High fat diet enhances stemness and tumorigenicity of intestinal progenitors

Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we find that high fat diet (HFD)-induced obesity augments the numbers and function of Lgr5+ intestinal stem-cells (ISCs) of the mammalian intestine. Mechanistically, HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-d) signature in intestinal stem and (non-ISC) progenitor cells, and pharmacologic activation of PPAR-d recapitulates the effects of a HFD on these cells. Like a HFD, ex vivo treatment of intestinal organoid cultures with fatty acid constituents of the HFD enhances the self-renewal potential of these organoid bodies in a PPAR-d dependent manner. Interestingly, HFD- and agonist-activated PPAR-d signaling endow organoid-initiating capacity to progenitors, and enforced PPAR-d signaling permits these progenitors to form in vivo tumors upon loss of the tumor suppressor Apc. These findings highlight how diet-modulated PPAR-d activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumors

Principi prakse zasnovane na dokazima kod primjene tehnika mobilizacije zglobova ramena i ramenog obruča

Tehnike manualne terapije u davnoj su se povijesti koristile za liječenje različitih mišićnih i koštanih stanja te poremećaja kralježnice, a danas se koriste kod disfunkcije zglobova, disfunkcije kralježnice, limfadema, glavobolje, cistične fibroze, nakon imobilizacije, kod uklještenja živaca i drugih stanja, s brojnim ciljevima kao što su povećanje opsega pokreta zglobova i kvalitete pokreta, smanjenje boli, razvijanje stabilnost, poboljšanje funkcije, ili povećanje pokretljivosti živaca. Tehnike manualne terapije koriste se na zglobovima, a zglob je mjesto na kojemu se spajaju dvije ili više kosti. Zglob ramena je najpokretljiviji zglob u čovjekovom tijelu, a u ramenu se nalaze tri zgloba; glenohumeralni zglob, akromioklavikularni zglob i skapulotorakalni zglob. U ramenom obruču nalaze se dva zgloba; articulatio sternoclavicularis te articulatio acromioclavicularis. Na zglobove ramena i ramenog obruča duhi niz godina primjenjuju se, i to uspješno, različite tehnike manualne terapije i mobilizacije, o čemu postoje brojni dokazi. U ovome radu ističe se važnost prakse zasnovane na dokazima u fizioterapiji na primjeru tehnika mobilizacije zglobova ramena i ramenog obruča. Praksa zasnovana na dokazima imperativ je suvremene fizioterapije. Nijedan fizioterapeut ne bi trebao koristiti neprovjerene metode, već bi na temelju usporedbe rezultata provedenih kliničkih istraživanja u kojima je istražena djelotvornost i sigurnost nekog fizioterapeutskog postupka trebao odlučiti o primjerenom postupku za svakog pacijenta

Principi prakse zasnovane na dokazima kod primjene tehnika mobilizacije zglobova ramena i ramenog obruča

Tehnike manualne terapije u davnoj su se povijesti koristile za liječenje različitih mišićnih i koštanih stanja te poremećaja kralježnice, a danas se koriste kod disfunkcije zglobova, disfunkcije kralježnice, limfadema, glavobolje, cistične fibroze, nakon imobilizacije, kod uklještenja živaca i drugih stanja, s brojnim ciljevima kao što su povećanje opsega pokreta zglobova i kvalitete pokreta, smanjenje boli, razvijanje stabilnost, poboljšanje funkcije, ili povećanje pokretljivosti živaca. Tehnike manualne terapije koriste se na zglobovima, a zglob je mjesto na kojemu se spajaju dvije ili više kosti. Zglob ramena je najpokretljiviji zglob u čovjekovom tijelu, a u ramenu se nalaze tri zgloba; glenohumeralni zglob, akromioklavikularni zglob i skapulotorakalni zglob. U ramenom obruču nalaze se dva zgloba; articulatio sternoclavicularis te articulatio acromioclavicularis. Na zglobove ramena i ramenog obruča duhi niz godina primjenjuju se, i to uspješno, različite tehnike manualne terapije i mobilizacije, o čemu postoje brojni dokazi. U ovome radu ističe se važnost prakse zasnovane na dokazima u fizioterapiji na primjeru tehnika mobilizacije zglobova ramena i ramenog obruča. Praksa zasnovana na dokazima imperativ je suvremene fizioterapije. Nijedan fizioterapeut ne bi trebao koristiti neprovjerene metode, već bi na temelju usporedbe rezultata provedenih kliničkih istraživanja u kojima je istražena djelotvornost i sigurnost nekog fizioterapeutskog postupka trebao odlučiti o primjerenom postupku za svakog pacijenta

Reinforcement regulates timing variability in thalamus

© Wang et al. Learning reduces variability but variability can facilitate learning. This paradoxical relationship has made it challenging to tease apart sources of variability that degrade performance from those that improve it. We tackled this question in a context-dependent timing task requiring humans and monkeys to flexibly produce different time intervals with different effectors. We identified two opposing factors contributing to timing variability: Slow memory fluctuation that degrades performance and reward-dependent exploratory behavior that improves performance. Signatures of these opposing factors were evident across populations of neurons in the dorsomedial frontal cortex (DMFC), DMFC-projecting neurons in the ventrolateral thalamus, and putative target of DMFC in the caudate. However, only in the thalamus were the performanceoptimizing regulation of variability aligned to the slow performance-degrading memory fluctuations. These findings reveal how variability caused by exploratory behavior might help to mitigate other undesirable sources of variability and highlight a potential role for thalamocortical projections in this process

Automatic reagent handling and assay processing of human biospecimens inside a transportation container for a medical disaster response against radiation.

