Serum levels of metalloproteinases and their inhibitors during infection with pathogens having integrin receptor-mediated cellular entry

Abstract Background: Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes with numerous roles in the normal immune response to infection. However, excess MMP activity following infection may lead to immunopathological processes that cause tissue damage. Their activity in normal tissues is subject to tight control, which is regulated by its specific endogenous tissue inhibitors (TIMPs). It is known that MMPs bind to cell surface proteins (e.g. integrins) and that such interactions can have modulatory effects on MMP functionality. The objective of this study was to determine whether there are differences in MMP and TIMP production during the acute phase of infection with different pathogens that use β-integrins as their receptors for cell entry. Methods: We measured the total amounts of soluble MMP-2, MMP-9, TIMP-1, and TIMP-2 in the sera from patients infected with Dobrava virus (DOBV), Coxiella burnetii, or uropathogenic Escherichia coli. Statistical analyses were used to correlate MMP/TIMP serum levels with different clinical laboratory parameters. Results: The results showed that both of the bacterial infections generally manifested the stronger effect on MMP production, while in contrast, viral infection introduced stronger changes to metalloproteinase inhibitors. MMPs and TIMPs were significantly correlated with some of the clinical laboratory parameters in both bacterial infections, but no correlations were found for DOBV infection. Conclusions: These findings suggest diverse mechanisms by which MMP activity could be implicated in the pathology of these 2 bacterial infections versus the viral DOBV infection, despite the type of their cellular entry receptors.     

Weak independent association signals between IDE polymorphisms, Alzheimer's disease and cognitive measures

Functional and genetic studies suggest that insulin-degrading enzyme (IDE) may be a strong functional and positional candidate. As there is a lack of consensus in regards to the level and location of IDE association signals we aimed to clarify these discrepancies through genotyping 28 SNPs in a large case-control collective together with quantitative measures of cognitive ability (MMSE). Four SNPs (rs11187007, rs2149632_ide12, rs11187033, rs11187040) were found to be associated with AD (nominal p<0.01). Tests with MMSE scores adjusted for disease duration identified associations, with the most significant result for rs1999763 (nominal p=0.008). Similarly, different reconstructed IDE haplotypes were associated with AD and higher MMSE scores. The association signals are only borderline significant after adjustment for multiple testing, but add further evidence to previous published results on the association between IDE and AD or MMSE. A subgroup analysis indicated more prominent associations with AD in younger, and with MMSE in older patients. There may be two independent effects mediated by IDE variants, risk for AD and modification of disease progression.     

Effects of low-level light therapy on xerostomia related to hyposalivation: a systematic review and meta-analysis of clinical trials

Lasers in Medical Science - Hyposalivation is a condition represented by a reduced salivary flow and may include symptoms such as mouth dryness (xerostomia), loss of taste, pain, dysphagia, and...     

Clinical characteristics and functional outcome of patients with West Nile neuroinvasive disease in Serbia

Neurologic manifestations are prominent characteristic of West Nile virus (WNV) infection. The aim of this article was to describe neurological manifestations in patients with WNV neuroinvasive disease and their functional outcome at discharge in the first human outbreak of WNV infection in Serbia. The study enrolled patients treated in the Clinic for Infectious and Tropical Diseases, Clinical Center Serbia in Belgrade, with serological evidence of acute WNV infection who presented with meningitis, encephalitis and/or acute flaccid paralyses (AFP). Functional outcome at discharge was assessed using modified Rankin Scale (mRS) and Barthel index. Fifty-two patients were analysed. Forty-four (84.6 %) patients had encephalitis, eight (15.4 %) had meningitis, and 13 (25 %) had AFP. Among patients with AFP, 12 resembled poliomyelitis and one had clinical and electrodiagnostic findings consistent with polyradiculoneuritis. Among patients with encephalitis, 17 (32.7 %) had clinical signs of rhombencephalitis, and eight (15.4 %) presented with cerebellitis. Respiratory failure with subsequent mechanical ventilation developed in 13 patients with WNE (29.5 %). Nine (17.3 %) patients died, five (9.6 %) were functionally dependent (mRS 3–5), and 38 (73.1 %) were functionally independent at discharge (mRS 0–2). In univariate analysis, the presence of AFP, respiratory failure and consciousness impairment were found to be predictors of fatal outcome in patients with WNV neuroinvasive disease (p < 0.001, p < 0.001, p = 0.018, respectively). The outbreak of human WNV infection in Serbia caused a notable case fatality ratio, especially in patients with AFP, respiratory failure and consciousness impairment. Rhombencephalitis and cerebellitis could be underestimated presentations of WNV neuroinvasive disease.     

