Soluble and Cell-Associated Insulin Receptor Dysfunction Correlates with Severity of HAND in HIV-Infected Women

Blood sugar metabolism abnormalities have been identified in HIV-infected individuals and associated with HIV-associated neurocognitive disorders (HAND). These abnormalities may occur as a result of chronic HIV infection, long-term use of combined antiretroviral treatment (CART), aging, genetic predisposition, or a combination of these factors, and may increase morbidity and mortality in this population.To determine if changes in soluble and cell-associated insulin receptor (IR) levels, IR substrate-1 (IRS-1) levels, and IRS-1 tyrosine phosphorylation are associated with the presence and severity of HAND in a cohort of HIV-seropositive women.This is a retrospective cross-sectional study using patient database information and stored samples from 34 HIV-seropositive women and 10 controls without history of diabetes from the Hispanic-Latino Longitudinal Cohort of Women. Soluble IR subunits [sIR, ectodomain (α) and full-length or intact (αβ)] were assayed in plasma and CSF samples by ELISA. Membrane IR levels, IRS-1 levels, and IRS-1 tyrosine phosphorylation were analyzed in CSF white cell pellets (WCP) using flow cytometry. HIV-seropositive women had significantly increased levels of intact or full-length sIR in plasma (p<0.001) and CSF (p<0.005) relative to controls. Stratified by HAND, increased levels of full-length sIR in plasma were associated with the presence (p<0.001) and severity (p<0.005) of HAND. A significant decrease in IRS-1 tyrosine-phosphorylation in the WCP was also associated with the presence (p<0.02) and severity (p<0.02) of HAND.This study provides evidence that IR secretion is increased in HIV-seropositive women, and increased IR secretion is associated with cognitive impairment in these women. Thus, IR dysfunction may have a role in the progression of HAND and could represent a biomarker for the presence and severity of HAND

Vampires in the village Žrnovo on the island of Korčula: following an archival document from the 18th century

Središnja tema rada usmjerena je na raščlambu spisa pohranjenog u Državnom arhivu u Mlecima (fond: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) koji se odnosi na događaj iz 1748. godine u korčulanskom selu Žrnovo, kada su mještani – vjerujući da su se pojavili vampiri – oskvrnuli nekoliko mjesnih grobova. U radu se podrobno iznose osnovni podaci iz spisa te rečeni događaj analizira u širem društvenom kontekstu i prate se lokalna vjerovanja.The main interest of this essay is the analysis of the document from the State Archive in Venice (file: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) which is connected with the episode from 1748 when the inhabitants of the village Žrnove on the island of Korčula in Croatia opened tombs on the local cemetery in the fear of the vampires treating. This essay try to show some social circumstances connected with this event as well as a local vernacular tradition concerning superstitions

Head Injuries

Traumatic brain injuries (TBIs) are the leading cause of mortality and morbidity in patients younger than 40 years, affecting 1.7 million people every year in the USA. They are responsible for one-third of all injury-related deaths, whereas patients who survive may develop severe debilitating long-term sequelae. They consist of a wide spectrum of diseases, defined as a whole as an “alteration in brain function, or other evidence of brain pathology, caused by an external force.” The causes may vary depending on patient’s age: abuse traumas are most commonly observed in infants, while traumatic and sports-related injuries are seen in toddlers and children. Motor vehicle accidents involve most commonly young adults, whereas the elderly population is more prone to accidental falls. TBIs are clinically divided into minor, mild, moderate, and severe traumas by using the Glasgow Coma Scale (GCS), the most commonly used grading scale to evaluate the entity of head injuries within the first 48 h, which aims to provide a uniform approach to the clinical assessment of patients involved in acute head traumas. GCS is the sum of three components which are eye opening, motor response, and verbal response; a minor trauma has a GCS = 15; mild, GCS > 13; moderate, GCS 9–12; and severe, GCS < 8. An additional TBI clinical classification is provided by the Brain Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine, based on the loss of consciousness, loss of memory for events occurred immediately before or after trauma, changes in mental status, and focal neurologic deficits. According to this classification, a mild trauma is defined as a physiologically disruption of brain functions, evaluated by the presence of one of the previous described criteria; additional findings are no abnormalities on computed tomography (CT) scan, GCS > 12, no surgical lesions, and length of hospital recovery less than 48 h. Moderate trauma is defined as a GCS of 9–12, hospital recovery of at least 48 h, surgical intracranial lesions, and positive CT scan findings. Severe traumas are evident at the moment of clinical presentation. Chronologically, TBIs are divided into primary (injuries occurring at the time of impact) and secondary lesions (lesions occurring after the initial injury, i.e., cerebral herniation, swelling, ischemia, infection, hydrocephalus), resulting from complication of physiological response to injury. Secondary injuries are potentially preventable by stabilizing the patient, by monitoring vital parameters, and, in some cases, by performing decompressive hemicraniectomy. Other classifications are based on the mechanism of injury (open or blunt trauma) and on the location, dividing them into intra-axial lesions (cortical contusions, diffuse axonal injury, intracerebral hematoma) and extra-axial lesions (subdural, epidural, subarachnoid, and intraventricular hematomas). Given these data, it is easy to understand the significative role of imaging in this clinical setting, since its goals are to identify treatable lesions, assist to prevent secondary damage, and provide prognostic information. In this chapter we aim to review the most commonly encountered and severe brain injuries and their complications