Point Tenderness for 35 Years: A Rare Presentation of a Glomus Tumor in the Proximal Upper Extremity.

Glomus tumors are rare benign neoplasms that are commonly found on the fingers and distal extremities. Clinically, they are often associated with a symptom triad of moderate pain, cold sensitivity, and point tenderness. These tumors are often not considered during a clinical workup due to their rarity and can be misdiagnosed due to their diverse clinical presentations. Glomus tumors are made up of mesenchymal cells derived from glomus bodies, which are specialized arteriovenous (AV) anastomoses primarily responsible for thermoregulation. Microscopically, they present as intricate nests of endothelial cells surrounding glomus bodies, which can clinically manifest as point tenderness. Glomus tumors are usually benign and are commonly found in locations with a high concentration of glomus bodies such as the fingers. Extradigital tumors are very rare and usually not considered in primary diagnosis. This can lead to patients experiencing years and, in this case, decades of unexplained pain. The diagnostic workup for glomus tumors should include an initial Doppler ultrasound and a definitive diagnosis via immunohistochemistry (IHC). They can be completely cured with surgical excision. Although most glomus tumors are benign and easily treatable, they are often not considered in differential diagnoses when assessing for point tenderness.  This case illustrates an atypical presentation of a glomus tumor that caused 35 years of chronic pain and was incidentally misdiagnosed on imaging, leading to treatment delay by an additional eight months. This exemplifies the necessity of including glomus tumors within the differential diagnosis and diagnostic workup for point tenderness and soft tissue masses of the upper extremity.

Sex differences in brain transcriptomes of juvenile Cynomolgus macaques.

Background: Behavioral, social, and physical characteristics are posited to distinguish the sexes, yet research on transcription-level sexual differences in the brain is limited. Here, we investigated sexually divergent brain transcriptomics in prepubertal cynomolgus macaques, a commonly used surrogate species to humans. Methods: A transcriptomic profile using RNA sequencing was generated for the temporal lobe, ventral midbrain, and cerebellum of 3 female and 3 male cynomolgus macaques previously treated with an Adeno-associated virus vector mix. Statistical analyses to determine differentially expressed protein-coding genes in all three lobes were conducted using DeSeq2 with a false discovery rate corrected P value of .05. Results: We identified target genes in the temporal lobe, ventral midbrain, and cerebellum with functions in translation, immunity, behavior, and neurological disorders that exhibited statistically significant sexually divergent expression. Conclusions: We provide potential mechanistic insights to the epidemiological differences observed between the sexes with regards to mental health and infectious diseases, such as COVID19. Our results provide pre-pubertal information on sexual differences in non-human primate brain transcriptomics and may provide insight to health disparities between the biological sexes in humans.

Disease correction in mucopolysaccharidosis type IIIB mice by intraparenchymal or cisternal delivery of a capsid modified AAV8 codon-optimized NAGLU vector.

Mucopolysaccharidosis type IIIB (MPS IIIB) is an autosomal recessive lysosomal storage disease caused by mutations in the gene that encodes the protein N-acetyl-glucosaminidase (NAGLU). Defective NAGLU activity results in aberrant retention of heparan sulfate within lysosomes leading to progressive central nervous system (CNS) degeneration. Intravenous treatment options are limited by the need to overcome the blood-brain barrier and gain successful entry into the CNS. Additionally, we have demonstrated that AAV8 provides a broader transduction area in the MPS IIIB mouse brain compared with AAV5, 9 or rh10. A triple-capsid mutant (tcm) modification of AAV8 further enhanced GFP reporter expression and distribution. Using the MPS IIIB mouse model, we performed a study using either intracranial six site or intracisterna magna injection of AAVtcm8-codon-optimized (co)-NAGLU using untreated MPS IIIB mice as controls to assess disease correction. Disease correction was evaluated based on enzyme activity, heparan sulfate storage levels, CNS lysosomal signal intensity, coordination, activity level, hearing and survival. Both histologic and enzymatic assessments show that each injection method results in supranormal levels of NAGLU expression in the brain. In this study, we have shown correction of lifespan and auditory deficits, increased CNS NAGLU activity and reduced lysosomal storage levels of heparan sulfate following AAVtcm8-coNAGLU administration and partial correction of NAGLU activity in several peripheral organs in the murine model of MPS IIIB.