Mucosal delivery of liposome-chitosan nanoparticles complexes

Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can become more inconvenient as a function of the specific characteristics of administration routes. To overcome these limitations, we developed a new drug delivery system that results from the combination of chitosan nanoparticles and liposomes, in an approach of combining their advantages, while avoiding their individual limitations. These lipid/chitosan nanoparticle complexes are, thus, expected to protect the encapsulated drug from harsh environmental conditions, while concomitantly providing its controlled release. To prepare these assemblies, two different strategies have been applied: one focusing on the simple hydration of a previously formed dry lipid film with a suspension of chitosan nanoparticles, and the other relying on the lyophilization of both basic structures (nanoparticles and liposomes) with a subsequent step of hydration with water. The developed systems are able to provide a controlled release of the encapsulated model peptide, insulin, evidencing release profiles that are dependent on their lipid composition. Moreover, satisfactory in vivo results have been obtained, confirming the potential of these newly developed drug delivery systems as drug carriers through distinct mucosal routes

Ordenha mecânica nas explorações de caprinos de Trás-os-Montes (Portugal): problemas e dificuldades para a sua divulgação

Na região de Trás-os-Montes (nordeste de Portugal) a exploração de cabras de leite, principalmente da raça Serrana, autóctone, é uma actividade relativamente importante do ponto de vista socioeconómico, porque se trata de uma região pobre e onde são raras as actividades económicas alternativas para a população rural. Para o desenvolvimento da actividade e para a melhoria da qualidade e quantidade de leite produzido, é importante melhorar as condições de ordenha, especialmente quanto às instalações e equipamentos; e às condições de trabalho do ordenhador. A maioria das explorações de caprinos da região pratica a ordenha manual. Este tipo de ordenha tem vários problemas quanto às condições de trabalho e à qualidade do leite recolhido. Nos últimos anos desenvolveram-se várias acções no sentido de melhorar as condições de ordenha e de incentivar os criadores para a adopção de ordenha mecânica. No entanto, verificam-se alguns problemas e dificuldades dos criadores na adopção e utilização destes equipamentos. Com este trabalho, pretende-se identificar os problemas e dificuldades que resultaram da adopção/utilização de equipamentos de ordenha mecânica em explorações de cabras de leite da região de Trás-os-Montes. O estudo da ordenha mecânica abrangeu vários aspectos: os equipamentos utilizados; a organização do trabalho e das instalações; e os procedimentos do ordenhador no trabalho de ordenha. Foram estudadas as explorações de caprinos de raça Serrana da região de Trás-os-Montes que utilizam qualquer tipo de ordenha mecânica. A informação recolhida permite concluir que há dificuldades na adaptação ao uso de novas técnicas de ordenha e equipamentos. Os problemas estão, principalmente, relacionados com a organização do trabalho e do local da ordenha, e com a aprendizagem da correcta utilização dos equipamentos. De futuro, será importante considerar o desenvolvimento de acções de apoio técnico aos criadores, no sentido de melhorar as instalações/local de ordenha e a utilização dos equipamentosIn the national context, the region of Trás-os-Montes, in Northeastern Portugal, is one of the most depopulated and least favoured areas. In this region, goat breeding has great socioeconomic importance due to the number of families that are economically dependent on these activities. This importance is particularly due to the scarcity of alternative economic activities. To improve goat breeding, milk production and milk quality, it is important to enhance milking conditions, mainly in facilities, equipment and working conditions. Presently, there are very few farms with milking machines. Mostly, goats are hand-milked inside the shelters. As a result of actions carried out over the recent years involving strategies to improve milking conditions on goat farms in the region, some breeders adopted mechanical milking. For these breeders, mechanical milking is a new technology, they are inexperienced and they lack knowledge about the correct use of these machines and best milking practices. To study mechanical milking we established the following aspects to consider: working organization and facilities, milking operations, and procedures performed by milkers. Goat farms that used mechanical milking in the region of Trás-os-Montes were studied. From the information collected, it was found some difficulties in the adaptation to the use of new milking techniques. Main problems are related to working organization, facilities and equipment utilization

