Identification and Characterisation of a Novel Pathogenic Mutation in the Human Lipodystrophy Gene AGPAT2 : C48R: A Novel Mutation in AGPAT2.

Loss-of-function mutations in AGPAT2, encoding 1-acylglycerol-3-phosphate-O-acyltransferase 2 (AGPAT2), produce congenital generalised lipodystrophy (CGL). We screened the AGPAT2 gene in two siblings who presented with pseudoacromegaly, diabetes and severe dyslipidaemia and identified a novel mutation in AGPAT2 causing a single amino acid substitution, p.Cys48Arg. We subsequently investigated the molecular pathogenic mechanism linking both this mutation and the previously reported p.Leu228Pro mutation to clinical disease. Wild-type and mutant AGPAT2 were expressed in control and AGPAT2-deficient preadipocyte cell lines. mRNA and protein expression was determined, and the ability of each AGPAT2 species to rescue adipocyte differentiation in AGPAT2-deficient cells was assessed. Protein levels of both p.Cys48Arg and p.Leu228Pro AGPAT2 were significantly reduced compared with that of wild-type AGPAT2 despite equivalent mRNA levels. Stable expression of wild-type AGPAT2 partially rescued adipogenesis in AGPAT2 deficient preadipocytes, whereas stable expression of p.Cys48Arg or p.Leu228Pro AGPAT2 did not. In conclusion, unusually severe dyslipidaemia and pseudoacromegaloid overgrowth in patients with diabetes should alert physicians to the possibility of lipodystrophy. Both the previously unreported pathogenic p.Cys48Arg mutation in AGPAT2, and the known p.Leu228Pro mutation result in decreased AGPAT2 protein expression in developing adipocytes. It is most likely that the CGL seen in homozygous carriers of these mutations is largely accounted for by loss of protein expression

Optimal parameters selection of particle swarm optimization based global maximum power point tracking of partially shaded PV

This paper presents optimal parameters selection of particle swarm optimization (PSO) algorithm for determining the global maximum power point tracking of photovoltaic array under partially shaded conditions. Under partial shading, the power-voltage characteristics have a more complex shape with several local peaks and one global peak. The two proposed controllers include dynamic Particle Swarm Optimization, and constant particle swarm optimization. The developed algorithms are implemented in MATLAB/Simulink platform, and their performances are evaluated. The results indicate that the dynamic particle swarm optimization algorithm can very fast track the GMPP within 128 ms for different shading conditions. In addition, the average tracking efficiency of the proposed algorithm is higher than 99.89%, which provides good prospects to apply this algorithm in the control search unit for the global maximum power point in stations

Comprehensive validation of transient stability calculations in electric power systems and hardware-software tool for its implementation

Reliability and survivability of electric power systems (EPS) depend on transient stability assessment (TSA). One of the most effective way to TSA is time-domain simulation. However, large-scale EPS mathematical model contains a stiff nonlinear system of high-order differential equations. Such system cannot be solved analytically. At the same time, numerical methods are imperfectly applied for such system due to limitation conditions. To make it appropriate, the EPS mathematical model is simplified and additional limitations are used. These simplifications and limitations reduce reliability of simulation results. Consequently, their validation is needed. The most reliable approach to provide it is to compare the simulation results with the field data. However, in practice, there are not enough data for such validation. This paper proposes an alternative approach for validation - the application of a reference model instead of field data. A hardware-software system HRTSim was used as a reference model. This power system simulator has all the necessary properties and capabilities to obtain reliable information required for comprehensive validation of transient stability calculations in EPSs. Main disturbances leading to instability in EPSs are investigated to conduct the validation (processes in cases of faults, single-phase auto-reclosing operation and power system interconnection). Fragments of corresponding experimental studies illustrate the efficiency of the proposed approach. Obtained results confirmed the possibility of the developed approach to identify the causes of numerical calculation errors and to determine disturbances calculated with the significant error. In addition, experimental studies have revealed that numerical calculations error depends on disturbances intensity

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Anal canal carcinoma treatment results: the experience of a single institution

