Familial Screening for the Prevention of Rare Diseases: A Focus on Lipodystrophy in Southern Saudi Arabia.

BACKGROUND: Lipodystrophy is a relatively rare, complex disease characterised by a deficiency of adipose tissue and can present as either generalised lipodystrophy (GLD) or partial lipodystrophy (PLD). The prevalence of this disease varies by region. This study aimed to identify the genetic variations associated with lipodystrophy in the southern part of Saudi Arabia. METHODOLOGY:  We conducted a retrospective study by recruiting nine patients from six families, recruiting the proband whole exome sequencing results or any other genetic test results, screening other family members using Sanger sequencing and analysing the carrier status of the latter. These patients were recruited from the Endocrinology and Diabetes Clinic at Jazan General Hospital and East Jeddah Hospital, both in the Kingdom of Saudi Arabia. RESULT: Eight patients were diagnosed with GLD, and one was diagnosed with PLD. Of the six families, four were consanguineously married from the same tribe, while the remaining belonged to the same clan. The majority of GLD patients had an AGPAT2 c.158del mutation, but some had a BSCL2 c.942dup mutation. The single PLD case had a PPARG c.1024C > T mutation but no family history of the disease. In all families evaluated in this study, some family members were confirmed to be carriers of the mutation observed in the corresponding patient. CONCLUSION:  Familial screening of relatives of patients with rare, autosomal recessive diseases, such as lipodystrophy, especially when there is a family history, allows the implementation of measures to prevent the onset or reduced severity of disease and reduces the chances of the pathogenic allele being passed onto future generations. Creating a national registry of patients with genetic diseases and carriers of familial pathogenic alleles will allow the assessment of preventive measures and accelerate disease intervention via gene therapy.

Perceptions of Saudis Toward Participating in the COVID-19 Convalescent Plasma Clinical Trial.

Introduction The COVID-19 pandemic has been a major public health and economic issue worldwide. Even though vaccines have been developed to reduce the spread of the infection, treating patients remains a significant challenge. This study aims to measure the perceptions of Saudis toward participating in the COVID-19 Convalescent Plasma Clinical Trial. Method A cross-sectional study measuring the perceptions of Saudis toward participating in the COVID-19 Convalescent Plasma Clinical Trial was conducted with participants who had recovered from COVID-19. The study used an online questionnaire covering variables related to demographics, awareness, attitudes, perceptions, and plans for improvement. Results A sample of 1,051 participants participated in the questionnaire. A total of 85% had recovered from COVID-19, only 2.76% had participated in clinical trials before, and 83.44% would participate if they were advised or knew about them. The participants showed a high level of education, with 88% having obtained a degree and most used social media. The results can be biased toward the participants who get their knowledge from social media and hope to learn about things on social media. The gap in knowledge about clinical trials among the participants indicated that certain age groups could be targeted through channels where they communicate the most. Conclusion Engaging the community in clinical trials and educating others about their value by sharing experiences would help promote clinical trials and activate donations.

Recent Methods for the Synthesis of Quinoxaline Derivatives and their Biological Activities.

Quinoxaline derivatives have been incorporated into numerous marketed drugs used for the treatment of various diseases. Examples include glecaprevir (Mavyret), voxilaprevir (Vosevi), Balversa (L01EX16) (erdafitinib), carbadox, XK469R (NSC698215), and becampanel (AMP397). These quinoxaline derivatives exhibit a diverse range of pharmacological activities, including antibacterial, antitubercular, antiviral, anti-HIV, anti-inflammatory, antifungal, anticancer, antiproliferative, antitumor, kinase inhibition, antimicrobial, antioxidant, and analgesic effects. Recognizing the significance of these bioactive quinoxaline derivatives, researchers have dedicated their efforts to developing various synthetic methods for their production. This review aimed to compile the most recent findings on the synthesis and biological properties of quinoxaline derivatives from 2015 to 2023.

Design, synthesis, antimicrobial screening and molecular modeling of novel 6,7 dimethylquinoxalin-2(1H)-one and thiazole derivatives targeting DNA gyrase enzyme.

New 6,7-dimethylquinoxalin-2(1H)-one and hydrazineylidene thiazol-4-one derivatives were synthesized, and evaluated for their in vitro antimicrobial activity. The obtained results revealed marked antimicrobial potential against four bacterial, and two fungal strains. Both 6,7-dimethyl-3-(2-(4-nitrophenyl)-2-oxoethyl)quinoxalin-2(1H)-one (4d), and 2-(2-(9H-fluoren-9-ylidene)hydrazineyl)-5-(2-(p-tolyl)hydrazineylidene)thiazol-4(5H)-one (11b) displayed significant antibacterial and antifungal activities having MIC ranges (1.98-15.6 mg/mL) and (1.98-3.9 mg/mL) compared to Tetracycline and Amphotericin B as standard drugs. In addition, they showed noticeable inhibitory activity against DNA gyrase enzyme. Interestingly the thiazole derivative (11b) showed marked inhibitory activity against DNA gyrase with IC50 = 7.82 ± 0.45 µM better than that of ciprofloxacin. The time-kill kinetics profile of the most active compounds against S. aureus and E. coli microorganisms displayed both concentration dependent and time dependent reduction in the number of viable cells. Furthermore, molecular docking study of both compounds in the DNA gyrase binding site was performed, showing agreement with the in vitro inhibitory activities.

