their migration potential and drug resistance properties. The lncRNAs putatively dysregulated in PC and diabetes were shortlisted by bioinformatics analysis followed by wet lab validation of function.
RESULTS
HG led to enhanced proliferation and drug refractoriness in PDAC cells. HULC was identified as one of the major deregulated lncRNAs following bioinformatics analysis. HULC was found to regulate the expression of the potent transcriptional regulator - YAP through selective histone modifications at the YAP promoter. siRNA-mediated ablation of HULC resulted in a concurrent decrease in YAP transcriptional activity. Importantly, HULC and YAP were found to co-operatively regulate the cellular homeostatic process autophagy, thus inculcating drug resistance and proliferative potential in PDAC cells. Moreover, inhibition of autophagy or YAP led to a decrease in HULC levels, suggesting the existence of an inter-regulatory feedback loop.
CONCLUSIONS
We observed that HG triggers aggressive properties in PDAC cells. Mechanistically, up-regulation of lncRNA HULC resulted in activation of YAP and differential regulation of autophagy coupled to increased proliferation of PDAC cells.
SIGNIFICANCE
Inhibition of HULC and YAP may represent a novel therapeutic strategy for PDAC. Furthermore, this study portrays the intricate molecular interplay between HULC, YAP and autophagy in PDAC pathogenesis.
PubMed: 38949568
DOI: 10.1111/boc.202400034 -
Molecular Cancer Research : MCR Jul 2024Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by loss of function mutations in fumarate hydratase (FH) and results in an aggressive subtype of...
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by loss of function mutations in fumarate hydratase (FH) and results in an aggressive subtype of renal cell carcinoma with limited treatment options. Loss of FH leads to accumulation of fumarate, an oncometabolite that disrupts multiple cellular processes and drives tumor progression. High levels of fumarate inhibit alpha ketoglutarate-dependent dioxygenases, including the ten eleven translocation (TET) enzymes and can lead to global DNA hypermethylation. Here, we report patterns of hypermethylation in FH-mutant cell lines and tumor samples are associated with silencing of nicotinate phosphoribosyl transferase (NAPRT), a rate-limiting enzyme in the Preiss-Handler pathway of NAD+ biosynthesis in a subset of HLRCC cases. NAPRT is hypermethylated at a CpG island in the promoter in cell line models and patient samples, resulting in loss of NAPRT expression. We find that FH-deficient RCC models with loss of NAPRT expression, as well as other oncometabolite-producing cancer models that silence NAPRT, are extremely sensitive to nicotinamide phosphoribosyl transferase inhibitors (NAMPTis). NAPRT silencing was also associated with synergistic tumor cell killing with poly(ADP)-ribose polymerase inhibitors (PARPis) and NAMPTis, which was associated with effects on PAR-mediated DNA repair. Overall, our findings indicate that NAPRT-silencing can be targeted in oncometabolite-producing cancers and elucidates how oncometabolite associated hypermethylation can impact diverse cellular processes and leads to therapeutically relevant vulnerabilities in cancer cells. Implications: NAPRT is a novel biomarker for targeting NAD+ metabolism in FH-deficient HLRCCs with NAMPTis alone and targeting DNA repair processes with the combination of NAMPTis and PARPis.
PubMed: 38949523
DOI: 10.1158/1541-7786.MCR-23-1003 -
Molecular Cancer Research : MCR Jul 2024Because of its insensitivity to existing radiotherapy, namely chemotherapy and targeted treatments, triple-negative breast cancer (TNBC) remains a great challenge to...
Because of its insensitivity to existing radiotherapy, namely chemotherapy and targeted treatments, triple-negative breast cancer (TNBC) remains a great challenge to overcome. Increasing evidence has indicated abnormal Wnt/β-catenin pathway activation in TNBC but not luminal or HER2+ breast cancer, and lncRNAs play a key role in a variety of cancers. Through lncRNA microarray profiling between activated and inactivated wnt/β-catenin pathway of TNBC tissues, lnc-WAL (wnt/β-catenin associated lncRNA; WAL) was selected as the top upregulated lncRNA in wnt/β-catenin pathway activation compared with the inactivation group. RIP-seq was used to compare the β-catenin and IgG groups, where lnc-WAL could interact with β-catenin. Clinically, increased lnc-WAL in TNBC tumor tissue was associated with shorter survival. lnc-WAL promoted EMT, the proliferation, migration and invasion of breast cancer stem cells (BCSCs), and TNBC cells. Mechanistically, lnc-WAL inhibited β-catenin protein degradation via Axin-mediated phosphorylation at serine 45. Subsequently, β-catenin accumulated in the nucleus and activated the target genes. Importantly, wnt/β-catenin pathway activation stimulated the transcription of lnc-WAL. These results pointed to a master regulatory role of lnc-WAL/Axin/β-catenin in the malignant progression of TNBC. Our findings provide important clinical translational evidence that lnc-WAL may be a potential therapeutic target against TNBC. Implications: The positive feedback between lnc-WAL and the Wnt/β-catenin pathway promotes TNBC progression, and lnc-WAL could be a potential prognostic marker for TNBC patients.
