Transcriptome from Paired Samples Improves the Power of Comprehensive COVID-19 Host-Viral Characterization.

Previous transcriptome profiling studies showed significantly upregulated genes and altered biological pathways in acute COVID-19. However, changes in the transcriptional signatures during a defined time frame are not yet examined and described. The aims of this study included viral metagenomics and evaluation of the total expression in time-matched and tissue-matched paired COVID-19 samples with the analysis of the host splicing profile to reveal potential therapeutic targets. Prospective analysis of paired nasopharyngeal swabs (NPS) and blood (BL) samples from 18 COVID-19 patients with acute and resolved infection performed using Kallisto, Suppa2, Centrifuge, EdgeR, PantherDB, and L1000CDS2 tools. In NPS, we discovered 6 genes with changed splicing and 40 differentially expressed genes (DEG) that yielded 88 altered pathways. Blood samples yielded 15 alternatively spliced genes. Although the unpaired DEG analysis failed, pairing identified 78 genes and 242 altered pathways with meaningful clinical interpretation and new candidate drug combinations with up to 65% overlap. Metagenomics analyses showed SARS-CoV-2 dominance during and after the acute infection, with a significant reduction in NPS (0.008 vs. 0.002, p = 0.019). Even though both NPS and BL give meaningful insights into expression changes, this is the first demonstration of how the power of blood analysis is vastly maximized by pairing. The obtained results essentially showed that pairing is a determinant between a failed and a comprehensive study. Finally, the bioinformatics results prove to be a comprehensive tool for full-action insights, drug development, and infectious disease research when designed properly.

Serum Concentration of Prostaglandin E2 as a Diagnostic Biomarker in Patients With Silicosis: A Case-Control Study.

OBJECTIVE: Silicosis is a prevalent incurable pneumoconiosis caused by inhalation of silica dust. Study aimed to investigate inflammatory, hematological, and biochemical parameters as additional biomarkers for diagnosing or monitoring silicosis. METHODS: Research enrolled 14 workers with silicosis and 7 healthy controls (without exposure and silicosis). The serum level of prostaglandin E2, C-reactive protein, fibrinogen, biochemical, and hematological parameters were measured. The receiver operating characteristic curve was used to determine diagnostic sensitivity of each biomarker. RESULTS: Patients with silicosis have a significantly higher level of prostaglandin E2, erythrocyte, hemoglobin, and hematocrit than patients without silicosis. Prostaglandin E2, hemoglobin, and the erythrocyte count are significant in separating the silicosis cases from healthy controls. CONCLUSIONS: Prostaglandin E2 might be an adjuvant peripheral diagnostic biomarker for silicosis, while hematological parameters (erythrocytes, hemoglobin, and hematocrit) might be prognostic biomarkers.

Nailfold capillary morphology and platelet function in patients with exfoliative glaucoma.

PURPOSE: The purpose of the present study was to evaluate the nailfold capillary morphological features in patients with exfoliative glaucoma (XFG) and compare them with those pertaining to primary open-angle glaucoma (POAG), normal controls and subjects with exfoliation syndrome (XFS). The second purpose was to investigate all parameters related to platelet function on the hemogram, including the platelet count (PLT), the mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) in patients with XFG. These parameters were subsequently compared with those belonging to normal controls, POAG and XFS subjects. METHODS: This case control study involved 152 consecutive patients that were examined at the Glaucoma Department of Clinic for Eye Diseases, Clinical Centre of Serbia, as the referral center for glaucoma in Serbia, between June 2016 and December 2017. RESULTS: Regarding capillaroscopic characteristics, statistically significant difference was found in capillary diameter and tortuosity between the XFG and POAG group (p = 0.050 and p = 0.035) and the XFG and NC group (p = 0.003 and p = 0.044), as well as in the distribution of capillary loops and avascular zones between the XFG and NC group (p = 0.014 and p = 0.004). The subjects with XFG had lower PLT values compared to POAG patients (p = 0.022). CONCLUSIONS: In conclusion, to the best of our knowledge, this study marks the first attempt to evaluate capillary morphology as well as to investigate all parameters related to platelet function on the hemogram, in patients with newly diagnosed XFG. Our findings revealed nailfold capillary morphological vascular changes in XFG patients. The subjects with XFG had lower PLT values and a higher MPV serum parameter compared to normal controls and patients with POAG. Further research in this field should therefore aim to evaluate the consequences of the aforementioned microvascular abnormalities in patients with XFG.

