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Background: Cathepsin C gene (CTSC) (MIM#602365) is a lysosomal cysteine proteinase coding gene which encodes for CTSC protein that plays a major role in the activation of granule serine proteases, particularly leukocyte elastase and granzymes A and B. This activity was proposed to play a role in epithelial differentiation and desquamation. Mutations that cause Disruption in the CTSC expression or function will result in loss of immunological response such as defects of phagocytic function and deregulation of localized polymorphonuclears response with subsequent clinical manifestation. Aim: The aim of this study is to detect the mutation in CTSC gene expected to be the cause of Papillon Lefèvre syndrome (PLS) in an Egyptian patient clinically diagnosed as PLS and to characterize the clinical features. Patient and methods: A 5 year and 3 month old girl from the outpatient's Oro-Dental Genetics clinic - National Research Center presented with the typical clinical findings of Papillon Lefevre syndrome. Genomic DNA was extracted from peripheral blood samples of the patient, her parents and 20 healthy Egyptian controls using standard procedures. All exons of the CTSC gene were amplified by PCR. Sequence analysis of the patient, her parents and controls was performed for mutation detection. Results: Mutation analysis of the CTSC gene in our patient revealed a novel homozygous nonsense mutation in exon 5 (W237X). Her parents revealed the presence of the same mutation in a heterozygous state. The 20 controls showed only the wild type sequence of all exons (no mutation). Conclusion: This study reported a novel nonsense mutation in the CTSC gene in an Egyptian patient. This novel nonsense mutation is predicted to produce truncated dipeptidyl-peptidase1 causing PLS phenotype in this patient. [ABSTRACT FROM AUTHOR]

Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne's disease in animals with zoonotic potential; it has been linked to many chronic diseases in humans, especially gastrointestinal diseases (GID). MAP has been extensively studied in Europe and America, but little reports were published from Africa. Sudan is a unique country with close contact between humans and livestock. Despite such interaction, the one health concept is neglected in dealing with cases of humans with GID. In this study, patients admitted to the reference GID hospital in the Sudan over a period of 8 months were screened for presence of MAP in their faeces or colonic biopsies. A total of 86 patients were recruited for this study, but only 67 were screened for MAP, as 19 did not provide the necessary samples for analysis. Both real-time PCR and culture were used to detect MAP in the collected samples and the microbial diversity in patients´ faecal samples was investigated using 16S rDNA nanopore sequencing. In total, 27 (40.3%) patients were MAP positive: they were 15 males and 12 females, of ages between 21 and 80 years. Logistic regression analysis revealed no statistical significance for all tested variables in MAP positive patients (occupation, gender, contact with animal, milk consumption, chronic disease, etc.). A unique microbiome profile of MAP-positive patients in comparison to MAP-negative was found. These findings suggest that a considerable proportion of the population could be MAP infected or carriers. Therefore, increase awareness at community level is urgently needed to decrease the risk of MAP at human/animal interface. This study represents the first report of MAP in humans in the Sudan; nevertheless, a better view of the situation of MAP in humans in the country requires a larger study including patients with other conditions. [ABSTRACT FROM AUTHOR]

Estimation of drill cuttings particle sizes provides near real-time information that can be utilized in drilling operations. The analysis and interpretations of these rock samples is largely manual. Results are qualitative and can be inconsistent. We propose a practical automated method for estimating drill cuttings particle sizes using digital images. The proposed method is robust and combines several well-known and time-tested techniques like: K-means clustering, numerically stable ellipse fitting, and standard morphological operations. Images are first preprocessed and clustered based on color values. The resultant grain mask is enhanced using binary morphological operations. Measurements are then extracted from the mask based on the major and minor axis fitted to the particles. The developed method is tested on drill cuttings digital images from four wells with varying lithologies and particle sizes. Sensitivity analysis on imperfect images shows the robustness of the methodology. The automated results validated against manual measurements show a difference of less than ten percent. Performance of the algorithm is in the order of seconds, which allows for its use in near real-time applications. • A method for automated drill cuttings size estimation is developed. • The automated results validated against manual measurements show a difference of less than ten percent. • The proposed method runtime is in the order of seconds per image, allowing near real-time applications. [ABSTRACT FROM AUTHOR]

