Influence of Adherence to the Mediterranean Diet and Level of Physical Activity with Liver Steatosis in People Aged > 50 Years and with a BMI > 25 kg/m2: Association with Biochemical Markers.

BACKGROUND: The main objective of this study is to determine the accuracy of different biochemical markers of hepatic steatosis and to correlate liver steatosis with adherence to the Mediterranean diet and level of physical activity. METHODS: A cross-sectional study was carried out, including subjects over 50 years of age, with a BMI > 25 kg/m2, but excluding any patient with documented hepatic pathology other than hepatic steatosis. Participants were divided into two groups: patients with hepatic steatosis diagnosed by ultrasound (SG) and a control group of individuals without hepatic steatosis (CG). The level of physical activity was recorded by the IPAQ-SF questionnaire and the adherence to the Mediterranean diet was recorded using the PREDIMED questionnaire. Biochemical markers analyzed included the Hepatic steatosis index (HSI), AST-to-Platelet ratio (APRI) and Fibrosis-4 (FIB-4). RESULTS: A total of 116 patients were included, 71 belonging to the SG and 45 to the CG. A total of 58.6% of the patients showed low adherence to the Mediterranean diet, 35.4% moderate adherence and 6% high adherence. The median estimated physical activity was 495 METS, with most participants reporting light activity. In the SG, significantly higher HSI values were observed (p < 0.001). A cut-off point of a HSI of 40 was established, with a sensitivity of 73.2% and a specificity of 65.8%. Significantly higher FIB-4 values (p = 0.039) were also observed in the SG. A cut-off point of FIB-4 was set at 0.27, with a sensitivity of 69% and a specificity of 57.9%. Patients in the SG showed lower scores in the PREDIMED. Patients in the SG tended to show lower METS scores. However, the higher number of patients with intense activity in the CG group stands out (p = 0.008). CONCLUSIONS: The HSI and FIB-4 showed a significant correlation with liver steatosis. Hepatic steatosis is associated with low adherence to the Mediterranean diet and patients with hepatic steatosis tended to have lower METS scores.

Pain assessment and management among adult patients in a gynecology ward: a best practice implementation project.

OBJECTIVES: This project aimed to improve compliance with evidence-based practice in pain assessment and management in a gynecology ward. INTRODUCTION: Effective pain control is important to prevent the negative consequences of pain that is poorly managed. However, it remains undervalued and inadequately treated. Applying evidence-based practices to correctly evaluate and manage pain is essential to improve pain relief. METHODS: This project followed the JBI Evidence Implementation Framework. A baseline audit of 41 women admitted to the gynecology ward was conducted and measured against 5 best practice criteria, along with a patient satisfaction questionnaire. Targeted strategies were then implemented and a follow-up audit was conducted using the same criteria, methods, and sample size as the baseline audit. RESULTS: The baseline audit revealed gaps between current and best practice. Barriers to implementation were identified and strategies to resolve the barriers were designed and implemented (nurse education, informative materials, electronic patient records system improvements). Comprehensive pain assessment, including dynamic and static pain assessment, use of a validated tool, and education provided to patients and carers, improved in the follow-up audit. There was no change in patient satisfaction levels; however, the discrepancy between pain measured by nurses and pain measured by patients was reduced. CONCLUSIONS: The JBI methodology was useful in improving compliance with evidence-based practice criteria. It also facilitated adaptation to new barriers, such as the COVID-19 pandemic. Improving nurses' knowledge of pain assessment can lead to more accurate assessment. Inadequate records systems also made it difficult to record the care that was provided. Subsequent audits will assess sustainability and the project will be escalated to other wards.

[Indicadores de salud perinatal en una región española entre los años 2015 y 2020.] / Perinatal health indicators in a region of Spain corresponding to the period 2015 to 2020.

