Maturation of the gastric microvasculature in Xenopus laevis (Lissamphibia, Anura) occurs at the transition from the herbivorous to the carnivorous lifestyle, predominantly by intussuceptive microvascular growth (IMG): a scanning electron microscope study of microvascular corrosion casts and correlative light microscopy

The microvascular bed of the stomach of Xenopus laevis and the changes it undergoes when the herbivorous tadpole becomes a carnivorous adult were studied by scanning electron microscopy of vascular corrosion casts and light microscopy of stained tissue sections. In tadpoles an upper and a lower gastric artery supplied, and upper, middle and lower medial and lateral gastric veins drained the vertically extending stomach. During metamorphosis, the stomach gained a horizontal cranio-caudal extension and vessels accordingly become dorsal and ventral gastric arteries, and anterior, middle and posterior gastric veins, respectively. Up to stage 64 (late climax) mucosal capillaries formed a polygonal network of wide immature-looking capillaries ensheathing gastric glands in a basket-like manner. From stage 64 onwards, blood vessels of the stomach appeared mature, revealed a clear hierarchy and were correlated closely with the histomorphology of the stomach, which had also gained the adult pattern. Within the gastric mucosa, ascending arterioles branched in a fountain-like pattern into wide subepithelial capillaries establishing a centripetal blood flow along the gastric glands, which makes an ultrashort control loop of glandular cells within the branched tubular gastric glands very unlikely. Formation of the stomach external muscular layer started at stage 57 when smooth muscle cells locally formed a single longitudinal and one-to-two single circular layers. Abundant signs of intussusceptive microvascular growth and rare vascular sprouts in vascular corrosion casts indicated that the larval-to-adult microvascular pattern formation of the stomach of Xenopus laevis Daudin occurs predominantly by non-sprouting angiogenesis

Mindfulness-and body-psychotherapy-based group treatment of chronic tinnitus: a randomized controlled pilot study

Background Tinnitus, the perception of sound in absence of an external acoustic source, impairs the quality of life in 2% of the population. Since in most cases causal treatment is not possible, the majority of therapeutic attempts aim at developing and strengthening individual coping and habituation strategies. Therapeutic interventions that incorporate training in mindfulness meditation have become increasingly popular in the treatment of stress-related disorders. Here we conducted a randomized, controlled clinical study to investigate the efficacy of a specific mindfulness- and body-psychotherapy based program in patients suffering from chronic tinnitus. Methods Thirty-six patients were enrolled in this pilot study. The treatment was specifically developed for tinnitus patients and is based on mindfulness and body psychotherapy. Treatment was performed as group therapy at two training weekends that were separated by an interval of 7 weeks (eleven hours/weekend) and in four further two-hour sessions (week 2, 9, 18 and 22). Patients were randomized to receive treatment either immediately or after waiting time, which served as a control condition. The primary study outcome was the change in tinnitus complaints as measured by the German Version of the Tinnitus Questionnaire (TQ). Results ANOVA testing for the primary outcome showed a significant interaction effect time by group (F = 7.4; df = 1,33; p = 0.010). Post hoc t-tests indicated an amelioration of TQ scores from baseline to week 9 in both groups (intervention group: t = 6.2; df = 17; p < 0.001; control group: t = 2.5; df = 16; p = 0.023), but the intervention group improved more than the control group. Groups differed at week 7 and 9, but not at week 24 as far as the TQ score was concerned. Conclusions Our results suggest that this mindfulness- and body-psychotherapy-based approach is feasible in the treatment of tinnitus and merits further evaluation in clinical studies with larger sample sizes. The study is registered with clinicaltrials.gov (NCT01540357)

Biallelic SZT2 Mutations Cause Infantile Encephalopathy with Epilepsy and Dysmorphic Corpus Callosum

Epileptic encephalopathies are genetically heterogeneous severe disorders in which epileptic activity contributes to neurological deterioration. We studied two unrelated children presenting with a distinctive early-onset epileptic encephalopathy characterized by refractory epilepsy and absent developmental milestones, as well as thick and short corpus callosum and persistent cavum septum pellucidum on brain MET. Using whole-exome sequencing, we identified biallelic mutations in seizure threshold 2 (SZT2) in both affected children. The causative mutations include a homozygous nonsense mutation and a nonsense mutation together with an exonic splice-site mutation in a compound-heterozygous state. The latter mutation leads to exon skipping and premature termination of translation, as shown by RT-PCR in blood RNA of the affected boy. Thus, all three mutations are predicted to result in nonsense-mediated mRNA decay and/or premature protein truncation and thereby loss of SZT2 function. Although the molecular role of the peroxisomal protein SZT2 in neuronal excitability and brain development remains to be defined, Szt2 has been shown to influence seizure threshold and epileptogenesis in mice, consistent with our findings in humans. We conclude that mutations in SZT2 cause a severe type of autosomal-recessive infantile encephalopathy with intractable seizures and distinct neuroradiological anomalies

Homozygous MED25 mutation implicated in eye-intellectual disability syndrome

Genetic syndromes involving both brain and eye abnormalities are numerous and include syndromes such as Warburg micro syndrome, Kaufman oculocerebrofacial syndrome, Cerebro-oculo-facio-skeletal syndrome, Kahrizi syndrome and others. Using exome sequencing, we have been able to identify homozygous mutation p.(Tyr39Cys) in MED25 as the cause of a syndrome characterized by eye, brain, cardiac and palatal abnormalities as well as growth retardation, microcephaly and severe intellectual disability in seven patients from four unrelated families, all originating from the same village. The protein encoded by MED25 belongs to Mediator complex or MED complex, which is an evolutionary conserved multi-subunit RNA polymerase II transcriptional regulator complex. The MED25 point mutation is located in the von Willebrand factor type A (MED25 VWA) domain which is responsible for MED25 recruitment into the Mediator complex; co-immunoprecipitation experiment demonstrated that this mutation dramatically impairs MED25 interaction with the Mediator complex in mammalian cells