Universidad del Valle

Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases. Currently, the most effective way to deliver drugs specifically to mitochondria is by covalent linking a lipophilic cation such as an alkyltriphenylphosphonium moiety to a pharmacophore of interest. Other delocalized lipophilic cations, such as rhodamine, natural and synthetic mitochondria-targeting peptides, and nanoparticle vehicles, have also been used for mitochondrial delivery of small molecules. Depending on the approach used, and the cell and mitochondrial membrane potentials, more than 1000-fold higher mitochondrial concentration can be achieved. Mitochondrial targeting has been developed to study mitochondrial physiology and dysfunction and the interaction between mitochondria and other subcellular organelles and for treatment of a variety of diseases such as neurodegeneration and cancer. In this Review, we discuss efforts to target small-molecule compounds to mitochondria for probing mitochondria function, as diagnostic tools and potential therapeutics. We describe the physicochemical basis for mitochondrial accumulation of lipophilic cations, synthetic chemistry strategies to target compounds to mitochondria, mitochondrial probes, and sensors, and examples of mitochondrial targeting of bioactive compounds. Finally, we review published attempts to apply mitochondria-targeted agents for the treatment of cancer and neurodegenerative diseases.

Assessing Biodiversity Declines Understanding human impact on biodiversity depends on sound quantitative projection. Pereira et al. (p. 1496 , published online 26 October) review quantitative scenarios that have been developed for four main areas of concern: species extinctions, species abundances and community structure, habitat loss and degradation, and shifts in the distribution of species and biomes. Declines in biodiversity are projected for the whole of the 21st century in all scenarios, but with a wide range of variation. Hoffmann et al. (p. 1503 , published online 26 October) draw on the results of five decades' worth of data collection, managed by the International Union for Conservation of Nature Species Survival Commission. A comprehensive synthesis of the conservation status of the world's vertebrates, based on an analysis of 25,780 species (approximately half of total vertebrate diversity), is presented: Approximately 20% of all vertebrate species are at risk of extinction in the wild, and 11% of threatened birds and 17% of threatened mammals have moved closer to extinction over time. Despite these trends, overall declines would have been significantly worse in the absence of conservation actions.

Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.

BACKGROUND: Poorly defined cohorts and weak study designs have hampered cross-cultural comparisons of course and outcome in schizophrenia. AIMS: To describe long-term outcome in 18 diverse treated incidence and prevalence cohorts. To compare mortality, 15- and 25-year illness trajectory and the predictive strength of selected baseline and short-term course variables. METHODS: Historic prospective study. Standardised assessments of course and outcome. RESULTS: About 75% traced. About 50% of surviving cases had favourable outcomes, but there was marked heterogeneity across geographic centres. In regression models, early (2-year) course patterns were the strongest predictor of 15-year outcome, but recovery varied by location; 16% of early unremitting cases achieved late-phase recovery. CONCLUSIONS: A significant proportion of treated incident cases of schizophrenia achieve favourable long-term outcome. Sociocultural conditions appear to modify long-term course. Early intervention programmes focused on social as well as pharmacological treatments may realise longer-term gains.

Predictive theory on how plant diversity promotes herbivore suppression through movement patterns, host associations, and predation promises a potential alternative to pesticide-intensive monoculture crop production. We used meta-analysis on 552 experiments in 45 articles published over the last 10 years to test if plant diversification schemes reduce herbivores and/or increase the natural enemies of herbivores as predicted by associational resistance hypotheses, the enemies hypothesis, and attraction and repellency model applications in agriculture. We found extensive support for these models with intercropping schemes, inclusion of flowering plants, and use of plants that repel herbivores or attract them away from the crop. Overall, herbivore suppression, enemy enhancement, and crop damage suppression effects were significantly stronger on diversified crops than on crops with none or fewer associated plant species. However, a relatively small, but significantly negative, mean effect size for crop yield indicated that pest-suppressive diversification schemes interfered with production, in part because of reducing densities of the main crop by replacing it with intercrops or non-crop plants. This first use of meta-analysis to evaluate the effects of diversification schemes, a potentially more powerful tool than tallies of significant positive and negative outcomes (vote-counting), revealed stronger overall effects on all parameters measured compared to previous reviews. Our analysis of the same articles used in a recent review facilitates comparisons of vote-counting and meta-analysis, and shows that pronounced results of the meta-analysis are not well explained by a reduction in articles that met its stricter criteria. Rather, compared to outcome counts, effect sizes were rarely neutral (equal to zero), and a mean effect size value for mixed outcomes could be calculated. Problematic statistical properties of vote-counting were avoided with meta-analysis, thus providing a more precise test of the hypotheses. The unambiguous and encouraging results from this meta-analysis of previous research should motivate ecologists to conduct more mechanistic experiments to improve the odds of designing effective crop diversification schemes for improved pest regulation and enhanced crop yield.

