scholarly journals Chronic Alcohol Use Induces Molecular Genetic Changes in the Dorsomedial Thalamus of People with Alcohol-Related Disorders

2021 ◽  
Vol 11 (4) ◽  
pp. 435
Author(s):  
Andreas-Christian Hade ◽  
Mari-Anne Philips ◽  
Ene Reimann ◽  
Toomas Jagomäe ◽  
Kattri-Liis Eskla ◽  
...  

The Mediodorsal (MD) thalamus that represents a fundamental subcortical relay has been underrepresented in the studies focusing on the molecular changes in the brains of subjects with alcohol use disorder (AUD). In the current study, MD thalamic regions from AUD subjects and controls were analyzed with Affymetrix Clariom S human microarray. Long-term alcohol use induced a significant (FDR ≤ 0.05) upregulation of 2802 transcripts and downregulation of 1893 genes in the MD thalamus of AUD subjects. A significant upregulation of GRIN1 (glutamate receptor NMDA type 1) and FTO (alpha-ketoglutarate dependent dioxygenase) was confirmed in western blot analysis. Immunohistochemical staining revealed similar heterogenous distribution of GRIN1 in the thalamic nuclei of both AUD and control subjects. The most prevalent functional categories of upregulated genes were related to glutamatergic and GABAergic neurotransmission, cellular metabolism, and neurodevelopment. The prevalent gene cluster among down-regulated genes was immune system mediators. Forty-two differentially expressed genes, including FTO, ADH1B, DRD2, CADM2, TCF4, GCKR, DPP6, MAPT and CHRH1, have been shown to have strong associations (FDR p < 10−8) with AUD or/and alcohol use phenotypes in recent GWA studies. Despite a small number of subjects, we were able to detect robust molecular changes in the mediodorsal thalamus caused by alcohol emphasizing the importance of deeper brain structures such as diencephalon, in the development of AUD-related dysregulation of neurocircuitry.

2017 ◽  
Vol 19 (73) ◽  
pp. 84-88
Author(s):  
I. Rublenko ◽  
V. Skripnik

Long-term use of antibiotics leads to antibiotic resistance in pathogens. In addition, there is a possibility of permanent genetic changes in strains due to environmental influences. Therefore there is a need for periodic study vaccine strains for sensitivity to antibiotics in order to study and control of their passport characteristics. The aim of our research was necessary to determine the sensitivity of the strain of Bacillus anthracis UA-07 to antibiotics. The results of studies of sensitivity of strain Bacillus anthracis UA–07 to 50 antibiotics were determined by the size of the diameter of the zones of growth retardation. Zone growth delay of 15 mm was considered a sign of a weak antibiotic sensitivity, zone 15–24 mm – a sign of sensitivity and area of more than 24 mm - a sign of the high sensitivity of the strain to this antibiotic. Lack of stunted growth areas points to the insensitivity of the strain to this antibiotic. The research results show that the strain of Bacillus anthracis UA–07 is highly sensitive to ofloxacin (Of5), ampicillin / sulbactam (A/S10/10), linezolid (LZ30), amoxicillin (AMX30), norfloxacin (NX10), cefalotin (CEP30), tetracycline (TE30). Not affect the development of the studied microorganism antibiotics, cefepime (SPM30), nystatin (NS100U) tsefuroksyn (CXM30) tsefeksym (CFM5), sulfadiazine (SZ300), metronidazole (MT4), cefazolin (Cz30).


2011 ◽  
Vol 70 (1) ◽  
pp. 5-11 ◽  
Author(s):  
Beat Meier ◽  
Anja König ◽  
Samuel Parak ◽  
Katharina Henke

This study investigates the impact of thought suppression over a 1-week interval. In two experiments with 80 university students each, we used the think/no-think paradigm in which participants initially learn a list of word pairs (cue-target associations). Then they were presented with some of the cue words again and should either respond with the target word or avoid thinking about it. In the final test phase, their memory for the initially learned cue-target pairs was tested. In Experiment 1, type of memory test was manipulated (i.e., direct vs. indirect). In Experiment 2, type of no-think instructions was manipulated (i.e., suppress vs. substitute). Overall, our results showed poorer memory for no-think and control items compared to think items across all experiments and conditions. Critically, however, more no-think than control items were remembered after the 1-week interval in the direct, but not in the indirect test (Experiment 1) and with thought suppression, but not thought substitution instructions (Experiment 2). We suggest that during thought suppression a brief reactivation of the learned association may lead to reconsolidation of the memory trace and hence to better retrieval of suppressed than control items in the long term.


