Fluids and Electrolytes under Confinement in Single-Digit Nanopores.

Confined fluids and electrolyte solutions in nanopores exhibit rich and surprising physics and chemistry that impact the mass transport and energy efficiency in many important natural systems and industrial applications. Existing theories often fail to predict the exotic effects observed in the narrowest of such pores, called single-digit nanopores (SDNs), which have diameters or conduit widths of less than 10 nm, and have only recently become accessible for experimental measurements. What SDNs reveal has been surprising, including a rapidly increasing number of examples such as extraordinarily fast water transport, distorted fluid-phase boundaries, strong ion-correlation and quantum effects, and dielectric anomalies that are not observed in larger pores. Exploiting these effects presents myriad opportunities in both basic and applied research that stand to impact a host of new technologies at the water-energy nexus, from new membranes for precise separations and water purification to new gas permeable materials for water electrolyzers and energy-storage devices. SDNs also present unique opportunities to achieve ultrasensitive and selective chemical sensing at the single-ion and single-molecule limit. In this review article, we summarize the progress on nanofluidics of SDNs, with a focus on the confinement effects that arise in these extremely narrow nanopores. The recent development of precision model systems, transformative experimental tools, and multiscale theories that have played enabling roles in advancing this frontier are reviewed. We also identify new knowledge gaps in our understanding of nanofluidic transport and provide an outlook for the future challenges and opportunities at this rapidly advancing frontier.

Electrically mediated self-assembly and manipulation of drops at an interface.

The fluid-fluid interface is a complex environment for a floating object where the statics and dynamics may be governed by capillarity, gravity, inertia, and other external body forces. Yet, the alignment of these forces in intricate ways may result in beautiful pattern formation and self-assembly of these objects, as in the case of crystalline order observed with bubble rafts or colloidal particles. While interfacial self-assembly has been explored widely, controlled manipulation of floating objects, e.g. drops, at the fluid-fluid interface still remains a challenge largely unexplored. In this work, we reveal the self-assembly and manipulation of water drops floating at an oil-air interface. We show that the assembly occurs due to electrostatic interactions between the drops and their environment. We highlight the role of the boundary surrounding the system by showing that even drops with a net zero electric charge can self-assemble under certain conditions. Using experiments and theory, we show that the depth of the oil bath plays an important role in setting the distance between the self-assembled drops. Furthermore, we demonstrate ways to manipulate the drops actively and passively at the interface.

Electrochemical Methods for Water Purification, Ion Separations, and Energy Conversion.

Agricultural development, extensive industrialization, and rapid growth of the global population have inadvertently been accompanied by environmental pollution. Water pollution is exacerbated by the decreasing ability of traditional treatment methods to comply with tightening environmental standards. This review provides a comprehensive description of the principles and applications of electrochemical methods for water purification, ion separations, and energy conversion. Electrochemical methods have attractive features such as compact size, chemical selectivity, broad applicability, and reduced generation of secondary waste. Perhaps the greatest advantage of electrochemical methods, however, is that they remove contaminants directly from the water, while other technologies extract the water from the contaminants, which enables efficient removal of trace pollutants. The review begins with an overview of conventional electrochemical methods, which drive chemical or physical transformations via Faradaic reactions at electrodes, and proceeds to a detailed examination of the two primary mechanisms by which contaminants are separated in nondestructive electrochemical processes, namely electrokinetics and electrosorption. In these sections, special attention is given to emerging methods, such as shock electrodialysis and Faradaic electrosorption. Given the importance of generating clean, renewable energy, which may sometimes be combined with water purification, the review also discusses inverse methods of electrochemical energy conversion based on reverse electrosorption, electrowetting, and electrokinetic phenomena. The review concludes with a discussion of technology comparisons, remaining challenges, and potential innovations for the field such as process intensification and technoeconomic optimization.

Orientational Ordering in Nano-confined Polar Liquids.

Water and other polar liquids exhibit nanoscale structuring near charged interfaces. When a polar liquid is confined between two charged surfaces, the interfacial solvent layers begin to overlap, resulting in solvation forces. Here, we perform molecular dynamics simulations of polar liquids with different dielectric constants and molecular shapes and sizes confined between charged surfaces, demonstrating strong orientational ordering in the nanoconfined liquids. To rationalize the observed structures, we apply a coarse-grained continuum theory that captures the orientational ordering and solvation forces of those liquids. Our findings reveal the subtle behavior of different nanoconfined polar liquids and establish a simple law for the decay length of the interfacial orientations of the solvents, which depends on their molecular size and polarity. These insights shed light on the nature of solvation forces, which are important in colloid and membrane science, scanning probe microscopy, and nano-electrochemistry.

