Several lines of evidence suggest aberrant immune response in schizophrenia, including elevated levels of cytokines. These cytokines are thought to be produced by activated microglia, the innate ...immune cells of the central nervous system. However, increase in translocator protein 18 kDa (TSPO), a marker of activated glia, has not been found in patients with chronic schizophrenia using second-generation radiotracers and positron emission tomography (PET)-based neuroimaging. In this study we focused on patients with recent onset of schizophrenia (within 5 years of diagnosis). Quantified levels of TSPO in the cortical and subcortical brain regions using the PET-based radiotracer (11)CDPA-713 were compared between the patients and healthy controls. Markers of inflammation, including interleukin 6 (IL-6), were assessed in the plasma and cerebrospinal fluid (CSF) in these participants. We observed no significant change in the binding of (11)CDPA-713 to TSPO in 12 patients with recent onset of schizophrenia compared with 14 controls. Nevertheless, the patients with recent onset of schizophrenia showed a significant increase in IL-6 in both plasma (P<0.001) and CSF (P=0.02). The CSF levels of IL-6 were significantly correlated with the levels of IL-6 in plasma within the total study population (P<0.001) and in patients with recent onset of schizophrenia alone (P=0.03). Our results suggest that increased levels of IL-6 may occur in the absence of changed TSPO PET signal in the brains of medicated patients with recent onset of schizophrenia. Future development of PET-based radiotracers targeting alternative markers of glial activation and immune response may be needed to capture the inflammatory signature present in the brains of patients with early-stage disease.
CONTEXT Although impunity for those responsible for trauma is widely thought
to be associated with psychological problems in survivors of political violence,
no study has yet investigated this issue. ...OBJECTIVE To examine the mental health and cognitive effects of war trauma and
how appraisal of redress for trauma and beliefs about justice, safety, other
people, war cause, and religion relate to posttraumatic stress responses in
war survivors. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional survey conducted between March 2000 and July 2002
with a population-based sample of 1358 war survivors who had experienced at
least 1 war-related stressor (combat, torture, internal displacement, refugee
experience, siege, and/or aerial bombardment) from 4 sites in former Yugoslavia,
accessed through linkage sampling. Control groups at 2 study sites were matched
with survivors on sex, age, and education. MAIN OUTCOME MEASURES Semi-structured Interview for Survivors of War, Redress for Trauma Survivors
Questionnaire, Emotions and Beliefs After War questionnaire, Structured Clinical
Interview for the Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition (DSM-IV). RESULTS The mean (SD) age was 39 (12) years, 806 (59%) were men, and 339 (25%)
had high school or higher level of education. Participants reported experiencing
a mean of 12.6 war-related events, with 292 (22%) and 451 (33%) having current
and lifetime posttraumatic stress disorder (PTSD), respectively, and 129 (10%)
with current major depression. A total of 1074 (79%) of the survivors reported
a sense of injustice in relation to perceived lack of redress for trauma.
Perceived impunity for those held responsible for trauma was only one of the
factors associated with sense of injustice. Relative to controls, survivors
had stronger emotional responses to impunity, greater fear and loss of control
over life, less belief in benevolence of people, greater loss of meaning in
war cause, stronger faith in God, and higher rates of PTSD and depression.
Fear and loss of control over life were associated with PTSD and depression
(odds ratio OR, 2.91; 95% CI, 2.27-3.74 and OR, 2.30; 95% CI, 1.75-3.03,
respectively), and emotional responses to impunity showed a relatively weaker
association with PTSD (OR, 1.53; 95% CI, 1.16-2.02) and depression (OR, 1.39;
95% CI, 1.02-1.91). Appraisal of redress for trauma was not associated with
PTSD or depression. CONCLUSIONS PTSD and depression in war survivors appear to be independent of sense
of injustice arising from perceived lack of redress for trauma. Fear of threat
to safety and loss of control over life appeared to be the most important
mediating factors in PTSD and depression. These findings may have important
implications for reconciliation efforts in postwar countries and effective
interventions for traumatized war survivors.
•Mavoglurant binds to same allosteric site on mGluR5 as the radioligand 11C-ABP688.•Mavoglurant penetrates brain and induces mGluR5 receptors occupancy in dose- and exposure-dependent manner.•Maximum ...concentrations of mavoglurant were observed around 2–3.25 h post-dose.•A single dose of 400 mg causes 85% receptor occupancy after 3–4 h of administration.
