MTARC1 and HSD17B13 Variants Have Protective Effects on Non-Alcoholic Fatty Liver Disease in Patients Undergoing Bariatric Surgery.

The severity of hepatic steatosis is modulated by genetic variants, such as patatin-like phospholipase domain containing 3 (PNPLA3) rs738409, transmembrane 6 superfamily member 2 (TM6SF2) rs58542926, and membrane-bound O-acyltransferase domain containing 7 (MBOAT7) rs641738. Recently, mitochondrial amidoxime reducing component 1 (MTARC1) rs2642438 and hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) rs72613567 polymorphisms were shown to have protective effects on liver diseases. Here, we evaluate these variants in patients undergoing bariatric surgery. A total of 165 patients who underwent laparoscopic sleeve gastrectomy and intraoperative liver biopsies and 314 controls were prospectively recruited. Genotyping was performed using TaqMan assays. Overall, 70.3% of operated patients presented with hepatic steatosis. NASH (non-alcoholic steatohepatitis) was detected in 28.5% of patients; none had cirrhosis. The increment of liver fibrosis stage was associated with decreasing frequency of the MTARC1 minor allele (p = 0.03). In multivariate analysis MTARC1 was an independent protective factor against fibrosis ≥ 1b (OR = 0.52, p = 0.03) and ≥ 1c (OR = 0.51, p = 0.04). The PNPLA3 risk allele was associated with increased hepatic steatosis, fibrosis, and NASH (OR = 2.22, p = 0.04). The HSD17B13 polymorphism was protective against liver injury as reflected by lower AST (p = 0.04) and ALT (p = 0.03) activities. The TM6SF2 polymorphism was associated with increased ALT (p = 0.04). In conclusion, hepatic steatosis is common among patients scheduled for bariatric surgery, but the MTARC1 and HSD17B13 polymorphisms lower liver injury in these individuals.

Encephalomyelitis associated with rheumatoid arthritis: a case report.

Encephalitis/encephalomyelitis in the course of rheumatoid arthritis (RA) remains a matter of debate. We present a case of a patient with encephalomyelitis associated with RA confirmed with post-mortem neuropathological examination. A 68-year-old woman with a long-standing, seropositive history of RA presented progressive disturbances of consciousness. Magnetic resonance imaging (MRI) of the brain and cervical spine revealed an increase of signal intensity on T2-weighted and fluid attenuated inversion recovery (FLAIR) images with corresponding restricted diffusion involving cerebral peduncles, pons, medulla oblongata, and cervical spinal cord and mild contrast-enhancement of the right cerebral peduncle. Extensive radiological and laboratory testing, including autoantibodies to paraneoplastic anti-neuronal and neuronal cell surface antigens, were all negative except for elevated rheumatoid factor. Cerebrospinal fluid (CSF) analysis revealed moderate pleocytosis with mononuclear cell predominance, mildly increased protein level, and negative viral PCRs, bacterial cultures, flow cytometry, and neuronal surface antibodies. Despite intensive treatment with corticosteroids, antibiotics, antiviral drugs, and intravenous immunoglobulin the patient died after 3 months of hospitalization. Post-mortem neuropathological examination revealed numerous, disseminated, heterochronous ischaemic lesions, rarely with haemorrhagic transformation, predominantly in the brainstem, and widespread, diffuse microglia and T-cell infiltrations with neuronal loss and astrogliosis, most severe in the frontal and temporal lobes. Mild, perivascular lymphocyte T infiltrations involved particularly small and medium-sized vessels and were associated with brainstem ischaemic lesions. The neuropathological picture confirmed diagnosis of encephalomyelitis, which together with the clinical course suggested association with RA. Concluding, encepha-lomyelitis due to RA remains a challenging, controversial entity that needs further research and the establishment of effective diagnostic and treatment guidelines.

Cardiac Morphology, Function, and Hemodynamics in Patients With Morbid Obesity and Nonalcoholic Steatohepatitis.

