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Human cerebral organoids undergo vascularization and maturation in the mouse brain. Differentiation of human pluripotent stem cells to small brain-like structures known as brain organoids offers an unprecedented opportunity to model human brain development and disease. To provide a vascularized and functional in vivo model of brain organoids, we established a method for transplanting human brain organoids into the adult mouse brain. Organoid grafts showed progressive neuronal differentiation and maturation, gliogenesis, integration of microglia, and growth of axons to multiple regions of the host brain. In vivo two-photon imaging demonstrated functional neuronal networks and blood vessels in the grafts. Finally, in vivo extracellular recording combined with optogenetics revealed intragraft neuronal activity and suggested graft-to-host functional synaptic connectivity. This combination of human neural organoids and an in vivo physiological environment in the animal brain may facilitate disease modeling under physiological conditions.

Alzheimer’s disease (AD) is the most common type of dementia in the elderly. Several hypotheses emerged from AD pathophysiological mechanisms. However, no neuronal protective or regenerative drug is available nowadays. Researchers still work in drug development and are finding new molecular targets to treat AD. Therefore, this study aimed to summarize main advances in AD pharmacological therapy. Clinical trials registered in the National Library of Medicine database were selected and analyzed accordingly to molecular targets, therapeutic effects, and safety profile. The most common outcome was the lack of efficacy. Only seven trials concluded that tested drugs were safe and induced any kind of therapeutic improvement. Three works showed therapeutic effects followed by toxicity. In addition to aducanumab recent FDA approval, antibodies against amyloid-β (Aβ) showed no noteworthy results. 5-HT6 antagonists, tau inhibitors and nicotinic agonists’ data were discouraging. However, anti-Aβ vaccine, BACE inhibitor and anti-neuroinflammation drugs showed promising results.

A guinea-pig model of cardiac injury is used to show that human embryonic stem-cell-derived cardiomyocyte grafts can electrically integrate into the injured heart, improving mechanical function and reducing spontaneous and induced ventricular tachycardia; this is a major step towards clinical adoption of cell replacement therapies for cardiovascular diseases using human cardiomyocytes. Heart repair by cell replacement This study extends previous findings that transplantation of fetal cardiomyocytes can improve the function of infarcted hearts, despite having only a modest effect on the organ's mechanical properties. The investigators developed a guinea pig model of cardiac injury, because the heart rate of these animals is at the upper end of what is tolerable to human cardiomyocytes, and much lower than that of the mice and rats often used as models. The authors show that cardiomyocytes derived from human embryonic stem cells can integrate electrically into the guinea pig heart and protect against arrhythmias. This is the first convincing evidence that cardiomyocytes generated from cultured human embryonic stem cells can integrate into the adult heart, and is therefore a major step towards the clinical adoption of cell-replacement therapies for cardiovascular disease. Transplantation studies in mice and rats have shown that human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) can improve the function of infarcted hearts 1 , 2 , 3 , but two critical issues related to their electrophysiological behaviour in vivo remain unresolved. First, the risk of arrhythmias following hESC-CM transplantation in injured hearts has not been determined. Second, the electromechanical integration of hESC-CMs in injured hearts has not been demonstrated, so it is unclear whether these cells improve contractile function directly through addition of new force-generating units. Here we use a guinea-pig model to show that hESC-CM grafts in injured hearts protect against arrhythmias and can contract synchronously with host muscle. Injured hearts with hESC-CM grafts show improved mechanical function and a significantly reduced incidence of both spontaneous and induced ventricular tachycardia. To assess the activity of hESC-CM grafts in vivo , we transplanted hESC-CMs expressing the genetically encoded calcium sensor, GCaMP3 (refs 4 , 5 ). By correlating the GCaMP3 fluorescent signal with the host ECG, we found that grafts in uninjured hearts have consistent 1:1 host–graft coupling. Grafts in injured hearts are more heterogeneous and typically include both coupled and uncoupled regions. Thus, human myocardial grafts meet physiological criteria for true heart regeneration, providing support for the continued development of hESC-based cardiac therapies for both mechanical and electrical repair.

The active workforce is increasingly aging. However workload, as well as working time and intensity, sometimes remains unchanged. This can be an even more critical situation in older people, since occupational exposure associated with aging, will further reduce the muscle's ability to generate energy, which in turn facilitates the development of these age-related syndromes. This study aims to identify the normative values of handgrip strength for Portuguese workers in the automotive industry. About 1225 employees were invited to participate in the study. The final sample consisted of 656 employees in the assembly area. The handgrip strength was measured in kilograms (kg) using the Jamar digital dynamometer. Sex-specific profiles of handgrip strength were designed by the Ordinary Least Square regression (OLS) analysis, where height, age, age squared, and height squared are entered into the models as determining factors of the maximum grip strength in both female and male groups. The peak mean values of handgrip strength in the group of women was 34 kg in the age group of 35-39 years, and in the group of men the peak mean was 52 kg in the age group of 25-34 years. The most pronounced decline in the female group appears in the age of 30-34 years of about 4 kg and the male group the decline occurs at 2kg below the peak force, in the age group of 40-57 year-olds. This study used a cut-off at 2 SD below by the sex-specific peak mean. Normative values can help delineate the career path of workers because they portray risk values according to age, height, and gender. The normative values assist health and engineering professionals and ergonomists in adjusting task demands to the morphological and strength characteristics of the workers.

