A disorder clinically resembling cystic fibrosis caused by biallelic variants in the AGR2 gene.

PURPOSE: We sought to describe a disorder clinically mimicking cystic fibrosis (CF) and to elucidate its genetic cause. METHODS: Exome/genome sequencing and human phenotype ontology data of nearly 40 000 patients from our Bio/Databank were analysed. RNA sequencing of samples from the nasal mucosa from patients, carriers and controls followed by transcriptome analysis was performed. RESULTS: We identified 13 patients from 9 families with a CF-like phenotype consisting of recurrent lower respiratory infections (13/13), failure to thrive (13/13) and chronic diarrhoea (8/13), with high morbidity and mortality. All patients had biallelic variants in AGR2, (1) two splice-site variants, (2) gene deletion and (3) three missense variants. We confirmed aberrant AGR2 transcripts caused by an intronic variant and complete absence of AGR2 transcripts caused by the large gene deletion, resulting in loss of function (LoF). Furthermore, transcriptome analysis identified significant downregulation of components of the mucociliary machinery (intraciliary transport, cilium organisation), as well as upregulation of immune processes. CONCLUSION: We describe a previously unrecognised autosomal recessive disorder caused by AGR2 variants. AGR2-related disease should be considered as a differential diagnosis in patients presenting a CF-like phenotype. This has implications for the molecular diagnosis and management of these patients. AGR2 LoF is likely the disease mechanism, with consequent impairment of the mucociliary defence machinery. Future studies should aim to establish a better understanding of the disease pathophysiology and to identify potential drug targets.

Understanding Breast Cancer Awareness, Perceptions, and Screening Practices Among the Population of Jazan, Saudi Arabia: A Cross-Sectional Study.

BACKGROUND:  Breast cancer represents a significant global health challenge, with Saudi Arabia experiencing high incidence rates, particularly among females. Early detection through screening methods such as mammography and breast self-examination offers promise in reducing mortality rates. However, participation in screening remains suboptimal, posing a barrier to effective cancer control. In regions like Jazan, situated in southwestern Saudi Arabia, comprehensive studies on breast cancer awareness and screening practices are lacking. METHODS: This cross-sectional study conducted in Jazan, Saudi Arabia, aimed to comprehensively assess breast cancer awareness, perceptions, and screening practices among the local population. An online survey platform was utilized to reach individuals aged 18 years or older residing in Jazan. Recruitment efforts utilized social media platforms, community networks, and local organizations to ensure diverse representation across socioeconomic backgrounds, education levels, and geographical locations. A meticulously designed questionnaire captured demographic information, breast cancer awareness, knowledge, health-seeking behaviors, screening practices, and barriers to mammogram screening. Participants provided electronic informed consent before self-administering the questionnaire. RESULTS:  The study conducted in Jazan, Saudi Arabia, encompassed 533 participants, predominantly young to middle-aged individuals. Most participants were Saudi nationals (97.6%), employed in the government sector (55.7%), and resided in urban areas (61.0%). Awareness of breast cancer was high, with 98.1% having heard of the disease. However, perceptions of age of onset and prevalence varied. While participants showed varied awareness of breast cancer warning signs and risk factors, family history was a commonly agreed-upon risk factor (54.4%). Health-seeking behavior for breast cancer symptoms varied, with nipple changes prompting the most immediate medical attention (36.4%). Although most participants were aware of self-breast examination (84.6%) and mammograms (56.7%), utilization rates were suboptimal, with barriers including fear (79.7%) and embarrassment (71.5%) hindering mammogram screening uptake. CONCLUSION:  This study provides insights into breast cancer awareness and screening practices among participants in Saudi Arabia. While awareness of breast self-examination and mammography is high, disparities in screening service access persist due to barriers like fear and embarrassment. Addressing these barriers through culturally sensitive interventions and collaborative efforts is crucial for enhancing screening uptake and promoting health equity.

Efficacy of Low-Dose Isotretinoin in the Treatment of Rosacea: A Systematic Review and Meta-Analysis.