Background The patients with nonalcoholic fatty liver disease demonstrate an increased cardiovascular risk. The adverse influence of liver abnormalities on cardiac function are among many postulated mechanisms behind this association. The aim of the study was to evaluate cardiac morphology and function in patients with morbid obesity referred for bariatric surgery with liver biopsy. Methods and Results We evaluated with echocardiography 171 consecutive patients without known cardiac disease (median age 42 [interquartile range, 37-48] years, median body mass index 43.7 [interquartile range, 41.0-47.5], 67% female patients. Based on the liver biopsy results, there were 44 patients with nonalcoholic steatohepatitis (NASH), 69 patients with isolated steatosis, and 58 patients without steatosis. Patients with NASH demonstrated signs of left ventricular concentric remodeling and hyperdynamic circulation, including indexed left ventricular end-diastolic diameter [cm/m2]: NASH 1.87 [0.22]; isolated steatosis 2.03 [0.33]; without steatosis 2.01 [0.19], P=0.001; relative wall thickness: NASH 0.49±0.05, isolated steatosis 0.47±0.06, without steatosis 0.46±0.06, P=0.011; cardiac index [L/m2]: NASH 3.05±0.54, isolated steatosis 2.80±0.44, without steatosis 2.79±0.50, P=0.013. After adjustment for sex, age, blood pressure, and heart rate, most of the measures of the left ventricular systolic and diastolic function, left atrial size, right ventricular function, and right ventricular size did not differ between groups. Conclusions In a group of patients with extreme obesity, NASH was associated with left ventricular concentric remodeling and hyperdynamic circulation. Increased cardiac output in NASH may represent an additional risk factor for incident cardiovascular events in this population.

COVID-19 Autopsies: A Case Series from Poland.

This paper presents autopsy findings of 3 COVID-19 patients randomly selected for post-mortem from two tertiary referral Polish hospitals. Analysis of macroscopic, histopathological findings with clinical features was performed. All 3 deceased patients were Caucasian males (average age 61 years, range from 56 to 68 years). Using real-time polymerase chain reaction assay, the patients were confirmed (antemortem) to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Two patients were obese, and 1 patient had type 2 diabetes mellitus. The medical history of 1 patient included hemorrhagic pancreatitis, gangrenous cholecystitis, Acinetobacter baumanii sepsis, and cholecystectomy. Pulmonary embolism was diagnosed in 2 patients. At autopsy, in 1 case, the lungs showed bilateral interstitial pneumonia with diffuse alveolar damage (DAD), while in another case, interstitial pulmonary lymphoid infiltrates and enlarged atypical pneumocytes were present but without DAD. Microthrombi in lung vessels and capillaries were observed in 2 cases. This study revealed thrombotic complications of COVID-19 and interstitial pneumonia with DAD presence as the main autopsy findings in patients with SARS-CoV-2 infection that was confirmed antemortem with molecular tests. Autopsy studies using tissue sections handled in accordance with SARS-CoV-2 biosafety guidelines are urgently needed, especially in the case of subjects who were below the age of 60.

White matter dissection with the Klingler technique: a literature review.

The aim of this literature review is to present a summary of the published literature relating the details of the different modifications of specimen preparation for white matter dissection with the Klingler technique. For this review, 3 independent investigators performed an electronic literature search that was carried out in the Pubmed, Scopus and Web of Science databses up to December 2019. Furthermore, we performed citation tracking for the articles missed in the initial search. Studies were eligible for inclusion when they reported details of at least the first 2 main steps of Klingler's technique: fixation and freezing. A total of 37 full-text articles were included in the analysis. We included original anatomical studies in which human white matter dissection was performed for study purposes. The main three steps of preparation are the same in each laboratory, but the details of each vary between studies. Ten percent formalin is the most commonly used (34 studies) solution for fixation. The freezing time varied between 8 h and a month, and the temperature varied from - 5 to - 80 °C. After thawing and during dissections, the specimens were most often kept in formalin solution (13), and the concentration varied from 4 to 10%. Klingler's preparation technique involves three main steps: fixation, freezing and thawing. Even though the details of the technique are different in most of the studies, all provide subjectively good quality specimens for anatomical dissections and studies.

