Interplay of Ritonavir-Boosted Oral Cabazitaxel with the Organic Anion-Transporting Polypeptide (OATP) Uptake Transporters and Carboxylesterase 1 in Mice.

Intravenously administered chemotherapeutic cabazitaxel is used for palliative treatment of prostate cancer. An oral formulation would be more patient-friendly and reduce the need for hospitalization. We therefore study determinants of the oral pharmacokinetics of cabazitaxel in a ritonavir-boosted setting, which reduces the CYP3A-mediated first-pass metabolism of cabazitaxel. We here assessed the role of organic anion-transporting polypeptides (OATPs) in the disposition of orally boosted cabazitaxel and its active metabolites, using the Oatp1a/b-knockout and the OATP1B1/1B3-transgenic mice. These transporters may substantially affect plasma clearance and hepatic and intestinal drug disposition. The pharmacokinetics of cabazitaxel and DM2 were not significantly affected by Oatp1a/b and OATP1B1/1B3 activity. In contrast, the plasma AUC0-120 min of DM1 in Oatp1a/b-/- was 1.9-fold (p < 0.05) higher than that in wild-type mice, and that of docetaxel was 2.4-fold (p < 0.05) higher. We further observed impaired hepatic uptake and intestinal disposition for DM1 and docetaxel in the Oatp-ablated strains. None of these parameters showed rescue by the OATP1B1 or -1B3 transporters in the humanized mouse strains, suggesting a minimal role of OATP1B1/1B3. Ritonavir itself was also a potent substrate for mOatp1a/b, showing a 2.9-fold (p < 0.0001) increased plasma AUC0-120 min and 3.5-fold (p < 0.0001) decreased liver-to-plasma ratio in Oatp1a/b-/- compared to those in wild-type mice. Furthermore, we observed the tight binding of cabazitaxel and its active metabolites, including docetaxel, to plasma carboxylesterase (Ces1c) in mice, which may complicate the interpretation of pharmacokinetic and pharmacodynamic mouse studies. Collectively, these results will help to further optimize (pre)clinical research into the safety and efficacy of orally applied cabazitaxel.

Coadministration of ABCB1/P-glycoprotein inhibitor elacridar improves tissue distribution of ritonavir-boosted oral cabazitaxel in mice.

Developing an oral formulation for the chemotherapeutic cabazitaxel might improve its patient-friendliness, costs, and potentially exposure profile. Cabazitaxel oral availability is restricted by CYP3A-mediated first-pass metabolism, but can be substantially boosted with the CYP3A inhibitor ritonavir. We here tested whether adding the ABCB1/P-glycoprotein inhibitor elacridar to ritonavir-boosted oral cabazitaxel could further improve its tissue exposure using wild-type, CYP3A4-humanized and Abcb1a/b-/- mice. The plasma AUC0-2h of cabazitaxel was increased 2.3- and 1.9-fold in the ritonavir- and ritonavir-plus-elacridar groups of wild-type, and 10.5- and 8.8-fold in CYP3A4-humanized mice. Elacridar coadministration did not influence cabazitaxel plasma exposure. The brain-to-plasma ratio of cabazitaxel was not increased in the ritonavir group, 7.3-fold in the elacridar group and 13.4-fold in the combined booster group in wild-type mice. This was 0.4-, 4.6- and 3.6-fold in CYP3A4-humanized mice, illustrating that Abcb1 limited cabazitaxel brain exposure also during ritonavir boosting. Ritonavir itself was also a potent substrate for the Abcb1 efflux transporter, limiting its oral availability (3.3-fold) and brain penetration (10.6-fold). Both processes were fully reversed by elacridar. The tissue disposition of ritonavir-boosted oral cabazitaxel could thus be markedly enhanced by elacridar coadministration without affecting the plasma exposure. This approach should be verified in selected patient populations.

The SHED Index: A Validation Study to Assess Sustainable HEalthy Diets in Portugal.

