Healthy Control Individuals Research Articles

Aggressiveness in the dreams of drug-naïve and clonazepam-treated patients with isolated REM sleep behavior disorder

BackgroundAlthough aggressive dream content is considered a distinctive feature of REM Sleep Behavior Disorder (RBD) and patients often report violent dreams during medical interviews, nonviolent behaviors (eating, drinking, urinating) and pleasant actions (e.g laughing, singing, dancing) or simply elemental, jerky limb movements are frequently observed during video-polysomnography. As a first-line pharmacological treatment, clonazepam has been shown to reduce motor symptoms during REM sleep, but its effect on dream content remains unclear. Here, we aimed to prospectively assess the dream content of individuals with drug-naïve isolated RBD (iRBD) and iRBD patients treated with clonazepam. MethodsThirteen (12 Male, 1 Female; age 65.38 ± 10.95) iRBD patients treated with clonazepam (iRBD-T), eleven (9 M, 2 F; age 68.90 ± 6.8) drug-naïve patients (iRBD-NT) and twelve (8 M, 1 F; age 63.33 ± 12.88) healthy control subjects of comparable age kept a dream diary over a 3-week period. Dream content analysis was conducted according to the Hall and Van de Castle method (HVdC). The Threat Simulation Scale (TSS) was employed to assess the frequency of threatening contents. ResultsA total of 214 dream reports were collected. No significant differences were found in the frequency of threatening dream contents between the iRBD subsamples and healthy control subjects (p = 0.732). The HVdC analysis detected higher levels of Friendliness in iRBD patients compared to the control group (p = 0.036). Increased levels of Aggressiveness were only observed when differentiating dreams in which dream enactment behaviors (DEB) were present compared to dreams without DEBs, both in the iRBD-T group (p = 0.007) and the iRBD-NT group (p = 0.012). ConclusionOur study shows no difference in the frequency of violent or threatening dreams in drug-naïve iRBD patients, clonazepam-treated iRBD patients and healthy control individuals. Aggressiveness is more frequent when DEBs are reported, suggesting motor disinhibition could require sufficiently dramatic and emotionally intense dreams, independent of clonazepam treatment.

Associations of Alcohol Consumption and Smoking With Disease Risk and Neurodegeneration in Individuals With Multiple Sclerosis in the United Kingdom

Understanding the effects of modifiable risk factors on risk for multiple sclerosis (MS) and associated neurodegeneration is important to guide clinical counseling. To investigate associations of alcohol use, smoking, and obesity with odds of MS diagnosis and macular ganglion cell layer and inner plexiform layer (mGCIPL) thickness. This cross-sectional study analyzed data from the community-based UK Biobank study on health behaviors and retinal thickness (measured by optical coherence tomography in both eyes) in individuals aged 40 to 69 years examined from December 1, 2009, to December 31, 2010. Risk factors were identified with multivariable logistic regression analyses. To adjust for intereye correlations, multivariable generalized estimating equations were used to explore associations of alcohol use and smoking with mGCIPL thickness. Finally, interaction models explored whether the correlations of alcohol and smoking with mGCIPL thickness differed for individuals with MS. Data were analyzed from February 1 to July 1, 2021. Smoking status (never, previous, or current), alcohol intake (never or special occasions only [low], once per month to ≤4 times per week [moderate], or daily/almost daily [high]), and body mass index. Multiple sclerosis case status and mGCIPL thickness. A total of 71 981 individuals (38 685 women [53.7%] and 33 296 men [46.3%]; mean [SD] age, 56.7 [8.0] years) were included in the analysis (20 065 healthy control individuals, 51 737 control individuals with comorbidities, and 179 individuals with MS). Modifiable risk factors significantly associated with MS case status were current smoking (odds ratio [OR], 3.05 [95% CI, 1.95-4.64]), moderate alcohol intake (OR, 0.62 [95% CI, 0.43-0.91]), and obesity (OR, 1.72 [95% CI, 1.15-2.56]) compared with healthy control individuals. Compared with the control individuals with comorbidities, only smoking was associated with case status (OR, 2.30 [95% CI, 1.48-3.51]). High alcohol intake was associated with a thinner mGCIPL in individuals with MS (adjusted β = -3.09 [95% CI, -5.70 to -0.48] μm; P = .02). In the alcohol interaction model, high alcohol intake was associated with thinner mGCIPL in control individuals (β = -0.93 [95% CI, -1.07 to -0.79] μm; P < .001), but there was no statistically significant association in individuals with MS (β = -2.27 [95% CI, -4.76 to 0.22] μm; P = .07). Smoking was not associated with mGCIPL thickness in MS. However, smoking was associated with greater mGCIPL thickness in control individuals (β = 0.89 [95% CI, 0.74-1.05 μm]; P < .001). These findings suggest that high alcohol intake was associated with retinal features indicative of more severe neurodegeneration, whereas smoking was associated with higher odds of being diagnosed with MS.

