Stereotactic anatomy of the third ventricle.

PURPOSE: Endoscopic third ventriculostomy (ETV) is a surgical procedure that can lead to complications and requires detailed preoperative planning. This study aimed to provide a more accurate understanding of the anatomy of the third ventricle and the location of important structures to improve the safety and success of ETV. METHODS: We measured the stereotactic coordinates of six points of interest relative to a predefined stereotactic reference point in 23 cadaver brain hemi-sections, 200 normal brain magnetic resonance imaging (MRI) scans, and 24 hydrocephalic brain MRI scans. The measurements were statistically analyzed, and comparisons were made. RESULTS: We found some statistically significant differences between genders in MRIs from healthy subjects. We also found statistically significant differences between MRIs from healthy subjects and both cadaver brains and MRIs with hydrocephalus, though their magnitude is very small and not clinically relevant. Some stereotactic points were more posteriorly and inferiorly located in cadaver brains, particularly the infundibular recess and the basilar artery. It was found that all stereotactic points studied were more posteriorly located in brains with hydrocephalus. CONCLUSION: The study describes periventricular structures in cadaver brains and MRI scans from healthy and hydrocephalic subjects, which can guide neurosurgeons in planning surgical approaches to the third ventricle. Overall, the study contributes to understanding ETV and provides insights for improving its safety and efficacy. The findings also support that practicing on cadaveric brains can still provide valuable information and is valid for study and training of neurosurgeons unfamiliar with the ETV technique.

Chemical Characterization and Bioactivity of Commercial Essential Oils and Hydrolates Obtained from Portuguese Forest Logging and Thinning.

Essential oils (EOs) and hydrolates (Hds) are natural sources of biologically active ingredients with broad applications in the cosmetic industry. In this study, nationally produced (mainland Portugal and Azores archipelago) EOs (11) and Hds (7) obtained from forest logging and thinning of Eucalyptus globulus, Pinus pinaster, Pinus pinea and Cryptomeria japonica, were chemically evaluated, and their bioactivity and sensorial properties were assessed. EOs and Hd volatiles (HdVs) were analyzed by GC-FID and GC-MS. 1,8-Cineole was dominant in E. globulus EOs and HdVs, and α- and ß-pinene in P. pinaster EOs. Limonene and α-pinene led in P. pinea and C. japonica EOs, respectively. P. pinaster and C. japonica HVs were dominated by α-terpineol and terpinen-4-ol, respectively. The antioxidant activity was determined by DPPH, ORAC and ROS. C. japonica EO showed the highest antioxidant activity, whereas one of the E. globulus EOs showed the lowest. Antimicrobial activity results revealed different levels of efficacy for Eucalyptus and Pinus EOs while C. japonica EO showed no antimicrobial activity against the selected strains. The perception and applicability of emulsions with 0.5% of EOs were evaluated through an in vivo sensory study. C. japonica emulsion, which has a fresh and earthy odour, was chosen as the most pleasant fragrance (60%), followed by P. pinea emulsion (53%). In summary, some of the studied EOs and Hds showed antioxidant and antimicrobial activities and they are possible candidates to address the consumers demand for more sustainable and responsibly sourced ingredients.

The Cofilin/Limk1 Pathway Controls the Growth Rate of Both Developing and Regenerating Motor Axons.

Regenerating axons often have to grow considerable distances to reestablish circuits, making functional recovery a lengthy process. One solution to this problem would be to co-opt the "temporal" guidance mechanisms that control the rate of axon growth during development to accelerate the rate at which nerves regenerate in adults. We have previously found that the loss of Limk1, a negative regulator of cofilin, accelerates the rate of spinal commissural axon growth. Here, we use mouse models to show that spinal motor axon outgrowth is similarly promoted by the loss of Limk1, suggesting that temporal guidance mechanisms are widely used during development. Furthermore, we find that the regulation of cofilin activity is an acute response to nerve injury in the peripheral nervous system. Within hours of a sciatic nerve injury, the level of phosphorylated cofilin dramatically increases at the lesion site, in a Limk1-dependent manner. This response may be a major constraint on the rate of peripheral nerve regeneration. Proof-of-principle experiments show that elevating cofilin activity, through the loss of Limk1, results in faster sciatic nerve growth, and improved recovery of some sensory and motor function.SIGNIFICANCE STATEMENT The studies shed light on an endogenous, shared mechanism that controls the rate at which developing and regenerating axons grow. An understanding of these mechanisms is key for developing therapies to reduce painful recovery times for nerve-injury patients, by accelerating the rate at which damaged nerves reconnect with their synaptic targets.

