Imaging the dynamics of murine uterine contractions in early pregnancy†.

Uterine muscle contractility is essential for reproductive processes including sperm and embryo transport, and during the uterine cycle to remove menstrual effluent. Even still, uterine contractions have primarily been studied in the context of preterm labor. This is partly due to a lack of methods for studying the uterine muscle contractility in the intact organ. Here, we describe an imaging-based method to evaluate mouse uterine contractility of both the longitudinal and circular muscles in the cycling stages and in early pregnancy. By transforming the image-based data into three-dimensional spatiotemporal contractility maps, we calculate waveform characteristics of muscle contractions, including amplitude, frequency, wavelength, and velocity. We report that the native organ is highly contractile during the progesterone-dominant diestrus stage of the cycle when compared to the estrogen-dominant proestrus and estrus stages. We also observed that during the first phase of uterine embryo movement when clustered embryos move toward the middle of the uterine horn, contractions are dynamic and non-uniform between different segments of the uterine horn. In the second phase of embryo movement, contractions are more uniform and rhythmic throughout the uterine horn. Finally, in Lpar3-/- uteri, which display faster embryo movement, we observe global and regional increases in contractility. Our method provides a means to understand the wave characteristics of uterine smooth muscle in response to modulators and in genetic mutants. Better understanding uterine contractility in the early pregnancy stages is critical for the advancement of artificial reproductive technologies and a possibility of modulating embryo movement during clinical embryo transfers.

Constrained public benefits from global catch share fisheries.

Across publicly owned natural resources, the practice of recovering financial compensation, commonly known as resource rent, from extractive industries influences wealth distribution and general welfare of society. Catch shares are the primary approach adopted to diminish the economically wasteful race to fish by allocating shares of fish quotas-public assets-to selected fishing firms. It is perceived that resource rent is concentrated within catch share fisheries, but there has been no systematic comparison of rent-charging practices with other extractive industries. Here, we estimate the global prevalence of catch share fisheries and compare rent recovery mechanisms (RRM) in the fishing industry with other extractive industries. We show that while catch share fisheries harvest 17.4 million tons (19% of global fisheries landings), with a value of 17.7 billion USD (17% of global fisheries landed value), rent charges occurred in only 5 of 18 countries with shares of fish quotas primarily allocated free of charge. When compared with other extractive industries, fishing is the only industry that consistently lacks RRM. While recovering resource rent for harvesting well-governed fishery resources represents a source of revenue to coastal states, which could be sustained indefinitely, overcharging the industry might impact fish supply. Different RRM occurred in extractive industries, though generally, rent-based charges can help avoid affecting deployment of capital and labor to harvest fish since they depend on the profitability of the operations. Our study could be a starting point for coastal states to consider adapting policies to the enhanced economic condition of the fishing industry under catch shares.

Mechanical and signaling mechanisms that guide pre-implantation embryo movement.

How a mammalian embryo determines and arrives at its attachment site has been studied for decades, but our understanding of this process is far from complete. Using confocal imaging and image analysis, we evaluate embryo location along the longitudinal oviductal-cervical axis of murine uteri. Our analysis reveals three distinct pre-implantation phases: embryo entry, unidirectional movement of embryo clusters and bidirectional scattering and spacing of embryos. We show that unidirectional clustered movement is facilitated by a mechanical stimulus of the embryo and is regulated by adrenergic uterine smooth muscle contractions. Embryo scattering, on the other hand, depends on embryo-uterine communication reliant on the LPAR3 signaling pathway and is independent of adrenergic muscle contractions. Finally, we demonstrate that uterine implantation sites in mice are neither random nor predetermined but are guided by the number of embryos entering the uterine lumen. These studies have implications for understanding how embryo-uterine communication is key to determining an optimal implantation site necessary for the success of a pregnancy.

Pre-implantation mouse embryo movement under hormonally altered conditions.

