How is metabolic syndrome related to dyslipidemia?

Godine 1967. Crepaldi je prvi zapazio da se u mnogo ljudi istovremeno pojavljuju pretilost, dislipidemija, šećerna bolest i hipertenzija. Kasnih sedamdesetih godina dvadesetog stoljeća njemački su istraživači takvo nakupljanje stanja nazvali metaboličkim sindromom. Otada je taj sindrom opisivan pod nekoliko naziva kao „sindrom inzulinske rezistencije", „sindrom X", „plurime-tabolički sindrom", te „metabolički sindrom". Sindrom zapravo predstavlja višekomponentnu bolest nastalu kombinacijom načina življenja i čimbenika okoline, s time da su neke populacije pokazale genetičku podložnost za razvoj tog sindroma. Metabolički sindrom povećava rizik za kardiovaskularnu bolest i šećernu bolest tipa 2. Nacionalni program obrazovanja o kolesterolu - Panel liječenja odraslih III (engl. National Cholesterol Education Program - Adult Treatment PanelIII, NCEP-ATP III) prepoznao je metabolički sindrom kao skup abnormalnih stanja koja povećavaju rizik, kako za kardiovaskularnu bolest (KVB), tako i za šećernu bolest tipa 2. Smjernice NCEP-ATP III također su istaknule središnju ulogu abdominalne pretilosti u razvoju tog sindroma. Rastuća prevalencija sindroma ima važne zdravstvene implikacije. Svaka sastavnica metaboličkog sindroma predstavlja potvrđeni čimbenik rizika za KVB, no prisutnost mnogih komponenti rezultira većim rizikom nego zbroj rizika povezanih s pojedinačnim komponentama. Dokazano je, primjerice, da su muškarci s istodobnom prisutnošću hiperin-zulinemije nakon gladovanja, s povišenim koncentracijama apolipoproteina B, te povišenim udjelom malih LDL-čestica imali 20 puta veći rizik razvijanja KVB tijekom petogodišnjeg razdoblja praćenja u studiji, nego muškarci bez tog skupa netradicionalnih biljega rizika. Usto, rizik za KVB povezan s tom aterogenom metaboličkom trojkom ostao je značajan čak i nakon prilagodbe za tradicionalne rizične čimbenike kao što su koncentracije LDL-kolesterola, triglicerida i HDL-kolesterola. Procjena rizika uključuje listu bioloških parametara u kojoj važnu ulogu imaju lipidi, posebice trigliceridi i HDL-čestice. Tradicionalni čimbenici povezani s metaboličkim sindromom su pretilost, inzulinska rezistencija, hiperglikemija, dislipemija, hipertenzija i mikroalbuminurija.The observation that obesity, dyslipidemia, diabetes and hypertension occur simultaneously in many people was first made by Crepaldi in 1967. In the late 1970s this clustering of conditions was termed "metabolic syndrome" by German researchers. Since then the syndrome has been described under a number of guises as "Insulin resistance syndrome", "Syndrome X", "Plurimetabolic syndrome" and the "Metabolic syndrome". The syndrome is a multi-component disease brought on by combination of lifestyle and environmental factors, with some populations exhibiting a genetic susceptibility for its development. Metabolic syndrome increases the risk of cardiovascular disease and type 2 diabetes. The National Cholesterol Education Program - Adult Treatment Panel III (NCEP-ATP III) has recognized the metabolic syndrome as a cluster of abnormalities increasing the risk for both cardiovascular disease (CVD) and type 2 diabetes. The NCEP-ATP III guidelines have also underlined the central role of abdominal obesity in the development of this syndrome. The escalating prevalence of the syndrome has important health implications. Each component of the metabolic syndrome is an established cardiovascular disease risk factor, and the presence of multiple components confer greater risk than the sum of the risks associated with the individual ones. For instance, it has been shown that men with the simultaneous presence of fasting hyperinsulinemia, elevated apolipoprotein B concentration and an increased proportion of small LDL particles were characterized by a 20-fold increase in the risk for developing CVD over the 5-year follow-up period of the study, compared with men without this cluster of non-traditional risk markers. In addition, the risk of CVD associated with the atherogenic metabolic triad remained significant even after adjustment for traditional risk factors such as LDL-cholesterol, triglyceride and HDL-cholesterol levels. Risk assessment includes a list of biological parameters wherein lipids play an important role, especially triglycerides and HDL-particles. The traditional factors associated with the syndrome are obesity, insulin resistance, hypergl-ycemia, dyslipemia, hypertension and microalbuminuria

