Molecular Aspects of MAFLD-New Insights on Pathogenesis and Treatment.

Metabolic-associated liver disease (MAFLD) affects up to 70% of overweight and more than 90% of morbidly obese people, and its pathogenesis is rather complex and multifactorial. The criteria for MAFLD include the presence of hepatic steatosis in addition to one of the following three criteria: overweight or obesity, presence of type 2 diabetes mellitus (T2DM), or evidence of metabolic dysregulation. If the specific criteria are present, the diagnosis of MAFLD can be made regardless of alcohol consumption and previous liver disease. The pathophysiological mechanisms of MAFLD, including inflammation, lipotoxicity, mitochondrial disfunction, and oxidative stress, as well as the impact of intestinal gut microbiota, are constantly being elucidated. Treatment strategies that are continually emerging are based on different key points in MAFLD pathogenesis. Yet, the ideal therapeutic option has still not been found and future research is of great importance, as MAFLD represents a multisystemic disease with numerous complications.

Database and AI Diagnostic Tools Improve Understanding of Lung Damage, Correlation of Pulmonary Disease and Brain Damage in COVID-19.

The COVID-19 pandemic caused a sharp increase in the interest in artificial intelligence (AI) as a tool supporting the work of doctors in difficult conditions and providing early detection of the implications of the disease. Recent studies have shown that AI has been successfully applied in the healthcare sector. The objective of this paper is to perform a systematic review to summarize the electroencephalogram (EEG) findings in patients with coronavirus disease (COVID-19) and databases and tools used in artificial intelligence algorithms, supporting the diagnosis and correlation between lung disease and brain damage, and lung damage. Available search tools containing scientific publications, such as PubMed and Google Scholar, were comprehensively evaluated and searched with open databases and tools used in AI algorithms. This work aimed to collect papers from the period of January 2019-May 2022 including in their resources the database from which data necessary for further development of algorithms supporting the diagnosis of the respiratory system can be downloaded and the correlation between lung disease and brain damage can be evaluated. The 10 articles which show the most interesting AI algorithms, trained by using open databases and associated with lung diseases, were included for review with 12 articles related to EEGs, which have/or may be related with lung diseases.

Significance of Biomarkers in Early Diagnosis of Abdominal Sepsis.

INTRODUCTION/OBJECTIVE: Peritonitis is one of the most important sources of abdominal sepsis. Since intra-abdominal infection leads to the activation of the inflammatory response, this suggested that some of these mediators could be used as markers of the severity of newly formed sepsis, but primarily to identify or rule out new-onset sepsis. The aim of this study was to evaluate the sensitivity and specificity of serum markers of inflammation: C-reactive protein, procalcitonin and serum amyloid A in the serum of patients with diffuse secondary peritonitis. Methods: The prospective cohort study was conducted at the Clinic for Emergency Surgery of the Clinical Center of Serbia in Belgrade. The study group consisted of 100 patients aged 18 to 70 years, with signs of acute abdomen due to diffuse secondary peritonitis. Results: CRP and PCT are so far among the most valuable preoperative markers for distinguishing sepsis from SIRS. On the first postoperative day the analysis of the relationship between sensitivity and specificity at the different breakpoints used indicates a greater diagnostic accuracy and greater sensitivity of SAA compared to CRP and PCT. In the remaining postoperative period in our study, the ROC curve mostly coincided with the diagonal line, so CRP, PCT, and SAA had little diagnostic accuracy. CONCLUSION: The results of our study suggest that finding a specific marker for the diagnosis of abdominal sepsis, a marker that would differentiate between SIRS and sepsis, pre- and postoperatively, would be very useful.

The New Therapeutic Approaches in the Treatment of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease which is characterized by extremely complex pathogenetic mechanisms and multifactorial etiology. Some of the many pathophysiological mechanisms involved in the development of NAFLD include oxidative stress, impaired mitochondrial metabolism, inflammation, gut microbiota, and interaction between the brain-liver-axis and the regulation of hepatic lipid metabolism. The new therapeutic approaches in the treatment of NAFLD are targeting some of these milestones along the pathophysiological pathway and include drugs like agonists of peroxisome proliferator-activated receptors (PPARs), glucagon-like peptide-1 (GLP-1) agonists, sodium/glucose transport protein 2 (SGLT2) inhibitors, farnesoid X receptor (FXR) agonists, probiotics, and symbiotics. Further efforts in biomedical sciences should focus on the investigation of the relationship between the microbiome, liver metabolism, and response to inflammation, systemic consequences of metabolic syndrome.

Brain changes in patients with posttraumatic stress disorder and associated alcoholism: MRI based study.