OBJECTIVE: The availability in the literature of data related to perinatal variables in the Spanish population is very scarce. The aim of this study was to know the evolution of perinatal health indicators according to the risk groups of prematurity and birth weight, the proportion of multiple births, caesarean section and stillbirths. METHODS: We conducted a population-based cross-sectional study of births in eleven hospitals in Castilla y León (January 2015 to June 2020). There were 70,024 newborns from 68,769 deliveries. Jointpoint regression analysis was used to identify changes in trend over the years, and binomial logistic regression was used to adjust for the potential interaction of hospital type, sex, type of delivery and multiple births on the frequencies of prematurity and death. RESULTS: There was a 19.9% decrease in deliveries and a 42% decrease in multiple births, with no change in preterm (7.7%) and stillbirths (0.44%). The percentage of caesarean sections was 21.5% with a slight downward trend over time. Death (stillbirth) was associated with preterm multiple birth; especially with the male-male combination (p<0.05). Late preterm and early term newborns showed higher risk of death compared to term newborns: OR 7.7 (95%CI 5.6-10.7) and 2.4 (95%CI 1.6-3.6), respectively; as well as the low birth weight group (OR 17.6; 95%CI 13.9-22.2) and small for gestational age (OR 3.4; 95%CI 1.9-5.8), compared to those of adequate weight. CONCLUSIONS: Prior to the development of the COVID-19 pandemic there is a decline in births, including multiple births, with no change in stillbirths or prematurity. Late preterm and early term newborns are at increased risk of intrauterine death.

OBJETIVO: La disponibilidad en la literatura de datos relacionados con variables perinatales en la población española son muy escasos. El objetivo de este estudio fue conocer la evolución de los indicadores de salud perinatal atendiendo a los grupos de riesgo de prematuridad y de peso al nacimiento, la proporción de parto múltiple, de cesárea y de mortinatos. METODOS: Se realizó un estudio transversal poblacional de los partos en once hospitales de Castilla y León (enero de 2015 a junio de 2020). Hubo 70.024 recién nacidos (RN) procedentes de 68.769 partos. Se utilizó el análisis de regresión Jointpoint para identificar cambios en la tendencia a lo largo de los años, y la regresión logística binomial para ajustar la potencial interacción del tipo de hospital, el sexo, el tipo de parto y el parto múltiple en las frecuencias de prematuridad y de fallecimiento. RESULTADOS: Hubo un descenso de partos del 19,9% y de los múltiples del 42%, sin cambios en los RN prematuros (7,7%) ni en los mortinatos (0,44%). El porcentaje de cesáreas fue del 21,5% con una ligera tendencia temporal descendente. El fallecimiento (mortinato) se asoció al parto múltiple pretérmino; especialmente a la combinación varón-varón (p<0,05). Los RN pretérminos tardíos y términos precoces mostraron mayor riesgo de fallecer frente a los RN a término: OR 7,7 (IC95% 5,6-10,7) y 2,4 (IC95% 1,6-3,6), respectivamente; así como el grupo de bajo peso (OR 17,6; IC95% 13,9-22,2) y el pequeño para la edad gestacional (OR 3,4; IC95% 1,9-5,8), frente a los de peso adecuado. CONCLUSIONES: Previo al desarrollo de la pandemia por COVID-19 existe un descenso de la natalidad, incluidos los partos múltiples, sin cambios en los mortinatos ni en la prematuridad. Los RN pretérminos tardío y términos precoces tienen mayor riesgo de fallecer intraútero.

Digital twin of a continuous direct compression line for drug product and process design using a hybrid flowsheet modelling approach.

The pharmaceutical industry is continuously overcoming ways to reduce its development times to market and bring new medicines to patients with the highest quality standards faster. This can be achieved with continuous manufacturing and digital design by minimising the amount of active pharmaceutical ingredient (API) needed in drug product design, early project de-risking, and reducing the use of clinical manufacturing equipment, rework, and quality investigations. This paper presents the digital twin of a continuous direct compression line combining first-principles models, residence time distribution (RTD) models obtained from discrete element method (DEM) simulations, science of scale tools and data-driven models from process data in a hybrid flowsheet approach. The flowsheet predicts critical process parameters in the feeders, blender, and tablet press, and critical quality attributes, like tablet composition, weight, thickness, and hardness. It allows the study of the steady state operation in the design space, the impact of operating conditions, material and process parameters, and the dynamic response to disturbances. This is used to de-risk and optimise drug product and process development while reducing the number of experiments. The digital twin also has the potential to guide manufacturing runs and respond to new drug product market approval queries using flowsheet modelling.