This study aims to adapt and validate the Sustainable HEalthy Diet (SHED) Index for the Portuguese adult population, which was developed to assess sustainable and healthy eating patterns. Data were collected using a web-based questionnaire administered through interviews with 347 individuals aged between 18 and 65 years old. The SHED Index evaluates 30 items, allowing for the assessment and scoring of sustainable and healthy eating patterns. The higher the SHED Index score, the more sustainable and healthier the diet. A semi-quantitative food frequency questionnaire was used to assess the participants' dietary intake. The criterion validity was examined by testing the relationship between the SHED Index score and adherence to the Mediterranean Diet. Reproducibility was assessed by determining agreement and reliability with test-retest. Construct validity was confirmed based on established criteria. A higher SHED Index score was associated with moderate to high adherence to the Mediterranean diet, while it was inversely related to the proportion of animal-sourced foods in the overall food intake (r = -0.281, p < 0.001). Good reliability and agreement were found for the SHED Index score. Our findings suggest that the SHED Index is a valid and reliable tool for assessing sustainable and healthy diets in the Portuguese adult population.

Cross-Classification Analysis of Food Products Based on Nutritional Quality and Degree of Processing.

This study aims to compare the classification of foods available in the Portuguese market using Nutri-Score and NOVA classifications and to analyse their ability to discriminate the fat, saturated fat, sugar, and salt content of foods. A sample of 2682 food products was collected. The nutritional quality of foods was established using the Nutri-Score, classifying them into five categories (from A to E). The NOVA classification was used to classify foods according to the degree of food processing into unprocessed/minimally processed foods, processed culinary ingredients, processed foods, and ultra-processed foods (UPF). The nutritional content of food products was classified using a Multiple Traffic Light label system. It was observed that 73.7% of UPF were classified as Nutri-Score C, D, and E, 10.1% as Nutri-Score A, and 16.2% as Nutri-Score B. Nutri-Score was positively correlated with NOVA classification (ρ = 0.140, p < 0.001) and with the Multiple Traffic Lights system (ρTotal Fat = 0.572, ρSaturated Fat = 0.668, ρSugar = 0.215, ρSalt = 0.321, p < 0.001). NOVA classification negatively correlated with the Multiple Traffic Lights system for total fat (ρ = -0.064, p < 0.001). Our findings indicate the presence of many UPFs in all Nutri-Score categories. Since food processing and nutritional quality are complementary, both should be considered in labelling.

P-glycoprotein (MDR1/ABCB1) Restricts Brain Penetration of the Main Active Heroin Metabolites 6-monoacetylmorphine (6-MAM) and Morphine in Mice.

BACKGROUND & PURPOSE: Heroin (diacetylmorphine; diamorphine) is a highly addictive opioid prodrug. Heroin prescription is possible in some countries for chronic, treatment-refractory opioid-dependent patients and as a potent analgesic for specific indications. We aimed to study the pharmacokinetic interactions of heroin and its main pharmacodynamically active metabolites, 6-monoacetylmorphine (6-MAM) and morphine, with the multidrug efflux transporters P-glycoprotein/ABCB1 and BCRP/ABCG2 using wild-type, Abcb1a/1b and Abcb1a/1b;Abcg2 knockout mice. METHODS & RESULTS: Upon subcutaneous (s.c.) heroin administration, its blood levels decreased quickly, making it challenging to detect heroin even shortly after dosing. 6-MAM was the predominant active metabolite present in blood and most tissues. At 10 and 30 min after heroin administration, 6-MAM and morphine brain accumulation were increased about 2-fold when mouse (m)Abcb1a/1b and mAbcg2 were ablated. Fifteen minutes after direct s.c. administration of an equimolar dose of 6-MAM, we observed good intrinsic brain penetration of 6-MAM in wild-type mice. Still, mAbcb1 limited brain accumulation of 6-MAM and morphine without affecting their blood exposure, and possibly mediated their direct intestinal excretion. A minor contribution of mAbcg2 to these effects could not be excluded. CONCLUSIONS: We show that mAbcb1a/1b can limit 6-MAM and morphine brain exposure. Pharmacodynamic behavioral/postural observations, while non-quantitative, supported moderately increased brain levels of 6-MAM and morphine in the knockout mouse strains. Variation in ABCB1 activity due to genetic polymorphisms or environmental factors (e.g., drug interactions) might affect 6-MAM/morphine exposure in individuals, but only to a limited extent.

Effect of Olive Pomace Extract Application and Packaging Material on the Preservation of Fresh-Cut Royal Gala Apples.

