Biocompatibility of Platinum Nanoparticles in Brain ex vivo Models in Physiological and Pathological Conditions

Platinum nanoparticles (PtNPs) have unique physico-chemical properties that led to their use in many branches of medicine. Recently, PtNPs gathered growing interest as delivery vectors for drugs, biosensors and as surface coating on chronically implanted biomedical devices for improving electrochemical properties. However, there are contradictory statements about their biocompatibility and impact on target organs such as the brain tissue, where these NPs are finding many applications. Furthermore, many of the reported studies are conducted in homeostasis conditions and, consequently, neglect the impact of the pathologic conditions on the tissue response. To expand our knowledge on the effects of PtNPs on neuronal and glial cells, we investigated the acute effects of monodisperse sodium citrate-coated PtNPs on rat organotypic hippocampal cultures in physiological or neuronal excitotoxic conditions induced by kainic acid (KA). The cellular responses of the PtNPs were evaluated through cytotoxic assays and confocal microscopy analysis. To mimic a pathologic scenario, 7-day organotypic hippocampal cultures were exposed to KA for 24 h. Subsequently, PtNPs were added to each slice. We show that incubation of the slices with PtNPs for 24 h, does not severely impact cell viability in normal conditions, with no significant differences when comparing the dentate gyrus (DG), as well as CA3 and CA1 pyramidal cell layers. Such effects are not exacerbated in KA-treated slices, where the presence of PtNPs does not cause additional neuronal propidium iodide (PI) uptake in CA3 and CA1 pyramidal cell layers. However, PtNPs cause microglial cell activation and morphological alterations in CA3 and DG regions indicating the establishment of an inflammatory reaction. Morphological analysis revealed that microglia acquire activated ameboid morphology with loss of ramifications, as a result of their response to PtNPs contact. Surprisingly, this effect is not increased in pathological conditions. Taken together, these results show that PtNPs cause microglia alterations in short-term studies. Additionally, there is no worsening of the tissue response in a neuropathological induced scenario. This work highlights the need of further research to allow for the safe use of PtNPs. Also, it supports the demand of the development of novel and more biocompatible NPs to be applied in the brain.The authors acknowledge the funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement No. 764977, in the framework of the mCBEEs project (Advanced integrative solutions to corrosion problems beyond micro-scale: toward long-term durability of miniaturized biomedical, electronic, and energy systems). This work was also financed by Portuguese funds through FCT/MCTES in the framework of the project “Institute for Research and Innovation in Health Sciences”– UIDB/04293/2020. The authors thank the support of the i3S Scientific Platforms Bioimaging and Advanced Light Microscopy (ALM), members of the national infrastructure PPBI–Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122). SS acknowledges FCT for her contract under the Norma Transitória–DL57/2016/CP/CP1360/CT0013

Citizens for Peace Minutes 1-11-11

This article presents data from a research that aims to show how mobilizations of mathematical knowledge occur when solving Physics tasks, considering the records of semiotic representation. To demonstrate the above, we present a qualitative analysis focused on the transformability of the records of semiotic representation of three tasks that were part of one of the instruments used in field research, as well as a summary explaining what they meant by Duval records of semiotic representation. In the end we present some considerations that point to the difficulties students may run into at the time of solving Physics tasks, which are somehow associated with the transformation of a record of semiotic representation

Head-to-head comparison of two online nomograms for prostate biopsy outcome prediction

LEVEL OF EVIDENCE: 2b. What's known on the subject? and What does the study add? In recent years, several nomograms were developed in an effort to decrease the number of unnecessary prostate biopsies. The European SWOP-PRI and the North American PCPT are among the most popular. However, evidence on the relative predictive accuracy is lacking. A head-to-head comparison on the diagnostic accuracy of two previously validated prostate cancer risk predictors on biopsy confirmed the superiority of these tools over PSA alone. Moreover, in the studied population, the European SWOP-PRI proved to be more accurate than the North American PCPT-CRC. OBJECTIVE: To compare the diagnostic accuracy of two previously validated prostate cancer risk predictors on biopsy. PATIENTS AND METHODS: In total, 390 consecutive patients submitted to 10-core systematic transrectal prostate biopsy at our institution were included in this retrospective study. External validation of a European (European Randomized Study of Screening for Prostate Cancer derived Prostate Risk Indicator; SWOP-PRI) and a North American (Prostate Cancer Prevention Trial Cancer Risk Calculator; PCPT-CRC) nomogram was performed. The predictive accuracy of these online available nomograms was calculated based on the area under the curve derived from receiver-operator characteristic curves and then compared using the DeLong method. RESULTS: Both tools were confirmed to be superior to prostate-specific antigen alone. Moreover, the SWOP-PRI (77.9%) displays a 7.96% increase in the predictive accuracy compared to the PCPT-CRC (69.9%) in a statistically significant fashion (P=0.002). CONCLUSIONS: The results obtained in the present study confirm the utility of nomograms with respect to biopsy outcome prediction in patients with suspicion of prostate cancer. In the current sample of patients, the European-based nomogram appears to be more accurate than the North American nonogram, which lacks information regarding prostate volume and prostatic ultrasonographic lesions. • To our knowledge, this is the first study to compare the accuracy of these popular risk calculators in a specific population