PubMed: 38949521
DOI: 10.1158/1541-7786.MCR-23-0334 -
Pain Practice : the Official Journal of... Jul 2024Gabapentin, a widely prescribed medication for various neuropathic pain conditions, has demonstrated efficacy in managing diverse neurological disorders. While...
BACKGROUND
Gabapentin, a widely prescribed medication for various neuropathic pain conditions, has demonstrated efficacy in managing diverse neurological disorders. While conventional side effects are well-documented, a growing body of evidence suggests the existence of atypical side effects, necessitating comprehensive exploration. This paper aims to systematically review and summarize the literature on the atypical side effects of gabapentin, shedding light on manifestations beyond the conventional spectrum.
METHODS
A systematic review was conducted, encompassing peer-reviewed articles published up to the knowledge cutoff date in November 2023. Databases, specifically PubMed, were searched for relevant studies, focusing on atypical side effects such as myoclonus, ataxia, pediatric aggression, respiratory depression, pneumonia, pregnancy complications, sleep interference, encephalopathy, peripheral edema, suicidal ideation, dyskinesia, anorgasmia, and myopathy. Inclusion criteria comprised studies with a focus on gabapentin-related atypical side effects, published in recognized journals and involving human subjects.
RESULTS
The review identified a spectrum of atypical side effects associated with gabapentin use, ranging from neurological manifestations like myoclonus and ataxia to behavioral changes such as pediatric aggression and suicidal ideation. Additionally, respiratory complications, pregnancy-related issues, sleep disturbances, and rare complications like encephalopathy and myopathy were observed. Literature synthesis provided insights into the incidence, clinical presentation, and potential mechanisms underlying these atypical side effects.
CONCLUSION
This comprehensive review highlights the diverse range of atypical side effects associated with gabapentin use, expanding beyond conventional knowledge. Healthcare practitioners must be cognizant of these manifestations, recognizing their potential impact on patient well-being. As clinical decision-making relies on a thorough understanding of a medication's side effect profile, this review contributes to enhancing awareness and fostering informed practices in the prescription and management of gabapentin. Further research is warranted to elucidate the mechanisms and risk factors associated with these atypical side effects, refining our understanding of gabapentin's safety profile.
PubMed: 38949515
DOI: 10.1111/papr.13400 -
Molecular Imaging and Radionuclide... Jun 2024Primary liver tumors constitute one of the most common tumors. These are aggressive tumors with poor survival. Fluorodeoxyglucose (FDG) positron emission...
OBJECTIVES
Primary liver tumors constitute one of the most common tumors. These are aggressive tumors with poor survival. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), most commonly used functional imaging, shows limited tracer retention and poor tumor to background ratios (TBR). Novel Ga-fibroblast-activation-protein inhibitor (FAPI) PET/CT has shown better tracer uptake and detection efficacy in liver tumors. However, most of the available literature is limited to single center studies with limited number of patients. So, we tried to review and analyze the head-to-head comparison of F-FDG PET/CT and Ga-FAPI PET/CT in evaluation of liver tumors.
METHODS
Literature available on head to head comparison of diagnostic accuracy of F-FDG PET/CT and Ga-FAPI PET/CT was searched in databases like PubMed, SCOPUS, EMBASE and Google Scholar for published original studies till April 2023. The relevant studies were selected and assessed using the Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. A random-effect model was used for calculating pooled sensitivity and specificity. They were represented with 95% confidence intervals (95% CI) and demonstrated in Forest plots. I-square statistic was used to assess heterogeneity in the studies.
RESULTS
Pooled sensitivity and specificity of FAPI PET/CT and F-FDG PET/CT for detection of primary liver tumors was 94.3% (95% CI: 90.6-96.8%); 89.3% (95% CI: 71.8-97.7%) and 56.1% (95% CI: 49.7-62.5%); 96.4% (95% CI: 81.7-99.9%) respectively. Pooled sensitivity for detection of extrahepatic metastatic disease was 92.2% (range: 88.1-100%; 95% CI: 87.8-95.4%) and 72.4% (range: 69.8-76.5; 95% CI: 65.9-78.2%) respectively. Also, the maximum standardized uptake value (SUV) and TBR were higher for FAPI PET/CT than F-FDG PET/CT in the included studies.
