Formulation and evaluation of topical halofuginone gel using a novel ex vivo model

Purpose: To formulate and study the kinetics of delivery and retention of three  halofuginone (HF) gels via different wall layers of an ex vivo model mimicking  urethral tissue.Methods: Three HF hydrogels (a, b and c) of the same concentration (0.03 % w/v) incorporating different levels of sodium carboxymethyl cellulose (Na-CMC), were prepared. The viscosity of the different gels was studied at 37 °C and at room temperature. The release of HF from these hydrogels and its diffusion into urethral tissue were evaluated using a new ex vivo model mimicking human urethral tissue. The amount of HF was determined by HPLC method.Results: The release of HF increased with increasing viscosity and duration of contact. Gel c showed the best drug release after 2 h of diffusion, with 65.7 % HF in the wall of the ureter. The model showed a uniform distribution of the drug throughout the ureter tissue. In comparison, HF was not detected in the receiver compartment until 2 h.Conclusion: Topical HF gel application is a suitable solution for the potential treatment of urethral stricture and/or recurrence. The formulation and  characterization of the ureter model should facilitate the development of new therapeutics for urethral diseases.Keywords: Halofuginone gel, Urethra, Wall diffusion, Urethral stenosi

Women’s political empowerment as a tool to combat corruption

تأتي المساواة بين الجنسين على رأس الاهتمامات الدولية، باعتبارها معطى اساسي للوصول الى حقوق المرأة والقضاء على جميع اشكالا التمييز ضدها. وتعتبر زيادة مستوى المشاركة السياسية للمرأة أحد مظاهر تحقيق المساواة بين الجنسبن . وضمن  هذا سياق تم  الإشارة والتأكيد  على فرضية أن المرأة يمكن أن تكون قوة سياسية فعالة لمكافة الفساد باعتباره ظاهرة عالمية؛ فهن أقل انخراطا  في الفساد من الرجال،  وعليه فإن التمكين السياسي للمرأة وزيادة معدلات مشاركتها في الحياة السياسية  سيقلل من  مستويات الفساد في المجتمع. "فرضية الجنس الأكثر عدالة"، وهي الفرضية التي تبناها  البنك الدولي، الذي حدد  المساواة بين الجنسين كأداة مهمة لكبح نشوء الفساد سنة 2001 ومذ ذاك قامت مناقشات جادة حول العلاقة بين الفساد والجنس. في هذه الورقة البحثية تم اختبار هذه الفرضية وأسسها ثم مدى تطبيقها والنتائج التي حققتها تحت عنوان: التمكين السياسي للمرأة كأداة لمكافحة الفساد.Gender equality, women's political participation is at the top of international attention. Within this context, the hypothesis that women are an effective political force against corruption was indicated and emphasized as a global phenomenon because they are less involved in it, and therefore the political empowerment of women by increasing their participation in political life will reduce levels of corruption in society. This is the "fairer sex hypothesis" that it adopted by The World Bank, which identified gender equality as an important tool to curb the emergence of corruption in 2001. this paper tested this hypothesis, its foundations, and the extent of its application and results achieved

Moisture sorption isotherms and thermodynamic properties of Asteriscus graveolens leaves

Asteriscus graveolens is a medicinal and aromatic plant which has been used to treat several diseases.Moisture equilibrium data of the plant leaves were determined by using the gravimetric static method at 30°C, 40°C, and 50°C for water activity

Congenital adrenal hyperplasia due to 11-Beta-hydroxylase deficiency in a Tunisian family

Congenital adrenal hyperplasia refers to a group of rare genetic disorders affecting the adrenal glands. 21-hydroxylase deficiency is the most prevalent and the most studied cause while the remaining enzymatic defects are less common, accounting for less than 10% of cases. We herein described the clinical, biological and molecular characteristics and outcome of patients of the same family diagnosed with 11-Beta-hydroxylase deficiency. The disorder was revealed by peripheral precocious puberty between the age of 2-3 years in males and by the virilization of the external genitalia in females. Genetics finding a homozygous p.Gly379Val mutation in the CYP11B1 gene. All patients received hydrocortisone supplementation therapy and mineralocorticoid-receptor antagonist. The females underwent a surgical correction of the ambiguous genitalia at the neonatal age. Long term follow-up revealed metabolic syndrome, obesity and hypertension in the first two patients, an impaired final height in the two females and hypokalemia in three patients

