Biallelic NAA60 variants with impaired n-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications.

Primary familial brain calcification (PFBC) is characterized by calcium deposition in the brain, causing progressive movement disorders, psychiatric symptoms, and cognitive decline. PFBC is a heterogeneous disorder currently linked to variants in six different genes, but most patients remain genetically undiagnosed. Here, we identify biallelic NAA60 variants in ten individuals from seven families with autosomal recessive PFBC. The NAA60 variants lead to loss-of-function with lack of protein N-terminal (Nt)-acetylation activity. We show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro. In cells, loss of NAA60 caused reduced surface levels of SLC20A2 and a reduction in extracellular phosphate uptake. This study establishes NAA60 as a causal gene for PFBC, provides a possible biochemical explanation of its disease-causing mechanisms and underscores NAA60-mediated Nt-acetylation of transmembrane proteins as a fundamental process for healthy neurobiological functioning.

Stroke and high-risk TIA outcomes with reduction of treatment duration when treatment initiated in emergency rooms (SHORTER-study).

BACKGROUND: Following transient ischemic attack (TIA) and minor stroke, the risk of recurrent stroke can be significantly reduced with short-duration dual antiplatelet therapy (DAPT). We wish to investigate whether 10 days of DAPT is as effective as 21 days' treatment. STUDY DESIGN: This is an open-label, randomized, parallel-group study comparing whether 10 days of DAPT treatment (ASA + clopidogrel) is non-inferior to 21 days of DAPT in patients with acute ischemic stroke (AIS) or high-risk TIA. In both groups, DAPT is started within 24 hours of symptom onset. This study is being conducted in approximately 15 study sites in the Kingdom of Saudi Arabia. The planned sample size is 1932. OUTCOMES: Non-inferiority of 10 days compared to 21 days of DAPT in the prevention of the composite endpoint of stroke and death at 90 days in AIS/TIA patients. The primary safety outcome is major intra-cranial and systemic hemorrhage. STUDY PERIOD: Enrolment started in the second quarter of 2023, and the completion of the study is expected in the fourth quarter of 2025. DISCUSSION: The trial is expected to show that 10 days of DAPT is non-inferior for the prevention of early recurrence of vascular events in patients with high-risk TIAs and minor strokes.

Teaching medical ethics and medical professionalism in Saudi public and private medical schools.

Medical ethics and professionalism are two essential parts of building up the identity of a competent physician. This study was conducted to determine the nature, content, and methods of medical ethics and professionalism education in Saudi public and private medical schools. It also sought to identify the challenges and obstacles in teaching and assessing medical ethics and professionalism and suggest appropriate changes. A cross-sectional study was carried out in Saudi private and public medical schools. To achieve the study's aim, an assessment tool in the form of a novel self-administered questionnaire was developed, piloted, and then used. A representative from each of the 28 Saudi medical schools participated in the study. Twenty-four (82.1%) responding medical schools have no medical ethics department. Most of the medical schools (64.2%) have 25% or less of their faculty staff who teach ethics holding a qualification in medical ethics. Most schools have a specific course for medical ethics and professionalism (85.7% and 57.1%, respectively). Multiple-choice questioning is the most popular assessment method in medical ethics and professionalism courses (89.3% and 60.7%, respectively). The need for more qualified staff and clear guidelines/resources is a significant drawback to the teaching of medical ethics. Therefore, the study recommends developing national guidelines dedicated to the undergraduate teaching curriculum from which courses would be designed to enhance medical ethics and medical professionalism.

Invasive fungal infection of the brain caused by Neoscytalidium dimidiatum in a post-renal transplant patient: A case report.