Mavoglurant binds to same allosteric site on metabotropic glutamate receptor 5 (mGluR5) as 11C-ABP688, a radioligand. This open-label, single-center pilot study estimates extent of occupancy of mGluR5 receptors following single oral doses of mavoglurant, using 11C-ABP688 positron emission tomography (PET) imaging, in six healthy males aged 20–40 years. This study comprised three periods and six subjects were divided into two cohorts. On Day 1 (Period 1), baseline clinical data and safety samples were obtained along with PET scan. During Period 2 (1–7 days after Period 1), cohort 1 and 2 received mavoglurant 25 mg and 100 mg, respectively. During Period 3 (7 days after Period 2), cohort 1 and 2 received mavoglurant 200 mg and 400 mg, respectively. Mavoglurant showed the highest distribution volumes in the cingulate region with lower uptake in cerebellum and white matter, possibly because myelinated axonal sheets maybe devoid of mGlu5 receptors. Maximum concentrations of mavoglurant were observed around 2–3.25 h post-dose. Mavoglurant passed the blood–brain barrier and induced dose- and exposure-dependent displacement of 11C-ABP688 from the mGluR5 receptors, 3–4 h post-administration (27%, 59%, 74%, 85% receptor occupancy for mavoglurant 25 mg, 100 mg, 200 mg, 400 mg dose, respectively). There were no severe adverse effects or clinically significant changes in safety parameters.
This is the first human receptor occupancy study completed with Mavoglurant. It served to guide the dosing of mavoglurant in the past and currently ongoing clinical studies. Furthermore, it confirms the utility of 11C-ABP688 as a unique tool to study drug-induced occupancy of mGlu5 receptors in the living human brain.
IMPORTANCE: Microglia, the resident immune cells of the central nervous system, play an important role in the brain’s response to injury and neurodegenerative processes. It has been proposed that ...prolonged microglial activation occurs after single and repeated traumatic brain injury, possibly through sports-related concussive and subconcussive injuries. Limited in vivo brain imaging studies months to years after individuals experience a single moderate to severe traumatic brain injury suggest widespread persistent microglial activation, but there has been little study of persistent glial cell activity in brains of athletes with sports-related traumatic brain injury. OBJECTIVE: To measure translocator protein 18 kDa (TSPO), a marker of activated glial cell response, in a cohort of National Football League (NFL) players and control participants, and to report measures of white matter integrity. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional, case-control study included young active (n = 4) or former (n = 10) NFL players recruited from across the United States, and 16 age-, sex-, highest educational level–, and body mass index–matched control participants. This study was conducted at an academic research institution in Baltimore, Maryland, from January 29, 2015, to February 18, 2016. MAIN OUTCOMES AND MEASURES: Positron emission tomography–based regional measures of TSPO using 11CDPA-713, diffusion tensor imaging measures of regional white matter integrity, regional volumes on structural magnetic resonance imaging, and neuropsychological performance. RESULTS: The mean (SD) ages of the 14 NFL participants and 16 control participants were 31.3 (6.1) years and 27.6 (4.9) years, respectively. Players reported a mean (SD) of 7.0 (6.4) years (range, 1-21 years) since the last self-reported concussion. Using 11CDPA-713 positron emission tomographic data from 12 active or former NFL players and 11 matched control participants, the NFL players showed higher total distribution volume in 8 of the 12 brain regions examined (P < .004). We also observed limited change in white matter fractional anisotropy and mean diffusivity in 13 players compared with 15 control participants. In contrast, these young players did not differ from control participants in regional brain volumes or in neuropsychological performance. CONCLUSIONS AND RELEVANCE: The results suggest that localized brain injury and repair, indicated by higher TSPO signal and white matter changes, may be associated with NFL play. Further study is needed to confirm these findings and to determine whether TSPO signal and white matter changes in young NFL athletes are related to later onset of neuropsychiatric symptoms.
The Remote Malnutrition Application (R-MAPP) was developed during the COVID-19 pandemic to provide support for health care professionals (HCPs) working in the community to complete remote nutritional ...assessments, and provide practical guidance for nutritional care. The aim of this study was to modify the R-MAPP into a version suitable for children, Pediatric Remote Malnutrition Application (Pedi-R-MAPP), and provide a structured approach to completing a nutrition focused assessment as part of a technology enabled care service (TECS) consultation.
A ten-step process was completed: 1) permission to modify adult R-MAPP, 2) literature search to inform the Pedi-R-MAPP content, 3) Pedi-R-MAPP draft, 4) international survey of HCP practice using TECS, 5) nutrition experts invited to participate in a modified Delphi process, 6) first stakeholder meeting to agree purpose/draft of the tool, 7) round-one online survey, 8) statements with consensus removed from survey, 9) round-two online survey for statements with no consensus and 10) second stakeholder meeting with finalisation of the Pedi-R-MAPP nutrition awareness tool.
