Availability and Geographic Access to Hospital-Based Breast Cancer Diagnostic Services in Ghana.

PURPOSE: Breast cancer is the most frequent cancer and second most common cause of cancer-related death in Ghana. Early detection and access to diagnostic services are vital for early treatment initiation and improved survival. This study characterizes the geographic access to hospital-based breast cancer diagnostic services in Ghana as a framework for expansion. METHODS: A cross-sectional hospital-based survey was completed in Ghana from November 2020 to October 2021. Early diagnostic services, as defined by the National Comprehensive Cancer Network (NCCN) Framework for Resource Stratification, was assessed at each hospital. Services were characterized as available >80% of the time in the previous year, <80%, or not available. ArcGIS was used to identify the proportion of the population within 20 and 45 km of services. RESULTS: Most hospitals in Ghana participated in this survey (95%; 328 of 346). Of these, 12 met full NCCN Basic criteria >80% of the time, with 43% of the population living within 45 km. Ten of the 12 met full NCCN Core criteria, and none met full NCCN Enhanced criteria. An additional 12 hospitals were identified that provide the majority of NCCN Basic services but lack select services necessary to meet this criterion. Expansion of services in these hospitals could result in an additional 20% of the population having access to NCCN Basic-level early diagnostic services within 45 km. CONCLUSION: Hospital-based services for breast cancer early diagnosis in Ghana are available but sparse. Many hospitals offer fragmented aspects of care, but only a limited number of hospitals offer the full NCCN Basic or Core level of care. Understanding current availability and geographical distribution of services provides a framework for potential targeted expansion of services.

Chondroitin sulfate proteoglycan 4, a targetable oncoantigen that promotes ovarian cancer growth, invasion, cisplatin resistance and spheroid formation.

Epithelial ovarian cancer (EOC) is a highly heterogeneous disease encompassing several distinct molecular subtypes and clinical entities. Despite the initial success of surgical debulking and adjuvant chemotherapy, recurrence with chemotherapy resistant tumors is common in patients with EOC and leads to poor overall survival. The extensive genetic and phenotypic heterogeneity associated with ovarian cancers has hindered the identification of effective prognostic and predictive biomarkers in EOC patients. In the current studies, we identify a tumor cell surface oncoantigen, chondroitin sulfate proteoglycan 4 (CSPG4), as an independent risk factor for decreased survival of patients with EOC. Our results show that CSPG4 promotes EOC cell invasion, cisplatin resistance and spheroid formation in vitro and tumor expansion in vivo. Mechanistically, spheroid formation and tumor cell invasion are due to CSPG4-stimulated expression of the mesenchymal transcription factor ZEB1. Furthermore, we have developed a novel monoclonal anti-CSGP4 antibody against the juxtamembrane domain of the core protein that limits CSPG4-stimulated ZEB1 expression, tumor cell invasion and promotes EOC apoptosis within spheroid cultures. We therefore propose that CSPG4 expression drives phenotypic heterogeneity and malignant progression in EOC tumors. These studies further demonstrate that CSPG4 expression levels are a potential diagnostic biomarker in EOC and indicate that targeting cells which express this oncoantigen could limit recurrence and improve outcomes in patients with EOC.

Clinical outcomes according to lesion complexity in patients with high bleeding risk treated with 1-month dual antiplatelet therapy following pci: analysis from the onyx one clear study