Rosacea is a common cutaneous condition caused by persistent, recurring lesions in facial skin vessels. It is a chronic skin condition with a variety of clinical symptoms and an unknown cause. Rosacea begins with the widening of capillaries and a flushed appearance. Following that, telangiectasia appears, and reddened patches persist, particularly on the cheeks and nose. Erythema persists due to repeated vasodilation and telangiectasia. In addition, skin inflammation manifests as papules, pustules, lymphedema, and fibrosis. Despite recent advances in treatment, rosacea, a chronic inflammatory relapsing central facial dermatosis, can be extremely difficult to manage.  The purpose of this meta-analysis and systematic review was to evaluate the effectiveness of low-dose isotretinoin in the treatment of rosacea. Following the guidelines set forth by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA), the researcher employed the following search terms in the EMBASE, Web of Science, PubMed, Cochrane Library, and Google Scholar databases to provide a therapeutic update relevant to clinical practice: "low dose isotretinoin," "isotretinoin and rosacea," "isotretinoin treatment of rosacea," and "effectiveness of isotretinoin in treating rosacea". The search was carried out by the researcher for articles published from February 2019 to February 2024. The articles included were all published in the English language. The overall frequency of patients with adverse events differed significantly between the groups treated with low-dose isotretinoin and the comparators (minocycline, pulsed dye laser, evening primrose oil, Lactobacillus plantarum, doxycycline, combined dose or placebo) (0.80, 95% CI 0.73 to 0.88, p = 0.0001). Sub-group analysis indicated that there was a difference between the interventions used in the treatments all in favor of low-dose isotretinoin treatment. The results showed that the moderate group had RR: 0.76, 95% CI: 0.44-1.30, I2 = 0%; the mild group had RR: 0.94, 95% CI: 0.56-1.57, I2 = 0%; and the group with severe rosacea had RR: 0.73, 95% CI: 0.47-1.13, I2 = 0%. According to this study, rosacea can be treated effectively with low-dose isotretinoin even in patients at severe stages of the disease by using the recommended dose once a week. Further, the intervention has also been shown to have fewer side effects on the patients. Therefore, this study recommends randomized controlled trials to be done to fully investigate the best combination options for isotretinoin on mild to severe rosacea based on the fact that some of the treatments combined have shown to be effective on treatment.

Lead-Free FACsSnI3 Based Perovskite Solar Cell: Designing Hole and Electron Transport Layer.

In recent years, lead-based perovskites solar cells have demonstrated excellent power-conversion efficiency. Despite their remarkable progress, the commercialization of lead-based perovskites is hampered by lead toxicity concerns. The recently discovered non-toxic FACsSnI3 perovskite has the potential to replace lead-based perovskites in solar cell applications. Since the perovskite material FACsSnI3 (FA0.85Cs0.15SnI3) is relatively new, there is a lack of information, particularly regarding the design features required for electron and hole-transport layers for efficient photovoltaic responses. The important variables, such as electron affinity, energy band gap, film thickness, and doping density of both electron and hole-transport layers, were simulated and modeled separately and iteratively in this study to achieve the most efficient photovoltaic response. Finally, the absorber layer thickness of FACsSnI3 perovskite is tuned to achieve a maximum power-conversion efficiency of slightly more than 24%. We hope that the findings of this study will serve as a strong guideline for future research and the design of lead-free perovskite solar cells for efficient photovoltaic responses.

Simulation Design of Novel Non-Fluorine Polymers as Electron Transport Layer for Lead-Free Perovskite Solar Cells.

Significant progress has been made in the advancement of perovskite solar cells, but their commercialization remains hindered by their lead-based toxicity. Many non-toxic perovskite-based solar cells have demonstrated potential, such as Cs2AgBi0.75Sb0.25Br6, but their power conversion efficiency is inadequate. To address this issue, some researchers are focusing on emerging acceptor-donor-acceptor'-donor-acceptor (A-DA'D-A)-type non-fullerene acceptors (NFAs) for Cs2AgBi0.75Sb0.25Br6 to find effective electron transport layers for high-performance photovoltaic responses with low voltage drops. In this comparative study, four novel A-DA'D-A-type NFAs, BT-LIC, BT-BIC, BT-L4F, and BT-BO-L4F, were used as electron transport layers (ETLs) for the proposed devices, FTO/PEDOT:PSS/Cs2AgBi0.75Sb0.25Br6/ETL/Au. Comprehensive simulations were conducted to optimize the devices. The simulations showed that all optimized devices exhibit photovoltaic responses, with the BT-BIC device having the highest power conversion efficiency (13.2%) and the BT-LIC device having the lowest (6.8%). The BT-BIC as an ETL provides fewer interfacial traps and better band alignment, enabling greater open-circuit voltage for efficient photovoltaic responses.

