A single blinded, phase IV, adaptive randomised control trial to evaluate the safety of coadministration of seasonal influenza and COVID-19 vaccines (The FluVID study).

OBJECTIVES: We evaluated the frequency of moderate and severe adverse events following coadministration of seasonal influenza vaccine (SIV) versus placebo with COVID-19 vaccines among adults to support practice guidelines. METHODS: FluVID is a participant-blinded, phase IV, randomised control trial. On the same day as the participant's scheduled COVID-19 vaccine, participants were randomised to receive SIV or saline placebo; those assigned placebo at visit one then received SIV a week later, and vice versa. Self-reported adverse events were collected daily for seven days following each visit. The primary endpoint was any solicited adverse event of at least moderate severity occurring up to seven days following receipt of SIV or placebo. This was modelled using a Bayesian logistic regression model. Analyses were performed by COVID-19 vaccine type and dose number. RESULTS: Overall, 248 participants were enrolled; of these, 195 had received BNT162b2 and 53 had received mRNA1273 COVID-19 vaccines according to national guidelines. After randomisation, 119 were assigned to receive SIV and 129 were assigned to receive placebo at visit one. Adverse events were most frequently reported as mild (grade 1) in nature. Among 142 BNT162b2 booster dose one and 43 BNT162b2 booster dose two recipients, the posterior median risk difference for moderate/severe adverse events following SIV versus placebo was 13% (95% credible interval [CrI] -0.03 to 0.27) and 13% (95%CrI -0.37 to 0.12), respectively. Among 18 mRNA1273 booster dose one and 35 mRNA1273 booster dose two recipients, the posterior median risk difference of moderate/severe adverse events following influenza vaccine versus placebo was 6% (95%CrI -0.29 to 0.41) and -4% (95%CrI -0.30 to 0.23), respectively. CONCLUSION: Adverse events following SIV and COVID-19 co-administration were generally mild and occurred with similar frequency to events following COVID-19 vaccine alone. We found no evidence to justify routine separation of SIV and COVID-19 vaccine doses. CLINICAL TRIAL REGISTRATION: ACTRN12621001063808.

Experiences that matter in bipolar disorder: a qualitative study using the capability, comfort and calm framework.

BACKGROUND: When assessing the value of an intervention in bipolar disorder, researchers and clinicians often focus on metrics that quantify improvements to core diagnostic symptoms (e.g., mania). Providers often overlook or misunderstand the impact of treatment on life quality and function. We wanted to better characterize the shared experiences and obstacles of bipolar disorder within the United States from the patient's perspective. METHODS: We recruited 24 individuals diagnosed with bipolar disorder and six caretakers supporting someone with the condition. Participants were involved in treatment or support services for bipolar disorder in central Texas. As part of this qualitative study, participants discussed their everyday successes and obstacles related to living with bipolar disorder during personalized, open-ended interviews. Audio files were transcribed, and Nvivo software processed an initial thematic analysis. We then categorized themes into bipolar disorder-related obstacles that limit the patient's capability (i.e., function), comfort (i.e., relief from suffering) and calm (i.e., life disruption) (Liu et al., FebClin Orthop 475:315-317, 2017; Teisberg et al., MayAcad Med 95:682-685, 2020). We then discuss themes and suggest practical strategies that might improve the value of care for patients and their families. RESULTS: Issues regarding capability included the struggle to maintain identity, disruptions to meaningful employment, relationship loss and the unpredictable nature of bipolar disorder. Comfort related themes included the personal perception of diagnosis, social stigma and medication issues. Calm themes included managing dismissive doctors, finding the right psychotherapist and navigating financial burdens. CONCLUSIONS: Qualitative data from patients with bipolar disorder helps identify gaps in care or practical limitations to treatment. When we listen to these individuals, it is clear that treatments must also address the unmet psychosocial impacts of the condition to improve patient care, capability and calm.

Core protocol for the adaptive Platform Trial In COVID-19 Vaccine priming and BOOsting (PICOBOO).