Screening commercial drivers for obstructive sleep apnea: Validation of STOP-Bang questionnaire.

OBJECTIVES: The main aim has been to examine psychometric properties of STOP-Bang (snoring, tiredness, observed apnea, high blood pressure, body mass index (BMI), age, neck circumference, male gender) scoring model (Serbian translation), an obstructive sleep apnea (OSA) screening tool, in a sample of commercial drivers. MATERIAL AND METHODS: After formal translation, validation was performed on a sample of bus and truck drivers evaluating test-retest reliability, construct and criterion validity. Overnight polysomnography or cardiorespiratory polygraphy were used for OSA diagnosis purposes. RESULTS: One hundred male participants, 24-62 years old, were included. STOP-Bang classified 69% as potential OSA patients. Polysomnography identified OSA in 57% of the sample. Test-retest reliability (Cohen's κ = 0.89) was adequate. STOP-Bang score was significantly correlated to apnea-hypopnea index (AHI) and OSA severity. Sensitivity was 100% for AHI ≥ 15, highest specificity was 53.5% (AHI ≥ 5). CONCLUSIONS: STOP-Bang showed good measurement properties, supporting its further use in OSA screening of commercial drivers. Int J Occup Med Environ Health 2016;30(5):751-761.

Efficacy of Early Rehabilitation After Surgical Repair of Acute Aneurysmal Subarachnoid Hemorrhage: Outcomes After Verticalization on Days 2-5 Versus Day 12 Post-Bleeding.

AIM: To develop a specific rehabilitation protocol for patients who have undergone surgical repair of acute aneurysmal subarachnoid hemorrhage (aSAH), and to determine the time at which verticalization should be initiated after aSAH. MATERIAL AND METHODS: Sixty-five patients who underwent acute-term surgery for aSAH and early rehabilitation were evaluated in groups: Group 1 (n=34) started verticalization on days 2-5 post-bleeding whereas Group 2 (n=31) started verticalization approximately day 12 post-bleeding. All patients were monitored for early complications, vasospasm and ischemia. Assessments of motor status, depression and anxiety (using Zung scales), and cognitive status (using the Mini-Mental State Examination (MMSE)) were conducted at discharge and at 1 and 3 months post-surgery. RESULTS: At discharge, Group 1 had a significantly higher proportion of patients with ischemia than Group 2 (p=0.004). Group 1 had a higher proportion of patients with hemiparesis than Group 2 three months post-surgery (p=0.015). Group 1 patients scored significantly higher on the Zung depression scale than Group 2 patients at 1 month (p=0.005) and 3 months post-surgery (p=0.001; the same applies to the Zung anxiety scale (p=0.006 and p=0.000, respectively). Group 2 patients scored significantly higher on the MMSE than those in Group 1 at discharge (p=0.040) and 1 month post-surgery (p=0.025). CONCLUSION: Early verticalization had no effect with respect to preventing early postoperative complications in this patient group. Once a patient has undergone acute surgical repair of aSAH, it is safe and preferred that rehabilitation be initiated immediately postsurgery. However, verticalization should not start prior to day 12 post-bleeding.

Analysis of chromosomal aberrations frequency, haematological parameters and received doses by nuclear medicine professionals.

PURPOSE: The purpose of this article was to analyse the impact of low-dose ionizing radiation to nuclear medicine professionals of the Nuclear Medicine Centre of Serbia (NMCRS). METHODS: Data from the previous/initial and the last medical check-ups, obtained from the medical records of 65 employees from NMCRS, were analysed. A typical checkup, haematological parameters analysis, as well as special cytogenetical analyses, such as unstable chromosomal aberrations and micronucleus test, were carried out. For analyses of chromosomal aberrations the modified Moorhead's micro method was applied to the culture of peripheral blood lymphocytes and conventional cytogenetic technique of chromosomal aberrations was applied. The received cumulative 5-year dose was measured by personal inactive thermoluminescent dosimeters (TLD) calibrated into personal doses equivalent Hp(10). RESULTS: An increased frequency of all unstable chromosomal aberration forms, such as acentric chromosomes and isochromatid lesions, was noticed in the last periodical check-up as compared to the previous/initial checkups (p<0.05). As for haematological parameters, a higher erythrocytes and monocytes count in the periodical checkups was noticed (p<0.01). There was a negative correlation between reticulocytes and received 5-year cumulative dose (p<0.01). The duration of exposure had significant influence on higher level of leucocytes in the last periodical check-up (p<0.05). CONCLUSIONS: Nuclear medicine employees have increased health risks and there is a need to monitor their health condition by periodical check-ups for prevention from occupational diseases (carcinoma).