Reinforcement Learning in Patients With Mood and Anxiety Disorders vs Control Individuals

Computational psychiatry studies have investigated how reinforcement learning may be different in individuals with mood and anxiety disorders compared with control individuals, but results are inconsistent. To assess whether there are consistent differences in reinforcement-learning parameters between patients with depression or anxiety and control individuals. Web of Knowledge, PubMed, Embase, and Google Scholar searches were performed between November 15, 2019, and December 6, 2019, and repeated on December 3, 2020, and February 23, 2021, with keywords (reinforcement learning) AND (computational OR model) AND (depression OR anxiety OR mood). Studies were included if they fit reinforcement-learning models to human choice data from a cognitive task with rewards or punishments, had a case-control design including participants with mood and/or anxiety disorders and healthy control individuals, and included sufficient information about all parameters in the models. Articles were assessed for inclusion according to MOOSE guidelines. Participant-level parameters were extracted from included articles, and a conventional meta-analysis was performed using a random-effects model. Subsequently, these parameters were used to simulate choice performance for each participant on benchmarking tasks in a simulation meta-analysis. Models were fitted, parameters were extracted using bayesian model averaging, and differences between patients and control individuals were examined. Overall effect sizes across analytic strategies were inspected. The primary outcomes were estimated reinforcement-learning parameters (learning rate, inverse temperature, reward learning rate, and punishment learning rate). A total of 27 articles were included (3085 participants, 1242 of whom had depression and/or anxiety). In the conventional meta-analysis, patients showed lower inverse temperature than control individuals (standardized mean difference [SMD], -0.215; 95% CI, -0.354 to -0.077), although no parameters were common across all studies, limiting the ability to infer differences. In the simulation meta-analysis, patients showed greater punishment learning rates (SMD, 0.107; 95% CI, 0.107 to 0.108) and slightly lower reward learning rates (SMD, -0.021; 95% CI, -0.022 to -0.020) relative to control individuals. The simulation meta-analysis showed no meaningful difference in inverse temperature between patients and control individuals (SMD, 0.003; 95% CI, 0.002 to 0.004). The simulation meta-analytic approach introduced in this article for inferring meta-group differences from heterogeneous computational psychiatry studies indicated elevated punishment learning rates in patients compared with control individuals. This difference may promote and uphold negative affective bias symptoms and hence constitute a potential mechanistic treatment target for mood and anxiety disorders.

Network meta-analysis of transcriptome expression changes in different manifestations of dengue virus infection

BackgroundSeveral studies have been performed to study transcriptome profiles after dengue virus infections with partly different results. Due to slightly different settings of the individual studies, different genes and enriched gene sets are reported in these studies. The main aim of this network meta-analysis was to aggregate a selection of these studies to identify genes and gene sets that are more generally associated with dengue virus infection, i.e. with less dependence on the individual study settings.MethodsWe performed network meta-analysis by different approaches using publicly available gene expression data of five selected studies from the Gene Expression Omnibus database. The study network includes dengue fever (DF), hemorrhagic fever (DHF), shock syndrome (DSS) patients as well as convalescent and healthy control individuals. After data merging and missing value imputation, study-specific batch effects were removed. Pairwise differential expression analysis and subsequent gene-set enrichment analysis were performed between the five study groups. Furthermore, mutual information networks were derived from the top genes of each group comparison, and the separability between the three patient groups was studied by machine learning models.ResultsFrom the 10 possible pairwise group comparisons in the study network, six genes (IFI27, TPX2, CDT1, DTL, KCTD14 and CDCA3) occur with a noticeable frequency among the top listed genes of each comparison. Thus, there is an increased evidence that these genes play a general role in dengue virus infections. IFI27 and TPX2 have also been highlighted in the context of dengue virus infection by other studies. A few of the identified gene sets from the network meta-analysis overlap with findings from the original studies. Mutual information networks yield additional genes for which the observed pairwise correlation is different between the patient groups. Machine learning analysis shows a moderate separability of samples from the DF, DHF and DSS groups (accuracy about 80%).ConclusionsDue to an increased sample size, the network meta-analysis could reveal additional genes which are called differentially expressed between the studied groups and that may help to better understand the molecular basis of this disease.