BACKGROUND Safety and effectiveness outcomes were examined at 1 year among high bleeding risk (HBR) patients treated with 1 month of dual antiplatelet therapy (DAPT) following PCI with zotarolimus eluting stents (ZES) (Resolute Onyx, Medtronic, Santa Rosa, Califor nia) according to lesion complexity (Table). METHODS The 1-year clinical outcomes were evaluated in HBR pa tients treated with ZES who were event-free following 1-month DAPT post-procedure with planned single antiplatelet therapy thereafter. Propensity score adjustment was performed to account for baseline differences (Table). RESULTS A total of 1,506 patients were stratified by complex (n » 395) or noncomplex (n » 1,111) PCI criteria (Table). Complex patients were more frequently men (72.2% vs. 66.1%; p » 0.03) and had higher rates of prior myocardial infarction (MI) (34.4% vs. 23.4%), prior CABG (24.1% vs. 8.9%), multivessel disease (78.2% vs. 39.8%), and B2/C lesion classification (84.2% vs. 75.6%), all p < 0.001. Complex patients had more lesions treated (1.7 vs. 1.2), longer stent length per patient (65.1 mm vs. 26.9 mm), and longer procedure time (58.8 min vs. 35.3 min), all p < 0.001. Procedural success was higher among noncomplex patients (90.8% vs. 82.0%; p < 0.001). In unadjusted analysis, the rate of MI was higher in patients with complex lesions (p » 0.04). How ever, no significant differences in any outcomes between patients with and without complex lesions were present after propensity score adjustment (Table). CONCLUSION Despite greater anatomic and procedural complexity, similar safety and effectiveness were observed in complex and noncomplex patients treated with 1-month DAPT following PCI with Resolute Onyx ZES after propensity score adjustment. These findings support 1-month DAPT among selected HBR patients undergoing PCI with Resolute Onyx ZES irrespective of lesion and procedural complexity.

Identification, design and synthesis of tubulin-derived peptides as novel hyaluronan mimetic ligands for the receptor for hyaluronan-mediated motility (RHAMM/HMMR).

Fragments of the extracellular matrix component hyaluronan (HA) promote tissue inflammation, fibrosis and tumor progression. HA fragments act through HA receptors including CD44, LYVE1, TLR2, 4 and the receptor for hyaluronan mediated motility (RHAMM/HMMR). RHAMM is a multifunctional protein with both intracellular and extracellular roles in cell motility and proliferation. Extracellular RHAMM binds directly to HA fragments while intracellular RHAMM binds directly to ERK1 and tubulin. Both HA and regions of tubulin (s-tubulin) are anionic and bind to basic amino acid-rich regions in partner proteins, such as in HA and tubulin binding regions of RHAMM. We used this as a rationale for developing bioinformatics and SPR (surface plasmon resonance) based screening to identify high affinity anionic RHAMM peptide ligands. A library of 12-mer peptides was prepared based on the carboxyl terminal tail sequence of s-tubulin isoforms and assayed for their ability to bind to the HA/tubulin binding region of recombinant RHAMM using SPR. This approach resulted in the isolation of three 12-mer peptides with nanomolar affinity for RHAMM. These peptides bound selectively to RHAMM but not to CD44 or TLR2,4 and blocked RHAMM:HA interactions. Furthermore, fluorescein-peptide uptake by PC3MLN4 prostate cancer cells was blocked by RHAMM mAb but not by CD44 mAb. These peptides also reduced the ability of prostate cancer cells to degrade collagen type I. The selectivity of these novel HA peptide mimics for RHAMM suggest their potential for development as HA mimetic imaging and therapeutic agents for HA-promoted disease.

Cognitive processes as mediators of the relation between mindfulness and change in social anxiety symptoms following cognitive behavioral treatment.

The present study examined whether pretreatment mindfulness exerts an indirect effect on outcomes following cognitive-behavioral therapy (CBT). Cognitive processes of probability and cost bias (i.e., overestimations of the likelihood that negative social events will occur, and that these events will have negative consequences when they do occur) were explored as potential mediators of the relation between mindfulness and social anxiety symptom change. People with higher levels of mindfulness may be better able to benefit from treatments that reduce biases because mindfulness may aid in regulation of attention. Sixty-seven individuals with a primary diagnosis of social phobia identifying public speaking as their greatest fear received eight sessions of one of two types of exposure-based CBT delivered according to treatment manuals. Participants completed self-report measures of mindfulness, probability bias, cost bias, and social anxiety symptoms. Mediation hypotheses were assessed by a bootstrapped regression using treatment outcome data. Pretreatment mindfulness was not related to change in social anxiety symptoms from pre- to posttreatment. However, mindfulness had an indirect effect on treatment outcome via its association with probability bias, but not cost bias, at midtreatment. These findings were consistent across three metrics of social anxiety symptoms. Mindfulness may play a role in response to CBT among individuals with social phobia through its relation with probability bias--even when the treatment does not target mindfulness.