Customizable and scalable automated assessment of C/C++ programming assignments

The correction of exercises in programming courses is a laborious task that has traditionally been performed in a manual way. This situation, in turn, delays the access by students to feedback that can contribute significantly to their training as future professionals. Over the years, several approaches have been proposed to automate the assessment of students' programs. Static analysis is a known technique that can partially simulate the process of manual code review performed by lecturers. As such, it is a plausible option to assess whether students' solutions meet the requirements imposed on the assignments. However, implementing a personalized analysis beyond the rules included in existing tools may be a complex task for the lecturer without a mechanism that guides the work. In this paper, we present a method to provide automated and specific feedback to immediately inform students about their mistakes in programming courses. To that end, we developed the CAC++ library, which enables constructing tailored static analysis programs for C/C++ practices. The library allows for great flexibility and personalization of verifications to adjust them to each particular task, overcoming the limitations of most of the existing assessment tools. Our approach to providing specific feedback has been evaluated for a period of three academic years in a course related to object-oriented programming. The library allowed lecturers to reduce the size of the static analysis programs developed for this course. During this period, the academic results improved and undergraduates positively valued the aid offered when undertaking the implementation of assignments.Universidad de Cádiz, Grant/Award Numbers: sol-201500054192-tra, sol-201600064680-tra; Ministerio de Ciencia, Innovación y Universidades, Grant/Award Number: RTI2018-093608-B-C33; European Regional Development Fun

Response of maize to different nutrient sources under different landscape positions in cereal mixed farming systems of tropical agroecosystems

Nutrient omission trials were conducted on farmers’ fields in 2020 and 2022. The experiment included nine treatments: three treatments with nitrogen (N), phosphorus (P), potassium (K), sulfur (S), zinc (Zn), and boron (B) as individual, blended, and compound fertilizer; four treatments with the omission of K, S, Zn, or B; NP-only; and control without any nutrient. Treatments were arranged in a randomized complete block design with three replications under foot slope (FS), mid-slope (MS), and hillslope (HS) positions. Results showed that soil properties and maize yield significantly varied among landscape positions, with substantial soil fertility and yield increasing trends from HS to FS position. The highest grain yield (6.18 t ha−1) was recorded at the FS position, with the respective yield increments of 14% and 16% compared to the MS and HS positions. Applying all nutrients in blended form resulted in the highest grain yield (6.52 t ha−1), but it was not significantly different from yields of compound and individual fertilizer forms. Applying all nutrients in blended form increased grain yield by 7.4% and 264.2% compared to the NP-only and the control, respectively, indicating the non-significant effects of K, S, Zn, and B on yield. Overall, N and P are the most yield-limiting nutrients for maize production, and site-specific NP fertilizer recommendations targeting landscape position are required to enhance nutrient use efficiency and sustainably intensify maize yield. Developing site-specific fertilizer recommendations advisory will enhance nutrient use efficiency, increase and sustain yield, and benefit farmers while improving soil and environmental quality

Influence of landscape position on sorghum yield response to different nutrient sources and soil properties in the semi-arid tropical environment

Understanding the response of crops to nutrient applications in undulating landscapes is imperative to improve nutrient use efficiency and crop yield. This study aimed to identify sorghum yield-limiting nutrients and characterize soil properties targeting landscape positions. The field experiments were conducted across 52 sites in four districts, covering three distinct landscape positions during the 2020 and 2022 cropping seasons. The treatments were All-blended, All- compound, All- individual, 150% of All- blended, All- blended-K, All- blended-S, All-blended-Zn, All -blended-B, recommended NP, 50% of All -blended, and control (no fertilizer). Treatment sequencing was randomized using a complete block design under foot slope (FS), mid-slope (MS), and hillslope (HS) positions. Results revealed that landscape position significantly affected the growth and yield of sorghum. Significantly higher yields were obtained from foot slopes than mid-slope and hillslope positions. Yield response to the application of nutrients significantly decreased with increasing slope. Overall, yield among all landscape positions was in the decreasing order of FS>MS>HS. The application of nutrients at different rates significantly improved sorghum total biomass and grain yield. Raising the all-blended treatment rate by 50% increased sorghum yield by 44% and 147% over the application of 50% of all nutrients and the unfertilized control treatment, respectively. Statistically significant yield differences were not observed among blended, compound, and separate applications of nutrients. The omission of K, S, Zn, and B did not show a significant variation in yield over the recommended NP fertilizer. The results of soil analysis results revealed that N and P are the most commonly deficient nutrients in sorghum-growing areas. The mean average volumetric soil moisture content ranged from 5.9-28.7% across landscape positions, with the highest at the foot slope and lowest at the hillslope position. Further research is suggested to determine economically optimum N and P rates across the three landscape positions

