A Review of Contemporary Assessment Tools for Use with Transgender and Gender Nonconforming Adults

There is increasing recognition of the need for culturally sensitive services for individuals who identify as transgender and gender nonconforming (TGNC), and only recently have empirical studies appeared in the literature that inform best practices for TGNC people. Competent, culturally appropriate clinical services and research depend upon methodologically sound assessment of key constructs, but it is unclear whether appropriate self-report or clinician-rated assessment tools for adults exist. This article reviewed existing published measures to identify areas of strength as well as existing gaps in the available research. The search strategy for this systematic review identified any published article describing a self-report or clinician-rated scale for assessing transgender-related concerns. Each measure was reviewed for information on its scope, reliability, validity, strengths, limitations, and source. The majority of these questionnaires was developed with the TGNC communities and targeted important factors that affect quality of life for TGNC people. Limitations included limited evidence for validity, reliability, and sensitivity to change. Overall, the field is moving in the direction of TGNC-affirming assessment, and promising measures have been created to monitor important aspects of quality of life for TGNC people. Future research should continue to validate these measures for use in assessing clinical outcomes and the monitoring of treatment progress

Trans Collaborations Clinical Check-In (TC3): Initial Validation of a Clinical Measure for Transgender and Gender Diverse Adults Receiving Psychological Services

One key aspect of evidence-based psychological services is monitoring progress to inform treatment decision making, often using a brief self-report measure. However, no such measure exists to support measurement based care given the distinct needs of transgender and gender diverse people (TGD), a group facing large documented health disparities and marginalization in healthcare. The purpose of the present study was to develop and provide initial psychometric validation of a short, behavioral health progress monitoring self-report measure, the Trans Collaborations Clinical Check-in (TC3). TGD communities, providers identified as TGD-affirmative, and relevant academic experts contributed to item and scale development. The final 18 item version was administered to 215 TGD adults (75 transfeminine, 76 transmasculine, 46 nonbinary, 18 unknown; mean age of 30 with a range of 19 to 73), who were recruited for an online study, with other questionnaires assessing negative affect, well-being, gender dysphoria, gender minority stressors, and resilience. Higher scores on the TC3 (indicating better adjustment and comfort with gender) were generally associated with lower depression, anxiety, minority stress, and gender dysphoria and greater life satisfaction, body congruence, and positive aspects of being TGD such as pride in identity and community belongingness. These results support the validity of the TC3 as a brief measure to be used as a clinical tool for TGD people receiving mental health services. Additional research is needed on the reliability and validity of the TC3 across multiple time points to determine utility as a progress monitoring measure. The TC3 should also be further validated with more culturally diverse samples

Detection of circulating tumour DNA is associated with inferior outcomes in Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group.

BackgroundNew prognostic markers are needed to identify patients with Ewing sarcoma (EWS) and osteosarcoma unlikely to benefit from standard therapy. We describe the incidence and association with outcome of circulating tumour DNA (ctDNA) using next-generation sequencing (NGS) assays.MethodsA NGS hybrid capture assay and an ultra-low-pass whole-genome sequencing assay were used to detect ctDNA in banked plasma from patients with EWS and osteosarcoma, respectively. Patients were coded as positive or negative for ctDNA and tested for association with clinical features and outcome.ResultsThe analytic cohort included 94 patients with EWS (82% from initial diagnosis) and 72 patients with primary localised osteosarcoma (100% from initial diagnosis). ctDNA was detectable in 53% and 57% of newly diagnosed patients with EWS and osteosarcoma, respectively. Among patients with newly diagnosed localised EWS, detectable ctDNA was associated with inferior 3-year event-free survival (48.6% vs. 82.1%; p = 0.006) and overall survival (79.8% vs. 92.6%; p = 0.01). In both EWS and osteosarcoma, risk of event and death increased with ctDNA levels.ConclusionsNGS assays agnostic of primary tumour sequencing results detect ctDNA in half of the plasma samples from patients with newly diagnosed EWS and osteosarcoma. Detectable ctDNA is associated with inferior outcomes

Sex Differences in Clinical Features of Early, Treated Parkinson\u27s Disease

INTRODUCTION: To improve our understanding of sex differences in the clinical characteristics of Parkinson\u27s Disease, we sought to examine differences in the clinical features and disease severity of men and women with early treated Parkinson\u27s Disease (PD) enrolled in a large-scale clinical trial. METHODS: Analysis was performed of baseline data from the National Institutes of Health Exploratory Trials in Parkinson\u27s Disease (NET-PD) Long-term Study-1, a randomized, multi-center, double-blind, placebo-controlled study of 10 grams of oral creatine/day in individuals with early, treated PD. We compared mean age at symptom onset, age at PD diagnosis, and age at randomization between men and women using t-test statistics. Sex differences in clinical features were evaluated, including: symptoms at diagnosis (motor) and symptoms at randomization (motor, non-motor, and daily functioning). RESULTS: 1,741 participants were enrolled (62.5% male). No differences were detected in mean age at PD onset, age at PD diagnosis, age at randomization, motor symptoms, or daily functioning between men and women. Differences in non-motor symptoms were observed, with women demonstrating better performance compared to men on SCOPA-COG (Z = 5.064, p\u3c0.0001) and Symbol Digit Modality measures (Z = 5.221, p\u3c0.0001). CONCLUSIONS: Overall, men and women did not demonstrate differences in clinical motor features early in the course of PD. However, the differences observed in non-motor cognitive symptoms suggests further assessment of the influence of sex on non-motor symptoms in later stages of PD is warranted

