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On Queering the Enlightenment: Kinship and Gender in Eighteenth-Century French Literature
Get PDFQueering the Enlightenment: Kinship and Gender in Eighteenth-Century French Literature by Tracy L. Rutler. Oxford University Studies in the Enlightenment. Liverpool: Liverpool University Press, 2021. Pp. 304. $79.99 paperback
Finger Ridge-Count Variation among African Rainforest Hunter-Gatherers: Implications for Origins and Diversification
No full textDermatoglyphic studies of traditional rainforest hunter-gatherers (RHG) have a long history, but as yet no one has synthesized the available data to develop a coherent picture of RHG relationships to one another and to their agricultural (AGR) neighbors. This has been due in part to absence of comparable data, which has now been remedied by the late H. Brehme of Freiburg University, who counted ridges and classified patterns on existing prints, mostly collected in the early 20th century. Thus, analyses of dermatoglyphic prints from most African RHG groups, done in the same way by the same observer, now exist. The present analysis uses finger ridge counts to examine the structure of RHG and AGR populations. Eastern RHG and some AGR samples come from the eastern Democratic Republic of the Congo, some eastern AGR samples are from Kenya, and western RHG and AGR samples come from Cameroon and adjacent countries. Statistical procedures include analysis of variance (ANOVA), multivariate analysis of variance (MANOVA), analysis of covariance, and canonical variates obtained from the discriminant procedure. The relationship of ridge counts to adult stature was also examined. Eastern and western RHG are clearly differentiated on ridge counts. Eastern RHG are differentiated from their AGR neighbors by virtue of very low ridge counts, but western RHG have higher ridge counts, more in line with their AGR neighbors. MANOVA results reveal significant variation among groups and sexes, as well as variation among groups in sex dimorphism. Beyond the marked differences between eastern and western RHG, the western AGR show a certain cohesion, but eastern AGR are highly dispersed. Variation in sex dimorphism involves primarily eastern and western AGR groups. Ridge counts also correlate with stature, suggesting that short stature has prenatal origins. The general conclusion is that ridge-count variation supports a difference between eastern and western RHG seen in cranial morphology and genetics. The unanswered question is why eastern RHG, with the lowest ridge counts in the world, are so differentiated. Variation in sex dimorphism, especially among the AGR neighbors, implies different responses to prenatal hormones. Ridge counts demonstrate variation in prenatal development, which is still poorly understood. Genes influencing limb and digit development have been identified, which along with postnatal anthropometric and disease associations provide a basis for future development and testing of hypotheses
Tim Winton’s In the Winter Dark and the Settler Condition
No full textTim Winton’s In the Winter Dark and the settler condition
Abstract
Settler colonies tend to resort to myths in order to settle contemporary anxieties. If myths have a settling function, what happens when the seams that hold a contentious past together are unpicked? Tim Winton’s In the Winter Dark (1988) demonstrates that colonial myths cannot account for a sequence of events that take place in bushland surrounding the protagonist’s farm. As the characters fail to resolve this mysterious violence through narrative, the contradictions that demanded the construction of foundational myths re-appear. Winton’s gothic tale engages with the idea of settler colonial trauma, but the object of trauma is displaced and treated allegorically. I demonstrate how John Docker’s concept of ‘Epistemological Vertigo’ can be used to propose a postcolonial reading of Winton’s novel.