Adherence to hypothermia guidelines in newborns with hypoxic-ischemic encephalopathy.

INTRODUCTION: We do not have population data in Spain on the application of therapeutic hypothermia (TH). The objective was to examine adherence to management standards during TH of infants with hypoxic-ischemic encephalopathy (HIE). METHOD: Multicenter observational cohort study from the beginning of TH (year 2010) in 5 hospitals in a Spanish region, until year 2019. RESULTS: 133 patients were recruited, 72% diagnosed with moderate HIE and the rest of them with severe HIE. In 84% of infants, passive hypothermia was started at birth. Active TH was started at a median age of 5 h of life (IQR 3.3; 6.3), although the central targeted temperature (33-34 °C) was reached at a median age of 3.5 h (IQR 1; 6). Those born extramural, initiated active TH 3.3 h on average later than those born intramural, but without differences in the age at which the targeted temperature was reached. Sedoanalgesia was used in 97%. 100% were monitored with amplitude-integrated EEG and 59% with cerebral oxymetry. MRI was performed in 94% with moderate HIE vs. 65% with severe; P < .001. Neuron-specific enolase in cerebrospinal fluid was determined in 42%. The average duration of rewarming was median 10 h (IQR 8; 12), with no differences depending on the degree of HIE (P = .57). CONCLUSIONS: The implementation of TH successfully met the standards. However, aspects of care that could be improved were detected. Auditing newborn care with HIE is crucial to achieving programs with a high quality of care in each region.

[Adherence to hypothermia guidelines in newborns with hypoxic-ischemic encephalopathy]. / Adherencia a los estándares en el tratamiento con hipotermia del recién nacido con encefalopatía hipóxico-isquémica.

INTRODUCTION: We do not have population data in Spain on the application of therapeutic hypothermia (TH). The objective was to examine adherence to management standards during TH of infants with hypoxic-ischemic encephalopathy (HIE). METHOD: Multicenter observational cohort study from the beginning of TH (year 2010) in 5 hospitals in a Spanish region, until year 2019. RESULTS: 133 patients were recruited, 72% diagnosed with moderate HIE and the rest of them with severe HIE. In 84% of infants, passive hypothermia was started at birth. Active TH was started at a median age of 5hours of life (IQR: 3.3-6.3), although the central targeted temperature (33-34°C) was reached at a median age of 3.5hours (IQR: 1-6). Those born extramural, initiated active TH 3.3hours on average later than those born intramural, but without differences in the age at which the targeted temperature was reached. Sedoanalgesia was used in 97%. The 100% were monitored with amplitude-integrated EEG and 59% with cerebral oxymetry. MRI was performed in 94% with moderate HIE vs. 65% with severe; P<.001. Neuron-specific enolase in cerebrospinal fluid was determined in 42%. The average duration of rewarming was median 10hours (IQR: 8-12), with no differences depending on the degree of HIE (P=.57). CONCLUSIONS: The implementation of TH successfully met the standards. However, aspects of care that could be improved were detected. Auditing newborn care with HIE is crucial to achieving programs with a high quality of care in each region.

Temporal Trends in the Severity and Mortality of Neonatal Hypoxic-Ischemic Encephalopathy in the Era of Hypothermia.

INTRODUCTION: There is a paucity of studies examining temporal trends in the incidence and mortality of moderate-to-severe hypoxic-ischemic encephalopathy (HIE) during the last decade of therapeutic hypothermia (TH). METHODS: Multicenter cross-sectional study of all infants ≥35 weeks gestational age diagnosed with moderate-to-severe HIE within 6 h of birth in an extensive region of Spain between 2011 and 2019, in order to detect trend changes over time in the (1) annual incidence, (2) severity of neurological and systemic organ involvement, and (3) neonatal death from HIE. RESULTS: Annual incidence rate of moderate-to-severe HIE was 0.84 (95% confidence interval [CI] 0.7-0.97) per 1,000 births, without trend changes over time (p = 0.8), although the proportion of severe HIE infants showed an average annual decline of 0.86 points (95% CI 0.75-0.98). There were 102 (70%) infants diagnosed with moderate HIE and 44 (30%) with severe HIE. TH was offered to 139/146 (95%) infants. Infants with clinical and/or electrical seizures showed a decreasing trend from 56 to 28% (p = 0.006). Mortality showed a nonstatistically significant decline (p = 0.4), and the severity of systemic damage showed no changes (p = 0.3). Obstetric characteristics remained unchanged, while higher perinatal pH values (p = 0.03) and Apgar scores (p = 0.05), and less need for resuscitation (p = 0.07), were found over time. CONCLUSION: The annual incidence of moderate-to-severe HIE has stabilized at around 1 per 1,000 births, with a temporal trend toward a decrease in severe HIE infants and a slight decline of mortality. No association was found between temporal trends and changes in perinatal/obstetric characteristics over time.