In this pithy two-part essay, Marshall Sahlins reinvigorates the debates on what constitutes kinship, building on some of the best scholarship in the field to produce an original outlook on the deepest bond humans can have. Covering thinkers from Aristotle and Levy-Bruhl to Emile Durkheim and David Schneider, and communities from the Maori and the English to the Korowai of New Guinea, he draws on a breadth of theory and a range of ethnographic examples to form an acute definition of kinship, what he calls the of being. Kinfolk are persons who are parts of one another to the extent that what happens to one is felt by the other. Meaningfully and emotionally, relatives live each other's lives and die each other's deaths. In the second part of his essay, Sahlins shows that mutuality of being is a symbolic notion of belonging, not a biological connection by blood. Quite apart from relations of birth, people may become kin in ways ranging from sharing the same name or the same food to helping each other survive the perils of the high seas. In a groundbreaking argument, he demonstrates that even where kinship is reckoned from births, it is because the wider kindred or the clan ancestors are already involved in procreation, so that the notion of birth is meaningfully dependent on kinship rather than kinship on birth. By formulating this reversal, Sahlins identifies what kinship truly is: not nature, but culture.

BACKGROUND: Previous research has identified a high risk of gastric carcinoma as well as a high prevalence of cancer precursor lesions in rural populations living in the province of Nariño, Colombia, in the Andes Mountains. METHODS: A randomized, controlled chemoprevention trial was conducted in subjects with confirmed histologic diagnoses of multifocal nonmetaplastic atrophy and/or intestinal metaplasia, two precancerous lesions. Individuals were assigned to receive anti-Helicobacter pylori triple therapy and/or dietary supplementation with ascorbic acid, beta-carotene, or their corresponding placebos. Gastric biopsy specimens taken at baseline were compared with those taken at 72 months. Relative risks of progression, no change, and regression from multifocal nonmetaplastic atrophy and intestinal metaplasia were analyzed with multivariate polytomous logistic regression models to estimate treatment effects. All statistical tests were two-sided. RESULTS: All three basic interventions resulted in statistically significant increases in the rates of regression: Relative risks were 4.8 (95% confidence interval [CI] = 1.6-14.2) for anti-H. pylori treatment, 5. 1 (95% CI = 1.7-15.0) for beta-carotene treatment, and 5.0 (95% CI = 1.7-14.4) for ascorbic acid treatment in subjects with atrophy. Corresponding relative risks of regression in subjects with intestinal metaplasia were 3.1 (95% CI = 1.0-9.3), 3.4 (95% CI = 1.1-9.8), and 3.3 (95% CI = 1.1-9.5). Combinations of treatments did not statistically significantly increase the regression rates. Curing the H. pylori infection (which occurred in 74% of the treated subjects) produced a marked and statistically significant increase in the rate of regression of the precursor lesions (relative risks = 8.7 [95% CI = 2.7-28.2] for subjects with atrophy and 5.4 [95% CI = 1.7-17.6] for subjects with intestinal metaplasia). CONCLUSIONS: In the very high-risk population studied, effective anti-H. pylori treatment and dietary supplementation with antioxidant micronutrients may interfere with the precancerous process, mostly by increasing the rate of regression of cancer precursor lesions, and may be an effective strategy to prevent gastric carcinoma.

The recent emergence and spread of dengue hemorrhagic fever in the Americas have been a major source of concern. Efforts to control this disease are dependent on understanding the pathogenicity of dengue viruses and their transmission dynamics. Pathogenicity studies have been hampered by the lack of in vitro or in vivo models of severe dengue disease. Alternatively, molecular epidemiologic studies which associate certain dengue virus genetic types with severe dengue outbreaks may point to strains with increased pathogenicity. The comparison of nucleotide sequences (240 bp) from the E/NS1 gene region of the dengue virus genome has been shown to reflect evolutionary relationships and geographic origins of dengue virus strains. This approach was used to demonstrate an association between the introduction of two distinct genotypes of dengue type 2 virus and the appearance of dengue hemorrhagic fever in the Americas. Phylogenetic analyses suggest that these genotypes originated in Southeast Asia and that they displaced the native, American genotype in at least four countries. Vaccination and other control efforts should therefore be directed at decreasing the transmission of these "virulent" genotypes.