2015 ◽  
Vol 2 (2) ◽  
pp. 26-31 ◽  
Author(s):  
A. Paliy ◽  
A. Zavgorodniy ◽  
B. Stegniy ◽  
A. Gerilovych

Due to the absence of elaborated effi cient means for specifi c prevention of bovine tuberculosis, it is ex- tremely important to detect and eliminate the source of infection and to take veterinary and sanitary preven- tive measures. Here the critical role is attributed to disinfection, which breaks the epizootic chain due to the elimination of pathogenic microorganisms in the environment and involves the application of disinfectants of different chemical groups. Aim. To study the tuberculocidal properties of new disinfectants DZPT-2 and FAG against atypical mycobacteria Mycobacterium fortitum and a TB agent Mycobacterium bovis. Methods. The bacteriological and molecular-genetic methods were used. Results. It was determined that DZPT-2 prepara- tion has bactericidal effect on M. fortuitum when used in the concentration of 2.0 % of the active ingredient (AI) when exposed for 5–24 h, while disinfectant FAG has a bactericidal effect in the concentration of 2.0 % when exposed for 24 h. Disinfectant DZPT-2 in the concentration of 2.0 % of the AI, when exposed for 5–24 h, and FAG preparation in the concentration of 2.0 %, when exposed for 24 h, and with the norm of consump- tion rate of 1 cubic decimeter per 1 square meter disinfect the test-objects (batiste, wood, glazed tile, metal, glass), contaminated with the TB agent M. bovis. Conclusions. Disinfecting preparations of DZPT-2 in the concentration of 2.0 % of AI when exposed for 5 h and FAG in the concentration of 2.0 % when exposed for 24 h may be used in the complex of veterinary and sanitary measures to prevent and control TB of farm ani- mals. The possibility of using the polymerase chain reaction as an additional method of estimating tuberculo- cide activity of disinfectants was proven.


Author(s):  
Diana Hart

All countries are faced with the problem of the prevention and control of non-communicable diseases (NCD): implement prevention strategies eff ectively, keep up the momentum with long term benefi ts at the individual and the population level, at the same time tackling hea lth inequalities. Th e aff ordability of therapy and care including innovative therapies is going to be one of the key public health priorities in the years to come. Germany has taken in the prevention and control of NCDs. Germany’s health system has a long history of guaranteeing access to high-quality treatment through universal health care coverage. Th r ough their membership people are entitled to prevention and care services maintaining and restoring their health as well as long term follow-up. Like in many other countries general life expectancy has been increasing steadily in Germany. Currently, the average life expectancy is 83 and 79 years in women and men, respectively. Th e other side of the coin is that population aging is strongly associated with a growing burden of disease from NCDs. Already over 70 percent of all deaths in Germany are caused by four disease entities: cardiovascular disease, cancer, chronic respiratory disease and diabetes. Th ese diseases all share four common risk factors: smoking, alcohol abuse, lack of physical activity and overweight. At the same time, more and more people become long term survivors of disease due to improved therapy and care. Th e German Government and public health decision makers are aware of the need for action and have responded by initiating and implementing a wide spectrum of activities. One instrument by strengthening primary prevention is the Prevention Health Care Act. Its overarching aim is to prevent NCDs before they can manifest themselves by strengthening primary prevention and health promotion in diff erent sett ings. One of the main emphasis of the Prevention Health Care Act is the occupational health promotion at the workplace.


2020 ◽  
Author(s):  
Joseph D. Deak ◽  
D. Angus Clark ◽  
Mengzhen Liu ◽  
C. Emily Durbin ◽  
William G. Iacono ◽  
...  

Objective: Molecular genetic studies of alcohol and nicotine have identified many genome-wide loci. We examined the predictive utility of drinking and smoking polygenic scores (PGS) for alcohol and nicotine use from late childhood to early adulthood, substance-specific versus broader-liability PGS effects, and if PGS performance varied between consumption versus pathological use. Methods: Latent growth curve models with structured residuals were used to assess the predictive utility of drinks per week and regular smoking PGS for measures of alcohol and nicotine consumption and problematic use from age 14 to 34. PGSs were generated from the largest discovery sample for alcohol and nicotine use to date (i.e., GSCAN), and examined for associations with alcohol and nicotine use in the Minnesota Twin Family Study (N=3225).Results: The drinking PGS was a significant predictor of age 14 problematic alcohol use and increases in problematic use during young adulthood. The smoking PGS was a significant predictor for all nicotine use outcomes. After adjusting for the effects of both PGSs, the smoking PGS demonstrated incremental predictive utility for most alcohol use outcomes and remained a significant predictor of nicotine use trajectories. Conclusions: Higher PGS for drinking and smoking were associated with more problematic levels of substance use longitudinally. The smoking PGS seems to capture both nicotine-specific and non-specific genetic liability for substance use, and may index genetic risk for broader externalizing behavior. Validation of PGS within longitudinal designs may have important clinical implications should future studies support the clinical utility of PGS for substance use disorders.


