Psychometric properties and observational data for COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) for post-COVID-19 syndrome.

BACKGROUND: The recently developed modified COVID-19 (coronavirus of 2019) Yorkshire Rehabilitation Scale (C19-YRSm) captures comprehensive biopsychosocial components of WHO's International Classification of Functioning, Disability, and Health related to the Long Covid or post-COVID syndrome. The scale response categories on C19-YRSm were done post hoc on data collected from the original version of C19-YRS. AIM: To evaluate the C19-YRSm scale using reliability and validity measures. DESIGN: Prospective, observational study. METHODS: The study includes 369 patients (clinical group) and 426 subjects of the general population (control group) and captures their post-COVID-19 symptoms. In addition, the reliability of C19-YRSm was estimated by Cronbach's alpha coefficients of internal consistency and inter-item correlations for subscales ('Symptom severity, Functional disability, and Other symptoms'). Convergent validity was established using correlations between C19-YRSm and Fatigue Severity Scale (FSS). The incremental validity of C19-YRSm was measured by introducing a hierarchical regression model using the C19-YRSm 'Overall health' subscale and FSS as criterion variables. RESULTS: C19-YRSm subscales have excellent internal consistencies (Cronbach's α value 0.81-0.96) and acceptable inter-item correlations (r value 0.23-0.79). Hereafter, the convergent validity of the C19-YRSm is good due to significant correlations between C19-YRSm subscales and FSS and C19-YRSm subscales. Finally, the hierarchical regression analysis supported consistent evidence for the incremental validity of the C19-YRSm subscales. CONCLUSION: C19-YRSm is a reliable and valid self-assessment scale for the assessment of post-COVID-19 syndrome.

High infection rate of bank voles (Myodes glareolus) with Puumala virus is associated with a winter outbreak of haemorrhagic fever with renal syndrome in Croatia.

An outbreak of haemorrhagic fever with renal syndrome (HFRS) started on Medvednica mountain near Zagreb in January 2012. In order to detect the aetiological agent of the disease in small rodents and to make the link with the human outbreak, rodents were trapped at four different altitudes. Using nested RT-PCR, Puumala virus (PUUV) RNA was detected in 41/53 (77·4%) bank voles (Myodes glareolus) and Dobrava virus (DOBV) RNA was found in 6/61 (9·8%) yellow-necked mice (Apodemus flavicollis). Sequence analysis of a 341-nucleotide region of the PUUV S segment, obtained from all infected bank voles and five HFRS patients, showed 98·8-100% sequence similarity, indicating that the patients were probably exposed to PUUV on Medvednica mountain. A very large bank-vole population combined with an extremely high infection rate of PUUV was responsible for this unusual winter outbreak of HFRS in Croatia.

Molecular characterization of dengue virus 1 from autochthonous dengue fever cases in Croatia.

In the summer of 2010, two autochthonous dengue fever cases were detected in Croatia. Here we report the retrospective detection of an additional case of dengue fever, representing the first sustained autochthonous transmission in Europe since 1928. In addition, we present the phylogenetic analyses based on two sequences from the Peljesac peninsula, southern Croatia. The sequences were identified as dengue virus genotype 1 and recovered from two out of the three Peljesac patients in whom infection occurred.

Clinical and laboratory findings in patients with oliguric and non-oliguric hantavirus haemorrhagic fever with renal syndrome: an analysis of 128 patients.

Patients with haemorrhagic fever with renal syndrome (HFRS) may present without significant oliguria. We compared different initial clinical symptoms and laboratory findings in patients who developed oliguric acute renal failure (ARF) with those in patients who did not develop oliguric ARF. Overall, 128 patients with serologically confirmed HFRS were hospitalized at the University Hospital for Infectious Disease, Zagreb, Croatia between January 1999 and December 2010. Clinical signs and laboratory findings were extracted from medical charts, and were assessed for their relationship to the development of oliguric ARF. Puumala virus infection was diagnosed in 101 (79%) patients, and Dobrava-Belgrade virus infection in 27 (21%). Oliguria or anuria developed in 30% of patients. We identified the following risk factors for the development of oliguria and anuria on multivariable analysis: conjunctival hyperaemia or bleeding (relative risk (RR) 1.84, 95% CI 1.09-3.10; p 0.023), diarrhoea (RR 1.45, 95% CI 1.07-1.97; p 0.017), serum sodium of ≤133 mM (RR 2.21, 95% CI 1.34-3.64; p 0.002), and dipstick protein value of >1.5 g/L (RR 1.59, 95% CI 1.09-2.33; p 0.016), as well as hiking in the forest (RR 1.92, 95% CI 1.13-3.26; p 0.016). Our findings may help physicians in the earlier identification of patients with a more severe form of HFRS caused by Puumala and Dobrava-Belgrade viruses. Particular attention should be given to findings such as conjunctival hyperaemia or bleeding, diarrhoea, a low serum sodium level, and proteinuria.