The distribution of Dishevelled in convergently extending mesoderm

Convergent extension (CE) is a conserved morphogenetic movement that drives axial lengthening of the primary body axis and depends on the planar cell polarity (PCP) pathway. In Drosophila epithelia, a polarised subcellular accumulation of PCP core components, such as Dishevelled (Dvl) protein, is associated with PCP function. Dvl has long been thought to accumulate in the mediolateral protrusions in Xenopus chordamesoderm cells undergoing CE. Here we present a quantitative analysis of Dvl intracellular localisation in Xenopus chordamesoderm cells. We find that, surprisingly, accumulations previously observed at mediolateral protrusions of chordamesodermal cells are not protrusion-specific but reflect yolk-free cytoplasm and are quantitatively matched by the distribution of the cytoplasm-filling lineage marker dextran. However, separating cell cortex-associated from bulk Dvl signal reveals a statistical enrichment of Dvl in notochord–somite boundary-(NSB)-directed protrusions, which is dependent upon NSB proximity. Dvl puncta were also observed, but only upon elevated overexpression. These puncta showed no statistically significant spatial bias, in contrast to the strongly posteriorly-enriched GFP-Dvl puncta previously reported in zebrafish. We propose that Dvl distribution is more subtle and dynamic than previously appreciated and that in vertebrate mesoderm it reflects processes other than protrusion as such

Emerging pharmacotherapy of tinnitus

Tinnitus, the perception of sound in the absence of an auditory stimulus, is perceived by about 1 in 10 adults, and for at least 1 in 100, tinnitus severely affects their quality of life. Because tinnitus is frequently associated with irritability, agitation, stress, insomnia, anxiety and depression, the social and economic burdens of tinnitus can be enormous. No curative treatments are available. However, tinnitus symptoms can be alleviated to some extent. The most widespread management therapies consist of auditory stimulation and cognitive behavioral treatment, aiming at improving habituation and coping strategies. Available clinical trials vary in methodological rigor and have been performed for a considerable number of different drugs. None of the investigated drugs have demonstrated providing replicable long-term reduction of tinnitus impact in the majority of patients in excess of placebo effects. Accordingly, there are no FDA or European Medicines Agency approved drugs for the treatment of tinnitus. However, in spite of the lack of evidence, a large variety of different compounds are prescribed off-label. Therefore, more effective pharmacotherapies for this huge and still growing market are desperately needed and even a drug that produces only a small but significant effect would have an enormous therapeutic impact. This review describes current and emerging pharmacotherapies with current difficulties and limitations. In addition, it provides an estimate of the tinnitus market. Finally, it describes recent advances in the tinnitus field which may help overcome obstacles faced in the pharmacological treatment of tinnitus. These include incomplete knowledge of tinnitus pathophysiology, lack of well-established animal models, heterogeneity of different forms of tinnitus, difficulties in tinnitus assessment and outcome measurement and variability in clinical trial methodology. © 2009 Informa UK Ltd.Fil: Langguth, Berthold. Universitat Regensburg; AlemaniaFil: Salvi, Richard. State University of New York; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

The International Cancer Expert Corps: A Unique Approach for Sustainable Cancer Care in Low and Lower-Middle Income Countries

The growing burden of non-communicable diseases including cancer in low- and lower-middle income countries (LMICs) and in geographic-access limited settings within resource-rich countries requires effective and sustainable solutions. The International Cancer Expert Corps (ICEC) is pioneering a novel global mentorship–partnership model to address workforce capability and capacity within cancer disparities regions built on the requirement for local investment in personnel and infrastructure. Radiation oncology will be a key component given its efficacy for cure even for the advanced stages of disease often encountered and for palliation. The goal for an ICEC Center within these health disparities settings is to develop and retain a high-quality sustainable workforce who can provide the best possible cancer care, conduct research, and become a regional center of excellence. The ICEC Center can also serve as a focal point for economic, social, and healthcare system improvement. ICEC is establishing teams of Experts with expertise to mentor in the broad range of subjects required to establish and sustain cancer care programs. The Hubs are cancer centers or other groups and professional societies in resource-rich settings that will comprise the global infrastructure coordinated by ICEC Central. A transformational tenet of ICEC is that altruistic, human-service activity should be an integral part of a healthcare career. To achieve a critical mass of mentors ICEC is working with three groups: academia, private practice, and senior mentors/retirees. While in-kind support will be important, ICEC seeks support for the career time dedicated to this activity through grants, government support, industry, and philanthropy. Providing care for people with cancer in LMICs has been a recalcitrant problem. The alarming increase in the global burden of cancer in LMICs underscores the urgency and makes this an opportune time fornovel and sustainable solutions to transform cancer care globally