Paclitaxel-Loaded Folate-Targeted Albumin-Alginate Nanoparticles Crosslinked with Ethylenediamine. Synthesis and In Vitro Characterization.

Among the different ways to reduce the secondary effects of antineoplastic drugs in cancer treatment, the use of nanoparticles has demonstrated good results due to the protection of the drug and the possibility of releasing compounds to a specific therapeutic target. The α-isoform of the folate receptor (FR) is overexpressed on a significant number of human cancers; therefore, folate-targeted crosslinked nanoparticles based on BSA and alginate mixtures and loaded with paclitaxel (PTX) have been prepared to maximize the proven antineoplastic activity of the drug against solid tumors. Nanometric-range-sized particles (169 ± 28 nm-296 ± 57 nm), with negative Z-potential values (between -0.12 ± 0.04 and -94.1± 0.4), were synthesized, and the loaded PTX (2.63 ± 0.19-3.56 ±0.13 µg PTX/mg Np) was sustainably released for 23 and 27 h. Three cell lines (MCF-7, MDA-MB-231 and HeLa) were selected to test the efficacy of the folate-targeted PTX-loaded BSA/ALG nanocarriers. The presence of FR on the cell membrane led to a significantly larger uptake of BSA/ALG-Fol nanoparticles compared with the equivalent nanoparticles without folic acid on their surface. The cell viability results demonstrated a cytocompatibility of unloaded nanoparticle-Fol and a gradual decrease in cell viability after treatment with PTX-loaded nanoparticle-Fol due to the sustainable PTX release.

Lack of changes in preterm delivery and stillbirths during COVID-19 lockdown in a European region.

Preliminary data in Europe have suggested a reduction in prematurity rates during the COVID-19 pandemic, implying that contingency measures could have an impact on prematurity rates. We designed a population-based prevalence proportion study to explore the potential link between national lockdown measures and a change in preterm births and stillbirths. Adjusted multivariate analyses did not show any decrease in preterm proportions during the lockdown period with respect to the whole prelockdown period or to the prelockdown comparison periods (2015-2019): 6.5% (95%CI 5.6-7.4), 6.6% (95%CI 6.5-6.8), and 6.2% (95%CI 5.7-6.7), respectively. Proportions of preterm live births did not change during lockdown when different gestational age categories were analyzed, nor when birthweight categories were considered. No differences in stillbirth rates among the different study periods were found: 0.33% (95%CI 0.04-0.61) during the lockdown period vs. 0.34% (95%CI 0.22-0.46) during the prelockdown comparison period (2015-2019).Conclusion: We did not find any link between prematurity and lockdown, nor between stillbirths and lockdown. Collaborative efforts are desirable to gather more data and additional evidence on this global health issue. What is Known: • Prematurity is associated with increased risk of morbidity and mortality. • Contingency measures during the COVID-19 pandemic may have an impact on reducing prematurity rates. What is New: • Prematurity and stillbirth rates remained stable in Castilla-y-León, a Spanish region, during COVID-19 lockdown. • The role of behavioral patterns and sociocultural factors in the prevention of preterm birth as a result of lockdown measures remains a subject for debate.

Impact of intertwin interval on short-term neonatal outcomes of the second twin in dichorionic pregnancies with vaginal delivery.