CONCLUSION
Overall, FAPI PET/CT showed higher sensitivity for detection of liver tumors with better SUV and TBR than F-FDG PET/CT.
PubMed: 38949417
DOI: 10.4274/mirt.galenos.2024.99705 -
Spine Jul 2024A retrospective, single-center, observational study.
STUDY DESIGN
A retrospective, single-center, observational study.
OBJECTIVE
This study investigated the risk factors associated with the failure of conservative treatment for adjacent vertebral fractures (AVFs).
SUMMARY OF BACKGROUND DATA
Adjacent vertebral fractures following vertebroplasty for osteoporotic vertebral compression fractures are not uncommon. Presently, there is a lack of consensus regarding the management of adjacent vertebral fractures.
METHODS
We included patients who developed adjacent vertebral fractures within two years post single-level vertebroplasty between January 2013 and December 2020. All patients initially underwent six weeks of conservative treatment, including pain medications, bracing, and physical therapy. Surgical intervention was offered to those with intractable back pain due to AVFs. Baseline demographics, AVF characteristics, and radiological measurements were systematically collected, and sequential univariable and multivariable logistic regression analyses were conducted to explore the risk factors.
RESULTS
Of the 114 patients with a mean age of 78.6 years, two-thirds (76 patients) tolerated conservative treatment well, while 38 required surgical interventions for adjacent vertebral fractures. Both groups demonstrated similar baseline demographics and radiological parameters regarding AVFs (P>0.05). The multivariable logistic regression analyses revealed that the development of AVFs later than six months post-vertebroplasty and their caudal location to the index vertebroplasty were the independent risk factors of unsuccessful conservative treatment, with odds ratios of 3.57 (95% confidence interval [CI]: 1.14-11.1, P=0.029) and 2.50 (95% CI: 1.09-5.88, P=0.032), respectively.
CONCLUSION
Adjacent vertebral fractures following percutaneous vertebroplasty generally have favorable outcomes under conservative treatment. However, the timing and the relative anatomical location of adjacent vertebral fractures are associated with treatment efficacy. Adjacent vertebral fractures occurring later than six months following the initial vertebroplasty or situated in the caudal location to the index vertebroplasty may exhibit reduced responsiveness to conservative treatment. These patients might benefit from a more aggressive therapeutic approach.
LEVEL OF EVIDENCE
3.
PubMed: 38949261
DOI: 10.1097/BRS.0000000000005085 -
Archives of Suicide Research : Official... Jul 2024The rate of worldwide mass shootings increased almost 400% over the last 40 years. About 30% are followed by the perpetrator's fatal or nonfatal suicide attempt.
OBJECTIVE
The rate of worldwide mass shootings increased almost 400% over the last 40 years. About 30% are followed by the perpetrator's fatal or nonfatal suicide attempt.
METHOD
We examined the rate of fatal and nonfatal attempts among 528 mass shooters over the last 40 years and their relationship to detected mental illness to better understand this specific context of suicide. We collected information on U.S.-based, personal-cause mass murders that involved one or more firearms, from online sources.
RESULTS
A greater proportion of mass shooters from 2000 to 2019 took or attempted to take their own lives (40.5%) compared with those from 1980 to 1999 (23.2%, < 0.001). More than double the proportion of perpetrators who made a fatal or nonfatal suicide attempt had a history of non-psychotic psychiatric/neurologic symptoms (38.9%), compared with perpetrators who did not make a fatal or nonfatal suicide attempt (18.1%; < 0.001). Among mass shooters who made fatal or nonfatal suicide attempts, 77 of 175 (44%) did not have any recorded psychiatric, neurologic, or substance use condition. Of the 98 mass shooters who made fatal or non-fatal suicide attempts and had a psychiatric, substance use, or neurologic condition, 41 had depressive disorders.
CONCLUSION
It is possible that a lack of information about the perpetrators' mental health or suicidal ideation led to an underestimation of their prevalence. These data suggest that suicide associated with mass shootings may represent a specific context for suicide, and approaches such as psychological autopsy can help to ascertain when psychiatric illness mediates the relationship between mass shootings and suicide.
PubMed: 38949252
DOI: 10.1080/13811118.2024.2345166