By showing how easily the most inflexible settler-farmer gives way to fear and irrational behaviour, this story reveals the fragility of the settler society. The settling myths that hold the nation together are not enough to hold back the violence associated with the colonial past which keeps coming to the surface of the present in the form or personal and collective trauma. The conclusion Winton reaches is that the settler is not settled. The bush defeats settler logic. Space defeats time too. In the Winter Dark challenges romanticised perceptions of the bush and promotes a non-anthropocentric view of space and nature. Only by moving away from traditional representations of nature can Australians re-establish a productive relationship with space
Implications of glyphosate-based herbicides on the female reproductive system and reproductive outcomes
Get PDFBackground
Glyphosate-based herbicides (GBHs) are the most widely used herbicides in the United States, accounting for 19% of estimated global use. Although the Environmental Protection Agency has reaffirmed that the active ingredient glyphosate (GLY) is safe for humans, recent studies on exposure have suggested an association with cancer, metabolic disorders, endocrine disruption and infertility, and Alzheimer’s and Parkinson’s disease. Recently, we have shown that GLY exposure deteriorates metaphase II oocyte quality through zinc deficiency, ROS accumulation, and chromosome disruption. In this work, we review the mechanisms of GLY toxicity in the female reproductive tract and discuss the potential clinical implications of GLY exposure on female reproductive health. Methods
PubMed was searched using the keywords “glyphosate,” “glyphosate-based herbicides,” “reproductive toxicity,” “reproductive function,” “ovarian function,” “female infertility,” “endocrine disruptors,” and “oxidative stress” up to March 2024. Results
Exposure to GLY is associated with adverse reproductive effects in all animal models and cell lines studied. GLY adversely affects the female reproductive tract through increased ROS generation, Zn deficiency, hormonal imbalances, aromatase inhibition, alterations in uterine morphology, and diminished oocyte quality and ovarian function. Collectively, the effects of GLY exposure on reproductive and endocrine function may increase the risk of female reproductive diseases, including PCOS, endometriosis, infertility, and miscarriage. Conclusions
The ongoing debate about the effects of GLY exposure increasingly exemplifies the public health issue surrounding its consequences on female reproductive health, fertility, and epigenetics. Thus, increased research efforts are warranted regarding the safety and efficacy of GBH on female reproduction
Understanding adolescent fear extinction: Identifying profiles and Connections to anxiety
Get PDFAnxiety disorders, the most prevalent mental health conditions, often emerge during adolescence. Core features include difficulties in regulating or extinguishing learned fear. However, compared to adults, less is known about fear extinction and its relationship with anxiety in youth. Most studies rely on group-level averages of single fear indicators, such as skin conductance responses (SCR) or self-reported fear, which may overlook individual variation, introduce bias, and miss critical manifestations like behavioral avoidance. Using a validated Pavlovian fear extinction paradigm, we applied k-means clustering to identify distinct fear extinction profiles in adolescents, examining their reliability and validity in relation to conditioned fear indicators and anxiety symptoms. A diverse community sample of 119 adolescents (54% female; M±SD age=13±2.25 years; 39% Black, 38% White, 5.7% Hispanic) completed a fear conditioning task, followed by a 10-minute delay and fear extinction. Anxiety symptoms were measured using the SCARED questionnaire. Complementary measures of conditioned fear included SCR, fear ratings, and behavioral avoidance. K-means clustering (k=3) identified distinct fear profiles, and their validity was evaluated through comparisons of fear indicators and associations with anxiety symptoms. Three fear profiles emerged: (1) high subjective fear (N=27), (2) high physiological but low behavioral fear (N=28), and (3) low physiological fear (N=49). Anxiety symptoms were lowest in Profile 3 (21.31±13.97) and remained significantly associated with profile membership after adjusting for sex. Distinct fear profiles in adolescents relate dimensionally to anxiety risk, emphasizing the need to move beyond single fear indicators to understand fear extinction and anxiety development
Gap Analysis of the Surgical Clerkships Experience According to the 2022 and 2023 AAMC GQ Survey
Get PDFBACKGROUND: Surgery remains a male-dominated field, and mediating factors for this discrepancy remain ill-defined. Little research has explored the experience of female medical students in surgical clerkships, which can exert strong influence over career choice. This study investigates whether disparities in clerkship experiences contribute to this gender gap.
METHODS: US medical students were surveyed on a variety of measures, including clerkship experiences, via the 2022 and 2023 AAMC GQ surveys. Differences in response pattern between male and female students were analyzed with chi-squared tests.
RESULTS: In surgical clerkships, female students reported less physician oversight when performing histories (2022: 79.60% vs 86.20%; p\u3c0.001, 2023: 82.40% vs 88.10%; p\u3c0.001), physical, and mental status exams relative to their male counterparts (2022: 83.60% vs 88.90%; p\u3c0.001, 2023: 86.70% vs 90.90%; p\u3c0.001). For both males and female students, there was a raw increase in reported oversight in both categories from 2022 to 2023.