Association of TP53 P72R and MDM2 SNP309 variants with susceptibil-ity to chronic myeloid leukaemia development in Algerian population: TP53 P72R C allele is a strong risk marker and MDM2 SNP309 G allele has a protective effect

Chronic myeloid leukaemia is a monoclonal myeloproliferative syndrome, whose development is related to disturbance of growth, survival, and apop-totic pathways, such as MDM2-p53 pathway, mainly due to the abnormal kinase activity of BCR-ABL. A lot of work has to be done to understand chron-ic myeloid leukaemia genetic predisposition. This is a pilot study that search-es for association between TP53 P72R variant (rs1042522); and MDM2 T309G variant (rs2279744), and the risk of chronic myeloid leukaemia occur-rence in the Algerian population. It is a case-control study using DNA sam-ples of 74 Algerian chronic myeloid leukaemia patients and 104 healthy con-trol individuals. Our results attested that TP53 P72R C allele (Pro) was strong-ly associated with increased risk of chronic myeloid leukaemia, and that TP53 P72R homozygous CC genotype should be a genetic susceptibility factor in the pathogenesis of chronic myeloid leukaemia independently of age and of gender. Furthermore, MDM2 SNP309 TT genotype was moderately associat-ed with a risk of chronic myeloid leukaemia occurrence. In conclusion, our data suggest that, in Algerian population, TP53 P72R C allele (Pro) could be a possible biomarker of chronic myeloid leukaemia susceptibility, and that MDM2 SNP309 TT genotype seems to be a low penetrance risk factor of chronic myeloid leukaemia susceptibility.

Influence of Severity and Duration of Anterior Knee Pain on Quadriceps Function and Self-Reported Function.

Little is known about how the combination of pain severity and duration affects quadriceps function and self-reported function in patients with anterior knee pain (AKP). To examine how severity (low [≤3 of 10] versus high [>3 of 10]) and duration (short [<2 years] versus long [>2 years]) of AKP affect quadriceps function and self-reported function. Cross-sectional study. Laboratory. Sixty patients with AKP (mean pain severity = 4 of 10 on the numeric pain rating scale, mean pain duration = 38 months) and 48 healthy control individuals. Patients with AKP were categorized into 3 subdivisions based on pain: (1) severity (low versus high); (2) duration (short versus long); and (3) severity and duration (low and short versus low and long versus high and short versus high and long). Quadriceps maximal (maximal voluntary isometric contraction) and explosive (rate of torque development) strength, activation (central activation ratio), and endurance (average peak torque) and self-reported function (Lower Extremity Functional Scale score). Compared with the healthy control group, (1) all AKP subgroups showed less quadriceps maximal strength (P < .005, d ≥ 0.78) and activation (P < .02, d ≥ 0.85), except for the AKP subgroup with low severity and short duration of pain (P > .32); (2) AKP subgroups with either high severity or long duration of pain showed less quadriceps explosive strength (P < .007, d ≥ 0.74) and endurance (P < .003, d ≥ 0.79), but when severity and duration were combined, only the AKP subgroup with high severity and long duration of pain showed less quadriceps explosive strength (P = .006, d = 1.09) and endurance (P = .0004, d = 1.21); and (3) all AKP subgroups showed less self-reported function (P < .0001, d ≥ 3.44). Clinicians should be aware of the combined effect of severity and duration of pain and incorporate both factors into clinical practice when rehabilitating patients with AKP.

Aortic intima media thickness in children and adolescents with type 1 diabetes: A systematic review.