Neoscytalidium is a phytopathogen that is often found in plants and soil. It mostly leads to skin and nail infections, and invasive diseases of the sinuses, lung, and brain have been described mostly in immunocompromised patients. We report a case of a post-renal transplant patient who received anti-thymocyte globulin for induction immunosuppression. A month after her transplant, she presented with fever and new-onset seizures, and computed tomography revealed a brain abscess with mass effects and herniation. The patient underwent abscess drainage and craniectomy. The pathological findings showed filamentous septate hyphae. The surgical culture rapidly grew wool-like colonies with a black reverse on Sabouraud agar. Lactophenol cotton blue staining showing septate branched hyphae with one to two arthroconidia cells with flattened ends. The patient was given a combination of amphotericin B and voriconazole but unfortunately died ten days after the diagnosis. This case highlights Neoscytalidium as a cause of invasive fungal disease in immunocompromised patients that is difficult to treat and is often fatal, even when combined surgical and medical therapies are used as treatment modalities.

Complications and Risk Factors of Patients Undergoing Computed Tomography-Guided Core Needle Lung Biopsy: A Single-Center Experience.

Objectives To determine the risk factors and complications of transthoracic computed tomography (CT)-guided core needle lung biopsy. Methods This is a retrospective study of 124 patients who underwent CT-guided core lung biopsy in King Khalid University Hospital (KKUH), Riyadh. This retrospective study was conducted between January 2016 and January 2020. Patient data were collected using a standardized data form that was entered into an Excel sheet in accordance with the variables. The Statistical Package for the Social Sciences software (SPSS, version 24.0 [SPSS Inc., Chicago, IL, USA]) was used to compute for the risk of complications after CT-guided core lung biopsy and perform all statistical comparisons, and the results were reported. Results The overall complication rate due to CT-guided core needle biopsy was 34.7% (43) (P<0.001) of the total sample. Of the total complications, 69.76% (n = 30) had pneumothorax, 20.94% (n = 9) had hemorrhage, 6.98% (n = 3) had both pneumothorax and hemorrhage, and 2.32% (n = 1) had both air embolism and pneumothorax. Of all patients who developed pneumothorax, 20% (n = 6) required chest tube insertion. Patients with secondary chronic obstructive pulmonary disease (COPD) had a complication rate of 80% among the whole sample. Lung lesions less than 3 cm had a complication rate of 48.8% (P<0.034). The needle size showed a higher rate of complications between 20 and 18 gauge with 47.4% (n = 9) and 32.4% (n = 34), respectively. Conclusions We conclude that CT-guided lung biopsy is a well-established low-risk procedure that is less invasive. However, it still carries a risk of complications with some risk factors, such as small lung lesion size and secondary COPD.

Association of elderly age and chronic illnesses: Role of gender as a risk factor.

BACKGROUND AND AIMS: Chronic diseases are the leading cause of death as well as disability worldwide. There is a little information about the prevalence of these diseases among Saudi elderly population. The aim of the study was to assess the role of gender as risk factor for chronic diseases among elderly patients seen at primary health care centers and identify the most common chronic comorbidities among the elderly. METHODS: A cross-sectional study was conducted by reviewing charts of elderly patients having chronic illnesses seeking consultation between January to December 2016. Based on WHO classification data for 19 chronic diseases were extracted using electronic charts of the patients. Chi-square test and logistic regression was used to access the gender as predictor for chronic illnesses with statistical significance was set at P < 0.05. RESULTS: The total number 319 elderly patients were included in the study after random sampling with a mean age of 75 ± 7 years. Around 83 (26%) of patients were severely obese (BMI >35) with a mean BMI of 30 ± 6.7. The most common chronic illnesses were cardiovascular diseases 229 (71.8%), dyslipidemia 183 (57.4%) and diabetes 179 (56.1%). The chronic respiratory and endocrine diseases were common among the elderly females (P value 0.004, P value < 0.001). The most significant problem among males was disease of genitourinary system. There was significant positive correlation of multimorbidity with number of times of consultation in a year (r = 0.442, P value < 0.001). CONCLUSION: The study concludes that females are more likely to have chronic diseases at elder age than males. However, disease of the genitourinary system was significantly higher among male elderly. Multimorbidity significantly increased the need for frequent visits to the hospital.