The efficiency of natural olive pomace extracts for enhancing the quality of fresh-cut apples was compared with commercial ascorbic acid and two different packaging films (biodegradable polylactic acid (PLA) and oriented polypropylene (OPP)) were tested. The composition of atmosphere inside the packages, the physicochemical parameters (firmness, weight loss and color), the microbial load, total phenolic content and antioxidant activity of fresh-cut apples were evaluated throughout 12 days of storage at 4 °C. After 12 days of refrigerated storage, a significant decrease in O2 was promoted in PLA films, and the weight loss of the whole packaging was higher in PLA films (5.4%) than in OPP films (0.2%). Natural olive pomace extracts reduced the load of mesophilic bacteria (3.4 ± 0.1 log CFU/g and 2.4 ± 0.1 log CFU/g for OPP and PLA films, respectively) and filamentous fungi (3.3 ± 0.1 log CFU/g and 2.44 ± 0.05 log CFU/g for OPP and PLA films, respectively) growth in fresh-cut apples after five days of storage at 4 °C, and no detection of coliforms was verified throughout the 12 days of storage. In general, the olive pomace extract preserved or improved the total phenolic index and antioxidant potential of the fruit, without significant changes in their firmness. Moreover, this extract seemed to be more effective when combined with the biodegradable PLA film packaging. This work can contribute to the availability of effective natural food additives, the sustainability of the olive oil industries and the reduction of environmental impact. It can also be useful in meeting the food industries requirements to develop new functional food products.

Organic anion-transporting polypeptide 2B1 knockout and humanized mice; insights into the handling of bilirubin and drugs.

Organic anion transporting polypeptide 2B1 (OATP2B1/SLCO2B1) facilitates uptake transport of structurally diverse endogenous and exogenous compounds. To investigate the roles of OATP2B1 in physiology and pharmacology, we established and characterized Oatp2b1 knockout (single Slco2b1-/- and combination Slco1a/1b/2b1-/-) and humanized hepatic and intestinal OATP2B1 transgenic mouse models. While viable and fertile, these strains exhibited a modestly increased body weight. In males, unconjugated bilirubin levels were markedly reduced in Slco2b1-/- compared to wild-type mice, whereas bilirubin monoglucuronide levels were modestly increased in Slco1a/1b/2b1-/- compared to Slco1a/1b-/- mice. Single Slco2b1-/- mice showed no significant changes in oral pharmacokinetics of several tested drugs. However, markedly higher or lower plasma exposure of pravastatin and the erlotinib metabolite OSI-420, respectively, were found in Slco1a/1b/2b1-/- compared to Slco1a/1b-/- mice, while oral rosuvastatin and fluvastatin behaved similarly between the strains. In males, humanized OATP2B1 strains showed lower conjugated and unconjugated bilirubin levels than control Slco1a/1b/2b1-deficient mice. Moreover, hepatic expression of human OATP2B1 partially or completely rescued the impaired hepatic uptake of OSI-420, rosuvastatin, pravastatin, and fluvastatin in Slco1a/1b/2b1-/- mice, establishing an important role in hepatic uptake. Expression of human OATP2B1 in the intestine was basolateral and markedly reduced the oral availability of rosuvastatin and pravastatin, but not of OSI-420 and fluvastatin. Neither lack of Oatp2b1, nor overexpression of human OATP2B1 had any effect on fexofenadine oral pharmacokinetics. While these mouse models still have limitations for human translation, with additional work we expect they will provide powerful tools to further understand the physiological and pharmacological roles of OATP2B1.

Enhancement of the Oral Availability of Cabazitaxel Using the Cytochrome P450 3A (CYP3A) Inhibitor Ritonavir in Mice.

There is currently great interest in developing oral taxanes due to their lower costs and greater patient friendliness. We here wanted to test whether oral ritonavir, a cytochrome P450 3A (CYP3A) inhibitor, could boost the pharmacokinetics and tissue distribution of orally administered cabazitaxel (10 mg/kg) in male wild-type, Cyp3a-/-, and Cyp3aXAV (transgenic overexpression of human CYP3A4 in liver and intestine) mice. Ritonavir was initially administered at a dose of 25 mg/kg, but lower dosages of 10 and 1 mg/kg were also studied to assess the remaining amount of boosting, aiming to minimize possible side effects. Compared to the respective vehicle groups, plasma exposure of cabazitaxel (AUC0-24h) was enhanced 2.9-, 10.9-, and 13.9-fold in wild-type mice and 1.4-, 10.1-, and 34.3-fold in Cyp3aXAV mice by treatment with 1, 10, and 25 mg/kg ritonavir, respectively. Upon treatment with 1, 10, and 25 mg/kg of ritonavir, the peak plasma concentration (Cmax) was increased by 1.4-, 2.3-, and 2.8-fold in wild-type mice, while it increased by 1.7-, 4.2-, and 8.0-fold in Cyp3aXAV mice, respectively. AUC0-24h and Cmax remained unchanged in Cyp3a-/-. Biotransformation of cabazitaxel to its active metabolites still took place when coadministered with ritonavir, but this process was delayed due to the Cyp3a/CYP3A4 inhibition. These data indicate that CYP3A is the primary limiting factor in the plasma exposure to cabazitaxel and that cabazitaxel oral bioavailability could be dramatically enhanced by coadministration of an effective CYP3A inhibitor such as ritonavir. These findings could be a starting point for the setup of a clinical study, which would be needed to verify the boosting of cabazitaxel by ritonavir in humans.