Background. Intracellular tenofovir diphosphate (TFV-DP) concentration in dried blood spots (DBSs) is used to monitor cumulative pre-exposure prophylaxis (PrEP) adherence. We evaluated TFV-DP in DBSs following daily oral PrEP (emtricitabine 200 mg/tenofovir diphosphate 300 mg) among pregnant and postpartum adolescent girls and young women (AGYW). Methods. Directly observed PrEP was administered for 12 weeks in a pregnancy (14–24 weeks’ gestation, n = 20) and postpartum (6–12 weeks postpartum, n = 20) group of AGYW aged 16–24 years in sub-Saharan Africa. Weekly DBS TFV-DP was measured by validated liquid chromatography–tandem mass spectrometry assay. Week 12 TFV-DP distributions were compared between groups with Wilcoxon test. Population pharmacokinetic models were fit to estimate steady-state concentrations and create benchmarks for adherence categories. Baseline correlates of TFV-DP were evaluated. Results. Median age was 20 (IQR, 19–22) years. Of 3360 doses, 3352 (>99%) were directly observed. TFV-DP median (IQR) half-life was 10 (7–12) days in pregnancy and 17 (14–21) days postpartum, with steady state achieved by 5 and 8 weeks, respectively. Observed median (IQR) steady-state TFV-DP was 965 fmol/punch (691–1166) in pregnancy versus 1406 fmol/punch (1053–1859) postpartum (P = .006). Modeled median steady-state TFV-DP was 881 fmol/punch (667–1105) in pregnancy versus 1438 fmol/punch (1178–1919) postpartum. In pooled analysis, baseline creatinine clearance was associated with observed TFV-DP concentrations. Conclusions. TFV-DP in African AGYW was approximately one-third lower in pregnancy than postpartum. These Populationspecific benchmarks can be used to guide PrEP adherence support in pregnant/postpartum African women. [ABSTRACT FROM AUTHOR]

Background: Ledipasvir/sofosbuvir increases tenofovir plasma exposures by up to 98% with tenofovir disoproxil fumarate (TDF), and exposures are highest with boosted PIs. There are currently no data on the combined use of the newer tenofovir prodrug, tenofovir alafenamide (TAF), boosted PIs and ledipasvir/sofosbuvir.Objectives: To compare the plasma and intracellular pharmacokinetics and renal safety of TAF with ledipasvir/sofosbuvir when co-administered with boosted PIs.Methods: Persons with HIV between 18 and 70 years and on a boosted PI with TDF were eligible. The study was comprised of four phases: (1) TDF 300 mg with boosted PI; (2) TAF 25 mg with boosted PI; (3) TAF 25 mg with boosted PI and ledipasvir/sofosbuvir; and (4) TAF 25 mg with boosted PI. Pharmacokinetic sampling, urine biomarker collection [urine protein (UPCR), retinol binding protein (RBP) and β2 microglobulin (β2M) normalized to creatinine] and safety assessments occurred at the end of each phase. Plasma, PBMCs and dried blood spots were collected at each visit.Results: Ten participants were enrolled. Plasma tenofovir exposures were 76% lower and tenofovir-diphosphate (TFV-DP) concentrations in PBMCs increased 9.9-fold following the switch to TAF. Neither of these measures significantly increased with ledipasvir/sofosbuvir co-administration, nor did TAF plasma concentrations. No significant changes in estimated glomerular filtration rate or UPCR occurred, but RBP:creatinine and β2M:creatinine improved following the switch to TAF.Conclusions: Ledipasvir/sofosbuvir did not significantly increase plasma tenofovir or intracellular TFV-DP in PBMCs with TAF. These findings provide reassurance that the combination of TAF, boosted PIs and ledipasvir/sofosbuvir is safe in HIV/HCV-coinfected populations. [ABSTRACT FROM AUTHOR]

Background. Helicobacter pylori (H. pylori) is ubiquitous among humans and one of the best-studied examples of an intimate association between bacteria and humans. Phylogeny and Phylogeography of H. pylori strains are known to mirror human migration patterns and reflect significant demographic events in human prehistory. In this study, we analyzed the molecular evolution of H. pylori strains detected from different tribes and regions of Sudan using 16S rRNA gene and the phylogenetic approach. Materials and methods. A total of 75 gastric biopsies were taken from patients who had been referred for endoscopy from different regions of Sudan. The DNA extraction was performed by using the guanidine chloride method. Two sets of primers (universal and specific for H. pylori) were used to amplify the 16S ribosomal gene. Sanger sequencing was applied, and the resulted sequences were matched with the sequences of the National Center for Biotechnology Information (NCBI) nucleotide database. The evolutionary aspects were analyzed using MEGA7 software. Results. Molecular detection of H. pylori has shown that 28 (37.33%) of the patients were positive for H. pylori and no significant differences were found in sociodemographic characteristics, endoscopy series, and H. pylori infection. Nucleotide variations were observed at five nucleotide positions (positions 219, 305, 578, 741, and 763–764), and one insertion mutation (750_InsC_751) was present in sixty-seven percent (7/12) of our strains. These six mutations were detected in regions of the 16S rRNA not closely associated with either tetracycline or tRNA binding sites; 66.67% of them were located in the central domain of 16S rRNA. The phylogenetic analysis of 16S rRNA sequences identified two lineages of H. pylori strains detected from different regions in Sudan. The presence of Sudanese H. pylori strains resembling Hungarian H. pylori strains could reflect the migration of Hungarian people to Sudan or vice versa. Conclusion. This finding emphasizes the significance of studying the phylogeny of H. pylori strains as a discriminatory tool to mirror human migration patterns. In addition, the 16S rRNA gene amplification method was found useful for bacterial identification and phylogeny. [ABSTRACT FROM AUTHOR]

