Experiences of deliberate practice orientated psychological skills training for cancer care staff: Barriers and facilitators to learning and implementation in practice.

This study explored participant-reported facilitators and barriers to learning and implementation from a 2-day training in psychological assessment and intervention skills for cancer staff, involving deliberate practice and supervision. Twenty-six semi-structured interviews were analysed using thematic analysis leading to four meta-themes: perceived practicality of training, impact of training: practice and its effects, implementation transfer processes and supervision engagement. Analysis identified a learning process to implementation: observation and practice of techniques during training facilitated participant learning; personal use and relevance of training content encouraged reflection, which enabled selection of appropriate tools for clinical practice; gains in commitment and confidence to use techniques supported participants to adapt clinical consultations, and supervision further facilitated implementation. Changing practice increased confidence, sense of achievement and engagement with participants' own wellbeing. Interactive training, deliberate practice and continuous learning were facilitators to implementation whilst time constraint and low confidence in using techniques in remote consultations were barriers.

Reducing Time to Diagnosis of Rare Genetic Diseases in a Medically Underserved Hispanic Population- Lessons Learned for Meaningful Engagement.

Background: The utilization of genomic information to improve health outcomes is progressively becoming more common in clinical practice. Nonetheless, disparities persist in accessing genetic services among ethnic minorities, individuals with low socioeconomic status, and other vulnerable populations. The Rio Grande Valley at the Texas-Mexico border is predominantly Hispanic with a high poverty rate and an increased prevalence of birth defects, with very limited access to genetics services. The cost of a diagnosis is often times out of reach for these underserved families. Funded by the National Center for Advancing Translational Sciences (NCATS), Project GIVE (Genetic Inclusion by Virtual Evaluation) was launched in 2022 to shorten the time to diagnosis and alleviate healthcare inequities in this region, with the goal of improving pediatric health outcomes. Methods: Utilizing Consultagene, an innovative electronic health record (EHR) agnostic virtual telehealth and educational platform, we designed the study to recruit 100 children with rare diseases over a period of two years from this region, through peer-to-peer consultation and referral. Conclusions: Project GIVE study has allowed advanced genetic evaluation and delivery of genome sequencing through the virtual portal, effectively circumventing the recognized socioeconomic and other barriers within this population. This paper explores the successful community engagement process and implementation of an alternate genomics evaluation platform and testing approach, aiming to reduce the diagnostic journey for individuals with rare diseases residing in a medically underserved region.

GIGYF1 disruption associates with autism and impaired IGF-1R signaling.

Autism spectrum disorder (ASD) represents a group of neurodevelopmental phenotypes with a strong genetic component. An excess of likely gene-disruptive (LGD) mutations in GIGYF1 was implicated in ASD. Here, we report that GIGYF1 is the second-most mutated gene among known ASD high-confidence risk genes. We investigated the inheritance of 46 GIGYF1 LGD variants, including the highly recurrent mutation c.333del:p.L111Rfs*234. Inherited GIGYF1 heterozygous LGD variants were 1.8 times more common than de novo mutations. Among individuals with ASD, cognitive impairments were less likely in those with GIGYF1 LGD variants relative to those with other high-confidence gene mutations. Using a Gigyf1 conditional KO mouse model, we showed that haploinsufficiency in the developing brain led to social impairments without significant cognitive impairments. In contrast, homozygous mice showed more severe social disability as well as cognitive impairments. Gigyf1 deficiency in mice led to a reduction in the number of upper-layer cortical neurons, accompanied by a decrease in proliferation and increase in differentiation of neural progenitor cells. We showed that GIGYF1 regulated the recycling of IGF-1R to the cell surface. KO of GIGYF1 led to a decreased level of IGF-1R on the cell surface, disrupting the IGF-1R/ERK signaling pathway. In summary, our findings show that GIGYF1 is a regulator of IGF-1R recycling. Haploinsufficiency of GIGYF1 was associated with autistic behavior, likely through interference with IGF-1R/ERK signaling pathway.

Inducible podocyte-specific deletion of CTCF drives progressive kidney disease and bone abnormalities.