Towards Highly Efficient Cesium Titanium Halide Based Lead-Free Double Perovskites Solar Cell by Optimizing the Interface Layers.

Lead halide perovskites are the most promising compared to the other recently discovered photovoltaic materials, but despite their enormous potential, these materials are facing some serious concerns regarding lead-based toxicity. Among many lead-free perovskites, the vacancy-ordered double perovskite cesium titanium halide family (Cs2TiX6, X = Cl, Br, I) is very popular and heavily investigated and reported on. The main objective of this study is to design and compare an efficient cesium titanium halide-based solar cell that can be used as an alternative to lead-based perovskite solar cells. For efficient photovoltaic requirements, the hole-transport layer and electron-transport layer materials such as PEDOT:PSS and Nb2O5 are selected, as these are the commonly reported materials and electronically compatible with the cesium titanium halide family. For the active layer, cesium titanium halide family members such as Cs2TiCl6, Cs2TiBr6, and Cs2TiI6 are reported here for the devices ITO/Nb2O5/Cs2TiI6/PEDOT:PSS/Au, ITO/Nb2O5/Cs2TiBr6/PEDOT:PSS/Au, and ITO/Nb2O5/Cs2TiCl6/PEDOT:PSS/Au, respectively. To determine the most efficient photovoltaic response, all the layers (PEDOT:PSS, Nb2O5, and active perovskite layer) of each device are optimized concerning thickness as well as doping density, and then each optimized device was systematically investigated for its photovoltaic responses through simulation and modeling. It is observed that the device ITO/Nb2O5/Cs2TiI6/PEDOT:PS/Au shows the most efficient photovoltaic response with little above 18.5% for maximum power-conversion efficiency.

Acute Inflammatory Pericarditis following First Dose of COVID-19 Vaccine (AstraZeneca).

Background: Clinical trials of the COVID-19 vaccine reported the safety and efficacy of mRNA vaccines (AstraZeneca) to help control the disease. Few previous reports have shown various side effects associated with COVID-19 vaccines that vary in severity. The possibility of pericarditis and myocarditis has been observed in people who have received an mRNA COVID-19 vaccine which we are reporting. Acute inflammatory pericarditis can be a rare presentation after receiving the first dose of this vaccine, and it is enriching to share such rare presentations in the era of COVID-19 for better management and outcomes after vaccination. Case Presentation. This is a case of acute inflammatory pericarditis with a small pericardial effusion after receiving the first dose of AstraZeneca COVID-19 vaccine in a healthy adult patient who had no other symptoms suggestive of other viral illness in addition to the negative COVID-19 PCR. A 48-year-old healthy male presented nine days after receiving the first dose of COVID-19 AstraZeneca vaccine. The symptoms started three days after the vaccine, when he complained of progressive retrosternal chest pain with low-grade fever and generalized fatigue, followed by exertional dyspnea after a few days. The diagnosis of acute inflammatory pericarditis with small pericardial effusion was established, and the patient was accordingly treated. One week later, the patient showed significant clinical improvement with the resolution of his pericardial effusion. After 39 days, there was a significant radiological resolution of signs of acute pericarditis. Conclusion: The ongoing COVID-19 outbreak is still under investigation, and guidelines are regularly modified since we are continuously learning about this novel disease, although multiple vaccines have been shown to be effective against COVID-19. However, we report a case of unique clinical manifestation that has not been reported widely in the literature, after receiving the first dose of AstraZeneca COVID-19 vaccine, and that it may help raise awareness of the possible diagnosis and the possibility of inflammatory pericarditis after COVID-19 vaccination.

Intra-articular hip joint osteoid osteoma: Challenging diagnosis and percutaneous radiofrequency ablation treatment.