Regulation of Bestrophins by Ca2+: A Theoretical and Experimental Study

Bestrophins are a recently discovered family of Cl− channels, for which no structural information is available. Some family members are activated by increased intracellular Ca2+ concentration. Bestrophins feature a well conserved Asp-rich tract in their COOH terminus (Asp-rich domain), which is homologous to Ca2+-binding motifs in human thrombospondins and in human big-conductance Ca2+- and voltage-gated K+ channels (BKCa). Consequently, the Asp-rich domain is also a candidate for Ca2+ binding in bestrophins. Based on these considerations, we constructed homology models of human bestrophin-1 (Best1) Asp-rich domain using human thrombospondin-1 X-ray structure as a template. Molecular dynamics simulations were used to identify Asp and Glu residues binding Ca2+ and to predict the effects of their mutations to alanine. We then proceeded to test selected mutations in the Asp-rich domain of the highly homologous mouse bestrophin-2. The mutants expressed in HEK-293 cells were investigated by electrophysiological experiments using the whole-cell voltage-clamp technique. Based on our molecular modeling results, we predicted that Asp-rich domain has two defined binding sites and that D301A and D304A mutations may impact the binding of the metal ions. The experiments confirmed that these mutations do actually affect the function of the protein causing a large decrease in the Ca2+-activated Cl− current, fully consistent with our predictions. In addition, other studied mutations (E306A, D312A) did not decrease Ca2+-activated Cl− current in agreement with modeling results

Regulation of Bestrophins by Ca2+: A Theoretical and Experimental Study

Bestrophins are a recently discovered family of Cl− channels, for which no structural information is available. Some family members are activated by increased intracellular Ca2+ concentration. Bestrophins feature a well conserved Asp-rich tract in their COOH terminus (Asp-rich domain), which is homologous to Ca2+-binding motifs in human thrombospondins and in human big-conductance Ca2+- and voltage-gated K+ channels (BKCa). Consequently, the Asp-rich domain is also a candidate for Ca2+ binding in bestrophins. Based on these considerations, we constructed homology models of human bestrophin-1 (Best1) Asp-rich domain using human thrombospondin-1 X-ray structure as a template. Molecular dynamics simulations were used to identify Asp and Glu residues binding Ca2+ and to predict the effects of their mutations to alanine. We then proceeded to test selected mutations in the Asp-rich domain of the highly homologous mouse bestrophin-2. The mutants expressed in HEK-293 cells were investigated by electrophysiological experiments using the whole-cell voltage-clamp technique. Based on our molecular modeling results, we predicted that Asp-rich domain has two defined binding sites and that D301A and D304A mutations may impact the binding of the metal ions. The experiments confirmed that these mutations do actually affect the function of the protein causing a large decrease in the Ca2+-activated Cl− current, fully consistent with our predictions. In addition, other studied mutations (E306A, D312A) did not decrease Ca2+-activated Cl− current in agreement with modeling results

Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination: A Phase 3 Randomized, Controlled Trial in Children and Young Infants at 11 African Sites