AimsGreater aortic intima media thickness (aIMT), a marker of subclinical atherosclerosis, can identify individuals at risk of CVD. This systematic review with meta‐analysis compared aIMT in youth with type 1 diabetes and healthy controls.MethodsA systematic search of published literature (to July 2021) was undertaken using electronic databases MEDLINE, EMBASE, Scopus, CINAHL and AMED. Eligible studies reported aIMT in participants aged <20 years with type 1 diabetes and healthy controls. Meta‐analysis was used to combine outcome data, presented as forest plots. Moderator analysis and metaregression were conducted to identify study and participant characteristics associated with aIMT. Publication bias was assessed by funnel plot inspection.ResultsMeta‐analysis of nine studies (n = 1030 with type 1 diabetes and n = 498 healthy control participants) indicated, with high heterogeneity (I2 98%), that youth with type 1 diabetes have higher aIMT compared with healthy controls (mean difference [95% CIs]: 0.11 [0.04, 0.18] mm, P = 0.003). Factors associated with greater aIMT in type 1 diabetes compared to controls included: use of a phased array probe versus linear array probe; longer diabetes duration; higher insulin dose; higher BMI z score and waist circumference; higher LDL cholesterol; higher triglycerides; and higher diastolic blood pressure.ConclusionsType 1 diabetes in youth is associated with higher aIMT compared with healthy control individuals. Longer duration of diabetes and major CVD risk factors were also associated with higher aIMT. Together, these findings provide a strong rationale for targeting modifiable risk factors in CVD prevention. Registered in PROSPERO on 8 August 2019 (CRD42019137559).

Comparison of White Matter Structure of Drug-Naïve Patients With Bipolar Disorder and Major Depressive Disorder Using Diffusion Tensor Tractography.

BackgroundThe presence of microstructural white matter (WM) abnormalities in individuals with bipolar disorder (BD) has previously been reported. However, the interpretation of data is challenging because pharmacological treatment has a potential effect on WM integrity. To date, no study has compared the differences in WM structure among drug-naïve BD patients, drug-naïve major depression disorder (MDD) patients, and healthy controls (HC) using the visual evaluation method of diffusion tensor tractography (DTT).MethodsThis retrospective study included 12 drug-naïve patients with BD, 15 drug-naïve patients with MDD, and 27 age- and sex-matched HC individuals. Visual evaluation, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were analysed in the anterior thalamic radiation (ATR) as a tract of interest using the optimal follow-up truncation threshold. They were also analysed in the cingulate fasciculus, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, and fornix.ResultsNo significant differences were found in the FA or ADC of any tract. However, visual evaluation revealed poorer depiction of ATR in patients with BD than in patients with MDD and HC individuals (p = 0.004). Our post-hoc analysis showed a significant difference between BD and HC patients (p = 0.018).ConclusionsThe visual evaluation method of DTT revealed poor depiction of ATR in patients with BD compared with HC individuals and MDD patients, suggesting microstructural WM abnormalities of ATR in BD.

Alteration of Gut Microbiome in Patients With Schizophrenia Indicates Links Between Bacterial Tyrosine Biosynthesis and Cognitive Dysfunction

BackgroundSchizophrenia (SCZ) is a heterogeneous neuropsychiatric disorder for which current treatment has insufficient efficacy and severe adverse effects. The modifiable gut microbiome might be a potential target for intervention to improve neurobiological functions through the gut-microbiome-brain axis. MethodsIn this case-control study, gut microbiota of 132 patients with SCZ and increased waist circumference were compared with gut microbiota of two age- and sex-matched control groups, composed of 132 healthy individuals and 132 individuals with metabolic syndrome. Shotgun sequencing was used to characterize fecal samples at the taxonomic and functional levels. Cognition of the patients with SCZ was evaluated using the Brief Assessment of Cognition instrument. ResultsSCZ gut microbiota differed significantly from those of healthy control subjects and individuals with metabolic syndrome in terms of richness and global composition. SCZ gut microbiota were notably enriched in Flavonifractor plautii, Collinsella aerofaciens, Bilophila wadsworthia, and Sellimonas intestinalis, while depleted in Faecalibacterium prausnitzii, Ruminococcus lactaris, Ruminococcus bicirculans, and Veillonella rogosae. Functional potential of the gut microbiota accounted for 11% of cognition variability. In particular, the bacterial functional module for synthesizing tyrosine, a precursor for dopamine, was in SCZ cases positively associated with cognitive score (ρ = 0.34, q ≤ .1). ConclusionsOverall, this study shows that the gut microbiome of patients with SCZ differs greatly from that of healthy control subjects or individuals with metabolic syndrome. Cognitive function of patients with SCZ is associated with the potential for gut bacterial biosynthesis of tyrosine, a precursor for dopamine, suggesting that gut microbiota might be an intervention target for alleviation of cognitive dysfunction in SCZ.