<b>Background and Objectives:</b> Prior to the mid-1980s, the treatment of choice for anal cancer was abdominoperineal resection. Currently, combined chemoradiation is the standard of care. Or objective was to analyze results of treatment for anal canal carcinoma treated with combined chemoradiation. <b>Design and Setting:</b> 0Retrospective review of data in local cancer registry at King Faisal Specialist Hospital and Research Centre (KFSHRC) from a 12-year period (1993 to 2005). <b>Methods:</b> We identified patients with confirmed diagnosis of anal canal squamous cell carcinoma. <b>Results:</b> Of 40 patients identified, 33 were considered eligible for our analysis. All patients were treated by concurrent chemoradiation with mandatory treatment break (MTB) There were 10 (30&#x0025;) local recurrences. Five-year progression-free survival (PFS) was 50.9&#x0025;; overall survival (OS) at 5 years was 73.4&#x0025;. Patients with stage II disease had a median PFS period of 10 years, with no relapses until their last follow-up. There was no statistically significant difference in PFS between patients with stage IIIA disease and those with stage IIIB disease-44.7&#x0025; and 45&#x0025;, respectively (<i>P</i>=.8). Five-year PFS according to &#x2032;T&#x2032; stages was as follows: T1, 66&#x0025;; T2, 71&#x0025;; T3, 59&#x0025;; T4, 30&#x0025; (<i>P</i>&gt;.05). The 5-year colostomy-free survival (CFS) for all patients was 74&#x0025;. Distant metastases were observed in 4 patients. <b>Conclusion:</b> Combined chemoradiation in treatment of anal cancer is effective in terms of local control and sphincter preservation. Five-year estimates of PFS, OS, as well as CFS, in patients treated with a MTB were surprisingly comparable to those determined in most non-MTB series. However, we reported a higher local failure rate, for which we are reevaluating our treatment protocol

Rumen fermentation and microbiota in Shami goats fed on condensed tannins or herbal mixture

Abstract Background Phytochemical compounds can modify the rumen microbiome and improve rumen fermentation. This study evaluated the impact of supplementation with tannin and an herbal mixture containing ginger (Zingiber officinale), garlic (Allium sativum), Artemisia (Artemisia vulgaris), and turmeric (Curcuma longa) on the rumen fermentation and microbiota, and histology of rumen tissue of goats. Eighteen Shami male goats were divided into three groups (n = 6): non-supplemented animals fed the basal diet (C, control); animals fed basal diet and supplemented with condensed tannin (T); and animals fed basal diet and supplemented with herbal mixture (HM). Each animal received a basal diet composed of Alfalfa hay and a concentrate feed mixture. Results Group HM revealed higher (P < 0.05) rumen pH, total volatile fatty acids (VFA), acetic, propionic, isobutyric, butyric, isovaleric, and valeric. Principal Co-ordinate analysis (PCoA) showed that rumen microbial communities in the control group and supplemented groups were distinct. The supplementation increased (P < 0.05) the relative abundances of phylum Bacteroidota and Proteobacteria and declined (P < 0.05) Firmicutes and Fibrobacterota. Additionally, the dominant genus Prevotella and Rikenellaceae RC9 gut group were increased (P < 0.05) and the family Ruminococcaceae was declined (P < 0.05) due to the supplementation. The supplementation decreased (P < 0.05) the archaeal genus Methanobrevibacter and increased (P < 0.05) Candidatus Methanomethylophilus. Tannin supplementation in T group shortened the rumen papillae. Conclusions The results revealed that the herbal mixture might be used to alter the rumen microbiota to improve rumen fermentation

Workshop Tunisie

Mahdia, ville millénaire tunisienne à l’âme marine, s’interroge sur le devenir de sa pierre. Son développement urbain côtoie aujourd’hui un nouvel horizon : la ligne de crête d’un ancien cordon littoral où se situent ses carrières. Exploitées, appropriées comme jardin nourricier et également délaissées, celles-ci s’intègrent au devenir de la ville. À peine visible de l’espace urbain, ces carrières ne sont pas des lieux communs. Elles font partie de son histoire. Le défi actuel est qu’elles contribuent aux desseins de cette ville, à son renouveau. Fruit d’une expérience internationale originale qui réunit étudiants, professeurs et experts en architecture de paysage, en architecture, en urbanisme et en études touristiques, ce livre raconte le travail d’expérimentation sur la réhabilitation paysagère des carrières de Mahdia. Misant sur l’apport créatif d’un arrimage culturel entre le Maghreb, le Moyen-Orient, l’Europe et l’Amérique du Nord, le workshop ravive les natures bien singulières des carrières et de leurs contextes. Et surtout, il expose un ensemble d’intentions en vue de leur mise en valeur et de leur développement. Véritable legs pour les citoyens de cette ville méditerranéenne, l’invention paysagère des carrières de Mahdia livre des solutions d’aménagement inédites en quête d’un lendemain