Cannabinoids help to unravel etiological aspects in common and bring hope for the treatment of autism and epilepsy

Desde 1843 que as propriedades anticonvulsivantes da Cannabis são conhecidas pela ciência ocidental. Em 1980, ensaios clínicos demonstraram que canabidiol possui atividade antiepilética em pacientes de epilepsia refratária, sendo sonolência o único efeito colateral. O embargo imposto pela proibição do uso medicinal da Cannabis, no entanto, prejudicou imensamente o desenvolvimento científico e a exploração dessas propriedades. Multiplicam-se, contudo, os casos bem sucedidos de uso ilegal e sem orientação para o tratamento de síndromes caracterizadas por epilepsia e autismo regressivo. Os resultados corroboram evidências científicas que indicam a existência de processos etiológicos comuns entre o autismo e a epilepsia. Estudos em modelos animais confirmam envolvimento do sistema endocanabinoide. Esses avanços apontam o início de uma revolução no entendimento e tratamento desses transtornos.Since 1843 the anticonvulsant properties of Cannabis are known by the Western science. In 1980, clinical trials have shown that cannabidiol has antiepileptic activity in refractory epilepsy patients, with drowsiness as the only side effect. The embargo imposed by banning medicinal Cannabis use, however, harmed scientific development and the exploration of these properties. However, there is a growing number of successful cases of illegal use without guidance for the treatment of syndromes characterized by epilepsy and regressive autism. The results corroborate scientific evidence that indicates the existence of common etiological aspects between autism and epilepsy. Studies in animal models have confirmed involvement of the endocannabinoid system. These advances indicate the beginning of a revolution in the understanding and treatment of these disorders

The time-depth of Corded Ware burial landscapes: A comparative study of Single Grave and Battle Axe burial alignments in Denmark, The Netherlands and Sweden

Barrow landscapes appeared in the third and second millennia BC throughout North-Western Europe; these first barrows were constructed by people of the Corded Ware culture and placed in alignments. This thesis is an interregional comparative study, to determine whether there is a pattern in the time-depths of the burial alignments of Trehuse-Sjørup-Dollerup in Denmark, Angelso-Emmerhout in The Netherlands and Lilla Beddinge in Sweden. The analysis is conducted by means of a literature study and the application of typochronologies. In recent research, the Corded Ware ‘culture’ is still seen as a widespread, unified social phenomenon that is the result of migration, but more emphasis is placed on the regional variability of this phenomenon. Regional variability is also what we see in the three case-studies; in fact, perhaps one may better speak of ‘local variability’, as each case-study reveals a remarkable variety even within one alignment. Even though there do seem to be interregionally shared traits, these are expressed in local practices. Despite the limitations of establishing a time-depth by means of typochronologies, all three alignments reveal a long use-life; even in the Bronze and Iron Ages, prehistoric people buried their dead here. Temporality seems to have been an important aspect of the ‘Corded Ware’ burial landscape

Kenya: West Kenya postmarks

HiWATER: The Multi-Scale Observation Experiment on Evapotranspiration over heterogeneous land surfaces (MUSOEXE) Dataset - Flux Observation Matrix (stable isotopic observations

Collaborative mental health care : changing the landscape of mental health care?

In this thesis two major changes in the organization of mental health care delivery are explored. The first is collaborative mental health care in primary care, developed as an alternative way to treat common mental health disorders compared to the traditional referral and treatment practice. The collaborative care program followed the principles of stepped care. The first and least intensive treatment step was provided within the collaborative care program in the primary care setting. Treatment intensity was only stepped up through referral to specialized mental health care for patients who did not sufficiently respond to the first step. The traditional practice was direct referral and treatment within specialized care. In several studies we investigated effectiveness, short- and long-term efficiency, cost-effectiveness and whether the stepped care approach was appropriate for all patients instead of the matched care approach. The second change was the integration of eHealth in the collaborative care treatment model. In this study, implementation factors that could either inhibit or promote the uptake and utilization of blended collaborative care by mental health professionals and patients were assessed