Author(s):  
Maureen L. Whittal ◽  
Melisa Robichaud

The cornerstone of cognitive treatment (CT) for OCD is based upon the knowledge that unwanted intrusions are essentially a universal experience. As such, it is not the presence of the intrusion that is problematic but rather the associated meaning or interpretation. Treatment is flexible, depending upon the nature of the appraisals and beliefs, but can include strategies focused on inflated responsibility and overestimation of threat, importance and control of thoughts, and the need for perfectionism and certainty. The role of concealment and the relationship to personal values are important maintaining and etiological factors. The short-term and long-term treatment outcome is reviewed, along with predictors of treatment response and mechanisms of action, and the chapter concludes with future directions regarding CT for OCD.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Estefanía Hernandez-Martin ◽  
Enrique Arguelles ◽  
Yifei Zheng ◽  
Ruta Deshpande ◽  
Terence D. Sanger

AbstractHigh-frequency peripheral nerve stimulation has emerged as a noninvasive alternative to thalamic deep brain stimulation for some patients with essential tremor. It is not known whether such techniques might be effective for movement disorders in children, nor is the mechanism and transmission of the peripheral stimuli to central brain structures understood. This study was designed to investigate the fidelity of transmission from peripheral nerves to thalamic nuclei in children with dystonia undergoing deep brain stimulation surgery. The ventralis intermediate (VIM) thalamus nuclei showed a robust evoked response to peripheral high-frequency burst stimulation, with a greatest response magnitude to intra-burst frequencies between 50 and 100 Hz, and reliable but smaller responses up to 170 Hz. The earliest response occurred at 12–15 ms following stimulation onset, suggesting rapid high-fidelity transmission between peripheral nerve and thalamic nuclei. A high-bandwidth, low-latency transmission path from peripheral nerve to VIM thalamus is consistent with the importance of rapid and accurate sensory information for the control of coordination and movement via the cerebello-thalamo-cortical pathway. Our results suggest the possibility of non-invasive modulation of thalamic activity in children with dystonia, and therefore the possibility that a subset of children could have beneficial clinical response without the need for invasive deep brain stimulation.


2021 ◽  
Vol 28 ◽  
pp. 107327482199743
Author(s):  
Ke Chen ◽  
Xiao Wang ◽  
Liu Yang ◽  
Zheling Chen

Background: Treatment options for advanced gastric esophageal cancer are quite limited. Chemotherapy is unavoidable at certain stages, and research on targeted therapies has mostly failed. The advent of immunotherapy has brought hope for the treatment of advanced gastric esophageal cancer. The aim of the study was to analyze the safety of anti-PD-1/PD-L1 immunotherapy and the long-term survival of patients who were diagnosed as gastric esophageal cancer and received anti-PD-1/PD-L1 immunotherapy. Method: Studies on anti-PD-1/PD-L1 immunotherapy of advanced gastric esophageal cancer published before February 1, 2020 were searched online. The survival (e.g. 6-month overall survival, 12-month overall survival (OS), progression-free survival (PFS), objective response rates (ORR)) and adverse effects of immunotherapy were compared to that of control therapy (physician’s choice of therapy). Results: After screening 185 studies, 4 comparative cohort studies which reported the long-term survival of patients receiving immunotherapy were included. Compared to control group, the 12-month survival (OR = 1.67, 95% CI: 1.31 to 2.12, P < 0.0001) and 18-month survival (OR = 1.98, 95% CI: 1.39 to 2.81, P = 0.0001) were significantly longer in immunotherapy group. The 3-month survival rate (OR = 1.05, 95% CI: 0.36 to 3.06, P = 0.92) and 18-month survival rate (OR = 1.44, 95% CI: 0.98 to 2.12, P = 0.07) were not significantly different between immunotherapy group and control group. The ORR were not significantly different between immunotherapy group and control group (OR = 1.54, 95% CI: 0.65 to 3.66, P = 0.01). Meta-analysis pointed out that in the PD-L1 CPS ≥10 sub group population, the immunotherapy could obviously benefit the patients in tumor response rates (OR = 3.80, 95% CI: 1.89 to 7.61, P = 0.0002). Conclusion: For the treatment of advanced gastric esophageal cancer, the therapeutic efficacy of anti-PD-1/PD-L1 immunotherapy was superior to that of chemotherapy or palliative care.


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