Effect of coping strategies on patient and physician perceptions of disease severity and disability in systemic sclerosis

Objective. Systemic sclerosis (SSc) results in impaired function, disability, and reduced health-related quality of life. We investigated the effect of coping strategies on the patient global assessment of health (PtGA) and Health Assessment Questionnaire–Disability Index (HAQ-DI), after controlling for clinical characteristics and disease activity. We also explored the relationship between coping strategies and the correlation between the PtGA and physician global assessment (PGA) in SSc. Methods. We undertook posthoc analyses using baseline data obtained from the Raynaud Symptom Study (RSS). The PtGA, Coping Strategies Questionnaire, Pain Catastrophizing Scale, and Scleroderma Health Assessment Questionnaire were collected alongside the PGA, clinical characteristics, and patient demographics. Multivariable linear regression models and correlations were used to evaluate the relationship between coping strategies with the PtGA, HAQ-DI, and PGA. Results. Of the 107 patients with SSc enrolled in the RSS, there were sufficient data available for the analysis of 91 participants. The mean PtGA was 40/100 (SD 27) and the mean HAQ-DI was 0.87/3.0 (SD 0.73). After controlling for clinical and patient demographics, pain catastrophizing and maladaptive coping skills were significantly associated with the PtGA and HAQ-DI scores (P &lt; 0.05 for both), but not the PGA. Conclusion. The effect of coping strategies on PtGA and HAQ-DI (but not PGA in SSc) could influence the result of composite measures incorporating these outcome measures. Interventions to improve patient coping skills may support increased resilience and improve patient-perceived functional status and PtGA in SSc.</p

Dermal denticle assemblages in coral reef sediments correlate with conventional shark surveys

Abstract It is challenging to assess long‐term trends in mobile, long‐lived and relatively rare species such as sharks. Despite ongoing declines in many coastal shark populations, conventional surveys might be too fleeting and too recent to describe population trends over decades to millennia. Placing recent shark declines into historical context should improve management efforts as well as our understanding of past ecosystem dynamics. A new palaeoecological approach for surveying shark abundance on coral reefs is to quantify dermal denticle assemblages preserved in sediments. This approach assumes that denticle accumulation rates correlate with shark abundances. Here, we test this assumption by comparing the denticle record in surface sediments to three conventional shark survey methods at Palmyra Atoll, Line Islands, central Pacific Ocean, where shark density is high and spatially heterogeneous. We generally found a significant positive correlation between denticle accumulation rates and shark abundances derived from underwater visual census, baited remote underwater video and hook and line surveys. Denticle accumulation rates reflected shark abundances, suggesting that denticle assemblages can preserve a signal of time‐averaged shark abundance in low‐energy coral reef environments. We offer suggestions for applying this tool to measure shark abundance over long time‐scales in other contexts

MiR203 Mediates Subversion of Stem Cell Properties During Mammary Epithelial Differentiation via Repression of ΔNP63α and Promotes Mesenchymal-to-Epithelial Transition

During reproductive life, the mammary epithelium undergoes consecutive cycles of proliferation, differentiation and apoptosis. Doing so relies on the retained proliferative capacity, prolonged lifespan and developmental potency of mammary stem cells (MaSCs). ΔNp63α, the predominant TP63 isoform in mammary epithelia, is robustly expressed in MaSCs and is required for preservation of self-renewing capacity in diverse epithelial structures. However, the mechanism(s) underlying subversion of this activity during forfeiture of self-renewing capacity are poorly understood. MicroRNAs (miRNAs) govern critical cellular functions including stem cell maintenance, development, cell cycle regulation and differentiation by disrupting translation of target mRNAs. Data presented here indicate that expression of miR203, a miRNA that targets ΔNp63α and ΔNp63β is activated during luminal epithelial differentiation and that this pattern is observed in the murine mammary hierarchy. In addition, we present evidence that the transcription factor Zeb1 represses miR203 expression, thus enhancing ΔNp63α protein levels. Furthermore, ectopic miR203 suppresses ΔNp63α expression, proliferation and colony formation. The anti-clonogenic effects mediated by miR203 require suppression of ΔNp63α. In addition, ectopic miR203 promotes mesenchymal-to-epithelial transition and disrupts activities associated with epithelial stem cells. These studies support a model in which induction of miR203 mediates forfeiture of self-renewing capacity via suppression of ΔNp63α and may also have anti-tumorigenic activity through its reduction of EMT and cancer stem cell populations

Non-perturbative Landau gauge and infrared critical exponents in QCD

We discuss Faddeev-Popov quantization at the non-perturbative level and show that Gribov's prescription of cutting off the functional integral at the Gribov horizon does not change the Schwinger-Dyson equations, but rather resolves an ambiguity in the solution of these equations. We note that Gribov's prescription is not exact, and we therefore turn to the method of stochastic quantization in its time-independent formulation, and recall the proof that it is correct at the non-perturbative level. The non-perturbative Landau gauge is derived as a limiting case, and it is found that it yields the Faddeev-Popov method in Landau gauge with a cut-off at the Gribov horizon, plus a novel term that corrects for over-counting of Gribov copies inside the Gribov horizon. Non-perturbative but truncated coupled Schwinger-Dyson equations for the gluon and ghost propagators $D(k)$ and $G(k)$ in Landau gauge are solved asymptotically in the infrared region. The infrared critical exponents or anomalous dimensions, defined by $D(k) \sim 1/(k^2)^{1 + a_D}$ and $G(k) \sim 1/(k^2)^{1 + a_G}$ are obtained in space-time dimensions $d = 2, 3, 4$. Two possible solutions are obtained with the values, in $d = 4$ dimensions, $a_G = 1, a_D = -2$, or $a_G = [93 - (1201)^{1/2}]/98 \approx 0.595353, a_D = - 2a_G$.Comment: 26 pages. Modified 2.25.02 to update references and to clarify Introduction and Conclusio