Pre-implantation embryo movement is crucial to pregnancy success, but the role of ovarian hormones in modulating embryo movement is not understood. We ascertain the effects of altered hormonal environment on embryo location using two delayed implantation mouse models: natural lactational diapause (ND); and artificially induced diapause (AD), a laboratory version of ND generated by ovary removal and provision of supplemental progesterone (P4). Previously, we showed that embryos in a natural pregnancy (NP) first display unidirectional clustered movement, followed by bidirectional scattering and spacing movement. In the ND model, we discovered that embryos are present as clusters near the oviductal-uterine junction for ∼24 h longer than NP, followed by locations consistent with a unidirectional scattering and spacing movement. Intriguingly, the AD model resembles embryo location in NP and not ND. When measuring serum hormone levels, unlike the popular paradigm of reduced estrogen (E2) levels in diapause, we observed that E2 levels are comparable across NP, ND and AD. P4 levels are reduced in ND and highly increased in AD when compared to NP. Further, exogenous administration of E2 or P4 modifies embryo location during the unidirectional phase, while E2 treatment also affects embryo location in the bidirectional phase. Taken together, our data suggest that embryo movement can be modulated by both P4 and E2. Understanding natural hormonal adaptation in diapause provides an opportunity to determine key players that regulate embryo location, thus impacting implantation success. This knowledge can be leveraged to understand pregnancy survival and implantation success in hormonally altered conditions in the clinic.

"Like it was just everyday business": A qualitative study of pharmacy-based naloxone and syringe customer experience.

BACKGROUND: As rates of overdoses involving opioids continue to rise in the United States, community pharmacies are uniquely positioned as a central access point of care for individuals to access harm reduction supplies, such as naloxone and nonprescription syringes (NPS). OBJECTIVES: This study aimed to identify the facilitators and barriers of obtaining naloxone and NPS at community pharmacies that participated in Respond to Prevent (R2P), a multicomponent intervention to increase dispensing rates of naloxone, buprenorphine, and NPS. METHODS: Pharmacy customers were recruited to participate in semistructured qualitative interviews conducted immediately after they obtained, or attempted to obtain, naloxone and NPS (when applicable) from R2P-participating pharmacies. Thematic analysis was conducted on the transcribed interviews, and content coding was applied to ethnographic notes and text messages from participants. RESULTS: Of the 32 participants, most (n = 28, 88%) successfully obtained naloxone and most of those seeking NPS successfully (n = 14, 82%) purchased them as well. Participants reported positive overall experiences at the community pharmacies. Participants described using the intervention advertising materials, as designed, to facilitate the request for naloxone. Many participants shared that they felt respected by pharmacists and that they valued naloxone counseling sessions that were tailored to meet their needs and allowed space for them to ask questions. Barriers included experiences where the intervention did not address structural challenges that prohibited the purchase of naloxone and where certain types of staff lacked knowledge, treated participants poorly, or did not adequately provide expected naloxone counseling. CONCLUSION: Pharmacy customer experiences obtaining naloxone and NPS in R2P-participating pharmacies identify facilitators and barriers to access that may be used to reform implementation and future interventions. Barriers identified can help enhance strategies or inform policies to improve pharmacy-based harm reduction supply distribution not addressed through existing interventions.

Urban poverty and nutrition challenges associated with accessibility to a healthy diet: a global systematic literature review.