Biological materials can be shipped off-site for diagnostic, therapeutic and research purposes. They usually are kept in certain environments for their final application during transportation. However, active reagent handling during transportation from a collection site to a laboratory or biorepository has not been reported yet. In this paper, we show the application of a micro-controlled centrifugal microfluidic system inside a shipping container that can add reagent to an actively cultured human blood sample during transportation to ensure a rapid biodosimetry of cytokinesis-block micronucleus (CBMN) assay. The newly demonstrated concept could have a significant impact on rapid biodosimetry triage for medical countermeasure in a radiological disaster. It also opens a new capability in accelerated sample processing during transportation for biomedical and healthcare applications

Diagnostic predictive values for sport-related concussions: a systematic review and diagnostic meta-analysis

OBJECTIVE: Sport-related concussions (SRCs) can cause significant neurological symptoms, and approximately 10%-15% of athletes with SRC experience a prolonged recovery. Given the lack of visible injury on brain imaging and their varied presentations, concussions can be difficult to diagnose. A variety of tests and examination methods have been used to elicit a concussion diagnosis; however, the sensitivity and specificity of these tests are variable. The authors performed a systematic review and meta-analysis to evaluate the sensitivity and specificity of standardized tests and visible signs like balance and vision changes in the diagnosis of SRC. METHODS: A PRISMA-adherent systematic review of concussion diagnostic examinations was performed using the PubMed, MEDLINE, Scopus, Cochrane, Web of Science, and Google Scholar databases on December 1, 2022. Search terms included concussion, traumatic brain injury, diagnosis, sensitivity, and specificity. Each method of examination was categorized into larger group-based symptomatologic presentations or standardized tools. The primary outcome was the diagnosis of concussion. Pooled specificity and sensitivity for each method were calculated using a meta-analysis of proportion and were hierarchically ranked using P-scores calculated from a diagnostic frequentist network meta-analysis. RESULTS: Thirty full-length articles were identified for inclusion, 13 of which evaluated grouped symptomology examinations (balance and overall clinical presentation) and 17 of which evaluated established formalized tools (ImPACT, King-Devick [K-D] Test, Sport Concussion Assessment Tool [SCAT]). The pooled specificity of the examination methods differed minimally (0.8-0.85), whereas the sensitivity varied to a larger degree (0.5-0.88). In a random effects model, the SCAT had the greatest diagnostic yield (diagnostic OR 31.65, 95% CI 11.06-90.57). Additionally, P-score hierarchical ranking revealed SCAT as having the greatest diagnostic utility (p = 0.9733), followed sequentially by ImPACT, clinical presentation, K-D, and balance. CONCLUSIONS: In deciphering which concussion symptom-focused examinations and standardized tools are most accurate in making a concussion diagnosis, the authors found that the SCAT examination has the greatest diagnostic yield, followed by ImPACT, clinical presentation, and K-D, which have comparable value for diagnosis. Given the indirect nature of this analysis, however, further comparative studies are needed to validate the findings

In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis.

In vivo interrogation of the function of genes implicated in tumorigenesis is limited by the need to generate and cross germline mutant mice. Here we describe approaches to model colorectal cancer (CRC) and metastasis, which rely on in situ gene editing and orthotopic organoid transplantation in mice without cancer-predisposing mutations. Autochthonous tumor formation is induced by CRISPR-Cas9-based editing of the Apc and Trp53 tumor suppressor genes in colon epithelial cells and by orthotopic transplantation of Apc-edited colon organoids. ApcΔ/Δ;Kras(G12D/+);Trp53Δ/Δ (AKP) mouse colon organoids and human CRC organoids engraft in the distal colon and metastasize to the liver. Finally, we apply the orthotopic transplantation model to characterize the clonal dynamics of Lgr5(+) stem cells and demonstrate sequential activation of an oncogene in established colon adenomas. These experimental systems enable rapid in vivo characterization of cancer-associated genes and reproduce the entire spectrum of tumor progression and metastasis.</p

Rift Valley Fever in Egypt and other African countries: Historical review, recent outbreaks and possibility of disease occurrence in Egypt

This article reviews and discusses the historical and recent status of Rift Valley Fever (RVF) in Egypt and the other African countries based on the available and scattered reports. The recent outbreaks in African countries were reviewed and mapped out. Four major epidemics have been recorded in Egypt (1977, 1978, 1993 and 2003). The outbreak resulted in unpredicted human disease with severe clinical manifestations and heavy mortality as well as many abortions and deaths in sheep, goats, cattle, water buffalo and camels. Of the 18 culicine mosquito species that occur in Egypt, Culex pipiens and Cx. antennatus were implicated as vectors of RVF in Egypt based on their natural infection with RVF virus. Aedes caspius was also suspected of disseminating the virus among livestock based on host feeding and vector competence studies. The epidemiological factors related to the introduction and spread of RVF in Egypt are discussed. The study concluded that due to the availability and abundance of the potential vectors, suitability of environmental conditions, continuous importation of livestock's from Sudan, and the close association of susceptible domestic animals with humans, the RVF virus could possibly occur and circulate in Egypt