Objective
Alterations in blood lipid concentrations in anorexia nervosa (AN) have been reported; however, the extent, mechanism, and normalization with weight restoration remain unknown. We conducted ...a systematic review and a meta‐analysis to evaluate changes in lipid concentrations in acutely‐ill AN patients compared with healthy controls (HC) and to examine the effect of partial weight restoration.
Method
A systematic literature review and meta‐analysis (PROSPERO: CRD42017078014) were conducted for original peer‐reviewed articles.
Results
Forty‐eight studies were eligible for review; 33 for meta‐analyses calculating mean differences (MD). Total cholesterol (MD = 22.7 mg/dL, 95% CI = 12.5, 33.0), high‐density lipoprotein (HDL; MD = 3.4 mg/dL, CI = 0.3, 7.0), low‐density lipoprotein (LDL; MD = 12.2 mg/dL, CI = 4.4, 20.1), triglycerides (TG; MD = 8.1 mg/dL, CI = 1.7, 14.5), and apolipoprotein B (Apo B; MD = 11.8 mg/dL, CI = 2.3, 21.2) were significantly higher in acutely‐ill AN than HC. Partially weight‐restored AN patients had higher total cholesterol (MD = 14.8 mg/dL, CI = 2.1, 27.5) and LDL (MD = 16.1 mg/dL, CI = 2.3, 30.0). Pre‐ versus post‐weight restoration differences in lipid concentrations did not differ significantly.
Discussion
We report aggregate evidence for elevated lipid concentrations in acutely‐ill AN patients compared with HC, some of which persist after partial weight restoration. This could signal an underlying adaptation or dysregulation not fully reversed by weight restoration. Although concentrations differed between AN and HC, most lipid concentrations remained within the reference range and meta‐analyses were limited by the number of available studies.
Resumen
Objetivo
En la anorexia nervosa (AN) han sido reportadas alteraciones en las concentraciones de lípidos sanguíneos; sin embargo, la extensión, mecanismo y normalización con la restauración del peso continúa aún desconocida. Hicimos una revisión sistemática y meta‐análisis para evaluar los cambios en las concentraciones de lípidos en pacientes agudamente enfermas de AN comparados con controles sanos (HC) y para examinar el efecto parcial de la restauración de peso.
Método
Una revisión sistemática de la literatura y meta‐análisis (PROSPERO: CRD42017078014) fueron llevados a cabo en artículos originales revisados por pares.
Resultados
Un total de cuarenta y ocho estudios fueron elegibles para revisión; 33 para meta‐análisis calculando las diferencias promedio (MD). Colesterol total (MD = 22.7 mg/dL, 95% CI = 12.5, 33.0), lipoproteína de alta densidad (HDL; MD = 3.4 mg/dL, CI = 0.3, 7.0), lipoproteína de baja densidad (LDL; MD = 12.2 mg/dL, CI = 4.4, 20.1), triglicéridos (TG; MD = 8.1 mg/dL, CI = 1.7, 14.5), y apolipoproteína B (Apo B; MD = 11.6 mg/dL, CI = 2.3, 21.2) fueron significativamente elevados en los pacientes agudamente enfermos de AN en comparación con los controles sanos (HC). Los pacientes con AN parcialmente recuperados de peso tuvieron niveles más elevados de colesterol total (MD = 14.8 mg/dL, CI = 2.1, 27.5) y de LDL (MD = 16.1 mg/dL, CI = 2.3, 30.0). Las diferencias pre‐ versus post‐ restauración de peso en las concentraciones de lípidos no difirieron significativamente.
Discusión
Reportamos evidencia agregada de concentraciones elevadas de lípidos en pacientes agudamente enfermos de AN comparados con controles sanos (HC), algunos de los cuales persisten después de la restauración parcial de peso. Esto podría señalar una adaptación subyacente o desregulación no completamente revertida por la restauración del peso. Aunque las concentraciones difirieron entre AN y HC, la mayoría de las concentraciones de lípidos permanecieron dentro del rango de referencia y los meta‐análisis fueron limitados por el número de estudios disponibles.