BACKGROUND: There is an increasing global trend towards urbanization. In general, there are less food access issues in urban than rural areas, but this "urban advantage" does not benefit the poorest who face disproportionate barriers to accessing healthy food and have an increased risk of malnutrition. OBJECTIVES: This systematic literature review aimed to assess urban poverty as a determinant of access to a healthy diet, and to examine the contribution of urban poverty to the nutritional status of individuals. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) methodology, our review included quantitative and qualitative studies published in English or in Spanish between 2000 and 2019. The articles were eligible if they focused on nutrition access (i.e. access to a healthy diet) or nutrition outcomes (i.e., anemia, overweight and obesity, micronutrient deficiency, micronutrient malnutrition) among urban poor populations. Articles were excluded if they did not meet pre-established criteria. The quality of the quantitative studies was assessed by applying Khan et al.'s methodology. Similarly, we assessed the quality of qualitative articles through an adapted version of the National Institute for Health and Care Excellence (NICE) methodology checklist. Finally, we systematically analyzed all papers that met the inclusion criteria based on a qualitative content and thematic analysis. RESULTS: Of the 68 papers included in the systematic review, 55 used quantitative and 13 used qualitative methods. Through the analysis of the literature we found four key themes: (i) elements that affect access to healthy eating in individuals in urban poverty, (ii) food insecurity and urban poverty, (iii) risk factors for the nutritional status of urban poor and (iv) coping strategies to limited access to food. Based on the systematization of the literature on these themes, we then proposed a conceptual framework of urban poverty and nutrition. CONCLUSIONS: This systematic review identified distinct barriers posed by urban poverty in accessing healthy diets and its association with poorer nutrition outcomes, hence, questioning the "urban advantage". A conceptual framework emerging from the existing literature is proposed to guide future studies and policies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Registration number: CRD42018089788 .

Experience-Dependent Intrinsic Plasticity During Auditory Learning.

Song learning in zebra finches (Taeniopygia guttata) requires exposure to the song of a tutor, resulting in an auditory memory. This memory is the foundation for later sensorimotor learning, resulting in the production of a copy of the tutor's song. The cortical premotor nucleus HVC (proper name) is necessary for auditory and sensorimotor learning as well as the eventual production of adult song. We recently discovered that the intrinsic physiology of HVC neurons changes across stages of song learning, but are those changes the result of learning or are they experience-independent developmental changes? To test the role of auditory experience in driving intrinsic changes, patch-clamp experiments were performed comparing HVC neurons in juvenile birds with varying amounts of tutor exposure. The intrinsic physiology of HVC neurons changed as a function of tutor exposure. Counterintuitively, tutor deprivation resulted in juvenile HVC neurons showing an adult-like phenotype not present in tutor-exposed juveniles. Biophysical models were developed to predict which ion channels were modulated by experience. The models indicate that tutor exposure transiently suppressed the Ih and T-type Ca2+ currents in HVC neurons that target the basal ganglia, whereas tutor exposure increased the resting membrane potential and decreased the spike amplitude in HVC neurons that drive singing. Our findings suggest that intrinsic plasticity may be part of the mechanism for auditory learning in the HVC. More broadly, models of learning and memory should consider intrinsic plasticity as a possible mechanism by which the nervous system encodes the lasting effects of experience.SIGNIFICANCE STATEMENT It is well established that learning involves plasticity of the synapses between neurons. However, the activity of a neural circuit can also be dramatically altered by changes in the intrinsic properties (ion channels) of the component neurons. The present experiments show experience-dependent changes in the intrinsic physiology of neurons in the cortical premotor nucleus HVC (proper name) in juvenile zebra finches (Taeniopygia guttata) during auditory learning of a tutor's song. Tutor deprivation does not "arrest" development of intrinsic properties, but rather results in neurons with a premature adult-like physiological phenotype. It is possible that auditory learning involves a form of nonsynaptic plasticity and that experience-dependent suppression of specific ion channels may work in concert with synaptic plasticity to promote vocal learning.

How do context variables affect food insecurity in Mexico? Implications for policy and governance.