Real-world effectiveness of palbociclib plus fulvestrant in advanced breast cancer: Results from a population-based cohort study.

BACKGROUND: Real-world (RW) data may provide valuable information on the effectiveness and safety of medicines, which is particularly relevant for clinicians, patients and third-party payers. Evidence on the effectiveness of palbociclib plus fulvestrant is scarce, which highlights the need of additional studies. The aim of this study was to evaluate the effectiveness of palbociclib plus fulvestrant in advanced breast cancer (ABC). MATERIALS AND METHODS: We conducted a population-based retrospective cohort study and cases of interest were identified through the Portuguese National Cancer Registry database and additional data sources. Patients aged≥18 years, diagnosed with ABC and exposed to palbociclib plus fulvestrant between May 31, 2017 and March 31, 2019 were included. Patients were followed-up until death or cut-off date (February 28, 2021). Primary outcome was rw-progression-free survival (rwPFS). Secondary outcomes were rw-overall survival (rwOS), rw-time to palbociclib failure (rwTPF) and rw-time to next treatment (rwTTNT). RESULTS: A total of 210 patients were included. Median age was 58 years (range 29-83) and 99.05% were female. Median follow-up time was 23.22 months and, at cut-off date, treatment had been discontinued in 189 patients, mainly due to disease progression (n = 152). Median rwPFS was 7.43 months (95% confidence interval [CI] 6.28-9.05) and 2-year rwPFS was 16.65% (95%CI 11.97-22.00). Median rwOS was 24.70 months (95%CI 21.58-29.27), median rwTPF was 7.5 months (95%CI 6.51-9.08) and median rwTTNT was 11.74 months (95%CI 10.33-14.08). CONCLUSION: Palbociclib plus fulvestrant seems an effective treatment for ABC in real-world context. Compared to registrations studies, rwPFS and rwOS were shorter in real-life setting.

Translation, Cross-Cultural Adaptation, and Measurement Properties of the Portuguese Version of the Global Trigger Tool for Adverse Events.

PURPOSE: To adapt and validate the Global Trigger Tool (IHI-GTT), which identifies and analyzes adverse events (AE) in hospitalized patients and their measurement properties in the Portuguese context. METHODS: A retrospective cross-sectional study was based on a random sample of 90 medical records. The stages of translation and cross-cultural adaptation of the IHI-GTT were based on the Cross-Cultural Adaptation Protocol that originated from the Portuguese version, GTT-PT, for the hospital context in medical-surgical departments. Internal consistency, reliability, reproducibility, diagnostic tests, and discriminatory predictive value were investigated. RESULTS: The final phase of the GTT-PT showed insignificant inconsistencies. The pre-test phase confirmed translation accuracy, easy administration, effectiveness in identifying AEs, and relevance of integrating it into hospital risk management. It had a sensitivity of 97.8% and specificity of 74.8%, with a cutoff point of 0.5, an accuracy of 83%, and a positive predictive value of 69.8% and a negative predictive value of 0.98%. CONCLUSION: The GTT-PT is a reliable, accurate, and valid tool to identify AE, with robust measurement properties.

Recovery of motricity and micturition after transplantation of mesenchymal stem cells in rats subjected to spinal cord injury.

The objective was to evaluate the effect of human adipose-derived stem cell (hADSC) infusion on impaired hindlimb function and urinary continence after spinal cord contusion in rats. hADSCs were transplanted into the injured spinal cords of rats 7 and 14 days after injury in two groups (B and C). Group C also received methylprednisolone sodium succinate (MPSS) after 3 h of injury. The control group (group A) did not receive corticoids or stem cells. Voiding and motor performance evaluations were performed daily for 90 days post-transplantation. Cells were labeled with PKH26 or PKH67 for in vitro monitoring. For in vivo screening, the cells were evaluated for bioluminescence. The levels of some cytokines were quantified in different times. Euthanasia was performed 90 days post-transplant. ß-tubulin III expression was evaluated in the spinal cord of the animals from all groups. As a result, we observed a recovery of 66.6 % and 61.9 % in urinary continence of animals from groups B and C, respectively. Partial recovery of motor was observed in 23.8 % and 19 % of the animals from groups B and C, respectively. Cells remained viable at the site up to 90 days after transplantation. No significant difference was observed in levels of cytokines and thickness of urinary bladders between groups. A smaller percentage of tissue injury and higher concentrations of neuropils were observed in the spinal cords of the animals from groups B and C than control group. Thus, hADSCs transplantation with or without MPSS, contributed to the improvement in voiding and motor performance of Wistar rats submitted to compressive spinal cord injury.