Modélisation des écoulements dans une mèche en pierres en canal

Dans cette étude, on s'intéresse aux écoulements dans un milieu poreux constitué de blocs de différentes dimensions. L'objectif de l'étude expérimentale, est de déterminer les pertes de charge pour différentes configurations l'écoulement, afin de vérifier la formule de Stephenson. Celle ci permet d'exprimer la perte de charge en fonction de la pente du canal, du débit, de la section du canal et des caractéristiques géométriques des pierres. Des essais ont été réalisés dans un nouveau canal rectangulaire construit à l'INAT, ayant une longueur 10 m, une largeur de 0.8 m et une hauteur de 0.6 m (Soualmia et al., 2012). Différentes conditions hydrodynamiques ont été réalisées pour des débits, et des tailles du milieu poreux variables. Les résultats de simulations des différents essais (à deux pentes différentes), ont été comparés aux résultats expérimentaux, une concordance correcte a été notée. Une étude de sensibilité à la forme de ligne d'eau montre qu'une expression de la perte de charge en α.V² permet de reproduire correctement la ligne d'eau mesurée. Parmi les termes composant le paramètre α de Stephenson, la porosité est le terme le plus sensible. Ceci est le travail préliminaire à d'autres expérimentations et améliorations en perspectives

Case report: 7p22.3 deletion and 8q24.3 duplication in a patient with epilepsy and psychomotor delay—Does both possibly act to modulate a candidate gene region for the patient’s phenotype?

Background: Psychomotor delay, epilepsy and dysmorphic features are clinical signs which are described in multiple syndromes due to chromosomal imbalances or mutations involving key genes implicated in the stages of Early Embryonic Development. In this context, we report a 10 years old Tunisian patient with these three signs. Our objective is to determine the cause of developmental, behavioral and facial abnormalities in this patient.Methods: We used banding cytogenetics (karyotype) and Array Comparative Genomic Hybridization (Array CGH) to this purpose.Results: The karyotype was in favor of a derivative of chromosome 7 in the patient and Array CGH analysis revealed a loss of genetic material in 7p22.3-p22.1 (4,56 Mb) with a gain at 8q24.23-q24 (9.20 Mb) resulting from maternal 7/8 reciprocal translocation. An in silico analysis of the unbalanced region was carried out and showed that the 7p22.3-p22.1 deletion contains eight genes. Among them, BRAT1 gene, previously described in several neurodevelopmental diseases, may be a candidate gene which absence could be correlated to the patient’s phenotype. However, the 8q24.23-q24 duplication could be involved in the phenotype of this patient.Conclusion: In this study, we report for the first time a 7p deletion/8q duplication in a patient with psychomoteur delay, epilepsy and facial dysmorphism. Our study showed that Array CGH still useful for delivering a conclusive genetic diagnosis for patients having neurodevelopmental abnormalities in the era of next-generation sequencing

Islamism and the state after the Arab uprisings: Between people power and state power

The authors would like to thank the Arts and Humanities Research Council for facilitating the research for this article through their support of the research network People Power versus State Power of the Centre for the Advanced Study of the Arab World.This paper examines the trajectories of different Islamist trends in the light of the Arab uprisings. It proposes a distinction between statist and non-statist Islamism to help understand the multiplicity of interactions between Islamists and the state, particularly after 2011. It is outlined how statist Islamists (Islamist parties principally) can contribute to the stabilization and democratization of the state when their interactions with other social and political actors facilitate consensus building in national politics. By contrast when these interactions are conflictual, it has a detrimental impact on both the statist Islamists, and the possibility of democratic politics at the national level. Non statist-Islamists (from quietist salafi to armed jihadi) who prioritize the religious community over national politics are directly impacted by the interactions between statist Islamists and the state, and generally tend to benefit from the failure to build a consensus over democratic national politics. Far more than nationally-grounded statist Islamists, non-statist Islamists shape and are shaped by the regional dynamics on the Arab uprisings and the international and transnational relations between the different countries and conflict areas of the Middle East. The Arab uprisings and their aftermath reshaped pre-existing national and international dynamics of confrontation and collaboration between Islamists and the state, and between statist and non-statists Islamists, for better (Tunisia) and for worse (Egypt).PostprintPeer reviewe

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed