Healthy Male Controls Research Articles

Effect of inhaled anaesthetics gases on cytokines and oxidative stress alterations for the staff health status in hospitals

ObjectivesThe present study aimed to evaluate the effects of waste anaesthetic gases on cytokines and oxidative stress of hospital health team members following exposure to waste anaesthetic gases (WAGs).Subjects and methodsIn total, 180 participants took part in this study; 60 of these were healthy male controls and the 120 participants in the intervention group were staff who work in the operating room. This latter group comprises six occupational subgroups (1) surgeons, (2) surgical assistants, (3) anaesthesiologists (4) anaesthesiology assistants, (5) nurses and (6) janitors. The following parameters were assessed: catalase (CAT), glutathione peroxidase (GSHpx) and superoxide dismutase (SOD) activities, plasma fluoride, serum interferon gamma (IFN-γ), serum interleukin 2 (IL2), serum interleukin 4 (IL4) and plasma thiobarbituric acid reactive substances (TBARS).ResultsAnaesthesiologists and their assistants exhibited the highest levels of plasma fluoride, serum IFN-γ and IL 2, exceeding the levels in detected in all the other occupational subgroups. Furthermore, the serum levels of IL4 were significantly raised in anaesthesiologists and the difference between this group and other groups was statistically significant. However, compared with the other subgroups, surgeons exhibited elevated plasma TBARS and reduced CAT, GSHpx and SOD; these variances were also statistically significant.Conclusion and recommendationsThe findings of this study indicate that operating room staff exposed to WAGs are vulnerable to experiencing immunotoxicity as the WAGs are considered to initiate oxidative stress and increase the levels of cytokines in serum. Thus, an education programme is warranted to inform staff working in environments where they may be subjected to WAGs on the effects that the gases can have upon their health and how to minimise their exposure to WAGs. An ongoing effort is also needed to ensure anaesthesia safety standards are maintained at all times. The findings of this study may provide a springboard for future research into occupational exposure to WAGs and their wider effect upon health.

Adolescent and Young Adult Urogenital Outcome following Childhood Hypospadias Repair: Perfection Revisited.

We assessed the long-term surgical, functional urinary and sexual outcomes of adolescent and young adult men who underwent childhood hypospadias repair. Men born with nonsyndromic hypospadias and healthy male controls aged 16-21 years old were recruited, and their surgical, urinary, sexual functional and aesthetic outcomes assessed. Good outcome was defined as a patent and orthotopic meatus without fistulas, and straight erections (<30 degree curvature) without erectile or ejaculatory problems. Statistics included regression analyses, chi-square/Fisher exact tests and Student's t/Mann-Whitney U and Kruskal-Wallis tests. A total of 193 patients and 50 controls participated 16.4 years (range 8.2-21.2) after initial repair. At least 1 reintervention was performed in 39.2%. The highest reintervention rate was found in those younger than 12 months at initial repair, even when excluding proximal hypospadias cases. A disturbed urinary and/or suboptimal sexual functional outcome was seen in 52.9% of cases. Suboptimal voiding was found in 22.1%, although few had relevant residual urine. More reinterventions and proximal hypospadias cases were associated with suboptimal urinary outcome, and the latter also with impaired sexual function. Poor inter-observer agreements were found between physician and patient genital appraisal. In 52.9% of cases, at least 1 concern was identified that required long-term followup. Hypospadias repair below 12 months was associated with more reinterventions. Adopting a restrictive attitude toward aesthetic refinement, unless on the patient's own request, could improve urinary outcomes.

The Effect of Obstructive Sleep Apnea and Continuous Positive Airway Pressure Therapy on Skeletal Muscle Lipid Content in Obese and Nonobese Men.

Obstructive sleep apnea (OSA), independently of obesity (OBS), predisposes to insulin resistance (IR) for largely unknown reasons. Because OSA-related intermittent hypoxia triggers lipolysis, overnight increases in circulating free fatty acids (FFAs) including palmitic acid (PA) may lead to ectopic intramuscular lipid accumulation potentially contributing to IR. Using 3-T-1H-magnetic resonance spectroscopy, we therefore compared intramyocellular and extramyocellular lipid (IMCL and EMCL) in the vastus lateralis muscle at approximately 7 am between 26 male patients with moderate-to-severe OSA (17 obese, 9 nonobese) and 23 healthy male controls (12 obese, 11 nonobese). Fiber type composition was evaluated by muscle biopsies. Moreover, we measured fasted FFAs including PA, glycated hemoglobin A1c, thigh subcutaneous fat volume (ScFAT, 1.5-T magnetic resonance tomography), and maximal oxygen uptake (VO2max). Fourteen patients were reassessed after continuous positive airway pressure (CPAP) therapy. Total FFAs and PA were significantly (by 178% and 166%) higher in OSA patients vs controls and correlated with the apnea-hypopnea index (AHI) (r ≥ 0.45, P < .01). Moreover, IMCL and EMCL were 55% (P < .05) and 40% (P < .05) higher in OSA patients, that is, 114% and 103% in nonobese, 24.4% and 8.4% in obese participants (with higher control levels). Overall, PA, FFAs (minus PA), and ScFAT significantly contributed to IMCL (multiple r = 0.568, P = .002). CPAP significantly decreased EMCL (–26%) and, by trend only, IMCL, total FFAs, and PA. Muscle fiber composition was unaffected by OSA or CPAP. Increases in IMCL and EMCL are detectable at approximately 7 am in OSA patients and are partly attributable to overnight FFA excesses and high ScFAT or body mass index. CPAP decreases FFAs and IMCL by trend but significantly reduces EMCL.

White matter deficits in cocaine use disorder: convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomic analysis

White matter (WM) abnormalities in patients with cocaine use disorder (CUD) have been studied; however, the reported effects on the human brain are heterogenous and most results have been obtained from male participants. In addition, biological data supporting the imaging findings and revealing possible mechanisms underlying the neurotoxic effects of chronic cocaine use (CU) on WM are largely restricted to animal studies. To evaluate the neurotoxic effects of CU in the WM, we performed an in vivo diffusion tensor imaging assessment of male and female cocaine users (n = 75) and healthy controls (HC) (n = 58). Moreover, we performed an ex vivo large-scale proteomic analysis using liquid chromatography-tandem mass spectrometry in postmortem brains of patients with CUD (n = 8) and HC (n = 12). Compared with the HC, the CUD group showed significant reductions in global fractional anisotropy (FA) (p < 0.001), and an increase in global mean (MD) and radial diffusion (RD) (both p < 0.001). The results revealed that FA, RD, and MD alterations in the CUD group were widespread along the major WM tracts, after analysis using the tract-based special statistics approach. Global FA was negatively associated with years of CU (p = 0.0421) and female sex (p < 0.001), but not with years of alcohol or nicotine use. Concerning the fibers connecting the left to the right prefrontal cortex, Brodmann area 9 (BA9), the CUD group presented lower FA (p = 0.006) and higher RD (p < 0.001) values compared with the HC group. A negative association between the duration of CU in life and FA values in this tract was also observed (p = 0.019). Proteomics analyses in BA9 found 11 proteins differentially expressed between cocaine users and controls. Among these, were proteins related to myelination and neuroinflammation. In summary, we demonstrate convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomics analysis of WM disruption in CUD.

Evaluation of Zn, Cu, and Se Levels in the North American Autism Spectrum Disorder Population

Metal ion dyshomeostasis and disparate levels of biometals like zinc (Zn), copper (Cu), and selenium (Se) have been implicated as a potential causative factor for Autism Spectrum Disorder (ASD). In this study, we have enrolled 129 children (aged 2–4 years) in North America, of which 64 children had a diagnosis of ASD and 65 were controls. Hair, nail, and blood samples were collected and quantitatively analyzed for Zn, Cu and Se using inductively coupled plasma mass spectrometry (ICP-MS). Of the analyzed biometals, serum Se (116.83 ± 14.84 ng/mL) was found to be significantly lower in male ASD cases compared to male healthy controls (128.21 ± 9.11 ng/mL; p < 0.005). A similar trend was found for nail Se levels in ASD (1.01 ± 0.15 mcg/g) versus that of controls (1.11 ± 0.17 mcg/g) with a p-value of 0.0132 using a stratified Wilcoxon rank sum testing. The level of Se in ASD cohort was co-analyzed for psychometric correlation and found a negative correlation between total ADOS score and serum Se levels. However, we did not observe any significant difference in Zn, Cu, and Zn/Cu ratio in ASD cases versus controls in this cohort of North American children. Further studies are recommended to better understand the biology of the relationship between Se and ASD status.

Prediction of sarcopenia using a battery of circulating biomarkers

Loss of muscle mass and strength with aging, termed sarcopenia is accelerated in several comorbidities including chronic heart failure (CHF) and chronic obstructive pulmonary diseases (COPD). However, the effective circulating biomarkers to accurately diagnose and assess sarcopenia are not known. We recruited male healthy controls and patients with CHF and COPD (n = 81–87/group), aged 55–74 years. Sarcopenia was clinically identified based on hand-grip strength, appendicular skeletal muscle index and physical capacity as recommended by the European working group for sarcopenia. The serum levels of amino-terminal pro-peptide of type-III procollagen, c-terminal agrin fragment-22, osteonectin, irisin, fatty acid-binding protein-3 and macrophage migration inhibitory factor were significantly different between healthy controls and patients with CHF and COPD. Risk scores for individual biomarkers were calculated by logistic regressions and combined into a cumulative risk score. The median cutoff value of 3.86 was used to divide subjects into high- and low-risk groups for sarcopenia with the area under the curve of 0.793 (95% CI = 0.738–0.845, p < 0.001). A significantly higher incidence of clinical sarcopenia was found in high-risk group. Taken together, the battery of biomarkers can be an effective tool in the early diagnosis and assessment of sarcopenia.

Gut microbial differences in breast and prostate cancer cases from two randomised controlled trials compared to matched cancer-free controls.

Implicated in several chronic diseases, the gastrointestinal microbiome is hypothesised to influence carcinogenesis. We compared faecal microbiota of newly diagnosed treatment-naïve overweight and obese cancer patients and matched controls. Cases were enrolled in presurgical weight-loss trials for breast (NCT02224807) and prostate (NCT01886677) cancers and had a body mass index (BMI) ≥25 kg/m2. Cancer-free controls were matched 1:1 by age (±5 years), race, gender, and BMI (±5 kg/m2). All participants provided faecal samples; isolated bacterial DNA were PCR amplified at the V4 region of the 16S rRNA gene and analysed using the QIIME pipeline. Tests compared cases versus controls, then separately by gender. Microbial alpha-diversity and beta-diversity were assessed, and relative abundance of Operational Taxonomic Units (OTU's) were compared at the genus level, with false discovery rate (FDR) correction. 22 overweight and obese cancer patients were matched with 22 cancer-free controls, with an average BMI of 30.5±4.3 kg/m2, age 54.4±5.3 years, and 54.5% were black. Fourteen matches were made between breast cancer cases and healthy female controls, and 8 matches were made with prostate cancer cases and healthy male controls. Comparison of all cases and controls revealed no differences in alpha diversity, though prostate cancer patients had higher Chao1 (P=0.006) and Observed Species (P=0.036) than cancer-free males. Beta-diversity metrics were significantly different between cases and controls (P<0.03 for all tests in whole sample and in men), though only unweighted Unifrac was different in women (P=0.005). Kruskal Wallis tests indicated significant differences among 16 genera in all matches, 9 in female, and 51 in male. This study suggests the faecal microbiota of treatment-naive breast and prostate cancer patients differs from controls, though larger samples are needed to substantiate these findings. Trial registration: NIH Clinical Trials, NCT01886677, NCT02224807, registered 26 June 2013, 25 Aug 2014 (respectively) - retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01886677; https://clinicaltrials.gov/ct2/show/NCT02224807.

Functional connectivity between brain regions underlying executive control and language in schizophrenia patients with history of auditory verbal hallucination

IntroductionSchizophrenia patients with auditory verbal hallucinations (AVH) demonstrate impaired functional connectivity (FC) between brain regions, involved in executive functions and language. However, as most studies compare patients to healthy controls, the specificity of these findings either for schizophrenia in general or for AVH is unclear.ObjectivesWe aimed to compare whole-brain resting-state FC of main language brain regions between schizophrenia patients with and without history of AVH and healthy controls.MethodsSchizophrenia male patients with (n=31; mean age 29,8±11,6) or without history of AVH (n=16; 29±12,4) and 39 healthy male controls (30±8,9) underwent resting-state fMRI on 3T Philips scanner. No between-group differences in age, illness duration, and severity of clinical symptoms except AVH were revealed. Regions of interest (ROIs) were taken from the independent fMRI study with conventional language localizer and included left inferior frontal gyrus (l_IFG) and superior temporal gyri (STG) bilaterally. Whole-brain FC of each ROI was compared between groups (ANCOVA; p&lt;.005 voxelwise; p(FDR)&lt;.017 clusterwise, corrected for number of ROIs) with post hoc tests.ResultsDecreased FC between each STG (left and right) and anterior cingulate cortex (ACC) was revealed in all patients, compared to healthy controls. Patients with history of AVH, compared to other groups, showed decreased FC between l_IFG and ACC.ConclusionsDisrupted fronto-temporal FC is non-specific for AVH and characterizes all schizophrenia patients. Patients with history of AVH have impaired FC between the l_IFG, underlying language production, and ACC, involved in differentiation between language production and comprehension. The study was supported by RFBR grant 18-013-01214.

Functional connectivity between brain regions underlying executive control and language in schizophrenia patients with history of auditory verbal hallucinations

IntroductionSchizophrenia patients with auditory verbal hallucinations (AVH) demonstrate impaired functional connectivity (FC) between brain regions, involved in executive functions and language. However, as most studies compare patients to healthy controls, the specificity of these findings either for schizophrenia in general or for AVH is unclear.ObjectivesWe aimed to compare whole-brain resting-state FC of main language brain regions between schizophrenia patients with and without history of AVH and healthy controls.MethodsSchizophrenia male patients with (n=31; mean age 29,8±11,6) or without history of AVH (n=16; 29±12,4) and 39 healthy male controls (30±8,9) underwent resting-state fMRI on 3T Philips scanner. No between-group differences in age, illness duration, and severity of clinical symptoms except AVH were revealed. Regions of interest (ROIs) were taken from the independent fMRI study with conventional language localizer and included left inferior frontal gyrus (l_IFG) and superior temporal gyri (STG) bilaterally. Whole-brain FC of each ROI was compared between groups (ANCOVA; p&lt;.005 voxelwise; p(FDR)&lt;.017 clusterwise, corrected for number of ROIs) with post hoc tests.ResultsDecreased FC between each STG (left and right) and anterior cingulate cortex (ACC) was revealed in all patients, compared to healthy controls. Patients with history of AVH, compared to other groups, showed decreased FC between l_IFG and ACC.ConclusionsDisrupted fronto-temporal FC is non-specific for AVH and characterizes all schizophrenia patients. Patients with history of AVH have impaired FC between the l_IFG, underlying language production, and ACC, involved in differentiation between language production and comprehension. The study was supported by RFBR grant 18-013-01214.Conflict of interestThe study was supported by RFBR grant 18-013-01214.

Cellular studies of the two main isoforms of human d-aspartate oxidase.

Human d-aspartate oxidase (hDASPO) is a FAD-dependent enzyme responsible for the degradation of d-aspartate (d-Asp). In the mammalian central nervous system, d-Asp behaves as a classical neurotransmitter, it is thought to be involved in neural development, brain morphology and behavior, and appears to be involved in several pathological states, such as schizophrenia and Alzheimer's disease. Apparently, the human DDO gene produces alternative transcripts encoding for three putative hDASPO isoforms, constituted by 341 (the 'canonical' form), 369, and 282 amino acids. Despite the increasing interest in hDASPO and its physiological role, little is known about these different isoforms. Here, the additional N-terminal peptide present in the hDASPO_369 isoform only has been identified in hippocampus of Alzheimer's disease female patients, while peptides corresponding to the remaining part of the protein were present in samples from male and female healthy controls and Alzheimer's disease patients. The hDASPO_369 isoform was largely expressed in E.coli as insoluble protein, hampering with its biochemical characterization. Furthermore, we generated U87 human glioblastoma cell clones stably expressing hDASPO_341 and, for the first time, hDASPO_369 isoforms; the latter protein showed a lower expression compared with the canonical isoform. Both protein isoforms are active (showing similar kinetic properties), localize to the peroxisomes, are very stable (a half-life of approximately 100h has been estimated), and are primarily degraded through the ubiquitin-proteasome system. These studies shed light on the properties of hDASPO isoforms with the final aim to clarify the mechanisms controlling brain levels of the neuromodulator d-Asp.