Age-related neurodegenerative diseases, like Alzheimer’s disease (AD), are challenging diseases for those affected with no cure and limited treatment options. Functional, human derived brain tissues that represent the diverse genetic background and cellular subtypes contributing to sporadic AD (sAD) are limited. Human stem cell derived brain organoids recapitulate some features of human brain cytoarchitecture and AD-like pathology, providing a tool for illuminating the relationship between AD pathology and neural cell dysregulation leading to cognitive decline. In this review, we explore current strategies for implementing brain organoids in the study of AD as well as the challenges associated with investigating age-related brain diseases using organoid models.

Brain organoids are proving to be physiologically relevant models for studying human brain development in terms of temporal transcriptional signature recapitulation, dynamic cytoarchitectural development, and functional electrophysiological maturation. Several studies have employed brain organoid technologies to elucidate human-specific processes of brain development, gene expression, and cellular maturation by comparing human-derived brain organoids to those of non-human primates (NHPs). Brain organoids have been established from a variety of NHP pluripotent stem cell (PSC) lines and many protocols are now available for generating brain organoids capable of reproducibly representing specific brain region identities. Innumerous combinations of brain region specific organoids derived from different human and NHP PSCs, with CRISPR-Cas9 gene editing techniques and strategies to promote advanced stages of maturation, will successfully establish complex brain model systems for the accurate representation and elucidation of human brain development. Identified human-specific processes of brain development are likely vulnerable to dysregulation and could result in the identification of therapeutic targets or disease prevention strategies. Here, we discuss the potential of brain organoids to successfully model human-specific processes of brain development and explore current strategies for pinpointing these differences.

Ovariohysterectomy (OVH) is a common procedure in bitches, where ovarian suspensory ligament (OSL) rupture facilitates hemostasis but may also have adverse effects. Given the importance of minimizing the surgical stress response, this study aimed to evaluate the impact of OSL rupture in 20 healthy bitches undergoing elective open OVH; a celiotomy via the ventral midline was performed, and hemostasis achieved using bipolar coagulation, either with OSL rupture (OSL-R) or without (OSL-NR). Pain was assessed over 24 h post-surgery using the Visual Analogue Scale and the Short Form of the Glasgow Composite Measure Pain Scale. The physical parameters, complete blood count, glucose levels, erythrocyte sedimentation rate, and neutrophil oxidative and phagocytic functions were evaluated pre-surgery and at 6, 12, 24, and 48 h, as well as 10 days after. Oxidative metabolism was assessed through vitamin C and protein thiols, reduced glutathione, and thiobarbituric acid reactive substances. No differences in trans- and postoperative pain were observed between techniques, except for analgesic rescue rates. Differences were noted in the heart rate, total leukocyte count, segmented neutrophils, eosinophils, and monocytes. Both techniques resulted in low oxidative and phagocytic changes. Overall, OSL rupture appears to elicit a slightly more intense surgical stress response than the non-rupture technique.

Astrocytes, the most abundant glial cell type in the brain, are underrepresented in traditional cortical organoid models due to the delayed onset of cortical gliogenesis. Here we introduce a new glia-enriched cortical organoid model that exhibits accelerated astrogliogenesis. We demonstrated that induction of a gliogenic switch in a subset of progenitors enabled the rapid derivation of astroglial cells, which account for 25–31% of the cell population within 8–10 weeks of differentiation. Intracerebral transplantation of these organoids reliably generated a diverse repertoire of cortical neurons and anatomical subclasses of human astrocytes. Spatial transcriptome profiling identified layer-specific expression patterns among distinct subclasses of astrocytes within organoid transplants. Using an in vivo acute neuroinflammation model, we identified a subpopulation of astrocytes that rapidly activates pro-inflammatory pathways upon cytokine stimulation. Additionally, we demonstrated that CD38 signaling has a crucial role in mediating metabolic and mitochondrial stress in reactive astrocytes. This model provides a robust platform for investigating human astrocyte function. Transplantation of glia-enriched organoids into the mouse brain enables the study of astrocyte subtypes.

ObjectiveTrigeminal schwannoma (TS), though a rare and benign tumor, becomes a significant surgical challenge due to its intricate location. This study aims to detail the long-term functional outcomes and tumor control post-surgical resection.MethodWe analyzed a multicentric retrospective cohort of 39 patients operated on for a TS in five tertiary centers between January 1993 and July 2022.ResultsSix TS (15%) were in the middle fossa (type M), two (5%) in the posterior fossa (type P), and two (5%) were extracranial (type E). Twenty-nine (75%) were Dumbbell shape: Eighteen (47%) were MP type, seven (18%) were MPE type, and four (10%) were ME type. Fifth nerve symptoms were the foremost preoperative complaint: hypesthesia (51%), trigeminal neuralgia (36%), and paresthesia (30%). We report a favorable evolution course for 61% of preexisting deficits (half of patients with preoperative paresthesia and neuralgia improved while only 5% of preoperative hypesthesia improved). Postoperative hypesthesia was the most frequent de novo deficit 14 (74%) and resolved in solely half the cases. Various approaches were used according to tumor type. Gross total resection (GTR), Subtotal resection (STR), and partial resection (PR) were achieved in respectively 33% (N = 13), 10% (N = 4), and 56% (N = 22) of patients. The mean clinical and radiological FU was 63 months (12 – 283 months). GTR led to no sign of recurrence (mean FU: 60 months – range: 12—283 months). For STR or PR (67%): 23 (88%) were assigned to a Wait-&-rescan policy (WS group) which offered stability in 70% (N = 16). Three cases (8%) underwent a complementary GKS (GammaKnife) on the residual lesion (GK group) without tumor change.ConclusionFor large TS, the completeness of resection must consider the potential functional burden of surgery. With giant infiltrating lesions, a strategy of planned subtotal resection, complemented by radiosurgery, either complementary or uppon regrowth, may provide similar oncological outcomes.