Phenotypic manifestations in FLNA-related periventricular nodular heterotopia: a case report and review of the literature.

Periventricular nodular heterotopia (PVNH) is an X-linked disease caused by loss-of-function variants in the filamin A (FLNA) gene. FLNA-PVNH is a heterogeneous disorder, and the phenotype is associated with neurological and non-neurological features including cardiovascular, gastrointestinal, pulmonary, haematological, cutaneous and skeletal manifestations. No clear definition of the FLNA-PVNH phenotype has been established, but the patients are predominantly females with seizures, cardiovascular manifestations, and normal intelligence or mild intellectual disability. Herein, we describe a PVNH patient diagnosed with a novel heterozygous missense variant in FLNA after an atypical presentation of deep vein thrombosis and thrombocytopenia. Clinical evaluation found hypermobility, cardiovascular and skin manifestations. Moreover, we conducted a literature review of 186 FLNA-PVNH patients to describe the phenotypic spectrum. In conclusion, our patient highlights the importance of thorough clinical evaluation to identify manifestations in this very heterogeneous disorder. The phenotypic review may guide clinicians in the assessment and follow-up of FLNA-PVNH patients.

Cancer prevention interdisciplinary education program at Purdue University: overview and preliminary results.

Cancer prevention is a broad field that crosses many disciplines; therefore, educational efforts to enhance cancer prevention research focused on interdisciplinary approaches to the field are greatly needed. In order to hasten progress in cancer prevention research, the Cancer Prevention Internship Program (CPIP) at Purdue University was designed to develop and test an interdisciplinary curriculum for undergraduate and graduate students. The hypothesis was that course curriculum specific to introducing interdisciplinary concepts in cancer prevention would increase student interest in and ability to pursue advanced educational opportunities (e.g., graduate school, medical school). Preliminary results from the evaluation of the first year which included ten undergraduate and five graduate students suggested that participation in CPIP is a positive professional development experience, leading to a significant increase in understanding of interdisciplinary research in cancer prevention. In its first year, the CPIP project has created a successful model for interdisciplinary education in cancer prevention research.

Assessment of Treatment Approaches and Outcomes in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Insights From a Pan-European Multicenter Study.

IMPORTANCE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug reactions associated with a high rate of mortality and morbidity. There is no consensus on the treatment strategy. OBJECTIVE: To explore treatment approaches across Europe and outcomes associated with the SJS/TEN disease course, as well as risk factors and culprit drugs. DESIGN, SETTING, AND PARTICIPANTS: A retrospective pan-European multicenter cohort study including 13 referral centers belonging to the ToxiTEN ERN-skin subgroup was conducted. A total of 212 adults with SJS/TEN were included between January 1, 2015, and December 31, 2019, and data were collected from a follow-up period of 6 weeks. MAIN OUTCOMES AND MEASURES: Risk factors for severe acute-phase complications (acute kidney failure, septicemia, and need for mechanical ventilation) and mortality 6 weeks following admission were evaluated using a multivariable-adjusted logistic regression model. One tool used in evaluation of severity was the Score of Toxic Epidermal Necrolysis (SCORTEN), which ranges from 0 to 7, with 7 the highest level of severity. RESULTS: Of 212 patients (134 of 211 [63.7%] women; mean [SD] age, 51.0 [19.3] years), the mean (SD) body surface area detachment was 27% (32.8%). In 176 (83.0%) patients, a culprit drug was identified. Antibiotics (21.2%), followed by anticonvulsants (18.9%), nonsteroidal anti-inflammatory drugs (11.8%), allopurinol (11.3%), and sulfonamides (10.4%), were the most common suspected agents. Treatment approaches ranged from best supportive care only (38.2%) to systemic glucocorticoids (35.4%), intravenous immunoglobulins (23.6%), cyclosporine (10.4%), and antitumor necrosis factor agents (3.3%). Most patients (63.7%) developed severe acute-phase complications. The 6-week mortality rate was 20.8%. Maximal body surface area detachment (≥30%) was found to be independently associated with severe acute-phase complications (fully adjusted odds ratio [OR], 2.49; 95% CI, 1.21-5.12; P = .01) and SCORTEN greater than or equal to 2 was significantly associated with mortality (fully adjusted OR, 10.30; 95% CI, 3.82-27.78; P < .001). Cyclosporine was associated with a higher frequency of greater than or equal to 20% increase in body surface area detachment in the acute phase (adjusted OR, 3.44; 95% CI, 1.12-10.52; P = .03) and an increased risk of infections (adjusted OR, 7.16; 95% CI, 1.52-33.74; P = .01). Systemic glucocorticoids and intravenous immunoglobulins were associated with a decreased risk of infections (adjusted OR, 0.40; 95% CI, 0.18-0.88; P = .02). No significant difference in 6-week mortality was found between treatment groups. CONCLUSIONS AND RELEVANCE: This cohort study noted differences in treatment strategies for SJS/TEN in Europe; the findings suggest the need for prospective therapeutic studies to be conducted and registries to be developed.

Treatment of music performance anxiety via psychological approaches: a review of selected CBT and psychodynamic literature.

