Two Unusual Recurrences of Intracranial Germinoma

Two recurrent cases of intracranial suprasellar germinoma, with relapses at 55 and 16 months, respectively, after the end of primary therapy strongly effective against pure germinoma, are presented. Human chorionic gonadotropin beta subunit was elevated in the cerebrospinal fluid and in the serum in both patients at the time of recurrence but not before. This and resulting treatment failures suggest that there were also other, more resistant elements within the primary tumor, which have not been identified in biopsy specimens. The problem of adequate diagnosis and its impact on patients' survival are discussed.     

The Emergence of SARS-CoV-2 within the Dog Population in Croatia: Host Factors and Clinical Outcome

Over a year into the COVID-19 pandemic, there is growing evidence that SARS-CoV-2 infections among dogs are more common than previously thought. In this study, the prevalence of SARS-CoV-2 antibodies was investigated in two dog populations. The first group was comprised of 1069 dogs admitted to the Veterinary Teaching Hospital for any given reason. The second group included dogs that shared households with confirmed COVID-19 cases in humans. This study group numbered 78 dogs. In COVID-19 infected households, 43.9% tested ELISA positive, and neutralising antibodies were detected in 25.64% of dogs. Those data are comparable with the secondary attack rate in the human population. With 14.69% of dogs in the general population testing ELISA positive, there was a surge of SARS-CoV-2 infections within the dog population amid the second wave of the pandemic. Noticeably seroprevalence of SARS-CoV-2 in the dog and the human population did not differ at the end of the study period. Male sex, breed and age were identified as significant risk factors. This study gives strong evidence that while acute dog infections are mostly asymptomatic, they can pose a significant risk to dog health. Due to the retrospective nature of this study, samples for viral isolation and PCR were unavailable. Still, seropositive dogs had a 1.97 times greater risk for developing central nervous symptoms.     

Bacterial Exposure to Nickel: Influence on Adhesion and Biofilm Formation on Orthodontic Archwires and Sensitivity to Antimicrobial Agents

The presence of nickel could modify bacterial behavior and susceptibility to antimicrobial agents. Adhesion and biofilm formation on orthodontic archwires can be a source of bacterial colonization and possible health hazards. Staphylococcus aureus was subjected to exposure and adaptation to various sub-inhibitory concentrations of nickel. Five strains of bacteria adapted to nickel in concentrations of 62.5–1000 μg/mL were tested for adhesion and biofilm formation on nickel-titanium archwires. Archwires were previously incubated in artificial saliva. Bacteria were incubated with orthodontic wire with stirring for 4 h (adhesion) and 24 h (biofilm formation). The number of adherent bacteria was determined after sonication and cultivation on the Muller-Hinton agar. Disk diffusion method was performed on all bacteria to assess the differences in antimicrobial susceptibility. Bacteria adapted to lower concentrations of nickel adhered better to nickel-titanium than strains adapted to higher concentrations of nickel (p < 0.05). Biofilm formation was highest in strains adapted to 250 and 500 μg/mL of nickel (p < 0.05). The highest biofilm biomass was measured for strains adapted to 250 μg/mL, followed by those adapted to 1000 μg/mL. Bacteria adapted to lower concentrations of nickel demonstrated lower inhibition zone diameters in the disk diffusion method (p < 0.05), indicating increased antimicrobial resistance. In conclusion, bacteria adapted to 250 μg/mL of nickel ions adhered better, demonstrated higher biofilm formation and often had higher antimicrobial resistance than other adapted and non-adapted strains.     

Azithromycin inhibits macrophage interleukin-1β production through inhibition of activator protein-1 in lipopolysaccharide-induced murine pulmonary neutrophilia

Macrolide antibiotics, including azithromycin, also possess anti-inflammatory properties. However, the molecular mechanism(s) of activity as well as the target cells for their action have not been unambiguously identified as yet. In this study, the effects of azithromycin on lipopolysaccharide (LPS)-induced pulmonary neutrophilia were investigated in mice. Using immunohistochemistry, mRNA and specific protein assays, we confirmed that azithromycin ameliorates LPS-induced pulmonary neutrophilia by inhibiting interleukin-1β (IL-1β) expression and production selectively in alveolar macrophages as well as in LPS-stimulated J774.2 macrophage-derived cells in vitro. Inhibition by azithromycin of neutrophilia and IL-1β was accompanied by prevention of nuclear expression of activator protein-1 (AP-1) in both alveolar macrophages and J774.2 cells. The macrolide did not alter nuclear factor kappa B (NF-κB) or extracellular signal-regulated kinase 1/2 (ERK1/2) expression, activation or localization in LPS-stimulated lungs or in J774.2 cells. In conclusion, we have shown that inhibition of LPS-induced pulmonary neutrophilia and IL-1β concentrations in lung tissue following azithromycin treatment is mediated through effects on alveolar macrophages. In addition, we have shown for the first time, in an in vivo model, that azithromycin inhibits AP-1 activation in alveolar macrophages, an action confirmed on J774.2 cells in vitro.     