The interruption of malaria transmission worldwide is one of the greatest challenges for international health and development communities. The current expert view suggests that, by aggressively scaling up control with currently available tools and strategies, much greater gains could be achieved against malaria, including elimination from a number of countries and regions; however, even with maximal effort we will fall short of global eradication. The Malaria Eradication Research Agenda (malERA) complements the current research agenda--primarily directed towards reducing morbidity and mortality--with one that aims to identify key knowledge gaps and define the strategies and tools that will result in reducing the basic reproduction rate to less than 1, with the ultimate aim of eradication of the parasite from the human population. Sustained commitment from local communities, civil society, policy leaders, and the scientific community, together with a massive effort to build a strong base of researchers from the endemic areas will be critical factors in the success of this new agenda.

Rising global concentrations of environmental microplastics and nanoplastics (MNPs) drive concerns for human exposure and health outcomes. Complementary methods for the robust detection of tissue MNPs, including pyrolysis gas chromatography-mass spectrometry, attenuated total reflectance-Fourier transform infrared spectroscopy and electron microscopy with energy-dispersive spectroscopy, confirm the presence of MNPs in human kidney, liver and brain. MNPs in these organs primarily consist of polyethylene, with lesser but significant concentrations of other polymers. Brain tissues harbor higher proportions of polyethylene compared to the composition of the plastics in liver or kidney, and electron microscopy verified the nature of the isolated brain MNPs, which present largely as nanoscale shard-like fragments. Plastic concentrations in these decedent tissues were not influenced by age, sex, race/ethnicity or cause of death; the time of death (2016 versus 2024) was a significant factor, with increasing MNP concentrations over time in both liver and brain samples (P = 0.01). Finally, even greater accumulation of MNPs was observed in a cohort of decedent brains with documented dementia diagnosis, with notable deposition in cerebrovascular walls and immune cells. These results highlight a critical need to better understand the routes of exposure, uptake and clearance pathways and potential health consequences of plastics in human tissues, particularly in the brain.

This article aims to explore the key factors on e-commerce adoption from elements of social psychology, such as attitude, subjective norms, perceived behavioral control, ease of use and perceived usefulness, introducing the study of non-traditional elements like buying impulse, compatibility, and self-efficacy in online stores, contrasting relationships in a cross-cultural environment. The proposed model is tested from quantitative research with a sample of 584 online consumers in Colombia and Spain. The following statistical analyses were conducted: CFA, structural equations, measurement instrument invariance, and multi-group analysis with EQS 6.3 software. The study reveals that self-efficacy in online stores is a key factor in adopting electronic commerce above the cultures studied. Also, there is significant evidence that proves the moderating effect of national culture on several relationships of the model proposed. Results highlight the importance of national culture to understand impulsive buying behavior. The article presents several considerations toward the main elements to generate online purchase intention among consumers in an emerging country and finds substantial differences with consumers in a developed country. Practical implications are made for companies to adopt online channels and expand internationally.

Abstract Twenty-five years since foundational publications on valuing ecosystem services for human well-being 1,2 , addressing the global biodiversity crisis 3 still implies confronting barriers to incorporating nature’s diverse values into decision-making. These barriers include powerful interests supported by current norms and legal rules such as property rights, which determine whose values and which values of nature are acted on. A better understanding of how and why nature is (under)valued is more urgent than ever 4 . Notwithstanding agreements to incorporate nature’s values into actions, including the Kunming-Montreal Global Biodiversity Framework (GBF) 5 and the UN Sustainable Development Goals 6 , predominant environmental and development policies still prioritize a subset of values, particularly those linked to markets, and ignore other ways people relate to and benefit from nature 7 . Arguably, a ‘values crisis’ underpins the intertwined crises of biodiversity loss and climate change 8 , pandemic emergence 9 and socio-environmental injustices 10 . On the basis of more than 50,000 scientific publications, policy documents and Indigenous and local knowledge sources, the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) assessed knowledge on nature’s diverse values and valuation methods to gain insights into their role in policymaking and fuller integration into decisions 7,11 . Applying this evidence, combinations of values-centred approaches are proposed to improve valuation and address barriers to uptake, ultimately leveraging transformative changes towards more just (that is, fair treatment of people and nature, including inter- and intragenerational equity) and sustainable futures.