Biogenesis of circular RNAs and their role in cellular and molecular phenotypes of neurological disorders.

Circular RNA (circRNA) is an unusual class of RNA-like structures composed by exonic and/or intronic sequences that are regulated by the backsplicing mechanism and by the spliceosome-mediated machinery. These circular transcripts tend to accumulate during aging in several human tissues, especially in the mammalian brain, and their expression is correlated with the occurrence of several human pathologies, including a broad spectrum of neurological disorders. Previous findings have also shown that circRNAs are significantly present in the neuronal tissue and are up-regulated during neurogenesis, with a significant number been derived from neural genes, suggesting these circular molecules are involved in the cellular and molecular phenotype of our brain. However, the complete biogenesis, the many types of circRNA molecules, and their involvement with neuronal phenotype and with the occurrence of pathologies are still a challenging avenue for researchers. In this updated review, we discuss the current findings of the biogenesis and the diversity of cirRNAs and their molecular involvement in neurological tissue phenotype. We also discuss how some circRNAs can act as sponge molecules, regulating the activity of microRNA expression over gene translation. Finally, we also show the correlation of altered circRNA expression in neurological disorders.

A multicenter, open-label, randomized, phase II study of cediranib with or without lenalidomide in iodine 131-refractory differentiated thyroid cancer.

BACKGROUND: Multitargeted tyrosine kinase inhibitors (TKIs) of the vascular endothelial growth factor receptor (VEGFR) pathway have activity in differentiated thyroid cancer (DTC). Lenalidomide demonstrated preliminary efficacy in DTC, but its safety and efficacy in combination with VEGFR-targeted TKIs is unknown. We sought to determine the safety and efficacy of cediranib, a VEGFR-targeted TKI, with or without lenalidomide, in the treatment of iodine 131-refractory DTC. PATIENTS AND METHODS: In this multicenter, open-label, randomized, phase II clinical trial, 110 patients were enrolled and randomized to cediranib alone or cediranib with lenalidomide. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, duration of response, toxicity, and overall survival (OS). Patients (≥18 years of age) with DTC who were refractory to further surgical or radioactive iodine (RAI) therapy as reviewed at a multispecialty tumor board conference, and evidence of disease progression within the previous 12 months and no more than one prior line of systemic therapy were eligible. RESULTS: Of the 110 patients, 108 started therapy and were assessable for efficacy. The median PFS was 14.8 months [95% confidence interval (CI) 8.5-23.8 months] in the cediranib arm and 11.3 months (95% CI 8.7-18.9 months) in the cediranib with lenalidomide arm (P = 0.36). The 2-year OS was 64.8% (95% CI 43.3% to 86.4%) and 75.3% (95% CI 59.4% to 91.0%), respectively (P = 0.80). The serious adverse event rate was 41% in the cediranib arm and 46% in the cediranib with lenalidomide arm. CONCLUSIONS: Single-agent therapy with cediranib showed promising efficacy in RAI-refractory DTC similar to other VEGFR-targeted TKIs, while the addition of lenalidomide did not result in clinically meaningful improvements in outcomes.

Transgenerational effects of maternal exposure to nicotine on structures of pituitary-gonadal axis of rats.

Smoking can lead to several diseases and cause a reduction in fertility in men and women. Among the various components of cigarettes harmful during pregnancy, nicotine stands out. It can cause a reduction in placental blood flow, compromising the development of the baby with neurological, reproductive and endocrine consequences. Thus, we aimed to evaluate the effects of nicotine on the pituitary-gonadal axis of rats exposed during pregnancy and breastfeeding (1st generation - F1), and whether the possible damage observed would reach the 2nd generation (F2). Pregnant Wistar rats received 2 mg/kg/day of nicotine throughout the entire gestation and lactation. Part of the offspring was evaluated on the first neonatal day (F1) for macroscopic, histopathological and immunohistochemical analyses of brain and gonads. Another part of the offspring was kept until 90 days-old for mating and obtainment of progenies that had the same parameters evaluated at the end of pregnancy (F2). The occurrence of malformations was more frequent and diversified in nicotine-exposed F2. Brain alterations, including reduced size and changes in cell proliferation and death, were seen in both generations of nicotine-exposed rats. Male and female gonads of F1 exposed rats were also affected. The F2 rats showed reduced cellular proliferation and increased cell death on the pituitary and ovaries, besides increased anogenital distance in females. The number of mast cells was not enough altered to indicate an inflammatory process in brain and gonads. We conclude that prenatal exposure to nicotine causes transgenerational alterations in the structures of pituitary-gonadal axis in rats.