No association between aortic stiffness and liver steatosis in morbidly obese patients.

BACKGROUND AND AIMS: Patients with non-alcoholic fatty liver disease are characterized by increased aortic stiffness, but it is unclear whether this is related to non-alcoholic fatty liver disease itself or concomitant metabolic syndrome components, including hypertension and diabetes. Previous studies were methodologically limited by ultrasound-based assessment of liver steatosis or performing liver biopsy in patients with more severe disease. Therefore, we prospectively measured aortic pulse wave velocity (aPWV) in non-selected obese subjects admitted for bariatric surgery with liver biopsy, allowing assessment of the association between aortic stiffness and biopsy-confirmed liver steatosis. METHODS: We evaluated 120 consecutive severely obese patients (79 females; mean age 42 ±â€¯10 years, mean body mass index 45.0 ±â€¯5.3 kg/m2) without cardiac disease or alcohol-induced liver disease, who were admitted for bariatric surgery. The presence or absence of liver steatosis was defined by wedge liver biopsy. aPWV was measured with the Doppler method at the time of preoperative transthoracic echocardiography. RESULTS: Based on liver biopsy results, 82 patients (68%) had liver steatosis and 38 (32%) had no steatosis. Univariate linear regression analysis showed that age, mean arterial pressure, liver steatosis, heart rate, female gender, and diabetes were significantly associated with aPWV. However, only age, mean arterial pressure, heart rate, and diabetes remained significant in the multivariate model (p ≤ 0.001). CONCLUSIONS: We found no independent association between biopsy-confirmed liver steatosis and aortic stiffness measured by Doppler aPWV in morbidly obese individuals. Aortic stiffness in these subjects is related to comorbidities and not to non-alcoholic fatty liver disease itself.

Matrix metalloproteinases-2, -7 and tissue metalloproteinase inhibitor-1 expression in human endometrium.

INTRODUCTION: Endometrium undergoes regular, cyclic tissue remodeling mostly associated to the endocrine system status. It is well-known fact that steroid hormones are strongly responsible for changes in endometrium. The precise mechanism of their action is still under investigation. The aim of the study was to evaluate the expression of metalloproteinases 2 and 7 (MMP-2, -7) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in human endometrium in relation to serum concentrations of estradiol and progesterone during different phases of menstrual cycle. MATERIAL AND METHODS: The study material consisted of 52 biopsy samples; 12 obtained in the proliferative phase, 11 in the secretory phase and 29 during menstruation. Expression of MMP-2, MMP-7 and TIMP-1 was assessed by immunohistochemistry. Serum concentrations of estradiol and progesterone at time of biopsy were evaluated by immunochemistry assay. Results of the study were statistically assessed by linear regression model. RESULTS: Increased serum concentration of estradiol was associated with increased MMP-2 expression in proliferative phase but decreased in secretory phase and during menstruation. No significant relationship was found between progesterone concentration and MMP-2 expression. Moreover, no difference in the expression of MMP-7 and TIMP-1 in the endometrium in relation to hormone levels and menstrual cycle phases were observed. CONCLUSIONS: The results of the study indicate that estradiol influence MMP-2 expression in the endometrium depends on the phase of menstrual cycle. Such relationships were not found for MMP-7 and TIMP-1 and further tests clarifying association between estradiol and MMPs are needed.

Transfer learning with deep convolutional neural network for liver steatosis assessment in ultrasound images.

