A Rare Case Report of a Corpus Callosal Splenial Lesion in the Context of Atypical Neuroleptic Malignant Syndrome.

In this report, we describe a case of atypical neuroleptic malignant syndrome (NMS) presenting with an isolated lesion in the splenium of the corpus callosum (ILSCC). There is a paucity of information regarding this topic within the literature and only 7 previous case reports have been published at the time of writing. To our knowledge, this case report is also the first to describe an atypical NMS variant in the context of an ILSCC. In this report, we describe the important considerations in formulating differential diagnosis for ILSCC and are the first report to propose a possible pathophysiological mechanism relating ILSCC with NMS

High Sugar-Induced Insulin Resistance in Drosophila Relies on the Lipocalin Neural Lazarillo

In multicellular organisms, insulin/IGF signaling (IIS) plays a central role in matching energy needs with uptake and storage, participating in functions as diverse as metabolic homeostasis, growth, reproduction and ageing. In mammals, this pleiotropy of action relies in part on a dichotomy of action of insulin, IGF-I and their respective membrane-bound receptors. In organisms with simpler IIS, this functional separation is questionable. In Drosophila IIS consists of several insulin-like peptides called Dilps, activating a unique membrane receptor and its downstream signaling cascade. During larval development, IIS is involved in metabolic homeostasis and growth. We have used feeding conditions (high sugar diet, HSD) that induce an important change in metabolic homeostasis to monitor possible effects on growth. Unexpectedly we observed that HSD-fed animals exhibited severe growth inhibition as a consequence of peripheral Dilp resistance. Dilp-resistant animals present several metabolic disorders similar to those observed in type II diabetes (T2D) patients. By exploring the molecular mechanisms involved in Drosophila Dilp resistance, we found a major role for the lipocalin Neural Lazarillo (NLaz), a target of JNK signaling. NLaz expression is strongly increased upon HSD and animals heterozygous for an NLaz null mutation are fully protected from HSD-induced Dilp resistance. NLaz is a secreted protein homologous to the Retinol-Binding Protein 4 involved in the onset of T2D in human and mice. These results indicate that insulin resistance shares common molecular mechanisms in flies and human and that Drosophila could emerge as a powerful genetic system to study some aspects of this complex syndrome

Prefrontal response and frontostriatal functional connectivity to monetary reward in abstinent alcohol-dependent young adults

Although altered function in neural reward circuitry is widely proposed in models of addiction, more recent conceptual views have emphasized the role of disrupted response in prefrontal regions. Changes in regions such as the orbitofrontal cortex, medial prefrontal cortex, and dorsolateral prefrontal cortex are postulated to contribute to the compulsivity, impulsivity, and altered executive function that are central to addiction. In addition, few studies have examined function in these regions during young adulthood, when exposure is less chronic than in typical samples of alcohol-dependent adults. To address these issues, we examined neural response and functional connectivity during monetary reward in 24 adults with alcohol dependence and 24 psychiatrically healthy adults. Adults with alcohol dependence exhibited less response to the receipt of monetary reward in a set of prefrontal regions including the medial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex. Adults with alcohol dependence also exhibited greater negative correlation between function in each of these regions and that in the nucleus accumbens. Within the alcohol-dependent group, those with family history of alcohol dependence exhibited lower mPFC response, and those with more frequent drinking exhibited greater negative functional connectivity between the mPFC and the nucleus accumbens. These findings indicate that alcohol dependence is associated with less engagement of prefrontal cortical regions, suggesting weak or disrupted regulation of ventral striatal response. This pattern of prefrontal response and frontostriatal connectivity has consequences for the behavior patterns typical of addiction. Furthermore, brain-behavior findings indicate that the potential mechanisms of disruption in frontostriatal circuitry in alcohol dependence include family liability to alcohol use problems and more frequent use of alcohol. In all, these findings build on the extant literature on reward-circuit function in addiction and suggest mechanisms for disrupted function in alcohol dependence. © 2014 Forbes et al

Insulin in the nervous system and the mind: Functions in metabolism, memory, and mood

Background: Insulin, a pleotrophic hormone, has diverse effects in the body. Recent work has highlighted the important role of insulin's action in the nervous system on glucose and energy homeostasis, memory, and mood. Scope of review: Here we review experimental and clinical work that has broadened the understanding of insulin's diverse functions in the central and peripheral nervous systems, including glucose and body weight homeostasis, memory and mood, with particular emphasis on intranasal insulin. Major conclusions: Implications for the treatment of obesity, type 2 diabetes, dementia, and mood disorders are discussed in the context of brain insulin action. Intranasal insulin may have potential in the treatment of central nervous system-related metabolic disorders. Keywords: Insulin, Intranasal insulin, Memory, Metabolism, Moo

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

The block-design monetary reward task employed in the current study.

<p>Participants were instructed to guess whether a number was low or high and to respond to win outcomes.</p

Association of Alcohol Dependent Adults' Drinking Characteristics with Function in Reward Circuitry.

<p><i>Note</i>: Analyses were thresholded at p_corrected<0.05 using AlphaSim and were constrained using findings for group differences in which the alcohol dependent group exhibited less response than the healthy control group. The contrast generated from the reward task was win > loss. Age was included as a covariate in model of frequency of use. Cluster size is in voxels. mPFC: medial prefrontal cortex.</p

Differences in Function of Reward Circuitry between Adults with Alcohol Dependence and Healthy Control Adults.

<p><i>Note</i>: Results are from region-of-interest analyses focusing on the OFC, mPFC, DLPFC, and ventral striatum. Analyses were thresholded at p_corrected<0.05 using AlphaSim. <i>df</i> = 135. The contrast generated from the reward task was win > loss. Cluster size is in voxels. There were no regions for which (1) alcohol dependent adults exhibited greater response than healthy adults or (2) less negative functional connectivity with the accumbens than healthy adults. There were null findings for positive functional connectivity. OFC: orbitofrontal cortex. mPFC: medial prefrontal cortex. DLPFC: dorsolateral prefrontal cortex.</p

Sample Characteristics.

<p><i>Note</i>: All participants in the alcohol dependent group met DSM-IV criteria for alcohol dependence but had undergone monitored abstinence prior to participating. Severity of alcohol dependence was measured with the Alcohol Dependence Scale <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094640#pone.0094640-Skinner1" target="_blank">[62]</a>. All daily smokers met criteria for nicotine dependence. Family history reflects alcoholism in any first- or second-degree relatives. Groups did not differ significantly for any demographic characteristics. N/A: other than confirming the absence of alcohol use disorders, we did not assess drinking behavior and drinking history in the healthy control group.</p