Trends in net survival from stomach cancer in six European Latin countries: results from the SUDCAN population-based study.

Gastric cancers are a clinical challenge. The aim of the SUDCAN collaborative study was to compare the net survival from gastric cancer between six European Latin countries (Belgium, France, Italy, Portugal, Spain and Switzerland) and explore the trends in net survival and in the dynamics of the excess mortality rates (EMRs) up to 5 years after diagnosis. The data were extracted from the EUROCARE-5 database. First, net survival was studied over the period 2000-2004 using the Pohar-Perme estimator. For trend analyses, the study period was specific to each country. The results are reported from 1992 to 2004 in France, Italy, Spain and Switzerland and from 2000 to 2004 in Belgium and Portugal. These trend analyses were carried out using a flexible excess rate modelling strategy. There were little differences between countries in age-standardized net survival for stomach cancer (2000-2004). The 5-year net survival ranged between 26 (Spain) and 32% (Italy). There was a small increase in the age-standardized net survival at 1 year between 1992 and 2004. The increase was also observed in the 5-year net survival, except in France, where the increase was less marked. A slight decrease in the EMR between 1992 and 2004 was limited to the 24 months after diagnosis. In addition, the decrease in the EMR was the same whatever the year of diagnosis. There were minor differences in survival from stomach cancer between European Latin countries. A slight improvement in the 5-year net survival was observed in all countries and the major gain was observed during the 24 months after diagnosis. Development of innovative treatments is needed to improve the prognosis.

Study of structure and orientation of mesentericin Y105, a bacteriocin from Gram-positive Leuconostoc mesenteroides, and its Trp-substituted analogues in phospholipid environments.

Mesentericin Y105 (Mes-Y105) is a bacteriocin secreted by Leuconostoc mesenteroides which is particularly active on Listeria. It is constituted by 37 residues and reticulated by one disulfide bridge. It has two W residues, W18 and W37, which can be studied by fluorescence. Two single substituted W/F analogues were synthesized (Mes-Y105/W18 and Mes-Y105/W37) to differentiate the local environment around each W and to study their changes in the presence of lipid vesicles. Fluorescence experiments show that, for the pure Trp-analogues, W18 and W37 are fully exposed to solvent whatever pH and buffer conditions. In the presence of lipid vesicles, both became buried. Lipid affinities were estimated: they are weak for zwitterionic phospholipids but an order of magnitude higher for negatively charged phosphatidylserine (PS) and phosphatidylglycerol (PG) lipids. On negatively charged PG lipids, Mes-Y105 and Mes-Y105/W37 display comparable lipid affinities. A decrease in lipid affinity is observed for Mes-Y105/W18 compared to Mes-Y105, which means that W37 would seem to be required for increased lipid selectivity. In the lipid-bound state W18 is strongly dehydrated, probably embedded into the acyl chains, while W37 stands more at the interface. Mes-Y105 was also studied by polarization modulation infrared reflection absorption spectroscopy (PMIRRAS), alone and in various phospholipid environments, to obtain structural information and to assess lipid perturbations. At nanomolar concentrations close to those required for anti-Listeria activity, Mes-Y105 forms films at the air/water interface and inserts into negatively charged lipid monolayers. In situ infrared data show that Mes-Y105 binding only affects the polar head group vibrations while the lipid order of the acyl chains remains unaffected. The PMIRRAS show that Mes-Y105 folds into an N-terminal antiparallel beta-sheet followed by an alpha-helix, both structures being tilted (40 degrees) compared to the normal at the interface, which is in agreement with the thickness estimated by Brewster angle microscopy (BAM). All these data support the proposal of a new model for Mes-Y105 at the membrane interface.