PURPOSE: The nonalcoholic fatty liver disease is the most common liver abnormality. Up to date, liver biopsy is the reference standard for direct liver steatosis quantification in hepatic tissue samples. In this paper we propose a neural network-based approach for nonalcoholic fatty liver disease assessment in ultrasound. METHODS: We used the Inception-ResNet-v2 deep convolutional neural network pre-trained on the ImageNet dataset to extract high-level features in liver B-mode ultrasound image sequences. The steatosis level of each liver was graded by wedge biopsy. The proposed approach was compared with the hepatorenal index technique and the gray-level co-occurrence matrix algorithm. After the feature extraction, we applied the support vector machine algorithm to classify images containing fatty liver. Based on liver biopsy, the fatty liver was defined to have more than 5% of hepatocytes with steatosis. Next, we used the features and the Lasso regression method to assess the steatosis level. RESULTS: The area under the receiver operating characteristics curve obtained using the proposed approach was equal to 0.977, being higher than the one obtained with the hepatorenal index method, 0.959, and much higher than in the case of the gray-level co-occurrence matrix algorithm, 0.893. For regression the Spearman correlation coefficients between the steatosis level and the proposed approach, the hepatorenal index and the gray-level co-occurrence matrix algorithm were equal to 0.78, 0.80 and 0.39, respectively. CONCLUSIONS: The proposed approach may help the sonographers automatically diagnose the amount of fat in the liver. The presented approach is efficient and in comparison with other methods does not require the sonographers to select the region of interest.

Expression of matrix metalloproteinase enzymes in endometrium of women with abnormal uterine bleeding.

OBJECTIVES: Abnormal uterine bleeding (AUB) is caused by derangement of physiological processes of tissue growth, shedding and regeneration. It is known that interplay between metalloproteinases (MMP's) and tissue inhibitors of metalloproteinases (TIMP's) may play a crucial role in its occurrence. AIM: To define if expression of proMMP-2, MMP-2 and TIMP-1 in endometrium of women with AUB is dependent on steroid sex hormone concentration and histopathological picture. MATERIALS AND METHODS: Endometrial scraps were taken from 21 women with AUB and 19 controls. Samples were evaluated in light microscopy by a certified pathologist. Activity of proMMP-2 and MMP-2 proteins levels were evaluated by gelatin zymography and TIMP-1 by reversed zymography. The results has been correlated with serum estradiol and progesterone concentrations in linear regression model. RESULTS: Expression: of proMMP-2 in endometrium of women with AUB is correlated with estradiol concentration and inversely correlated with progesterone levels. It was significantly higher in women with dysfunctional endometrium (p<0.001). Expression of MMP-2 was highest in women with endometrial polyps and longer bleeding (p<0.01), while expression of TIMP-1 was independent from hormone concentration. CONCLUSION: Lack of correlation between proMMP-2 and MMP-2 levels suggest different pathway of their activation in AUB. ProMMP-2 is up regulated by estradiol and down regulated by progesterone while MMP-2 levels increase with the length of bleeding.

The effects of Nordic Walking training on selected upper-body muscle groups in female-office workers: A randomized trial.

BACKGROUND: Regular Nordic Walking training could improve fitness and reduce tenderness in selected muscle groups in office workers. OBJECTIVE: An assessment of the effects of a 12-week Nordic Walking training program on the perceived pain threshold (PPT) and the flexibility of selected upper-body muscle groups in postmenopausal female office workers. METHODS: 39 office workers were selected at random for the treatment group (NWg, n = 20) and the control group (Cg, n = 19). The persons from the NW group completed a 12-week Nordic Walking training program (3 times a week/1 hour). PPTs measurements in selected muscles and functional tests evaluating upper-body flexibility (Back Scratch - BS) were carried out twice in every participant of the study: before and after the training program. RESULTS: A significant increase in PPT (kg/cm2) was observed in the following muscles in the NW group only: upper trapezius (from 1,32 kg/cm2 to 1,99 kg/cm2), mid trapezius (from 2,92 kg/cm2 to 3,30 kg/cm2), latissimus dorsi (from 1,66 kg/cm2 to 2,21 kg/cm2) and infraspinatus (from 1,63 kg/cm2 to 2,93 kg/cm2). Moreover, a significant improvement in the BS test was noted in the NW group compared with the control group (from -1,16±5,7 cm to 2,18±5,1 cm in the NW group vs from -2,52±6,1 to -2,92±6,2 in the control group). CONCLUSIONS: A 12-week Nordic Walking training routine improves shoulder mobility and reduces tenderness in the following muscles: trapezius pars descendens and middle trapezius, infraspinatus and latissimus dorsi, in female office workers.