HOMER software is a powerful tool for modeling and optimization of hybrid energy system (HES). The main two default control strategies in HOMER are load following (LF) and cycle charging (CC) ...strategies. In these strategies, the decision to use the generator or battery at each time step is made based on the lowest-cost choice. Therefore, these strategies are difficult to be implemented in practice especially in countries with continuous fuel price fluctuations. In this study, a new dispatch strategy based on HOMER-MATLAB Link Controller for an isolated wind/diesel/battery HES is proposed to overcome the limitations of the default HOMER strategies. A detailed technical, economic, and greenhouse gas emission analysis is presented for the system under LF, CC, and the proposed dispatch strategies. Besides offering more realistic optimization, the results show that the proposed strategy offers the best economic and environmental performance with a net present cost of $56473 and annual CO2 emissions of 6838 kg. Furthermore, the sensitivity analysis reveals that the proposed strategy is not affected by the fuel price variation, in opposite to LF, and CC strategies which is affected dramatically by this variation. The findings are of paramount importance towards more realistic and efficient energy management strategies.
•A new dispatch strategy for wind/diesel/battery hybrid energy systems using HOMER-MATLAB Link Controller is proposed.•Overcome HOMER default strategies limitation in dealing with continuous fuel price fluctuations.•The proposed strategy is compared with HOMER default strategies in terms of techno-economic and environmental performance.•Sensitivity analysis is conducted by considering variations in critical parameters.•The proposed strategy is more realistic and has better economic and environmental performance than HOMER default strategies.
Neovascular age-related macular degeneration (nAMD) treatment has been revolutionized by the introduction of vascular endothelial growth factor antagonists (anti-VEGF), but the need for frequent ...intravitreal injections poses a heavy burden to patients and physicians. Evolving anti-VEGF therapies include longer duration agents, approaches that target multiple pathways, topical anti-VEGF agents, sustained-release, and genetic therapies. Abicipar pegol, a designed ankyrin repeat protein (DARPin), demonstrated the ability to maintain stable visual acuity with 12-week dosing, but was not approved by the FDA due to higher than usual rates of intraocular inflammation. Conbercept, a recombinant anti-VEGF fusion protein, has been approved in China, and is in Phase 3 trials globally. KSI-301 is an anti-VEGF antibody biopolymer conjugate that allowed 66% of nAMD patients to maintain at least a 6-month treatment-free interval in Phase 1b studies. OPT-302, an inhibitor of VEGF-C/D, will be tested in phase 3 studies that compare anti-VEGF-A monotherapy against combination therapy with OPT-302. Faricimab is a bispecific anti-VEGF/Ang-2 antibody that upregulates the Tie-2 signaling pathway and promotes vascular stability; it is undergoing phase 3 trials with potential for 12- or 16-week dosing. PAN-90806 is a topical anti-VEGF agent that showed the ability to reduce injection frequency by 79% compared to ranibizumab monotherapy in a phase 1/2a trial. Sustained-release anti-VEGF therapies include the ranibizumab Port Delivery System (in phase 3 studies), GB-102 (Phase 2b), OTX-TKI (phase 1), and Durasert (preclinical). Suprachoroidal delivery of the tyrosine kinase inhibitor, axitinib, is in preclinical studies. Genetic therapies in phase 1 studies include RGX-314 and ADVM-022, which introduce a viral vector that modifes the retina's cellular apparatus to create an anti-VEGF biofactory, potentially serving as a one-time treatment. Further investigation is warranted for drugs and delivery systems that hope to advance visual outcomes and reduce treatment burden of nAMD. Keywords: ADVM-022, age-related macular degeneration, abicipar pegol, CLS-AX, conbercept, faricimab, GB-102, KSI-301, PAN-90806, OTX-TKI, ranibizumab port delivery system, RGX-314, VEGF
Long term success of composite restorations depends greatly on their color stability and esthetic appearance. This study aimed to assess the effects of commonly consumed beverage and bleaching on the ...color of composite restoration.
Two resin composite were used Filtek™ Z350 XT (3M/ESPE) and Briliant EverGlow (Coltene). Fifteen discs were made from each resin composite then baseline color measurements were made. The specimens divided into 3 groups (n=5) according to the storage solution. The storage solutions that used in this study are distilled water, tea and coffee. The specimens were stored in the solutions for 3h/day for 40 days and then second color measurements were done. Specimens were bleached by using of 40% H2O2 Opalescence boost. Then the specimens color were measured for the third time. For measuring color change CIE L* a* b* system was used. The results were statistically analyzed using Two-way analysis of variance (ANOVA) and Bonferroni tests. Level of significance was set at
< 0.05.
