Is Paromomycin an Effective and Safe Treatment against Cutaneous Leishmaniasis? A Meta-Analysis of 14 Randomized Controlled Trials

Millions of people worldwide are suffering from cutaneous leishmaniasis that is caused by parasites of the genus Leishmania. Although pentavalent antimony compounds are the treatment of choice, their use is limited by high cost, poor compliance, and systemic toxicity. Paromomycin was developed to overcome such limitations. However, there is no consensus on its efficacy. This meta-analysis assessed the efficacy and safety of paromomycin compared with placebo and pentavalent antimony compounds. Fourteen randomized controlled trials, including 1,221 patients, met our selection criteria. Topical paromomycin appeared to have therapeutic activity against the old world and new world cutaneous leishmaniasis, with increased local reactions, when combined with methylbenzethonium chloride. Topical paromomycin was not significantly different from intralesional pentavalent antimony compounds in treating the old world form, whereas it was inferior to parenteral pentavalent antimony compounds in treating the new world form. However, a similar efficacy was found between parenteral paromomycin and pentavalent antimony compounds in treating the new world form. Fewer systemic side effects were observed with topical and parenteral paromomycin than pentavalent antimony compounds. These results suggest that topical paromomycin with methylbenzethonium chloride could be a therapeutic alternative to pentavalent antimony compounds for selected cases of the old world cutaneous leishmaniasis

Pemphigus autoimmunity: Hypotheses and realities

The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients

The separation-preconcentration and determination of ultra-trace gold in water and solid samples by dispersive liquid-liquid microextraction using 4-ethyl-1(2-(4-(4-nitrophenyl)piperazin-1-yl)acetyl)thiosemicarbazide) as chelating agent and flame atomic absorption spectrometry

Soylak, Mustafa/0000-0002-1017-0244WOS: 000431928200014A selective separation and preconcentration method for the determination of gold ions in water and ore samples has been developed using dispersive liquid-liquid microextraction, followed by flame atomic absorption spectrometry. 4-Ethyl-1(2-(4-(4-nitrophenyl)piperazin-1-yl)acetyl)thiosemicarbazide) (NPPTSC) has been used for the first time as new chelating reagent. A mixture of ethanol (dispersive solvent) and carbon tetrachloride (extraction solvent) was used. Some parameters affecting the extraction procedure including the type and volume of the extracting and dispersive solvents, HNO3 concentration, the chelating agent amount, volume of sample, and foreign ions have optimized. Also, the complex formation between gold ions and the ligand has been investigated in a methanol-water solution (1:1) using UV-visible spectrometry. The spectrophotometric titration data showed that of Au-NPPTSC complex composition was found to be 3:2. After optimizing the instrumental and experimental parameters, we achieved a detection limit of 1.5 mu g L-1, a preconcentration factor of 50, and a linear dynamic range of 10.0-400.0 mu g L-1. The relative standard deviation obtained 2.1% at 50 mu g L-1 for gold ions (n = 10). The proposed method was successfully performed for the determination of gold in certified reference material, environmental water, and ore samples.Scientific Research Projects of Giresun University [101016-131]The financial support of the unit of the Scientific Research Projects of Giresun University (Project No.: 101016-131) (Giresun Turkey) is gratefully acknowledged and also gratitude to Karadeniz Technical University (Trabzon, Turkey) for laboratory facilities

Enhanced dynamic functional connectivity (whole-brain chronnectome) in chess experts

Multidisciplinary approaches have demonstrated that the brain is potentially modulated by the long-term acquisition and practice of specific skills. Chess playing can be considered a paradigm for shaping brain function, with complex interactions among brain networks possibly enhancing cognitive processing. Dynamic network analysis based on resting-state magnetic resonance imaging (rs-fMRI) can be useful to explore the effect of chess playing on whole-brain fluidity/dynamism (the chronnectome). Dynamic connectivity parameters of 18 professional chess players and 20 beginner chess players were evaluated applying spatial independent component analysis (sICA), sliding-time window correlation, and meta-state approaches to rs-fMRI data. Four indexes of meta-state dynamic fluidity were studied: i) the number of distinct meta-states a subject pass through, ii) the number of switches from one meta-state to another, iii) the span of the realized meta-states (the largest distance between two meta-states that subjects occupied), and iv) the total distance travelled in the state space. Professional chess players exhibited an increased dynamic fluidity, expressed as a higher number of occupied meta-states (meta-state numbers, 75.8 ± 7.9 vs 68.8 ± 12.0, p = 0.043 FDR-corrected) and changes from one meta-state to another (meta-state changes, 77.1 ± 7.3 vs 71.2 ± 11.0, p = 0.043 FDR-corrected) than beginner chess players. Furthermore, professional chess players exhibited an increased dynamic range, with increased traveling between successive meta-states (meta-state total distance, 131.7 ± 17.8 vs 108.7 ± 19.7, p = 0.0004 FDR-corrected). Chess playing may induce changes in brain activity through the modulation of the chronnectome. Future studies are warranted to evaluate if these potential effects lead to enhanced cognitive processing and if "gaming" might be used as a treatment in clinical practice