High Plasma Cystine Levels Are Associated with Blood Pressure and Reversed by CPAP in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) independent of obesity (OBS) imposes severe cardiovascular risk. To what extent plasma cystine concentration (CySS), a novel pro-oxidative vascular risk factor, is increased in OSA with or without OBS is presently unknown. We therefore studied CySS together with the redox state and precursor amino acids of glutathione (GSH) in peripheral blood mononuclear cells (PBMC) in untreated male patients with OSA (apnea-hypopnea-index (AHI) > 15 h−1, n = 28) compared to healthy male controls (n = 25) stratifying for BMI ≥ or < 30 kg m−2. Fifteen OSA patients were reassessed after 3–5-months CPAP. CySS correlated with cumulative time at an O2-saturation <90% (Tu90%) (r = 0.34, p < 0.05) beside BMI (r = 0.58, p < 0.001) and was higher in subjects with “hypoxic stress” (59.4 ± 2.0 vs. 50.1 ± 2.7 µM, p < 0.01) defined as Tu90% ≥ 15.2 min (corresponding to AHI ≥ 15 h−1). Moreover, CySS significantly correlated with systolic (r = 0.32, p < 0.05) and diastolic (r = 0.31, p < 0.05) blood pressure. CPAP significantly lowered CySS along with blood pressure at unchanged BMI. Unexpectedly, GSH antioxidant capacity in PBMC was increased with OSA and reversed with CPAP. Plasma CySS levels are increased with OSA-related hypoxic stress and associated with higher blood pressure. CPAP decreases both CySS and blood pressure. The role of CySS in OSA-related vascular endpoints and their prevention by CPAP warrants further studies.

Global, segmental and layer specific analysis of myocardial involvement in Duchenne muscular dystrophy by cardiovascular magnetic resonance native T1 mapping

BackgroundProgressive cardiomyopathy accounts for almost all mortality among Duchenne muscular dystrophy (DMD) patients.‍ Thus, our aim was to comprehensively characterize myocardial involvement by investigating the heterogeneity of native T1 mapping in DMD patients using global and regional (including segmental and layer-specific) analysis across a large cohort.MethodsWe prospectively enrolled 99 DMD patients (8.8 ± 2.5 years) and 25 matched male healthy controls (9.5 ± 2.5 years). All subjects underwent cardiovascular magnetic resonance (CMR) with cine, T1 mapping and late gadolinium enhancement (LGE) sequences. Native T1 values based on the global and regional myocardium were measured, and LGE was defined.ResultsLGE was present in 49 (49%) DMD patients. Global native T1 values were significantly longer in LGE-positive (LGE +) patients than in healthy controls, both in basal slices (1304 ± 55 vs. 1246 ± 27 ms, p < 0.001) and in mid-level slices (1305 ± 57 vs. 1245 ± 37 ms, p < 0.001). No significant difference in global native T1 was found between healthy controls and LGE-negative (LGE−) patients. In segmental analysis, LGE + patients had significantly increased native T1 in all analyzed segments compared to the healthy control group. Meanwhile, the comparison between LGE− patients and healthy controls showed significantly elevated values only in the basal anterolateral segment (1273 ± 62 vs. 1234 ± 40 ms, p = 0.034). Interestingly, the epicardial layer had a significantly higher native T1 in LGE− patients than in healthy controls (p < 0.05), whereas no such pattern was noticed in the global myocardium. Epicardial layer native T1 resulted in the highest diagnostic performance for distinguishing between healthy controls and DMD patients in receiver operating curve analyses (area under the curve [AUC] 0.84 for basal level and 0.85 for middle level) when compared to global native T1 and endocardial layer native T1.ConclusionsMyocardial regional native T1, particularly epicardial native T1, seems to have potential as a novel robust marker of very early cardiac involvement in DMD patients.Trial registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx) ChiCTR1800018340, 09/12/2018, Retrospectively registered.

Immune function in X-linked retinoschisis subjects in an AAV8-RS1 phase I/IIa gene therapy trial

This study explored systemic immune changes in 11 subjects with X-linked retinoschisis (XLRS) in a phase I/IIa adeno-associated virus 8 (AAV8)-RS1 gene therapy trial (ClinicalTrials.gov: NCT02317887). Immune cell proportions and serum analytes were compared to 12 healthy male controls. At pre-dosing baseline the mean CD4/CD8 ratio of XLRS subjects was elevated. CD11c+ myeloid dendritic cells (DCs) and the serum epidermal growth factor (EGF) level were decreased, while CD123+ plasmacytoid DCs and serum interferon (IFN)-γ and tumor necrosis factor (TNF)-α were increased, indicating that the XLRS baseline immune status differs from that of controls. XLRS samples 14days after AAV8-RS1 administration were compared with the XLRS baseline. Frequency of CD11b+CD11c+ DCc was decreased in 8 of 11 XLRS subjects across all vector doses (1e9-3e11 vector genomes [vg]/eye). CD8+human leukocyte antigen-DR isotype (HLA-DR)+ cytotoxic Tcells and CD68+CD80+ macrophages were upregulated in 10 of 11 XLRS subjects, along with increased serum granzyme B in 8 of 11 XLRS subjects and elevated IFN-γ in 9 of 11 XLRS subjects. The six XLRS subjects with ocular inflammation after vector application gave a modestly positive correlation of inflammation score to their respective baseline CD4/CD8 ratios. This exploratory study indicates that XLRS subjects may exhibit a proinflammatory, baseline immune phenotype, and that intravitreal dosing with AAV8-RS1 leads to systemic immune activation with an increase of activated lymphocytes, macrophages, and proinflammatory cytokines.