Preclinical assessment of an anti-HTLV-1 heterologous DNA/MVA vaccine protocol expressing a multiepitope HBZ protein.

BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load. METHODS: We have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4+ and T CD8+) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen. RESULTS: T CD4+ and T CD8+ lymphocytes cells stimulated by HBZ-peptides (HBZ42-50 and HBZ157-176) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8+ cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44+High/CD62L-Low), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8+ T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA. CONCLUSIONS: Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.

Burden of non-communicable diseases and the achievement of the sustainable development goals in 2030 in Mercosur countries.

OBJECTIVES: The aims of this article were to analyse the burden of NCDs and their RFs in the Mercosur countries between 1990 and 2019 and to project mortality trends for 2030. STUDY DESIGN: Epidemiological study of time series. METHODS: The present study used data from the Global Burden of Disease study. The absolute number of deaths, mortality rates, disability-adjusted life years, years of life lost, years lived with disability and the burden of premature mortality by NCD attributable to the RFs were evaluated. Projections were made up to 2030. Age-standardised rates were used to draw comparisons by years and by countries. The analysis was conducted using the RStudio software. RESULTS: Between 1990 and 2019, a decrease was found in the premature mortality rates caused by NCDs in all the countries, except for Paraguay, which remained stable. When analysing premature mortality rates due to NCDs up to 2030, it was predicted that none of the countries would achieve the sustainable development goal of a one-third reduction in premature mortality by NCDs. Regarding the impacts of the RFs for NCDs, smoking, dietary risks, high blood pressure (BP) and high body mass index (BMI) were the main risks attributable to premature deaths due to NCDs. CONCLUSIONS: The results showed that mortality rates are declining in Mercosur countries; however, none of the countries are predicted to achieve the sustainable development goal of a one-third reduction in mortality due to NCDs by 2030. In addition to access to adequate treatment, progress is required in public regulation actions to reduce RFs, such as smoking, dietary risks, high BP and high BMI.

Aqueous extract OF Moringa oleifera Lam leaves added to freezing extenders damages goat sperm membranes.

BACKGROUND: Semen cryopreservation is a biotechnology used frequently in animal production; however, there are some obstacles, such as those caused by high levels of reactive oxygen species (ROS). Moringa oleifera (MO) is known as a potent source of antioxidants and might be an important adjuvant. OBJECTIVE: The objective of this study was to determine the effect of different concentrations of MO extract supplementation on goat semen cryopreservation efficiency. MATERIALS AND METHODS: Ejaculates (n=6) from four goat breeders were pooled and diluted in skimmed milk (SM) or Tris-egg yolk (TEY)-based extenders and supplemented with different concentrations of MO extract (0, 1, 2 and 5 mg/mL). After the freeze-thaw cycle, sperm kinetics and viability were assessed. RESULTS: With the SM extender, straightness, wobble and plasma membrane integrity were lower than in the control group (P < 0.05). With the TEY extender, wobble was lower in with 5 mg/mL MO extract than in the control group (P < 0.05). As regards sperm ultrastructure, evaluated by SEM, the MO extract, regardless of the diluent used, damaged the membrane of sperm cells in a dose-dependent manner. CONCLUSION: The addition of aqueous extract of MO leaves in both diluents at all concentrations tested affects the parameters of sperm progressivity and damages the plasma membrane in a dose-dependent manner. DOI: 10.54680/fr23310110712.

Rectified and Salt Concentration Dependent Wetting of Hydrophobic Nanopores.