Progressive chronic kidney diseases (CKDs) are on the rise worldwide. However, the sequence of events resulting in CKD progression remain poorly understood. Animal models of CKD exploring these issues are confounded by systemic toxicities or surgical interventions to acutely induce kidney injury. Here we report the generation of a CKD mouse model through the inducible podocyte-specific ablation of an essential endogenous molecule, the chromatin structure regulator CCCTC-binding factor (CTCF), which leads to rapid podocyte loss (iCTCFpod-/-). As a consequence, iCTCFpod-/- mice develop severe progressive albuminuria, hyperlipidemia, hypoalbuminemia, and impairment of renal function, and die within 8-10 weeks. CKD progression in iCTCFpod-/- mice leads to high serum phosphate and elevations in fibroblast growth factor 23 (FGF23) and parathyroid hormone that rapidly cause bone mineralization defects, increased bone resorption, and bone loss. Dissection of the timeline leading to glomerular pathology in this CKD model led to the surprising observation that podocyte ablation and the resulting glomerular filter destruction is sufficient to drive progressive CKD and osteodystrophy in the absence of interstitial fibrosis. This work introduces an animal model with significant advantages for the study of CKD progression, and it highlights the need for podocyte-protective strategies for future kidney therapeutics.

Comparison of Fecal Calprotectin Methods for Predicting Relapse of Pediatric Inflammatory Bowel Disease.

Background. Pediatric inflammatory bowel disease (IBD) is on the rise worldwide. Endoscopies are necessary for IBD assessment but are invasive, expensive, and inconvenient. Recently, fecal calprotectin (FCal) was proposed as a noninvasive and specific marker of gut inflammation. We evaluated the analytical performance of three FCal assays and their clinical performance in predicting relapse in pediatric IBD. Methods. This study used 40 pediatric IBD and 40 random non-IBD patients' fecal samples. Two automated ELISAs (Bühlmann and PhiCal® Calprotectin-EIA) and an EliA (Phadia 250 EliA-Calprotectin) were used to evaluate the analytical performance. The clinical performance was assessed by PhiCal Calprotectin-EIA, EliA-Calprotectin, and Bühlmann immunochromatographic point-of-care test (POCT). Results. All assays displayed acceptable analytical performance below and above the medical decision cut-off [imprecision (CV < 10% intra-assay; <15% interassay); linearity (overall mean % deviation < 16.5%)]. The agreement with PhiCal Calprotectin-EIA was 100% and 78.6% for Bühlmann (95% CI, 87.5-100; Kappa: 1) and EliA-Calprotectin (95% CI, 60.5-89.8; Kappa: 0.32), respectively, and 63.6% between Bühlmann and EliA-Calprotectin (95% CI, 46.6-77.8; Kappa: 0.16). All assays evaluated had similar clinical performance [AUC: 0.84 (EliA-Calprotectin); 0.83 (POCT and PhiCal Calprotectin-EIA)]. Conclusion. FCal levels determined using the same method and assay together with clinical history would be a noninvasive and useful tool in monitoring pediatric IBD.

Changing sexually transmitted infection screening protocol will result in improved case finding for trichomonas vaginalis among high-risk female populations.

BACKGROUND: Trichomonas vaginalis is a sexually transmitted infection, which is largely underestimated because of ineffective screening protocols and lack of public health attention. METHODS: Two studies were conducted to assess the frequency of missed diagnosis of T. vaginalis when using current routine practices for T. vaginalis screening in high-risk female populations. The first study compares the rate of positivity detected using wet preparation microscopy to the number of cases found using polymerase chain reaction (PCR) using residual samples from women attending a public health sexually transmitted disease clinic. The second study compares universal to targeted screening of symptomatic women using PCR on vaginal samples from women screened for sexually transmitted disease at a correctional facility. RESULTS: In the first study, a 5-fold increased incidence of T. vaginalis infection was detected when PCR was performed instead of wet mount microscopy in a sample of 222 women screened at a sexually transmitted disease clinic. The second study detected a 5-fold increase in cases among a sample of 471 incarcerated women when universal screening was implemented. CONCLUSIONS: Improving detection of T. vaginalis is critical, given that when left untreated, T. vaginalis increases susceptibility to coinfections including human immunodeficiency virus. Changing screening protocols to use improved diagnostic tools and applying universal screening resulted in increased case finding for T. vaginalis among high-risk women. The prevalence of T. vaginalis coupled with its negative impact on health necessitate greater public health attention is needed in order to reduce incidence rates, improve diagnosis, and to better understand this important, yet underestimated, pathogen.