Titers of IgG and IgA against SARS-CoV-2 proteins and their association with symptoms in mild COVID-19 infection.

Humoral immunity in COVID-19 includes antibodies (Abs) targeting spike (S) and nucleocapsid (N) SARS-CoV-2 proteins. Antibody levels are known to correlate with disease severity, but titers are poorly reported in mild or asymptomatic cases. Here, we analyzed the titers of IgA and IgG against SARS-CoV-2 proteins in samples from 200 unvaccinated Hospital Workers (HWs) with mild COVID-19 at two time points after infection. We analyzed the relationship between Ab titers and patient characteristics, clinical features, and evolution over time. Significant differences in IgG and IgA titers against N, S1 and S2 proteins were found when samples were segregated according to time T1 after infection, seroprevalence at T1, sex and age of HWs and symptoms at infection. We found that IgM + samples had higher titers of IgG against N antigen and IgA against S1 and S2 antigens than IgM - samples. There were significant correlations between anti-S1 and S2 Abs. Interestingly, IgM + patients with dyspnea had lower titers of IgG and IgA against N, S1 and S2 than those without dyspnea. Comparing T1 and T2, we found that IgA against N, S1 and S2 but only IgG against certain Ag decreased significantly. In conclusion, an association was established between Ab titers and the development of infection symptoms.

The 2023 Latin America report of the Lancet Countdown on health and climate change: the imperative for health-centred climate-resilient development.