OBJECTIVE: To assess, from a systems perspective, how climate vulnerability and socio-economic and political differences at the municipal and state levels explain food insecurity in Mexico. DESIGN: Using a cross-sectional design with official secondary data, we estimated three-level multinomial hierarchical linear models. SETTING: The study setting is Mexico's states and municipalities in 2014. PARTICIPANTS: Heads of households in a representative sample of the general population. RESULTS: At the municipal level, vulnerability to climate disasters and a poverty index were significant predictors of food insecurity after adjusting for household-level variables. At the state level, gross domestic product and the number of nutrition programmes helped explain different levels of food insecurity but change in political party did not. Predictors varied in strength and significance according to the level of food insecurity. CONCLUSIONS: Findings evidence that, beyond food assistance programmes and household characteristics, multiple variables operating at different levels - like climate vulnerability and poverty - contribute to explain the degree of food insecurity. Food security governance is a well-suited multisectoral approach to address the complex challenge of hunger and access to a nutritious diet.

Academic and sociodemographic predictors of anxiety and psychological well-being in Mexican medical students. A cross-sectional study.

INTRODUCTION: Medical students report higher levels of anxiety than students from other majors. Knowledge about their psychological well-being is scarce. OBJECTIVE: To identify sociodemographic and academic factors that predict the level of anxiety and psychological well-being in Mexican medical students. METHOD: Cross-sectional study of Mexican medical students of first (n = 59), third (n = 43) and fifth semester (n = 59), who answered a sociodemographic questionnaire, Beck Anxiety Inventory, the Psychological Well-being Scale for adults and the Family Adaptability and Cohesion Evaluation Scale. RESULTS: Females showed higher levels of anxiety (p < 0.01). Anxiety in males was similar in the different semesters (p > 0.05); women of third and fifth semesters were more anxious than those at first semester (p < 0.01). Anxiety and psychological well-being were negatively correlated (p < 0.001). The "Less anxiety, higher level of well-being" and "More anxiety, lower level of well-being" subgroups were characterized, and a logistic regression identified that being a woman (OR = 4.70) and not practicing any religion (OR = 2.49) are predictive factors of higher levels of anxiety. CONCLUSIONS: Female medical students constitute a population at risk for higher levels of anxiety and less psychological well-being, which compromises their learning, quality of life and future professional practice.

INTRODUCCIÓN: Estudiantes de medicina reportan mayor ansiedad que estudiantes de otras carreras. El conocimiento sobre su bienestar psicológico es escaso. OBJETIVO: Identificar factores sociodemográficos y académicos predictores del nivel de ansiedad y bienestar psicológico en estudiantes mexicanos de medicina. MÉTODO: Estudio transversal de estudiantes mexicanos de medicina de primer (n = 59), tercer (n = 43) y quinto semestre (n = 59), que contestaron un cuestionario sociodemográfico, la Escala de Ansiedad de Beck, la Escala de Bienestar Psicológico para Adultos y la Escala de Evaluación de la Cohesión y la Adaptabilidad Familiar. RESULTADOS: Las mujeres presentaron mayor ansiedad (p < 0.01). La ansiedad en hombres fue similar en los distintos semestres (p > 0.05); las mujeres de tercer y quinto semestre fueron más ansiosas que las del primero (p < 0.01). Ansiedad y bienestar psicológico correlacionaron negativamente (p < 0.001). Se identificaron los subgrupos "Menor ansiedad, mayor bienestar" y "Mayor ansiedad, menor bienestar", y una regresión logística identificó que ser mujer (OR = 4.70) y no profesar alguna religión (OR = 2.49) son factores predictores de mayor ansiedad. CONCLUSIONES: Las estudiantes de medicina constituyen una población de riesgo para mayor ansiedad y menor bienestar psicológico, lo que compromete su aprendizaje, calidad de vida y futuro ejercicio profesional.

Mitochondrial implications in human pregnancies with intrauterine growth restriction and associated cardiac remodelling.