Hypoglycemia Impairs the Heat Shock Protein Response: A Risk for Heat Shock in Cattle?

BackgroundHeat stress (HS) in cattle is a major debilitating problem, affecting health and milk yield. Physiologically, HS has been shown to lower blood glucose levels to 2.5 mmol/l (45 mg/dl) and results in upregulation of heat shock proteins (HSPs), eliciting the heat shock response (HSR) of which HSP90, 70 and 27 have been shown to be protective. However, it is unclear if the HSP response is blunted by decreased glucose, thereby preventing adaptive mechanisms. To address this question, this exploratory reverse translational study on the effects of hypoglycemia on the HSP pathway was undertaken.MethodsA human prospective, study in healthy control individuals (n = 23) was undertaken. Subjects underwent hyperinsulinemic-induced hypoglycemia [≤2.0 mmol/L (36 mg/dl)] with blood sampling at baseline, at hypoglycemia and for a 24-h post-hypoglycemia follow-up period. Proteomic analysis of the heat shock-related protein pathway, the pathway associated with HS in cattle, was performed.ResultsIn response to hypoglycemia, HS pathway proteins were significantly decreased (p < 0.05): HSP70 and HSP27 (at hypoglycemia); DnaJ homolog subfamily B member 1 (DNAJB1), Stress-induced-phosphoprotein 1 (STIP1) and the ubiquitin pathway proteins, Ubiquitin-conjugating enzyme (UBE2L3) and Ubiquitin-conjugating enzyme E2 N (UBE2N) (at 30-min post-hypoglycemia); HSP90 (at 2-h post-hypoglycemia). STIP1, UBE2L3, and UBE2N remained suppressed at 24-h.ConclusionHeat stress in cattle reduces blood glucose that, in turn, may blunt the HS pathway protective response, including HSP 90, 70, 27 and the ubiquitin proteins, leading to adverse outcomes. Monitoring of blood glucose in susceptible cattle may allow for earlier intervention and may also identify those animals at greatest risk to ensure that milk yield is not compromised.

Differential Circulating Fungal Microbiome in Prostate Cancer Patients Compared to Healthy Control Individuals.

Backgrounds Infection and inflammation play an important role in prostate cancer (PCa) etiology and pathogenesis. However, the environmental drivers for PCa are not fully understood. Methods In a cross-sectional study, we analyzed circulating fungal microbiome in plasma samples from age and race-matched healthy control men (n = 34) and preoperative PCa patients (n = 31). Results The fungal community in the plasma exhibited differences between individuals with PCa and healthy controls according to the beta diversity; there was no difference in the alpha diversity. Moreover, the relative abundance of several fungi differed between the two study groups from the class to species levels. The most significant differences were Filobasidiales family, Pyronemataceae family, and Cryptococcus ater species, which were enriched in PCa patients compared to controls. The increased Bipolaris genus was associated with low prostate-specific antigen (PSA) levels, increased Sordariomycetes class was associated with severe pathological stage, and decreased Phoma herbarum species was associated with disease relapse, compared to corresponding controls. Several fungi from class to species levels were increased in the controls compared to patients. Conclusion This is the first study to show plasma distinct fungal microbiome and its associations with PSA levels, relapse, and pathology stages in PCa patients.

The association of oxidative stress and DNA damage with XRCC1 and XRCC3 polymorphisms in radiology technicians.

