Background and Objectives: Saffron treatment and photobiomodulation (PBM) are non-invasive therapeutic approaches able to mitigate and stabilize retinal degenerative diseases such as age-related macular degeneration (AMD). Although different, these therapies partially match their modulated pattern of genes. Recent attempts to find an additive effect by coadministration of saffron and PBM have failed. Instead, in this study, a different protocol to increase neuroprotection by providing consecutive saffron and PBM treatment administration is suggested. Materials and Methods: Albino rats, whose retinal damage was caused by light exposure (LD, light damage), were subjected to differential treatment protocols before and after LD: (1) PBM followed by saffron; and (2) single treatments of PBM. Thinning of the photoreceptor layer and neuro-inflammatory markers for gliosis and microglia were assessed via immune-histochemical techniques. Results: Results confirm that PBM and saffron alone cope with retinal neurodegenerative processes, preserving retinal thickness and gliosis and microglia invasion in a differential way. However, the synergistic effect of the combined treatment was restricted to the early neuroinflammation, even when provided sequentially. Conclusion: The broad spectra of action of both neuroprotectants require further investigation to identify other key pathways helpful in enhancing the effects of these two approaches in combination. Full article

Urogenital schistosomiasis is caused by Schistosoma haematobium (S. haematobium) infection, which has been linked to the development of bladder cancer. In this study, three repurposing drugs, ivermectin, arteether and praziquantel, were screened to find the potent drug-repurposing candidate against the Schistosoma-associated bladder cancer (SABC) in humans by using computational methods. The biology of most glutathione S-transferases (GSTs) proteins and vascular endothelial growth factor (VEGF) is complex and multifaceted, according to recent evidence, and these proteins actively participate in many tumorigenic processes such as cell proliferation, cell survival and drug resistance. The VEGF and GSTs are now widely acknowledged as an important target for antitumor therapy. Thus, in this present study, ivermectin displayed promising inhibition of bladder cancer cells via targeting VEGF and GSTs signaling. Moreover, molecular docking and molecular dynamics (MD) simulation analysis revealed that ivermectin efficiently targeted the binding pockets of VEGF receptor proteins and possessed stable dynamics behavior at binding sites. Therefore, we proposed here that these compounds must be tested experimentally against VEGF and GST signaling in order to control SABC. Our study lies within the idea of discovering repurposing drugs as inhibitors against the different types of human cancers by targeting essential pathways in order to accelerate the drug development cycle. Full article

The COVID-19 pandemic was and still is a global burden with more than 178,000,000 cases reported so far. Although it mainly affects respiratory organs, COVID-19 has many extrapulmonary manifestations, including, among other things, liver injury. Many hypotheses have been proposed to explain direct and indirect impacts of the SARS-CoV-2 virus on the liver. Studies have shown that around 15–30% of patients with COVID-19 have underlying liver disease, and 20–35% of patients with COVID-19 had altered liver enzymes at admission. One of the hypotheses is reactivation of an underlying liver disease, such as non-alcoholic fatty liver disease (NAFLD). Some studies have shown that NAFLD is associated with severe COVID-19 and poor outcome; nevertheless, other studies showed no significant difference between groups in comparing complications and clinical outcomes. Patients with NAFLD may suffer severe COVID-19 due to other comorbidities, especially cardiovascular diseases. The link between NAFLD and COVID-19 is not clear yet, and further studies and research are needed. Full article

Background and Objectives: The aim of the present study was to report the safety and efficacy of percutaneous navigation under local anesthesia for computed tomography-guided microwave ablation of malignant liver lesions located in the hepatic dome. Patients with primary and secondary malignant liver lesions located in the hepatic dome who underwent percutaneous computed tomography-guided microwave ablation using a computer-assisted navigation system under local anesthesia were prospectively evaluated. The primary objective was technical success. Materials and Methods: The sample consisted of 10 participants (16 lesions) with a mean age of 60.60 years (SD = 9.25 years) and a mean size of 20.37 ± 7.29 cm, and the mean follow-up time was 3.4 months (SD = 1.41) months. Results: Primary technical success was 93.75%. Tumor remnant was noticed at one month follow-up in a single metastatic lesion, which was re-treated with an ablation session, and no tumor remnant was depicted in the subsequent imaging follow-up (secondary technical success 100%). Grade I self-limited complications (according to the CIRSE classification system) included small pleural effusion (n = 1) and minor bleeding post antenna removal (n = 1) requiring nothing but observation. Conclusions: the findings of the present study indicate that percutaneous navigation under local anesthesia is a safe and efficacious approach for computed tomography-guided microwave ablation of malignant liver lesions located in the hepatic dome. Large randomized controlled studies are warranted to observe treatment effectiveness and compare the results with those of other options. Full article