BACKGROUND: Zika virus (ZIKV) infection has been linked to the Guillain-Barré syndrome. From November 2015 through March 2016, clusters of cases of the Guillain-Barré syndrome were observed during the outbreak of ZIKV infection in Colombia. We characterized the clinical features of cases of Guillain-Barré syndrome in the context of this ZIKV infection outbreak and investigated their relationship with ZIKV infection. METHODS: A total of 68 patients with the Guillain-Barré syndrome at six Colombian hospitals were evaluated clinically, and virologic studies were completed for 42 of the patients. We performed reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays for ZIKV in blood, cerebrospinal fluid, and urine, as well as antiflavivirus antibody assays. RESULTS: A total of 66 patients (97%) had symptoms compatible with ZIKV infection before the onset of the Guillain-Barré syndrome. The median period between the onset of symptoms of ZIKV infection and symptoms of the Guillain-Barré syndrome was 7 days (interquartile range, 3 to 10). Among the 68 patients with the Guillain-Barré syndrome, 50% were found to have bilateral facial paralysis on examination. Among 46 patients in whom nerve-conduction studies and electromyography were performed, the results in 36 patients (78%) were consistent with the acute inflammatory demyelinating polyneuropathy subtype of the Guillain-Barré syndrome. Among the 42 patients who had samples tested for ZIKV by RT-PCR, the results were positive in 17 patients (40%). Most of the positive RT-PCR results were in urine samples (in 16 of the 17 patients with positive RT-PCR results), although 3 samples of cerebrospinal fluid were also positive. In 18 of 42 patients (43%) with the Guillain-Barré syndrome who underwent laboratory testing, the presence of ZIKV infection was supported by clinical and immunologic findings. In 20 of these 42 patients (48%), the Guillain-Barré syndrome had a parainfectious onset. All patients tested were negative for dengue virus infection as assessed by RT-PCR. CONCLUSIONS: The evidence of ZIKV infection documented by RT-PCR among patients with the Guillain-Barré syndrome during the outbreak of ZIKV infection in Colombia lends support to the role of the infection in the development of the Guillain-Barré syndrome. (Funded by the Bart McLean Fund for Neuroimmunology Research and others.).

To evaluate the association between human papillomavirus (HPV) and cervical cancer, we performed a population-based case-control study in Columbia and Spain, the former country having an incidence rate of cervical cancer about 8 times higher than the latter. It included 436 cases of histologically confirmed invasive cervical cancer and 387 randomly selected population controls. Information on demographic variables, sexual behaviour and other risk factors was obtained by interview. HPV-DNA was measured in cervical-swab specimens with 3 hybridization assays: ViraPap, Southern hybridization (SH) and polymerase chain reaction (PCR). The presence of HPV-DNA and detection of types 16, 18, 31, 33 and 35 were strongly associated with cervical cancer in each country regardless of the assay used. For both countries combined the adjusted odds ratios and 95% confidence intervals were: ViraPap OR = 25.9 (10.0-66.7); SH OR = 6.8 (3.4-13.4); and PCR OR = 28.8 (15.7-52.6). HPV-16 was the most common type detected in both cases and controls. Our results indicate that there is a very strong association between HPV 16, 18, 31, 33 and 35 and invasive cervical cancer and that this association is probably causal.

Abstract In this commentary we critically discuss the suitability of payments for ecosystem services and the most important challenges they face. While such instruments can play a role in improving environmental governance, we argue that over‐reliance on payments as win‐win solutions might lead to ineffective outcomes, similar to earlier experience with integrated conservation and development projects. Our objective is to raise awareness, particularly among policy makers and practitioners, about the limitations of such instruments and to encourage a dialogue about the policy contexts in which they might be appropriate.