In 2023, a series of climatological and political events unfolded, partly driving forward the global climate and health agenda while simultaneously exposing important disparities and vulnerabilities to climate-related events. On the policy front, a significant step forward was marked by the inaugural Health Day at COP28, acknowledging the profound impacts of climate change on health. However, the first-ever Global Stocktake showed an important gap between the current progress and the targets outlined in the Paris Agreement, underscoring the urgent need for further and decisive action. From a Latin American perspective, some questions arise: How do we achieve the change that is needed? How to address the vulnerabilities to climate change in a region with long-standing social inequities? How do we promote intersectoral collaboration to face a complex problem such as climate change? The debate is still ongoing, and in many instances, it is just starting. The renamed regional centre Lancet Countdown Latin America (previously named Lancet Countdown South America) expanded its geographical scope adding Mexico and five Central American countries: Costa Rica, El Salvador, Guatemala, Honduras, and Panama, as a response to the need for stronger collaboration in a region with significant social disparities, including research capacities and funding. The centre is an independent and multidisciplinary collaboration that tracks the links between health and climate change in Latin America, following the global Lancet Countdown's methodologies and five domains. The Lancet Countdown Latin America work hinges on the commitment of 23 regional academic institutions, United Nations agencies, and 34 researchers who generously contribute their time and expertise. Building from the first report, the 2023 report of the Lancet Countdown Latin America, presents 34 indicators that track the relationship between health and climate change up to 2022, aiming at providing evidence to public decision-making with the purpose of improving the health and wellbeing of Latin American populations and reducing social inequities through climate actions focusing on health. This report shows that Latin American populations continue to observe a growing exposure to changing climatic conditions. A warming trend has been observed across all countries in Latin America, with severe direct impacts. In 2022, people were exposed to ambient temperatures, on average, 0.38 °C higher than in 1986-2005, with Paraguay experiencing the highest anomaly (+1.9 °C), followed by Argentina (+1.2 °C) and Uruguay (+0.9 °C) (indicator 1.1.1). In 2013-2022, infants were exposed to 248% more heatwave days and people over 65 years old were exposed to 271% more heatwave days than in 1986-2005 (indicator 1.1.2). Also, compared to 1991-2000, in 2013-2022, there were 256 and 189 additional annual hours per person, during which ambient heat posed at least moderate and high risk of heat stress during light outdoor physical activity in Latin America, respectively (indicator 1.1.3). Finally, the region had a 140% increase in heat-related mortality from 2000-2009 to 2013-2022 (indicator 1.1.4). Changes in ecosystems have led to an increased risk of wildfires, exposing individuals to very or extremely high fire danger for more extended periods (indicator 1.2.1). Additionally, the transmission potential for dengue by Aedes aegypti mosquitoes has risen by 54% from 1951-1960 to 2013-2022 (indicator 1.3), which aligns with the recent outbreaks and increasing dengue cases observed across Latin America in recent months. Based on the 2023 report of the Lancet Countdown Latin America, there are three key messages that Latin America needs to further explore and advance for a health-centred climate-resilient development. Latin American countries require intersectoral public policies that simultaneously increase climate resilience, reduce social inequities, improve population health, and reduce greenhouse gas (GHG) emissions. The findings show that adaptation policies in Latin America remain weak, with a pressing need for robust vulnerability and adaptation (V&A) assessments to address climate risks effectively. Unfortunately, such assessments are scarce. Up to 2021, Brazil is the only country that has completed and officially reported a V&A to the 2021 Global Survey conducted by the World Health Organization (WHO). Argentina, Guatemala, and Panama have also conducted them, but they have not been reported (indicator 2.1.1). Similarly, efforts in developing and implementing Health National Adaptation Plans (HNAPs) are varied and limited in scope. Brazil, Chile, and Uruguay are the only countries that have an HNAP (indicator 2.1.2). Moreover, self-reported city-level climate change risk assessments are very limited in the region (indicator 2.1.3). The collaboration between meteorological and health sectors remains insufficient, with only Argentina, Brazil, Colombia, and Guatemala self-reporting some level of integration (indicator 2.2.1), hindering comprehensive responses to climate-related health risks in the region. Additionally, despite the urgent need for action, there has been minimal progress in increasing urban greenspaces across the region since 2015, with only Colombia, Nicaragua, and Venezuela showing slight improvements (indicator 2.2.2). Compounding these challenges is the decrease in funding for climate change adaptation projects in Latin America, as evidenced by the 16% drop in funds allocated by the Green Climate Fund (GCF) in 2022 compared to 2021. Alarmingly, none of the funds approved in 2022 were directed toward climate change and health projects, highlighting a critical gap in addressing health-related climate risks (indicator 2.2.3). From a vulnerability perspective, the Mosquito Risk Index (MoRI) indicates an overall decrease in severe mosquito-borne disease risk in the region due to improvements in water, sanitation, and hygiene (WASH) (indicator 2.3.1). Brazil and Paraguay were the only countries that showed an increase in this indicator. It is worth noting that significant temporal variation within and between countries still persists, suggesting inadequate preparedness for climate-related changes. Overall, population health is not solely determined by the health sector, nor are climate policies a sole responsibility of the environmental sector. More and stronger intersectoral collaboration is needed to pave development pathways that consider solid adaptation to climate change, greater reductions of GHG emissions, and that increase social equity and population health. These policies involve sectors such as finance, transport, energy, housing, health, and agriculture, requiring institutional structures and policy instruments that allow long-term intersectoral collaboration. Latin American countries need to accelerate an energy transition that prioritises people's health and wellbeing, reduces energy poverty and air pollution, and maximises health and economic gains. In Latin America, there is a notable disparity in energy transition, with electricity generation from coal increasing by an average of 2.6% from 1991-2000 to 2011-2020, posing a challenge to efforts aimed at phasing out coal (indicator 3.1.1). However, this percentage increase is conservative as it may not include all the fossil fuels for thermoelectric electricity generation, especially during climate-related events and when hydropower