OBJECTIVE: To examine the effect of intertwin interval on umbilical cord pH and Apgar scores of the second twin after vaginal delivery. METHODS: A retrospective study of twin deliveries at a university hospital in Spain between August 2012 and September 2017. Inclusion criteria were vaginal delivery of both twins at 32 gestational weeks or more. Exclusion criteria were monochorionic pregnancies and indication for cesarean delivery. The sample was dichotomized by intertwin interval (<10 and ≥10 minutes). Neonatal outcomes including Apgar scores and umbilical cord pH were evaluated. RESULTS: Overall, 323 twin deliveries were included. Intertwin interval was less than 10 minutes in 277 (85.6%) cases, and 10 minutes or longer in 46 (14.2%). There were no differences in maternal or obstetric characteristics between the groups. Incidence of instrumental delivery (P<0.001) and internal podalic version (P<0.001) for the second twin was higher in the longer interval group. A longer interval was associated with higher frequencies of 1-minute Apgar score below 4 (P=0.009), 5-minute Apgar score below 7 (P<0.001), and umbilical cord pH below 7.15 (P<0.001). CONCLUSION: Second twins with an intertwin interval of 10 minutes or longer are more likely to have poorer Apgar scores and arterial blood pH below 7.15.

Biocompatibility studies of intravenously administered ionic-crosslinked chitosan-BSA nanoparticles as vehicles for antitumour drugs.

In this study, a new alternative of ionic crosslinked nanoparticles (NPs) based on chitosan (C) and bovine serum albumin (A; BSA) was evaluated as drug delivery system for antitumour compounds (doxorubicin hydrochloride as a model). The different responses to the pH of the medium were determined by the electrostatic interactions induced by each polymeric combination (C50/A50; C80/A20; C20/A80). NPs revealed a nanoscale size (167-392 nm) and a positive net charge (12-26 mV), modulated by doxorubicin (DOX) loading. Drug loading capacity was higher than 5.2 ±â€¯1.8 µgDOX/mgNP (Encapsulation efficiency = 34%), and an initial burst release was followed by a sustained delivery. Cellular uptake assays confirmed the entry of NPs in three human tumor cells (MCF7, T47D and Hela), triggering antioxidant responses (superoxide dismutase, catalase, glutathione reductase and total glutathione content) in those cells. This was also consistent with the decreased in IC50 values observed after the incubation of these cells with C20/A80-DOX and C50/A50-DOX NPs (1.90-3.48 µg/mL) compared with free DOX (2.36-6.025 µg/mL). In vivo results suggested that the selected proportions of chitosan-BSA created nonhemolytic and biocompatible stable NPs at the selected dose of 20 mg/kg. Despite the different formulations, this study demonstrated that these NPs could serve as safe drug carriers in further in vivo investigations.

The Role of Anionic Polysaccharides in the Preparation of Nanomedicines with Anticancer Applications.

Cancer has become one of the main causes of death in developed countries, and it is expected to be declared as the disease with the highest worldwide morbidity and mortality indexes in the coming decades. Nanomedicine aims to overcome some problems related to this prevalent disease, particularly the lack of efficient diagnostic and therapeutic tools. The most recent scientific advances, which have conducted to a more personalized medicine, were focused on the production of nanocarriers involved into the transport and the delivery of drugs to targeted cells. A wide variety of nanocarriers composed by different materials have been designed for their use as drug delivery systems. Polysaccharides have emerged as very useful biopolymers among all raw materials used in the preparation of these nanoplatforms. They are highly stable, non-toxic and biodegradable molecules, and also present some chemical properties which are very difficult to reproduce using artificial polymers. Anionic polymers, such as hyaluronic acid, heparin or alginate, present some structural and chemical characteristics which make them ideal polymers to prepare nanosystems with anticancer applications. This review will focus on the description of some anionic polysaccharides and the possibilities they offer towards the preparation of nanosystems with applications in cancer treatment and diagnostics.

Cooperative effect of 5-aminolevulinic acid and gold nanoparticles for photodynamic therapy of cancer.