The international survey completed by 463 HCPs, 55% paediatricians, 38% dietitians, 7% nurses/others. When HCPs were asked to look back over the last 12 months, dietitians (n = 110) reported that 5.7 ± 10.6 out of every 10 appointments were completed in person; compared to paediatricians (n = 182) who reported 7.5 ± 7.0 out of every 10 appointments to be in person (p < 0.0001), with the remainder completed as TECS consultations.
Overall, 74 articles were identified and used to develop the Pedi-R-MAPP which included colour-coded advice using a traffic light system; green, amber, red and purple. Eighteen participants agreed to participate in the Delphi consensus and completed both rounds of the modified Delphi survey. Agreement was reached at the first meeting on the purpose and draft sections of the proposed tool. In round-one of the online survey, 86% (n = 89/104) of statements reached consensus, whereas in round-two 12.5% (n = 13/104) of statements reached no consensus. At the second expert meeting, contested statements were discussed until agreement was reached and the Pedi-R-MAPP could be finalised.
The Pedi-R-MAPP nutrition awareness tool was developed using a modified Delphi consensus. This tool aims to support the technological transformation fast-tracked by the COVID-19 pandemic by providing a structured approach to completing a remote nutrition focused assessment, as well as identifying the frequency of follow up along with those children who may require in-person assessment.
Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and ...chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence.
The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity.
The present guideline was developed according to the standard operating procedure for ESPEN guidelines, following the Scottish Intercollegiate Guidelines Network (SIGN) grading system (A, B, 0, and good practice point (GPP)). The procedure included an online voting (Delphi) and a final consensus conference.
In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity – including sarcopenic obesity – is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician.
The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
Patients with chronic gastrointestinal disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and ...chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean gastrointestinal patients. The present guideline addresses this question according to current knowledge and evidence.
The present practical guideline is intended for clinicians and practitioners in general medicine, gastroenterology, surgery and other obesity management, including dietitians and focuses on obesity care in patients with chronic gastrointestinal diseases.
The present practical guideline is the shortened version of a previously published scientific guideline developed according to the standard operating procedure for ESPEN guidelines. The content has been re-structured and transformed into flow-charts that allow a quick navigation through the text.
In 100 recommendations (3× A, 33× B, 24 × 0, 40× GPP, all with a consensus grade of 90% or more) care of gastrointestinal patients with obesity – including sarcopenic obesity – is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially metabolic associated liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician.
The present practical guideline offers in a condensed way evidence-based advice how to care for patients with chronic gastrointestinal diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
Altered function of the alpha7 nicotinic acetylcholine receptor (α7-nAChR) is implicated in several neuropsychiatric diseases. Nevertheless, studies of the human cerebral α7-nAChR even in healthy ...aging are limited in number and to postmortem tissue.
The distribution of the cerebral α7-nAChR was estimated in nine brain regions in 25 healthy volunteers (ages 21–86 years; median 57 years, interquartile range 52 years) using 18FASEM with positron emission tomography (PET) imaging. Regional total distribution volume (VT) measurements were calculated using the Logan method from each subject's 90 min dynamic PET data and their metabolite-corrected plasma input function. Spearman's rank or Pearson's correlation analysis was used depending on the normality of the data. Correlation between age and regional 1) volume relative to intracranial volume (volume ratio) and 2) 18FASEM VT was tested. Correlation between regional volume ratio and 18FASEM VT was also evaluated. Finally, the relationship between 18FASEM VT and neuropsychological measures was investigated in a subpopulation of 15 elderly healthy participants (those 50 years of age and older). Bonferroni correction for multiple comparisons was applied to statistical analyses.
A negative correlation between tissue volume ratio and age was observed in six of the nine brain regions including striatum and five cortical (temporal, occipital, cingulate, frontal, or parietal) regions. A positive correlation between 18FASEM VT and age was observed in all nine brain regions of interest (ROIs). There was no correlation between 18FASEM VT and volume ratio in any ROI after controlling for age. Regional 18FASEM VT and neuropsychological performance on each of eight representative subtests were not correlated among the well-performing subpopulation of elderly healthy participants.
Our results suggest an increase in cerebral α7-nAChR distribution over the course of healthy aging that should be tested in future longitudinal studies. The preservation of the α7-nAChR in the aging human brain supports the development of therapeutic agents that target this receptor for use in the elderly. Further study of the relationship between α7-nAChR availability and cognitive impairment over aging is needed.
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