Ionizing radiation has widespread use in medicine in the diagnosis and treatment of many medical conditions. Radiology technicians are one group that is occupationally exposed to low doses of radiation. There are questions regarding whether low dose exposure to radiation could have long-term health consequences. Assessing the effect of radiation on genetic material is essential for appraising long-term health results. Hereditary variations in DNA repair genes cause differentiation in individual responses to radiation related health effects. This study aimed to determine oxidative stress and DNA damage, and their relationship to XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) polymorphisms in radiology technicians occupationally exposed to low dose radiation. Peripheral blood samples were collected from 45 radiology technicians and age-matched with 40 healthy control individuals working in office environments. Our results showed that radiology technicians had significantly greater oxidative stress and DNA damage than the control group, and women appeared more susceptible to occupational radiation exposure than men. Individuals with wild-type genotypes for XRCC1 (Arg/Arg) and XRCC3 (Thr/Thr) had less DNA damage. Lower DNA damage levels could be explained by the enhanced capacity to repair low dose radiation induced DNA damage. Further studies are needed to evaluate the role of DNA repair genes in individuals that are occupationally exposed to low dose radiation.

NSD1 mutations deregulate transcription and DNA methylation of bivalent developmental genes in Sotos syndrome.

Sotos syndrome (SS), the most common overgrowth with intellectual disability (OGID) disorder, is caused by inactivating germline mutations of NSD1, which encodes a histone H3 lysine 36 methyltransferase. To understand how NSD1 inactivation deregulates transcription and DNA methylation (DNAm), and to explore how these abnormalities affect human development, we profiled transcription and DNAm in SS patients and healthy control individuals. We identified a transcriptional signature that distinguishes individuals with SS from controls and was also deregulated in NSD1-mutated cancers. Most abnormally expressed genes displayed reduced expression in SS; these downregulated genes consisted mostly of bivalent genes and were enriched for regulators of development and neural synapse function. DNA hypomethylation was strongly enriched within promoters of transcriptionally deregulated genes: overexpressed genes displayed hypomethylation at their transcription start sites while underexpressed genes featured hypomethylation at polycomb binding sites within their promoter CpG island shores. SS patients featured accelerated molecular aging at the levels of both transcription and DNAm. Overall, these findings indicate that NSD1-deposited H3K36 methylation regulates transcription by directing promoter DNA methylation, partially by repressing polycomb repressive complex 2 (PRC2) activity. These findings could explain the phenotypic similarity of SS to OGID disorders that are caused by mutations in PRC2 complex-encoding genes.

Alterations of host-gut microbiome interactions in multiple sclerosis.

SummaryBackgroundMultiple sclerosis (MS) has a complex genetic, immune and metabolic pathophysiology. Recent studies implicated the gut microbiome in MS pathogenesis. However, interactions between the microbiome and host immune system, metabolism and diet have not been studied over time in this disorder.MethodsWe performed a six-month longitudinal multi-omics study of 49 participants (24 untreated relapse remitting MS patients and 25 age, sex, race matched healthy control individuals. Gut microbiome composition and function were characterized using 16S and metagenomic shotgun sequencing. Flow cytometry was used to characterize blood immune cell populations and cytokine profiles. Circulating metabolites were profiled by untargeted UPLC-MS. A four-day food diary was recorded to capture the habitual dietary pattern of study participants.FindingsTogether with changes in blood immune cells, metagenomic analysis identified a number of gut microbiota decreased in MS patients compared to healthy controls, and microbiota positively or negatively correlated with degree of disability in MS patients. MS patients demonstrated perturbations of their blood metabolome, such as linoleate metabolic pathway, fatty acid biosynthesis, chalcone, dihydrochalcone, 4-nitrocatechol and methionine. Global correlations between multi-omics demonstrated a disrupted immune-microbiome relationship and a positive blood metabolome-microbiome correlation in MS. Specific feature association analysis identified a potential correlation network linking meat servings with decreased gut microbe B. thetaiotaomicron, increased Th17 cell and greater abundance of meat-associated blood metabolites. The microbiome and metabolome profiles remained stable over six months in MS and control individuals.InterpretationOur study identified multi-system alterations in gut microbiota, immune and blood metabolome of MS patients at global and individual feature level. Multi-OMICS data integration deciphered a potential important biological network that links meat intakes with increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker.FundingThis work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI); R01 NS10263304 (Zhou Y, Piccio L); the Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-180531003) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-190734474). Anne Cross was supported by The Manny & Rosalyn Rosenthal-Dr. John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Effect of Esomeprazole on serum creatinine and urea in patients with Peptic Ulcer