An enhanced capacity for protoporphyrin IX (PpIX) synthesis through 5-aminolevulinic acid (ALA) administration has been reported in cancer cells. We compared the effect of ALA and ALA combined with gold nanoparticles (ALA-AuNPs) for photodynamic therapy (PDT) on human cervical cancer cell line. Because PpIX after photoactivation produces reactive oxygen species (ROS), ALA-AuNPs combinations can enhance this production and then induce higher phototoxicity. With this aim, two different-sized AuNPs (14 and 136 nm, AuNP1 and AuNP2, respectively) were successfully synthesized and characterized by UV-visible spectrophotometry and transmission electron microscopy. AuNPs were combined with ALA to evaluate their cooperative action in the intracellular ROS production, cell viability, and cell death mechanism. Results showed that ALA-AuNPs combinations induced cell death via ROS-mediated apoptosis after PDT. When exposed to light at their resonance wavelength, AuNP2 combined with ALA result in cytotoxicity and cell injury in greater extension than ALA and ALA-AuNP1 combination.

Olive oil quality and ripening in super-high-density Arbequina orchard.

BACKGROUND: The aim of this work was to evaluate the evolution of the quality of extra virgin olive oil obtained from a super-high-density Arbequina orchard, under a drip irrigation system, throughout the ripening process. For this objective, physicochemical, nutritional and sensory parameters were studied. In addition, the oxidative stability, pigment content and colour evolution of olive oil were analysed during the ripening process. RESULTS: Free acidity increased slightly throughout the ripening process, while peroxide value and extinction coefficient decreased. Total phenol content and oxidative stability showed a similar trend, increasing at the beginning of ripening up to a maximum and thereafter decreasing. α-Tocopherol and pigment contents decreased with ripening, leading to changes in colour coordinates. Sensory parameters were correlated with total phenol content, following a similar trend throughout the maturation process. CONCLUSION: By sampling and monitoring the ripeness index weekly, it would be possible to determine an optimal harvesting time for olives according to the industrial yield and the physicochemical, nutritional and sensory properties of the olive oil.

Novel methods and devices to enhance transdermal drug delivery: the importance of laser radiation in transdermal drug delivery.

Skin permeation-enhancement technology is a rapidly developing field, which could significantly increase the number of drugs suitable for transdermal delivery. In this review, we highlight recent advances in both 'passive' and 'active' transdermal drug-delivery technologies, as well as in the laser ablation method. This paper concludes with a brief forward-looking perspective discussing what can be expected as laser technology continues to develop in the coming years.

In vitro transdermal and biological evaluation of ALA-loaded poly(N-isopropylacrylamide) and poly(N-isopropylacrylamide-co-acrylic acid) microgels for photodynamic therapy.

Poly(N-isopropylacrylamide) (PNIPA) and Poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPA-co-AA)) microgels loaded with 5-aminolevulinic acid (ALA) were prepared by the spray-drying method. The amount of drug loaded was 290 µg ALA/mg microgel for PNIPA and 244 µg ALA/mg microgel for P(NIPA-co-AA) microgels. Maximum in vitro drug release took place within 15-30 min for PNIPA and 1-1.5 h for P(NIPA-co-AA) microgels as a function of pH, at 37°C. Transdermal delivery from microgels showed permeation fluxes 10 times higher than the passive diffusion flux. The cytotoxicity of microgels synthesized in HeLa cells after the application of photodynamic therapy (PDT) was superior compared with the administration of ALA in solution alone. Finally, the use of these microgels as a delivery vehicle for ALA constitutes a system capable of enhancing its topical administration and PDT effectiveness.

Tamoxifen-loaded nanoparticles based on a novel mixture of biodegradable polyesters: characterization and in vitro evaluation as sustained release systems.

Nanoparticles (NP) from mixtures of two poly(D,L-lactide-co-caprolactone) (PLC) copolymers, PLC 40/60 and PLC 86/14, with poly(D,L-lactide) (PDLLA) and PCL were prepared: PLC 40/60-PCL (25:75), PLC 86/14-PCL (75:25) and PLC 86/14-PLA (75:25). Tamoxifen was loaded with encapsulation efficiency between 65% and 75% (29.9-36.3 µg TMX/ mg NP). All selected systems showed spherical shape and nano-scale size. TMX-loaded NPs were in the range of 293-352 nm. TMX release from NP took place with different profiles depending on polymeric composition of the particles. After 60 days, 59.81% and 82.65% of the loaded drug was released. The cytotoxicity of unloaded NP in MCF7 and HeLa cells was very low. Cell uptake of NP took place in both cell types by unspecific internalization in a time dependent process. The administration of 6 and 10 µm TMX by TMX-loaded NP was effective on both cellular types, mainly in MCF7 cells.