Burden and severity of children's hospitalizations by respiratory syncytial virus in Portugal, 2015-2018.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection (ALRI) in young children and is of considerable burden on healthcare systems. Our study aimed to evaluate ALRI hospitalizations related to RSV in children in Portugal. METHODS: We reviewed hospitalizations potentially related to RSV in children aged <5 years from 2015 to 2018, using anonymized administrative data covering all public hospital discharges in mainland Portugal. Three case definitions were considered: (a) RSV-specific, (b) (a) plus unspecified acute bronchiolitis (RSV-specific & Bronchiolitis), and (c) (b) plus unspecified ALRI (RSV-specific & ALRI). RESULTS: A total of 9697 RSV-specific hospitalizations were identified from 2015 to 2018-increasing to 26 062 for RSV-specific & ALRI hospitalizations-of which 74.7% were during seasons 2015/2016-2017/2018 (November-March). Mean hospitalization rates per season were, for RSV-specific, RSV-specific & Bronchiolitis, and RSV-specific & ALRI, respectively, 5.6, 9.4, and 11.8 per 1000 children aged <5 years and 13.4, 22.5, and 25.9 in children aged <2 years. Most RSV-specific hospitalizations occurred in healthy children (94.9%) and in children aged <2 years (96.3%). Annual direct costs of €2.4 million were estimated for RSV-specific hospitalizations-rising to €5.1 million for RSV-specific & ALRI-mostly driven by healthy children (87.6%). CONCLUSION: RSV is accountable for a substantial number of hospitalizations in children, especially during their first year of life. Hospitalizations are mainly driven by healthy children. The variability of the potential RSV burden across case definitions highlights the need for a universal RSV surveillance system to guide prevention strategies.

Pharyngoplasty for obstructive sleep apnea: The influence of surgical technique.

INTRODUCTION AND OBJECTIVES: Obstructive sleep apnea is the most frequent sleep disorder worldwide, with rising incidence. Pharyngoplasty is an alternative treatment in patients not suitable to continuous positive airway pressure devices (CPAP). The aim of this study is to compare different surgical techniques of pharyngoplasty for treatment of obstructive sleep apnea and evaluate its influence in surgical success. MATERIAL AND METHODS: Retrospective study of 92 patients that underwent pharyngoplasty for treatment of obstructive sleep apnea from 2001 to 2020. Included patients performed classic uvulopalatopharyngoplasty (UPPP), radiofrequency assisted uvulopalatopharyngoplasty (RF-UPPP) or barbed reposition pharyngoplasty (BRP). Surgical success was defined and outcomes and complications assessed for each procedure. RESULTS: Most patients were male, with a mean age of 49.36±9.6 years and a mean apnea hypopnea index (AHI) of 29.14±2.94events/h. Thirty-six patients performed classic UPPP, thirty-one underwent RF-UPPP and the remaining twenty-five performed BRP. BRP achieved the highest success rate (66%) in comparison with UPPP (57%) and RF-UPPP (54%) (p=0.032). Mean relative AHI reduction after surgery was not statistically different between three procedures (p=0.098), although there was a tendency for greater reduction with BRP. Most symptoms improved after surgery and snoring was the most recurrent symptom. BRP had less foreign body sensation after surgery, however, it was the procedure with highest rate of post-operative tonsillar bleeding. CONCLUSIONS: In our department, the introduction of recent techniques of velopharyngeal surgery, focused in functional and lateral muscular collapse, has translated into an increase in success rate after surgery. The relative ease of the procedure and reduction of long term complications make BRP an attractive alternative option for CPAP in OSA, in carefully selected patients.

Predictive factors for repeated tympanostomy tube placement in children.