A retrospective study of pituitary-thyroid interaction in patients with first-episode of bipolar disorder type I in Mania State.

Bipolar disorder (BD)-mania is related to the dysfunction of anterior pituitary gland, but the pituitary-thyroid interaction on the acute stage of BD has been controversial. In order to rule out the effects of drugs, we aimed to determine the upstream interaction of first-episode of BD type I in mania state, and tried to find the relationship between thyroid-stimulating-hormone (TSH) and Prolactin (PRL)This study included 70 real-world patients diagnosed with first-episode BD-mania recuited and 70 healthy controls (HC) matched for age and sex from 2016 to 2017 in the same district of Shanghai. We compared the levels of thyroid hormones and prolactin between the two groups, and linear regression and curve estimation were used for the correlation analysis of TSH and PRLThere were differences in triiodothyronine (TT3), total thyroxin (TT4), and free thyroxine (FT4) concentrations between the groups (P's < .05). After being grouped by sex, higher PRL in the male and female BD-mania subgroup were observed compared to each isosexual HC [(P's < .01, Cohen's d = 0.82/1.08, 95%CI (0.33, 1.31)/(0.58, 1.58)]. Higher FT4 in the male BD-mania group was observed compared to the HC males [(P's < .01, Cohen's d = 0.90, 95%CI (0.41, 1.39)] while the female BD-mania group showed lower TT3 and TT4 compared to the HC females [(P's < .01, Cohen's d = 0.93/0.88, 95%CI (0.43, 1.42)/(0.39, 1.37)]. In the female BD-mania group, correlation analysis established an inverse relationship between PRL and TSH (r2 = 0.25, F = 11.11, P < .01).The findings demonstrate that sex impacts the concentration of hormones secreted by the anterior pituitary of patients with first-episode BD-mania. The increased PRL may be a putative mechanism that underlies the onset in female patients with a moderate inverse relationship between TSH and PRL. Thyroid hormones and prolactin levels may be developed as potential markers for identifying BD-manic.

Acute opioid use may cause choroidal thinning and retinal nerve fiber layer increase

The number of optical coherence tomography (OCT) examinations in substance use disorders is gradually increasing. However, OCT findings in opioid use disorder (OUD) have not yet been investigated. In this study, we compared the retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), the inner plexiform layer (IPL), and choroid thickness (CT) of OUD and control groups. We included 43 male patients and 43 healthy male controls of similar age (p = 0.296) in the study, prospectively. On the day of OCT application, urine toxic screening test results of all OUD patients were positive for opioid use. There was a significant difference between OUD and control groups in terms of CT (p < 0.05), nasal superior (NS), and nasal (N) sectors of the RNFL (p < 0.05) values of both eyes. According to the binary logistic regression analysis, the sensitivity of mean NS (p = 0.001) and mean CT (p = 0.007) related to the diagnosis of OUD was 72.1 percent, and the specificity was 65.1 percent. Receiver operating characteristic (ROC) analysis revealed that the sensitivity and specificity of mean CT for the diagnosis of OUD were 18.6% and 97.7%, respectively. This is the first study to investigate the OCT findings in OUD. Our findings are important in terms of showing thinning in the choroidal layer and an increase in the volume of the NS and N sectors of RNFL while detecting opioids in the body/urine. Further studies are needed to clarify whether these differences are due to the acute and/or chronic effects of opioids.

