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Abstract Background Induced pluripotent stem cell-derived microglia (iMGL) represent an excellent tool in studying microglial function in health and disease. Yet, since differentiation and survival of iMGL are highly reliant on colony-stimulating factor 1 receptor (CSF1R) signaling, it is difficult to use iMGL to study microglial dysfunction associated with pathogenic defects in CSF1R. Methods Serial modifications to an existing iMGL protocol were made, including but not limited to changes in growth factor combination to drive microglial differentiation, until successful derivation of microglia-like cells from an adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) patient carrying a c.2350G > A (p.V784M) CSF1R variant. Using healthy control lines, the quality of the new iMGL protocol was validated through cell yield assessment, measurement of microglia marker expression, transcriptomic comparison to primary microglia, and evaluation of inflammatory and phagocytic activities. Similarly, molecular and functional characterization of the ALSP patient-derived iMGL was carried out in comparison to healthy control iMGL. Results The newly devised protocol allowed the generation of iMGL with enhanced transcriptomic similarity to cultured primary human microglia and with higher scavenging and inflammatory competence at ~ threefold greater yield compared to the original protocol. Using this protocol, decreased CSF1R autophosphorylation and cell surface expression was observed in iMGL derived from the ALSP patient compared to those derived from healthy controls. Additionally, ALSP patient-derived iMGL presented a migratory defect accompanying a temporal reduction in purinergic receptor P2Y12 (P2RY12) expression, a heightened capacity to internalize myelin, as well as heightened inflammatory response to Pam3CSK4. Poor P2RY12 expression was confirmed to be a consequence of CSF1R haploinsufficiency, as this feature was also observed following CSF1R knockdown or inhibition in mature control iMGL, and in CSF1R WT/KO and CSF1R WT/E633K iMGL compared to their respective isogenic controls. Conclusions We optimized a pre-existing iMGL protocol, generating a powerful tool to study microglial involvement in human neurological diseases. Using the optimized protocol, we have generated for the first time iMGL from an ALSP patient carrying a pathogenic CSF1R variant, with preliminary characterization pointing toward functional alterations in migratory, phagocytic and inflammatory activities. Graphical Abstract

Background: Knee pain is primarily caused by knee osteoarthritis (OA). As a result, the quality of life and physical function of patients are affected. This study aimed to evaluate prevalence of knee pain and its influence on quality of life and physical function in the adult population of Jazan region of Saudi Arabia. Methods: A cross-sectional study among 480 above 40 years adults who had knee pain and diagnosed with knee OA was conducted. A questionnaire containing the Arabic validated versions of the International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC) and the health-related quality of life (FS-12) was used. Data analysis included descriptive statistics, correlation and regression analysis. Results: IKDC mean score was 40.05 with SD 9.75. Pain was present in 77.8%; 12.4% indicated continuous pain and 6.5% indicated worst pain intensity. Physical function was normal in 14%, 48% could perform light activities without pain, and 11% are unable to perform any activity. Results show a statistically significant relationship between pain intensity and sex, age, and BMI and, between age and knee function. Regression analysis showed significant association with sex and age. Pain is four times more common in females. Mean HRQoL score was 39.46 with subscale: MCS (39.41) and PCS (39.50) scores. Conclusions: Low IKDC scores were reported among the adult population with OA. The majority suffered from pain in different degrees and intensities. Physical function was also impaired and the quality of life is affected. Better pain management is recommended for OA patients.

Sickle cell anemia (SCA) is a common inherited kind of hemolytic anemia in Africa and some areas of Asia. In Saudi Arabia, SCA is prevalent as well. The patient of SCA is prone to some bacteria species more than the others, and Salmonella is one of the most prevalent infections in SCA that were known to cause bacteremia, osteomyelitis, septic arthritis, and gastroenteritis. Herein, we report a 7-years old girl who presented with a history of fever for five days and jaundice with abdominal pain and mild respiratory distress. Later, the patient was diagnosed to have infective endocarditis due to Salmonella enterica subspecies salamae (subgroup II). The patient improved completely after receiving proper antibiotics. To the best of our knowledge, there is only one case of adult SCA that has been reported with infective endocarditis due to Salmonella entrica but no reported case in pediatric.