Atypical intra-articular osteoid osteoma can be difficult to diagnose and challenging to treat. We report a case of a right acetabular subchondral intra-articular osteoid osteoma in a young male patient which was initially diagnosed as femoroacetabular impingement due to its atypical clinical and radiological presentations. After fully working up the patient the lesion was successfully treated with percutaneous CT-guided low-power bipolar radiofrequency ablation using several per procedural articular cartilage thermal protective measures including intra-articular thermocouple, and continuous per procedural joint space cooling with Dextrose 5% solution. A precise RFA electrode placement, using the No-touch technique, and applying different passive and active thermal protective measures were helpful in avoiding collateral damage of the hip joint articular cartilages. atypical intra-articular osteoid osteomas necessitate pertinent correlation between the clinical and radiological presentations. As far as intra-articular or subchondral nidus ablation is concerned, thermal protective measures should be considered.

Unusual Manifestation of Benign Squamous Papilloma of the Uvula: A Case Report and Review of Literature.

Squamous papilloma is an exophytic overgrowth of the soft tissue that is associated with human papillomavirus infection. It is rarely reported in the literature and uncommonly located on the uvula. We report a rare case of a squamous papilloma located in the uvula. Despite the small size of the tumor, the patient complaints were significant to mass-related symptoms. In addition, related literature was reviewed and results were discussed.

Case Report: Klippel-Trenaunay Syndrome - Recurrent Venous Thromboembolism and Vascular Malformation.

Klippel-Trenaunay Syndrome (KTS) is a rare genetic vascular disorder characterized by a limb affected by varicose veins, port wine stains, and hypertrophy of bone and soft tissue. It can also present with vascular malformations in the gastrointestinal tract, liver, spleen, genitourinary tract, and heart. We present a 27-year-old case of KTS diagnosed in adulthood associated with recurrent venous thromboembolism and gastrointestinal bleeding.

M.ALSHEIKH Technique: Modification to the Soft Tissue Reduction in the Baha® Attract Surgery.

To describe a modification to the Baha® Attract surgical technique that aims to enhance skin closure, create smooth skin across the surface of the wound, reduce surgery time, and improve cosmetics of the surgical site. Retrospective chart review. Patients were implanted between 2014 and 2016 at King Fahad General Hospital (KFGH) (Jeddah, Kingdom of Saudi Arabia). 20 adult patients (11 males, 9 females), all eligible for Baha® Attract system. One patient only had a previous Baha® surgery. The normal Baha® Attract surgical technique with modification to the soft tissue reduction stage is described. The mean surgical time was 35.25 min (range 25-55). Bleeding was present but not significant and easily controlled in four patients. All patients received the 4 mm implant. None of the patients experienced severe pain. The postoperative follow-up period was 6 months for 7 patients and 8 months for 13 patients. Patient feedback and monitoring indicates a good hearing performance and comfort in all patients. The modified Baha® Attract surgical method causes less postoperative complication, improve cosmetic effect, and provide shorter operative time compared to the conventional Attract procedure.

A Comparison of Surgical Auditory Nerve Response and Speech Outcomes in Patients with Post-meningitic Deafness and Without Cochlear Osteogenesis Who Underwent Cochlear Implantation.

Objective Patients with post-meningitis deafness remain challenging candidates for cochlear implantation (CI) which can be difficult due to fibrosis or ossification of the inner ear, and their outcomes remain doubtful. We assessed the surgical and audiological outcomes of CI in patients with profound sensorineural hearing loss caused by meningitis and compared those outcomes to patients without cochlear ossification. Methods This retrospective cross-sectional study was carried out at King Fahad General Hospital, Jeddah, Saudi Arabia. Among 246 patients who underwent cochlear implantation, 13 patients with post-meningitic deafness were identified (Group 1). A matched control group, including patients with deafness due to other causes who did not have cochlea osteogenesis, was selected (Group 2). For all patients, data were collected from medical records, including surgical and audiological outcomes. Results Sclerosis of the cochlea was high in Group 1 (46.2%). There were no postoperative surgical complications in either group. Responses of the auditory nerve action potential obtained through auditory response telemetry (ART) or the neural response telemetry (NRT) were recorded. There was no significant difference between the two groups regarding the intraoperative and the postoperative ART or NRT at selected electrodes representing the entire cochlea. Likewise, no significant difference regarding the speech recognition test (SRT) was detected. Conclusions Cochlear implantation is a safe procedure without surgical complications in post-meningitis patients. Furthermore, early CI in children was associated with favorable outcomes in terms of preservation of the auditory nerve response, restoration of speech discrimination, and recognition to levels comparable to patients with deafness due to other causes. Early audiological assessment in meningitis patients is recommended to identify hearing loss and eventually to offer CI.