From the Gut to the Brain: Is Microbiota a New Paradigm in Parkinson's Disease Treatment?

Parkinson's disease (PD) is recognized as the second most prevalent primary chronic neurodegenerative disorder of the central nervous system. Clinically, PD is characterized as a movement disorder, exhibiting an incidence and mortality rate that is increasing faster than any other neurological condition. In recent years, there has been a growing interest concerning the role of the gut microbiota in the etiology and pathophysiology of PD. The establishment of a brain-gut microbiota axis is now real, with evidence denoting a bidirectional communication between the brain and the gut microbiota through metabolic, immune, neuronal, and endocrine mechanisms and pathways. Among these, the vagus nerve represents the most direct form of communication between the brain and the gut. Given the potential interactions between bacteria and drugs, it has been observed that the therapies for PD can have an impact on the composition of the microbiota. Therefore, in the scope of the present review, we will discuss the current understanding of gut microbiota on PD and whether this may be a new paradigm for treating this devastating disease.

Do social protection programmes affect the burden of breast and cervical cancer? A systematic review.

Background: Socioeconomic conditions are strongly associated with breast and cervical cancer incidence and mortality patterns; therefore, social protection programmes (SPPs) might impact these cancers. This study aimed to evaluate the effect of SPPs on breast and cervical cancer outcomes and their risk/protective factors. Methods: Five databases were searched for articles that assessed participation in PPS and the incidence, survival, mortality (primary outcomes), screening, staging at diagnosis and risk/protective factors (secondary outcomes) for these cancers. Only peer-reviewed quantitative studies of women receiving SPPs compared to eligible women not receiving benefits were included. Independent reviewers selected articles, assessed eligibility, extracted data, and assessed the risk of bias. A harvest plot represents the included studies and shows the direction of effect, sample size and risk of bias. Findings: Of 17,080 documents retrieved, 43 studies were included in the review. No studies evaluated the primary outcomes. They all examined the relationship between SPPs and screening, as well as risk and protective factors. The harvest plot showed that in lower risk of bias studies, participants of SPPs had lower weight and fertility, were older at sexual debut, and breastfed their infants for longer. Interpretation: No studies have yet assessed the effect of SPPs on breast and cervical cancer incidence, survival, or mortality; nevertheless, the existing evidence suggests positive impacts on risk and protective factors.

Application of 4 birthweight curves and local reference range at a University Hospital of Rio de Janeiro, Brazil.

BACKGROUND: Numerous fetal growth curves have been developed from various subpopulations and geographic locations worldwide. OBJECTIVE: To determine the birthweight standard at the Maternity School and compare it to currently used standards in the clinical practice services. STUDY DESIGN: Cross-sectional, observational, and descriptive study. Data from infants born between 2011 and 2016 were collected from the Maternity School Hospital of the Federal University of Rio de Janeiro to define the 10th, 25th, 50th, 75th, and 90th percentiles of the birthweight by gestational age. It was determined the performance of the INTERGROWTH-21st, Fenton, Alexander, and Lubchenco for the Maternity School standards. RESULTS: After the 33rd week of pregnancy, the INTERGROWTH standard was similar to the local standard for small-for-gestational-age infants and Fenton for large-for-gestational-age infants at Maternity School Hospital. The INTERGROWTH standard was found to be inadequate to classify small-for-gestational-age infants, which are babies at major risk for morbidity and mortality at the onset of the 33rd week of pregnancy. CONCLUSION: It was possible to define reference values for birthweight for the maternal school hospital considering at least 33 weeks of pregnancy with a 95% confidence interval. The comparison of the INTERGROWTH, Fenton, Alexander, and Lubchenko standards to the maternal school hospital curve showed that the Fenton curve was the most suitable for the diagnosis of small for gestational age.

Glial-restricted precursors stimulate endogenous cytogenesis and effectively recover emotional deficits in a model of cytogenesis ablation.