Mycoplasma pneumoniae-induced rash and mucositis: a recently described entity

Mycoplasmapneumoniae is a common cause of respiratory infections. Although most cases are mild, some patients have extrapulmonary complications including mucocutaneous eruptions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and erythemamultiforme (EM). Recently, a new entity, called M. pneumoniae-induced rash and mucositis (MIRM) was described. The authors present a clinical case difficult to classify attending to the classical classification of epidermolytic syndromes that meets the criteria proposed for the diagnosis of MIRM. The mucocutaneous disease associated with M. pneumoniae presents predominant mucositis, with scarce or absent cutaneous involvement. Because of the distinct morphology, pathophysiology and benign clinical course, MIRM should be considered as a new entity, distinct from SJS/TEN and EM.info:eu-repo/semantics/publishedVersio

Cannabis arteritis: ever more important to consider

Cannabis arteritis (CA) is a major and underdiagnosed cause of peripheral arterial disease in young patients. A 34-year-old man, daily smoker of 20 cigarettes and two cannabis cigarettes for 14 years, presented with a necrotic plaque of left hallux for 3 weeks. The Doppler ultrasound and angiography were compatible with severe Buerger's disease. Submitted to a revascularisation procedure and hypocoagulation with rivaroxaban. He had ceased smoking but maintained consumption of cannabis. Owing to the persistence of distal necrosis, amputation of the hallux was performed with good evolution. CA is a subtype of Buerger's disease. It is poorly known but increasingly prevalent and manifests in cannabis users regardless of tobacco use. The drug is considered at least a cofactor of the arteriopathy. The most effective treatment is cessation of consumption. Being cannabis one of the most consumed drugs, its mandatory to ask about its use in all young patients with arteriopathy.info:eu-repo/semantics/publishedVersio

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

Central nervous system (CNS) disorders encompass a vast spectrum of pathological conditions and represent a growing concern worldwide. Despite the high social and clinical interest in trying to solve these pathologies, there are many challenges to bridge in order to achieve an effective therapy. One of the main obstacles to advancements in this field that has hampered many of the therapeutic strategies proposed to date is the presence of the CNS barriers that restrict the access to the brain. However, adequate brain biodistribution and neuronal cells specific accumulation in the targeted site also represent major hurdles to the attainment of a successful CNS treatment. Over the last few years, nanotechnology has taken a step forward towards the development of therapeutics in neurologic diseases and different approaches have been developed to surpass these obstacles. The versatility of the designed nanocarriers in terms of physical and chemical properties, and the possibility to functionalize them with specific moieties, have resulted in improved neurotargeted delivery profiles. With the concomitant progress in biology research, many of these strategies have been inspired by nature and have taken advantage of physiological processes to achieve brain delivery. Here, the different nanosystems and targeting moieties used to achieve a neuronal delivery reported in the open literature are comprehensively reviewed and critically discussed, with emphasis on the most recent bioinspired advances in the field. Finally, we express our view on the paramount challenges in targeted neuronal delivery that need to be overcome for these promising therapeutics to move from the bench to the bedside.This work was financially supported by the project PTDC/CTM-NAN/3547/2014 (POCI-01-0145-FEDER-016639) funded by FEDER funds through the Programa Operacional Competitividade e Internacionalização-COMPETE 2020 and Portuguese funds through FCT–Fundação para a Ciência e a Tecnologia. A.P.S., B.C. and S.D.S. acknowledge FCT for the Ph.D. scholarships (SFRH/BD/137073/2018 and SFRH/BD/145652/2019) and the contract under the Norma Transitória–DL57/2016/CP/CP1360/CT0013, respectively. V.L. acknowledges her contract in the framework of the project NORTE-01-0247-FEDER-033399, funded by FEDER funds through the Sistema de Incentivos à Investigação e Desenvolvimento Tecnológico (SI I&DT), Aviso nº 03/SI/2017, Projetos em Co-promoção do Programa Interfac

Hypertension as An Atypical Presentation of Unilateral Ureteral Obstruction

Ureteral obstruction (ureteropelvic or ureterovesical junction obstruction) is frequently diagnosed during the workup investigation of an asymptomatic infant or child with upper urinary tract dilatation, commonly identified in a prenatal ultrasound. In older children, recurrent lumbar pain is a red flag for ureteral obstruction. Although less frequent, hypertension may be the initial and only manifestation of ureteral obstruction. The authors present two pediatric cases of unilateral ureteral obstruction with hypertension, in which the surgical treatment of the obstruction leads to blood pressure normalisation. In all pediatric age groups, a systematic investigation for secondary causes of hypertension is of paramount importance. In some cases, especially those of an obstructive nature, early surgical management can be curative, with normalization of blood pressure levels and prevention of renal injury.info:eu-repo/semantics/publishedVersio

Amniotic Fluid Embolism. Is a New Pregnancy Possible? Case Report.