Nanopores lined with hydrophobic groups function as switches for water and all dissolved species, such that transport is allowed only when applying a sufficiently high transmembrane pressure difference or voltage. Here we show a hydrophobic nanopore system whose wetting and ability to transport water and ions is rectified and can be controlled with salt concentration. The nanopore we study contains a junction between a hydrophobic zone and a positively charged hydrophilic zone. The nanopore is closed for transport at low salt concentrations and exhibits finite current only when the concentration reaches a threshold value that is dependent on the pore opening diameter, voltage polarity and magnitude, and type of electrolyte. The smallest nanopore studied here had a 4 nm diameter and did not open for transport in any concentration of KCl or KI examined. A 12 nm nanopore was closed for all KCl solutions but conducted current in KI at concentrations above 100 mM for negative voltages and opened for both voltage polarities at 500 mM KI. Nanopores with a hydrophobic/hydrophilic junction can thus function as diodes, such that one can identify a range of salt concentrations where the pores transport water and ions for only one voltage polarity. Molecular dynamics simulations together with continuum models provided a multiscale explanation of the observed phenomena and linked the salt concentration dependence of wetting with an electrowetting model. Results presented are crucial for designing next-generation chemical and ionic separation devices as well as understanding fundamental properties of hydrophobic interfaces under nanoconfinement.

What is an appropriate caesarean delivery rate for China: a multicentre survey.

OBJECTIVE: To assess the current status of caesarean delivery (CD) in China, propose reference CD rates for China overall, and by regions, investigate the main indications for CDs and identify possible areas for safe reduction. DESIGN: A multicentre cross-sectional study. SETTING: A total of 94 hospitals across 23 provinces in China. POPULATION: A total of 73 977 randomly selected deliveries. METHODS: We used a modified Robson classification to characterise CDs in subgroups and by regions, and the World Health Organization (WHO) C-Model to calculate reference CD rates. MAIN OUTCOME MEASURES: CD rates in China. RESULTS: In 2015-2016, the overall CD rate in China was 38.9% (95% CI 38.6-39.3%). Considering the obstetric characteristics of the population, the multivariable model-based reference CD rate was estimated at 28.5% (95% CI 28.3-28.8%). Accordingly, an absolute reduction of 10.4% (or 26.7% relative reduction) may be considered. The CD rate varied substantially by region. Previous CD was the most common indication in all regions, accounting for 38.2% of all CDs, followed by maternal request (9.8%), labour dystocia (8.3%), fetal distress (7.7%) and malpresentation (7.6%). Overall, 12.7% of women had prelabour CDs, contributing to 32.8% of the total CDs. CONCLUSIONS: Nearly 39% of births were delivered by caesarean in China but a reduction of this rate by a quarter may be considered attainable. Repeat CD contributed more than one-third of the total CDs. Given the large variation in maternal characteristics, region-specific or even hospital-specific reference CD rates are needed for precision management of CD. TWEETABLE ABSTRACT: The caesarean rate in 2015-2016 in China was 38.9%, whereas the reference rate was 28.5%.

Binding Energy of Triplet Excitons in Nonfullerene Acceptors: The Effects of Fluorination and Chlorination.

One strategy to improve the photovoltaic properties of nonfullerene acceptors (NFAs), employed in state-of-art organic solar cells, is the rational fluorination or chlorination of these molecules. Although this modification improves important acceptor properties, little is known about the effects on the triplet states. Here, we combine the polarizable continuum model with an optimally tuned range-separated hybrid functional to investigate this issue. We find that fluorination or chlorination of NFAs decreases the degree of the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) overlap along these molecules. Consequently, the energy gap between T1 and S1 states, ΔEST = ES1 - ET1, also decreases. This effect reduces the binding energy of triplet excitons, which favors their dissociation into free charges. Furthermore, the reduction of ΔEST can contribute to mitigating the losses produced by the nonradiative deactivation of the T1 excitons. Interestingly, although Cl has a lower electronegativity than F, chlorination is more effective to reduce ΔEST. Since the chlorination of NFAs is easier than fluorination, Cl substitution can be a useful approach to enhance solar energy harvesting using triplet excitons.

Polar liquids at charged interfaces: A dipolar shell theory.

The structure of polar liquids and electrolytic solutions, such as water and aqueous electrolytes, at interfaces underlies numerous phenomena in physics, chemistry, biology, and engineering. In this work, we develop a continuum theory that captures the essential features of dielectric screening by polar liquids at charged interfaces, including decaying spatial oscillations in charge and mass, starting from the molecular properties of the solvent. The theory predicts an anisotropic dielectric tensor of interfacial polar liquids previously studied in molecular dynamics simulations. We explore the effect of the interfacial polar liquid properties on the capacitance of the electrode/electrolyte interface and on hydration forces between two plane-parallel polarized surfaces. In the linear response approximation, we obtain simple formulas for the characteristic decay lengths of molecular and ionic profiles at the interface.