Adult cytogenesis, the continuous generation of newly-born neurons (neurogenesis) and glial cells (gliogenesis) throughout life, is highly impaired in several neuropsychiatric disorders, such as Major Depressive Disorder (MDD), impacting negatively on cognitive and emotional domains. Despite playing a critical role in brain homeostasis, the importance of gliogenesis has been overlooked, both in healthy and diseased states. To examine the role of newly formed glia, we transplanted Glial Restricted Precursors (GRPs) into the adult hippocampal dentate gyrus (DG), or injected their secreted factors (secretome), into a previously validated transgenic GFAP-tk rat line, in which cytogenesis is transiently compromised. We explored the long-term effects of both treatments on physiological and behavioral outcomes. Grafted GRPs reversed anxiety-like deficits and demonstrated an antidepressant-like effect, while the secretome promoted recovery of only anxiety-like behavior. Furthermore, GRPs elicited a recovery of neurogenic and gliogenic levels in the ventral DG, highlighting the unique involvement of these cells in the regulation of brain cytogenesis. Both GRPs and their secretome induced significant alterations in the DG proteome, directly influencing proteins and pathways related to cytogenesis, regulation of neural plasticity and neuronal development. With this work, we demonstrate a valuable and specific contribution of glial progenitors to normalizing gliogenic levels, rescuing neurogenesis and, importantly, promoting recovery of emotional deficits characteristic of disorders such as MDD.

Electrochemical Diselenation of BODIPY Fluorophores for Bioimaging Applications and Sensitization of 1 O2.

Invited for the cover of this issue are the groups of Holger Braunschweig at the Julius-Maximilians-Universität Würzburg, Germany and Eufrânio N. da Silva Júnior at the Universidade Federal de Minas Gerais, UFMG, Brazil. The image depicts the electrochemical synthesis of selenium-containing BODIPY molecules with lightning symbolizing the electrifying synthetic process, while the surrounding elemental chaos hints at the red-shifted absorption and emission and the transformative photophysical properties of these new compounds. Read the full text of the article at 10.1002/chem.202303883.

A morphofunctional study of the jumping apparatus in globular springtails.

Springtails are notable for their jumping apparatus and latch-mediated spring mechanism. The challenge, in the light of the tiny size and rapid movement of these organisms, has been to understand the morphological intricacies of this spring system. This study takes an approach that integrates SEM, MicroCT, cLSM and high-speed video recordings to understand the composition and functionality of the jumping apparatus in Megalothorax minimus (Neelipleona), Dicyrtomina ornata and Dicyrtomina minuta (Symphypleona). We focus on reconstructing, describing, and understanding the functioning of structures such as basal plates, musculature and furca. The dimensions of the jumping apparatus in Dicyrtomina and Megalothorax differ significantly from those in elongated springtails. A hypothesis of functional coherence between taxa, based on muscle connections and basal plates, is postulated. High-speed video recordings provide information on: 1) furca release timing and function during jumping and self-righting; 2) performance properties of manubrium, dens and mucro in interaction with the ground and in take-off; 3) possible pre-release furca moves. The study underscores the need for further research employing a variety of visualization methods in order to explore additional aspects such as retinaculum unlatching and furca flexion/extension muscles.

Selective excavation and ozone therapy: new frontier of mini-invasive caries treatment in MIH paediatric patients. A case report.

BACKGROUND: The term hypomineralisation of molars and incisors (MIH), introduced in 2001 by Weerheijm et al., describes a clinical state of hypomineralisation of permanent molars with frequent involvement of the incisors. MIH is considered a global dental problem with a prevalence ranging from 2.4% to 40.2% in the entire world paediatric population. The continuous increase in the prevalence of enamel anomalies, including MIH, indicates the need to define new intervention protocols based on the technological advances that are revolutionising paediatric dentistry. The use of ozone associated with the selective and minimally invasive excavation of the dental tissue combines the antibacterial properties of the gas with an ultra-conservative approach aimed at the maximum conservation of the dental tissue. The operative protocol described can be an important tool in the prevention and treatment of MIH. The aim of this work is to illustrate an operative clinical protocol based on the combined use of selective excavation and ozone for the treatment of carious lesions in paediatric patients with MIH.

Electrochemical Diselenation of BODIPY Fluorophores for Bioimaging Applications and Sensitization of 1 O2.