Plasma acetylcholine and nicotinic acid are correlated with focused preference for photographed females in depressed males: an economic game study

Interpersonal difficulties are often observed in major depressive disorder (MDD), while the underlying psychological and biological mechanisms have not yet been elucidated. In the present case–control study, a PC-based trust game was conducted for 38 drug-free MDD patients and 38 healthy controls (HC). In the trust game, participants invested money in a partner (trusting behaviors), and also rated each partner’s attractiveness (preference for others). In addition, blood biomarkers including metabolites were measured. Both MDD and HC males exhibited more trusting behaviors compared to females. MDD males’ preference for ordinary-attractive partners (lay-person photographs) was lower than HC males, whereas their preference for high-attractive females (fashion-model photographs) was similar levels to HC males. This tendency in MDD males could reflect a “focused (narrowed) preference for females”. As for blood biomarker analysis, the levels of 37 metabolites including acetylcholine, AMP, GMP, nicotinic acid and tryptophan were significantly different between two groups. Interestingly, among male participants, acetylcholine and nicotinic acid were negatively correlated with the level of focused preference for photographed females. In sum, we have revealed some behavioral, psychological and biological traits of trusting behaviors and preference for others especially in MDD males. Larger studies should be conducted to validate our preliminary findings.

Brain structure and clinical profile point to neurodevelopmental factors involved in pedophilic disorder.

ObjectivePedophilic disorder (PD) is characterized bypersistent, intense sexual attraction to prepubertal children that the individual has acted on, or causes marked distress or interpersonal difficulty. Although prior research suggests that PD has neurodevelopmental underpinnings, the evidence remains sparse. To aid the understanding of etiology and treatment development, we quantified neurobiological and clinical correlates of PD.MethodWe compared 55 self‐referred, help‐seeking, non‐forensic male patients with DSM‐5 PD with 57 age‐matched, healthy male controls (HC) on clinical, neuropsychological, and structural brain imaging measures (cortical thickness and surface area, subcortical and white matter volumes). Structural brain measures were related to markers for aberrant neurodevelopment including IQ, and the 2nd to 4th digit ratio (2D:4D).ResultsPD was associated with psychiatric disorder comorbidity and ADHD and autism spectrum disorder symptoms. PD patients had lower total IQ than HC. PD individuals exhibited cortical surface area abnormalities in regions belonging to the brain's default mode network and showed abnormal volume of white matter underlying those regions. PD subjects had smaller hippocampi and nuclei accumbens than HC. Findings were not related to history of child‐related sexual offending. IQ correlated negatively with global expression of PD‐related brain features and 2D:4D correlated with surface area in PD.ConclusionsIn the largest single‐center study to date, we delineate psychiatric comorbidity, neurobiological and cognitive correlates of PD. Our morphometric findings, their associations with markers of aberrant neurodevelopment, and psychiatric comorbidities suggest that neurodevelopmental mechanisms are involved in PD. The findings may need consideration in future development of clinical management of PD patients.

Αlpha 5 subunit-containing GABAA receptors in temporal lobe epilepsy with normal MRI.

GABAA receptors containing the α5 subunit mediate tonic inhibition and are widely expressed in the limbic system. In animals, activation of α5-containing receptors impairs hippocampus-dependent memory. Temporal lobe epilepsy is associated with memory impairments related to neuron loss and other changes. The less selective PET ligand [11C]flumazenil has revealed reductions in GABAA receptors. The hypothesis that α5 subunit receptor alterations are present in temporal lobe epilepsy and could contribute to impaired memory is untested. We compared α5 subunit availability between individuals with temporal lobe epilepsy and normal structural MRI (‘MRI-negative’) and healthy controls, and interrogated the relationship between α5 subunit availability and episodic memory performance, in a cross-sectional study. Twenty-three healthy male controls (median ± interquartile age 49 ± 13 years) and 11 individuals with MRI-negative temporal lobe epilepsy (seven males; 40 ± 8) had a 90-min PET scan after bolus injection of [11C]Ro15-4513, with arterial blood sampling and metabolite correction. All those with epilepsy and six controls completed the Adult Memory and Information Processing Battery on the scanning day. ‘Bandpass’ exponential spectral analyses were used to calculate volumes of distribution separately for the fast component [VF; dominated by signal from α1 (α2, α3)-containing receptors] and the slow component (VS; dominated by signal from α5-containing receptors). We made voxel-by-voxel comparisons between: the epilepsy and control groups; each individual case versus the controls. We obtained parametric maps of VF and VS measures from a single bolus injection of [11C]Ro15-4513. The epilepsy group had higher VS in anterior medial and lateral aspects of the temporal lobes, the anterior cingulate gyri, the presumed area tempestas (piriform cortex) and the insulae, in addition to increases of ∼24% and ∼26% in the ipsilateral and contralateral hippocampal areas (P < 0.004). This was associated with reduced VF:VS ratios within the same areas (P < 0.009). Comparisons of VS for each individual with epilepsy versus controls did not consistently lateralize the epileptogenic lobe. Memory scores were significantly lower in the epilepsy group than in controls (mean ± standard deviation −0.4 ± 1.0 versus 0.7 ± 0.3; P = 0.02). In individuals with epilepsy, hippocampal VS did not correlate with memory performance on the Adult Memory and Information Processing Battery. They had reduced VF in the hippocampal area, which was significant ipsilaterally (P = 0.03), as expected from [11C]flumazenil studies. We found increased tonic inhibitory neurotransmission in our cohort of MRI-negative temporal lobe epilepsy who also had co-morbid memory impairments. Our findings are consistent with a subunit shift from α1/2/3 to α5 in MRI-negative temporal lobe epilepsy.