Peptic ulcers are best treated by proton pump inhibitors (PPIs), however, other simple gastrointestinal (GIT) disorders should be better treated by other acid neutralizing or anti-secretory agents. Unfortunately, most GIT diseases were reported to be treated by PPIs even though non-indicated cases. The reasons might include ease availability with/without prescription, reduce patient awareness, and overprescription of PPIs by the health care professionals. This study aims to highlight the effect of these drugs on the renal function test. Patients were recruited and enrolled in the study from outpatients private clinics and plasma samples were withdrawn from control healthy, esomeprazole and omeprazole users individuals. Plasma samples were frozen for further analysis, creatinine and urea test were conducted on overall samples and the results were displayed confirming significant dysfunctioning of the renal system from PPIs use. The study concluded that creatinine and urea are higher in a patient on esomeprazole than omeprazole and the control group. The study recommends general awareness of the society about regular use of these medications unless otherwise carefully required.

Effects of progressive resistance training in individuals with type 2 diabetic polyneuropathy: a randomised assessor-blinded controlled trial.

The aim of this study was to evaluate the effects of progressive resistance training (PRT) on muscle strength, intraepidermal nerve fibre density (IENFD) and motor function in individuals with type 2 diabetic polyneuropathy (DPN) and to compare potential adaptations to those of individuals with type 2 diabetes without DPN and healthy controls. This was an assessor-blinded trial conducted at the Neurology department, Aarhus University Hospital. Adults with type 2 diabetes, with and without DPN and healthy control participants were randomised to either supervised PRT or non-PRT for 12 weeks. Allocation was concealed by a central office unrelated to the study. The co-primary outcomes were muscle strength in terms of the peak torque of the knee and ankle extensors and flexors, and IENFD. Secondary outcome measures included the 6 min walk test (6MWT), five-time sit-to-stand test (FTSST) and postural stability index obtained by static posturography. A total of 109 individuals were enrolled in three groups (type 2 diabetes with DPN [n = 42], type 2 diabetes without DPN [n = 32] and healthy control [n = 35]). PRT resulted in muscle strength gains of the knee extensors and flexors in all three groups using comparative analysis (DPN group, PRT 10.3 ± 9.6 Nm vs non-PRT -0.4 ± 8.2 Nm; non-DPN group, PRT 7.5 ± 5.8 Nm vs non-PRT 0.6 ± 8.8 Nm; healthy control group, PRT 6.3 ± 9.0 Nm vs non-PRT -0.4 ± 8.4 Nm; p<0.05, respectively). Following PRT the DPN group improved the 6MWT (PRT 34.6 ± 40.9 m vs non-PRT 2.7 ± 19.6 m; p=0.001) and the FTSST (PRT -1.5 ± 2.2 s vs non-PRT 1.5 ± 4.6 s; p=0.02). There was no change in IENFD following PRT in any of the groups. PRT improved muscle strength of the knee extensors and flexors and motor function in individuals with type 2 diabetic polyneuropathy at levels comparable with those seen in individuals with diabetes without DPN and healthy control individuals, while no effects were observed in IENFD. ClinicalTrials.gov NCT03252132 FUNDING: Research reported in this paper is part of the International Diabetic Neuropathy Consortium (IDNC) research programme, supported by a Novo Nordisk Foundation Challenge Program grant (grant no. NNF14OC0011633) and Aarhus University.

Bronchial asthma control, quality of life, and psychiatric disorders vicious cycle: Asyut society point of view

BackgroundPoorly controlled bronchial asthma limits patients’ quality of life (QOL), the condition which may potentiate the development of psychiatric disorders. The aim of this study was the assessment of anxiety and depression in bronchial asthma patients, and their interrelation with both level of asthma control and quality of life in our society.ResultsThis study included 102 bronchial asthma patients, and 50 healthy control individuals. Patients had poorer QOL, and higher anxiety and depression scores compared to healthy control, moreover these scores were higher in uncontrolled asthma patients compared to controlled group. Poor QOL, frequent hospital admissions, and poor asthma control were the predictors for psychiatric disorders.ConclusionDepression and anxiety are frequently encountered in patients with bronchial asthma in our society; poor symptom control, poor QOL, and frequent hospital admissions are the main predictors for these psychiatric disorders.

