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.     

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.     

A preliminary observation: Male pattern hair loss among hospitalized COVID‐19 patients in Spain – A potential clue to the role of androgens in COVID‐19 severity

A preliminary observation of high frequency of male pattern hair loss among admitted COVID‐19 patients and suggest that androgen expression might be a clue to COVID‐19 severity.     

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.     

Novel Mutations Including Deletions of the Entire OFD1 Gene in 30 Families with Type 1 Orofaciodigital Syndrome: A Study of the Extensive Clinical Variability

OFD1, now recognized as a ciliopathy, is characterized by malformations of the face, oral cavity and digits, and is transmitted as an X‐linked condition with lethality in males. Mutations in OFD1 also cause X‐linked Joubert syndrome (JBTS10) and Simpson–Golabi–Behmel syndrome type 2 (SGBS2). We have studied 55 sporadic and six familial cases of suspected OFD1. Comprehensive mutation analysis in OFD1 revealed mutations in 37 female patients from 30 families; 22 mutations have not been previously described including two heterozygous deletions spanning OFD1 and neighbouring genes. Analysis of clinical findings in patients with mutations revealed that oral features are the most reliable diagnostic criteria. A first, detailed evaluation of brain MRIs from seven patients with cognitive defects illustrated extensive variability with the complete brain phenotype consisting of complete agenesis of the corpus callosum, large single or multiple interhemispheric cysts, striking cortical infolding of gyri, ventriculomegaly, mild molar tooth malformation and moderate to severe cerebellar vermis hypoplasia. Although the OFD1 gene apparently escapes X‐inactivation, skewed inactivation was observed in seven of 14 patients. The direction of skewing did not correlate with disease severity, reinforcing the hypothesis that additional factors contribute to the extensive intrafamilial variability.