Optimization of Alumina Ceramics Corrosion Resistance in Nitric Acid

The development of ceramic materials resistance in various aggressive media combined with required mechanical properties is of considerable importance for enabling the wider application of ceramics. The corrosion resistance of ceramic materials depends on their purity and microstructure, the kind of aggressive media used and the ambient temperature. Therefore, the corrosion resistance of alumina ceramics in aqueous HNO₃ solutions of concentrations of 0.50 mol dm⁻³, 1.25 mol dm⁻³ and 2.00 mol dm⁻³ and different exposure times—up to 10 days—have been studied. The influence of temperature (25, 40 and 55 °C) was also monitored. The evaluation of Al₂O₃ ceramics corrosion resistance was based on the concentration measurements of eluted Al³⁺, Ca²⁺, Fe³⁺, Mg²⁺, Na⁺ and Si⁴⁺ ions obtained by inductively coupled plasma atomic emission spectrometry (ICP-AES), as well as density measurements of the investigated alumina ceramics. The response surface methodology (RSM) was used for the optimization of parameters within the experimental “sample-corrosive media” area. The exposure of alumina ceramics to aqueous HNO₃ solutions was conducted according to the Box–Behnken design. After the regression functions were defined, conditions to achieve the maximum corrosion resistance of the sintered ceramics were determined by optimization within the experimental area.     

Clinical Impacts of Copy Number Variations in B-cell Differentiation and Cell Cycle Control Genes in Pediatric B-cell Acute Lymphoblastic Leukemia: a Single Centre Experience

BackgroundIKZF1 gene deletions have been identified as a poor prognostic factor in pediatric B-cell acute lymphoblastic leukemia (B-ALL), especially in the presence of co-occurring deletions (IKZF1^plus profile). This study aimed to determine the frequency of IKZF1 deletions and deletions in other B-cell differentiation and cell cycle control genes, and their prognostic impact in Slovenian pediatric B-ALL patients.Patients and methodsWe studied a cohort of 99 patients diagnosed with B-ALL from January 2012 to December 2020 and treated according to the ALL IC-BFM 2009 protocol. Eighty-eight bone marrow or peripheral blood samples were analysed for copy number variations (CNVs) using the SALSA MLPA P335 ALL-IKZF1 probemix.ResultsAt least one CNV was detected in more than 65% of analysed samples. The most frequently altered genes were PAX5 and CDKN2A/B (30.7%, 26.1%, and 25.0%, respectively). Deletions in IKZF1 were present in 18.2% of analysed samples and were associated with an inferior 5-year event-free survival (EFS; 54.8% vs. 85.9%, p = 0.016). The IKZF1^plus profile was identified in 12.5% of the analysed samples, and these patients had an inferior 5-year EFS than those with deletions in IKZF1 only and those without deletions (50.8% vs. 75.0% vs. 85.9%, respectively, p = 0.049). Overall survival (OS) was also worse in patients with the IKZF1^plus profile than those with deletions in IKZF1 only and those without deletions (5-year OS 76.2% vs. 100% vs. 93.0%, respectively). However, the difference between the groups was not statistically significant.ConclusionsOur results are in concordance with the results obtained in larger cooperative clinical trials. Copy number variations analysis using the SALSA MLPA kit is a reliable tool for initial diagnostic approach in children with B-ALL, even in smaller institutions in low- and middle-income countries.Key words: B-acute lymphoblastic leukemia, IKZF1 deletions, IKZF1 ^plus , MLPA, pediatric, copy number variations (CNVs)     

Ruptured intramural intestinal hematoma in an adolescent patient with severe hemophilia A

We report on a 17-year-old patient with severe hemophilia A without inhibitors who developed abdominal bleeding after an episode of severe cough. Abdominal ultrasound showed intramural intestinal hematoma as well as large amount of peritoneal fluid appearing as blood and right hematocele. Abdominal CT revealed markedly thickened intestinal wall in sigmoidal region. Patient was managed with replacement therapy as well as peritoneal drainage with favorable outcome. This is the first report on a hematoperitoneum in a hemophiliac due to ruptured intramural sigmoidal hematoma.     

Obstetrics services - womens' perspectives

To obtain women's views of obstetric care 400 randomly selected mothers were interviewed postnatally. Since family planning is a constitutional right and all related services free of charge and virtually 100% of pregnant women attend the antenatal clinic, the questions asked were mainly oriented to evaluation of existing obstetric practice. Women were generally satisfied with labor and delivery care (71.2%), but as many as 88.2% of them expressed their dissatisfaction with postnatal care practice. Our women opted for optimal hospital perinatal care — a home-like postnatal care, possibilities for better bonding between mothers and newborn infants and more open, individually oriented communication with medical staff.