Extensive research on the effect of spark-plasma sintering and free forging on the microstructure, transformation temperature, and superelasticity of Ti-23 at% Nb shape-memory alloys (SMAs) was undertaken. Based on the obtained results, it was found that the specimen showed significant results after deformation than the homogenization step, from which it can be concluded that the deformation has considerable effects on the mechanical properties and shape-memory characteristics of Ti-based SMAs. The microstructure of homogenized and deformed Ti-23 at% Nb SMAs consists of β, α, α′ and ω phases, while the sintered sample shows only β and α phases. Endothermic and exothermic peaks of the austenite ↔ martensite transformation are seen in the homogenized sample, then after being deformed, the exothermic peak disappeared. The highest austenite start and finish temperatures were observed with the deformed sample due to disappearance of TiNb 4 intermetallic compounds and a high percentage of β phase. The ductility of the deformed sample shows the highest value compared with the homogenized sample due the elimination of coarse α precipitates and brittle intermetallic compounds of TiNb 4 , along with the suppression of the brittle ω phase and retaining β matrix. [ABSTRACT FROM AUTHOR]

Objective: The study was to determine the Sudanese pharmacy students' opinions and to measure their satisfaction about education instructions and to reveal their impact on the future carrier. Materials and Methods: Cross-sectional study was conducted by using pretested self-administered questionnaire among final year pharmacy students in Sudan. Results: A total of 455 students from both public and private colleges were participated in the study. Combined one-way direct with interactive method was dominant (74.5%) and was preferred by (74.3%). The English was the major instruction language (62.9%), which was preferred by (66.6%) of the participants. More than 3-quarters of the students had chosen the pharmacy as first choice. Students believed that pharmacy provides good future career. There was a significant association between the students' satisfaction about choosing pharmacy as career and current academic performance (P = 0.004). Conclusion: The obtained results provide an insight into students' opinions on different issues concerning pharmacy education instructions. These data could be utilized as an indicator of the general trends and a guideline for improving pharmacy education in Sudan. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To reach the upper thoracic vertebrae, a number of extensive approaches have been proposed. The purpose of this study is to provide a clear perspective for the selection of surgical approaches in patients who undergo vertebral body resection, reconstruction, and stabilization for upper thoracic and cervicothoracic junction instabilities. Methods: Seventeen patients with upper thoracic or cervicothoracic junction (C7-T6) instability underwent surgery between January 1999 and May 2004. All patients presented with pain and/or neurological deficits. The causes of instabilities were 10 traumas and 7 pathological fractures. The approach chosen was primarily dictated by 3 factors including (1) type of injury, (2) level of lesion, and (3) time of admission. Ventral surgical approach was performed to all pathological and traumatic fractures causing anterior spinal cord compression. Level of lesion determined the selection of the type of ventral surgical approach, namely, supramanubrial, transmanubrial, or lateral transthoracic. On the other hand, combined (anterior and posterior) approach was performed to all late admitted trauma patients. Results: Twelve anterior, 2 combined (anterior and posterior), and 3 posterior approaches were performed in this study. Anterior approaches included 3 transmanubrial, 5 upper lateral transthoracic, and 4 supramanubrial cervical dissection procedures for decompression, fusion, and plate-screw fixation depending on the levels of the lesion. The mean follow-up period was 18 months, ranging from 10 to 58 months. Nonunion or instrument-related complications were not observed. The postoperative neurological conditions were statistically significantly better than the preoperative ones (P = .003). Conclusion: Consideration of the type of injury, level of lesion, and time of admission can provide a perspective for the selection of side of surgical approach for this transitional part of the spinal column. This study also suggests that supramanubrial cervical approach achieves sufficient exposure up to T2, transmanubrial approach for T3, and lateral transthoracic approach below T3. [Copyright &y& Elsevier]

