Age-related oxidative decline of mitochondrial functions in rat brain is prevented by long term oral antioxidant supplementation

A combination of antioxidants (N-acetyl cysteine, α-lipoic acid, and α-tocopherol) was selected for long term oral supplementation study in rats for protective effects on age-related mitochondrial alterations in the brain. Four groups of rats were chosen: young control (6–7 months); aged rats (22–24 months); aged rats (22–24 months) on daily antioxidant supplementation from 18 month onwards and young rats (6–7 months) on daily antioxidant supplementation from 2 month onwards. The brain mitochondrial functional parameters, status of antioxidant enzymes and accumulation of oxidative damage markers were measured in the four groups of rats. A significant decrease in complex IV activity and a loss of transmembrane potential and phosphorylation capacity along with an increased accumulation of oxidative damage markers and compromised antioxidant enzyme status were noticed in aged rat brain mitochondria as compared to that in young controls, but in aged rats supplemented with oral antioxidants the mitochondrial alterations were largely prevented. Antioxidant supplementation in young rats had no effect on mitochondrial parameters investigated in this study. The results have implications in biochemical and functional deficits of brain during aging as well as in neurodegenerative disorders.     

Mutant C9orf72 human iPSC-derived astrocytes cause non-cell autonomous motor neuron pathophysiology

Mutations in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS). Accumulating evidence implicates astrocytes as important non-cell autonomous contributors to ALS pathogenesis, although the potential deleterious effects of astrocytes on the function of motor neurons remains to be determined in a completely humanized model of C9orf72-mediated ALS. Here, we use a human iPSC-based model to study the cell autonomous and non-autonomous consequences of mutant C9orf72 expression by astrocytes. We show that mutant astrocytes both recapitulate key aspects of C9orf72-related ALS pathology and, upon co-culture, cause motor neurons to undergo a progressive loss of action potential output due to decreases in the magnitude of voltage-activated Na⁺ and K⁺ currents. Importantly, CRISPR/Cas-9 mediated excision of the C9orf72 repeat expansion reverses these phenotypes, confirming that the C9orf72 mutation is responsible for both cell-autonomous astrocyte pathology and non-cell autonomous motor neuron pathophysiology.     

Frosted Branch Angiitis in a Patient with Typhoid Fever

Frosted branch angiitis (FBA), a rare form of retinal vasculitis presenting as bilateral perivascular sheathing, resembling the appearance of frosted tree branches in winter, was first reported by Ito et al.¹ in 1976, in a young immunocompetent boy. FBA predominantly affects healthy young patients, the youngest reported in an 11-month-old infant² and oldest in a 42-year-old patient.³ Classical symptoms include sudden onset of blurred vision with floaters and photopsiae. Fundus examination shows widespread perivascular translucent sheathing affecting both arterioles and venules, more commonly latter. Fluorescein angiography shows late staining of vessels with no obstruction of blood flow. Electroretinogram shows reduced amplitude and visual fields show generalized constriction. Medline search did not show any case of frosted branch angiitis in a patient with typhoid fever.     

Anatomy and White Matter Connections of the Superior Frontal Gyrus

The superior frontal gyrus (SFG) is an important region implicated in a variety of tasks including motor movement, working memory, resting-state, and cognitive control. A detailed understanding of the subcortical white matter of the SFG could improve postoperative morbidity related to surgery around this gyrus. Through DSI-based fiber tractography validated by gross anatomical dissection, we characterized the fiber tracts of the SFG based on their relationships to other well-known neuroanatomic structures. Diffusion imaging from the Human Connectome Project from 10 healthy adult subjects was used for fiber tractography. We evaluated the SFG as a whole based on its connectivity with other regions. All tracts were mapped in both hemispheres, and a lateralization index was calculated based on resultant tract volumes. Ten cadaveric dissections were then performed using a modified Klingler technique to delineate the location of major tracts integrated within the SFG. We identified four major SFG connections: the frontal aslant tract connecting to the inferior frontal gyrus; the inferior fronto-occipital fasciculus connecting to the cuneus, lingual gyrus, and superior parietal lobule; the cingulum connecting to the precuneus and parahippocampal gyrus/uncus; and a callosal fiber bundle connecting the SFG bilaterally. The functional networks of the SFG involve a complex series of white matter tracts integrated within the gyrus, including the FAT, IFOF, cingulum, and callosal fibers. Postsurgical outcomes related to this region may be better understood in the context of the fiber-bundle anatomy highlighted in this study. Clin. Anat. 33:823–832, 2020. © 2019 Wiley Periodicals, Inc.     

Assessment of stigma associated with tuberculosis in Mexico

Background: Stigma is a major barrier to health care access and impacts the quality of life for individuals affected by tuberculosis (TB). Assessing TB stigma is essential to addressing health disparities. However, no such instrument was available in Mexico at the time of our study. This study examined the adaptability of the TB and human immunodeficiency virus (HIV) stigma scales previously used in Thailand.Methods: The original scale, developed in English, was linguistically adapted to Spanish and administered to 217 individuals affected by TB in five states in Mexico. The TB-HIV stigma subscales were designed to assess individual and community perspectives. Additional data collected included general information and socio-demographics. Assessment of psychometric properties included basic statistical tests, evaluation of Cronbach''s alpha and factor analysis.Results: We found no significant statistical differences associated with higher stigma scores by location, age, marital status, education and stigma scores. Factor analysis did not create any new factors. Internal consistency reliability coefficients were satisfactory (Cronbach α = 0.876–0.912).Conclusion: The use of the stigma scales has implications for 1) health improvements, 2) research on stigma and health disparities, and 3) TB and HIV stigma interventions. Further research is needed to examine transferability among larger and randomly selected Spanish-speaking populations.