BACKGROUND: The need for coronavirus 2019 (COVID-19) vaccination in different age groups and populations is a subject of great uncertainty and an ongoing global debate. Critical knowledge gaps regarding COVID-19 vaccination include the duration of protection offered by different priming and booster vaccination regimens in different populations, including homologous or heterologous schedules; how vaccination impacts key elements of the immune system; how this is modified by prior or subsequent exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and future variants; and how immune responses correlate with protection against infection and disease, including antibodies and effector and T cell central memory. METHODS: The Platform Trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, multi-arm, Bayesian, adaptive, randomised controlled platform trial. PICOBOO will expeditiously generate and translate high-quality evidence of the immunogenicity, reactogenicity and cross-protection of different COVID-19 priming and booster vaccination strategies against SARS-CoV-2 and its variants/subvariants, specific to the Australian context. While the platform is designed to be vaccine agnostic, participants will be randomised to one of three vaccines at trial commencement, including Pfizer's Comirnaty, Moderna's Spikevax or Novavax's Nuvaxovid COVID-19 vaccine. The protocol structure specifying PICOBOO is modular and hierarchical. Here, we describe the Core Protocol, which outlines the trial processes applicable to all study participants included in the platform trial. DISCUSSION: PICOBOO is the first adaptive platform trial evaluating different COVID-19 priming and booster vaccination strategies in Australia, and one of the few established internationally, that is designed to generate high-quality evidence to inform immunisation practice and policy. The modular, hierarchical protocol structure is intended to standardise outcomes, endpoints, data collection and other study processes for nested substudies included in the trial platform and to minimise duplication. It is anticipated that this flexible trial structure will enable investigators to respond with agility to new research questions as they arise, such as the utility of new vaccines (such as bivalent, or SARS-CoV-2 variant-specific vaccines) as they become available for use. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12622000238774. Registered on 10 February 2022.

In Search of Safe Spaces: An Exploratory Study of the Anticipated Help-Seeking Needs and Preferences of Protestant Christian Women in Singapore with Respect to a Hypothetical Abortion Scenario.

Research suggests that religious beliefs may contribute to abortion stigma, resulting in increased secrecy, reduced social support and help-seeking as well as poor coping and negative emotional consequences such as shame and guilt. This study sought to explore the anticipated help-seeking preferences and difficulties of Protestant Christian women in Singapore with regard to a hypothetical abortion scenario. Semi-structured interviews were conducted with 11 self-identified Christian women recruited through purposive and snowball sampling. The sample was largely Singaporean and all participants were ethnically Chinese females of a similar age range (late twenties to mid-thirties). All willing participants were recruited regardless of denomination. All participants anticipated experiences of felt, enacted and internalized stigma. These were affected by their perceptions of God (e.g., how they see abortion), their personal definitions of "life" and their perceptions of their religio-social environment (e.g., perceived social safety and fears). These concerns contributed to participants choosing both faith-based and secular formal support sources with caveats, despite a primary preference for faith-based informal support and secondary preference for faith-based formal support. All participants anticipated negative post-abortion emotional outcomes, coping difficulties and short-term decision dissatisfaction. However, participants who reported more accepting views of abortion also anticipated an increase in decision satisfaction and well-being in the longer term.

Translin facilitates RNA polymerase II dissociation and suppresses genome instability during RNase H2- and Dicer-deficiency.

The conserved nucleic acid binding protein Translin contributes to numerous facets of mammalian biology and genetic diseases. It was first identified as a binder of cancer-associated chromosomal translocation breakpoint junctions leading to the suggestion that it was involved in genetic recombination. With a paralogous partner protein, Trax, Translin has subsequently been found to form a hetero-octomeric RNase complex that drives some of its functions, including passenger strand removal in RNA interference (RNAi). The Translin-Trax complex also degrades the precursors to tumour suppressing microRNAs in cancers deficient for the RNase III Dicer. This oncogenic activity has resulted in the Translin-Trax complex being explored as a therapeutic target. Additionally, Translin and Trax have been implicated in a wider range of biological functions ranging from sleep regulation to telomere transcript control. Here we reveal a Trax- and RNAi-independent function for Translin in dissociating RNA polymerase II from its genomic template, with loss of Translin function resulting in increased transcription-associated recombination and elevated genome instability. This provides genetic insight into the longstanding question of how Translin might influence chromosomal rearrangements in human genetic diseases and provides important functional understanding of an oncological therapeutic target.