Intrauterine growth restriction (IUGR) is an obstetric complication characterised by placental insufficiency and secondary cardiovascular remodelling that can lead to cardiomyopathy in adulthood. Despite its aetiology and potential therapeutics are poorly understood, bioenergetic deficits have been demonstrated in adverse foetal and cardiac development. We aimed to evaluate the role of mitochondria in human pregnancies with IUGR. In a single-site, cross-sectional and observational study, we included placenta and maternal peripheral and neonatal cord blood mononuclear cells (PBMC and CBMC) from 14 IUGR and 22 control pregnancies. The following mitochondrial measurements were assessed: enzymatic activities of mitochondrial respiratory chain (MRC) complexes I, II, IV, I + III and II + III, oxygen consumption (cell and complex I-stimulated respiration), mitochondrial content (citrate synthase [CS] activity and mitochondrial DNA copy number), total ATP levels and lipid peroxidation. Sirtuin3 expression was evaluated as a potential regulator of bioenergetic imbalance. Intrauterine growth restriction placental tissue showed a significant decrease of MRC CI enzymatic activity (P < 0.05) and CI-stimulated oxygen consumption (P < 0.05) accompanied by a significant increase of Sirtuin3/ß-actin protein levels (P < 0.05). Maternal PBMC and neonatal CBMC from IUGR patients presented a not significant decrease in oxygen consumption (cell and CI-stimulated respiration) and MRC enzymatic activities (CII and CIV). Moreover, CS activity was significantly reduced in IUGR new-borns (P < 0.05). Total ATP levels and lipid peroxidation were preserved in all the studied tissues. Altered mitochondrial function of IUGR is especially present at placental and neonatal level, conveying potential targets to modulate obstetric outcome through dietary interventions aimed to regulate Sirtuin3 function.

Avian haemosporidian infections in rufous-collared sparrows in an Andean dry forest: diversity and factors related to prevalence and parasitaemia.

Despite intensive research during the last few decades, understanding of ecological and physiological factors related to haemosporidian infections in birds is still fragmentary. Since more model organisms are needed in order to understand these infections in the wild, we analysed avian haemosporidian infections in the rufous-collared sparrow (Zonotrichia capensis, Emberizidae) in a dry forest of the Ecuadorian Andes. Parasite diversity was screened using molecular and morphological approaches. By molecular diagnosis, we identified three linages that were phylogenetically placed in the context of molecular haemosporidian diversity and associated with a morphospecies. By microscopy, we identified five described morphospecies and one additional undescribed morphospecies. We found that avian haemosporidian prevalence on the study site was 76.3%. Additionally, we used a series of generalized linear models to explore the potential relationship of parasite prevalence and parasitaemia with a set of variables related to physiological and environmental conditions. Although our results revealed associations of haemosporidian infections with precipitation, age and sampling site, the models only explained a small fraction of the variation.

Perfluorooctanoic acid disrupts gap junction intercellular communication and induces reactive oxygen species formation and apoptosis in mouse ovaries.

Perfluorooctanoic acid (PFOA) is a member of the perfluoroalkyl acid family of compounds. Due to the presence of strong carbon-fluorine bonds, it is practically nonbiodegradable and highly persistent in the environment. PFOA has been detected in the follicular fluid of women, and positively associated with reduced fecundability and infertility. However, there are no reports concerning the experimental evaluation of PFOA on oocyte toxicity in mammals. The aim of the present study was to determine if PFOA is able to induce oxidative stress in fetal ovaries and cause apoptosis in oocytes in vitro. In addition, since inhibition of the gap junction intercellular communication (GJIC) by PFOA has been demonstrated in liver cells in vivo and in vitro, the effect of PFOA on the GJIC between the oocyte and its supportive cumulus cells was studied. Results show that PFOA induced oocyte apoptosis and necrosis in vitro (medium lethal concentration, LC50 = 112.8 µM), as evaluated with Annexin-V-Alexa 508 in combination with BOBO-1 staining. Reactive oxygen species (ROS) levels, as assessed by DCFH-DA, increased significantly in fetal ovaries exposed to » LC50 (28.2 µM, a noncytotoxic and relevant occupational exposure concentration) and LC50 PFOA ex vivo. This perfluorinated compound also caused the blockage of GJIC in cumulus cells-oocyte complexes (COCs) obtained from female mice exposed in vivo, as evaluated by calcein transfer from cumulus cells to the oocyte. The ability of PFOA of disrupting the GJIC in COCs, generating ROS in the fetal ovary and causing apoptosis and necrosis in mammal's oocytes, might account for the reported association between increasing maternal plasma concentrations of PFOA with reduced fertility in women.

