Brain lesions disrupting addiction map to a common human brain circuit

Drug addiction is a public health crisis for which new treatments are urgently needed. In rare cases, regional brain damage can lead to addiction remission. These cases may be used to identify therapeutic targets for neuromodulation. We analyzed two cohorts of patients addicted to smoking at the time of focal brain damage (cohort 1 n = 67; cohort 2 n = 62). Lesion locations were mapped to a brain atlas and the brain network functionally connected to each lesion location was computed using human connectome data (n = 1,000). Associations with addiction remission were identified. Generalizability was assessed using an independent cohort of patients with focal brain damage and alcohol addiction risk scores (n = 186). Specificity was assessed through comparison to 37 other neuropsychological variables. Lesions disrupting smoking addiction occurred in many different brain locations but were characterized by a specific pattern of brain connectivity. This pattern involved positive connectivity to the dorsal cingulate, lateral prefrontal cortex, and insula and negative connectivity to the medial prefrontal and temporal cortex. This circuit was reproducible across independent lesion cohorts, associated with reduced alcohol addiction risk, and specific to addiction metrics. Hubs that best matched the connectivity profile for addiction remission were the paracingulate gyrus, left frontal operculum, and medial fronto-polar cortex. We conclude that brain lesions disrupting addiction map to a specific human brain circuit and that hubs in this circuit provide testable targets for therapeutic neuromodulation.Lesions resulting in addiction remission occur in multiple different brain locations but map to a specific brain circuit and that hubs in this circuit provide testable targets for therapeutic neuromodulation.</p

Insular Cortex Damage from Stroke and Disruption of Nicotine Dependence : The MINDS Study

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Public Health Sciences, 2015.Current pharmacotherapies for treating smoking dependence have profuse side effects and relatively high rates of relapse, and primarily target the brains’ mesocorticolimbic “reward” pathway. Recent evidence suggests that the insular cortex, a central cerebral hemispheric region not part of the mesocorticolimbic structure, may also play an important role in cognitive and emotional processes that facilitate drug use. We hypothesized that current cigarette smokers admitted for ischemic stroke in the insula would demonstrate less severe withdrawal symptoms during admission, greater reduction in smoking-related urges, and a higher likelihood of quitting compared to patients admitted for non-insular strokes. A total of 156 smokers (38 insula and 118 non-insula strokes verified by 3 neuroradiologists using CT and MRI) were recruited from 3 acute care stroke units in Rochester, NY. Validated questionnaires were administered during admission to assess urge (Questionnaire on Smoking Urges, QSU) before and after the stroke as well as withdrawal intensity after stroke (Wisconsin Smoking Withdrawal Scale, WSWS). Continuous abstinence was assessed at 3 months post-discharge. Bivariate statistics and multivariable linear regression were used to evaluate differences in withdrawal, urge, and cessation between insular and non-insular groups, controlling for age, baseline nicotine dependence, stroke severity, nicotine replacement use during admission, pre-stroke intent to quit and damage to other regions in the reward pathway. On average, smokers with insular lesions had a lower WSWS score during admission compared to those with non-insular lesions (adjusted β=-3.12, 95% CI: -4.97, -1.27). Insular damaged participants also had a greater decrease in urges from baseline to hospitalization (adjusted β=-1.15, 95% CI: -1.85, -0.44) and 3 months post-stroke (adjusted β=-0.93, 95% CI: -1.79, -0.07) relative to the non-insular group. The insular damaged group had 2.45 times the odds (95% CI: 0.93, 6.49) of continuous abstinence at follow-up and a reduced instantaneous risk of relapse (HR=0.48, 95% CI: 0.24, 0.98) relative to the non-insular group. Among the quitters, insular damage was associated with higher relative odds of experiencing a disruption of addiction compared to non-insular damage (OR=5.60, 95% CI: 1.52, 20.56). These findings support the potential role of the insula in the mechanism responsible for maintaining addictive behaviors

Experimental studies on the viscosity of Fe nanoparticles dispersed in ethylene glycol and water mixture

In this paper, experimental studies are conducted in order to measure the viscosity of Fe nanoparticles dispersed in various weight concentration (25/75%, 45/55% and 55/45%) of ethylene glycol and water (EG-water) mixture. The experimental measurements are performed at various volume concentrations up to 2% and temperature ranging from 10°C to 60°C. The experimental results disclose that the viscosity of nanofluids increases with increase in Fe particle volume fraction, and decreases with increase in temperature. Maximum enhancement in viscosity of nanofluids is 2.14 times for 55/45% EG-water based nanofluid at 2% volume concentration compared to the base fluid. Moreover, some comparisons between experimental results and theoretical models are drawn. It is also observed that the prior theoretical models do not estimate the viscosity of nanofluid accurately. Finally, a new empirical correlation is proposed to predict the viscosity of nanofluids as a function of volume concentration, temperature, and the viscosity of base fluid

Qualitative Structural Characterization of Two Lignin Samples and Quantitative Determination of Hydroxyl and Methoxyl Functional Groups in Kraft Lignin via Acetylation

In this research, two types of lignin, i.e. one extracted from industrial waste water of the Iran wood and paper (choka) factory as black liquor and another provided from Aldrich company, were studied. Firstly, the lignin was precipitated from its black liquor by a dilute acid and was then purified by dissolving in tetrahydrofuran (THF). Lignin samples were characterized using Fourier transform infrared (FTIR) and proton nuclear magnetic resonance (1HNMR) spectroscopies. It was found from results that the Aldrich lignin has a structure similar with the lignosulfonate while lignin extracted from black liquor does not have a hydrophilic sulfonate group and has a Kraft lignin structure. Using acetylation of Kraft lignin and complementary characterization with 1HNMR spectroscopy, the ratio of hydroxyl functional groups to methoxy groups was calculated to be 1.11 to 1, and amount of the hydroxyl groups was calculated to be 5.91 mmol/g of acetylated lignin, where 53% of the hydroxyl groups is related to the aromatic hydroxyl groups. By having the molecular weight of the Kraft lignin which was obtained from the gel permeation chromatography (GPC) analysis of the acetylated Kraft lignin to be 1260 g/mol, average number of the hydroxyl groups per acetylated lignin chain was calculated to be 7.44