Influence of Pulmonary Rehabilitation on Lung Function Changes After the Lung Resection for Primary Lung Cancer in Patients with Chronic Obstructive Pulmonary Disease.

Influence of physiotherapy on the outcome of the lung resection is still controversial. Study aim was to assess the influence of physiotherapy program on postoperative lung function and effort tolerance in lung cancer patients with chronic obstructive pulmonary disease (COPD) that are undergoing lobectomy or pneumonectomy. The prospective study included 56 COPD patients who underwent lung resection for primary non small-cell lung cancer after previous physiotherapy (Group A) and 47 COPD patients (Group B) without physiotherapy before lung cancer surgery. In Group A, lung function and effort tolerance on admission were compared with the same parameters after preoperative physiotherapy. Both groups were compared in relation to lung function, effort tolerance and symptoms change after resection. In patients with tumors requiring a lobectomy, after preoperative physiotherapy, a highly significant increase in FEV1, VC, FEF50 and FEF25 of 20%, 17%, 18% and 16% respectively was registered with respect to baseline values. After physiotherapy, a significant improvement in 6-minute walking distance was achieved. After lung resection, the significant loss of FEV1 and VC occurred, together with significant worsening of the small airways function, effort tolerance and symptomatic status. After the surgery, a clear tendency existed towards smaller FEV1 loss in patients with moderate to severe, when compared to patients with mild baseline lung function impairment. A better FEV1 improvement was associated with more significant loss in FEV1. Physiotherapy represents an important part of preoperative and postoperative treatment in COPD patients undergoing a lung resection for primary lung cancer.

Oncological and functional outcome after surgical treatment of early glottic carcinoma without anterior commissure involvement.

INTRODUCTION: Glottic carcinoma can be successfully diagnosed in its early stages and treated with high percentage of success. Organ preservation and optimal functional outcomes could be achieved with wide array of surgical techniques for early glottic cancer, including endoscopic approaches or open laryngeal preserving procedures, making surgery the preferred method of treatment of early glottic carcinoma in the last few years. MATERIAL AND METHODS: Prospective study was done on 59 patients treated for Tis and T1a glottic carcinoma over a one-year time period in a tertiary medical center. Patients were treated with endoscopic laser cordectomy (types II-IV cordectomies according to European Laryngological Society classification of endoscopic cordectomies) and open cordectomy through laryngofissure. Follow-up period was 60 months. Clinical and oncological results were followed postoperatively. Voice quality after the treatment was assessed using multidimensional voice analysis 12 months after the treatment. RESULTS: There were no significant differences between oncological and functional results among two groups of patients, though complications were more frequent in patients treated with open cordectomy. CONCLUSION: Endoscopic laser surgery should be the first treatment of choice in treatment of early glottic carcinomas, though open approach through laryngofissure should be available for selected cases where anatomical factors present limiting adequate tumor removal.

Preoperative pulmonary rehabilitation in patients with non-small cell lung cancer and chronic obstructive pulmonary disease.

INTRODUCTION: The aim of this study was to assess the effects of preoperative pulmonary rehabilitation (PPR) on preoperative clinical status changes in patients with chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC), and net effects of PPR and cancer resection on residual pulmonary function and functional capacity. MATERIAL AND METHODS: This prospective single group study included 83 COPD patients (62 ±8 years, 85% males, FEV1 = 1844 ±618 ml, Tiffeneau index = 54 ±9%) with NSCLC, on 2-4-week PPR, before resection. Pulmonary function, and functional and symptom status were evaluated by spirometry, 6-minute walking distance (6MWD) and Borg scale, on admission, after PPR and after surgery. RESULTS: Following PPR significant improvement was registered in the majority of spirometry parameters (FEV1 by 374 ml, p < 0.001; VLC by 407 ml, p < 0.001; FEF50 by 3%, p = 0.003), 6MWD (for 56 m, p < 0.001) and dyspnoeal symptoms (by 1.0 Borg unit, p < 0.001). A positive correlation was identified between preoperative increments of FEV1 and 6MWD (r s = 0.503, p = 0.001). Negative correlations were found between basal FEV1 and its percentage increment (r s = -0.479, p = 0.001) and between basal 6MWD and its percentage change (r s = -0.603, p < 0.001) during PPR. Compared to basal values, after resection a significant reduction of most spirometry parameters and 6MWD were recorded, while Tiffeneau index, FEF25 and dyspnoea severity remained stable (p = NS). CONCLUSIONS: Preoperative pulmonary rehabilitation significantly enhances clinical status of COPD patients before NSCLC resection. Preoperative increase of exercise tolerance was the result of pulmonary function improvement during PPR. The beneficial effects of PPR were most emphasized in patients with initially the worst pulmonary function and the weakest functional capacity.

