Fcgamma receptors are crucial for the expression of acquired resistance to virulent Salmonella enterica serovar Typhimurium in vivo but are not required for the induction of humoral or T-cell-mediated immunity

Antibodies play an important role in immunity to Salmonella enterica. Here we evaluated the requirement for Fcgamma receptors in host resistance to S. enterica using an in vivo model of systemic infection. We show that mice lacking FcgammaRI, II and III can control and clear a primary infection with S. enterica micro-organisms of low virulence, but are impaired in the expression of vaccine-induced acquired immunity to oral challenge with virulent bacteria. We also show that, in vivo, FcgammaRI, II, III(-/-) mice were able to mount efficient T-helper 1 type T-cell responses and antibody responses specific for S. enterica. The work indicates that targeting S. enterica to FcgammaR is needed for the expression of vaccine-induced acquired immunity, but is not essential for the engenderment of T- and B-cell immunity to the bacterium in vivo.     

Significance of uroplakin III expression in recurrence of solitary muscle non-invasive bladder cancer

Numerous immunohistochemical biomarkers for patients with urothelial bladder cancer have been identified in order to predict their biological behavior. The aim of this present study was to examine the uroplakin III (UPIII) expression in homogenous group of non-muscle invasive bladder cancer and to correlate its value with clinico-pathological characteristics of patients and moreover with COX-2 expression and tumor infiltrating lymphocytes (TILs).     

Seasonal distribution of multiclass pesticide residues in the surface waters of northwest Croatia

As part of our OPENTOX project, we evaluated the incidence and mass concentrations of multiclass pesticide residues in 23 river/stream water samples collected in urban and agricultural areas of northwest Croatia at various points of the pesticide application season in 2015. The study included 16 compounds of five herbicide classes and seven compounds of three insecticide classes. Pesticide residues were accumulated from water by solid-phase extraction and analysed using high performance liquid chromatography with UV-diode array detection and/or gas chromatography-mass spectrometry. Herbicide residues were more common than the insecticide ones, and, as expected, they peaked in the middle of the application season. Metolachlor showed the highest concentrations and was found in 91 % of all samples, followed by terbuthylazine, found in 70 % of the samples. The highest total mass concentration of detected pesticides was measured in the water samples of the Krapina (3992 ng/L) and Sutla (3455 ng/L) collected in rural areas with intensive agriculture. Our findings strongly speak in favour of continued monitoring of surface waters and possibly extending the list of priority water pollutants.KEY WORDS: degradation products, herbicides, insecticides, pesticide residues, river water, seasonal variations     

New Drugs on the Block—Emerging Treatments for Nonalcoholic Steatohepatitis

Patients with nonalcoholic steatohepatitis (NASH) are at higher risk of progression to advanced stages of fibrosis, cirrhosis, hepatocellular carcinoma and othe...     

Actinic keratosis and surrounding skin exhibit changes in corneocyte surface topography and decreased levels of filaggrin degradation products

Actinic keratosis (AK) is a frequent premalignant skin lesion mainly caused by chronic sun exposure. AK lesions are often surrounded by invisible, subclinical alterations, called field of cancerization (FoC). Definition of FoC is of importance for therapy management; however, the criteria and non-invasive tools to characterize FoC are lacking. Atomic force microscopy (AFM) proved to be a suitable tool for detection of changes in the corneocyte surface topography in inflammatory skin diseases, which share similar clinical features with AK such as hyper- and parakeratosis. Therefore, in this study we applied AFM to investigate AK and surrounding skin obtained by non-invasive collection of the stratum corneum (SC) with adhesive tapes. Furthermore, we determined degradation products of structural protein filaggrin (natural moisturizing factor, NMF), which previously showed association with the changes in corneocyte surface topography. Ten patients with multiple AK on the face were recruited from the outpatient clinic. SC samples were collected from the AK lesion, skin sites adjacent to the AK, 5 cm from the AK and retroauricular area. Corneocyte surface topography was determined by AFM, and NMF by liquid chromatography. The AK lesion showed alterations of the corneocyte surface topography characterized by an increased number of nanosize protrusions, which gradually decreased with the distance from the lesion. NMF levels show an inverse pattern. Atomic force microscopy showed to be a suitable tool to detect changes in the corneocyte surface topography on the AK lesion and surrounding skin in a non-invasive manner.     