Serum apoptosis markers in HIV-infected patients with human herpesvirus type 8 and herpes simplex virus type 2 co-infection.

This study aimed to examine the influence of human herpesvirus type 8 (HHV-8) and herpes simplex virus type 2 (HSV-2) co-infections on apoptosis serum markers in human immunodeficiency virus (HIV)-infected patients. Sera from 110 HIV-infected and 59 HIV-uninfected individuals were analyzed for soluble Fas (sFas), sFas ligand (sFasL), caspase-8, and Bcl-2. The findings of HIV-infected patients with no co-infection (n = 37), HIV-infected patients with HHV-8 co-infection (n = 22), HIV-infected patients with HSV-2 co-infection (n = 51), and patients with HSV-2 co-infection and no HIV infection (n = 20) were compared to controls (reference group) with no HIV, HSV-2, and HHV-8 co-infections (n = 39). Soluble Fas and sFasL concentrations were the highest in HIV and HHV-8 co-infected patients (medians, 912.7 pg/ml and 74.3 pg/mL, respectively). No difference in caspase-8 concentrations was found, whereas Bcl-2 concentrations were the highest in HIV and HHV-8 co-infected individuals. Older age was associated with higher sFas (p < 0.001) and lower sFasL (p = 0.04) concentrations. In a robust regression model adjusted for age, the log-transformed sFas concentrations were significantly lower in HIV-infected patients with no co-infections (ß = -0.244; p < 0.001) and higher in HIV and HHV-8 co-infected patients (ß = 0.216; p = 0.012) compared to the reference group. Soluble FasL was significantly lower in HIV-infected patients with no co-infections (ß = -0.284; p = 0.005) and in HIV-infected patients with HSV-2 co-infection (ß = -0.381; p < 0.001) compared to the reference group. Soluble FasL was also higher in HIV and HHV-8 co-infected patients compared to controls (ß = 0.248; p = 0.036). Our results suggest that HHV-8 and HSV-2 may have a significant effect on Fas-FasL-mediated apoptosis in HIV-1 patients. HHV-8 upregulates while HSV-2 downregulates sFas and sFasL.

Macrolides for the treatment of chronic bacterial prostatitis: an effective application of their unique pharmacokinetic and pharmacodynamic profile (Review).

Chronic bacterial prostatitis (CBP) is a persistent infection of the prostate characterized by poor quality of life mainly due to frequent relapse episodes caused by incomplete eradication of causative pathogens. Aggressive antibacterial therapy is required to attenuate the severe symptoms of CBP and to achieve a permanent cure. Although fluoroquinolones are currently recommended as first-choice agents, macrolide antibiotics are emerging as a noteworthy option for the treatment of CBP. Macrolide antibiotics are characterized by an impressive array of distinct pharmacokinetic (PK) and pharmacodynamic (PD) properties. These properties include high intracellular accumulation in phagocytes and at sites of infection, including the prostate; broad antibiotic but also biofilm-inhibiting properties; immunomodulating and inflammation-resolving activities. These features offer particular advantages for the treatment of chronic infections of the prostate gland, which are not easily amenable to drug therapy. Macrolides may be exploited to counteract the unsatisfactory rates of clinical symptom improvement and pathogen eradication. The results of a number of clinical trials support this proposal.

Biochemical, pathological and oncological relevance of Gb3Cer receptor.

Glycosphingolipids are amphipathic molecules composed of hydrophilic oligosaccharide chain and a hydrophobic ceramide part, located primarily in the membrane microdomains of animal cells. Their oligosaccharide chains make them excellent candidates for the cell surface recognition molecules. Natural glycosphingolipid, globotriaosylceramide (Gal α1-4, Gal ß1-4, Glc ß1-1, ceramide), is also called CD77 and its expression was previously associated with proliferating centroblasts undergoing somatic hypermutation, but it has been demonstrate that globotriaosylceramide is not a reliable marker to discriminate human centroblasts from centrocytes. Globotriaosylceramide constitutes rare P k blood group antigen on erythrocytes, and it is also known as Burkitt's lymphoma antigen. On endothelial cells, globotriaosylceramide plays as the receptor for bacterial toxins of the Shiga family, also called verotoxins. Precise biological function and significance of globotriaosylceramide expression on endothelial cells remains to be the subject of many studies and it is believed globotriaosylceramide represents an example of a glycolipid antigen able to transduce a signal leading to apoptosis. In past decade, cancer researches put a great afford in determining new therapeutic agents such as bacterial toxins against tumor malignancies. Reports have demonstrated that verotoxin-1 induces apoptosis in solid tumor cell lines expressing globotriaosylceramide such as astrocytoma, renal cell carcinoma, colon cancer and breast cancer due to verotoxin-1 high specificity and apoptosis-inducing properties, and therefore, it is suggested to be an anticancer agent. Verotoxins have been investigated weather they could reduce treatment side-effects and toxicity to normal tissues and become a new oncological tool in cancer labeling.