We report a rapid, efficient, and scope-extensive approach for the late-stage electrochemical diselenation of BODIPYs. Photophysical analyses reveal red-shifted absorption - corroborated by TD-DFT and DLPNO-STEOM-CCSD computations - and color-tunable emission with large Stokes shifts in the selenium-containing derivatives compared to their precursors. In addition, due to the presence of the heavy Se atoms, competitive ISC generates triplet states which sensitize 1 O2 and display phosphorescence in PMMA films at RT and in a frozen glass matrix at 77 K. Importantly, the selenium-containing BODIPYs demonstrate the ability to selectively stain lipid droplets, exhibiting distinct fluorescence in both green and red channels. This work highlights the potential of electrochemistry as an efficient method for synthesizing unique emission-tunable fluorophores with broad-ranging applications in bioimaging and related fields.

Piriform Rim Asymmetry in Unilateral Cleft Lip and Palate Patients Before Orthognathic Surgery.

BACKGROUND: Complete unilateral cleft lip and palate (UCLP) creates a continuity defect on the nasal floor, which contributes to nasal asymmetry. Traditionally, piriform rim symmetry has been evaluated by comparing cleft and noncleft sides. No study has compared the magnitude of perinasal asymmetry in UCLP patients with a control group of patients without clefts. PURPOSE: To address the following question: In UCLP patients, whose alveolar clefts are reconstructed with alveolar bone grafts (ABGs), is the magnitude of remaining piriform rim asymmetry similar to that of patients without UCLP? STUDY DESIGN SETTING, SAMPLE: This is a retrospective cohort study that used the cone beam computed tomography of UCLP and non-UCLP patients to evaluate the piriform rim symmetry. The sample was derived from patients who presented for orthognathic surgery between January 2015 and December 2022. To be included, patients had to have a maxillary deficiency. The cleft group had ABG performed with symphyseal bone harvest and bone morphogenetic protein application. Patients were excluded from the control group if they had clinical asymmetry and nasal septum deviation. Patients from the UCLP group were excluded if they failed the first attempt of ABG or had a syndrome. Preorthognathic cone beam computed tomography was used to measure the distance from the inferior and lateral aspects of the piriform rim to reference lines. PREDICTOR VARIABLE: UCLP status grouped as present or absent (control). OUTCOME VARIABLES: The magnitude of piriform rim asymmetry defined as the millimetric distance from the inferior and lateral aspects of the piriform rim to reference lines. COVARIATES: The covariates were age, sex, tissue thickness at the level of the alar base, and turbinate size. ANALYSIS: Welch's two-sample t-test was utilized to compare means. A level of significance of 5% (P < .05) was used for all analyses. To analyze the reliability of the measurements intraexaminer and interexaminer errors were tested using the Weir method. RESULTS: A total of 60 patients were included, 30 in each group. The mean age of UCLP patients was 16.76 (range 13 to 25), and the control group was 17 (range 13 to 25), P = .71. The UCLP group had 12 girls, and the control had 18 girls (P = .12). In the UCLP group, the mean discrepancy between affected and unaffected sides at the inferior aspect of the piriform rim was 3.9 mm (range 0.9 to 7 mm, P < .01), and in the control group the discrepancy between right and left sides was 0.1 mm (0-2.1 mm, P = .87). The mean discrepancy between affected and unaffected sides at the lateral aspect of the piriform rim was 3.6 mm (range 0.7 to 7.6 mm, P < .01) in the UCLP group, and in the control group the discrepancy between right and left sides was 0.1 mm (range 0.1 to 5.8 mm, P = .78) in the control group. The mean alar base soft tissue thickness discrepancy was 3.1 mm (range 0.9 to 7.9 mm, P < .01) in the UCLP group and 0 mm (range -1.8 to 1.9 mm, P = .97) in the control group. The mean difference in the turbinate area in the UCLP group was 314 mm2 (range 797 to 2,898) and in the control group 35 mm2 (range 702 to 2,302) (P = .19). CONCLUSION: ABG with symphyseal bone and bone morphogenetic protein was not able to provide the same level of piriform symmetry observed in patients without a cleft. Alar base tissue was thicker on the cleft side, and the turbinate size demonstrated greater variability in the UCLP patients.