Gelation, clustering, and crowding in the electrical double layer of ionic liquids.

Understanding the bulk and interfacial properties of super-concentrated electrolytes, such as ionic liquids (ILs), has attracted significant attention lately for their promising applications in supercapacitors and batteries. Recently, McEldrew et al. [J. Phys. Chem. B 125, 2677 (2021)] developed a theory for reversible ion associations in bulk ILs, which accounted for the formation of all possible (Cayley tree) clusters and a percolating ionic network (gel). Here, we adopt and develop this approach to understand the associations of ILs in the electrical double layer at electrified interfaces. With increasing charge of the electrode, the theory predicts a transition from a regime dominated by a gelled or clustered state to a crowding regime dominated by free ions. This transition from gelation to crowding is conceptually similar to the overscreening to crowding transition.

In vivo kinetics of oleic, linoleic, and α-linolenic acid biohydrogenation in the rumen of dairy cows.

Ruminal biohydrogenation (BH) of unsaturated fatty acids (FA) reduces absorption of essential FA and can result in formation of bioactive FA that cause milk fat depression. Rates of biohydrogenation of unsaturated FA are commonly observed using in vitro systems and are not well described in vivo. Seven ruminally cannulated cows were enrolled in a 3 × 3 Latin square design study to quantify biohydrogenation of 18:1n-9, 18:2n-6, and 18:3n-3 using a recently developed in vivo BH assay. All cows were fed a common high corn silage basal diet. Biohydrogenation was quantified using a perturbation model that consisted of a bolus dose of 200 g of an oil enriched in each unsaturated FA (oleic acid, OA = 87% 18:1n-9 sunflower oil; linoleic acid, LA = 70% 18:2n-6 safflower oil; and α-linolenic acid, ALA = 54% 18:3n-3 flaxseed oil) and 12 g of 17:0 as a marker of rumen outflow. Rumen contents were sampled before and after the bolus and enrichment of the bolused FA modeled. Using first-order kinetics to model FA disappearance, the fractional rates of disappearance of 18:1n-9 was 0.597 per hour, 18:2n-6 was 0.618 per hour, and 18:3n-3 was 0.834 per hour, similar to rates previously reported with this approach. Rumen turnover of 17:0 was 0.123 per hour, 0.065 per hour, and 0.106 per hour during the OA, LA, and ALA treatments, respectively. The extents of BH were calculated to be 82.8, 90.4, and 88.6% for 18:1n-9, 18:2n-6, and 18:3n-3, respectively. Finally, compartmental modeling was used to quantify the amount of each unsaturated FA metabolized through trans-10 and trans-11 BH pathways. The recently developed in vivo BH assay was able to predict rates of BH and provide insight into rumen metabolism of individual FA and may be useful to future investigations.

Increasing levels of calcium salts of palm fatty acids affect production responses during the immediate postpartum and carryover periods in dairy cows.

Our objective was to determine the dose-response effects of calcium salts of palm fatty acids (CSPF) on nutrient digestibility and production responses of early-lactation dairy cows grazing on tropical pastures and to evaluate carryover effects throughout mid and late lactation. Forty multiparous dairy cows (Jersey × Holstein) with (mean ± standard error of the mean) 20 ± 1.69 kg of milk/d and 20 ± 5.0 d in milk were used in a randomized complete block design. During the treatment period, all cows were kept in a grazing system. The treatments were offered for 90 d (treatment period) and consisted of 4 increasing levels of CSPF: 0 (0 kg/d), 0.2 (0.2 kg/d), 0.4 (0.4 kg/d), and 0.6 (0.6 kg/d). Each treatment had 10 animals. Increasing CSPF from 0 to 0.6 kg/d replaced an equivalent amount of a corn-based concentrate supplement offered at 10 kg/d on an as-fed basis (8.96 kg/d as a dry matter basis). All cows were housed and received a diet without fat inclusion fed as total mixed ration once a day from 91 to 258 d of the experiment (carryover period). During the treatment period, increasing CSPF linearly decreased dry matter intake (1.20 kg/d), linearly increased neutral detergent fiber digestibility (3.90 percentage units), and quadratically increased total fat digestibility (6.30 percentage units at 0.4 kg/d CSPF). Increasing CSPF linearly increased the yields of milk (4.10 kg/d), milk fat (0.11 kg/d), milk lactose (0.19 kg/d), energy-corrected milk (ECM; 3.30 kg/d), and feed efficiency (ECM/dry matter intake, 0.34 kg/kg), and linearly decreased milk protein content (0.38 g/100 g), body weight change (0.05 kg/d), and body condition score (0.37). We observed interactions between CSPF and time during the carryover period. Overall, CSPF supplementation linearly increased or tended to increase milk yield until 202 d of the experiment with a similar pattern observed for all the other yield variables. In conclusion, supplementing CSPF from 0 to 0.6 kg/d during 90 d increased neutral detergent fiber and total fat digestibility and the yields of milk, milk fat, and ECM in early-lactation dairy cows grazing on tropical pastures. Most production measurements linearly increased during the treatment period, indicating that 0.6 kg/d CSPF was the best dose. Also, supplementing CSPF from 0 to 0.6 kg/d for 90 d during early lactation had positive carryover effects across mid and late lactation.