A switch therapy protocol with intravenous azithromycin and ciprofloxacin combination for severe, relapsing chronic bacterial prostatitis: a prospective non-comparative pilot study.

Chronic bacterial prostatitis (CBP) is characterized by intense clinical symptoms, frequent relapse episodes and poor quality of life. Aggressive antibacterial therapy is warranted to eradicate the causative pathogens and to achieve a permanent cure. We administered a "switch-therapy" protocol to 30 patients showing severe CBP symptoms and two or more relapse episodes in the previous 12 months. Patients received intravenous azithromycin (500 mg/day) and ciprofloxacin (800 mg/day) for 3 days, followed by oral ciprofloxacin (1 g/day) for 25 days.Twenty-seven (90%) patients showed pathogen eradication at test-of-cure (TOC) visit. Five cases of infection relapse were detected at follow-up. At the TOC visit, 25 patients (83%) showed mild/absent symptoms, measured with the NIH-chronic prostatitis symptom index.These results indicate the efficacy of a "switch-therapy" protocol, based on combined azithromycin and ciprofloxacin. Comparative studies on larger CBP patient populations are warranted to confirm these encouraging results.

Eradication of Chlamydia trachomatis parallels symptom regression in chronic bacterial prostatitis patients treated with a fluoroquinolone-macrolide combination.

To investigate the association between eradication of Chlamydia trachomatis (CT) and symptom regression in chronic prostatitis, 55 symptomatic patients were subjected to segmented tests to localise CT in first voided urine (VB1), prostatic secretions (EPS), post-massage voided (VB3) or semen specimens. Patients were divided in three treatment groups: the 'urethral involvement' group ('U': VB1 positive, EPS/VB3/Semen negative) was treated with 500 mg day(-1) azithromycin for 3 days. The 'prostatitis' group ('P': VB1 negative, EPS/VB3/semen positive) with 4-week levofloxacin-azithromycin combination. A third group, 'U+P' (VB1, EPS/VB3/semen positive) received both treatments in sequence. In P patients, eradication of CT was paralleled by marked, sustained symptom improvement and by significant decrease of serum prostate-specific antigen (PSA) levels. Compared with U patients, undergoing rapid regression of symptoms related to painful micturition after short-term azithromycin, U+P patients showed symptom and pathogen persistence in VB3/EPS/semen and required additional treatment with 4-week levofloxacin-azithromycin to achieve pathogen eradication, symptom regression, and decrease of PSA. Our results support a causative role of CT in chronic bacterial prostatitis. In the presence of a positive urethral localisation of the pathogen, thorough microbiological investigation together with focused symptom analysis may reveal an underlying chlamydial prostatitis and direct effective therapy with appropriate antibacterial agents.

A serosurvey reveals Bosnia and Herzegovina as a Europe's hotspot in hantavirus seroprevalence.

The extent of hantavirus seroprevalence in the healthy population from Bosnia and Herzegovina has not yet been investigated; therefore, the aim of this study was to assess the hantavirus seroprevalence in the population from different regions of Bosnia and Herzegovina and in different risk groups. The serosurvey included 1331 subjects from endemic and non-endemic regions in Bosnia and Herzegovina. All sera samples were examined using IgG ELISA, and Western blot (Bunyavirus IgG) tests. Hantavirus seroprevalence was 7.4% in the endemic region and 2.4% in the non-endemic region (P<0.05). Former soldiers from the endemic region had significantly the highest seroprevalence (16.1%) compared to the general population from the endemic region (6.2%), the occupational risk group from the non-endemic region (5.6%) and the general population from the non-endemic region (0.8%) (P<0.01). No difference in hantavirus seroprevalence between gender or age groups was observed. Hantavirus seroprevalence in different populations in Bosnia and Herzegovina was found to be highest compared to other central European countries.

Is the clinical picture of Schnitzler syndrome always Schnitzler syndrome?