Patterns of Thyroid Cancer Mortality and Incidence in Saudi Arabia: A 30-Year Study.

Thyroid cancer is the most prevalent endocrine cancer among the female population in the Kingdom of Saudi Arabia (KSA) and the ninth most common in the male population in Saudi Arabia. Over the past years, an increasing incidence of thyroid cancer has been reported in Saudi Arabia. However, the etiology of thyroid cancer is still not clear. Therefore, this study aimed to estimate thyroid cancer incidence and mortality trends in Saudi Arabia from 1990 to 2019. The current study utilized the Global Burden of Disease and the Institute for Health Metrics and Evaluation databases to extract prevalence data of thyroid cancer in Saudi Arabia from 1990 to 2019. Moreover, the current project utilizes Global Burden of Disease (GBD) web-based tools to visualize these data. In total, 23,846 cases (17,220 females and 6626 males) were diagnosed with thyroid cancer in Saudi Arabia from 1990 to 2019. The incidence is higher in females than in males. Over these 30 years, women's incidence steadily increased by 15-fold versus a 22-fold increase in men. Moreover, there were 2056 deaths in total caused by thyroid cancer in KSA. The mortality rate in women steadily increased by threefold in the same period. However, the increase in mortality was higher in males (sixfold). A high percentage of YLLs was observed in males, with around 24.8% ranging from 30 to 34 and 40 to 45 years. Thyroid cancer incidence rates have increased exponentially between 1990 and 2019. The expansion of the incidence of thyroid cancer in Saudi Arabia could be due to the increased development in detection and diagnosis. The current study provided evidence of the need to increase awareness and diagnosis in the male population.

Persistent Fever and Cough in a Patient With Good's Syndrome: A Case Report.

Good's syndrome is a rare, acquired immunodeficiency condition characterized by thymoma and hypogammaglobulinemia, which increases the risk of recurrent infections. Immunoglobulin replacement therapy (IgRT) is the key treatment for recurrent infections. We describe the case of a 57-year-old male with a history of an anterior mediastinal mass and a persistent cough lasting for a few years. Based on the clinical history and immunological analysis, he was diagnosed with Good's syndrome. He was being managed conservatively with immunoglobulin until he underwent a thymectomy. Subsequently, he developed his first pneumonia. His conditions gradually worsened despite the initiation of IgRT. He was diagnosed to have hypersensitivity pneumonitis based on strong exposure history, consistent radiological images, and good clinical response to antigen avoidance and steroid therapy. To our knowledge, this is the first case of Good's syndrome with hypersensitivity pneumonitis that was unmasked after immune augmentation by the initiation of IgRT. Moreover, surgical intervention should not be considered unless unavoidable. Additionally, close clinical monitoring and laboratory testing are indicated, and IgRT should be considered when the patient begins to exhibit symptoms to prevent severe infections.

Neonatal Gastric Necrosis and Perforation Treated by Subtotal Gastrectomy and Esogastric Anastomosis: A Case Report.

BACKGROUND Gastric necrosis and perforation are rare life-threatening conditions in preterm neonates, which require urgent diagnosis and surgical intervention. CASE REPORT We report a case of a 4-day-old patient with neonatal gastric necrosis. The patient presented with sudden acute abdominal distension, respiratory distress, and metabolic acidosis. The abdomen was markedly distended, tender, and tympanic with collateral circulation. An X-ray of the abdomen showed a huge pneumoperitoneum. An urgent exploratory laparotomy revealed 2 wide horizontal perforations and necrosis of the fundus and gastric body. Subtotal gastrectomy with esogastric anastomosis was done. Postoperatively, the patient was administered total parenteral nutrition and triple antibiotics and improved gradually. He passed stool and the abdomen was soft, lax, and non-distended and the wound healed. An upper gastrointestinal tract (UGIT) contrast study 1 week after the operation showed no leakage or stricture. The patient was discharged 2 months postoperatively with a bodyweight of 2 kg and was followed in the Outpatient Department (OPD). The patient survived after 80% gastric resection for necrosis of the stomach, which was a unique outcome for this major surgery. CONCLUSIONS Gastric perforation is a rare life-threatening condition in preterm neonates, usually managed by direct closure in layers. Exceptionally, partial gastrectomy is needed, which is a major operation, with a high mortality rate and poor outcome. We present a case of a preterm neonate who survived after 80% gastric resection for stomach necrosis.

Outcome of Orchidopexy in Spigelian Hernia-Undescended Testis Syndrome.

Spigelian hernia-undescended testes (SH-UDT) syndrome is a rare disorder, with only 57 cases reported in the literature. The presentation can be asymptomatic or symptomatic in the form of pain, tenderness, or a lump. We present a case of a 50-day-old boy with SH-UDT syndrome. The patient presented with signs and symptoms of acute intestinal obstruction. Exploration confirmed a Spigelian hernia containing small bowel loops and right undescended testis. Orchidopexy was done after ligation of the hernial sac. A follow-up visit after two years revealed right testicular atrophy.