In all groups there were a significant color change (∆E>3.3). The discs that were made from Filtek™ Z350 XT (3M/ESPE) and immersed in coffee show the highest color change whereas the discs that were made from Briliant EverGlow and stored in distilled water show the least color change. Significant improvements in the color of specimens were demonstrated after bleaching, however bleaching couldn't restore the composite color to clinically acceptable level (∆E<3.3).
Both tested materials were susceptible to staining in the three-staining solution; Filtek™ Z350 XT showed more staining susceptibility than Briliant EverGlow. In office bleaching reverse some of the effect of staining from the surface of the composite but it couldn't restore the composite color to its original color before staining.
Staining, color change, resin composite, bleaching.
Myelin regeneration is a major therapeutic goal in demyelinating diseases, and the failure to remyelinate rapidly has profound consequences for the health of axons and for brain function. However, ...there is no efficient treatment for stimulating myelin repair, and current therapies are limited to anti-inflammatory agents. Males are less likely to develop multiple sclerosis than females, but often have a more severe disease course and reach disability milestones at an earlier age than females, and these observations have spurred interest in the potential protective effects of androgens. Here, we demonstrate that testosterone treatment efficiently stimulates the formation of new myelin and reverses myelin damage in chronic demyelinated brain lesions, resulting from the long-term administration of cuprizone, which is toxic for oligodendrocytes. In addition to the strong effect of testosterone on myelin repair, the number of activated astrocytes and microglial cells returned to low control levels, indicating a reduction of neuroinflammatory responses. We also identify the neural androgen receptor as a novel therapeutic target for myelin recovery. After the acute demyelination of cerebellar slices in organotypic culture, the remyelinating actions of testosterone could be mimicked by 5α-dihydrotestosterone, a metabolite that is not converted to oestrogens, and blocked by the androgen receptor antagonist flutamide. Testosterone treatment also failed to promote remyelination after chronic cuprizone-induced demyelination in mice with a non-functional androgen receptor. Importantly, testosterone did not stimulate the formation of new myelin sheaths after specific knockout of the androgen receptor in neurons and macroglial cells. Thus, the neural brain androgen receptor is required for the remyelination effect of testosterone, whereas the presence of the receptor in microglia and in peripheral tissues is not sufficient to enhance remyelination. The potent synthetic testosterone analogue 7α-methyl-19-nortestosterone, which has been developed for long-term male contraception and androgen replacement therapy in hypogonadal males and does not stimulate prostate growth, also efficiently promoted myelin repair. These data establish the efficacy of androgens as remyelinating agents and qualify the brain androgen receptor as a promising drug target for remyelination therapy, thus providing the preclinical rationale for a novel therapeutic use of androgens in males with multiple sclerosis.
Amblyopia, the most common visual impairment of childhood, is a public health concern. An extended period of optical treatment before patching is recommended by the clinical guidelines of several ...countries. The aim of this study was to compare an intensive patching regimen, with and without extended optical treatment (EOT), in a randomised controlled trial.
EuPatch was a randomised controlled trial conducted in 30 hospitals in the UK, Greece, Austria, Germany, and Switzerland. Children aged 3–8 years with newly detected, untreated amblyopia (defined as an interocular difference ≥0·30 logarithm of the minimum angle of resolution logMAR best corrected visual acuity BCVA) due to anisometropia, strabismus, or both were eligible. Participants were randomly assigned (1:1) via a computer-generated sequence to either the EOT group (18 weeks of glasses use before patching) or to the early patching group (3 weeks of glasses use before patching), stratified for type and severity of amblyopia. All participants were initially prescribed an intensive patching regimen (10 h/day, 6 days per week), supplemented with motivational materials. The patching period was up to 24 weeks. Participants, parents or guardians, assessors, and the trial statistician were not masked to treatment allocation. The primary outcome was successful treatment (ie, ≤0·20 logMAR interocular difference in BCVA) after 12 weeks of patching. Two primary analyses were conducted: the main analysis included all participants, including those who dropped out, but excluded those who did not provide outcome data at week 12 and remained on the study; the other analysis imputed this missing data. All eligible and randomly assigned participants were assessed for adverse events. This study is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN51712593) and is no longer recruiting.