Thelazia callipaeda: infection in dogs: a new parasite for Spain.

BACKGROUND: Thelazia callipaeda (Spirurida, Thelaziidae), eyeworms, are known as the causative agents of thelaziosis, initially described in Asia and, later on, over the last decade, also in some European countries (e.g., Italy, France, Germany and Switzerland). In June 2010, the first case of canine thelaziosis was observed in central western Spain (La Vera region, Cáceres) and subsequent epidemiological investigation is reported in the present study. RESULTS: This study describes the first autochthonous cases of infection by T. callipaeda in dogs from central western Spain where the first case of eyeworm infection was reported.A total of 456 dogs was examined in this geographical area. Thelazia callipaeda eyeworms were observed in 182 (39.9%) animals, of which 28 showed apparent clinical signs (i.e., conjunctivitis, oedema, epiphora and petechiae). A total of 762 adult nematodes (214 males, 548 females; mean infection rate of 4.18; SD 4.74) were collected with cotton swabs or by flushing of the conjunctival sac of infected animals using physiological saline solution. Nematodes were identified as T. callipaeda according to the morphological keys and molecular analysis of sequences of a portion of the mitochondrial cytochrome c oxidase subunit 1 (cox 1) gene. The sequences were identical to those representing T. callipaeda haplotype 1, previously reported in Europe. CONCLUSIONS: The high infection rate of canine thelaziosis herein reported suggests that practitioners should include this eye infection amongst differential diagnoses of ocular diseases in dogs from this area of Spain or those moving across this area of Spain. Based on the high infection prevalence recorded, the potential public health risk to humans from this region is also discussed.

Tamoxifen-loaded folate-conjugate poly[(p-nitrophenyl acrylate)-co-(N-isopropylacrylamide)] sub-microgel as antitumoral drug delivery system.

Folate-conjugate poly[(p-nitrophenyl acrylate)-co-(N-isopropylacrylamide)] sub-microgel (F-SubMG) was loaded with tamoxifen (TMX) to obtain low (9.0 ± 0.4 µg TMX/mg F-SubMG) and high (112.0 ± 15.0 µg TMX/mg F-SubMG) load TMX-loaded F-SubMGs. Maximum in vitro drug release (77 ± 2% to 90 ± 2% of loaded TMX) took place between 47 and 168 h. The cytotoxicity of unloaded F-SubMGs in MCF-7 and HeLa cells was low; although it increased for high F-SubMG concentration. The administration of 10 µM TMX by TMX-loaded F-SubMGs was effective on both cellular types. Cell uptake of F-SubMGs took place in both cell types, but it was larger in HeLa cells because they are folate receptor positive. After subcutaneous administration (2.8 mg TMX/kg b.w.) in Wistar rats, F-SubMGs were detected at the site of injection under the skin, and a significant amount of them were included inside adipocytes. Signs of rejection were not observed after 60 days of injection. Pharmacokinetic study showed an increase in mean residence time of TMX and 4-hydroxytamoxifen (4-OHTMX), as well as a metabolite ratio (MR = AUC(4OHTMX) /AUC(TMX) ) nine times larger, when TMX was administered by drug-loaded F-SubMGs. Since 4-OHTMX is a more potent (at least 100-fold higher) antiestrogen than TMX, administration of TMX-loaded F-SubMGs can be considered an advantage.

Dynamics of pruning waste and spent horse litter co-composting as determined by chemical parameters.

Co-composting of pruning waste and horse manure was monitored by different parameters. A windrow composting pile, having the dimensions 2.5m (height) x 30m (length) was established. The maturation of pruning waste and horse manure compost was accompanied by a decline in NH(4)(+)-N concentration, water soluble C and an increase in NO(3)(-)-N content. Organic matter (OM) content during composting followed a first-order kinetic equation. This result was in agreement with the microbiological activity measured by the CO(2) respiration during the process. The correlation at a high level of probability found between the OM loss and CO(2) evolution showed that both parameters could be used to indicate the degree of OM degradation that is the maturity and stability phases of the compost studied. Humification parameters data from the organic matter fractionation did not show a clear tendency during the composting time, suggesting that these parameters are not suitable for evaluating the dynamics of the process.