Cytogenetic analyses using C-banding and DAPI/CMA3 staining of four populations of the maize weevil Sitophiluszeamais Motschulsky, 1855 (Coleoptera, Curculionidae).

Cytogenetic data avalaible for the maize weevil Sitophiluszeamais Motschulsky, 1855 (Coleoptera: Curculionidae), one of the most destructive pests of stored cereal grains, are controversial. Earlier studies focused on single populations and emphasized chromosome number and sex determination system. In this paper, the karyotypes of four populations of Sitophiluszeamais were characterized by conventional staining, C-banding and sequential staining with the fluorochromes chromomycin-A3/4-6-diamidino-2-phenylindole (CMA3/DAPI). The analyses of metaphases obtained from the cerebral ganglia of last instar larvae and the testes of adults showed that the species had 2n = 22 chromosomes, with 10 autosomal pairs and a sex chromosome pair (XX in females and Xyp in males). Chromosome number, however, ranged from 2n = 22 to 26 due to the presence of 0-4 supernumerary chromosomes in individuals from the populations of Viçosa, Unai and Porto Alegre. With the exception of the Y chromosome, which was dot-like, all other chromosomes of this species were metacentric, including the supernumeraries. The heterochromatin was present in the centromeric regions of all autosomes and in the centromere of the X chromosome. The B chromosomes were partially or totally heterochromatic, and the Y chromosome was euchromatic. The heterochromatic regions were labeled with C-banding and DAPI, which showed that they were rich in AT base pairs.

Human serum is a suitable supplement for the osteogenic differentiation of human adipose-derived stem cells seeded on poly-3-hydroxibutyrate-co-3-hydroxyvalerate scaffolds.

Human adipose-derived stem cells (hASCs) are currently a point of focus for bone tissue engineering applications. However, the ex vivo expansion of stem cells before clinical application remains a challenge. Fetal bovine serum (FBS) is largely used as a medium supplement and exposes the recipient to infections and immunological reactions. In this study, we evaluated the osteogenic differentiation process of hASCs in poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHB-HV) scaffolds with the osteogenic medium supplemented with pooled allogeneic human serum (aHS). The hASCs grown in the presence of FBS or aHS did not show remarkable differences in morphology or immunophenotype. The PHB-HV scaffolds, which were developed by the freeze-drying technique, showed an adequate porous structure and mechanical performance as observed by micro-computed tomography, scanning electron microscopy (SEM), and compression test. The three-dimensional structure was suitable for allowing cell colonization, which was revealed by SEM micrographs. Moreover, these scaffolds were not toxic to cells as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The differentiation capacity of hASCs seeded on scaffolds was confirmed by the reduction of the proliferation, the alkaline phosphatase (AP) activity, expression of osteogenic gene markers (AP, collagen type I, Runx2, and osteocalcin), and the expression of bone markers, such as osteopontin, osteocalcin, and collagen type I. The osteogenic capacity of hASCs seeded on PHB-HV scaffolds indicates that this scaffold is adequate for cell growth and differentiation and that aHS is a promising supplement for the in vitro expansion of hASCs. In conclusion, this strategy seems to be useful and safe for application in bone tissue engineering.

Stereological evaluation of the seminiferous tubules of rats after maternal undernutrition during the lactation period.

The goal of this study is to evaluate, through stereological methods, some structural aspects of offspring testes whose dams were submitted to protein and energy-restricted diets during the lactation period. At birth, dams were separated into 3 groups: control group (C), receiving a diet with 23% protein; protein-restricted group (PR), receiving a diet with 8% protein; energy-restricted group (ER), receiving a diet with 23% protein in restricted quantities. At weaning, the offspring was anesthetized and perfused with formalin solution. Then, the testes were excised and processed using routine histological methods. Compared to the C group, both PR and ER groups had a significant reduction in the testis weight (PR = 65%, ER = 60%, p < 0.01), in the total area (PR = 23%, ER = 32%, p < 0.01), in the luminal area (PR = 30%, ER = 36%, p < 0.01), in the epithelial area (PR = 21%, ER = 27%, p < 0.01), and in the epithelial height (PR = 17%, ER = 23%, p < 0.01) of the seminiferous tubule. We conclude that maternal malnutrition during lactation leads to structural changes in the testis that could be responsible for future alterations in this organ physiology.