Longitudinal mapping of cortical surface changes in Huntington's Disease.

This paper investigated cortical folding in Huntington's disease to understand how disease progression impacts the surface of the cortex. Cortical morphometry changes in eight gyral based regions of interest (i.e. the left and right hemispheres of the lateral occipital, precentral, superior frontal and rostral middle gyri) were examined. We used existing neuroimaging data from IMAGE-HD, comprising 26 pre-symptomatic, 26 symptomatic and 24 healthy control individuals at three separate time points (baseline, 18-month, 30-month). Local gyrification index and cortical thickness were derived as the measures of cortical morphometry using FreeSurfer 6.0's longitudinal pipeline. The gyral based regions of interest were identified using the Desikan-Killiany Atlas. A Group by Time repeated measures ANCOVA was conducted for each region of interest. We found significantly lower LGI at a group level in the right hemisphere lateral occipital region and both hemispheres of the precentral region; as well as significantly reduced cortical thickness at a group level in both hemispheres of the lateral occipital and precentral regions and the right hemisphere of the superior frontal region. We also found a Group by Time interaction for Local gyrification index in the right hemisphere lateral occipital region. This change was largely driven by a significant decrease in the symptomatic group between baseline and 18-months. Additionally, lower local gyrification index and cortical thickness were associated with higher disease burden score. These findings demonstrate that significant longitudinal decline in right hemisphere local gyrification index is evident during manifest disease in lateral occipital cortex and that these changes are more profound in individuals with greater disease burden score.

Stroke survivors with the same levels of exercise as healthy individuals have lower levels of physical activity.

Physical activity and exercise are different constructs. However, professionals usually employ heterogeneous definitions for these distinct constructs, resulting in nonspecific and inaccurate assessments, which compromise clinical decision making. The aim of this study was to verify if the levels of physical activity behave similarly between individuals with stroke and healthy-control individuals with the same levels of exercise. Seventy-five stroke survivors and 75 healthy-control individuals matched by levels of exercise, age, and sex were evaluated. The level of exercise was classified as inactive, insufficient, and moderate/vigorous according to the Centers for Disease Control and Prevention criteria. The level of physical activity was assessed with the Human Activity Profile (HAP) and classified as "inactive," "moderately active," and "active." The physical activity level was compared between groups of subjects (stroke versus healthy-control) and subgroups of the level of exercise ("inactive," "insufficient," and "moderate/vigorous" level of exercise) (α = 5%). Stroke survivors had a significantly lower level of physical activity (HAP: 51 ± 22 and 71 ± 19 points, respectively). Only for individuals with stroke, a statistically significant difference was found in the levels of physical activity between subgroups of level of exercise, specifically between "inactive" and "moderate/vigorous" subgroups (HAP:47 ± 22 and 70 ± 8 points, respectively). Physical activity behaved differently between individuals with stroke and healthy-control individuals with the same levels of exercise. Individuals with stroke had worse physical activity levels than matched controls. Furthermore, different from individuals with stroke, in healthy-control individuals with different levels of exercise, the level of physical activity was similar.

How do I know how I am doing? Use of different types of comparison in judgment of well-being in patients seeking psychological treatment and healthy controls.

Judgment of well-being is formed on the spot, and we know little about its foundations. We aimed at examining the role of comparison standards in informing evaluations of well-being in a clinical and a nonclinical sample. In a semi-structured face-to-face interview, individuals seeking psychological treatment and healthy control individuals rated how they have been feeling in general and relative to specific comparison standards and were each time invited to substantiate their ratings. Independent coders assessed number, type, direction, and specificity of reported comparisons. When asked to explain why they chose a particular rating of their well-being, 93% of clinical participants and 61% of nonclinical participants spontaneously reported some type of comparison standard. Both groups reported highest well-being ratings relative to social and past temporal comparisons and lowest relative to prospective temporal comparison. Furthermore, clinical participants engaged in more upward than downward comparisons, whereas this was not the case for healthy control participants. Our findings suggest that evaluations of well-being are informed by different comparison types and that individuals with clinical complaints use more comparisons when evaluating their well-being. The results encourage further investigation of comparative thinking as an underlying mechanism of judgment of well-being and ill-being.