MicroRNA Transcriptome in Swine Small Intestine during Weaning Stress

<div><p>MicroRNAs (miRNAs) play important roles in intestinal diseases; however, the role of miRNAs during weaning stress is unknown. In our study, six jejunal small RNA libraries constructed from weaning piglets at 1, 4 and 7 d after weaning (libraries W1, W4 and W7, respectively) and from suckling piglets on the same days as the weaning piglets (libraries S1, S4 and S7, respectively) were sequenced using Solexa high-throughput sequencing technology. Overall, 260 known swine miRNAs and 317 novel candidate miRNA precursors were detected in the six libraries. The results revealed that 16 differentially expressed miRNAs were found between W1 and S1; 98 differentially expressed miRNAs were found between W4 and S4 (ssc-mir-146b had the largest difference); and 22 differentially expressed miRNAs were found between W7 and S7. Sequencing miRNA results were validated using RT-qPCR. Approximately 11,572 miRNA-mRNA interactions corresponding to 3,979 target genes were predicted. The biological analysis further describe that the differentially expressed miRNAs regulated small intestinal metabolisms, stressful responses and immune functions in piglets. Therefore, the small intestine miRNA transcriptome was significantly different between weaning and suckling piglets; the difference varied with the number of days after weaning.</p></div

Distribution of novel candicate miRNAs in Chromosomes.

<p>The y-axis is the number of novel candidate miRNA uniques predictecd in six libraries (W1, W4, W7, S1, S4, S7). W1, W4 and W7, the samples from piglets on days1, 4 and 7 after weaning, respectively. S1, S4 and S7, the samples from suckling piglets on the same days on which the weaning samples were collected.</p

Validation of sequencing results by real-time quantitative PCR.

<p>Four biological replicates were used, and U6 snRNA was used as an internal control. The y-axis is the fold-change between W4 and S4 samples (fold quantity values for real-time PCR; Log (W4/S4, 2) for Solexa sequencing). Means with the star on the column differ significantly (P<0.05). W4, the samples from piglets on days 4 after weaning. S4, the samples from suckling piglets on the same days on which W4 samples were collected.</p

Heatmap of differentially expressed miRNAs in weaning and control groups.

<p>W1, W4 and W7, the samples from piglets on days1, 4 and 7 after weaning, respectively. S1, S4 and S7, the samples from suckling piglets on the same days on which the weaning samples were collected. Color levels were normalized row scales and the values of scale were the log10(FPKM+1) values transformed by the FPKMs of miRNAs. Green indicates upregulated expression, and red indicates downregulated expression compared to a reference expression level.</p

Analysis of Serum microRNA Expression Profiles and Comparison with Small Intestinal microRNA Expression Profiles in Weaned Piglets

<div><p>Weaning stress induces tissue injuries and impairs health and growth in piglets, especially during the first week post-weaning. MicroRNAs (miRNAs) play vital roles in regulating stresses and diseases. Our previous study found multiple differentially expressed miRNAs in small intestine of piglets at four days post-weaning. To better understand the roles of miRNAs during weaning stress, we analyzed the serum miRNA expressional profile in weaned piglets (at four days post-weaning) and in suckling piglets (control) of the same age using miRNA microarray technology. We detected a total of 300 expressed miRNAs, 179 miRNAs of which were differentially expressed between the two groups. The miRNA microarray results were validated by RT-qPCR. The biological functions of these differentially expressed miRNAs were predicted by GO terms and KEGG pathway annotations. We identified 10 highly expressed miRNAs in weaned piglets including miR-31, miR-205, and miR-21 (upregulated) and miR-144, miR-30c-5p, miR-363, miR-194a, miR-186, miR-150, and miR-194b-5p (downregulated). Additionally, miR-194b-5p expression was significantly downregulated in serum and small intestine of weaned piglets. Our results suggest that weaning stress affects serum miRNA profiles in piglets. And serum miR-194b-5p levels can reflect its expressional changes in small intestine of piglets by weaning stress.</p></div

Heatmap of differentially expressed miRNAs in suckling and weaned piglets.

<p>Green indicates downregulated expression, and red indicates upregulated expression compared to a reference expression level.</p