is affected (Panel 4). Yet, renewable energy sources have been growing, increasing by an average of 5.7% during the same period. Access to clean fuels for cooking remains a concern, with 46.3% of the rural population in Central America and 23.3% in South America lacking access to clean fuels in 2022 (indicator 3.1.2). It is crucial to highlight the concerning overreliance on fossil fuels, particularly liquefied petroleum gas (LPG), as a primary cooking fuel. A significant majority of Latin American populations, approximately 74.6%, rely on LPG for cooking. Transitioning to cleaner heating and cooking alternatives could also have a health benefit by reducing household air pollution-related mortality. Fossil fuels continue to dominate road transport energy in Latin America, accounting for 96%, although some South American countries are increasing the use of biofuels (indicator 3.1.3). Premature mortality attributable to fossil-fuel-derived PM2.5 has shown varied trends across countries, increasing by 3.9% from 2005 to 2020 across Latin America, which corresponds to 123.5 premature deaths per million people (indicator 3.2.1). The Latin American countries with the highest premature mortality rate attributable to PM2.5 in 2020 were Chile, Peru, Brazil, Colombia, Mexico, and Paraguay. Of the total premature deaths attributable to PM2.5 in 2020, 19.1% was from transport, 12.3% from households, 11.6% from industry, and 11% from agriculture. From emission and capture of GHG perspective, commodity-driven deforestation and expansion of agricultural land remain major contributors to tree cover loss in the region, accounting for around 80% of the total loss (indicator 3.3). Additionally, animal-based food production in Latin America contributes 85% to agricultural CO2 equivalent emissions, with Argentina, Brazil, Panama, Paraguay, and Uruguay ranking highest in per capita emissions (indicator 3.4.1). From a health perspective, in 2020, approximately 870,000 deaths were associated with imbalanced diets, of which 155,000 (18%) were linked to high intake of red and processed meat and dairy products (indicator 3.4.2). Energy transition in Latin America is still in its infancy, and as a result, millions of people are currently exposed to dangerous levels of air pollution and energy poverty (i.e., lack of access to essential energy sources or services). As shown in this report, the levels of air pollution, outdoors and indoors, are a significant problem in the wholeregion, with marked disparities between urban and rural areas. In 2022, Peru, Chile, Mexico, Guatemala, Colombia, El Salvador, Brazil, Uruguay, Honduras, Panama, and Nicaragua were in the top 100 most polluted countries globally. Transitioning to cleaner sources of energy, phasing out fossil fuels, and promoting better energy efficiency in the industrial and housing sectors are not only climate mitigation measures but also huge health and economic opportunities for more prosperous and healthy societies. Latin American countries need to increase climate finance through permanent fiscal commitments and multilateral development banks to pave climate-resilient development pathways. Climate change poses significant economic costs, with investments in mitigation and adaptation measures progressing slowly. In 2022, economic losses due to weather-related extreme events in Latin America were US$15.6 billion -an amount mainly driven by floods and landslides in Brazil-representing 0.28% of Latin America's Gross Domestic Product (GDP) (indicator 4.1.1). In contrast to high-income countries, most of these losses lack insurance coverage, imposing a substantial financial strain on affected families and governments. Heat-related mortality among individuals aged 65 and older in Latin America reached alarming levels, with losses exceeding the equivalent of the average income of 451,000 people annually (indicator 4.1.2). Moreover, the total potential income loss due to heat-related labour capacity reduction amounted to 1.34% of regional GDP, disproportionately affecting the agriculture and construction sectors (indicator 4.1.3). Additionally, the economic toll of premature mortality from air pollution was substantial, equivalent to a significant portion of regional GDP (0.61%) (indicator 4.1.4). On a positive note, clean energy investments in the region increased in 2022, surpassing fossil fuel investments. However, in 2020, all countries reviewed continued to offer net-negative carbon prices, revealing fossil fuel subsidies totalling US$23 billion. Venezuela had the highest net subsidies relative to current health expenditure (123%), followed by Argentina (10.5%), Bolivia (10.3%), Ecuador (8.3%), and Chile (5.6%) (indicator 4.2.1). Fossil fuel-based energy is today more expensive than renewable energy. Fossil fuel burning drives climate change and damages the environment on which people depend, and air pollution derived from the burning of fossil fuels causes seven million premature deaths each year worldwide, along with a substantial burden of disease. Transitioning to sustainable, zero-emission energy sources, fostering healthier food systems, and expediting adaptation efforts promise not only environmental benefits but also significant economic gains. However, to implement mitigation and adaptation policies that also improve social wellbeing and prosperity, stronger and solid financial systems are needed. Climate finance in Latin American countries is scarce and strongly depends on political cycles, which threatens adequate responses to the current and future challenges. Progress on the climate agenda is lagging behind the urgent pace required. While engagement with the intersection of health and climate change is increasing, government involvement remains inadequate. Newspaper coverage of health and climate change has been on the rise, peaking in 2022, yet the proportion of climate change articles discussing health has declined over time (indicator 5.1). Although there has been significant growth in the number of scientific papers focusing on Latin America, it still represents less than 4% of global publications on the subject (indicator 5.3). And, while health was mentioned by most Latin American countries at the UN General Debate in 2022, only a few addressed the intersection of health and climate change, indicating a lack of awareness at the governmental level (indicator 5.4). The 2023 Lancet Countdown Latin America report underscores the cascading and compounding health impacts of anthropogenic climate change, marked by increased exposure to heatwaves, wildfires, and vector-borne diseases. Specifically, for Latin America, the report emphasises three critical messages: the urgent action to implement intersectoral public policies that enhance climate resilience across the region; the pressing need to prioritise an energy transition that focuses on health co-benefits and wellbeing, and lastly, that need for increasing climate finance by committing to sustained fiscal efforts and engaging with multilateral development banks. By understanding the problems, addressing the gaps, and taking decisive action, Latin America can navigate the challenges of climate change, fostering a more sustainable and resilient future for its population. Spanish and Portuguese translated versions of this Summary can be found in Appendix B and C, respectively. The full translated report in Spanish is available in Appendix D.