Here we present two cases, a female and a male patient with Schnitzler-like syndrome. Both patients had two major (monoclonal gammopathy and chronic urticaria) and almost all minor symptoms (e.g. arthralgia, bone pain, fever, etc.) of Schnitzler syndrome. It is considered that interleukine (IL)-1 has important influence on immunopathogenesis of Schnitzler syndrome. However, when looked at the immune response in our two patients, we found significant differences between them. In the sera of the female patient, IL-1beta was increased. However, the highest increase was found for granulocyte- colony stimulating factor (G-CSF), IL-32 alpha and IL-17E (IL-25). The male patient had a significant increase in the percentage of NK-cells, a decrease in CD4+ helper cells and no increase in cytokine levels. In both patients an increase in CD40L (CD154) was found. Our statement is that, besides clinical symptoms and signs, additional immune parameters should be tested before diagnosis of Schnitzler syndrome is established.

Comparison of clinical symptoms scored according to the National Institutes of Health chronic prostatitis symptoms index and assessment of antimicrobial treatment in patients with chronic prostatitis syndrome.

We examined a total of 194 patients over 18 years of age with chronic prostatitis syndrome and no evidence of structural or functional lower genitourinary tract abnormalities. The following data were obtained for each patient: clinical history--the severity of chronic prostatitis symptoms scored by a Croatian translation of the NiH CPSI questionnaire, clinical status including digitorectal examination, urethral swab specimens, and selective samples of urine and expressed prostatic secretion, according to the 4-glass localization test (meares and Stamey localization technique). Patients were treated orally with antimicrobial agents in doses and duration according to clinical practice in Croatia. An infectious etiology was determined in 169 (87%) patients. Chlamydia trachomatis was the causative pathogen in 38 (20%), Trichomonas vaginalis in 35 (18%), Enterococcus in 36 (19%) and Escherichia coli in 35 (18%) patients. In the remaining 25 patients the following causative pathogens were found: Ureaplasma urealyticum, Proteus mirabilis, Klebsiella pneumoniae, Streptococcus agalactiae and Pseudomonas aeruginosa. Comparison of symptoms scores and effect on quality of life has shown that the most severe clinical presentation of disease was recorded in patients with chronic bacterial prostatitis caused by E. coli and Enterococcus (p<0.001). Clinical success was paralleled by bacteriological eradication in chronic bacterial prostatitis caused by C. trachomatis, Enterococcus and E. coli (kappa >0.2<0.5), but not in inflammatory chronic pelvic pain syndrome caused by T. vaginalis.

The significance of Chlamydia trachomatis in urethritis and prostatitis - differences in therapeutic approach - Croatian experience.

We examined a total of 1014 patients over 18 years of age; 252 with urethritis and 762 with chronic prostatitis syndrome. the mean age of patients with urethritis was 32.7 and with prostatitis syndrome 37.6 years. Clinical symptoms of urethritis were present from a few days to several months. in patients with chronic prostatitis syndrome, symptoms were present for at least 3 months. Chlamydia trachomatis alone was confirmed in 26 (10%) and in combination with Ureaplasma urealyticum in 6 (2%) patients with urethritis. in 171 (68%) patients with urethritis neither C. trachomatis nor U. urealyticum or Mycoplasma hominis were found. C. trachomatis alone was confirmed in 70 (9%), and in combination with other microorganisms in 7 (1%) patients with chronic prostatitis syndrome. in Croatia, the frequency of chronic chlamydial prostatitis has not significantly changed in the last 10 years, while the frequency of infections among adolescents decreased. the recommended regimen for acute chlamydial urethritis in Croatia is azithromycin 1.0 g as a single dose, and a total dose of 4-4.5 g azithromycin for chronic chlamydial prostatitis.

Immunohistochemical analysis of hepatic ganglioside distribution following a partial hepatectomy and exposure to different hyperbaric oxygen treatments.

Ganglioside GM3(Neu5Ac) expression is highly increased in liver 54h following 15% partial hepatectomy in pre-operatively oxygenated rats. GM3(Neu5Gc), GM2, GalNAc-GM1b and gangliosides of the neolacto-series are less affected. GM3(Neu5Ac) is a potent inhibitor of epidermal growth factor signaling. Since GM3(Neu5Ac) growth inhibitory effect depends on its cellular localization, the aim of this study was to detect ganglioside cellular localization during liver regeneration. The experiment was performed using the same rat model which previously showed increased ganglioside expression and more efficient liver regeneration. Frozen sections of liver were analyzed using confocal microscopy after labeling for binding of five ganglioside-specific antibodies, with or without hepatocyte membrane permeabilization. Ganglioside precursors, ceramide (Cer), monohexaosylceramide and lactosylceramide (LacCer) were determined by high-performance thin-layer chromatography. Apoptosis was assessed by fluorescein-dUTP end-labeling of fragmented DNA. Liver of pre-operative oxygenated rats showed high perinuclear labeling of GM3(Neu5Ac) which was absent in post-operative oxygenated and control animals. In the same group, Cer content was lower, monohexaosylceramide and LacCer were absent, and content of apoptotic cells was significantly the lowest, compared to other groups examined (F=20.36, p=0.0001). These findings indicate that ganglioside GM3(Neu5Ac) may be involved in mediation of beneficial effects of pre-operatively oxygenation during the liver regeneration.