Between June 20, 2013, and March 12, 2020, after exclusion of eight participants found ineligible after detailed screening, we randomly assigned 334 participants (170 to the EOT group and 164 to the early patching group), including 188 (56%) boys, 146 (44%) girls, and two (1%) participants whose sex was not recorded. 317 participants (158 in the EOT group and 159 in the early patching group) were analysed for the primary outcome without imputation of missing data (median follow-up time 42 weeks IQR 42 in the EOT group vs 27 weeks 27 in the early patching group). 24 (14%) of 170 participants in the EOT group and ten (6%) of 164 in the early patching group were excluded or dropped out of the study, mostly due to loss to follow-up and withdrawal of consent; ten (6%) in the EOT group and three (2%) in the early patching group missed the 12 week visit but remained on the study. A higher proportion of participants in the early patching group had successful treatment (107 67% of 159) than those in the EOT group (86 54% of 158; 13% difference; p=0·019) after 12 weeks of patching. No serious adverse events related to the interventions occurred.
The results from this trial indicate that early patching is more effective than EOT for the treatment of most children with amblyopia. Our findings also provide data for the personalisation of amblyopia treatments.
Action Medical Research, NIHR Clinical Research Network, and Ulverscroft Foundation.
Abstract Background Robot-assisted radical cystectomy (RARC) has evolved as a minimally invasive alternative to open radical cystectomy for patients with invasive bladder cancer. Objective We sought ...to define the learning curve for RARC by evaluating results from a multicenter, contemporary, consecutive series of patients who underwent this procedure. Design, setting, and participants Utilizing the International Robotic Cystectomy Consortium database, a prospectively maintained and institutional review board-approved database, we identified 496 patients who underwent RARC by 21 surgeons at 14 institutions from 2003 to 2009. Measurements Cut-off points for operative time, lymph node yield (LNY), estimated blood loss (EBL), and margin positivity were identified. Using specifically designed statistical mixed models, we were able to inversely predict the number of patients required for an institution to reach the predetermined cut-off points. Results and limitations Mean operative time was 386 min, mean EBL was 408 ml, and mean LNY was 18. Overall, 34 of 482 patients (7%) had a positive surgical margin (PSM). Using statistical models, it was estimated that 21 patients were required for operative time to reach 6.5 h and 8, 20, and 30 patients were required to reach an LNY of 12, 16, and 20, respectively. For all patients, PSM rates of <5% were achieved after 30 patients. For patients with pathologic stage higher than T2, PSM rates of <15% were achieved after 24 patients. Conclusions RARC is a challenging procedure but is a technique that is reproducible throughout multiple centers. This report helps to define the learning curve for RARC and demonstrates an acceptable level of proficiency by the 30th case for proxy measures of RARC quality.
Introduction: Antibiotic resistance is a global threat that has been increasing recently, especially with antibiotic overuse and misuse. The search for new antibiotics is becoming more and more ...indispensable. Methods: Design and synthesis of isatin derivatives as surrogates of SB-239629, a bacterial tyrosine-tRNA synthetases (TyrRS) inhibitor. The newly synthesized compounds were screened for their antimicrobial and antibiofilm activities. Docking studies were used to investigate potential binding modes of these compounds with TyrRS. Results and Discussion: Newly synthesized isatin-decorated thiazole derivatives (7b, 7d, and 14b) have shown potent antimicrobial activities against E. coli, a representative of gram-negative bacteria. Also, 7f showed the best activity against Methicillin Resistant Staphylococcus aureus (MRSA). In addition, 7h and 11f were found to have antifungal activities against Candida albicans equivalent to that of the reference Nystatin. All the new isatin derivatives with antimicrobial activities were found to exhibit strong biofilm distortion effects at half their minimum inhibitory concentrations (MIC). Moreover, thiazole derivatives 11a-f showed promising biofilm formation inhibition. Finally, molecular docking studies were used to investigate possible binding modes of target compounds with S. aureus and E. coli TyrRS. Conclusion: The novel isatin-decorated thiazole derivatives show strong antimicrobial and antifungal activities with potential action on TyrRS. Keywords: 5-bromoisatin, thiosemicarbazone, hydrazonoyl chlorides, thiazoles, Tyrosyl-tRNA synthetases (TyrRS) inhibitors, antimicrobial, molecular docking, MRSA, antibiofilm
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