Magnetic resonance spectroscopy as marker for neurodegeneration in X-linked adrenoleukodystrophy

X-linked adrenoleukodsytrophy (ALD) is a genetic neuro-metabolic disorder, causing a slowly progressive myelopathy in adult male and female patients. New disease modifying therapies for myelopathy are under development. This calls for new (imaging) markers able to measure disease severity and progression in clinical trials. In this prospective cohort study, we measured cerebral metabolite levels with Magnetic Resonance Spectroscopy (MRS), and evaluated their potential as biomarkers for disease severity and neurodegeneration in ALD. We used a comprehensive protocol of 3T Magnetic Resonance Spectroscopic Imaging (MRSI) and 7T Single Voxel Spectroscopy (SVS) in a large cohort of adult ALD males without cerebral demyelination. One hundred seven baseline scans – 59 obtained in ALD patients (42 3T MRSI and 17 7T SVS) and 48 obtained in healthy male controls (32 3T MRSI and 16 7T SVS) – and 82 one and two-year follow-up scans (66 3T MRSI and 16 7T SVS) of ALD patients were included. Both protocols showed significantly lower concentration ratios of N-acetylaspartate/creatine (tNAA/tCr) and Glx (glutamine + glutamate)/tCr in the grey and white matter of patients, compared to controls. A novel finding is the higher level of inositol (Ins)/tCr and choline containing compounds (tCho)/tCr in ALD patients without cerebral demyelination. Furthermore, tNAA/tCr correlated strongly with clinical measures of severity of myelopathy. There was no detectable change in metabolite ratios after one-year or two-year follow-up. Our results imply that cerebral metabolite levels – and more specifically the tNAA/tCr ratio – measured with MRS, have potential value as (imaging) biomarkers in ALD.

Effect of inhaled anesthetic gases on immune status alterations in health care workers

The objective of this research was to evaluate consequences to the immune system of long-term exposure to waste anesthetic gases (WAG) by medical theater personnel. Two groups were recruited: (i) 60 healthy male controls; (ii) 120 medical professionals exposed to WAG, subdivided according to theater role, i.e. surgeons, surgical assistants (SA), anesthetists, anesthetic assistants (AA), nurses, and workers. Serum levels of fluoride, hexafluoroisopropanol (HFIP), total lymphocyte counts, as well as of CD3, CD4, and CD8 cells, CD4/CD8 ratios, and immunoglobulins IgA, IgG, IgM, and IgE were assayed. The results showed that fluoride and HFIP titers were significantly increased in anesthetists and AA compared with the other exposed groups. All exposed groups demonstrated significant elevation in lymphocyte count, CD4+ cell levels, CD4/CD8 ratios, as well as levels of IgE, IgM and IgG compared with the controls. With regard to the latter outcomes, a significant increase in IgE was seen in the surgeon, nurse, and worker groups compared with the other professions. Surgeons, anesthetists and AA exhibited higher IgM titers compared with their colleagues. Significantly higher IgG levels were identified in the SA, anesthetists, AA, and workers than in their nurses and surgeon coworkers. Of the six sub-groups, only the anesthetists and their assistants (AA) displayed a significant increase in CD4+ cells and CD4/CD8 ratios and a decrease of CD8+ cells compared with the controls. This spectrum of results suggests that variation exists in immunomodulatory responses to WAG exposure amongst hospital personnel.