Predictors of Global Non-Motor Symptoms Burden Progression in Parkinson’s Disease. Results from the COPPADIS Cohort at 2-Year Follow-Up

Background and Objective: Non-motor symptoms (NMS) progress in different ways between Parkinson's disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group. Material and Methods: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable). Results: After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) (p < 0.0001). NMSS total score at baseline (β = -0.52), change from V0 to V2 in PDSS (Parkinson's Disease Sleep Scale) (β = -0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (β = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865). Conclusions: Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression

Falls Predict Acute Hospitalization in Parkinson's Disease

[Background] There is a need for identifying risk factors for hospitalization in Parkinson’s disease (PD) and also interventions to reduce acute hospital admission.[Objective] To analyze the frequency, causes, and predictors of acute hospitalization (AH) in PD patients from a Spanish cohort.[Methods] PD patients recruited from 35 centers of Spain from the COPPADIS-2015 (COhort of Patients with PArkinson’s DIsease in Spain, 2015) cohort from January 2016 to November 2017, were included in the study. In order to identify predictors of AH, Kaplan-Meier estimates of factors considered as potential predictors were obtained and Cox regression performed on time to hospital encounter 1-year after the baseline visit.[Results] Thirty-five out of 605 (5.8%) PD patients (62.5±8.9 years old; 59.8% males) presented an AH during the 1-year follow-up after the baseline visit. Traumatic falls represented the most frequent cause of admission, being 23.7% of all acute hospitalizations. To suffer from motor fluctuations (HR [hazard ratio] 2.461; 95% CI, 1.065–5.678; p = 0.035), a very severe non-motor symptoms burden (HR [hazard ratio] 2.828; 95% CI, 1.319–6.063; p = 0.008), falls (HR 3.966; 95% CI 1.757–8.470; p = 0.001), and dysphagia (HR 2.356; 95% CI 1.124–4.941; p = 0.023) was associated with AH after adjustment to age, gender, disease duration, levodopa equivalent daily dose, total number of non-antiparkinsonian drugs, and UPDRS-IIIOFF. Of the previous variables, only falls (HR 2.998; 95% CI 1.080–8.322; p = 0.035) was an independent predictor of AH.[Conclusion] Falls is an independent predictor of AH in PD patients.Peer reviewe

Differentiating between Monofloral Portuguese Bee Pollens Using Phenolic and Volatile Profiles and Their Impact on Bioactive Properties

Nowadays, bee products are commended by consumers for their medicinal and dietary properties. This study aimed to differentiate between monofloral bee pollens originating from Portugal using phenolic and volatile profiles and investigate their antioxidant and cytotoxic activity. Total phenolic and flavonoid compounds were recorded between 2.9–35.8 mg GAE/g and 0.7–4.8 mg QE/g, respectively. The LC/DAD/ESI-MSn analytical results allowed us to identify and quantify a total of 72 compounds, including phenolic and phenylamide compounds, whereas GC-MS results revealed the presence of 49 different compounds, mostly ketones, aldehydes, esters, hydrocarbons, and terpenes. The highest DPPH• radical scavenging activity, EC50: 0.07 mg/mL, was recorded in the sample dominated by Castanae sp. pollen, whereas the Rubus sp. (1.59 mM Trolox/mg) and Cistaceae sp. (0.09 mg GAE/g) pollen species exhibited the highest antioxidant activity in ABTS•+ and reducing power assays, respectively. Regarding the anti-carcinogenic activity, only Carduus sp. showed remarkable cytotoxic potential against MCF-7

Prevalence and Factors Associated with Drooling in Parkinson’s Disease: Results from a Longitudinal Prospective Cohort and Comparison with a Control Group