BACKGROUND: Studies imposing rigorous control over lifetime alcohol intake usually have not found smaller hippocampal volumes in persons with posttraumatic stress disorder (PTSD). Since the majority of negative studies have used adolescent samples, it has been suggested that chronicity is a necessary condition for such findings. We have hypothesized that the volumes of hippocampus, amygdale, prefrontal cortex and the intracranial volume are reduced in the patients with PTSD and excessive alcohol intake. SUBJECTS AND METHODS: Study has been carried out on 54 therapy naive PTSD suffering subjects and healthy controls, divided in two groups: 29 with PTSD and consequent alcoholism, 25 with PTSD but without problems of excessive alcohol intake, and 25 healthy volunteers. All of the patients underwent same magnetic resonance imaging (MRI) protocol and volumetric evaluation of the region of interest. RESULTS: Only hippocampal volume appeared to be significantly reduced in patients with PTSD and alcoholism. Other differences in the volumes obtained remained to be insignificant. CONCLUSION: Alcohol intake definitely worsens the deterioration of the hippocampal formation in PTSD suffering patients. Nevertheless, other structures of interest for this study did not manifest any kind of statistical differences in volumetric analysis.

Frontal theta oscillations during emotion regulation in people with borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is a severe psychiatric disorder conceptualised as a disorder of emotion regulation. Emotion regulation has been linked to a frontolimbic network comprising the dorsolateral prefrontal cortex and the amygdala, which apparently synchronises its activity via oscillatory coupling in the theta frequency range. AIMS: To analyse whether there are distinct differences in theta oscillatory coupling in frontal brain regions between individuals with BPD and matched controls during emotion regulation by cognitive reappraisal. METHOD: Electroencephalogram (EEG) recordings were performed in 25 women diagnosed with BPD and 25 matched controls during a cognitive reappraisal task in which participants were instructed to downregulate negative emotions evoked by aversive visual stimuli. Between- and within-group time-frequency analyses were conducted to analyse regulation-associated theta activity (3.5-8.5 Hz). RESULTS: Oscillatory theta activity differed between the participants with BPD and matched controls during cognitive reappraisal. Regulation-associated theta increases were lower in frontal regions in the BPD cohort compared with matched controls. Functional connectivity analysis for regulation-associated changes in the theta frequency band revealed a lower multivariate interaction measure (MIM) increase in frontal brain regions in persons with BPD compared with matched controls. CONCLUSIONS: Our findings support the notion of alterations in a frontal theta network in BPD, which may be underlying core symptoms of the disorder such as deficits in emotion regulation. The results add to the growing body of evidence for altered oscillatory brain dynamics in psychiatric populations, which might be investigated as individualised treatment targets using non-invasive stimulation methods.

Morphometric and volumetric analysis of lacrimal glands in patients with thyroid eye disease.

Assessment of morphometric and volumetric changes in lacrimal glands in thyroid eye disease, its clinical manifestations in relation of disease progression. Retrospective volumetric analysis included both genders and was performed on total of 183 patients - 91 patients with diagnosed Grave's disease and thyroid eye disease and 92 patients without Grave's disease and thyroid eye disease who underwent multidetector computed tomography (MDCT) examination in routine daily work according to other medical indications. In the group of females, there was statistical significance between patients with thyroid eye disease and controls who were smoking and had body weight gain. We found statistical significance in volumetric enlargements for both orbits in both genders for the patients group when compared to controls. There was also statistical significance in morphometric characteristics for the lacrimal gland diameters measured. Determination planimetric morphometric parameters of importance were coronary height of lacrimal gland of the right eye, coronary height of lacrimal gland of the left eye and coronary width of lacrimal gland of the left eye for the group of males. In a group of females the established determination parameters of importance were the coronary height of lacrimal gland of the left eye, the axial width of lacrimal gland of the left eye, volume of lacrimal gland of the right eye and the volume of lacrimal gland of the left eye. When we compared the displaced lacrimal gland coming forward (proptosis) in time progressing disease between group of patients and controls, we also found statistical significant connection. Evaluation of lacrimal gland volumetric and morphometric data may increase validity of defining this anatomical substrate and its morphology disruption as liable tool for thyroid eye disease progression follow up and treatment planning and outcome.

The Role of Psychotherapy in the Treatment of Patients with Non- alcoholic Fatty Liver Disease and Obstructive Sleep Apnea.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease with extensive multi- organ involvement, whose extra-hepatic manifestations include diabetes mellitus type 2, cardiovascular disease, obstructive sleep apnea (OSA), chronic kidney disease, and polycystic ovary syndrome. Our hypothesis was that there was a strong psychological component in NAFLD and OSA suffering patients and that psychotherapy would be helpful in the treatment of the mentioned diseases. METHODS: Of 144 initially selected patients (with NAFLD, obesity and OSA), 32 patients agreed to undergo psychotherapy, and 31 therapy-naive NAFLD and OSA patients agreed to participate as controls. RESULTS: Psychological evaluation revealed that self-esteem rose significantly after one-year psychotherapy (p=0.005). Body mass index (BMI) was significantly lower after psychotherapy, followed by the changes in laboratory results. Binomial logistic regression revealed that the reduction of BMI in high probability led to self-esteem improvement (p=0.03). CONCLUSIONS: Psychotherapy was an efficient supporting method in the treatment of patients with NAFLD, obesity and OSA. It raised self-esteem and stimulated the motivation for further treatment of obesity, as one of the important factors for NAFLD and OSA. Still, it is advisable to use psychotherapy in combination with other clinical methods of treatment.