Background: Spontaneous hepatic rupture associated with the syndrome characterized by hemolysis, elevated liver enzymes, and a low platelet count (HELLP syndrome) is a rare and life-threatening condition, and only a few cases regarding the management of this condition through transcatheter arterial embolization (TAE) have been previously reported. Case summary: Herein, we report a case involving a 35-year-old pregnant woman who presented at 28 weeks of gestation with right upper quadrant pain, hypotension, and elevated levels of liver enzymes. Transabdominal ultrasound revealed fetal death. She required an emergency cesarean section, and hepatic rupture was identified after the fetus had been delivered. Hepatic packing and TAE were performed. The postprocedural course was uneventful, and the patient was discharged 14 days after she had been admitted to our hospital. Conclusions: Spontaneous hepatic rupture associated with HELLP syndrome is a very serious condition that requires prompt and decisive management. The high maternal and fetal mortality rates associated with this condition can be reduced through early accurate diagnosis and adequate management. The findings in the reported case indicate that TAE may be an attractive alternative to surgery for the management of spontaneous hepatic rupture associated with HELLP syndrome. Full article

Background and Objectives: Periodontal disease is a chronic inflammatory disease in which gradual destruction of tissues around teeth is caused by plaque formed by pathogenic bacteria. The purpose of this study was to evaluate the potential of 75% ethanol extract of Colocasia antiquorum var. esculenta (CA) as a prophylactic and improvement agent for periodontal disease in vitro and in vivo. Materials and Methods: The antimicrobial efficacy of CA against Porphyromonas gingivalis (P. gingivalis, ATCC 33277) was evaluated using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) test, and cytotoxicity was confirmed by CCK-8 assay. For the in vivo study, P. gingivalis was applied by oral gavage to BALB/c mice. Forty-two days after the first inoculation of P. gingivalis, intraoral swabs were taken for microbiome analysis, and the mice were sacrificed to evaluate the alveolar bone loss. Results: The MIC of CA against P. gingivalis was 31.3 μg/mL, the MBC was 62.5 μg/mL, with no cytotoxicity. The diversity of the oral microbiome decreased in the positive control group, while those of the VA (varnish) and VCA (varnish added with CA) groups increased as much as in the negative control group, although the alveolar bone loss was not induced in the mouse model. Conclusions: CA showed antibacterial effects in vitro, and the VA and VCA groups exhibited increased diversity in the oral microbiome, suggesting that CA has potential for improving periodontal disease. Full article

Ischemic stroke (IS) is a cerebrovascular disease with a high rate of disability and mortality. It is classified as the second leading cause of death that arises from the sudden occlusion of small vessels in the brain with consequent lack of oxygen and nutrients in the brain tissue. Following an acute ischemic event, the cascade of events promotes the activation of multiple signaling pathways responsible for irreversible neuronal damage. The mitogen-activated protein kinase (MAPK) signaling pathway transmits signals from the cell membrane to the nucleus in response to different stimuli, regulating proliferation, differentiation, inflammation, and apoptosis. Several lines of evidence showed that MAPK is an important regulator of ischemic and hemorrhagic cerebral vascular disease; indeed, it can impair blood–brain barrier (BBB) integrity and exacerbate neuroinflammation through the release of pro-inflammatory mediators implementing neurovascular damage after ischemic stroke. This review aims to illustrate the miRNAs involved in the regulation of MAPK in IS, in order to highlight possible targets for potential neuroprotective treatments. We also discuss some miRNAs (miR), including miR-145, miR-137, miR-493, and miR-126, that are important as they modulate processes such as apoptosis, neuroinflammation, neurogenesis, and angiogenesis through the regulation of the MAPK pathway in cerebral IS. To date, limited drug therapies are available for the treatment of IS; therefore, it is necessary to implement preclinical and clinical studies aimed at discovering novel therapeutic approaches to minimize post-stroke neurological damage. Full article