Factors associated with general and health-related quality of life in menopausal transition among women from Serbia

ABSTRACT

This study assessed factors associated with quality of life (QOL) among Serbian peri- and postmenopausal women using two menopause-specific scales. This cross-sectional study included 500 women aged 40–65 years who had a gynecologic check-up in one of two Community Health Centers in Belgrade during February 2014 to January 2015. Women completed: a questionnaire about socio-demographics, habits, and health status; a menopause-specific questionnaire, Utian’s Quality of Life Scale (UQOL); and a Women’s Health Questionnaire (WHQ) and Beck’s Depression Inventory (BDI). Higher education was associated with better occupational UQOL and memory/concentration, but with lower emotional UQOL and more anxiety/fears. City center residency was associated with better occupational and sexual UQOL. Being employed was associated with better occupational UQOL and lower anxiety/fears. Higher income was associated with better emotional UQOL. Not having uterine prolapse, insomnia, or tachycardia was associated with better occupational UQOL and fewer sleep problems. Higher parity was associated with better sexual UQOL. Having regular recreation was associated with better health and sexual UQOL but with more frequent vasomotor symptoms. Leaner women felt more attractive. QOL during the menopausal transition does not entail only somatic symptoms and therefore requires a more comprehensive approach that includes psychosocial underpinnings.     

Epidemiological and clinical features of Croatian children and adolescents with a PCR-confirmed coronavirus disease 2019: differences between the first and second epidemic wave

MethodsData on patients aged ≤19 years with a positive SARS-CoV-2 PCR test recorded in the period March 12-May 12 (first wave) and June 19-July 19, 2020 (second wave) were retrospectively analyzed. The periods were separated by several weeks with no incident cases.ResultsWe analyzed data on 289 children and adolescents (6.5% of all cases; incidence rate [IR] = 3.54, 95% confidence interval [CI] 3.14-3.97/million person-days), 124 in the first wave (IR = 2.27) and 165 in the second wave (IR = 6.37): IRR second/first = 2.71 (2.13-3.44). During the first wave, the incidence was highest in infants (IR = 3.48), while during the second wave it progressively increased to IR = 7.37 in 15-19-year olds. Family members were the key epidemiological contacts (72.6% cases), particularly during the first wave (95.8% vs 56.3%). Overall, 41.3% patients were asymptomatic, 25.3% in the first and 52.6% in the second wave. Age 15-19 years (vs younger) was associated with a higher (RR = 1.26, 1.02-1.54) and infection in the second wave with a lower probability (RR = 0.66, 0.53-0.81) of being symptomatic. The most common symptoms were fever, cough, and rhinorrhea. In children aged ≥7 years, headache, anosmia/ageusia, and sore throat were also recorded. Only one child suffered a severe disease. All but 18 (7.8%) children were treated only symptomatically, and all fully recovered.ConclusionA large proportion of SARS-CoV-2 PCR-positive children/adolescents were asymptomatic. The associated disease was predominantly mild, comparably so in the first and second pandemic wave.