This systematic review of 58 observational studies identified hypothetical causal mechanisms explaining the effects of short and long intervals between pregnancies on maternal, perinatal, infant, and child health, and critically examined the scientific evidence for each causal mechanism hypothesized. The following hypothetical causal mechanisms for explaining the association between short intervals and adverse outcomes were identified: maternal nutritional depletion, folate depletion, cervical insufficiency, vertical transmission of infections, suboptimal lactation related to breastfeeding-pregnancy overlap, sibling competition, transmission of infectious diseases among siblings, incomplete healing of uterine scar from previous cesarean delivery, and abnormal remodeling of endometrial blood vessels. Women's physiological regression is the only hypothetical causal mechanism that has been proposed to explain the association between long intervals and adverse outcomes. We found growing evidence supporting most of these hypotheses.

For centuries, wastewater has been improperly used in agriculture, presenting potential risks to public health and the environment. In the context of scientific development, and confronted by an increasing water crisis, wastewater reuse merits consideration because the practice helps decrease water use pressure and moderates water pollution. Thus, this article presents a literature review that addresses the effects, both positive and negative, of wastewater use in agriculture, emphasizing the effects on the soil environment. The literature review reveals that, until the 1990s, research studies promoted the use of wastewater for irrigation purposes from a treatment approach, while proposing “end of pipe” conventional solutions. However, more recent research studies (2012–2016) reveal that agricultural reuse significantly affects soil texture properties, while also causing possible alterations of the biomass and microbiota. In addition, research in this period has been oriented to the quantitative evaluation of microbiological risk.

Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in the emergency departments worldwide. The cornerstones of effective treatment of IAIs are early recognition, adequate source control, and appropriate antimicrobial therapy. Prompt resuscitation of patients with ongoing sepsis is of utmost important. In hospitals worldwide, non-acceptance of, or lack of access to, accessible evidence-based practices and guidelines result in overall poorer outcome of patients suffering IAIs. The aim of this paper is to promote global standards of care in IAIs and update the 2013 WSES guidelines for management of intra-abdominal infections.

Preeclampsia (PE) is an often fatal pathology characterized by hypertension and proteinuria at the 20th week of gestation that affects 5-10% of the pregnancies. The problem is particularly important in developing countries in where the incidence of hypertensive disorders of pregnancy is higher and maternal mortality rates are 20 times higher than those reported in developed countries. Risk factors for the development of PE include obesity, insulin resistance and hyperlipidemia that stimulate inflammatory cytokine release and oxidative stress leading to endothelial dysfunction (ED). However, how all these clinical manifestations concur to develop PE is still not very well understood. The related poor trophoblast invasion and uteroplacental artery remodeling described in PE, increases reactive oxygen species (ROS), hypoxia and ED. Here we aim to review current literature from research showing the interplay between oxidative stress, ED and PE to the outcomes of current clinical trials aiming to prevent PE with antioxidant supplementation.

Studies have documented biodiversity losses due to intensification of coffee management (reduction in canopy richness and complexity). Nevertheless, questions remain regarding relative sensitivity of different taxa, habitat specialists, and functional groups, and whether implications for biodiversity conservation vary across regions.We quantitatively reviewed data from ant, bird, and tree biodiversity studies in coffee agroecosystems to address the following questions: Does species richness decline with intensification or with individual vegetation characteristics? Are there significant losses of species richness in coffee-management systems compared with forests? Is species loss greater for forest species or for particular functional groups?and Are ants or birds more strongly affected by intensification? Across studies, ant and bird richness declined with management intensification and with changes in vegetation. Species richness of all ants and birds and of forest ant and bird species was lower in most coffee agroecosystems than in forests, but rustic coffee (grown under native forest canopies) had equal or greater ant and bird richness than nearby forests. Sun coffee(grown without canopy trees) sustained the highest species losses, and species loss of forest ant, bird, and tree species increased with management intensity. Losses of ant and bird species were similar, although losses of forest ants were more drastic in rustic coffee. Richness of migratory birds and of birds that forage across vegetation strata was less affected by intensification than richness of resident, canopy, and understory bird species. Rustic farms protected more species than other coffee systems, and loss of species depended greatly on habitat specialization and functional traits. We recommend that forest be protected, rustic coffee be promoted,and intensive coffee farms be restored by augmenting native tree density and richness and allowing growth of epiphytes. We also recommend that future research focus on potential trade-offs between biodiversity conservation and farmer livelihoods stemming from coffee production.