Optimizacija mikrokapsulacije aktivnog sastojka umrežavanjem i metodom premazivanja za liječenje bolesti debelog crijeva

The aim of this study was to prepare microcapsules based on a natural polymer chitosan solution (high degree of deacetylation (DDA), low molecular weight (MW), and low viscosity)/sodium alginate in the presence of a crosslinking agent (glutaraldehyde), in order to encapsulate and vectorise the active principle towards the diseased organ (colon), without being diffused into other levels of the digestive tract, to increase the therapeutic effectiveness of treatment by chemotherapy and to reduce undesirable effects. The method of preparation of the microcapsules obtained from the sodium alginate/chitosan solution/active ingredients system was examined by conventional optical microscopy. In addition, an in vitro study was carried out on the active ingredients’ release profiles, depending on the pH simulating the gastric and intestinal media for the seven systems proposed. It should be mentioned that, in the basic medium (pH(colon) = 8), the release of the active ingredients is of the utmost importance. Nevertheless, control of this release can be improved by a crosslinking agent and the coating method. The dry [sodium alginate / chitosan solution / active ingredients + crosslinking 2 %] formulation coated with non-crosslinked chitosan (Formulation 7) is the standard formula that meets all the criteria from our earlier work, with a core release rate of 67 %. The PSD was unimodal, with sizes ranging from 750 µm to 900 µm. This work is licensed under a Creative Commons Attribution 4.0 International License.Cilj ove studije bio je pripremiti mikrokapsule na bazi prirodne polimerne otopine kitozana (visokog stupnja deacetiliranja (DDA), niske molekulske mase (MW) i niske viskoznosti)/natrijeva alginata u prisutnosti umreženog agensa (glutaraldehida), za inkapsuliranje i vektoriziranje aktivnog sastojka prema bolesnom organu (debelom crijevu), bez difuzije u druge razine probavnog trakta, kako bi se povećala terapijska učinkovitost liječenja kemoterapijom i smanjili neželjeni učinci. Metoda pripreme mikrokapsula dobivenih iz sustava natrijeva alginata/otopine kitozana/aktivnih sastojaka ispitana je uobičajenom optičkom mikroskopijom. Uz to, provedeno je istraživanje in vitro na profilima oslobađanja aktivnih sastojaka, ovisno o pH koji simulira želučani i crijevni medij za sedam predloženih sustava. Treba napomenuti da je u osnovnom mediju (pH(debelog crijeva) = 8) oslobađanje aktivnih sastojaka od najveće važnosti. Ipak, kontrola tog ispuštanja može se poboljšati sredstvom za umrežavanje i metodom premazivanja. Suha formulacija [otopina natrijeva alginata/kitozana/aktivnih sastojaka + umreženog 2 %] presvučena neumreženim kitozanom (formulacija 7) standardna je formula koja udovoljava svim kriterijima iz našeg ranijeg rada s brzinom otpuštanja jezgre od 67 %. PSD je bio unimodalan s veličinama koje su se kretale od 750 µm do 900 µm. Ovo djelo je dano na korištenje pod licencom Creative Commons Imenovanje 4.0 međunarodna

Cholécystectomie par Célioscopie de Lithiases Biliaires Symptomatiques chez une Jeune Femme de 34 Ans et Revue de la Littérature (Un Cas Clinique)

Introduction : La lithiase biliaire est une pathologie d’une grande fréquence ; elle est le plus souvent asymptomatique, mais peut se compliquer en impactant négativement la qualité de vie. L’ablation de la vésicule sous endoscopie est prometteuse. Nous rapportons un cas clinique pour discuter des modalités thérapeutiques à travers une revue de la littérature. Nous rapportons, l’observation d’une femme de 34 ans avec antécédent obese  Elle nous a consulté en juin 2020 pour des vomissements post prandiaux chroniques avec altération de l’état générale. Les examens paraclinques réalisés n’ont pas révélé une cause évidente. Evacuée à la polyclinique Hammamet à Tunis le diagnostic d’une lithiase vésiculaire a été posé et une ablation sous célioscopie était réalisée avec extraction de 13 gros calculs d’aspect cholestéroliques dont le diamètre moyen de 3 cm, et la pièce opératoire a trouvé un aspect histologique d’une cholécystite chronique diverticulaire en poussée aiguë modérée. La patiente est totalement guérie de sa maladie.   Cholelithiasis is a very common pathology; it is most often asymptomatic, but can become complicated by negatively impacting quality of life. Removal of the gallbladder under endoscopy is promising. We report a clinical case to discuss therapeutic modalities through a review of the literature. We report the observation of a 34-year-old woman with a history of obesity. She consulted us in June 2020 for chronic postprandial vomiting with deterioration in general condition. Paraclinical examinations carried out did not reveal an obvious cause. Evacuated to the Hammamet polyclinic in Tunis, the diagnosis of gallbladder lithiasis was made and an ablation under laparoscopy was carried out with extraction of 13 large cholesterol-looking stones with an average diameter of 3 cm, and the operating specimen found an appearance histology of chronic diverticular cholecystitis in moderate acute attack. The patient is completely cured of her illness. Conclusion: The interest of the work lies in the atypical case of symptomatic cholelithiasis which our technical platform did not allow to easily treat in our country

PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability

The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability. We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants. We next performed functional studies on the disease-associated variants in cultured cells and knock-down of ptpa in Drosophila melanogaster. We first identified a homozygous PTPA variant, c.893T&gt;G (p.Met298Arg), in patients from a South African family with early-onset parkinsonism and intellectual disability. Screening of a large series of additional families yielded a second homozygous variant, c.512C&gt;A (p.Ala171Asp), in a Libyan family with a similar phenotype. Both variants co-segregate with disease in the respective families. The affected subjects display juvenile-onset parkinsonism and intellectual disability. The motor symptoms were responsive to treatment with levodopa and deep brain stimulation of the subthalamic nucleus. In overexpression studies, both the PTPA p.Ala171Asp and p.Met298Arg variants were associated with decreased PTPA RNA stability and decreased PTPA protein levels; the p.Ala171Asp variant additionally displayed decreased PTPA protein stability. Crucially, expression of both variants was associated with decreased PP2A complex levels and impaired PP2A phosphatase activation. PTPA orthologue knock-down in Drosophila neurons induced a significant impairment of locomotion in the climbing test. This defect was age-dependent and fully reversed by L-DOPA treatment. We conclude that bi-allelic missense PTPA variants associated with impaired activation of the PP2A phosphatase cause autosomal recessive early-onset parkinsonism with intellectual disability. Our findings might also provide new insights for understanding the role of the PP2A complex in the pathogenesis of more common forms of neurodegeneration.</p

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Radio k-Labelings for Cartesian Products of Graphs

International audienceFrequency planning consists in allocating frequencies to the transmitters of a cellular network so as to ensure that no pair of transmitters interfere. We study the problem of reducing interference by modeling this by a radio k-labeling problem on graphs: For a graph G and an integer k ≥ 1, a radio k-labeling of G is an assignment f of non negative integers to the vertices of G such that |f(x)−f(y)| ≥ k+1−dG(x,y), for any two vertices x and y, where dG(x,y) is the distance between x and y in G. The radio k-chromatic number is the minimum of max{f(x)−f(y):x,y ∈ V(G)} over all radio k-labelings f of G. In this paper we present the radio k-labeling for the Cartesian product of two graphs, providing upper bounds on the radio k-chromatic number for this product. These results help to determine upper and lower bounds for radio k-chromatic numbers of hypercubes and grids. In particular, we show that the ratio of upper and lower bounds of the radio number and the radio antipodal number of the square grid is asymptotically [3/2]

Linear and cyclic radio k-labelings of trees

Motivated by problems in radio channel assignments, we consider radio k-labelings of graphs. For a connected graph G and an integer k ≥ 1, a linear radio k-labeling of G is an assignment f of non negative integers to the vertices of G such that |f(x) − f(y) | ≥ k + 1 − dG(x, y), for any two distinct vertices x and y, where dG(x, y) is the distance between x and y in G. A cyclic k-labeling of G is defined analogously by using the cyclic metric on the labels. In both cases, we are interested in minimizing the span of the labeling. The linear (cyclic, respectively) radio k-labeling number of G is the minimum span of a linear (cyclic, respectively) radio k-labeling of G. In this paper, linear and cyclic radio k-labeling numbers of paths, stars and trees are studied. For the path Pn of order n ≤ k + 1, we completely determine the cyclic and linear radio k-labeling numbers. For 1 ≤ k ≤ n − 2, a new improved lower bound for the linear radio k-labeling number is presented. Moreover, we give the exact value of the linear radio k-labeling number of stars and we present an upper bound for the linear radio k-labeling number of trees. Keywords: Graph theory; Radio channel assignment; Cyclic and linear radio k-labeling

Radio k-labelings for Cartesian products of graphs

Frequency planning consists in allocating frequencies to the transmitters of a cellular network so as to ensure that no pair of transmitters interfere. We study the problem of reducing interference by modeling this by a radio k-labeling problem on graphs: For a graph G and an integer k ≥ 1, a radio k-labeling of G is an assignment f of non negative integers to the vertices of G such that $|f(x)-f(y)| ≥ k+1-d_G(x,y)$, for any two vertices x and y, where $d_G(x,y)$ is the distance between x and y in G. The radio k-chromatic number is the minimum of max{f(x)-f(y):x,y ∈ V(G)} over all radio k-labelings f of G. In this paper we present the radio k-labeling for the Cartesian product of two graphs, providing upper bounds on the radio k-chromatic number for this product. These results help to determine upper and lower bounds for radio k-chromatic numbers of hypercubes and grids. In particular, we show that the ratio of upper and lower bounds of the radio number and the radio antipodal number of the square grid is asymptotically [3/2]