Background and Objectives: Although vitamin D insufficiency or deficiency is prevalent in children with allergic diseases, recommendations for supplementation dosing regimens are imprecise and variable in the literature, because clinical trials aiming to determine optimal doses were scarce in the past. This study aimed to investigate supplementation of vitamin D3 that may achieve therapeutically effective but not toxic serum levels in a subpopulation of children with allergic diseases and concomitant hypovitaminosis D. Materials and Methods: The retrospective, observational study with a cross-sectional design included 94 children suffering from allergic diseases and having vitamin D deficiency/insufficiency who were prescribed high-dose vitamin D3 supplementation by a pediatrician for at least 6 weeks and not more than 9 weeks. Serum levels of the major metabolite of vitamin D (25-(OH)D) were determined in all children twice: before and two weeks after the end of vitamin D3 supplementation. Results: An increase in serum level of the 25-(OH)D after supplementation was significant. However, if the subjects had higher serum levels of the 25-(OH)D before the supplementation, and if the supplementation lasted 8 instead of 6 weeks, the absolute increase in serum level of the 25-(OH)D was lower. Patients taking corticosteroids as inhalation or intranasally had a more intense effect of vitamin D3 supplementation, i.e., the absolute increase in levels of 25-(OH)D was higher than in patients not using such medication. Conclusions: Vitamin D deficiency and insufficiency in children with allergic diseases can be treated with maximal recommended doses of vitamin D3 for a short period of time, especially if they were prescribed with inhalation or intranasal corticosteroids. Full article

Factures in ankylosing spondylitis (AS) patients tend to occur due to the absence of motion between vertebrae, poor bone quality, and a long lever arm that generates extension force. However, most patients have a history of at least minor trauma. The aim of this report was that a vertebral fracture in a patient with AS can be caused not only by minor trauma, but also by position changes or maintenance of position for examination due to structural weakness. A 75-year-old woman with AS visited her local hospital on foot for back pain. She usually had back pain. However, she had increased back pain after falling over three weeks prior. In plain radiographs, no fracture was apparent. The doctor tried to perform magnetic resonance imaging (MRI) for further evaluation. However, several attempts of MRI failed due to continuous movement arising from pain. As a result, MRI was performed under spinal anesthesia for pain control. However, complete paraplegia developed during the MRI examination. MRI showed extension-type vertebral fracture with displacement and the patient was transferred to our hospital. We performed emergency posterior fusion, but neurological symptoms did not improve. This case suggests the need for careful positioning, sedation, or anesthesia when performing an examination or surgery in AS patients. We recommend that all patients with AS should be carefully positioned at all times during testing or surgery. Full article

Background and Objectives: Methotrexate is widely prescribed for the treatment of moderate-to-severe psoriasis. As drug survival encompasses efficacy, safety, and treatment satisfaction, such studies provide insights into successful drug treatments in the real-life scenario. The objective was to define methotrexate drug survival and reasons for discontinuation, along with factors associated with drug survival, in a cohort of adult patients with moderate-to-severe plaque psoriasis. Materials and Methods: Data on methotrexate treatment were extracted from our institutional registry. Drug survival was estimated by Kaplan–Meier analysis, and predictors of drug survival were analyzed by Cox proportional hazards regression. Results: We included 133 patients treated with methotrexate. Due to significant effects of the year of treatment initiation, drug survival analysis was performed for 117 patients who started methotrexate in 2010 or later. Median methotrexate drug survival was 11.0 months. Overall, 89% of patients discontinued treatment, with over half of these (51%) due to lack of efficacy. Significantly longer drug survival was seen for patients who discontinued treatment due to lack of efficacy versus drug safety (p = 0.049); when stratified by sex, this remained significant only for women (p = 0.002). The patient ABCC2 rs717620 genotype was significantly associated with drug survival in both univariate log-rank and multivariate Cox regression analyses, with variant T allele associated with longer drug survival (hazard ratio, 0.606; 95% confidence interval, 0.380–0.967; p = 0.036). Conclusions: We have identified the novel association of patient ABCC2 rs717620 genotype with methotrexate drug survival. This pharmacogenetic marker might thus help in the management of psoriasis patients in daily practice. Full article

Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease with autosomal recessive transmission, characterized by periodic fever attacks with self-limited serositis. Secondary amyloidosis due to amyloid A renal deposition represents the most fearsome complication in up to 8.6% of patients. Amyloidosis A typically reveals a nephrotic syndrome with a rapid progression to end-stage kidney disease still. It may also involve the cardiovascular system, the gastrointestinal tract and the central nervous system. Other glomerulonephritis may equally affect FMF patients, including vasculitis such as IgA vasculitis and polyarteritis nodosa. A differential diagnosis among different primary and secondary causes of nephrotic syndrome is mandatory to determine the right therapeutic choice for the patients. Early detection of microalbuminuria is the first signal of kidney impairment in FMF, but new markers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL) may radically change renal outcomes. Serum amyloid A protein (SAA) is currently considered a reliable indicator of subclinical inflammation and compliance to therapy. According to new evidence, SAA may also have an active pathogenic role in the regulation of NALP3 inflammasome activity as well as being a predictor of the clinical course of AA amyloidosis. Beyond colchicine, new monoclonal antibodies such as IL-1 inhibitors anakinra and canakinumab, and anti-IL-6 tocilizumab may represent a key in optimizing FMF treatment and prevention or control of AA amyloidosis. Full article

Background and Objectives: Studies have shown a lower prevalence of anti-SARS-CoV-2 antibodies in patients with inflammatory bowel disease (IBD), including amongst those receiving biological therapy. Aims were to determine the seroprevalence of anti-SARS-CoV-2 antibodies in IBD patients and to assess any association between seropositivity and IBD characteristics. Materials and Methods: Serum from adult IBD patients was prospectively collected between December 2020 and January 2021 and analyzed for anti-SARS-CoV-2 antibodies. Information about IBD characteristics and SARS-CoV-2 exposure risk factors was collected and analyzed. Serum from non-IBD healthcare workers formed the control group. Results: 311 IBD patients on biologics and 75 on mesalazine were enrolled. Ulcerative colitis (UC) extension (p < 0.001), Crohn’s disease (CD) phenotype (p = 0.009) and use of concomitant corticosteroids (p < 0.001) were significantly different between the two IBD groups. Overall seroprevalence among IBD patients was 10.4%. The control group showed a prevalence of 13.0%, not significantly different to that of IBD patients (p = 0.145). Only a close contact with SARS-CoV-2 positive individuals and the use of non-FFP2 masks were independently associated with a higher likelihood of seropositivity amongst IBD patients. Conclusion: In IBD patients, the prevalence of anti-SARS-CoV-2 antibodies is not determined by their ongoing treatment. Disease-related characteristics are not associated with a greater risk of antibody seropositivity. Full article

Inflammatory processes are deeply involved in ischemia-reperfusion injuries (IRI) and ventricular remodelling (VR) after a ST-segment elevation myocardial infarction (STEMI). They are associated with clinical adverse events (heart failure and cardiovascular death) adding damage to the myocardium after reperfusion. Moreover, acute myocardial infarction (AMI) induces a local sympathetic denervation leading to electrical instability and arrythmia. Colchicine, a well-known alkaloid with direct anti-inflammatory effects, was shown to reduce the myocardial necrosis size and limit the VR. In a recent proof of concept study, colchicine appears to prevent sympathetic denervation in a mice model of ischemia/reperfusion, but not in the necrosis or in the border zone areas. The Colchicine to Prevent Sympathetic Denervation after an AMI study (COLD-MI) is an ongoing, confirmative, prospective, monocentre, randomized, open-label trial. The COLD-MI trial aims to evaluate the intensity of sympathetic denervation after AMI and its potential modulation due to low dose colchicine. Sympathetic denervation will be noninvasively evaluated using single-photon emission computed tomography (SPECT). After a first episode of STEMI (Initial TIMI flow ≤ 1) and primary percutaneous coronary intervention (PPCI), patients will be randomized (n = 56) in a 1:1 ratio to either receive colchicine or not for 30 days. The primary end point will be the percentage of myocardial denervation measured by 123I-metaiodobenzylguanidine (123I-MIBG) SPECT at a 6-month follow-up. The main secondary end points will be basic ECG parameters (QRS duration, corrected QT) and HRV parameters from a 24 hour-recording Holter at 1- and 6-months follow-up. Results from this study will contribute to a better understanding of the cardioprotective effect of colchicine after AMI. The present study describes the rationale, design, and methods of the trial. Full article

