Joubert Syndrome with Orofacial Digital Features.

Joubert syndrome (JS) is an autosomal recessive inherited disorder characterized by hypotonia, cerebellar vermis hypoplasia, ocular abnormalities (e.g., pigmentary retinopathy, oculomotor apraxia, and nystagmus), renal cysts, and hepatic fibrosis. Respiratory abnormalities, as apnea and hyperpnea, may be present, as well as mental retardation. Since the clinical findings of JS are quite heterogeneous, determination of radiological findings is essential.

Continuing Medical Education and Firearm Violence Counseling.

Firearm violence is a significant and increasing cause of mortality. Although physicians view firearm counseling as their professional obligation, few engage in the practice. This study examines medical education and firearm counseling among physicians in North Carolina. While 65 percent of physicians reported knowing how to counsel patients about gun safety, only 25 percent reported having conversations with patients about firearms or firearm safety often or very often. Physicians reporting continuing medical education (CME) attendance on gun safety, however, were more likely to report providing patients with firearm safety counseling and asking patients with depression about firearms. Increasing availability of and physician participation in firearm violence prevention CME could significantly increase physicians' knowledge of and engagement in firearm counseling.

Cancer-related search for meaning increases willingness to participate in mindfulness-based stress reduction.

OBJECTIVE: A cancer diagnosis can prompt an examination and reevaluation of life's meaning, purpose, and priorities. There is evidence that mindfulness-based stress reduction (MBSR) may help facilitate the meaning-making process. This study examined the influence of meaning in life on willingness to participate (WTP) in MBSR and identified factors associated with the search for and/or presence of meaning. METHODS: A cross-sectional survey study of 300 patients undergoing radiation therapy was conducted. WTP in MBSR was dichotomized into yes/no by asking, "Would you participate in an MBSR program if it was offered at the cancer center?" The search for, and the presence of, meaning were assessed using the Meaning in Life Questionnaire. RESULTS: Eighty patients (27%) indicated WTP in MBSR. In a multivariate logistic regression model, search for meaning was the only significant predictor of WTP in MBSR (adjusted odds ratio [AOR] =1.04, P ≤ .001, 95% CI = 1.01-1.08). Identifying as non-white (adjusted ß = 4.62; 95% CI = 2.22-7.02; P < .001), and reporting subclinical (adjusted ß = 3.59; 95% CI = 0.84-6.34; P = .01) or clinical levels (adjusted ß = 5.52; 95% CI = 2.41-8.63; P = .001) of anxiety were the strongest predictors of search for meaning. CONCLUSION: Our study indicates that patients searching for meaning are receptive to MBSR. Nonwhite patients and those experiencing high levels of anxiety are most likely to endorse a search for meaning. Future research is needed to understand how best to support patients who are searching for meaning and remove barriers to evidence-based programs like MBSR.

Induction of G-quadruplex DNA structure by Zn(II) 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin.

G-quadruplexes (GQ) are formed by the association of guanine-rich stretches of DNA. Certain small molecules can influence kinetics and thermodynamics of this association. Understanding the mechanism of ligand-assisted GQ folding is necessary for the design of more efficient cancer therapeutics. The oligonucleotide d(TAGGG)(2) forms parallel bimolecular GQ in the presence of ≥66 mM K(+); GQs are not formed under Na(+), Li(+) or low K(+) conditions. The thermodynamic parameters for GQ folding at 60 µM oligonucleotide and 100 mM KCl are ΔH = -35 ± 2 kcal mol(-1) and ΔG(310) = -1.4 kcal mol(-1). Quadruplex [d(TAGGG)(2)](2) binds 2-3 K(+) ions with K(d) of 0.5 ± 0.2 mM. Our work addresses the question of whether metal free 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4) and its Zn(II), Cu(II), and Pt(II) derivatives are capable of facilitating GQ folding of d(TAGGG)(2) from single stranded, or binding to preformed GQ, using UV-vis and circular dichroism (CD) spectroscopies. ZnTMPyP4 is unique among other porphyrins in its ability to induce GQ structure of d(TAGGG)(2), which also requires at least a low amount of potassium. ZnTMPyP4 binds with 2:1 stoichiometry possibly in an end-stacking mode with a ~10(6) M(-1) binding constant, determined through UV-vis and ITC titrations. This process is entropically driven and has ΔG(298) of -8.0 kcal mol(-1). TMPyP4 binds with 3:1 stoichiometry and K(a) of ~10(6) M(-1). ZnTMPyP4 and TMPyP4 are efficient stabilizers of [d(TAGGG)(2)](2) displaying ΔT(1/2) of 13.5 and 13.8 °C, respectively, at 1:2 GQ to porphyrin ratio; CuTMPyP4 shows a much weaker effect (ΔT(1/2) = 4.7 °C) and PtTMPyP4 is weakly destabilizing (ΔT(1/2) = -2.9 °C). The selectivity of ZnTMPyP4 for GQ versus dsDNA is comparable to that of TMPyP4. The ability of ZnTMPyP4 to bind and stabilize GQ, to induce GQ formation, and speed up its folding may suggest an important biological activity for this molecule.