Non-coding Natural Antisense Transcripts: Analysis and Application.

Non-coding natural antisense transcripts (ncNATs) are regulatory RNA molecules that are overlapping with as well as complementary to other transcripts. These transcripts are implicated in a broad variety of biological and pathological processes, including tumorigenesis and oncogenic progression. With this complex field still in its infancy, annotations, expression profiling and functional characterisations of ncNATs are far less comprehensive than those for protein-coding genes, pointing out substantial gaps in the analysis and characterisation of these regulatory transcripts. In this review, we discuss ncNATs from an analysis perspective, in particular regarding the use of high-throughput sequencing strategies, such as RNA-sequencing, and summarize the unique challenges of investigating the antisense transcriptome. Finally, we elaborate on their potential as biomarkers and future targets for treatment, focusing on cancer.

Physical activity for individuals living with a physical disability in Quebec: Issues and opportunities of access.

BACKGROUND: Individuals living with a physical disability have reported difficulty in meeting their healthy living and leisure needs which could be a result of poor accessibility. OBJECTIVE: This qualitative study aimed to understand the relative accessibility of physical activity from the perspective of individuals living with a physical disability in Quebec, Canada. METHODS: Twenty semi-structured interviews were conducted with current, past, non-members, and staff members of an adapted physical activity program. A qualitative approach with an inductive thematic analysis was used to interpret the data. RESULTS: We identified five overarching themes focusing on participants' experiences related to access: (i) physical activity opportunities; (ii) social interactions; (iii) relationships; (iv) infrastructure; (v) policies and public services. Participants highlighted that access to physical activity programming is shaped by a complex interaction of these overarching themes and their sub-themes. CONCLUSIONS: Access to physical activity opportunities for individuals living with a physical disability cannot be understood in isolation from the broader public policies, infrastructure, social interactions, and relationships that shape their experiences. Policy makers and other health and recreational professionals must consider these broader factors when recommending or creating physical activity opportunities for individuals with physical disabilities.

Translin-Trax: Considerations for Oncological Therapeutic Targeting.

Dicer-deficient cancers have poor prognoses, which is linked to the degradation of tumour-suppressing miRNA precursors by the Translin-Trax (Tn-Tx) ribonuclease. Inhibition of Tn-Tx potentially offers a new therapeutic intervention point. However, Tn-Tx functions in an array of biological processes, and here we consider how this complexity could influence therapeutic design strategies.

Brachyury: Strategies for Drugging an Intractable Cancer Therapeutic Target.

New approaches to drug discovery are unlocking enormous therapeutic potential residing in cancer-specific molecules. Brachyury is emerging as an exciting new drug target for the rare bone cancer chordoma. Here, recent advances targeting Brachyury in chordoma are discussed and how these might open doors to the targeting of other, more common cancer types.

Treatment with potassium bromide mitigates ataxia and reduces tremor in lambs with perennial ryegrass toxicosis.