Introduction. Drooling in Parkinson’s disease (PD) is frequent but often goes underrecognized. Our aim was to examine the prevalence of drooling in a PD cohort and compare it with a control group. Specifically, we identified factors associated with drooling and conducted subanalyses in a subgroup of very early PD patients. Patients and Methods. PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30-day follow-up (V2) from 35 centers in Spain from the COPPADIS cohort were included in this longitudinal prospective study. Subjects were classified as with or without drooling according to item 19 of the NMSS (Nonmotor Symptoms Scale) at V0, V1 (1-year ± 15 days), and V2 for patients and at V0 and V2 for controls. Results. The frequency of drooling in PD patients was 40.1% (277/691) at V0 (2.4% (5/201) in controls; p < 0.0001), 43.7% (264/604) at V1, and 48.2% (242/502) at V2 (3.2% (4/124) in controls; p < 0.0001), with a period prevalence of 63.6% (306/481). Being older (OR = 1.032; p = 0.012), being male (OR = 2.333; p < 0.0001), having greater nonmotor symptom (NMS) burden at the baseline (NMSS total score at V0; OR = 1.020; p < 0.0001), and having a greater increase in the NMS burden from V0 to V2 (change in the NMSS total score from V0 to V2; OR = 1.012; p < 0.0001) were identified as independent predictors of drooling after the 2-year follow-up. Similar results were observed in the group of patients with ≤2 years since symptom onset, with a cumulative prevalence of 64.6% and a higher score on the UPDRS-III at V0 (OR = 1.121; p = 0.007) as a predictor of drooling at V2. Conclusion. Drooling is frequent in PD patients even at the initial onset of the disease and is associated with a greater motor severity and NMS burden

Sex Differences in Motor and Non-Motor Symptoms among Spanish Patients with Parkinson’s Disease

Background and objective: Sex plays a role in Parkinson’s disease (PD) mechanisms. We analyzed sex difference manifestations among Spanish patients with PD. Patients and Methods: PD patients who were recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. A cross-sectional and a two-year follow-up analysis were conducted. Univariate analyses and general linear model repeated measure were used. Results: At baseline, data from 681 PD patients (mean age 62.54 ± 8.93) fit the criteria for analysis. Of them, 410 (60.2%) were males and 271 (39.8%) females. There were no differences between the groups in mean age (62.36 ± 8.73 vs. 62.8 ± 9.24; p = 0.297) or in the time from symptoms onset (5.66 ± 4.65 vs. 5.21 ± 4.11; p = 0.259). Symptoms such as depression (p p p p p p p p = 0.002). Perception of quality of life was generally worse in females (PDQ-39, p = 0.002; EUROHIS-QOL8, p = 0.009). After the two-year follow-up, the NMS burden (Non-Motor Symptoms Scale total score) increased more significantly in males (p = 0.012) but the functional capacity (Schwab and England Activities of Daily Living Scale) was more impaired in females (p = 0.001). Conclusion: The present study demonstrates that there are important sex differences in PD. Long-term prospective comparative studies are needed

Staging Parkinson's disease according to the MNCD classification correlates with caregiver burden

Abstract Background and objective Recently, we demonstrated that staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on four axes (motor, non‐motor, cognition, and dependency) and five stages, correlated with disease severity and patients’ quality of life. Here, we analyzed the correlation of MNCD staging with PD caregiver's status. Patients and methods Data from the baseline visit of PD patients and their principal caregiver recruited from 35 centers in Spain from the COPPADIS cohort from January 2016 to November 2017 were used to apply the MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) in this cross‐sectional analysis. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory‐II (BDI‐II), PQ‐10, and EUROHIS‐QOL 8‐item index (EUROHIS‐QOL8). Results Two hundred and twenty‐four PD patients (63 ± 9.6 years old; 61.2% males) and their caregivers (58.5 ± 12.1 years old; 67.9% females) were included. The frequency of MNCD stages was 1, 7.6%; 2, 58.9%; 3, 31.3%; and 4–5, 2.2%. A more advanced MNCD stage was associated with a higher score on the ZCBI (p < .0001) and CSI (p < .0001), and a lower score on the PQ‐10 (p = .001), but no significant differences were observed in the BDI‐II (p = .310) and EUROHIS‐QOL8 (p = .133). Moderate correlations were observed between the MNCD total score and the ZCBI (r = .496; p < .0001), CSI (r = .433; p < .0001), and BDI‐II (r = .306; p < .0001) in caregivers. Conclusion Staging PD according to the MNCD classification is correlated with caregivers’ strain and burden