Toxoplasma gondii in a Remote Subsistence Hunting-Based Indigenous Community of the Peruvian Amazon.

Toxoplasma gondii is a ubiquitous zoonotic protozoan parasite that infects a wide variety range of warm-blooded animals. This study describes the epidemiological scenario of T. gondii in an indigenous community that relies on subsistence hunting in a well-conserved and isolated area of the Peruvian Amazon. The high seropositivity against T. gondii in humans (83.3% IgG and 6.1% IgM), wild mammals (30.45%, 17 species), peri-domestic rodents (10.0% Rattus sp.), and domestic animals (94.1% dogs and 100% cats) indicates the existence of a sylvatic cycle in the community under study. Individual age was found to be positively associated with IgG detection against T. gondii but not with IgM. It is estimated that each family consumed 5.67 infected animals per year with terrestrial species having higher infective rates than arboreal species. The main risk factors included improper handling and cooking of wild meat, poor hygiene practices, and feeding uncooked offal to domestic animals. This scenario results in a continuous process of infection and reinfection within the indigenous community with cats, dogs, and peri-domestic animals becoming infected through the ingestion of infected raw viscera. Our results emphasize the need to promote safe food handling practices and disposal of waste materials from hunted animals in such communities.

Circulation of DENV-2 serotype associated with increased risk of cumulative incidence of severe dengue and dengue with warning signs: A 16-year retrospective study in Peru.

Background: Dengue poses a significant public health challenge in Peru and other endemic countries worldwide. While severe dengue is known to be associated with secondary infection at the individual level, the factors that elevate the risk of severe dengue at the population level remain poorly understood. This study leverages over 16 years of secondary data from a Peruvian dengue surveillance system to assess which type of serotype-specific circulation is associated with an increased risk of cumulative incidence of severe dengue or dengue with warning signs (SD-DWS). Methodology: This is a retrospective analysis of secondary data using the Peruvian Ministry of Health databases of dengue cases and serotyping. A mixed negative binomial regression model for repeated measures over time was employed to estimate the association between the cumulative incidence of reported SD-DWS cases per 100,000 inhabitants and serotype-specific circulation. Crude and adjusted incidence ratios (IRR) were estimated. Principal findings: The study analyzed data from 2007 to 2022 across 19 regions of Peru, totaling 304 region-years. Data from nearly 58,000 serotype identification reports and 57,966 cases of SD-DWS were analyzed. The regions with most cumulative incidence of SD-DWS per 100,000 inhabitants during 2007 to 2022 were Madre de Dios (3859), Loreto (1518), Ucayali (1492), Tumbes (1335), and Piura (722). The adjusted model revealed a higher risk of cumulative incidence of SD-DWS when there was specific circulation of DENV-123 (aIRR 7.57 CI 4.00 - 14.31), DENV-12 (aIRR 4.66 CI 2.57 - 8.44), DENV-23 (aIRR 3.55 CI 1.75 - 7.21), or when there was circulation of DENV-2 alone or co-circulating with other serotypes (aIRR 27.7 CI 15.46 -49.63). Conclusions: Circulation of DENV-2 was associated with higher average incidence rate ratios of SD-DWS. Author summary: We investigated how the circulation of different dengue virus (DENV) serotypes are associated with the incidence of severe dengue and dengue with warning signs in Peru, a country where dengue is endemic. We analyzed 16 years of data from the dengue surveillance system, including nearly 58,000 serotype identification reports and 57,966 cases of severe dengue and dengue with warning signs. We found that regions with specific circulation of DENV-2, either alone or in combination with other serotypes, had higher incidence rates of severe dengue and dengue with warning signs. Our findings highlight the importance of monitoring DENV serotype circulation to manage and prevent severe dengue, especially in regions where DENV-2 is prevalent.

Lack of paternal silencing and ecotype-specific expression in head and body lice hybrids.

