Pertussis-Specific Memory B-Cell and Humoral IgG Responses in Adolescents after a Fifth Consecutive Dose of Acellular Pertussis Vaccine

In order to impede the increase in pertussis incidence in the adolescent group, a school-leaving booster dose administered at the age of 14 to 16 years will be introduced in Sweden in 2016. Preceding this introduction, an open-label, randomized, multicenter, clinical trial without a control group and with blinded analysis was performed, investigating both safety and immunogenicity. Reported here are the memory B-cell and serological responses detected in a smaller cohort (n = 34) of the 230 subjects recruited to the study. All subjects had received primary vaccination consisting of three doses of diphtheria–tetanus–5-component pertussis (DTaP5) vaccine, at 3, 5, and 12 months of age, and a tetanus–low-dose diphtheria–5-component pertussis (Tdap5) vaccine booster at 5.5 years. In this study, the subjects were randomly assigned and received either a Tdap1 or Tdap5 booster. Of the 230 participants, 34 subjects had samples available for evaluation of IgG-producing memory B-cell responses. Both vaccine groups had significant increases in pertussis toxin-specific serum IgG levels, but only the 1-component group showed significant increases in pertussis toxin-specific memory B cells. The 5-component group had significant increases in filamentous hemagglutinin- and pertactin-specific memory B-cell and serum IgG levels; these were not seen in the 1-component group, as expected. In conclusion, this study shows that a 5th consecutive dose of an acellular pertussis vaccine induces B-cell responses in vaccinated adolescents. (This study has been registered at EudraCT under registration no. 2008-008195-13 and at ClinicalTrials.gov under registration no. NCT00870350.)     

GABA is localized in dopaminergic synaptic vesicles in the rodent striatum

Recently, electrophysiological evidence was given for inhibitory postsynaptic responses at dopaminergic striatal synapses. These responses were independent of the vesicular GABA transporter, VGAT, but dependent on the vesicular dopamine transporter VMAT2. The identity and the exact source of the released molecule, as well as the presence of the putative inhibitory transmitter in VMAT2 containing synaptic vesicles remain to be shown. To clarify this, in particular to determine whether GABA is responsible for the inhibitory response at dopaminergic synapses, we used the electron microscopic immunogold method to label in vivo perfusion fixed striatal tissue with antibodies recognising GABA, VGAT, VMAT2 and tyrosine hydroxylase. We show that about 13 % of tyrosine hydroxylase positive and 11 % of VMAT2 axonal terminals in the caudo-putamen contain significant labelling for GABA. Immunogold signals for tyrosine hydroxylase and VGAT was totally segregated into different pools of nerve terminals. Quantitative analyses of the distance between gold particles signalling GABA and synaptic vesicles showed that GABA was as closely associated with synaptic vesicles in tyrosine hydroxylase positive as in tyrosine hydroxylase negative nerve terminals. Likewise, in dopaminergic terminals GABA and VMAT2 immunogold particles showed a close spatial localization, strongly suggesting the presence of GABA in VMAT2 positive synaptic vesicles. Our results suggest that GABA is exocytosed together with dopamine from dopaminergic nerve terminals in the caudo-putamen through VGAT negative and VMAT2 positive synaptic vesicles.     

Executive Functions in Preschool Children With ADHD and DBD: An 18-Month Longitudinal Study

In this longitudinal study, we examined the stability of the association between executive functions and externalizing behavior problems, and the developmental change of executive functions in a predominately clinically diagnosed preschool sample (N = 200). Inhibition and working memory performance were assessed three times in 18 months. Across time, poorer inhibition performance in young children was associated with attention deficit hyperactivity disorder (ADHD) and disruptive behavior disorders (DBD), and poorer working memory performance was associated with ADHD. Inhibition and working memory performance increased over time, especially in the early preschool period. The improvement of inhibition performance was more pronounced in the clinically diagnosed children compared to the TD children.     

Prevention of congenital toxoplasmosis in Slovenia by serological screening of pregnant women

A programme for the prevention of congenital toxoplasmosis in Slovenia involving the screening of pregnant women for Toxoplasma infection is presented. Of 21,270 pregnant women screened for toxoplasmosis between, 1996 and the end of 1999, 13,987 (66%) were seronegative, 7,151 (34%) seropositive and 132 had primary infection; approximately 9/1,000 women were at risk of acquiring the primary infection. One hundred live-born infants of primary infected women were available for follow-up. Nine infected but asymptomatic children were born to mothers who were screened and treated in time and two congenitally infected babies were born to mothers in whom infection was detected too late in pregnancy and who therefore received no adequate treatment. It is suggested that the results obtained in this study outweigh the cost of screening for toxoplasmosis in pregnancy. Pregnant women should always be tested at the beginning of pregnancy and, in cases of seronegativity, should be re-tested in the second and third trimesters of the pregnancy. Toxoplasma primary infected pregnant women and neonates should be treated as soon as possible. However, long-term follow-up of children born to primary infected women would be necessary for an accurate evaluation of the effectiveness of the screening because of the possibility of late onset of symptoms.     

