Strategic use of organoids and organs-on-chip as biomimetic tools.

Organoid development and organ-on-a-chip are technologies based on differentiating stem cells, forming 3D multicellular structures resembling organs and tissues in vivo. Hence, both can be strategically used for disease modeling, drug screening, and host-pathogen studies. In this context, this review highlights the significant advancements in the area, providing technical approaches to organoids and organ-on-a-chip that best imitate in vivo physiology.

Ruminal Fermentation Pattern, Bacterial Community Composition, and Nutrient Digestibility of Nellore Cattle Submitted to Either Nutritional Restriction or Intake of Concentrate Feedstuffs Prior to Adaptation Period.

Beef cattle are key contributors to meat production and represent critical drivers of the global agricultural economy. In Brazil, beef cattle are reared in tropical pastures and finished in feedlot systems. The introduction of cattle into a feedlot includes a period where they adapt to high-concentrate diets. This adaptation period is critical to the success of incoming cattle, as they must adjust to both a new diet and environment. Incoming animals are typically reared on a variety of diets, ranging from poor quality grasses to grazing systems supplemented with concentrate feedstuffs. These disparate pre-adaptation diets present a challenge, and here, we sought to understand this process by evaluating the adaptation of Nellore calves raised on either grazing on poor quality grasses (restriction diet) or grazing systems supplemented with concentrate (concentrate diet). Given that nutrient provisioning from the diet is the sole responsibility of the ruminal microbial community, we measured the impact of this dietary shift on feeding behavior, ruminal fermentation pattern, ruminal bacterial community composition (BCC), and total tract digestibility. Six cannulated Nellore bulls were randomly assigned to two 3 × 3 Latin squares, and received a control, restriction, or concentrate diet. All cohorts were then fed the same adaptation diet to mimic a standard feedlot. Ruminal BCC was determined using Illumina-based 16S rRNA amplicon community sequencing. We found that concentrate-fed cattle had greater dry matter intake (P < 0.01) than restricted animals. Likewise, cattle fed concentrate had greater (P = 0.02) propionate concentration during the adaptation phase than control animals and a lower Shannon's diversity (P = 0.02), relative to the restricted animals. We also found that these animals had lower (P = 0.04) relative abundances of Fibrobacter succinogenes when compared to control animals during the pre-adaptation phase and lower abundances of bacteria within the Succinivibrio during the finishing phase, when compared to the control animals (P = 0.05). Finally, we found that animals previously exposed to concentrate were able to better adapt to high-concentrate diets when compared to restricted animals. Our study presents the first investigation of the impact of pre-adaptation diet on ruminal BCC and metabolism of bulls during the adaptation period. We suggest that these results may be useful for planning adaptation protocols of bulls entering the feedlot system and thereby improve animal production.

Therapy With Mesenchymal Stem Cells in Parkinson Disease: History and Perspectives.

BACKGROUND: Parkinson disease (PD) is a neurodegenerative disorder affecting the basal nuclei, causing motor and cognitive disorders. Bearing in mind that standard treatments are ineffective in delaying the disease progression, alternative treatments capable of eliminating symptoms and reversing the clinical condition have been sought. Possible alternative treatments include cell therapy, especially with the use of mesenchymal stem cells (MSC). REVIEW SUMMARY: MSC are adult stem cells which have demonstrated remarkable therapeutic power in parkinsonian animals due to their differentiation competence, migratory capacity and the production of bioactive molecules. This review aims to analyze the main studies involving MSC and PD in more than a decade of studies, addressing their different methodologies and common characteristics, as well as suggesting perspectives on the application of MSC in PD. CONCLUSIONS: The results of MSC therapy in animal models and some clinical trials suggest that such cellular therapy may slow the progression of PD and promote neuroregeneration. However, further research is needed to address the limitations of an eventual clinical application.

Pontine activation during focal status epilepticus secondary to hamartoma of the floor of the fourth ventricle.

Epileptic seizures associated with hamartoma of the floor of the fourth ventricle (HFFV) are generally resistant to antiepileptic medication, may evolve into status epilepticus, and can respond favorably to surgical therapy. HFFV are rare, and during the neonatal or infantile period may be associated with repetitive and stereotyped attacks of hemifacial spasm, eye blinking, facial movements, head deviation and dysautonomic manifestations. Similarly, to gelastic seizures provoked by hypothalamic hamartomas, it has been suggested that these spells arise from within the HFFV, thus constituting a type of non-cortical seizure. We report an infant female patient that developed continuous left hemifacial attacks since she was 2-month-old, and that underwent presurgical investigation when she was 18-month-old. MRI disclosed a left sided HFFV, Video-EEG showed non-localizing and non-lateralizing findings, and SPECT aligned with MRI showed marked hyperperfusion within the hamartoma, spreading to ipsilateral cerebellar parenchyma and brainstem nuclei. Patient underwent lesionectomy and became seizure-free. We found two evidences on literature supporting the hypothesis of non-cortical seizures related to HFFV. The first, intra-cerebellar recordings surrounding hamartoma showed electrical activity related to seizures. The second, subtracted SPECT co-registered MRI showed hyperemia within hamartoma. The present report provides the third additional evidence. We found the involvement not only of the hamartoma, and pars of cerebellar hemisphere, but also an intense hyperemia involving brainstem nuclei during seizures. We believe that all these findings suggest a short subcortical network responsible for generating seizures in HFFV patients.