Background:A malaria vaccine could be an important addition to current control strategies. We report the safety and vaccine efficacy (VE) of the RTS,S/AS01 vaccine during 18 mo following vaccination at 11 African sites with varying malaria transmission.Methods and Findings:6,537 infants aged 6-12 wk and 8,923 children aged 5-17 mo were randomized to receive three doses of RTS,S/AS01 or comparator vaccine.VE against clinical malaria in children during the 18 mo after vaccine dose 3 (per protocol) was 46% (95% CI 42% to 50%) (range 40% to 77%; VE, p<0.01 across all sites). VE during the 20 mo after vaccine dose 1 (intention to treat [ITT]) was 45% (95% CI 41% to 49%). VE against severe malaria, malaria hospitalization, and all-cause hospitalization was 34% (95% CI 15% to 48%), 41% (95% CI 30% to 50%), and 19% (95% CI 11% to 27%), respectively (ITT).VE against clinical malaria in infants was 27% (95% CI 20% to 32%, per protocol; 27% [95% CI 21% to 33%], ITT), with no significant protection against severe malaria, malaria hospitalization, or all-cause hospitalization.Post-vaccination anti-circumsporozoite antibody geometric mean titer varied from 348 to 787 EU/ml across sites in children and from 117 to 335 EU/ml in infants (per protocol).VE waned over time in both age categories (Schoenfeld residuals p<0.001). The number of clinical and severe malaria cases averted per 1,000 children vaccinated ranged across sites from 37 to 2,365 and from -1 to 49, respectively; corresponding ranges among infants were -10 to 1,402 and -13 to 37, respectively (ITT). Meningitis was reported as a serious adverse event in 16/5,949 and 1/2,974 children and in 9/4,358 and 3/2,179 infants in the RTS,S/AS01 and control groups, respectively.Conclusions:RTS,S/AS01 prevented many cases of clinical and severe malaria over the 18 mo after vaccine dose 3, with the highest impact in areas with the greatest malaria incidence. VE was higher in children than in infants, but even at modest levels of VE, the number of malaria cases averted was substantial. RTS,S/AS01 could be an important addition to current malaria control in Africa.Trial registration:http://www.ClinicalTrials.gov NCT00866619. Please see later in the article for the Editors' Summary

IMPLEMENTASI BADAN USAHA MILIK DESA DI DESA KEMBUAN SATU KECAMATAN TONDANO UTARA KABUPATEN MINAHASA

Tujuan utama dari penelitian ini adalah untuk Untuk mendeskripsikan implementasi kebijakan Badan Usaha Milik Desa di Desa Kembuan Satu Kecamatan Tondano Utara Kabupaten Minahasa dan Untuk mendeskripsikan, menganalisis serta menginterpretasikan faktor-faktor determinan implementasi kebijakan Badan Usaha Mlik Desa di Desa Kembuan Satu Kecamatan Tondano Utara Kabupaten Minahasa. Analisis data yang di gunakan dalam penenlitian ini adalah analisis data secara kualitatif. Hasil penelitian menunjukan bahwa Efektivitas dan efisiensi implementasi BUMDesa Kembuan Satu melalui indicator kondisi keberdaan BUMDesa, program kerja, mekanisme pelaksanaan dan system bagi laba serta pelaksanaan monitoring dan evaluasi terhadap unit usaha air bersih sudah berjalan dengan baik sesuai dengan aturan yang ada dan sesuai dengan harapan warga desa, dan Faktor determinan pendukung dalam implementasi BUMDesa ini yakni partisipasi aktif Masyarakat, sumber daya manusia pengurus dan staf yang cukup memadai, penggunaan WA atau kotak saran dan aduan sudah memberikan kontribusi positif dalam meningkatkan layanan air bersih kepada warga Masyarakat desa Kembuan Satu. Sedangkan factor determinan penghambat antara lain: pendampingan dalam bimtek dan peningkatan kompetensi pengurus dan staf BUMDesa kurang maksimal, permodalan yang masih kurang dalam menciptakan berbagai jenis usaha dalam peningkatan perekonomian warga desa, begitu pula kurangnya permodalan dalam mendukung pelayanan penyediaan air bersih dapat dilakukan pada area tertentu serta pembangunan IT dan digitalisasi dalam pelayanan dan pembuatan laporan keuangan belum dilaksanakan secara maksimal

Salting-in with a salting-out agent : explaining the cation specific effects on the aqueous solubility of amino acids

Although the understanding of ion specific effects on the aqueous solubilities of biomolecules is crucial for the development of many areas of biochemistry and life sciences, a consensual and well-supported molecular picture of the phenomena has not yet been established. Mostly, the influence of cations and the nature of the molecular interactions responsible for the reversal of the Hofmeister trend in aqueous solutions of amino acids and proteins are still defectively understood. Aiming at contributing to the understanding of the molecular-level mechanisms governing the cation specific effects on the aqueous solubilities of biocompounds, experimental solubility measurements and classical molecular dynamics simulations were performed for aqueous solutions of three amino acids (alanine, valine, and isoleucine), in the presence of a series of inorganic salts. The evidence gathered suggests that the mechanism by which salting-in inducing cations operate in aqueous solutions of amino acids is different from that of anions, and allows for a novel and consistent molecular description of the effect of the cation on the solubility based on specific interactions of the cations with the negatively charged moieties of the biomolecules