Aims: To assess the use of potassium bromide (KBr) as a therapeutic intervention for perennial ryegrass toxicosis (PRGT) in lambs fed ryegrass seed containing lolitrem B. Methods: Male lambs aged 10-12 months (n = 43) were assigned to receive ryegrass seed containing lolitrem B, at a dose of 0.16 mg/kg/day (Groups 2, 3 and 4), or lucerne chaff and molasses (Groups 1 and 5). Lambs in Groups 2 and 3 were observed for clinical signs and gait changes until defined signs of PGRT were observed, when they were transferred, with lambs in Group 1, to the Testing phase of the trial. Lambs in Group 3 were then treated with a single oral dose of 300 mg/kg bromide. Lambs in Groups 4 and 5 received KBr daily from the start of the trial (540 mg/kg bromide over 3 days then 20 mg/kg daily) and were transferred to the Testing phase after 18 days. Clinical examination and gait assessment, and surface electromyography of the triceps muscle, measuring root-mean-square (RMS) voltages, were carried out on Days 0, 1 and 2 of the Testing phase followed by necropsy, histopathology, measurement of concentrations of bromide in serum and CSF and faecal cortisol metabolites (FCM). Results: In Group 3 lambs, mean composite gait scores decreased between Testing phase Day 0 and Days 1 and 2 (p < 0.001), but increased in lambs in Group 2 between Day 0 and Day 2 (p = 0.015). Scores for lambs in Group 3 on Day 2 were lower than for lambs in Group 2 (p < 0.001). Mean RMS voltages on Day 2 were higher in lambs in Group 2 than Group 3 (p = 0.045). Mean concentrations of bromide in serum were >800 µg/mL in lambs in Groups 3 and 4 on Day 2. Concentrations of FCM were higher in lambs from Group 2 than in Groups 1 or 5, but were similar in Groups 2, 3 and 4. Histopathological findings in the cerebellum of lambs from Groups 2, 3 and 4 were similar, showing pyknosis of neurons within the granular layer of the cerebellum and Purkinje neuron proximal axonal spheroid formation. Conclusions and clinical relevance: A single oral dose of 300 mg/kg bromide in lambs with neurological signs of PRGT resulted in reduced composite gait scores and reduced RMS voltages, indicating a significant improvement in clinical signs of ataxia, movement disorder and muscle tremor associated with the neurotoxic effects of lolitrem B.

The prevalence of elevated gamma-glutamyltransferase and sorbitol dehydrogenase activity in racing Thoroughbreds and their associations with viral infection.

BACKGROUND: In racehorses, serum gamma-glutamyltransferase (GGT) activity is positively correlated with cumulative days in training and, when ≥100 IU/L, has been associated with poor performance. The prevalence of increased GGT activity in North American Thoroughbreds and its aetiopathogenesis are unknown. Four emerging viruses, pegivirus E (PgV E; equine pegivirus), hepacivirus A (HcV A; equine hepacivirus), pegivirus D (PgV D; Theiler's disease virus), and equine parvovirus-hepatitis (EqPV-H) have been identified in horses with clinical and subclinical hepatopathy. Available prevalence data indicate these viruses may commonly infect racehorses and contribute to increased liver enzyme activity in this population. OBJECTIVES: To investigate the association between viral infection and increased liver enzyme activity in racing Thoroughbreds. STUDY DESIGN: Cross-sectional study. METHODS: Prerace blood samples were collected from 802 Thoroughbreds and tested for GGT and sorbitol dehydrogenase (SDH) activity, and the presence of PgV E, HcV A, PgV D and EqPV-H nucleic acid. RESULTS: Increased SDH and/or GGT were detected in 56.2% of the 802 serum samples. The infection prevalence and relative risk (RR) of having concurrently increased liver enzyme activity were: PgV E = 18.2% (RR = 0.820, 95% CI = 0.662-0.978, P = 0.03), HcV A = 2.5% (RR = 1.132, 95% CI = 0.719-1.466, P = 0.6), PgV D = 0.5% (RR = 0.875, 95% CI = 0.165-1.598, P>0.9), EqPV-H = 2.9% (RR = 0.916, 95% CI = 0.564-1.266, P = 0.7). MAIN LIMITATIONS: Longitudinal samples were not tested. CONCLUSIONS: While viral infection was common among Thoroughbreds in this study, infection did not explain the high prevalence of increased liver enzyme activity. In fact, PgV E infection was associated with a reduced risk of having increased liver enzyme activity, indicating PgV E is unlikely to be a cause of hepatitis in horses. Importantly, like GGT, increased SDH activity was highly prevalent in this study, and provides additional evidence that hepatocellular injury was occurring in these horses.

Language of ADHD in Adults on Social Media.