OBJECTIVES: To determine the rate and risk factors for additional tympanostomy tube (TT) placement after first set of TT extrusion in children. MATERIALS AND METHODS: Single-centre cohort study. Clinical records of children undergoing TT placement from January 2015 to December 2017 were reviewed and factors related to the need for subsequent TT were evaluated. RESULTS: A total of 183 children were included, with a mean age of 5.45±2.672 years old. All surgeries were performed simultaneously with adenoidectomy and 64.3% with tonsillectomy. The mean TT retention time was 12.13±6.033 months and the rate of second TT insertion was 21.9%. The TT retention time was significantly lower in children who needed a second TT (8.97±3.962 vs 13.05±6.229, p<.001). Other factors significantly associated with the need for a second TT in the univariate analysis were the presence of otorrhoea and snoring after TT placement (p=.042 and p=.02), RAOM (p=.016), passive smoking (p=.038) and rhinorrhoea (p=.008). However, on multivariate analysis only TT retention time (OR=.831, 95% CI: .727-.950) and RAOM as an indication for surgery (OR: 5.767; 95% CI: 1.696-19.603) were predictors of a second TT. Gender, age, asthma, prematurity, and low birth weight were not significantly associated with a second TT. CONCLUSIONS: RAOM and a short TT retention time were significantly associated with additional TT placement, enhancing the need for and importance of follow up of these children after TT extrusion.

Predictive factors for repeated tympanostomy tube placement in children

Objectives: To determine the rate and risk factors for additional tympanostomy tube (TT) placement after first set of TT extrusion in children.Materials and methodsSingle-centre cohort study. Clinical records of children undergoing TT placement from January 2015 to December 2017 were reviewed and factors related to the need for subsequent TT were evaluated.ResultsA total of 183 children were included, with a mean age of 5.45±2.672 years old. All surgeries were performed simultaneously with adenoidectomy and 64.3% with tonsillectomy. The mean TT retention time was 12.13±6.033 months and the rate of second TT insertion was 21.9%. The TT retention time was significantly lower in children who needed a second TT (8.97±3.962 vs 13.05±6.229, p<.001). Other factors significantly associated with the need for a second TT in the univariate analysis were the presence of otorrhoea and snoring after TT placement (p=.042 and p=.02), RAOM (p=.016), passive smoking (p=.038) and rhinorrhoea (p=.008). However, on multivariate analysis only TT retention time (OR=.831, 95% CI: .727–.950) and RAOM as an indication for surgery (OR: 5.767; 95% CI: 1.696–19.603) were predictors of a second TT. Gender, age, asthma, prematurity, and low birth weight were not significantly associated with a second TT.ConclusionsRAOM and a short TT retention time were significantly associated with additional TT placement, enhancing the need for and importance of follow up of these children after TT extrusion. (AU)

Objetivos: Determinar la tasa y los factores de riesgo para la colocación de tubos de timpanostomía (TT) adicional después de la extrusión de los primeros TT en niños.Materiales y métodosEstudio retrospectivo de los registros médicos de los niños sometidos a la colocación de TT desde enero del 2015 hasta diciembre del 2017; se evaluaron los factores relacionados con la necesidad de TT posterior.ResultadosSe incluyó a 183 niños, con una edad media de 5,45±2,672 años. Todas las cirugías se realizaron simultáneamente con adenoidectomía y el 64,3% con amigdalectomía. El tiempo medio de retención del TT fue de 12,13±6,033 meses y la tasa de segunda inserción del TT fue del 21,9%. El tiempo de retención del TT fue significativamente menor en los niños que necesitaron un segundo TT (8,97±3,962 vs. 13,05±6,229, p<0,001). Otros factores asociados significativamente a la necesidad de un segundo TT en el análisis univariable fueron la presencia de otorrea y ronquidos tras la colocación del TT (p=0,042 y p=0,02, respectivamente), la otitis media aguda de repetición (OMAr) (p=0,016), el tabaquismo pasivo (p=0,038) y la rinorrea (p=0,008). Sin embargo, en el análisis multivariado solo el tiempo de retención del TT (OR=0,831, IC del 95%: 0,727-0,950) y la OMAr como indicación de cirugía (OR: 5,767; IC del 95%: 1,696-19,603) fueron predictores de un segundo TT. El sexo, la edad, el asma, la prematuridad y el bajo peso al nacer no se asociaron significativamente con un segundo TT.ConclusionesLa OMAr y un corto tiempo de retención del TT se asociaron significativamente con la colocación de un segundo TT, lo que refuerza la necesidad e importancia del seguimiento de estos niños tras la extrusión del TT. (AU)

