NF-κB Signaling in the Brain of Autistic Subjects

Autism is a neurodevelopmental disorder characterized by problems in communication, social skills, and repetitive behavior. Recent studies suggest that apoptotic and inflammatory mechanisms may contribute to the pathogenesis of this disorder. Nuclear factor-κB (NF-κB) is an important gene transcriptional factor involved in the mediation of inflammation and apoptosis. This study examined the activities of the NF-κB signaling pathway in the brain of autistic subjects and their age-matched controls. The NF-κB activation is also determined in the brain of BTBR mice, which is a promising animal model for study of pathogenic mechanisms responsible for autism. Our results showed that the level of IKKα kinase, which phosphorylates the inhibitory subunit IκBα, is significantly increased in the cerebellum of autistic subjects. However, the expression and phosphorylation of IκBα are not altered. In addition, our results demonstrated that the expression of NF-κB (p65), and the phosphorylation/activation of NF-κB (p65) at Ser536 are not significantly changed in the cerebellum and cortex of both autistic subjects and BTBR mice. Our findings suggest that the NF-κB signaling pathway is not disregulated in the brain of autistic subjects and thus may not be significantly involved in the processes of abnormal inflammatory responses suggested in autistic brain

Public health and state power in Pakistan: case studies of medical interventions from British Raj to military rule

This thesis provides the first historical survey of medical interventions and public health policies implemented by the governments that ruled in the territories of Pakistan over the 20th century. It sheds light on the objectives and challenges of governance during this period with respect to population health and welfare, and seeks to contribute to our understanding of the impact of colonial rule in the territories which became Pakistanâwhich are not well-represented in the literature on the history of medicine of British Indiaâand to expand our knowledge of developments in the postcolonial period. The narrative begins with the twilight of colonial rule, when the British Indian government was hindered from undertaking public health reform due to the growth of nationalist and anti-colonial sentiment in the North-West Frontier, Bengal, and the Punjab. The demand for local autonomy and public accountability in health decision-making in these provinces came at a time when Indians were simultaneously resisting Britainâs political dominance over India. Even after independence, the conflict between provincial governments and successive central governments with respect to health policymaking persisted. Such tensions were exacerbated by the economic pressures of scarcity in Pakistanâs early years which worsened pre-existing social and political cleavages between different groups. This material deprivation along with the historical legacy of tropical medicine in Asia resulted in acceptance of the countryâs status as an underdeveloped, backwards state by the countryâs leaders in return for international health aid from richer nations. Pakistan subsequently became a laboratory for developed world experiments on poverty and population control. The developments in health over the period from 1900 to 1960 make evident the manifold challenges to the sovereignty and authority of the colonial, parliamentary, and military rulers as they attempted to intervene in the lives of subjects and citizens of British India and Pakistan.</p

Public health and state power in Pakistan: case studies of medical interventions from British Raj to military rule

This thesis provides the first historical survey of medical interventions and public health policies implemented by the governments that ruled in the territories of Pakistan over the 20th century. It sheds light on the objectives and challenges of governance during this period with respect to population health and welfare, and seeks to contribute to our understanding of the impact of colonial rule in the territories which became Pakistan—which are not well-represented in the literature on the history of medicine of British India—and to expand our knowledge of developments in the postcolonial period. The narrative begins with the twilight of colonial rule, when the British Indian government was hindered from undertaking public health reform due to the growth of nationalist and anti-colonial sentiment in the North-West Frontier, Bengal, and the Punjab. The demand for local autonomy and public accountability in health decision-making in these provinces came at a time when Indians were simultaneously resisting Britain’s political dominance over India. Even after independence, the conflict between provincial governments and successive central governments with respect to health policymaking persisted. Such tensions were exacerbated by the economic pressures of scarcity in Pakistan’s early years which worsened pre-existing social and political cleavages between different groups. This material deprivation along with the historical legacy of tropical medicine in Asia resulted in acceptance of the country’s status as an underdeveloped, backwards state by the country’s leaders in return for international health aid from richer nations. Pakistan subsequently became a laboratory for developed world experiments on poverty and population control. The developments in health over the period from 1900 to 1960 make evident the manifold challenges to the sovereignty and authority of the colonial, parliamentary, and military rulers as they attempted to intervene in the lives of subjects and citizens of British India and Pakistan.</p

Vision Loss In Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Case Series

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired, immune-mediated, and clinically heterogeneous disease affecting the nerve roots and peripheral nerves. CIDP classically presents with gradually progressive and often proximal limb weakness and numbness accompanied by areflexia, elevated cerebrospinal fluid (CSF) protein without pleocytosis, and electrodiagnostic or pathologic evidence of demyelination. We report three cases where vision loss was an early and prominent symptom in new onset CIDP: two cases of papilledema, and one case of optic neuropathy

The Impact of Prefilled Syringes on Endophthalmitis Following Intravitreal Injection of Ranibizumab.

PURPOSE: To compare the rates of infectious endophthalmitis following intravitreal injection of ranibizumab using prefilled syringes vs conventional preparation. DESIGN: Multicenter retrospective cohort study. METHODS: All eyes receiving intravitreal injection of 0.5 mg ranibizumab for retinal vascular diseases at 10 retina practices across the United States (2016 to 2017) and Japan (2009 to 2017) were included. The total numbers of eyes and injections were determined from billing codes. Endophthalmitis cases were determined from billing records and evaluated with chart review. Primary outcome was the rate of postinjection acute endophthalmitis. Secondary outcomes were visual acuity and microbial spectrum. RESULTS: A total of 243 754 intravitreal 0.5 mg ranibizumab injections (165 347 conventional and 78 407 prefilled) were administered to 43 132 unique patients during the study period. In the conventional ranibizumab group, a total of 43 cases of suspected endophthalmitis occurred (0.026%; 1 in 3845 injections) and 22 cases of culture-positive endophthalmitis occurred (0.013%; 1 in 7516 injections). In the prefilled ranibizumab group, 12 cases of suspected endophthalmitis occurred (0.015%; 1 in 6534 injections) and 2 cases of culture-positive endophthalmitis occurred (0.0026%; 1 in 39 204 injections). Prefilled syringes were associated with a trend toward decreased risk of suspected endophthalmitis (odds ratio 0.59; 95% confidence interval 0.31-1.12; P = .10) and a statistically significant decreased risk of culture-positive endophthalmitis (odds ratio 0.19; 95% confidence interval 0.045-0.82; P = .025). Average logMAR vision loss at final follow-up was significantly worse for eyes that developed endophthalmitis from the conventional ranibizumab preparation compared to the prefilled syringe group (4.45 lines lost from baseline acuity vs 0.38 lines lost; P = .0062). Oral-associated flora was found in 27.3% (6/22) of conventional ranibizumab culture-positive endophthalmitis cases (3 cases of Streptococcus viridans, 3 cases of Enterococcus faecalis) compared to 0 cases in the prefilled ranibizumab group. CONCLUSION: In a large, multicenter, retrospective study the use of prefilled syringes during intravitreal injection of ranibizumab was associated with a reduced rate of culture-positive endophthalmitis, including from oral flora, as well as with improved visual acuity outcomes