Heavy Metal Enrichment Factors in Fluvial Sediments of an Amazonian Basin Impacted by Gold Mining.

Artisanal and small-scale gold mining (ASGM) has been performed in the southern Ecuadorian Amazon since the colonial period. However, its effects on fluvial systems have been poorly investigated. Thus, in order to calculate the normalized enrichment factors (NEF) of several heavy metals in fluvial sediments of the Zamora River basin (Ecuadorian Amazon), we analyzed bottom sediments along ASGM-affected and unaffected river sections. The results indicated that sediments of the Congüime River have NEF between 2.2 and 2.3 for Cu (moderate contamination) and higher than 3 for Mn, Zn, Pb, and Hg (severe contamination). Similarly, a severe contamination is also observed in the lower Nangaritza River, due to sediments of this sector have NEF > 3 for Zn, Pb, and Hg. Bottom sediments from the Nambija and Zamora rivers showed a severe contamination with Hg (NEF > 3), suggesting the existence of ASGM activities in the upper Zamora River basin.

Exhaustion of mitochondrial and autophagic reserve may contribute to the development of LRRK2 G2019S -Parkinson's disease.

BACKGROUND: Mutations in leucine rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD). Mitochondrial and autophagic dysfunction has been described as etiologic factors in different experimental models of PD. We aimed to study the role of mitochondria and autophagy in LRRK2 G2019S -mutation, and its relationship with the presence of PD-symptoms. METHODS: Fibroblasts from six non-manifesting LRRK2 G2019S -carriers (NM-LRRK2 G2019S ) and seven patients with LRRK2 G2019S -associated PD (PD-LRRK2 G2019S ) were compared to eight healthy controls (C). An exhaustive assessment of mitochondrial performance and autophagy was performed after 24-h exposure to standard (glucose) or mitochondrial-challenging environment (galactose), where mitochondrial and autophagy impairment may be heightened. RESULTS: A similar mitochondrial phenotype of NM-LRRK2 G2019S and controls, except for an early mitochondrial depolarization (54.14% increased, p = 0.04), was shown in glucose. In response to galactose, mitochondrial dynamics of NM-LRRK2 G2019S improved (- 17.54% circularity, p = 0.002 and + 42.53% form factor, p = 0.051), probably to maintain ATP levels over controls. A compromised bioenergetic function was suggested in PD-LRRK2 G2019S when compared to controls in glucose media. An inefficient response to galactose and worsened mitochondrial dynamics (- 37.7% mitochondrial elongation, p = 0.053) was shown, leading to increased oxidative stress. Autophagy initiation (SQTSM/P62) was upregulated in NM-LRRK2 G2019S when compared to controls (glucose + 118.4%, p = 0.014; galactose + 114.44%, p = 0.009,) and autophagosome formation increased in glucose media. Despite of elevated SQSTM1/P62 levels of PD-NM G2019S when compared to controls (glucose + 226.14%, p = 0.04; galactose + 78.5%, p = 0.02), autophagosome formation was deficient in PD-LRRK2 G2019S when compared to NM-LRRK2 G2019S (- 71.26%, p = 0.022). CONCLUSIONS: Enhanced mitochondrial performance of NM-LRRK2 G2019S in mitochondrial-challenging conditions and upregulation of autophagy suggests that an exhaustion of mitochondrial bioenergetic and autophagic reserve, may contribute to the development of PD in LRRK2 G2019S mutation carriers.

