Lysosomal acidification dysfunction in microglia: an emerging pathogenic mechanism of neuroinflammation and neurodegeneration.

Microglia are the resident innate immune cells in the brain with a major role in orchestrating immune responses. They also provide a frontline of host defense in the central nervous system (CNS) through their active phagocytic capability. Being a professional phagocyte, microglia participate in phagocytic and autophagic clearance of cellular waste and debris as well as toxic protein aggregates, which relies on optimal lysosomal acidification and function. Defective microglial lysosomal acidification leads to impaired phagocytic and autophagic functions which result in the perpetuation of neuroinflammation and progression of neurodegeneration. Reacidification of impaired lysosomes in microglia has been shown to reverse neurodegenerative pathology in Alzheimer's disease. In this review, we summarize key factors and mechanisms contributing to lysosomal acidification impairment and the associated phagocytic and autophagic dysfunction in microglia, and how these defects contribute to neuroinflammation and neurodegeneration. We further discuss techniques to monitor lysosomal pH and therapeutic agents that can reacidify impaired lysosomes in microglia under disease conditions. Finally, we propose future directions to investigate the role of microglial lysosomal acidification in lysosome-mitochondria crosstalk and in neuron-glia interaction for more comprehensive understanding of its broader CNS physiological and pathological implications.

A Comprehensive Assessment of Cleft Lip and Palate Websites and Patient Education Information.

OBJECTIVE: The objective of this study is to evaluate online educational resources on cleft lip and palate teams. DESIGN: A Cross-Sectional Study. SETTING: An International, Multi-Institutional Study. PARTICIPANTS: All American Cleft Palate and Craniofacial Association-approved teams with websites. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Websites were assessed for patient education and support content. Affiliation between presence of materials and U.S. Newsweek Top 100 Hospitals was also assessed. RESULTS: 187 teams were included. Presence of educational videos were available in 29.4% of websites, educational infographics in 18.2%, written materials in 66.8%, perioperative instructions in 19.3%, diagnosis information in 34.8% and treatment information in 63.1%. Information on team members were available on 77.0% of websites, resources in languages other than English in 38.5%, and support group resources in 25.7%. Cleft lip and palate diagnosis information was significantly associated with geographic region, with the largest impact from the West region (P = .03). There was a significant difference between teams affiliated with U.S. Newsweek Top 100 hospitals: Top 100 hospitals had a higher presence of educational infographics, perioperative instructions, definitions, diagnosis, and treatment (P < .01). There was no significant difference between presence of educational videos (P = .37). CONCLUSION: While many websites had basic educational materials, very few included detailed information on peri-operative planning, as well as additional forms of information including videos, infographics, and non-English languages. Providing comprehensive patient education materials online is an important supplement for patients with cleft lip and palate and should be prioritized by cleft teams.

Correction: A Review of Medical Student First-Author Publications in Plastic Surgery.

[This corrects the article DOI: 10.7759/cureus.43025.].

A 10-Year Retrospective Review of Playground-Associated Craniofacial Injuries in the Pediatric Patient Population.

This retrospective study utilized the National Electronic Injury Surveillance System (NEISS) database to identify pediatric emergency department (ED) patients with playground-associated craniofacial injuries between January 2012 and December 2021. A total of 25 414 patients were identified. The majority of injuries occurred in preschool and elementary school-age children (90.3%) and patients were more commonly boys (59.3%). Injuries most often involved the head/scalp (52.4%), face (30.4%), and mouth (11.9%). Infant (32.7%) and teen (40.0%) injuries most commonly involved swings, whereas preschool (23.1%) and elementary school (28.1%) injuries were mostly associated with slides and climbers, respectively. Most patients were treated in the ED and discharged to home (96.5%), a small portion required hospitalization (1.6%), and one death was reported. Although the majority of the injuries were relatively minor and resulted in same-day discharges, these injuries can result in serious physical harm, emotional stress, and unexpected financial burdens. Proper education and supervision regarding safe play is important to prevent these injuries.

A Review of Medical Student First-Author Publications in Plastic Surgery.

The integrated plastic surgery residency match is a highly competitive process. If performed wisely, medical research is an opportunity to differentiate applications from peers, and productivity is closely evaluated by residency programs. In this study, the authors aimed to characterize medical student research productivity for integrated plastic surgery residency programs and their respective medical schools. To this end, the authors performed a retrospective review of senior author publications from the 81 integrated plastic surgery programs from January 1, 2016, to December 31, 2020. The primary outcome was a publication with a medical student as the first author. Secondary outcomes included the number of faculty from each program, the geographic region of the program, and the ranking of associated medical schools. It was found that the average number of medical student first-author publications and faculty members per institution were 14.0 and 11.0, respectively. There was a positive correlation between the number of faculty members and several medical student first-author publications for a program (R = 0.54, P < 0.0001). The average number of medical student first-author publications was higher in the top 25 programs than for the remaining programs (P < 0.001), and most medical student first-author publications in the United States were produced by 10 plastic surgery programs. From these findings, it was concluded that these programs associated with higher-ranking medical schools produce greater numbers of medical student first-author publications. These analyses of medical student academic productivity should be a highly useful guide for current and future medical students as they strategize their successful match into plastic surgery.

Rapid restitution of contractile dysfunction by synthetic copolymers in dystrophin-deficient single live skeletal muscle fibers.

Duchenne muscular dystrophy (DMD) is caused by the lack of dystrophin, a cytoskeletal protein essential for the preservation of the structural integrity of the muscle cell membrane. DMD patients develop severe skeletal muscle weakness, degeneration, and early death. We tested here amphiphilic synthetic membrane stabilizers in mdx skeletal muscle fibers (flexor digitorum brevis; FDB) to determine their effectiveness in restoring contractile function in dystrophin-deficient live skeletal muscle fibers. After isolating FDB fibers via enzymatic digestion and trituration from thirty-three adult male mice (9 C57BL10, 24 mdx), these were plated on a laminin-coated coverslip and treated with poloxamer 188 (P188; PEO75-PPO30-PEO75; 8400 g/mol), architecturally inverted triblock (PPO15-PEO200-PPO15, 10,700 g/mol), and diblock (PEO75-PPO16-C4, 4200 g/mol) copolymers. We assessed the twitch kinetics of sarcomere length (SL) and intracellular Ca2+ transient by Fura-2AM by field stimulation (25 V, 0.2 Hz, 25 °C). Twitch contraction peak SL shortening of mdx FDB fibers was markedly depressed to 30% of the dystrophin-replete control FDB fibers from C57BL10 (P < 0.001). Compared to vehicle-treated mdx FDB fibers, copolymer treatment robustly and rapidly restored the twitch peak SL shortening (all P < 0.05) by P188 (15 µM = + 110%, 150 µM = + 220%), diblock (15 µM = + 50%, 150 µM = + 50%), and inverted triblock copolymer (15 µM = + 180%, 150 µM = + 90%). Twitch peak Ca2+ transient from mdx FDB fibers was also depressed compared to C57BL10 FDB fibers (P < 0.001). P188 and inverted triblock copolymer treatment of mdx FDB fibers increased the twitch peak Ca2+ transient (P < 0.001). This study shows synthetic block copolymers with varied architectures can rapidly and highly effectively enhance contractile function in live dystrophin-deficient skeletal muscle fibers.