Pharyngoplasty for obstructive sleep apnea: The influence of surgical technique

Introduction and objectives: Obstructive sleep apnea is the most frequent sleep disorder worldwide, with rising incidence. Pharyngoplasty is an alternative treatment in patients not suitable to continuous positive airway pressure devices (CPAP). The aim of this study is to compare different surgical techniques of pharyngoplasty for treatment of obstructive sleep apnea and evaluate its influence in surgical success.Material and methodsRetrospective study of 92 patients that underwent pharyngoplasty for treatment of obstructive sleep apnea from 2001 to 2020. Included patients performed classic uvulopalatopharyngoplasty (UPPP), radiofrequency assisted uvulopalatopharyngoplasty (RF-UPPP) or barbed reposition pharyngoplasty (BRP). Surgical success was defined and outcomes and complications assessed for each procedure.ResultsMost patients were male, with a mean age of 49.36±9.6 years and a mean apnea hypopnea index (AHI) of 29.14±2.94events/h. Thirty-six patients performed classic UPPP, thirty-one underwent RF-UPPP and the remaining twenty-five performed BRP. BRP achieved the highest success rate (66%) in comparison with UPPP (57%) and RF-UPPP (54%) (p=0.032). Mean relative AHI reduction after surgery was not statistically different between three procedures (p=0.098), although there was a tendency for greater reduction with BRP. Most symptoms improved after surgery and snoring was the most recurrent symptom. BRP had less foreign body sensation after surgery, however, it was the procedure with highest rate of post-operative tonsillar bleeding.ConclusionsIn our department, the introduction of recent techniques of velopharyngeal surgery, focused in functional and lateral muscular collapse, has translated into an increase in success rate after surgery. The relative ease of the procedure and reduction of long term complications make BRP an attractive alternative option for CPAP in OSA, in carefully selected patients. (AU)

Introducción y objetivos: La apnea obstructiva del sueño es el trastorno del sueño más frecuente en todo el mundo, con una incidencia creciente. La faringoplastia es una alternativa de tratamiento en pacientes no aptos para dispositivos de presión positiva continua en la vía aérea (CPAP). El objetivo de este estudio es comparar diferentes técnicas quirúrgicas de faringoplastia para el tratamiento de la apnea obstructiva del sueño y evaluar su influencia en el éxito quirúrgico.Material y métodosEstudio retrospectivo de 92 pacientes que fueron sometidos a faringoplastia para el tratamiento de la apnea obstructiva del sueño desde 2001 hasta 2020. Los pacientes incluidos se sometieron a uvulopalatoplastia clásica (UPPP), uvulopalatoplastia asistida por radiofrecuencia (RF-UPPP) o faringoplastia de reposición con sutura barbada (BRP). Se definió el éxito quirúrgico y se evaluaron los resultados y las complicaciones de cada procedimiento.ResultadosLa mayoría de los pacientes fueron varones, con una edad media de 49,36±9,6 años y un índice de apnea-hipopnea (IAH) medio de 29,14±2,94 eventos/hora. Treinta y seis pacientes realizaron UPPP clásica, 31 se sometieron a RF-UPPP y los 25 restantes realizaron BRP. La BRP obtuvo la mayor tasa de éxito (66%) en comparación con la UPPP (57%) y la RF-UPPP (54%) (p=0,032). La reducción relativa media del IAH tras la cirugía no fue estadísticamente diferente entre los 3 procedimientos (p=0,098), aunque hubo una tendencia a una mayor reducción con la BRP. La mayoría de los síntomas mejoraron tras la cirugía y el ronquido fue el síntoma más recurrente. La BRP tuvo menos sensación de cuerpo extraño después de la cirugía, sin embargo, fue el procedimiento con mayor tasa de hemorragia postoperatoria. (AU)

Evaluation of the Polyphenolic Composition and Bioactivities of Three Native Cabo Verde Medicinal Plants.