Enumeration of haemagglutinin-specific CD8+ T cells after influenza vaccination using MHC class I peptide tetramers.

With emergence of MHC class I tetramers loaded with CD8+ T-cell viral epitopes, it is possible to study virus-specific CD8 cells in humans during infection and after vaccination. MHC class I tetramers was used to detect the frequency of haemagglutinin (HA)-specific T cells in 26 healthy influenza-vaccinated humans. Peripheral blood was collected before, and 7, 14 and 28 days after vaccination. Four-colour flow cytometry was used for monitoring of vaccine induced T-cell response. In 15 donors, two- to fivefold increase in frequency of HA-specific T cells was observed 7 days after vaccination. In addition, in 12 of these donors, this increase was accompanied with fourfold increase of H1N1 antibody titre. The increase in frequency of HA-specific CD8+/IFN-gamma+ cells was low and peaked 28 days after vaccination in three of the six donors tested. Frequencies of HA-specific CD8+ T cells and antibody titre returned to prevaccination values 1 year after vaccination. Subunit influenza vaccines have the ability to induce HA-specific CD8+ cells. As the immune response to this vaccine decreased significantly after 1 year, our results confirm the importance of annual immunization for adequate protection.

131 I-induced changes in rat thyroid gland function.

Therapeutic doses of (131)I administered to thyrotoxic patients may cause thyroid failure. The present study used a rat model to determine thyroid function after the administration of different doses of (131)I (64-277 microCi). Thirty male Fisher rats in the experimental group and 30 in the control group (untreated) were followed for 6 months. The animals were 4 months old at the beginning of the experiment and were sacrificed at an age of 9 months. Hormone concentration was determined before (131)I administration (4-month-old animals) and three times following (131)I administration, when the animals were 7, 8, and 9 months old. The thyroid glands were removed and weighed, their volume was determined and histopathological examination was performed at the end of the experiment. Significant differences in serum triiodothyronine and thyroid-stimulating hormone concentration, measured at the age of 7, 8, and 9 months, were found in the experimental group. During aging of the animals, the concentration of thyroxin fell from 64.8 +/- 8.16 to 55.0 +/- 6.1 nM in the control group and from 69.4 +/- 6.9 to 25.4 +/- 3.2 nM in the experimental group. Thyroid gland volume and weight were significantly lower in the experimental than in the control group. Thyroid glands from the experimental group showed hyaline thickness of the blood vessel wall, necrotic follicles, a strong inflammatory reaction, and peeling of necrotic cells in the follicles. In conclusion, significant differences in hormone levels and histopathological findings indicated prolonged hypothyroidism after (131)I administration to rats, which was not (131)I dose dependent.

131I-induced changes in rat thyroid gland function

Therapeutic doses of 131I administered to thyrotoxic patients may cause thyroid failure. The present study used a rat model to determine thyroid function after the administration of different doses of 131I (64-277 µCi). Thirty male Fisher rats in the experimental group and 30 in the control group (untreated) were followed for 6 months. The animals were 4 months old at the beginning of the experiment and were sacrificed at an age of 9 months. Hormone concentration was determined before 131I administration (4-month-old animals) and three times following 131I administration, when the animals were 7, 8, and 9 months old. The thyroid glands were removed and weighed, their volume was determined and histopathological examination was performed at the end of the experiment. Significant differences in serum triiodothyronine and thyroid-stimulating hormone concentration, measured at the age of 7, 8, and 9 months, were found in the experimental group. During aging of the animals, the concentration of thyroxin fell from 64.8 ± 8.16 to 55.0 ± 6.1 nM in the control group and from 69.4 ± 6.9 to 25.4 ± 3.2 nM in the experimental group. Thyroid gland volume and weight were significantly lower in the experimental than in the control group. Thyroid glands from the experimental group showed hyaline thickness of the blood vessel wall, necrotic follicles, a strong inflammatory reaction, and peeling of necrotic cells in the follicles. In conclusion, significant differences in hormone levels and histopathological findings indicated prolonged hypothyroidism after 131I administration to rats, which was not 131I dose dependent.