P2Y12 inhibitor monotherapy versus dual antiplatelet therapy in patients with acute coronary syndromes undergoing coronary stenting: rationale and design of the NEOMINDSET Trial

Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y12 inhibitor is safe and associated with less bleeding. However, to date, no randomised trial has tested the impact of initiating SAPT immediately after PCI, particularly in patients with acute coronary syndromes (ACS). NEOMINDSET is a multicentre, randomised, open-label trial with a blinded outcome assessment designed to compare SAPT versus DAPT in 3,400 ACS patients undergoing PCI with the latest-generation drug-eluting stents (DES). After successful PCI and up to 4 days following hospital admission, patients are randomised to receive SAPT with a potent P2Y12 inhibitor (ticagrelor or prasugrel) or DAPT (aspirin plus a potent P2Y12 inhibitor) for 12 months. Aspirin is discontinued immediately after randomisation in the SAPT group. The choice between ticagrelor and prasugrel is at the investigator's discretion. The primary hypothesis is that SAPT will be non-inferior to DAPT with respect to the composite endpoint of all-cause mortality, stroke, myocardial infarction or urgent target vessel revascularisation, but superior to DAPT on rates of bleeding defined by Bleeding Academic Research Consortium 2, 3 or 5 criteria. NEOMINDSET is the first study that is specifically designed to test SAPT versus DAPT immediately following PCI with DES in ACS patients. This trial will provide important insights on the efficacy and safety of withdrawing aspirin in the early phase of ACS.

From ecological functions to ecosystem services: linking coastal lagoons biodiversity with human well-being.

In this review we highlight the relevance of biodiversity that inhabit coastal lagoons, emphasizing how species functions foster processes and services associated with this ecosystem. We identified 26 ecosystem services underpinned by ecological functions performed by bacteria and other microbial organisms, zooplankton, polychaetae worms, mollusks, macro-crustaceans, fishes, birds, and aquatic mammals. These groups present high functional redundancy but perform complementary functions that result in distinct ecosystem processes. Because coastal lagoons are located in the interface between freshwater, marine and terrestrial ecosystems, the ecosystem services provided by the biodiversity surpass the lagoon itself and benefit society in a wider spatial and historical context. The species loss in coastal lagoons due to multiple human-driven impacts affects the ecosystem functioning, influencing negatively the provision of all categories of services (i.e., supporting, regulating, provisioning and cultural). Because animals' assemblages have unequal spatial and temporal distribution in coastal lagoons, it is necessary to adopt ecosystem-level management plans to protect habitat heterogeneity and its biodiversity, ensuring the provision of services for human well-being to multi-actors in the coastal zone.

Regenerative Engineering of a Biphasic Patient-Fitted Temporomandibular Joint Condylar Prosthesis.

Regenerative medicine approaches to restore the mandibular condyle of the temporomandibular joint (TMJ) may fill an unmet patient need. In this study, a method to implant an acellular regenerative TMJ prosthesis was developed for orthotopic implantation in a pilot goat study. The scaffold incorporated a porous, polycaprolactone-hydroxyapatite (PCL-HAp, 20wt% HAp) 3D printed condyle with a cartilage-matrix-containing hydrogel. A series of material characterizations was used to determine the structure, fluid transport, and mechanical properties of 3D printed PCL-HAp. To promote marrow uptake for cell seeding, a scaffold pore size of 152 ± 68 µm resulted in a whole blood transport initial velocity of 3.7 ± 1.2 mm·s-1 transported to the full 1 cm height. The Young's modulus of PCL was increased by 67% with the addition of HAp, resulting in a stiffness of 269 ± 20 MPa for etched PCL-HAp. In addition, the bending modulus increased by 2.06-fold with the addition of HAp to 470 MPa for PCL-HAp. The prosthesis design with an integrated hydrogel was compared with unoperated contralateral control and no-hydrogel group in a goat model for 6 months. A guide was used to make the condylectomy cut, and the TMJ disc was preserved. MicroCT assessment of bone suggested variable tissue responses with some regions of bone growth and loss, although more loss may have been exhibited by the hydrogel group than the no-hydrogel group. A benchtop load transmission test suggested that the prosthesis was not shielding load to the underlying bone. Although variable, signs of neocartilage formation were exhibited by Alcian blue and collagen II staining on the anterior, functional surface of the condyle. Overall, this study demonstrated signs of functional TMJ restoration with an acellular prosthesis. There were apparent limitations to continuous, reproducible bone formation, and stratified zonal cartilage regeneration. Future work may refine the prosthesis design for a regenerative TMJ prosthesis amenable to clinical translation.