The use of medicinal plants in a variety of health conditions remains essential for the discovery of new treatments. The present study aimed to investigate the bioactive properties of three native plants from Cabo Verde Islands, namely Artemisia gorgonum Webb, Sideroxylon marginatum (Decne. ex Webb) Cout., and Tamarix senegalensis DC., contributing to the characterization of less-known medicinal plants and their potential benefits for human health. Known compounds, such as kaempferol, quercetin, caffeyolquinic, and apigenin derivatives, among others, were detected in the plant species under study. Overall, all species demonstrated good antioxidant capacity, especially the ethanolic extracts of A. gorgonum (EC50 = 0.149 mg/mL) in TBARS assay. Moreover, the ethanolic extracts of the studied plants showed cytotoxic properties against tumor cells, and again the A. gorgonum extract proved to be the most effective in inhibiting tumor growth, mainly in the CaCO2 (GI50 = 17.3 µg/mL) and AGS (GI50 = 18.2 µg/mL) cell lines. Only the ethanolic extracts of T. senegalensis and S. marginatum demonstrated anti-inflammatory activity, albeit weak (EC50 = 35 and 43 µg/mL, respectively). The present study contributed to increased knowledge about the bioactive properties of these plants commonly used in traditional medicine, some of which was discussed for the first time, opening new perspectives for their use in a wider range of health conditions, especially in African countries, where access to modern health care is more limited.

Excess hospitalizations and mortality associated with seasonal influenza in Portugal, 2008-2018.

BACKGROUND: Influenza can have a domino effect, triggering severe conditions and leading to hospitalization or even death. Since influenza testing is not routinely performed, statistical modeling techniques are increasingly being used to estimate annual hospitalizations and deaths associated with influenza, to overcome the known underestimation from registers coded with influenza-specific diagnosis. The aim of this study was to estimate the clinical and economic burden of severe influenza in Portugal. METHODS: The study comprised ten epidemic seasons (2008/09-2017/18) and used two approaches: (i) a direct method of estimating the seasonal influenza hospitalization incidence, based on the number of National Health Service hospitalizations with influenza-specific International Classification of Diseases (ICD) codes (ICD-9: 487-488; ICD-10: J09-J11), as primary or secondary diagnosis; (ii) an indirect method of estimating excess hospitalizations and deaths using broader groups of ICD codes in time-series models, computed for six age groups and four groups of diagnoses: pneumonia or influenza (ICD-9: 480-488, 517.1; ICD-10: J09-J18), respiratory (ICD-9: 460-519; ICD-10: J00-J99), respiratory or cardiovascular (R&C, ICD-9: 390-459, 460-519; ICD-10: I00-I99, J00-J99), and all-cause. Means are reported excluding the H1N1pdm09 pandemic (2009/10). RESULTS: The mean number of hospitalizations coded as due to influenza per season was 1,207, resulting in 11.6 cases per 100,000 people. The mean direct annual cost of these hospitalizations was €3.9 million, of which 78.6% was generated by patients with comorbidities. Mean annual influenza-associated R&C hospitalizations were estimated at 5356 (min: 456; max: 8776), corresponding to 51.5 cases per 100,000 (95% CI: 40.9-62.0) for all age groups and 199.6 (95% CI: 163.9-235.8) for the population aged ≥ 65 years. The mean direct annual cost of the estimated excess R&C hospitalizations was €15.2 million for all age groups and €12.8 million for the population aged ≥ 65 years. Mean annual influenza-associated all-cause deaths per 100,000 people were estimated at 22.7 for all age groups. CONCLUSIONS: The study findings suggest that there is an under-detection of influenza in the Portuguese population. A high burden of severe influenza remains to be addressed, not only in the elderly population but also in younger people.

Membrane Technology for Valorization of Mango Peel Extracts.

Mango peel is rich in nutritional and functional compounds, such as carbohydrates, dietary fibers, proteins, and phenolic compounds, with high potential to be applied in the food industry. Most of the investigation about recovery of bioactive compounds from fruit bioproducts involves extraction techniques and further separation of target compounds. There is still a lack of information about the potential of membrane processes to recover the nutritive/functional compounds present in aqueous extracts of those bioproducts. This research is addressed to study the performance of ultrafiltration (UF), followed by nanofiltration (NF) of UF permeates, to fractionate the compounds present in aqueous extracts of mango peel. Both UF and NF concentration processes were carried up to a volume concentration factor of 2.0. Membranes with molecular weight cut-offs of 25 kDa and 130 Da were used in the UF and NF steps, respectively. UF and NF concentrates showed antioxidant activity, attributed to the presence of phenolic compounds, with rejections of about 75% and 98.8%, respectively. UF membranes totally rejected the higher molecular weight compounds, and NF membranes almost totally concentrated the fermentable monosaccharides and disaccharides. Therefore, it is envisaged that NF concentrates can be utilized by the food industry or for bioenergy production.