Determination of ΛMS‾\Lambda_{\overline{MS}} from quenched and Nf=2N_f = 2 dynamical QCD

The scale parameter $\Lambda_{\overline{MS}}$ is computed on the lattice in the quenched approximation and for $N_f = 2$ flavors of light dynamical quarks. The dynamical calculation is done with non-perturbatively $O(a)$ improved Wilson fermions. In the continuum limit we obtain $\Lambda_{\overline{MS}}^{N_f=0} = 243(1)(10)$ MeV and $\Lambda_{\overline{MS}}^{N_f=2} = 217(16)(11)$ MeV, respectively.Comment: 16 pages, 6 figures. Minor changes. Final version to be published in Phys. Lett.

Alterations of EGFR, p53 and PTEN that mimic changes found in basal-like breast cancer promote transformation of human mammary epithelial cells

Breast cancer can be classified into different molecular subtypes with varying clinical and pathological characteristics. The basal-like breast cancer subtype represents one of the most aggressive and lethal types of breast cancer, and due to poor mechanistic understanding, it lacks targeted therapy. Many basal-like breast cancer patient samples display alterations of established drivers of cancer development, including elevated expression of EGFR, p53 inactivating mutations and loss of expression of the tumor suppressor PTEN; however, their contribution to human basal-like breast cancer pathogenesis remains ill-defined. Using non-transformed human mammary epithelial cells, we set out to determine whether altering EGFR, p53 and PTEN in different combinations could contribute to basal-like breast cancer progression through transformation of cells. Altering PTEN in combination with either p53 or EGFR in contrast to any of the single alterations caused increased growth of transformed colonies in soft agar. Concomitantly modifying all three genes led to the highest rate of cellular proliferation and the greatest degree of anchorage-independent colony formation. Results from our effort to engineer a model of BBC expressing alterations of EGFR, p53 and PTEN suggest that these changes are cooperative and likely play a causal role in basal-like breast cancer pathogenesis. Consideration should be given to targeting EGFR and restoring p53 and PTEN signaling simultaneously as a strategy for treatment of this subtype of breast cancer

The origins of estrogen receptor alpha-positive and estrogen receptor alpha-negative human breast cancer

Current hormonal therapies have benefited millions of patients with breast cancer. Their success, however, is often temporary and limited to a subset of patients whose tumors express estrogen receptor alpha (ER). The therapies are entirely ineffective in ER-negative disease. Recent studies suggest that there are many biological pathways and alterations involved in determining whether ER is expressed and how it is regulated during breast cancer evolution. Improving hormonal therapies, in addition to perfecting current strategies, will also target these newly discovered pathways and alterations, and others yet to be found. The present commentary will briefly highlight a few important observations and unanswered questions regarding ER status and growth regulation during breast cancer evolution, which hopefully will help to stimulate new thinking and progress in this important area of medial research

2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153772/1/acr24131.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153772/2/acr24131_am.pd

Prevalence of Fabry disease and GLA variants in young patients with acute stroke: the challenge to widen the screening. The Fabry-Stroke Italian Registry

Background: Fabry disease (FD) is a treatable X-linked lysosomal storage disorder caused by GLA gene variants leading to alpha-galactosidase A deficiency. FD is a rare cause of stroke, and it is still controversial whether in stroke patients FD should be searched from the beginning or at the end of the diagnostic workup (in cryptogenic strokes). Methods: Fabry-Stroke Italian Registry is a prospective, multicentric screening involving 33 stroke units. FD was sought by measuring α-galactosidase A activity (males) and by genetic tests (males with reduced enzyme activity and females) in patients aged 18–60 years hospitalized for TIA, ischemic stroke, or intracerebral hemorrhage. We diagnosed FD in patients with 1) already known pathogenic GLA variants; 2) novel GLA variants if additional clinical, laboratory, or family-derived criteria were present. Results: Out of 1906 patients, we found a GLA variant in 15 (0.79%; 95%CI 0.44–1.29) with a certain FD diagnosis in 3 (0.16%; 95%CI 0.03–0.46) patients, none of whom had hemorrhage. We identified 1 novel pathogenic GLA variant. Ischemic stroke etiologies in carriers of GLA variants were: cardioaortic embolism (33%), small artery occlusion (27%), other causes (20%), and undetermined (20%). Mild severity, recurrence, previous TIA, acroparesthesias, hearing loss, and small artery occlusion were predictors of GLA variant. Conclusion: In this large multicenter cohort the frequency of FD and GLA variants was consistent with previous reports. Limiting the screening for GLA variants to patients with cryptogenic stroke may miss up to 80% of diagnoses. Some easily recognizable clinical features could help select patients for FD screening