Central nervous system metastasis from osteosarcoma: Case report and literature review.

Osteosarcoma is the most common primary malignancy of bone in children and young adults, the highest incidence peak is during adolescence and doesn't have any gender predominance. The main site of metastasis are the lungs and extrapulmonary cases are occasional. The incidence of metastasis in the Central Nervous System (CNS) is 2-6.5%, increase to 10-15% in patients with pulmonary metastases. Therefore, metastatic disease of the CNS is rare and the information on such patients is limited. Here, we describe a case of a 20-year old patient diagnosed with osteosarcoma in the left distal femur stage IIB, he developed pulmonary disease, during palliative chemotherapy experienced relapse to the brain classified as recursive partitioning analysis (RPA) class II, and was treated with external radiotherapy (30 Gy in 10 fractions) and later he had a poor evolution and died.

HIV-1 promonocytic and lymphoid cell lines: an in vitro model of in vivo mitochondrial and apoptotic lesion.

To characterize mitochondrial/apoptotic parameters in chronically human immunodeficiency virus (HIV-1)-infected promonocytic and lymphoid cells which could be further used as therapeutic targets to test pro-mitochondrial or anti-apoptotic strategies as in vitro cell platforms to deal with HIV-infection. Mitochondrial/apoptotic parameters of U1 promonocytic and ACH2 lymphoid cell lines were compared to those of their uninfected U937 and CEM counterparts. Mitochondrial DNA (mtDNA) was quantified by rt-PCR while mitochondrial complex IV (CIV) function was measured by spectrophotometry. Mitochondrial-nuclear encoded subunits II-IV of cytochrome-c-oxidase (COXII-COXIV), respectively, as well as mitochondrial apoptotic events [voltage-dependent-anion-channel-1(VDAC-1)-content and caspase-9 levels] were quantified by western blot, with mitochondrial mass being assessed by spectrophotometry (citrate synthase) and flow cytometry (mitotracker green assay). Mitochondrial membrane potential (JC1-assay) and advanced apoptotic/necrotic events (AnexinV/propidium iodide) were measured by flow cytometry. Significant mtDNA depletion spanning 57.67% (P < 0.01) was found in the U1 promonocytic cells further reflected by a significant 77.43% decrease of mitochondrial CIV activity (P < 0.01). These changes were not significant for the ACH2 lymphoid cell line. COXII and COXIV subunits as well as VDAC-1 and caspase-9 content were sharply decreased in both chronic HIV-1-infected promonocytic and lymphoid cell lines (<0.005 in most cases). In addition, U1 and ACH2 cells showed a trend (moderate in case of ACH2), albeit not significant, to lower levels of depolarized mitochondrial membranes. The present in vitro lymphoid and especially promonocytic HIV model show marked mitochondrial lesion but apoptotic resistance phenotype that has been only partially demonstrated in patients. This model may provide a platform for the characterization of HIV-chronicity, to test novel therapeutic options or to study HIV reservoirs.

Imbalance in mitochondrial dynamics and apoptosis in pregnancies among HIV-infected women on HAART with obstetric complications.