P2Y12 inhibitor monotherapy versus dual antiplatelet therapy in patients with acute coronary syndromes undergoing coronary stenting: rationale and design of the NEOMINDSET Trial.

Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y12 inhibitor is safe and associated with less bleeding. However, to date, no randomised trial has tested the impact of initiating SAPT immediately after PCI, particularly in patients with acute coronary syndromes (ACS). NEOMINDSET is a multicentre, randomised, open-label trial with a blinded outcome assessment designed to compare SAPT versus DAPT in 3,400 ACS patients undergoing PCI with the latest-generation drug-eluting stents (DES). After successful PCI and up to 4 days following hospital admission, patients are randomised to receive SAPT with a potent P2Y12 inhibitor (ticagrelor or prasugrel) or DAPT (aspirin plus a potent P2Y12 inhibitor) for 12 months. Aspirin is discontinued immediately after randomisation in the SAPT group. The choice between ticagrelor and prasugrel is at the investigator's discretion. The primary hypothesis is that SAPT will be non-inferior to DAPT with respect to the composite endpoint of all-cause mortality, stroke, myocardial infarction or urgent target vessel revascularisation, but superior to DAPT on rates of bleeding defined by Bleeding Academic Research Consortium 2, 3 or 5 criteria. NEOMINDSET is the first study that is specifically designed to test SAPT versus DAPT immediately following PCI with DES in ACS patients. This trial will provide important insights on the efficacy and safety of withdrawing aspirin in the early phase of ACS. (ClinicalTrials.gov: NCT04360720).

Effect of kelp gull harassment on southern right whale calf survival: a long-term capture-recapture analysis.

Kelp gulls (Larus dominicanus) commonly feed on the skin and blubber of surfacing southern right whales (SRW, Eubalaena australis) in the near shore waters of Península Valdés (PV), Argentina. Mothers and especially calves respond to gull attacks by changing their swimming speeds, resting postures and overall behaviour. Gull-inflicted wounds per calf have increased markedly since the mid-1990s. Unusually high mortality of young calves occurred locally after 2003, and increasing evidence points to gull harassment as a factor contributing to the excess deaths. After leaving PV, calves undertake a long migration with their mothers to summer feeding areas; their health during this strenuous exertion is likely to affect their probabilities of first-year survival. To explore the effects of gull-inflicted wounds on calf survival, we analysed 44 capture-recapture observations between 1974 and 2017, for 597 whales photo-identified in their years of birth between 1974 and 2011. We found a marked decrease in first-year survival associated with an increase in wound severity over time. Our analysis supports recent studies indicating that gull harassment at PV may impact SRW population dynamics.

The prevalence and perinatal repercussions of preeclampsia after the implementation of a prophylaxis protocol with aspirin.

OBJECTIVES: To evaluate the prevalence and perinatal repercussions of preeclampsia (PE) after the implementation of a prophylaxis protocol with aspirin in singleton pregnancy at Maternity School of Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (2015-2106). METHODOLOGY: PE prevalence according to gestational age (GA) and the prevalence ratio (PR) between PE and prematurity, small for gestational age (SGA), and fetal death were calculated in patients assisted during 2015 and 2016. RESULTS: PE occurred in 373(10.75%) of 3468 investigated cases, where PE < 37 weeks was of 2.79% and PE greater than 37 weeks was of 7.95%. A total of 413 (11.9%) prematurity cases, 320 SGA (9.22%), and 50 fetal deaths (1.44%) occurred. In the PE group, 97 premature newborns (PR 0.90) and 51 SGA (PR 1.16) were born, and two fetal deaths occurred (PR 7.46). Concerning PE < 37 weeks, 27 SGA cases (PR 1.42) and two fetal deaths (PR 2.62) were observed. Regarding PE greater than 37 weeks, 24 SGA (PR 1.09) were born, and no fetal deaths were observed. Our findings were compared to previously published results. CONCLUSIONS: PE was significantly associated with SGA newborns, especially premature PE. Prescribing aspirin for PE prophylaxis based only on clinical risk factors in a real-life scenario does not appear to be effective but resulted in a PE screening and prophylaxis protocol review and update at ME/UFRJ.