Paclitaxel-Induced Peripheral Neuropathy Using NCI-CTCin Isfahan, Iran: Paclitaxel-induced peripheral neuropathy

Paclitaxel is a highly effective anticancer agent. It is active against a broad range of cancers that are generally considered refractory to conventional chemotherapy.Paclitaxel induces a peripheral neuropathy (PN) that is characterized by sensory symptoms such as numbness and paresthesia in a glove and stocking distribution.PN may be severe and dose limiting at initial doses above 275 mg/m2. Our purpose was to evaluate the incidence, severity, dose dependency, and reversibility of paclitaxel-induced neuropathy. We studied 45 patients with breast cancer, treated with Paclitaxel (240, 270, 300 mg/m2) in an average of 4 cycles of treatment.Paclitaxel was administered by a 3 h intravenous infusion every 3 weeks in all patients.We used National Cancer Institute-Common Toxicity Criteria (NCI-CTC) to evaluate peripheral neuropathy. The cumulative dose of paclitaxel in each patient was also measured. The severity of symptoms was graded. Incidence and reversibility of neuropathy was measured in an interview with the patient. Paresthesias appeared in 39 (86.6%) patients after an average cumulative dose of 394 mg/m2.In most patients, PN was seen after the first or second dose (68%) of paclitaxel and then stabilized in 36%, improved in 36%, resolved completely in 24% and progressed in 4%. There was no need to discontinue Paclitaxel in any of the patients due to PN.In view of our experience in the present study, we found that Paclitaxel-induced neuropathy is a dose-dependent phenomenon, and most of the symptoms occurred after the first or second phase of treatment

Effects of aspirin in combination with EPA and DHA on HDL-C cholesterol and ApoA1 exchange in individuals with type 2 diabetes mellitus

Background/synopsisLow-dose aspirin is an effective drug for the prevention of cardiovascular disease (CVD) events but individuals with diabetes mellitus can be subject to 'aspirin resistance'. Thus, aspirin's effect in these individuals is controversial. Higher blood levels of seafood-derived omega-3 polyunsaturated fatty acids (ω3) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) also have beneficial effects in reducing risk of CVD events but few studies have examined the interaction of plasma EPA and DHA with aspirin ingestion.Objective/purposeOur study examined the combinatory effects of EPA, DHA, and aspirin ingestion on HDL-cholesterol (HDL-C) and apoA-I exchange (shown to be associated with CVD event risk).Methods30 adults with Type 2 diabetes mellitus ingested aspirin (81mg/day) for 7 consecutive days, EPA+DHA (2.6g/day) for 28 days, then both for 7 days. Plasma was collected at baseline and at 5 subsequent visits including 4h after each aspirin ingestion. Mixed model methods were used to determine HDL-C-concentrations and apoA-I exchange compared to the baseline visit values. LOWESS curves were used for non-linear analyses of outcomes to help discern change patterns, which was followed by piecewise linear functions for formal testing of curvilinear relationships.ResultsSignificant changes (p &lt; 0.05) compared to baseline in both HDL-C-concentrations and apoA-I exchange were present at different times. After 7 days of aspirin-only ingestion, apoA-I exchange was significantly modified by increasing levels of DHA concentration, with increased apoA-I exchange observed up until log(DHA) of 4.6 and decreased exchange thereafter (p = 0.03). These LOWESS curve effects were not observed for EPA or HDL-C (p &gt; 0.05). Aspirin's effects on apoA-I exchange were the greatest when EPA or DHA concentrations were moderate compared to high or low. Comparison of EPA, DHA, and EPA+DHA LOWESS curves, demonstrated that the majority of the effect is due to DHA.ConclusionOur results strongly suggest that plasma concentrations of EPA and DHA influence aspirin effects on lipid mediators of CVD event risk where their concentrations are most beneficial when moderate, not high or low. These effects on HDL-C cholesterol and apoA-I exchange are novel. Personalized dosing of DHA in those who take aspirin may be a beneficial option for patients with type 2 diabetes mellitus

Clinical and Molecular Evaluation of a Case of Giant Primary Splenic Hydatid Cyst: A Case Report

Spleen is an unusual location for hydatid cyst. Here we report a case of primary splenic hydatid cyst in a 41-yr-old Iranian woman from Yasuj, southwest of Iran. The patient had been admitted to Shahid Beheshti Hospital because of abdominal pain. Abdominal sonography revealed a hypoechoic lesion of 150 X 130 mm in the spleen, suggestive of hydatid cyst. Splenectomy was performed for the patient and surgical interventions revealed a hydatid cyst occupying most of splenic parenchyma. She was discharged on the 5 day of her operation. Postoperative diagnosis and confirmation of hydatid cyst was done by histopathological, molecular and serological approaches. Histopathological evaluation revealed the classical laminated layer of hydatid cyst. DNA was extracted from a part of cyst and PCR amplified. Sequencing and analysis of PCR product revealed that the isolate has the most similarity with G1 strain of Echinococcus granulosus. Patient’s serum was positive for IgG anti-hydatid cyst antibodies, using antigen-B ELISA