Oxidative stress precedes mitochondrial dysfunction in gerbil brain after aluminum ingestion.

Several studies suggest that aluminum (Al) intake might increase an individual's risk of developing Alzheimer disease. The dynamic of changes in acetylcholinesterase (AChE), cytochrome c oxidase (COX), Complex I, superoxide dismutase (SOD) and catalase (CAT) activities, and the lipid peroxide (MDA), superoxide anion (O2(-)) and thiol (SH) group levels in gerbil's brain after aluminum ingestion were analyzed. Gerbils that orally received aluminum chloride (LD25 or LD50) were sacrificed 2, 6 or 24 h later. Another group was subacutely treated (21 days; LD10). Controls received saline. Biochemical parameters were measured in cortex, hippocampus, thalamus and nucleus caudatus. Two hours after acute Al exposure AChE activity and SH group content were decreased and MDA and O2(-) levels were elevated in all investigated brain structures. The changes of COX and CAT were structure specific. SOD was increased after 6 h. Changes of investigated parameters were also seen after subacute Al treatment. These results might suggest the presence of additional source of free radicals in early phase of Al poisoning.

Fatigue in sarcoidosis: detection and treatment.

Fatigue is a prominent symptom in a large number of medical conditions, malignant and infectious diseases. Fatigue is also a prominent symptom of sarcoidosis. The occurrence of fatigue in sarcoidosis is well known but exact incidence has not been established and varies from 30-70% of patients depending on age, sex and organ involvement by the granulomatous process. The exact definition of fatigue varies broadly. It can be both physical and mental. The patients describe their sensation of fatigue qualitatively different from that fatigue they experienced before they became sick. Fatigue has a major impact on the quality of life in sarcoidosis. Establishing the extent of fatigue in sarcoidosis provides relevant insight regarding the patient's quality of life. Unfortunately there is no objective parameter for assessing fatigue in sarcoidosis. Generally, fatigue is detected by means of questionnaires. Regarding the therapy, there is no effective treatment for fatigue in sarcoidosis.

Acute low back pain with radiculopathy: a double-blind, randomized, placebo-controlled study.

OBJECTIVE: The aim of this study was to investigate the clinical effects of low-level laser therapy (LLLT) in patients with acute low back pain (LBP) with radiculopathy. BACKGROUND DATA: Acute LBP with radiculopathy is associated with pain and disability and the important pathogenic role of inflammation. LLLT has shown significant anti-inflammatory effects in many studies. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled trial was performed on 546 patients. Group A (182 patients) was treated with nimesulide 200 mg/day and additionally with active LLLT; group B (182 patients) was treated only with nimesulide; and group C (182 patients) was treated with nimesulide and placebo LLLT. LLLT was applied behind the involved spine segment using a stationary skin-contact method. Patients were treated 5 times weekly, for a total of 15 treatments, with the following parameters: wavelength 904 nm; frequency 5000 Hz; 100-mW average diode power; power density of 20 mW/cm(2) and dose of 3 J/cm(2); treatment time 150 sec at whole doses of 12 J/cm(2). The outcomes were pain intensity measured with a visual analog scale (VAS); lumbar movement, with a modified Schober test; pain disability, with Oswestry disability score; and quality of life, with a 12-item short-form health survey questionnaire (SF-12). Subjects were evaluated before and after treatment. Statistical analyses were done with SPSS 11.5. RESULTS: Statistically significant differences were found in all outcomes measured (p < 0.001), but were larger in group A than in B (p < 0.0005) and C (p < 0.0005). The results in group C were better than in group B (p < 0.0005). CONCLUSIONS: The results of this study show better improvement in acute LBP treated with LLLT used as additional therapy.