Trends and patterns of cause-specific hospitalizations in mainland Portugal between 2000 and 2016.

OBJECTIVES: This study aimed to describe trends and patterns of cause-specific hospitalizations in mainland Portugal between 2000 and 2016. STUDY DESIGN: This was a retrospective observational study based on hospital discharge data during the period 2000-2016 in mainland Portugal. METHODS: All inpatient hospital discharges among mainland Portuguese public hospitals were considered to evaluate trends and patterns over the years through hospitalization proportions, number of hospitalizations, age-standardized hospitalization rates (direct standardization using the European standard population), and the number of in-hospital stay days (bed-days). Health Cost and Utilization Project Clinical Classifications Software was used to categorize and cluster inpatients' principal diagnosis. RESULTS: Between 2000 and 2002 and between 2014 and 2016, age-standardized hospitalization rates decreased by 8.6%. Moreover, "liveborn," "diseases of the heart," and "respiratory infections" were the leading hospitalization causes in both periods with a variation of -8.8%, -8.3%, and 13.4% on age-standardized hospitalization rate, respectively. The age-standardized hospitalization rate due to "bacterial infection" increased by 108.7%. "Respiratory diseases" are the leading cause responsible for more in-hospital stay days in the period 2014-2016 (48.6% increase). All Portuguese regions presented decreasing overall trends in their age-standardized hospitalization rates in the study period, yet increasing trends were observed until 2004 except for the Lisbon region; in addition, the number of in-hospital stay days remained relatively stable through time. CONCLUSIONS: Hospitalizations in mainland Portugal decreased between 2000 and 2016 with heterogeneous patterns considering time, age group, and gender. "Aspiration pneumonitis; food/vomitus," "diseases of the white blood cells," "other nutritional, endocrine, and metabolic disorders," "bacterial infection," and "pathological fractures" revealed substantial increases, and further evaluations and monitoring are required.

Does maternal exposure to nicotine affect the oocyte quality and reproductive capacity in adult offspring?

Gonadal development begins in the intrauterine phase and females from most species are born with an established oocyte reserve. Exposure to drugs during gestation can compromise the offspring health, also affecting the gametes quality. Nicotine, the main component of cigarettes, is an oxidant agent capable of altering the fertility in men and women. As female gametes are susceptible to oxidative stress, this drug can damage the oolemma and affect oocyte maturation, induce errors during chromosomal segregation and DNA fragmentation. Oocyte mitochondria are particularly susceptible to injuries, contributing to the oocyte quality loss and embryonic development disruption. Thus, considering the high number of women who smoke during pregnancy, while significant events are occurring in the embryo for future fertility of offspring, we seek to verify the quality of the oocytes from adult rats exposed to nicotine during intrauterine phase and breastfeeding. Pregnant Wistar rats received nicotine by osmotic mini-pumps and the female progenies were evaluated in adulthood for oocyte quality (viability, lipid peroxidation, generation of reactive oxygen species and mitochondrial integrity) and reproductive capacity. Embryos (3dpc) and fetuses (20dpc) generated by these rats were also evaluated. The results showed that the dose of 2 mg/kg/day of nicotine through placenta and breast milk does not affect the number of oocytes and the fertility capacity of adult rats. However, it causes some morphological alterations in oocytes, mitochondrial changes, embryonic fragmentation and disruption of fetal development. The malformations in fetuses generated from these gametes can also indicate the occurrence of epigenetic modifications.