Variant Transcript of ROR1 ENST00000545203 Does Not Encode ROR1 Protein.

Drs. John and Ford reported in biomedicines that a variant transcript encoding receptor tyrosine kinase-like orphan receptor 1 (ROR1), namely ENST00000545203 or variant 3 (ROR1V3), was a predominant ROR1 transcript of neoplastic or normal cells in the Bioinformatic database, including GTEx and the 33 datasets from TCGA. Unlike the full-length ROR1 transcript, Drs. John and Ford deduced that ROR1V3 encoded a cytoplasmic ROR1 protein lacking an apparent signal peptide necessary for transport to the cell surface, which they presumed made it unlikely to function as a surface receptor for Wingless/Integrated (Wnt) factors. Moreover, they speculated that studies evaluating ROR1 via immunohistochemistry using any one of several anti-ROR1 mAbs actually may have detected cytoplasmic protein encoded by ROR1V3 and that anti-cancer therapies targeting surface ROR1 thus would be ineffective against "cytoplasmic ROR1-positive" cancers that express predominately ROR1V3. We generated lentivirus vectors driving the expression of full-length ROR1 or the ROR1v3 upstream of an internal ribosome entry site (IRES) of the gene encoding a red fluorescent reporter protein. Although we find that cells that express ROR1 have surface and cytoplasmic ROR1 protein, cells that express ROR1v3 neither have surface nor cytoplasmic ROR1, which is consistent with our finding that ROR1v3 lacks an in-frame initiation codon for ribosomal translation into protein. We conclude that the detection of ROR1 protein in various cancers cannot be ascribed to the expression of ROR1v3.

Striking the Balance: Bipolar Disorder in the Perinatal Period.

The authors reviewed the literature, published between 2018 and 2023, on treating bipolar disorder in the perinatal period in order to summarize current treatment perspectives. Mood episodes occur during pregnancy and there are high rates of both initial onset and recurrence in the postpartum period. Bipolar disorder itself is associated with higher risks of adverse pregnancy outcomes, including gestational hypertension, hemorrhage, cesarean delivery, and small for gestational age infants. A general principle of perinatal treatment includes maintaining psychiatric stability of the pregnant person while reducing medication exposure risk to the fetus. A variety of factors can compromise psychiatric stability, including rapid discontinuation of stabilizing medications, decreased efficacy due to physiologic changes of pregnancy, and exacerbation of underlying psychiatric illness. Psychosocial interventions include optimizing sleep, increasing support, and reducing stress. The American College of Obstetricians and Gynecologists recommends against discontinuing or withholding medications solely due to pregnancy or lactation status. Individualized treatment involves a discussion of the risks of undertreated bipolar disorder weighed against the risks of individual medication choice based on available evidence regarding congenital malformations, adverse neonatal and obstetrical events, and neurodevelopmental outcomes. Valproate is not a first-line treatment due to higher risks. Data are lacking on safety for many newer medications. The authors review current safety data regarding lithium, lamotrigine, and antipsychotics, which are the most commonly used treatments for managing bipolar disorder in the perinatal period. Due to physiologic changes during pregnancy, frequent therapeutic drug monitoring and dose adjustments are required.

The use of intraperitoneal chemotherapy for advanced ovarian cancer - The experience of a tertiary referral centre.

BACKGROUND: Platinum-based chemotherapy is the backbone of the medical management of ovarian cancer. The dose, route and timing of treatment are ongoing areas of debate. Intraperitoneal (IP) chemotherapy is an alternative delivery method treatment to the conventional intravenous (IV) route for patients with epithelial ovarian cancer, with efficacy supported by Level 1 evidence. AIMS: To compare the outcomes and feasibility of IP to IV delivery of platinum-based chemotherapy in patients with advanced epithelial ovarian cancer. MATERIALS AND METHODS: In a single institution, patients receiving adjuvant chemotherapy (IP and IV) for Stages III and IV epithelial ovarian cancer over the period January 2006-December 2018 were identified through a prospectively maintained database. All patients with an IP port inserted were included. A control group of patients treated with IV chemotherapy was created using criteria identified during the study and in the randomised trials that tested IP chemotherapy. Assessments were made for relapse-free survival (RFS) and overall survival (OS) for each cohort. RESULTS: A total of 639 patients received adjuvant chemotherapy (73 IP and 566 IV) during the study period. Both the IP group and matched IV control group (65 patients) had a median RFS of 26 months. The median OS in the IP group was 63.9 months, and in the IV group was 57.2 months. At ten years, a significantly higher proportion of patients were alive in the IP group cohort (16% vs 3%, relative risk 5.5, 95% CI 1.29-24, P = 0.012). IP chemotherapy was well tolerated by our cohort. In the IP group, 73% had four or more IP cycles and 99% received six or more cycles of chemotherapy. CONCLUSIONS: Our cohort had a high rate of completion of IP chemotherapy with excellent rates of completion of six cycles of any treatment. The RFS and OS in the IP chemotherapy group were comparable to each other and reflected those in the published literature. A significantly higher proportion of patients in the IP cohort were alive at ten years than in the IV cohort.

Advancing Medical Education Through Innovations in Teaching During the COVID-19 Pandemic.