Influence of F1 hybridization on the metal uptake behaviour of pine trees (Pinus nigra x Pinus thunbergiana; Pinus thunbergiana x Pinus nigra).

Pine needles have been considered to be useful bio-indicators for air pollution. This phenomenon can be used for environmental studies for monitoring purposes. Additionally, this fact offers the possibility to study uptake and accumulation behaviour not only in different species, but also in hybrids obtained from common pine trees to inheritage processes. Therefore, needles of Pinus nigra Arnold and Pinus thunbergiana Franco as well as of their F1 hybrids were investigated for essential and non-essential metals, such as Al, B, Ba, Ca, Cd, Co, Cu, Cr, Fe, K, Mg, Mn, Mo, Na, Ni, Pb, Sr, and Zn. The samples underwent acidic microwave-assisted digestion prior to analysis inductively coupled plasma atomic emission spectrometry (ICP-AES). Furthermore flavonoids were quantitatively determined to prove hybrid character. Regarding all determined analytes, increase and decrease of uptake in the needles of the hybrids were evaluated in comparison to the needles of the parent pine species to see which parent is the dominant one. In the hybrids higher amounts of Al, Cd, Mo, Ni, Mg, Mn, and Zn were found. Different behaviour was registered for flavonoids than for metals, due to different metabolic pathways.

Glucocorticoid levels after exposure to predator odor and chronic psychosocial stress with dexamethasone application in rats.

This study was conducted to explore the effects of specific psychosocial paradigm on predator animal posttraumatic stress model and to test the hypothesis that psychosocially stressed rats would exibit abnormal levels of cortisol and a larger suppression of cortisol levels after the application of dexamethasone. Animals were divided in two groups: experimental and control groups. The experimental group was exposed to two types of stressors: acute immobilization stress, and combined predator stress and daily social stress with application of dexamethasone. Blood sampling was performed at three different times. We found statistically significant results after analyzing the differences between cortisol levels in different times of blood sampling in the group of animals exposed to stress with dexamethasone application. Statistical significance was found when we compared the experimental group with the control group in terms of elevated cortisol levels during blood sampling after stress paradigm exposition. Many significant disruptions in the functioning of the hypothalamic-pituitary-adrenal axis were observed, such as decrease in basal cortisol levels and enhanced dexamethasone-induced inhibition of cortisol levels. These findings are important because their impact can translate to human individuals with posttraumatic stress disorder, which is the most important role of every animal model in research.

Volumetric analysis of amygdala, hippocampus, and prefrontal cortex in therapy-naive PTSD participants.

OBJECTIVE: In our study we have hypothesized that volume changes of amygdala, hippocampus, and prefrontal cortex are more pronounced in male posttraumatic stress disorder participants. MATERIAL AND METHODS: We have conducted a study of 79 male participants who underwent MRI brain scanning. PTSD diagnosis was confirmed in 49 participants. After MRI was taken all scans were software based volume computed and statistically processed. RESULTS: We found that left amygdala is the most significant parameter for distinction between PTSD participants and participants without PTSD. There were no significant differences in volumes of hippocampi and prefrontal cortices. Roc curve method outlined left amygdala AUC = 0.898 (95% CI = 0.830-0.967) and right amygdala AUC = 0.882 (95% CI = 0.810-0.954) in the group of PTSD participants which makes both variables highly statistically significant. CONCLUSION: The present investigation revealed significant volume decrease of left amygdala in PTSD patients. Concerning important functions of the amygdala and her neuroanatomical connections with other brain structures, we need to increase number of participants to clarify the correlation between impared amygdala and possible other different brain structures in participants with PTSD.

Profiling differences in chemical composition of brain structures using Raman spectroscopy.

Raman spectroscopy enables non-invasive investigation of chemical composition of biological tissues. Due to similar chemical composition, the analysis of Raman spectra of brain structures and assignment of their spectral features to chemical constituents presents a particular challenge. In this study we demonstrate that standard and independent component analysis of Raman spectra is capable of assessment of differences in chemical composition between functionally related gray and white matter structures. Our results show the ability of Raman spectroscopy to successfully depict variation in chemical composition between structurally similar and/or functionally connected brain structures. The observed differences were attributed to variations in content of proteins and lipids in these structures. Independent component analysis enabled separation of contributions of major constituents in spectra and revealed spectral signatures of low-concentration metabolites. This provided finding of discrepancies between structures of striatum as well as between white matter structures. Raman spectroscopy can provide information about variations in contents of major chemical constituents in brain structures, while the application of independent component analysis performed on obtained spectra can help in revealing minute differences between closely related brain structures.