Paternal genome elimination (PGE) is a non-Mendelian inheritance system, described in numerous arthropod species, in which males develop from fertilized eggs, but their paternally inherited chromosomes are eliminated before or during spermatogenesis. Therefore, PGE males only transmit their maternally inherited set of chromosomes to their offspring. In addition to the elimination of paternal chromosomes, diverse PGE species have also repeatedly evolved the transcriptional silencing of the paternal genome, making males effectively haploid. However, it is unclear if this paternal chromosome silencing is mechanistically linked to the chromosome elimination or has evolved at a later stage, and if so, what drives the haploidization of males under PGE. In order to understand these questions, here we study the human louse, Pediculus humanus, which represents an ideal model system, as it appears to be the only instance of PGE where males eliminate, but not silence their paternal chromosomes, although the latter remains to be shown conclusively. In this study, we analyzed parent-of-origin allele-specific expression patterns in male offspring of crosses between head and body lice ecotypes. We show that hybrid adult males of P. humanus display biparental gene expression, which constitutes the first case of a species with PGE in which genetic activity of paternal chromosomes in the soma is not affected by embryonic silencing or (partial or complete) elimination. We did however also identify a small number of maternally biased genes (potentially imprinted genes), which may be involved in the elimination of paternal chromosomes during spermatogenesis. Finally, we have identified genes that show ecotype-specific expression bias. Given the low genetic diversity between ecotypes, this is suggestive for a role of epigenetic processes in ecotype differences.

Study protocol: improving response to malaria in the Amazon through identification of inter-community networks and human mobility in border regions of Ecuador, Peru and Brazil.

INTRODUCTION: Understanding human mobility's role in malaria transmission is critical to successful control and elimination. However, common approaches to measuring mobility are ill-equipped for remote regions such as the Amazon. This study develops a network survey to quantify the effect of community connectivity and mobility on malaria transmission. METHODS: We measure community connectivity across the study area using a respondent driven sampling design among key informants who are at least 18 years of age. 45 initial communities will be selected: 10 in Brazil, 10 in Ecuador and 25 in Peru. Participants will be recruited in each initial node and administered a survey to obtain data on each community's mobility patterns. Survey responses will be ranked and the 2-3 most connected communities will then be selected and surveyed. This process will be repeated for a third round of data collection. Community network matrices will be linked with each country's malaria surveillance system to test the effects of mobility on disease risk. ETHICS AND DISSEMINATION: This study protocol has been approved by the institutional review boards of Duke University (USA), Universidad San Francisco de Quito (Ecuador), Universidad Peruana Cayetano Heredia (Peru) and Universidade Federal Minas Gerais (Brazil). Results will be disseminated in communities by the end of the study.

Posttraumatic Stress and Alcohol Use Among Hispanic/Latinx University Students: A Moderated Indirect Effect Model of Coping-Related Drinking and Anxiety Sensitivity.

OBJECTIVE: Posttraumatic stress symptoms (PTSS) and anxiety sensitivity (AS) are associated with increased alcohol use and coping-motivated drinking among university students. This study among trauma-exposed Hispanic/Latinx university students sought to examine the indirect effect of PTSS on alcohol use severity through coping-motivated drinking and test the moderating role of AS and AS subfacets. METHODS: University students who identified as Hispanic/Latinx (N = 830) were recruited from a large, urban, southern university and completed online, self-report questionnaires. RESULTS: A significant interactive effect of PTSS and AS on coping-motivated drinking emerged. PTSS exerted a significant indirect effect on alcohol use severity, through coping-motivated drinking. Simple slope analyses revealed that PTSS was associated with coping-motivated drinking across all levels of AS. Post hoc results revealed unique biological sex differences in probable diagnosis odds ratios. CONCLUSIONS: These findings indicate that PTSS and AS are associated with coping-motivated drinking and alcohol use severity in trauma-exposed, Hispanic/Latinx university students.

Post-traumatic stress disorder, food insecurity, and social capital after the 2017 coastal El Niño flooding among mothers from Piura, Peru: A mixed method study.

