Alopecia areata (AA) is a common non-scarring hair loss disease of defined patterns with varied patches size and body sites. The etiology of AA has a complex basis of autoimmunity, environment, and genetic variations. The latter factor is found to play a crucial role in AA risk. Thus, this study aimed to investigate the potential impact of specific immune-related gene polymorphisms among a cohort of Jordanian patients, which was previously reported in other populations. Blood samples of AA patients and control subjects were collected for genomic DNA (gDNA) extraction. Targeted single nucleotide polymorphisms (SNPs) of MASP2, TLR1, CTLA4, and C11orf30 were genotyped in duplicate using the Sequenom MassARRAY® system (iPLEX GOLD). Genotype and allele analysis reveals statistical differences in TLR1 rs4833095 (allele C, P = 0.044), MASP2 rs2273346 (genotype AA, P = 0.0026), and C11orf30 rs2155219 (genotype GG, P = 0.0069) distribution. These findings present the significant contribution of genetic variations in AA susceptibility in the Jordanian population, which is infrequently studied.

Interleukin-1-receptor-associated kinase 4 (IRAK4) possesses a crucial function in the toll-like receptor (TLR) signaling pathway, and the dysfunction of this molecule could lead to various infectious and immune-related diseases in addition to cancers. IRAK4 genetic variants have been linked to various types of diseases. Therefore, we conducted a comprehensive analysis to recognize the missense variants with the most damaging impacts on IRAK4 with the employment of diverse bioinformatics tools to study single-nucleotide polymorphisms’ effects on function, stability, secondary structures, and 3D structure. The residues’ location on the protein domain and their conservation status were investigated as well. Moreover, docking tools along with structural biology were engaged in analyzing the SNPs’ effects on one of the developed IRAK4 inhibitors. By analyzing IRAK4 gene SNPs, the analysis distinguished ten variants as the most detrimental missense variants. All variants were situated in highly conserved positions on an important protein domain. L318S and L318F mutations were linked to changes in IRAK4 secondary structures. Eight SNPs were revealed to have a decreasing effect on the stability of IRAK4 via both I-Mutant 2.0 and Mu-Pro tools, while Mu-Pro tool identified a decreasing effect for the G198E SNP. In addition, detrimental effects on the 3D structure of IRAK4 were also discovered for the selected variants. Molecular modeling studies highlighted the detrimental impact of these identified SNP mutant residues on the druggability of the IRAK4 ATP-binding site towards the known target inhibitor, HG-12-6, as compared to the native protein. The loss of important ligand residue-wise contacts, altered protein global flexibility, increased steric clashes, and even electronic penalties at the ligand–binding site interfaces were all suggested to be associated with SNP models for hampering the HG-12-6 affinity towards IRAK4 target protein. This given model lays the foundation for the better prediction of various disorders relevant to IRAK4 malfunction and sheds light on the impact of deleterious IRAK4 variants on IRAK4 inhibitor efficacy.

Background: A widely studied model of hypoxia is represented by high altitude (HA). Hence, HA hypoxia (HAH) is a challenge for people residing in or visiting high altitudes (Young and Reeves, 2002). Adaptation to HAH affects the homeostasis of several organs and the endocrine and metabolic functions. The aim of this study was to investigate the effect of HAH on the rat’s semen and oxidative stress parameters. Methods: This experimental study was carried out at Abha city, Saudi Arabia, high altitude, 2,800 m above sea level; Jazan city, 43 m above sea level, low altitude. A total of 72 rats were used in this study—8 rats as control; groups 1, 2, and 3 each of 8 rats and group 4 of 40 rats were kept at high altitude for 8, 16, 24, and 32 days, respectively. From group 4, 32 rats were taken to low altitude to testify the reversibility of the semen parameters. Results: There were significant gradual decreases in the number and motility of the epididymal sperms in groups of rats exposed to HA during the first 3 weeks of HA exposure (HG1-HG3) with a maximum decreases to be seen in HG3 (− 57.3 and − 39.1%, respectively). However, the sperm count started to recover gradually on week 4 of HA exposure (HG4) and during all the periods of the reversal protocol achieved by returning the rats to the LA area (RG1-RG4). The maximum improvement in the sperm count and motility was seen in RG3 and RG4 which were not significantly different when compared with each other. The ANOVA test revealed that, in spite of the improvement in the sperm count which reach (109.3 ± 6.057 and 113.9 ± 8.967) in RG3 and RG4, their levels remained significantly low as those obtained in the control LA rats (129.2 ± 11.67). Conclusion: Exposure of rats to hypoxia resulted in a decrease in the sperm count and motility and an increase in the sperm morphological abnormalities. To conclude, the current study showed that the adverse effect of hypobaric hypoxia on semen parameters is transient and reversible.

The study was carried out at two different altitudes in the southern region of Saudi Arabia: Abha, 2,800 meters above sea level, the high altitude (HA) area and Jazan, 40 meters above sea level the low altitude (LA) area. Following exposure to high altitude, and up to the third week of postnatal development, some of the seminiferous tubules showed detachment from the basal lamina, spaces of different sizes within the epithelial layer with vacuoles in the center and Pyknotic nuclei were noted in the spermatogonia and primordial germ cells. Rounded spermatids were seen in the lumen only on day 35 of hypoxic group, no spermatozoa were recognized until day 45 of postnatal development. On day 45 hypoxic rat testes revealed various types of atrophy and degeneration in the seminiferous tubules and in the interstitial tissue, there was detachment of the basal laminae of the tubules and a profound decrease in cellularity. Significant decrease in epithelial height was noticed in these animals (P <0.05). Also, the diameter of the tubules showed slight decrease with concomitant increase in interstitial spaces in all hypoxic rats.

Hepatobiliary surgery through laparoscopic approach is becoming a routine. Knowledge of extrahepatic arterial tree is essential for surgical and imaging procedures. Anatomical complexity is expected since the liver is developed by mergingof lobules with its separate blood supply. This makes a wide range of variations in the pattern of vascular arrangement and so reinforces the need for an accurate understanding of full spectrum of variations. This study aimed to investigate the variations in origin and distribution of extrahepatic arterial supply. Fifty volunteers (32 males and 18 females) aged 20–70 years were randomly recruited from the department of CT scan in Al Amal Hospital, Khartoum North, Sudan. The patients were already candidates for CT angiography with contrast for conditions other than hepatobiliary diseases. The reported data is related to those who accepted to participate in the study. Patients with history of hepatobiliary disease were excluded. 3D views of the scans were treated and the extrahepatic arterial tree was traced in a computer-based software. Key findings suggest that Michel’s classification was considered the standard template for description – 76% of them showed Michel’s type I classification. Types III and V constituted about 2%. About 4% of the cases were represented by types VI and IX. Other types of variations constituted about 12%. To conclude, although type I classification which describes the textbook pattern of hepatic artery distribution was significantly detected among the Sudanese population, other variants were to be considered since they are related to major arteries like aorta and superior mesenteric.