Objective: We computationally analyze the language of social media users diagnosed with ADHD to understand what they talk about, and how their language is correlated with users' characteristics such as personality and temporal orientation. Method: We analyzed approximately 1.3 million tweets written by 1,399 Twitter users with self-reported diagnoses of ADHD, comparing their posts with those used by a control set matched by age, gender, and period of activity. Results: Users with ADHD are found to be less agreeable, more open, to post more often, and to use more negations, hedging, and swear words. Posts are suggestive of themes of emotional dysregulation, self-criticism, substance abuse, and exhaustion. A machine learning model can predict which of these Twitter users has ADHD with an out-of-sample AUC of .836. Conclusion: Based on this emerging technology, conjectures of future uses of social media by researchers and clinicians to better understand the naturalistic manifestations and sequelae of ADHD.

Development of a model for investigation of perennial ryegrass toxicosis in sheep.

AIMS To develop a clinical model of perennial ryegrass toxicosis (PRGT) based on feeding a known dose of lolitrem B and ergotamine, and to produce a consistent clinical presentation for assessment of disease pathophysiology, neurological changes and neurohistopathology. METHODS Male lambs, aged between 10-12 months, were randomly assigned to either Treatment (n=9) or Control (n=9) groups. Lambs in the Treatment group received feed containing a novel endophyte-infested perennial ryegrass seed, commencing on Day 0 of the Feeding phase with a low induction dose, then increasing after 3 days to provide 0.16 mg/kg live bodywight (LBW)/day of lolitrem B and 0.054 mg/kg LBW/day ergotamine. Lambs were examined daily and when defined signs of PRGT were observed they were transferred to the Testing phase. Neurological examinations, assessment of gait, surface electromyography (EMG) and mechanosensory nociceptive threshold testing were carried out and blood samples collected during both phases of the trial, with a full necropsy, histopathological examination and measurement of faecal cortisol metabolites (FCM) performed on Day 2 of the Testing phase. RESULTS Typical clinical signs of PRGT, including ataxia of vestibulocerebellar origin leading to stumbling, were observed in all Treatment lambs. The median interval from the start of the Feeding phase to entry into the Testing phase was 21 (min 18, max 34) days. Histopathological characterisation of neurological lesions included the presence of Purkinje cell vacuolation, pyknotic granular layer neurons and proximal axonal Purkinje cell spheroids. Lesions were most apparent within the vestibulocerebellum. Mean root-mean-square voltages from triceps EMG increased in Treatment lambs between Feeding phase Day 0 and Testing phase Day 2 (p<0.001). Daily water intake during the Testing phase for the Treatment group was less than in Control group lambs (p=0.002), and concentrations of FCM at necropsy were higher in Treatment compared to Control lambs (p=0.02). CONCLUSIONS AND CLINICAL RELEVANCE Lolitrem B and ergotamine dosing in feed on a live weight basis combined with neurological/gait assessment provides an effective model for investigation of PRGT and potential therapeutics. Assessment of gait changes using defined criteria and RMS voltages from EMG appear to be useful tools for the assessment of the severity of neurological changes.

Transcranial direct current brain stimulation decreases impulsivity in ADHD.

BACKGROUND: Impulsivity is a core deficit in attention deficit hyperactivity disorder (ADHD). Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) has been shown to modulate cognitive control circuits and could enhance DLPFC activity, leading to improved impulse control in ADHD. OBJECTIVE: Hypothesis: We predicted 2.0 mA anodal stimulation (tDCS) versus sham stimulation applied over the left DLPFC would improve Conners Continuous Performance Task (CPT) scores. Our secondary hypothesis predicted that stop signal task (SST) reaction time (SSRT) would decrease with tDCS (versus sham). METHODS: Thirty-seven participants completed two periods of three tDCS (or sham) sessions two weeks apart in a within-subject, double-blind, counterbalanced order. Participants performed a fractal N-back training task concurrent with tDCS (or sham) stimulation. Participants completed the CPT and SST at the beginning of treatment (baseline), at the end of the treatment, and at a 3-day post-stimulation follow-up. RESULTS: There was a significant stimulation condition by session interaction for CPT false positive scores (χ2 = 15.44, p < 0.001) driven by a decrease in false positive errors from baseline to end of treatment in the tDCS group (ß = -0.36, 95% Confidence Interval (CI) -0.54 to -0.18, p < 0.001). This effect did not persist at follow-up (ß = -0.13, p > 0.05). There was no significant stimulation condition by session interaction effect on CPT true positive errors or response time (ps > 0.05). No significant change in SSRT performance was observed (p > 0.05). CONCLUSION: These findings suggest that stimulation of the left DLPFC with tDCS can improve impulsivity symptoms in ADHD, supporting the therapeutic potential for tDCS in adult ADHD patients.