CONCLUSION: Female medical students reported less physician oversight in surgical clerkships. This may stem from gender disparities in mentorship, bias towards male students, or conversely, greater trust in female students to perform histories and physicals. Regardless of etiology, gender disparities in clerkship oversight must be addressed as they hinder learning opportunities for female students and may contribute to the persistent gender gap in surgery. Notably, for both genders, oversight increased in 2023 compared to 2022, suggesting change in a positive direction. However, solutions are still needed to address gender discrepancies in the learning environment and empower a future generation of female surgeons
Multi-omics analysis reveals CMTR1 upregulation in cancer and roles in ribosomal protein gene expression and tumor growth
Get PDFBackground: CMTR1 (cap methyltransferase 1), a key nuclear mRNA cap methyltransferase, catalyzes 2\u27-O-methylation of the first transcribed nucleotide, a critical step in mRNA cap formation. Previous studies have implicated CMTR1 in embryonic stem cell differentiation and immune responses during viral infection; however, its role in cancer biology remains largely unexplored. This study aims to elucidate CMTR1\u27s function in cancer progression and evaluate its potential as a novel therapeutic target across multiple cancer types.
Methods: We conducted a comprehensive multi-omics analysis of CMTR1 across various human cancers using TCGA and CPTAC datasets. Functional studies were performed using CRISPR-mediated knockout and siRNA knockdown in human and mouse basal-like breast cancer models. Transcriptomic and pathway enrichment analyses were carried out in CMTR1 knockout/knockdown models to identify CMTR1-regulated genes. In silico screening and biochemical assays were employed to identify novel CMTR1 inhibitors.
Results: Multi-omics analysis revealed that CMTR1 is significantly upregulated at the mRNA, protein, and phosphoprotein levels across multiple cancer types. Functional studies demonstrated that CMTR1 depletion significantly inhibits tumor growth both in vitro and in vivo. Transcriptomic analysis of CMTR1 knockout cells revealed that CMTR1 primarily regulates ribosomal protein genes and other transcripts containing 5\u27 Terminal Oligopyrimidine (TOP) motifs. Additionally, CMTR1 affects the expression of snoRNA host genes and snoRNAs, suggesting a broader role in RNA metabolism. Mechanistic studies indicated that CMTR1\u27s target specificity is partly determined by mRNA structure, particularly the presence of 5\u27TOP motifs. Finally, through in silico screening and biochemical assays, we identified several novel CMTR1 inhibitors, including N97911, which demonstrated in vitro growth inhibition activity in breast cancer cells.
Conclusions: Our findings establish CMTR1 as a key player in cancer biology, regulating critical aspects of RNA metabolism and ribosome biogenesis. The study highlights CMTR1\u27s potential as a therapeutic target across multiple cancer types and provides a foundation for developing novel cancer treatments targeting mRNA cap methylation
Assessing the Efficacy of Amniotic Bladder Therapy for Female Sexual Dysfunction in Patients with Radiation Cystitis
Get PDFIntroduction and Objectives: Female sexual dysfunction (FSD) and radiation cystitis (RC) are complications of pelvic radiation with limited treatment options. Both conditions result from radiation-induced inflammation and scarring of pelvic organs, leading to symptoms such as dysuria in RC and dyspareunia in FSD, with significant impacts on quality of life. Amniotic Bladder Therapy (ABT), which we have previously demonstrated improves symptoms of RC through immunomodulatory and anti-fibrotic effects, may also offer therapeutic potential for FSD. In this study, we assessed the efficacy of intra-detrusor micronized amniotic membrane (AM) injections on FSD symptoms in patients with concomitant RC, using the Female Sexual Function Index (FSFI) and a pain visual analog scale (VAS).
Methods: Five females (mean age: 64.4 ± 20.1 years) with FSD recalcitrant to multiple therapies received intra-detrusor injections under general anesthesia of reconstituted 100 mg micronized AM. The FSFI questionnaire and pain VAS were obtained preoperatively and at 4, 8, 12, 16, 20, and 24 weeks post-injection.