Long-term subcutaneous morphine administration after surgery in newborns

AIM: To analyze the management of newborns after major surgery receiving morphine subcutaneously and to identify possible side effects. METHODS: Morphine was administered via a subcutaneous catheter (Insuflon) in 20 newborns after major surgery. Side effects like hypotension, pain during morphine administration and local infection were noted. Morphine dose was adjusted according to the hospital guidelines with the Neonatal Infant Pain Score (NIPS) and the Finnegan withdrawal score. RESULTS: Surgery was performed at the median age of 38 5/7 weeks (range: 32 1/7-49 5/7 weeks). Before starting subcutaneous morphine administration, patients received intravenous morphine for a median of two weeks (range six days to seven weeks). All patients showed good pain relief with no severe side effects. Three patients reacted with crying to the first dose of subcutaneous morphine. No other side effects occurred. CONCLUSION: Subcutaneous application of morphine with the Insuflon catheter is an alternative to intravenous treatment of postoperative pain in neonates. In this small group pain relief was good and side effects were harmless.     

Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma

Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.     

Standardization of Quality of Diagnoses,Interventions, and Outcomes (Q-DIO) Measurement Instrument for Use in Slovenia

PurposeTo describe the cross-cultural adaptation of the Quality of Diagnoses, Interventions and Outcomes (Q-DIO) Instrument into the Slovene language.MethodsBased on general international guidelines, a six-step process of localization to translate and adjust the instrument from English into the Slovene language was used. Content validity was quantified based on an agreement of eight experts. The instrument was tested using a sample of 140 nursing documentations from two Slovenian tertiary hospitals.Results26 of 29 items showed an excellent content validity index ranging from 0.857 to 1.000, and a modified kappa index above 0.856. The content validity indexes of the three remaining items adjusted based on experts’ comments were subsequently estimated at 1.000. Construct validity was significantly different between the two groups of documentations. The Cronbach coefficient for the whole questionnaire was 0.860. Cronbach’s alpha if item deleted reamins above 0.80 for all items. The criteria for the difficulty grades of items and discrimination validity were acceptably met for more than 75% of items.ConclusionBased on the results of the study, it may be concluded that Q-DIO is a reliable instrument for measuring the quality of nursing documentation. The deviations in the results of some items are due to poor nursing documentation quality, and indicate that nursing classifications have not yet been fully implemented into practice in the study setting. Additional testing of the instrument is recommended.     

Solvothermal synthesis and structural characterization of three polyoxotitanium-organic acid clusters

Three new titanium oxo-clusters Ti₄O₂(OⁱPr)₁₀(OOCPhMe)₂ (I), Ti₆O₄(OEt)₈(OOCPhMe)₈ (II) and Ti₆O₆(OEt)₆(OOCCHPh₂)₆ (III) were obtained by easy one-step solvothermal reactions of titanium(iv) isopropoxide, alcohols and carboxylic acids. The three compounds were characterized by single-crystal and powder X-ray diffraction, TGA/DSC, optical and electron microscopy, and FTIR and NMR spectroscopy. X-ray powder diffraction and spectroscopy confirmed the purity of the compounds. Structural analysis indicates that in all compounds the titanium(iv) ions are six-coordinated (distorted octahedra). (I) is a tetranuclear complex containing a Ti₄(μ₄-O)(μ₂-O) core, which is linked by two (μ₂-OOCPhMe), four (μ₂-OⁱPr) and six OⁱPr ligands. (II) and (III) are hexanuclear complexes with different cores, respectively Ti₆(μ₃-O)₂(μ₂-O)₂ and Ti₆(μ₃-O)₆. The coordination sphere of the Ti atoms is filled by eight (μ₂-OOCPhMe), two (μ₂-OEt) and six OEt in (II) and six (μ₂-OOCHPh₂) and six OEt in (III). Different steric hindrance of substituents attached to the carboxyl group or different concentrations lead to three main different cluster geometries with two ligands. The tetranuclear and the hexanuclear clusters were obtained with the OOCPhMe ligand, while the hexagonal prism cluster was obtained with the OOCCHPh₂ ligand. Hirshfeld surface calculations indicated that the packing is driven by C–O⋯H–C weak hydrogen bonds. The clusters can be used as molecular models of organic molecules bonded to titania surface, used in organic photovoltaic (dye sensitized solar cells) or other optoelectronic applications.

Crystal structures of three novel titanium oxo-clusters with different cores and ligands obtained by an easy and convenient solvothermal method.