The relation between mindfulness and fear of negative evaluation over the course of cognitive behavioral therapy for social anxiety disorder.

OBJECTIVES: This study examined the relation between mindfulness and fear of negative evaluation over the course of nonmindfulness based cognitive-behavioral therapy (CBT) for social anxiety disorder (SAD). We expected that higher levels of mindfulness would be associated with a more positive response to treatment. METHOD: This study is a secondary report from a randomized controlled trial in which participants (N = 65) diagnosed with SAD were randomly assigned to receive 8 weeks of 1 of 2 manualized treatments (exposure group therapy, n = 33; or virtual reality exposure therapy, n = 32) either immediately or following an 8 week waiting period. RESULTS: Fear of negative evaluation decreased following treatment and was negatively related to mindfulness throughout treatment and follow-up. Mindfulness did not moderate treatment outcome. CONCLUSIONS: These findings indicate that while mindfulness is related to fear, it is not a moderator of symptom reduction in nonmindfulness-based treatment. Implications for treatment and future research are discussed.

Mindfulness Moderates the Relationship Between Disordered Eating Cognitions and Disordered Eating Behaviors in a Non-Clinical College Sample.

Psychological flexibility and mindfulness are two related, but distinct, regulation processes that have been shown to be at the core of psychological wellbeing. The current study investigated whether these two processes independently moderated the association between disordered eating cognitions and psychological distress as well as the relation between disordered eating cognitions and disordered eating behaviors. Non-clinical, ethnically diverse college undergraduates completed a web-based survey. Of 278 participants (nfemale=208; nmale=70) aged 18-24 years old, disordered eating cognitions, mindfulness, and psychological flexibility were related to psychological distress after controlling for gender, ethnicity, and body mass index. Disordered eating cognitions and mindfulness accounted for unique variance in disordered eating behaviors. Finally, mindfulness was found to moderate the association between disordered eating cognitions and disordered eating behaviors.

Failure to respond to endogenous or exogenous melatonin may cause nonphotoresponsiveness in Harlan Sprague Dawley rats.

BACKGROUND: Responsiveness to changing photoperiods from summer to winter seasons is an important but variable physiological trait in most temperate-zone mammals. Variation may be due to disorders of melatonin secretion or excretion, or to differences in physiological responses to similar patterns of melatonin secretion and excretion. One potential cause of nonphotoresponsiveness is a failure to secrete or metabolize melatonin in a pattern that reflects photoperiod length. METHODS: This study was performed to test whether a strongly photoresponsive rat strain (F344) and strongly nonphotoresponsive rat strain (HSD) have similar circadian urinary excretion profiles of the major metabolite of melatonin, 6-sulfatoxymelatonin (aMT6s), in long-day (L:D 16:8) and short-day (L:D 8:16) photoperiods. The question of whether young male HSD rats would have reproductive responses to constant dark or to supplemental melatonin injections was also tested. Urinary 24-hour aMT6s profiles were measured under L:D 8:16 and L:D 16:8 in young male laboratory rats of a strain known to be reproductively responsive to the short-day photoperiod (F344) and another known to be nonresponsive (HSD). RESULTS: Both strains exhibited nocturnal rises and diurnal falls in aMT6s excretion during both photoperiods, and the duration of the both strains' nocturnal rise was longer in short photoperiod treatments. In other experiments, young HSD rats failed to suppress reproduction or reduce body weight in response to either constant dark or twice-daily supplemental melatonin injections. CONCLUSION: The results suggest that HSD rats may be nonphotoresponsive because their reproductive system and regulatory system for body mass are unresponsive to melatonin.