Since the late December 2019, coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread quickly worldwide and as of early December accounts for more than 65 million cases diagnosed in more than 200 countries (1). At this point, the most affected countries in Europe are Russia, Spain, France, United Kingdom (UK), and Italy with consequently the highest mortality rates. The first case in Croatia was reported in the late February 2020, and within the next two months the infection expanded nationwide. During this first epidemic wave, Croatia was under a one-month lockdown, which rapidly decreased the disease incidence, and only a few newly diagnosed cases were reported between May 25 and June18, 2020. Easing of restrictions increased the incidence in late June, causing a second wave of COVID-19 in Croatia, with >147 000 cases reported so far (1,2).Over the last two decades, there were two other coronavirus outbreaks. Severe acute respiratory syndrome coronavirus appeared in 2002, affecting around 8000 people, with 10% mortality. Children (4 months-17 years) accounted for <0.02% of total cases, and there was no reported death in this age group. During the outbreak of the Middle East respiratory syndrome coronavirus, around 2300 people were infected, and children (<19 years of age) were rarely affected as well (2% of total cases; 2 reported deaths) (3,4). COVID-19 has exhibited a similar epidemiological pattern. Although early reports from China, Italy, and the United States (US) suggested that children and adolescents accounted for only 1%-2% of the overall COVID-19 cases (5-7), later reports around the world indicated a higher proportions of pediatric cases, between 1%-8% (8-10). Children of all ages can be affected by SARS-CoV-2 infection, but in contrast to other respiratory viruses, they usually suffer a mild or asymptomatic infection. Compared with adults, severe infections and fatal outcomes in children are rare, and several immunopathological mechanisms could be responsible for such differences in disease severity (11). Although many studies have reviewed the features of adults with COVID-19, overall data regarding pediatric cases are scarce, and most of them are reports from China and the US, with only a few studies describing disease in children from European countries.We aimed to describe epidemiological and clinical features of children and adolescents with COVID-19 confirmed by the polymerase chain reaction (PCR) test for SARS-CoV-2 in Croatia and to assess potential differences between the first (March-May 2020) and second (on-going) pandemic wave (June-July 2020).     

The association of multiple sclerosis and Hodgkin's disease: the role of Epstein-Barr virus infection

The aetiology of multiple sclerosis (MS) is still an unresolved question. Several recently reported studies are implicating Epstein-Barr virus (EBV) as one of the key players in MS pathogenesis. We present a 21-year-old male patient with a history of EBV-related infectious mononucleosis in puberty and Hodgkin's disease two years previously treated with irradiation and chemotherapy. The patient presented with spastic paraparesis that resolved promptly on corticosteroid treatment. There were no signs of Hodgkin's disease relapse. In the next three years he had three more bouts of the disease and he was diagnosed with relapse-remitting MS. There is evidence of EBV involvement in MS pathogenesis; the association of MS with EBV-related infectious mononucleosis and Hodgkin's disease being just one of them. Although there are many unanswered questions, it is clear that without EBV seropositivity MS in adults is extremely rare.     

MEG biomarker of Alzheimer's disease: Absence of a prefrontal generator during auditory sensory gating

Magnetoencephalography (MEG), a direct measure of neuronal activity, is an underexplored tool in the search for biomarkers of Alzheimer's disease (AD). In this study, we used MEG source estimates of auditory gating generators, nonlinear correlations with neuropsychological results, and multivariate analyses to examine the sensitivity and specificity of gating topology modulation to detect AD. Our results demonstrated the use of MEG localization of a medial prefrontal (mPFC) gating generator as a discrete (binary) detector of AD at the individual level and resulted in recategorizing the participant categories in: (1) controls with mPFC generator localized in response to both the standard and deviant tones; (2) a possible preclinical stage of AD participants (a lower functioning group of controls) in which mPFC activation was localized to the deviant tone only; and (3) symptomatic AD in which mPFC activation was not localized to either the deviant or standard tones. This approach showed a large effect size (0.9) and high accuracy, sensitivity, and specificity (100%) in identifying symptomatic AD patients within a limited research sample. The present results demonstrate high potential of mPFC activation as a noninvasive biomarker of AD pathology during putative preclinical and clinical stages. Hum Brain Mapp 38:5180–5194, 2017. © 2017 Wiley Periodicals, Inc.