Meiosis-like Functions in Oncogenesis: A New View of Cancer.

Cancer cells have many abnormal characteristics enabling tumors to grow, spread, and avoid immunologic and therapeutic destruction. Central to this is the innate ability of populations of cancer cells to rapidly evolve. One feature of many cancers is that they activate genes that are normally associated with distinct developmental states, including germ cell-specific genes. This has historically led to the proposal that tumors take on embryonal characteristics, the so called embryonal theory of cancer. However, one group of germline genes, not directly associated with embryonic somatic tissue genesis, is the one that encodes the specific factors to drive the unique reductional chromosome segregation of meiosis I, which also results in chromosomal exchanges. Here, we propose that meiosis I-specific modulators of reductional segregation can contribute to oncogenic chromosome dynamics and that the embryonal theory for cancer cell growth/proliferation is overly simplistic, as meiotic factors are not a feature of most embryonic tissue development. We postulate that some meiotic chromosome-regulatory functions contribute to a soma-to-germline model for cancer, in which activation of germline (including meiosis) functions drive oncogenesis, and we extend this to propose that meiotic factors could be powerful sources of targets for therapeutics and biomonitoring in oncology. Cancer Res; 77(21); 5712-6. ©2017 AACR.

Atlas-based automatic measurements of the morphology of the tibiofemoral joint.

PURPOSE: Anatomical metrics of the tibiofemoral joint support assessment of joint stability and surgical planning. We propose an automated, atlas-based algorithm to streamline the measurements in 3D images of the joint and reduce user-dependence of the metrics arising from manual identification of the anatomical landmarks. METHODS: The method is initialized with coarse registrations of a set of atlas images to the fixed input image. The initial registrations are then refined separately for the tibia and femur and the best matching atlas is selected. Finally, the anatomical landmarks of the best matching atlas are transformed onto the input image by deforming a surface model of the atlas to fit the shape of the tibial plateau in the input image (a mesh-to-volume registration). We apply the method to weight-bearing volumetric images of the knee obtained from 23 subjects using an extremity cone-beam CT system. Results of the automated algorithm were compared to an expert radiologist for measurements of Static Alignment (SA), Medial Tibial Slope (MTS) and Lateral Tibial Slope (LTS). RESULTS: Intra-reader variability as high as ~10% for LTS and 7% for MTS (ratio of standard deviation to the mean in repeated measurements) was found for expert radiologist, illustrating the potential benefits of an automated approach in improving the precision of the metrics. The proposed method achieved excellent registration of the atlas mesh to the input volumes. The resulting automated measurements yielded high correlations with expert radiologist, as indicated by correlation coefficients of 0.72 for MTS, 0.8 for LTS, and 0.89 for SA. CONCLUSIONS: The automated method for measurement of anatomical metrics of the tibiofemoral joint achieves high correlation with expert radiologist without the need for time consuming and error prone manual selection of landmarks.

Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis.

