Discrete Superconducting Phases in FeSe-Derived Superconductors.

A general feature of unconventional superconductors is the existence of a superconducting dome in the phase diagram. Here we report a series of discrete superconducting phases in the simplest iron-based superconductor, FeSe thin flakes, by continuously tuning the carrier concentration through the intercalation of Li and Na ions with a solid ionic gating technique. Such discrete superconducting phases are robust against the substitution of 20% S for Se, but they are vulnerable to the substitution of 2% Cu for Fe, highlighting the importance of the iron site being intact. The superconducting phase diagram for FeSe derivatives is given, which is distinct from that of other unconventional superconductors.

Self-complementary AAV-mediated gene therapy restores cone function and prevents cone degeneration in two models of Rpe65 deficiency.

To test whether fast-acting, self-complimentary (sc), adeno-associated virus-mediated RPE65 expression prevents cone degeneration and/or restores cone function, we studied two mouse lines: the Rpe65-deficient rd12 mouse and the Rpe65-deficient, rhodopsin null ('that is, cone function-only') Rpe65(-/-)::Rho(-/-) mouse. scAAV5 expressing RPE65 was injected subretinally into one eye of rd12 and Rpe65(-/-)::Rho(-/-) mice at postnatal day 14 (P14). Contralateral rd12 eyes were injected later, at P35. Rd12 behavioral testing revealed that rod vision loss was prevented with either P14 or P35 treatment, whereas cone vision was only detected after P14 treatment. Consistent with this observation, P35 treatment only restored rod electroretinogram (ERG) signals, a result likely due to reduced cone densities at this time point. For Rpe65(-/-)::Rho(-/-) mice in which there is no confounding rod contribution to the ERG signal, cone cells and cone-mediated ERGs were also maintained with treatment at P14. This work establishes that a self-complimentary AAV5 vector can restore substantial visual function in two genetically distinct models of Rpe65 deficiency within 4 days of treatment. In addition, this therapy prevents cone degeneration but only if administered before extensive cone degeneration, thus supporting continuation of current Leber's congenital amaurosis-2 clinical trials with an added emphasis on cone subtype analysis and early intervention.

Lymphatic venous anastomosis (LVA) for treatment of secondary arm lymphedema. A prospective study of 11 LVA procedures in 10 patients with breast cancer related lymphedema and a critical review of the literature.

OBJECTIVE: The incidence of breast cancer related lymphedema (BCRL) varies between 7-35% depending on the combination of treatment modalities. Early detection of BCRL is crucial in order to start an effective non-operative treatment program. Because of the lack of prospective research on this topic, this study was undertaken to prospectively determine the effect of Lympho Venous Anastomosis (LVA) on BCRL and to review the current literature. STUDY DESIGN AND METHODS: Ten patients who were previously treated for breast cancer by surgery, radiotherapy, and chemotherapy, and were unresponsive to 12-weeks of non-operative treatment, underwent an LVA procedure (Degni-Cordeiro). Objective measurements were gathered for circumferential measurement and water volumetry, and quality of life. Various types of lymphoscintigraphy were carried out pre-operatively and post-operatively at 3 and 12 months. Treatment was embedded in a multidisciplinary setting. RESULTS: Post-operative volume measurements initially showed a 4.8% reduction of lymphedema at 3 months and a 2% reduction after one year. Various scintigraphic parameters showed some improvement. Quality of life questionnaires reported minimal improvement. Reviewing the literature, only retrospective studies were found; these reported varying results for LVA procedures. The selection of patients, classification of lymphedema, indications and types of LVA, and additional therapeutic options were heterogeneous, not comparable, and lacked a validated method of effect-assessment. CONCLUSIONS: Our results showed a minimal reduction in volume of lymphedema following LVA; in the literature, there was no convincing evidence of the success of LVA. Non-operative treatment and elastic stockings are still preferred by most patients with lymphedema, especially in early stages with few irreversible changes.

Uraemia suppresses central dopaminergic metabolism and impairs motor activity in rats.

OBJECTIVE: Uraemia often provokes various neurological disorders, such as mental changes, malperception, confusion, seizures and coma. Since changes in neurotransmissions induce neurological symptoms, we investigated changes in the monoamine metabolism and motor activity in uraemic rats. DESIGN: Prospective, randomised, controlled animal study. SUBJECTS: Male Wistar rats. INTERVENTIONS: Acute renal failure was induced by occlusion of bilateral renal arteries for 60 min, and the motor activity and brain monoamine turnover were examined 48 h later. The brain monoamine turnover was evaluated by the depletion of norepinephrine (NE) and dopamine (DA) induced by alpha-methyl-p-tyrosine (alpha-MT), or the accumulation of 5-hydroxyindoleacetic acid (5-HIAA) induced by probenecid. MEASUREMENTS AND RESULTS: Marked damage in renal function was found in animals subjected to renal ischaemia 48 h after the operation. The motor activity of the uraemic rats was impaired. The turnover of DA in the striatum, mesencephalon and hypothalamus was decreased in these rats. The turnover of NE and 5-hydroxytryptamine (5-HT) was unchanged in all regions examined. CONCLUSIONS: Suppression of the central DA turnover appears to be involved in the impairment of motor activity in uraemic rats.

Different roles of neuronal and endothelial nitric oxide synthases on ischemic nitric oxide production in gerbil striatum.

The production of nitric oxide (NO) in gerbil striatum during ischemia and reperfusion was monitored by measuring total NO metabolites in dialysates, and the effects of 7-nitroindazole (7-NI), a selective inhibitor of neuronal NO synthase, and N(G)-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor of NO synthase, were examined. The effects of these agents on ischemic neuronal damage were histologically evaluated 7 days after transient ischemia for 5 or 10 min. 7-NI and L-NAME decreased the NO production to similar extents in non-ischemic gerbils. 7-NI inhibited the increased NO production after 5 min of ischemia, and partly attenuated the increase in NO production after 10 min of ischemia, but had no effect on the increase after 15 min of ischemia. L-NAME completely abolished the increased NO production after different durations of ischemia. The extent of ischemic neuronal damage by 5-min ischemia was aggravated by either 7-NI or L-NAME, while damage by 10-min ischemia was marked in all groups. These results indicate that neuronal and endothelial NO synthases make different contributions to the post-ischemic NO production and the histological outcomes in gerbil striatum.