Whole-Exome Sequencing in Familial Parkinson Disease

IMPORTANCE: Parkinson disease (PD) is a progressive neurodegenerative disease for which susceptibility is linked to genetic and environmental risk factors. OBJECTIVE: To identify genetic variants contributing to disease risk in familial PD. DESIGN, SETTING, AND PARTICIPANTS: A 2-stage study design that included a discovery cohort of families with PD and a replication cohort of familial probands was used. In the discovery cohort, rare exonic variants that segregated in multiple affected individuals in a family and were predicted to be conserved or damaging were retained. Genes with retained variants were prioritized if expressed in the brain and located within PD-relevant pathways. Genes in which prioritized variants were observed in at least 4 families were selected as candidate genes for replication in the replication cohort. The setting was among individuals with familial PD enrolled from academic movement disorder specialty clinics across the United States. All participants had a family history of PD. MAIN OUTCOMES AND MEASURES: Identification of genes containing rare, likely deleterious, genetic variants in individuals with familial PD using a 2-stage exome sequencing study design. RESULTS: The 93 individuals from 32 families in the discovery cohort (49.5% [46 of 93] female) had a mean (SD) age at onset of 61.8 (10.0) years. The 49 individuals with familial PD in the replication cohort (32.6% [16 of 49] female) had a mean (SD) age at onset of 50.1 (15.7) years. Discovery cohort recruitment dates were 1999 to 2009, and replication cohort recruitment dates were 2003 to 2014. Data analysis dates were 2011 to 2015. Three genes containing a total of 13 rare and potentially damaging variants were prioritized in the discovery cohort. Two of these genes (TNK2 and TNR) also had rare variants that were predicted to be damaging in the replication cohort. All 9 variants identified in the 2 replicated genes in 12 families across the discovery and replication cohorts were confirmed via Sanger sequencing. CONCLUSIONS AND RELEVANCE: TNK2 and TNR harbored rare, likely deleterious, variants in individuals having familial PD, with similar findings in an independent cohort. To our knowledge, these genes have not been previously associated with PD, although they have been linked to critical neuronal functions. Further studies are required to confirm a potential role for these genes in the pathogenesis of PD

A Randomized Controlled Trial of Folate Supplementation When Treating Malaria in Pregnancy with Sulfadoxine-Pyrimethamine

OBJECTIVES: Sulfadoxine-pyrimethamine (SP) is an antimalarial drug that acts on the folate metabolism of the malaria parasite. We investigated whether folate (FA) supplementation in a high or a low dose affects the efficacy of SP for the treatment of uncomplicated malaria in pregnant women. DESIGN: This was a randomized, placebo-controlled, double-blind trial. SETTING: The trial was carried out at three hospitals in western Kenya. PARTICIPANTS: The participants were 488 pregnant women presenting at their first antenatal visit with uncomplicated malaria parasitaemia (density of ≥ 500 parasites/μl), a haemoglobin level higher than 7 g/dl, a gestational age between 17 and 34 weeks, and no history of antimalarial or FA use, or sulfa allergy. A total of 415 women completed the study. INTERVENTIONS: All participants received SP and iron supplementation. They were randomized to the following arms: FA 5 mg, FA 0.4 mg, or FA placebo. After 14 days, all participants continued with FA 5 mg daily as per national guidelines. Participants were followed at days 2, 3, 7, 14, 21, and 28 or until treatment failure. OUTCOME MEASURES: The outcomes were SP failure rate and change in haemoglobin at day 14. RESULTS: The proportion of treatment failure at day 14 was 13.9% (19/137) in the placebo group, 14.5% (20/138) in the FA 0.4 mg arm (adjusted hazard ratio [AHR], 1.07; 98.7% confidence interval [CI], 0.48 to 2.37; p = 0.8), and 27.1% (38/140) in the FA 5 mg arm (AHR, 2.19; 98.7% CI, 1.09 to 4.40; p = 0.005). The haemoglobin levels at day 14 were not different relative to placebo (mean difference for FA 5 mg, 0.17 g/dl; 98.7% CI, −0.19 to 0.52; and for FA 0.4 mg, 0.14 g/dl; 98.7% CI, −0.21 to 0.49). CONCLUSIONS: Concomitant use of 5 mg FA supplementation compromises the efficacy of SP for the treatment of uncomplicated malaria in pregnant women. Countries that use SP for treatment or prevention of malaria in pregnancy need to evaluate their antenatal policy on timing or dose of FA supplementation