In this article, a Quasi D-Shape dual core Photonic Crystal Fiber Surface Plasmon Resonance sensor is offered and numerically analyzed. The offered model is established comprising of circular air holes having an external sensing polishing layer coated with gold (Au) in order to ensure simple and straightforward design. The performance parameters are examined by means of modal analysis incorporated finite element method utilizing COMSOL multiphysics software. The sensor performance is analyzed with modifying the geometrical parameters like metal (Au) layer and pitch. It is observed; this model shows maximum amplitude sensitivity of 230 RIU−1 and wavelength sensitivity of 15,000 nm-RIU−1 incorporating amplitude interrogation method and wavelength interrogation method, respectively. The Figure of Merit is similarly considered and measured to 45 per RIU inbetween the refractive index ranging 1.42 RIU to 1.46 RIU. As a final point, a comparison has been given among the work explained in this paper with existing works. [ABSTRACT FROM AUTHOR]

The shapes of particles play a crucial role in the transport and mechanical behavior of granular media. How densely particles of a specific shape can be arranged in a given volume has an enormous practical significance for many scientific and industrial fields. We developed a numerical workflow to investigate the effects of irregularly shaped frictionless, convex particles combined with the polydispersity of particle sizes on the porosity, permeability, and elastic bulk modulus of granular porous media. The workflow is based on the computationally generated three‐dimensional granular assemblies of both regular and irregularly shaped particles and pore‐scale simulation of physics to estimate the absolute permeability and elastic bulk modulus of the generated digital granular porous media. Our numerical results show that the porosity decreases by 14–25%, absolute permeability decreases by 45–76%, and elastic bulk modulus increases by 20–66% as we deviate from the regular‐shaped particle with the specified particle size distribution. How rapidly and to what degree these properties of granular assemblies of irregularly shaped particles change depends on particle size distribution. However, once the maximal densest packings of irregularly shaped particles with the prescribed aspect ratio are generated, any further change in the shape of particles has either a minimal impact or an opposite effects are observed. Overall, our numerical observations suggest that the irregular shape of particles has the greatest effect on permeability and the least effect on porosity in both monodisperse and polydisperse granular media. Key Points: We developed a numerical workflow to investigate the effects of irregularly shaped frictionless, convex particles combined with the polydispersity of particle sizes on the physical properties of granular porous mediaHow rapidly and to what degree the properties of granular packings of irregularly shaped particles change depends on the particle size distributionThe irregular shape of particles has the greatest impact on permeability and the least effect on porosity in both monodisperse and polydisperse granular assemblies [ABSTRACT FROM AUTHOR]

Mechanical trapping of fine particles in the pores of granular materials is an essential mechanism in a wide variety of natural and industrial filtration processes. The progress of invading particles is primarily limited by the network of pore throats and connected pathways encountered by the particles during their motion through the porous medium. Trapping of invading particles is limited to a depth defined by the size, shape, and distribution of the invading particles with respect to the size, shape, and distribution of the host porous matrix. Therefore, the trapping process, in principle, can be used to obtain information about geometrical properties, such as pore throat and particle size, of the underlying host matrix. A numerical framework is developed to simulate the mechanical trapping of fine particles in porous granular media with prescribed host particle size, shape, and distribution. The trapping of invading particles is systematically modeled in host packings with different host particle distributions: monodisperse, bidisperse, and polydisperse distributions of host particle sizes. Our simulation results show quantitatively and qualitatively to what extent trapping behavior is different in the generated monodisperse, bidisperse, and polydisperse packings of spherical particles. Depending on host particle size and distribution, the information about extreme estimates of minimal pore throat sizes of the connected pathways in the underlying host matrix can be inferred from trapping features, such as the fraction of trapped particles as a function of invading particle size. The presence of connected pathways with minimum and maximum of minimal pore throat diameters can be directly obtained from trapping features. This limited information about the extreme estimates of pore throat sizes of the connected pathways in the host granular media inferred from our numerical simulations is consistent with simple geometrical estimates of extreme value of pore and throat sizes of the densest structural arrangements of spherical particles and geometrical Delaunay tessellation analysis of the pore space of host granular media. Our results suggest simple relations between the host particle size and trapping features. These relationships can be potentially used to describe both the dynamics of the mechanical trapping process and the geometrical properties of the host granular media. [ABSTRACT FROM AUTHOR]