Results: All five patients exhibited an improvement in FSFI scores from baseline to 16 weeks, with this improvement diminishing at 20 and 24 weeks. Pain (VAS) associated with intercourse decreased from 8.9±1.0 at baseline to 5.4±1.1 at 16 weeks, with an increase to 6.1±0.9 at 24 weeks. No adverse events arose during the study.
Conclusion: ABT in female RC patients with severe FSD symptoms demonstrated an improvement in sexual function and pain up to 16 weeks with a diminishing response at 20 to 24 weeks post-injection. Further studies are needed to correlate these results and elucidate the mechanism through which patients relapse in FSD symptoms following ABT
Clinical and Imaging Correlates of Cognitive Impairment Patterns in Early Unilateral Brain Injury Associated with Sturge-Weber Syndrome
Get PDFBackground: Sturge-Weber syndrome (SWS) is a rare neurocutaneous disease characterized by cerebral venous malformations leading to early damage of affected brain regions. Clinical symptoms include seizures, motor and cognitive impairment. Most SWS patients have unilateral brain involvement, and previous studies reveal substantial neurological plasticity in some of them. Some children with left-hemispheric damage demonstrate, paradoxically, preserved verbal functions and reduced nonverbal functions (a “crowding” effect), suggesting contralateral functional reorganization from damaged cortical regions. We evaluated the incidence as well as clinical and imaging correlates of such functional reorganization/crowding.
Methods: Forty-six patients (age: 2.5-24 years) with unilateral SWS underwent neurocognitive evaluations and magnetic resonance imaging (MRI) prospectively. Cases were stratified by hemisphere and assigned to a cognitive group: 1=normal, 2=traditional (expected deficit), 3=reorganized (contralateral deficit), and 4=global impairment (bilateral deficits). Age, IQ, seizure variables, and neuroimaging characteristics were compared across groups.
Results: Evidence of functional reorganization/crowding was seen only in left-hemispheric patients (n=20, 35%; right, n=26; 0%). In left-sided cases, the global deficit group demonstrated more extensive vascular malformations (p=0.003), atrophy (p=0.003), enlarged medullary veins (p=0.017), and lower age at seizure onset (p=0.016) than the normal group. Reorganized cases demonstrated shorter epilepsy duration (p=0.02) and more variable seizure onset age compared to the global group.
Conclusions: Evidence of functional reorganization, associated with crowding, in only left-sided cases suggests prioritization of verbal over non-verbal functions. Earlier and longer duration of seizures may interfere with optimal reorganization. Future studies may focus on modifying clinical characteristics that interfere with optimal reorganization of cognitive function
Socioeconomic and Demographic Factors in Genetic Testing Utilization Among Advanced Prostate Cancer Patients: A Retrospective Single-Institution Study
Get PDFIntroduction
Germline genetic testing in patients with advanced prostate cancer (PCa) is underutilized. Socioeconomic and demographic factors are hypothesized to affect low rates of testing, but causality has not been established. This single institution, retrospective study aimed to understand what barriers may affect germline genetic testing for PCa patients.
Methods
The Henry Ford Health (HFH) tumor registry was queried for new diagnoses of stage 3, 4A and 4B PCa from 2017-2022. Census tract levels were assigned using patient addresses and neighborhood-based geocoding was completed for Median household income (gMHI) and Social vulnerability index (SVI). gMHI and SVI were divided into tertiles. Outcomes were referral for genetic counseling and completion of genetic testing. Univariable and multivariable logistic regression analyses were performed.
Results
Multivariable analysis identified a decrease in testing by 3% for each 1-year increase in age (OR=0.97, 95% CI [0.95,0.99]; p=.0052). Middle gMHI tertile patients had 52% lower OR for referral than lowest gMHI tertile patients (OR=0.48, 95% CI [0.30, 0.78]; p=0.0027). For completion of testing, the odds were 2.84 times higher for those with substage 4B than 4A (OR=2.84, 95% CI [1.70, 4.74]; p\u3c.0001). No significant association was shown between gMHI and completion of testing.
Conclusion
Although socioeconomic factors have been hypothesized barriers to genetic testing, we found no evidence of such an association in our patient population. Instead, lowest gMHI tertile patients were equally likely to complete genetic testing as highest gMHI tertile patients, indicating that if such barriers exist, they can be overcome