Background: HIV infection and HAART trigger genetic and functional mitochondrial alterations leading to cell death and adverse clinical manifestations. Mitochondrial dynamics enable mitochondrial turnover and degradation of damaged mitochondria, which may lead to apoptosis. Objectives: To evaluate markers of mitochondrial dynamics and apoptosis in pregnancies among HIV-infected women on HAART and determine their potential association with obstetric complications. Methods: This controlled, single-site, observational study without intervention included 26 HIV-infected pregnant women on HAART and 18 control pregnancies and their newborns. Maternal PBMCs and neonatal cord blood mononuclear cells (CBMCs) were isolated at the first trimester of gestation and at delivery. The placenta was homogenized at 5% w/v. Mitochondrial dynamics, fusion events [mitofusin 2 (Mfn2)/ß-actin] and fission events [dynamin-related protein 1 (Drp1/ß-actin)] and apoptosis (caspase 3/ß-actin) were assessed by western blot analysis. Results: Obstetric complications were significantly more frequent in pregnancies among HIV-infected women [OR 5.00 (95% CI 1.21-20.70)]. Mfn2/ß-actin levels in PBMCs from controls significantly decreased during pregnancy (202.13 ±â€¯57.45%), whereas cases maintained reduced levels from the first trimester of pregnancy and no differences were observed in CBMCs. Mfn2/ß-actin and Drp1/ß-actin contents significantly decreased in the placenta of cases. Caspase 3/ß-actin levels significantly increased during pregnancy in PBMCs of cases (50.00 ±â€¯7.89%), remaining significantly higher than in controls. No significant differences in caspase 3/ß-actin content of neonatal CBMCs were observed, but there was a slight increased trend in placenta from cases. Conclusions: HIV- and HAART-mediated mitochondrial damage may be enhanced by decreased mitochondrial dynamics and increased apoptosis in maternal and placental compartments but not in the uninfected fetus. However, direct effects on mitochondrial dynamics and implication of apoptosis were not demonstrated in adverse obstetric outcomes.

The risk of use small matrices to measure specialization in host-parasite interaction networks: a comment to Rivera-García et al. (2016).

In the last years, there were a growing number of studies using the metric H 2' to calculate complementary specialization in host-parasite interaction networks. However, only a few studies have explored the sensitivity of H 2' to network dimensions (i.e. species richness and number of interactions), which consequently could generate studies that are not comparable among them or lead to biased conclusions. In this study, we used the recent published study conducted by Rivera-García et al. in 2016 involving host-bat fly networks as an example to call attention to the risk of using H 2' to calculate specialization for small matrices. After conducting analyses based on both empirical and simulated data, we show that H 2' values are strongly affected by randomly allocation of species interactions to another cell in the matrix for small networks and that therefore the results and conclusions presented in Rivera-García et al. in 2016 are only an artefact of the dataset used. Therefore, we fully recommended taking into account the careful use of small networks to measuring specialization in host-parasite interactions.

Oxidative stress as a damage mechanism in porcine cumulus-oocyte complexes exposed to malathion during in vitro maturation.

Malathion is one of the most commonly used insecticides. Recent findings have demonstrated that it induces oxidative stress in somatic cells, but there are not enough studies that have demonstrated this effect in germ cells. Malathion impairs porcine oocyte viability and maturation, but studies have not shown how oxidative stress damages maturation and which biochemical mechanisms are affected in this process in cumulus-oocyte complexes (COCs). The aims of the present study were to determine the amount of oxidative stress produced by malathion in porcine COCs matured in vitro, to define how biochemical mechanisms affect this process, and determine whether trolox can attenuate oxidative damage. Sublethal concentrations 0, 750, and 1000 µM were used to evaluate antioxidant enzyme expressions, reactive oxygen species (ROS production), protein oxidation, and lipid peroxidation, among other oxidation products. COCs viability and oocyte maturation decreased in a concentration-dependent manner. Malathion increased Cu, Zn superoxide dismutase (SOD1), glutathione-S-transferase (GST), and glucose 6 phosphate dehydrogenase (G6PD) protein level and decreased glutathione peroxidase (GSH-Px) and catalase (CAT) protein level. Species reactives of oxygen (ROS), protein oxidation and Thiobarbituric acid reactive substances (TBARS) levels increased in COCs exposed to the insecticide, but when COCs were pre-treated with the trolox (50 µM) 30 min before and during malathion exposure, these parameters decreased down to control levels. This study showed that malathion has a detrimental effect on COCs during in vitro maturation, inducing oxidative stress, while trolox attenuated malathion toxicity by decreasing oxidative damage.