The Dopamine Agonist Bromocriptine Differentially Affects Fronto-Striatal Functional Connectivity During Working Memory

We investigated the effect of bromocriptine, a dopamine agonist, on individual differences in behavior as well as frontal-striatal connectivity during a working memory task. After dopaminergic augmentation, frontal-striatal connectivity in low working memory capacity individuals increases, corresponding with behavioral improvement whereas decreases in connectivity in high working memory capacity individuals are associated with poorer behavioral performance. These findings corroborate an inverted U-shape response of dopamine function in behavioral performance and provide insight on the corresponding neural mechanisms

Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) Significantly Improve Prostate Cancer Detection at Initial Biopsy in a Total PSA Range of 2-10 ng/ml

Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2-10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), %fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p < 0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2-10 ng/ml at initial biopsy, outperforming currently used %fPSA

Depth-specific fluctuations of gene expression and protein abundance modulate the photophysiology in the seagrass <i>Posidonia oceanica</i>

Here we present the results of a multiple organizational level analysis conceived to identify acclimative/adaptive strategies exhibited by the seagrass Posidonia oceanica to the daily fluctuations in the light environment, at contrasting depths. We assessed changes in photophysiological parameters, leaf respiration, pigments, and protein and mRNA expression levels. The results show that the diel oscillations of P. oceanica photophysiological and respiratory responses were related to transcripts and proteins expression of the genes involved in those processes and that there was a response asynchrony between shallow and deep plants probably caused by the strong differences in the light environment. The photochemical pathway of energy use was more effective in shallow plants due to higher light availability, but these plants needed more investment in photoprotection and photorepair, requiring higher translation and protein synthesis than deep plants. The genetic differentiation between deep and shallow stands suggests the existence of locally adapted genotypes to contrasting light environments. The depth-specific diel rhythms of photosynthetic and respiratory processes, from molecular to physiological levels, must be considered in the management and conservation of these key coastal ecosystems

A functional role for the motor system in language understanding: Evidence from Theta-Burst Transcranial Magnetic Stimulation

Does language comprehension depend, in part, on neural systems for action? In previous studies, motor areas of the brain were activated when people read or listened to action verbs, but it remains unclear whether such activation is functionally relevant for comprehension. In the experiments reported here, we used off-line theta-burst transcranial magnetic stimulation to investigate whether a causal relationship exists between activity in premotor cortex and action-language understanding. Right-handed participants completed a lexical decision task, in which they read verbs describing manual actions typically performed with the dominant hand (e.g., “to throw,” “to write”) and verbs describing nonmanual actions (e.g., “to earn,” “to wander”). Responses to manual-action verbs (but not to nonmanual-action verbs) were faster after stimulation of the hand area in left premotor cortex than after stimulation of the hand area in right premotor cortex. These results suggest that premotor cortex has a functional role in action-language understanding

Synergic use of botulinum toxin injection and radial extracorporeal shockwave therapy in multiple sclerosis spasticity

Background and aim: In Multiple Sclerosis (MS) spasticity worsens the patient’s quality of life. Botulinum NeuroToxin TypeA (BoNT-A) is extensively used in focal spasticity, frequently combined with physical therapies. Radial extracorporeal shock waves (rESW) were already used in association with BoNTA. Considering that loss of efficacy and adverse events are determinants of BoNT-A treatment interruption, this study aimed to evaluate the possibility to prolong BoNT-A’s effect by using rESW in MS focal spasticity. Methods: Sixteen MS patients with spasticity of triceps surae muscles were first subjected to BoNT-A therapy and, four months later, to 4 sections of rESWT. Patients were evaluated before, 30, 90 days after the end of the treatments, by using Modified Ashworth Scale (MAS), Modified Tardieu Scale (MTS), and kinematic analysis of passive and active ankle ROM. Results: BoNT-A determined a significant reduction of spasticity evaluated by MAS with a reduction of positive effects after 4months (p&lt;0.05); MTS highlighted the efficacy only 90 days after injection (p&lt;0.05). rESWT decreased MAS values at the end and 30 days later the treatment (p&lt;0.01); MTS values showed instead a prolonged effect (p&lt;0.01). BoNT-A determined a gain of passive and active ankle ROM, persisting along with treatment and peaking the maximum value after rESWT (p&lt;0.05). Conclusions: rESWT can prolong BoNT-A effect inducing a significant reduction of spasticity and improvement in passive and active ankle ROM in MS patients. The use of rESWT following BoNT-A injection is useful to avoid some limitations and to prolong the therapeutic effects of BoNT-A therapy. (www.actabiomedica.it)