N-Acetylcysteine Treatment May Compensate Motor Impairments through Dopaminergic Transmission Modulation in a Striatal 6-Hydroxydopamine Parkinson's Disease Rat Model.

Preventing degeneration and the loss of dopaminergic neurons (DAn) in the brain while mitigating motor symptoms remains a challenge in Parkinson's Disease (PD) treatment development. In light of this, developing or repositioning potential disease-modifying approaches is imperative to achieve meaningful translational gains in PD research. Under this concept, N-acetylcysteine (NAC) has revealed promising perspectives in preserving the dopaminergic system capability and modulating PD mechanisms. Although NAC has been shown to act as an antioxidant and (neuro)protector of the brain, it has yet to be acknowledged how this repurposed drug can improve motor symptomatology and provide disease-modifying properties in PD. Therefore, in the present work, we assessed the impact of NAC on motor and histological deficits in a striatal 6-hydroxydopamine (6-OHDA) rat model of PD. The results revealed that NAC enhanced DAn viability, as we found that it could restore dopamine transporter (DAT) levels compared to the untreated 6-OHDA group. Such findings were positively correlated with a significant amelioration in the motor outcomes of the 6-OHDA-treated animals, demonstrating that NAC may, somehow, be a modulator of PD degenerative mechanisms. Overall, we postulated a proof-of-concept milestone concerning the therapeutic application of NAC. Nevertheless, it is extremely important to understand the complexity of this drug and how its therapeutical properties interact with the cellular and molecular PD mechanisms.

On latches in biological systems: a comparative morphological and functional study of the retinaculum and the dens lock in Collembola.

BACKGROUND: Springtails have the ability to jump using morphological structures consisting of a catapult, the furca, and a latching system constructed with interaction of the retinaculum and the dens lock. The retinaculum engages in the furca at the dens lock in order to form a spring mechanism. They exhibit diversified morphological traits that serve as adaptations to a variety of terrestrial strata and aquatic surface environments. This comparative morphofunctional study centered on the retinaculum and the furcular region of the dens lock aims to describe the morphological variation between taxa and provide insights into the functional dynamics of the latching mechanism at work in the jumping apparatus. Using SEM, µCT and cLSM, we compared representatives of Collembola taxa, Poduromorpha (Neanura muscorum and Podura aquatica), Symphypleona (Dicyrtomina ornata) and Neelipleona (Megalothorax minimus), and examined extracts of the environment in which they were collected. RESULTS: A retinaculum is absent in N. muscorum, although vestigial muscles were found. Abdominal musculature varies significantly, being more abundant in springtails with clear segmentation (N. muscorum and P. aquatica), and reduced in springtails with fused segmentation (D. ornata and M. minimus). The M.a-ret varies as regards architecture and point of connection with the ramus, which is lateral in P. aquatica and median in the other species studied. The number of teeth in the retinaculum ramus also varies between three in M. minimus and four in the other species. The dens lock of all species studied has two locks and two furrows. CONCLUSIONS: The retinaculum and dens lock interact in a key-lock relationship. The latching and unlatching mechanism from the retinaculum and dens lock appear to be similar in all the taxa examined, occurring by muscle force. This leads us to question the hypothesis that hemolymph pressure may be a force generator in jumping. We offer a reconstruction of the ground pattern of the retinaculum and dens lock and, in addition, an explanation of their functioning and the interaction between them. Finally, we frame the interaction between the retinaculum and the dens lock as a latch in a biological system, a mechanism which functions by force of physical contact.