Multi-Target Alternative Approaches to Promoting Fresh-Cut Carrots' Bioactive and Fresh-like Quality.

Fresh-cut fruits and vegetables, as near-fresh foods, are a quick and easy solution to a healthy and balanced diet. The rapid degradation of nutritional and sensory quality during the processing and storage of a product is critical and plant-type-dependent. The introduction of disruptive technological solutions in fresh-cut processing, which could maintain fresh-like quality with less environmental impact, is an emerging research concept. The application of abiotic stress treatments (heat shock and UV-C) induces metabolic responses and microbial effects in plant tissues, potentially slowing down several quality senescence pathways. The previously selected combined and single effects of heat shock (100 °C/45 s; in the whole root) and UV-C (2.5 kJ/m2) treatments and two packaging conditions (oriented polypropylene (OPP) vs. micro-perforated OPP films) on controlling critical degradation pathways of fresh-cut carrots and on promoting bioactive and sensory quality during storage (5 °C, 14 days) were studied. Among the tested combinations, synergistic effects on the quality retention of fresh-cut carrots were only attained for applying heat shock associated with micro-perforated OPP film packaging. Its effects on reducing (3.3 Log10 CFU/g) the initial contamination and controlling microbiological spoilage (counts below the threshold limit of 7.5 Log10 CFU/g), increasing the bioactive content (38% and 72% in total phenolic content and chlorogenic acid, respectively), and preserving fresh quality attributes prove to be a viable alternative technology for shredded carrot processing.

Storage Stability and In Vitro Bioaccessibility of Microencapsulated Tomato (Solanum Lycopersicum L.) Pomace Extract.

Tomato pomace is rich in carotenoids (mainly lycopene), which are related to important bioactive properties. In general, carotenoids are known to react easily under environmental conditions, which may create a barrier in producing stable functional components for food. This work intended to evaluate the storage stability and in vitro release of lycopene from encapsulated tomato pomace extract, and its bioaccessibility when encapsulates were incorporated in yogurt. Microencapsulation assays were carried out with tomato pomace extract as the core material and arabic gum or inulin (10 and 20 wt%) as wall materials by spray drying (160 and 200 °C). The storage stability results indicate that lycopene degradation was highly influenced by the presence of oxygen and light, even when encapsulated. In vitro release studies revealed that 63% of encapsulated lycopene was released from the arabic gum particles in simulated gastric fluid, whereas for the inulin particles, the release was only around 13%. The feed composition with 20% inulin showed the best protective ability and the one that enabled releasing the bioactives preferentially in the intestine. The bioaccessibility of the microencapsulated lycopene added to yogurt increased during simulated gastrointestinal digestion as compared to the microencapsulated lycopene alone. We anticipate a high potential for the inulin microparticles containing lycopene to be used in functional food formulations.

Application of an Eco-Friendly Antifungal Active Package to Extend the Shelf Life of Fresh Red Raspberry (Rubus idaeus L. cv. 'Kweli').

The main objective of this study was to extend the shelf life of fresh red raspberry (Rubus idaeus. L. cv. 'Kweli') by using active film-pads inside commercial compostable packages. The pads were produced with chitosan (Ch) with the incorporation of green tea (GTE) and rosemary (RSME) ethanolic extracts as natural antifungal agents. Pads were placed on the bottom of commercial fruit trays underneath the fruits, and the trays were heat-sealed with a polyacid lactic (PLA) film. Preservation studies were carried out over 14 days of storage at refrigeration temperature (4 °C). Raspberry samples were periodically analyzed throughout storage, in terms of quality attributes (fungal decay, weight loss, firmness, surface color, pH, total soluble solids), total phenolic content and antioxidant activity. Gas composition inside the packages was also analyzed over time. From the packaging systems tested, the ones with active film-pads Ch + GTE and Ch + RSME were highly effective in reducing fungal growth and decay of raspberry during storage, showing only around 13% and 5% of spoiled fruits after 14 days, respectively, in contrast with the packages without pads (around 80% of spoiled fruits detected). In addition, fruits preserved using packages with Ch + RSME active film-pads showed lower mass loss (5.6%), decreased firmness (3.7%) and reduced antioxidant activity (around 9% and 15% for DPPH and FRAP methods, respectively). This sustainable packaging presents a potential strategy for the preservation of raspberries and other highly perishable small fruits.