From eye care to hair growth: bimatoprost

Background: Bimatoprost has emerged as a significant medication in the field of medicine over the past several decades, with diverse applications in ophthalmology, dermatology, and beyond. Originally developed as an ocular hypotensive agent, it has proven highly effective in treating glaucoma and ocular hypertension. Its ability to reduce intraocular pressure has established it as a first-line treatment option, improving management and preventing vision loss. In dermatology, bimatoprost has shown promising results in the promotion of hair growth, particularly in the treatment of alopecia and hypotrichosis. Its mechanism of action, stimulating the hair cycle and prolonging the growth phase, has led to the development of bimatoprost-containing solutions for enhancing eyelash growth. Aim: The aim of our review is to provide a brief description, overview, and studies in the current literature regarding the versatile clinical use of bimatoprost in recent years. This can help clinicians determine the most suitable individualized therapy to meet the needs of each patient. Methods: Our methods involve a comprehensive review of the latest advancements reported in the literature in bimatoprost formulations, which range from traditional eye drops to sustained-release implants. These innovations offer extended drug delivery, enhance patient compliance, and minimize side effects. Results: The vast literature published on PubMed has confirmed the clinical usefulness of bimatoprost in lowering intraocular pressure and in managing patients with glaucoma. Numerous studies have shown promising results in dermatology and esthetics in promoting hair growth, particularly in treating alopecia and hypotrichosis. Its mechanism of action involves stimulating the hair cycle and prolonging the growth phase, leading to the development of solutions that enhance eyelash growth. The global use of bimatoprost has expanded significantly, with applications growing beyond its initial indications. Ongoing research is exploring its potential in glaucoma surgery, neuroprotection, and cosmetic procedures. Conclusions: Bimatoprost has shown immense potential for addressing a wide range of therapeutic needs through various formulations and advancements. Promising future perspectives include the exploration of novel delivery systems such as contact lenses and microneedles to further enhance drug efficacy and patient comfort. Ongoing research and future perspectives continue to shape its role in medicine, promising further advancements and improved patient outcomes

Selective inhibition of genomic and non-genomic effects of thyroid hormone regulates muscle cell differentiation and metabolic behavior

Thyroid hormones (THs) are key regulators of different biological processes. Their action involves genomic and non-genomic mechanisms, which together mediate the final effects of TH in target tissues. However, the proportion of the two processes and their contribution to the TH-mediated effects are still poorly understood. Skeletal muscle is a classical target tissue for TH, which regulates muscle strength and contraction, as well as energetic metabolism of myofibers. Here we address the different contribution of genomic and non-genomic action of TH in skeletal muscle cells by specifically silencing the deiodinase Dio2 or the β3-Integrin expression via CRISPR/Cas9 technology. We found that myoblast proliferation is inversely regulated by integrin signal and the D2-dependent TH activation. Similarly, inhibition of the nuclear receptor action reduced myoblast proliferation, confirming that genomic action of TH attenuates proliferative rates. Contrarily, genomic and non-genomic signals promote muscle differentiation and the regulation of the redox state. Taken together, our data reveal that integration of genomic and non-genomic signal pathways finely regulates skeletal muscle physiology. These findings not only contribute to the understanding of the mechanisms involved in TH modulation of muscle physiology but also add insight into the interplay between different mechanisms of action of TH in muscle cells

Computational fluid dynamics with imaging of cleared tissue and of in vivo perfusion predicts drug uptake and treatment responses in tumours

Understanding the uptake of a drug by diseased tissue, and the drug’s subsequent spatiotemporal distribution, are central factors in the development of effective targeted therapies. However, the interaction between the pathophysiology of diseased tissue and individual therapeutic agents can be complex, and can vary across tissue types and across subjects. Here, we show that the combination of mathematical modelling, high-resolution optical imaging of intact and optically cleared tumour tissue from animal models, and in vivo imaging of vascular perfusion predicts the heterogeneous uptake, by large tissue samples, of specific therapeutic agents, as well as their spatiotemporal distribution. In particular, by using murine models of colorectal cancer and glioma, we report and validate predictions of steady-state blood flow and intravascular and interstitial fluid pressure in tumours, of the spatially heterogeneous uptake of chelated gadolinium by tumours, and of the effect of a vascular disrupting agent on tumour vasculature