Performance anxiety, or stage fright, is anxiety aroused about potential mishaps in performance that expose feared inadequacies before an audience and which evoke feelings of embarrassment and humilation. For affected musicians, performance anxiety can be emotionally devastating, as their career choice in music may be terminated or severely compromised. This paper focuses on the cognitive and psychodynamic literature about music performance anxiety, with the emphasis that for treatment "one size does not fit all." It reviews the factors underlying performance anxiety and those factors which can exacerbate the condition in musicians. The two major clinical treatment modalities within contemporary psychology, cognitive behavior therapy (CBT) and psychodynamic treatments, are reviewed. While there are more empirical studies of CBT in various populations in the literature, until recently there was an indifference to empirical research by psychodynamic investigators. However, meta-analyses show strong efficacy for psychodynamic psychotherapy (in various disorders, not specifically music performance anxiety), but also that the benefits of psychodynamic psychotherapy may endure longer and increase with time.

Psychoanalytic and musical perspectives on shame in Donizetti's Lucia Di Lammermoor.

Two disciplines, psychoanalysis and music, are synthesized here with an eye to the origins and vicissitudes of shame and guilt as seen in the emotional disintegration of the eponymous heroine of Donizetti's opera Lucia di Lammermoor. Lucia's affects and her intrapsychic and interpersonal dynamics are heard in the music itself. A psychoanalytic and musical analysis of the opera, taking Lucia's dynamics as a quasi-substitute for clinical material, illuminates the intersections between certain theoretical aspects of the two disciplines. Both manifest and latent themes are expressed through the music of Donizetti's score.

Psychoanalytic perspectives on music: an intersection on the oral and aural road.

This paper is organized around two ideas. The first invites the reader to consider the importance of music in emotional life, suggesting that for some people, music can have profound, deep, and transformative effects, both in loosening defenses and in deepening the psychoanalytic experience. The second idea is that analysis of the formal properties of music have both specific and overdetermined meanings that share elements with psychoanalytic principles. I suggest that, if the verbal analysis of dreams paves a royal road to the unconscious, the formal properties of music provide an aural road to the same destination. Two clinical vignettes and scenes from Verdi's opera Otello are used to illustrate these interrelated ideas.

Memory Slip: Stage Fright and Performing Musicians.

This paper discusses stage fright as seen primarily in classical music performers. A confluence of narcissistic sensitivities, developmental issues, shame dynamics, physical injury and pain, and terrors pertaining to both psychic and bodily disintegration can fuel anxiety reactions in many people but hold particular relevance for the performing musician. Two classical music performers who struggled with stage fright are discussed: one was in treatment with the author; the other is the author herself, reflecting on her own performance anxiety as revealed through her analysis and her countertransference to her patient.

Psychoanalytic and musical ambiguity: the tritone in gee, officer krupke.

The poignant and timeless Broadway musical West Side Story is viewed from the standpoint of taking musical forms as psychoanalytic data. The musical configuration of notes called the tritone (or diabolus in musica) is taken as a sonic metaphor expressing ambiguity both in musical vocabulary and in mental life. The tritone, which historically and harmonically represents instability, is heard throughout the score and emphasizes the intrapsychic, interpersonal, and social dramas that unfold within and between the two gangs in West Side Story. Particular emphasis is given to the comic but exceedingly sober song Gee, Officer Krupke. Bernstein's sensitivity to the ambiguity and tension inherent in the tritone in West Side Story is conceptualized as an intersection of music theory and theories of mind; this perspective holds implications for clinical practice and transports psychoanalytic concepts from the couch to the Broadway stage and into the community to address the complexities of love, hate, aggression, prejudice, and violence. Ultimately, West Side Story cross-pollinates music and theater, as well as music and psychoanalytic concepts.

Population growth impairment of aliphatic alcohols to Tetrahymena.

The toxicity of a series of 120 aliphatic alcohols was evaluated using the Tetrahymena pyriformis population growth impairment assay. For tertiary propargylic alcohols; primary, secondary, and tertiary homopropargylic alcohols; allylic alcohols; and saturated alcohols, a statistically robust structure-activity model was developed for toxicity data [log (IGC(50) (-1))] using the 1-octanol/water partition coefficient (log K(ow)) as the lone descriptor [log (IGC(50))(-1) = 0.74 (log K(ow)) - 1.73; n = 97; r(2) (adj.) = 0.933; r(2) (pred.) = 0.932; s = 0.298; F = 1328; Pr > F = 0.0001]. Analysis of data for the primary propargylic alcohols yielded a separate, high-quality log K(ow)-dependent quantitative structure-activity relationship (QSAR) [log (IGC(50))(-1) = 0.65 (log K(ow)) - 1.22; n = 10; r(2) (adj.) = 0.969; r(2) (pred.) = 0.964; s = 0.222; F = 254; Pr > F = 0.0001]. A comparison of the observed toxicity and that predicted by the first QSAR showed that the primary propargylic alcohols with log K(ow) values < 2.00 exhibited enhanced toxicity and that this increased toxicity was inversely related to hydrophobicity. In sharp contrast, analysis of the data for the secondary propargylic alcohols exhibited little relationship with log K(ow) (r(2) = 0.339). Although the initial QSAR can be used to model the toxicity of any aliphatic alcohol for the T. pyriformis population growth impairment end point, the estimated potency would be underestimated for primary propargylic alcohols with log K(ow) values < 2.00. Moreover, estimates of toxic potency of secondary propargylic alcohols based on this QSAR should be viewed with limited confidence. The findings for beta-unsaturated alcohols in Tetrahymena were sharply different from that reported for fathead minnow acute mortality; this difference in toxicity is a result of a difference in the protocol used rather than in metabolism.