Background and Objectives: Anemia is the most frequent complication of inflammatory bowel diseases. Clinically, anemia can affect important quality-of-life (QoL) components, such as exercise capacity, cognitive function, and the ability to carry out social activities. The disease activity has a significant impact on QoL, mainly due to clinical manifestations, which are more severe during the periods of disease activity. Our aim was to estimate the impact of anemia on QoL in patients with Crohn’s disease. Material and Methods. We made a prospective study on 134 patients with Crohn’s disease (CD) in a Romanian tertiary center. The CD diagnosis was established by colonoscopy and histopathological examination. In particular cases, additional examinations were required (small bowel capsule endoscopy, computed tomography enterography, and magnetic resonance enterography). Anemia was defined according to the World Health Organization’s definition, the activity of the disease was assessed by Crohn’s disease activity index (CDAI) score, and the QoL was evaluated by Inflammatory Bowel Disease Questionnaire 32 (IBDQ 32). Results: 44.8% patient had anemia, statistically related to the activity of the disease and corticoids use. We found a strong association between QoL and disease activity on all four sub-scores: patients with more severe activity had a significantly lower IBDQ (260.38 ± 116.96 vs. 163.85 ± 87.20, p = 0.001) and the presence of anemia (127.03 vs. 148.38, p = 0.001). In multiple regression analyses, both disease activity and anemia had an impact on the QoL. Conclusions: Anemia has high prevalence in the CD in northeastern region of Romania. Anemia was more common in female patients, in patients undergoing corticosteroid treatment, and in those with active disease. Both anemia and disease activity had a strong negative and independent impact on QoL. Full article

Background and Objectives: In Poland, the rates of morbidity and mortality due to cervical cancer are amongst the highest in Europe. A significant percentage of newly diagnosed cases of cervical cancer are at an advanced stage. Unfortunately, only about 20% of Polish women take part in cervical cancer screening. The aim of the study was to assess students’ knowledge of cervical cancer risk factors and prevention. Materials and Methods: The study was provided to Polish students from various universities and faculties between May 2020 and November 2020. The questionnaire was designed specifically for this study and was validated. The chi-square test was used to compare the responses between subgroups. Results: The study was carried out on a group of 995 students (80.6% women, 19% men, 0.4% no data), (average age 21.9 years). Most students knew that the main risk factor for cervical cancer is human papillomavirus (HPV) infection (82% of all responders; 86% of medical students; 73% of non-medical students; p < 0.001). Only 40% of students knew that in Poland the Population Prevention and Early Diagnosis Program is carried out on women aged 25–59 years every three years. Most students correctly indicated that cervical cancer screening in Poland is performed using cervical cytology and were familiar with the basis of cytology. Only 57% of students knew that there are no specific early symptoms of cervical cancer. A total of 78% of all respondents knew that HPV vaccination reduces the risk of cervical cancer. Medical students and students who are sexually active demonstrated a better knowledge of cervical cancer. Conclusions: The Polish students had some knowledge of cervical cancer risk factors and primary and secondary prevention. Significantly better knowledge was demonstrated by medical students. Some efforts should be made to ensure that young people, who are not associated with medicine are better educated about cervical cancer in order to reduce the overall incidence and improve early detection rates. Full article