In order to understand the impacts in the post-disaster scenario of the 2017 El Niño events in the Piura region-Peru, we examined post-traumatic stress disorder (PTSD), food insecurity (FI), and social capital (SC) across three-time points in mothers in highly affected areas. In the Piura, Castilla, and Catacaos districts, we studied mothers combining mixed-method assessments at three (June-July 2017), eight and 12 months after the flooding. Each outcome was measured with the PTSD-Checklist-Civilian (PCL-C), the Household-Food-Insecurity-Access-Scale (HFIAS), the Adapted-Social-Capital-Assessment-Tool (SASCAT) surveys. In-depth interviews at the first evaluation were also conducted. At the first evaluation, 38.1% (n = 21) of 179 mothers reported PTSD; eight months and one year after the flooding, it dropped to 1.9% and virtually zero, respectively. Severe FI also declined over time, from 90.0% three months after the flooding to 31.8% eight months after, to 13.1% one year after. Conversely, high-cognitive SC was increased three months after the flooding (42.1%) and much greater levels at eight and 12 months after (86.7% and 77.7%, respectively). High levels of PTSD and severe FI three months after the flooding consistently decreased to nearly zero one-year post-disaster. High levels of high-cognitive SC may have helped mothers to recover from PTSD and FI in Piura.

Helicobacter pylori cagA, vacA, iceA and babA Genotypes from Peruvian Patients with Gastric Intestinal Metaplasia.

We explored the clinical-stage association of gastric intestinal metaplasia (IM) compared to cases of chronic non-atrophic gastritis (CNAG) and its relationship with virulence genotypes of Helicobacter pylori (H. pylori) clinical isolates from patients with dyspepsia in Peru. This study was cross-sectional and included 158 H. pylori clinical isolates; each isolate corresponded to a different Peruvian patient, genotyped by polymerase chain reaction to detect cagA gene and EPIYA motifs, the vacA gene (alleles s1, s2, i1, i2, d1, d2, m1, m2 and subtypes s1a, s1b and s1c), the iceA gene (alleles 1 and 2), and the babA gene (allele 2). We observed that 38.6% presented with IM and that all clinical isolates were CagA positive. The EPIYA-ABC motif was predominant (68.4%), and we observed a high frequency for the vacA gene alleles s1 (94.9%), m1 (81.7%), i1 (63.9%), and d1 (70.9%). Strains with both iceA alleles were also detected (69.6%) and 52.2% were babA2 positive. In addition, it was observed that the cagA+/vacAs1m1 (PR: 2.42, 1.14 to 5.13, p < 0.05) and cagA+/vacAs1am1 (PR: 1.67, 1.13 to 2.45, p < 0.01) genotypes were associated with IM. Our findings revealed the cagA and vacA risk genotypes predominance, and we provided clinically relevant associations between Peruvian patients with H. pylori infection and IM clinical stage.

Functional characterization of biodegradable films obtained from whole Paecilomyces variotii biomass.

The indiscriminate use of petroleum-based polymers and plastics for single-use food packaging has led to serious environmental problems due the non-biodegradable characteristics. Thus, much attention has been focused on the research of new biobased and biodegradable materials. Yeast and fungal biomass are low-cost and abundant sources of biopolymers with highly promising properties for the development of biodegradable materials. This study aimed to select a preparation method to develop new biodegradable films using the whole biomass of Paecilomyces variotii subjected to successive physical treatments including ultrasonic homogenization (US) and heat treatment. Sterilization process had an important impact on the final filmogenic dispersion and mechanical properties of the films. Longer US treatments produced a reduction in the particle size and the application of an intermediate UT treatment contributed favorably to the breaking of agglomerates allowing the second US treatment to be more effective, achieving an ordered network with a more uniform distribution. Samples that were not filtrated after the sterilization process presented mechanical properties similar to plasticized materials. On the other hand, the filtration process after sterilization eliminated soluble and hydratable compounds, which produced a reduction in the hydration of the films.

Illuminating a Solvent-Dependent Hierarchy for Aromatic CH/π Complexes with Dynamic Covalent Glyco-Balances.