The effect of gestational diabetes,pre-gravid maternal obesity,and their combination (‘diabesity’) on outcomes of singleton gestations

Objective: To assess the effect of the combination of gestational diabetes mellitus (GDM) and pre-gravid obesity (‘diabesity’) in singleton gestations.

Methods: We compared perinatal outcomes of singleton gestations in mothers with GDM and pre-gravid obesity, with GDM but with normal pre-gravid BMI, and obese mothers without GDM.

Results: We compared diabesity mothers (n?=?1525, 24.4% of mothers with GDM, 9.9% of all obese women) to mothers with GDM but with normal BMI (n?=?4704, 75.6% of mothers with GDM) and to obese mothers without GDM (n?=?13,937, 90.1% of all obese mothers). Obesity, with and without GDM, increased the odds of having chronic hypertension whereas preeclampsia appears to be influenced by obesity only, as were the risk of births at <33 weeks’ gestation, of birth weight >4000?g, low 5-min Apgar scores and NICU admissions.

Conclusion: Obesity (without diabetes) is more frequently associated with adverse perinatal outcomes than diabesity or GDM in non-obese mothers. A campaign to decrease pre-gravid obesity should have at least the same priority as any campaign to control GDM.     

Synthesis and antibacterial activity of isomeric 15-membered azalides

A series of 3-keto and 3-O-acyl derivatives of both 6-O-alkyl-8a-aza-8a-homoerythromycin A and 6-O-alkyl-9a-aza-9a-homo-erythromycin A were synthesised and tested against Gram-positive and Gram-negative bacteria. Derivatives of 8a-aza-8a-homoerythromycin A have potent antibacterial activity against not only azithromycin-susceptible strains, but also efflux (M) and inducible macrolide-lincosamide-streptogramin (iMLSB) resistant Gram-positive pathogens, while the corresponding 9a-isomers were less active. Introduction of an additional ring such as 11,12-cyclic carbonate reduced antibacterial activity of both series. 3-Keto and 3-O-(4-nitrophenyl)-acetyl derivatives of 6-O-methyl-8a-aza-8a-homo-erythromycin A show typical macrolide pharmacokinetics in preliminary in vivo studies in mice, and their in vivo efficacy is demonstrated.     

Cervical intraepithelial neoplasia: prognosis by combined LOH analysis of multiple loci

OBJECTIVE: Cervical intraepithelial neoplasias (CIN) show markedly variable clinical behavior. Clinically, it is important to distinguish CIN lesions with different behaviors and identify those likely to persist and progress. The purpose of this study is to explore whether CIN lesions with different clinical behaviors can be stratified by analysis of loss of heterozygosity (LOH) at multiple loci. METHODS: One hundred sixty-four cases of CIN (54 CIN1, 59 CIN2 and 51 CIN3) were screened for LOH at 12 microsatellite markers including 10 from 3p14, 3p21-22, 6p21 and 11q23. LOH was correlated with clinical follow-up data and high-risk HPV infection. RESULTS: In a pilot study of 71 cases of CIN, screening of 12 microsatellite markers identified four (D3S1300, D3S1260, D11S35, and D11S528) at which LOH was significantly associated with disease persistence/progression. These four markers were further investigated in a larger cohort, which brought the total number of cases examined to 164. Combined analysis of LOH at the above four loci permitted the identification of 22-47% of CIN lesions depending on the histological grade, which showed disease persistence/progression. LOH at these loci was significantly associated with HPV16 infection. Bioinformatic analysis identified several candidate genes including the fragile histidine triad gene and progesterone receptor gene that may be the target of deletions. CONCLUSIONS: LOH at D3S1300, D3S1260, D11S35 and D11S528 was significantly associated with cins that showed persistence/progression, and combined LOH analyses at these loci could be used to identify such cases.