Amniotic fluid embolism (AFE) is a rare but potentially catastrophic clinical condition, characterized by a combination of signs and symptoms that reflect respiratory distress, cardiovascular collapse and disseminated intravascular coagulation (DIC). Its pathogenesis is still unclear. More recently, the traditional view of obstruction of pulmonary capillary vessels by amniotic fluid emboli as the main explanation for the etiology has been ruled out, and immunologic factors and the activation of the inflammatory cascade took on an important role. Amniotic fluid embolism has an unpredictable character, its diagnosis is exclusively clinical, and the treatment consists mainly of cardiovascular support and administration of blood products to correct the DIC. No diagnostic test is recommended until now, though multiple blood markers are currently being studied. The authors present a case report of a woman who had survived AFE in her previous pregnancy and had a subsequent pregnancy without recurrence, providing one more clinical testimony of the low risks for the pregnancy after AFE.info:eu-repo/semantics/publishedVersio

Prevalence of constipation in adults with obesity class II and III and associated factors

BACKGROUND: Constipation and obesity have common risk factors. However, little is known about the occurrence of constipation in individuals with severe obesity and the associated factors. OBJECTIVE: To evaluate the prevalence of intestinal constipation and its associated factors in adults with obesity class II and III. METHOD: This study analyzed baseline data from a randomized clinical trial with adults aged 18–64 with a Body Mass Index (BMI) ≥ 35 kg/m2, living in the metropolitan region of Goiânia, Brazil. Data were collected using a questionnaire containing sociodemographic, lifestyle, level of obesity, presence of comorbidities, water intake and food consumption variables. The outcome variable was constipation assessed by the Rome III criteria and the Bristol Stool Form Scale. Multiple Poisson regression analysis was used to assess the association between explanatory variables and the outcome. RESULTS: Among the 150 participants, the prevalence of constipation was 24.67% (95% CI: 17.69–31.64). After multiple regression analyses constipation was associated with polypharmacy (adjusted PR: 2.99, 95% CI: 1.18–7.57, p = 0.021), younger age group i.e. 18–29 years (adjusted PR: 3.12, 95% CI: 1.21–8.06, p = 0.019) and former smoking (adjusted PR: 3.24, 95% CI: 1.28–9.14, p = 0.014). There was no statistically significant association between constipation and daily consumption of fiber-rich foods, however, the non-consumption of whole grains was borderline significant (adjusted PR: 2.92, 95% CI: 1.00 to 8.49, p = 0.050). CONCLUSION: A high prevalence of constipation was found in adults with obesity class II and III. Constipation was significantly associated with the simultaneous use of five or more medications, younger age group and being a former smoker

In Medicago truncatula, water deficit modulates the transcript accumulation of components of small RNA pathways

<p>Abstract</p> <p>Background</p> <p>Small RNAs (sRNAs) are 20-24 nucleotide (nt) RNAs and are involved in plant development and response to abiotic stresses. Plants have several sRNA pathways implicated in the transcriptional and post-transcriptional silencing of gene expression. Two key enzyme families common to all pathways are the Dicer-like (DCL) proteins involved in sRNAs maturation and the Argonautes (AGOs) involved in the targeting and functional action of sRNAs. Post-transcriptional silencing mediated by AGOs may occur by cleavage or translational repression of target mRNA's, while transcriptional silencing may be controlled by DNA methylation and chromatin remodeling. Thus far, these gene families have not been characterized in legumes, nor has their involvement in adaptation to water deficit been studied.</p> <p>Results</p> <p>A bioinformatic search in <it>Medicago truncatula </it>genome databases, using <it>Arabidopsis thaliana </it>AGO and DCL cDNA and protein sequences, identified three sequences encoding for putative Dicer-like genes and twelve sequences encoding for putative Argonaute genes. Under water deficit conditions and mainly in roots, MtDCL1 and MtAGO1, two enzymes probably involved in the processing and activation of microRNAs (miRNAs), increased their transcript levels. mir162 which target DCL1 mRNA and mir168 which target AGO1 mRNA reduced their expression in the roots of plants subjected to water deficit. Three putative genes, MtDCL3, MtAGO4b and MtAGO4c probably involved in DNA methylation mechanisms, increased their mRNA levels. However, the mRNA levels of MtAGO6 reduced, which probably encodes a protein with functions similar to MtAGO4. MtAGO7 mRNA levels increased and possibly encodes a protein involved in the production of trans-acting small interfering RNAs. The transcript abundance of MtAGO12a, MtAGO12b and MtAGO12c reduced under water deprivation. Plants recovered from water deprivation reacquire the mRNA levels of the controls.</p> <p>Conclusions</p> <p>Our work demonstrates that in <it>M. truncatula </it>the transcript accumulation of the components of small RNA pathways is being modulated under water deficit. This shows that the transcriptional and post-transcriptional control of gene expression mediated by sRNAs is probably involved in plant adaptation to abiotic environmental changes. In the future this will allow the manipulation of these pathways providing a more efficient response of legumes towards water shortage.</p