BACKGROUND: Cancer/testis (CT) genes have expression normally restricted to the testis, but become activated during oncogenesis, so they have excellent potential as cancer-specific biomarkers. Evidence is starting to emerge to indicate that they also provide function(s) in the oncogenic programme. Human TEX19 is a recently identified CT gene, but a functional role for TEX19 in cancer has not yet been defined. METHODS: siRNA was used to deplete TEX19 levels in various cancer cell lines. This was extended using shRNA to deplete TEX19 in vivo. Western blotting, fluorescence activated cell sorting and immunofluorescence were used to study the effect of TEX19 depletion in cancer cells and to localize TEX19 in normal testis and cancer cells/tissues. RT-qPCR and RNA sequencing were employed to determine the changes to the transcriptome of cancer cells depleted for TEX19 and Kaplan-Meier plots were generated to explore the relationship between TEX19 expression and prognosis for a range of cancer types. RESULTS: Depletion of TEX19 levels in a range of cancer cell lines in vitro and in vivo restricts cellular proliferation/self-renewal/reduces tumour volume, indicating TEX19 is required for cancer cell proliferative/self-renewal potential. Analysis of cells depleted for TEX19 indicates they enter a quiescent-like state and have subtle defects in S-phase progression. TEX19 is present in both the nucleus and cytoplasm in both cancerous cells and normal testis. In cancer cells, localization switches in a context-dependent fashion. Transcriptome analysis of TEX19 depleted cells reveals altered transcript levels of a number of cancer-/proliferation-associated genes, suggesting that TEX19 could control oncogenic proliferation via a transcript/transcription regulation pathway. Finally, overall survival analysis of high verses low TEX19 expressing tumours indicates that TEX19 expression is linked to prognostic outcomes in different tumour types. CONCLUSIONS: TEX19 is required to drive cell proliferation in a range of cancer cell types, possibly mediated via an oncogenic transcript regulation mechanism. TEX19 expression is linked to a poor prognosis for some cancers and collectively these findings indicate that not only can TEX19 expression serve as a novel cancer biomarker, but may also offer a cancer-specific therapeutic target with broad spectrum potential.

Assessment and monitoring of treatment response in adult ADHD patients: current perspectives.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome that emerges in childhood or early adolescence and persists into adulthood for a majority of individuals. There are many other adults with ADHD who may not seek out evaluation and treatment until adulthood, having been able to "get by" before struggling with inattention, hyperactivity, and/or impulsivity in adulthood, in addition to facing the associated features of disorganization, poor time management, and procrastination among many others. A lifetime diagnosis of ADHD is associated with a wide range of life impairments, which makes a comprehensive and accurate diagnostic assessment essential in order to obtain appropriate treatment. Moreover, while there are effective medical and psychosocial treatments for ADHD, it is important to be able to track treatment response in order to evaluate whether adjustments in specific interventions are needed or referrals for adjunctive treatments and supports are indicated to facilitate optimal therapeutic outcomes. The goal of this article is to provide a clinically useful review of the various measures that practicing clinicians can use to aid in the diagnostic assessment and monitoring of psychosocial and medical treatment of ADHD in adult patients. This review includes various structured interviews, screening scales, adult ADHD symptom inventories, measures of associated features of ADHD, as well as ratings of impairment and functioning which can be adapted to clinicians' practice needs in order to track treatment progress and optimize treatments for adults with ADHD.

Translin and Trax differentially regulate telomere-associated transcript homeostasis.

Translin and Trax proteins are highly conserved nucleic acid binding proteins that have been implicated in RNA regulation in a range of biological processes including tRNA processing, RNA interference, microRNA degradation during oncogenesis, spermatogenesis and neuronal regulation. Here, we explore the function of this paralogue pair of proteins in the fission yeast. Using transcript analysis we demonstrate a reciprocal mechanism for control of telomere-associated transcripts. Mutation of tfx1+ (Trax) elevates transcript levels from silenced sub-telomeric regions of the genome, but not other silenced regions, such as the peri-centromeric heterochromatin. In the case of some sub-telomeric transcripts, but not all, this elevation is dependent on the Trax paralogue, Tsn1 (Translin). In a reciprocal fashion, Tsn1 (Translin) serves to repress levels of transcripts (TERRAs) from the telomeric repeats, whereas Tfx1 serves to maintain these elevated levels. This reveals a novel mechanism for the regulation of telomeric transcripts. We extend this to demonstrate that human Translin and Trax also control telomere-associated transcript levels in human cells in a telomere-specific fashion.