BACKGROUND: Medicine relies on education of trainees for growth of the field. Medical education has benefitted from a rapid pace of innovation, but due to the coronavirus disease 2019 (COVID-19) pandemic, many paradigms underpinning the medical education of trainees shifted-rendering numerous teaching modalities unusable. The COVID-19 pandemic, however, accelerated the development of novel teaching methodologies, which our trainees are now adapting to. We sought to examine emerging teaching methodologies to understand the opportunities available for medical education to innovate our teaching practices for learners in the midst of the COVID-19 pandemic. METHODS: In this narrative review, we drew upon the experiences of the authors as both life-long learners and educators. We then reviewed literature pertaining to novel teaching methodologies developed in medical education since the start of the COVID-19 pandemic. RESULTS: Several medical specialties have employed novel teaching methodologies including use of telemedicine, remote teaching, online curricula, virtual rotations, virtual conferences, simulations, and learning consortia to continue engaging trainees during the COVID-19 pandemic. There is a paucity of literature that addresses efficacy of novel teaching methodologies compared to more traditional teaching methodologies. CONCLUSIONS: The COVID-19 pandemic presents an opportunity for medical education to combine new and innovative teaching methodologies to create novel, accessible, and engaging learning opportunities for our trainees.

Advancing the Mission of Consultation-Liaison Psychiatry Through Innovation in Teaching.

BACKGROUND: Consultation-liaison (C-L) psychiatry, similar to other medical specialties, relies on the education of students, residents, fellows, and life-long learners for growth of the field. C-L psychiatry is unique as it exists at the intersection of psychiatry with other medical subspecialties. Traditional teaching methods have been used in C-L psychiatry programs for more than 50 years, while technology has recently advanced as available resources and the learning styles of today's learners have evolved. A growing number of younger trainees are taking advantage of new ways to learn. OBJECTIVES: We sought to examine both traditional and novel teaching methodologies and how each of these educational methodologies fits within adult learning theory and in the context of how digital natives learn about C-L psychiatry. METHODS: In this narrative review, we drew upon the experiences of the authors as both life-long learners and educators. We then reviewed the literature pertaining to teaching methods that have been used in C-L psychiatry as well as emerging methods that could potentially be used in C-L psychiatry. RESULTS: C-L psychiatry has used traditional teaching methods such as readings, didactic lectures, case-based rounds, and problem-based learning. Novel teaching methodologies such as teaching rotations, simulations, social media, podcasts, movie clubs, and the use of mobile tablet computers have been used in general psychiatry and other medical specialties, while literature specific to C-L psychiatry was sparse. CONCLUSIONS: Opportunities abound to make use of new teaching methodologies and technologies to appeal to future generations of C-L psychiatrists.

Cessation of targeted therapy after a complete response in BRAF-mutant advanced melanoma: a case series.

BACKGROUND: It is unknown whether melanoma patients achieving complete response (CR) with targeted therapy can safely discontinue treatment. METHODS: All patients treated with BRAF/MEK inhibitors achieving CR and ceasing treatment before progression were identified. Clinical data at treatment initiation, cessation and progression were examined. RESULTS: A total of 12 eligible patients were identified, with median follow-up of 16 months, of whom 6 (50%) recurred at a median of 6.6 months after treatment cessation. One patient lost to follow-up until presentation with symptomatic recurrence was the only relapser to die. At relapse, the remaining five patients had an LDH <1.2 times ULN, four were ECOG 0 and one ECOG 1. Baseline characteristics and time to CR and to discontinuation did not influence the rate of relapse. CONCLUSIONS: A large proportion of patients achieving CR with BRAF/MEK inhibitors relapse after treatment cessation. The optimal treatment duration in such patients is unclear, particularly where alternative treatments are available.

General and Child and Adolescent Psychiatry Resident Training in Integrated Care: a Survey of Program Directors.

OBJECTIVE: Integrated care models are an evidence-based approach for integrating physical and behavioral health services. The American Association of Directors of Psychiatric Residency Training Integrated Care Task Force sought to describe current practices for providing training in integrated care to general and child and adolescent psychiatry residents. METHODS: Directors of US general and child and adolescent psychiatric residency training programs were anonymously surveyed to examine current practices in educating their residents in integrated care. Based on themes that emerged from the survey, the authors make recommendations for integrated care education of general and child and adolescent psychiatry residents. RESULTS: Fifty-two of 197 (26%) general and 36 of 111 (32%) child and adolescent program directors responded. Results demonstrate that a majority of responding general psychiatry (78%) and child and adolescent psychiatry (CAP) (72%) training programs offer integrated care rotations, many of which are electives for senior residents. The Veterans Health Administration (VA) and Federally Qualified Health Centers are common venues for such rotations. Sustainable funding of these rotations is a concern. Fewer than half of programs offer integrated care didactics. CONCLUSIONS: This report is intended to help program directors consider options for starting or optimizing their own integrated care curricula. Future research should examine the educational value, and the overall value to health care systems, of training in the integrated care model.

Depression and related disorders during the female reproductive cycle.

For some women, times of reproductive transition represent times of high risk for the onset or exacerbation of depressive symptoms. In order to maintain emotional stability, the female brain must adapt to fluctuations in hormones that affect neurotransmitter functioning. Difficulty with this adaptation, along with stresses related to social role transitions, may confer heightened vulnerability to depression. In this review, we summarize data regarding the course, expression and risks of depression and related symptoms during puberty and menarche, the luteal phase of the menstrual cycle, the perinatal period and perimenopause. We note treatment strategies that have been found to be effective for depressive symptoms during specific phases of the female reproductive cycle.