CH/π interactions are prevalent among aromatic complexes and represent invaluable tools for stabilizing well-defined molecular architectures. Their energy contributions are exceptionally sensitive to various structural and environmental factors, resulting in a context-dependent nature that has led to conflicting findings in the scientific literature. Consequently, a universally accepted hierarchy for aromatic CH/π interactions has remained elusive. Herein, we present a comprehensive experimental investigation of aromatic CH/π complexes, employing a novel approach that involves isotopically labeled glyco-balances generated in situ. This innovative strategy not only allows us to uncover thermodynamic insights but also delves into the often less-accessible domain of kinetic information. Our analyses have yielded more than 180 new free energy values while considering key factors such as solvent properties, the interaction geometry, and the presence and nature of accompanying counterions. Remarkably, the obtained results challenge conventional wisdom regarding the stability order of common aromatic complexes. While it was believed that cationic CH/π interactions held the highest strength, followed by polarized CH/π, nonpolarized CH/π, and finally anionic CH/π interactions, our study reveals that this hierarchy can be subverted depending on the environment. Indeed, the performance of polarized CH/π interactions can match or even outcompete that of cationic CH/π interactions making them a more reliable stabilization strategy across the entire spectrum of solvent polarity. Overall, our results provide valuable guidelines for the selection of optimal interacting partners in every chemical environment, allowing the design of tailored aromatic complexes with applications in supramolecular chemistry, organocatalysis, and/or material sciences.

Assessing Fuchs Corneal Endothelial Dystrophy Using Artificial Intelligence-Derived Morphometric Parameters From Specular Microscopy Images.

PURPOSE: The aim of this study was to evaluate the efficacy of artificial intelligence-derived morphometric parameters in characterizing Fuchs corneal endothelial dystrophy (FECD) from specular microscopy images. METHODS: This cross-sectional study recruited patients diagnosed with FECD, who underwent ophthalmologic evaluations, including slit-lamp examinations and corneal endothelial assessments using specular microscopy. The modified Krachmer grading scale was used for clinical FECD classification. The images were processed using a convolutional neural network for segmentation and morphometric parameter estimation, including effective endothelial cell density, guttae area ratio, coefficient of variation of size, and hexagonality. A mixed-effects model was used to assess relationships between the FECD clinical classification and measured parameters. RESULTS: Of 52 patients (104 eyes) recruited, 76 eyes were analyzed because of the exclusion of 26 eyes for poor quality retroillumination photographs. The study revealed significant discrepancies between artificial intelligence-based and built-in microscope software cell density measurements (1322 ± 489 cells/mm 2 vs. 2216 ± 509 cells/mm 2 , P < 0.001). In the central region, guttae area ratio showed the strongest correlation with modified Krachmer grades (0.60, P < 0.001). In peripheral areas, only guttae area ratio in the inferior region exhibited a marginally significant positive correlation (0.29, P < 0.05). CONCLUSIONS: This study confirms the utility of CNNs for precise FECD evaluation through specular microscopy. Guttae area ratio emerges as a compelling morphometric parameter aligning closely with modified Krachmer clinical grading. These findings set the stage for future large-scale studies, with potential applications in the assessment of irreversible corneal edema risk after phacoemulsification in FECD patients, as well as in monitoring novel FECD therapies.

Spin-Crossing in the (Z)-Selective Alkyne Semihydrogenation Mechanism Catalyzed by Mo3S4 Clusters: A Density Functional Theory Exploration.

Semihydrogenation of internal alkynes catalyzed by the air-stable imidazolyl amino [Mo3S4Cl3(ImNH2)3]+ cluster selectively affords the (Z)-alkene under soft conditions in excellent yields. Experimental results suggest a sulfur-based mechanism with the formation of a dithiolene adduct through interaction of the alkyne with the bridging sulfur atoms. However, computational studies indicate that this mechanism is unable to explain the experimental outcome: mild reaction conditions, excellent selectivity toward the (Z)-isomer, and complete deuteration of the vinylic positions in the presence of CD3OD and CH3OD. An alternative mechanism that explains the experimental results is proposed. The reaction begins with the hydrogenation of two of the Mo3(µ3-S)(µ-S)3 bridging sulfurs to yield a bis(hydrosulfide) intermediate that performs two sequential hydrogen atom transfers (HAT) from the S-H groups to the alkyne. The first HAT occurs with a spin change from singlet to triplet. After the second HAT, the singlet state is recovered. Although the dithiolene adduct is more stable than the hydrosulfide species, the large energy required for the subsequent H2 addition makes the system evolve via the second alternative pathway to selectively render the (Z)-alkene with a lower overall activation barrier.

Potent antibody-dependent cellular cytotoxicity of a V2-specific antibody is not sufficient for protection of macaques against SIV challenge.

Fc-mediated antibody effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can contribute to the containment HIV-1 replication but whether such activities are sufficient for protection is unclear. We previously identified an antibody to the variable 2 (V2) apex of the HIV-1 Env trimer (PGT145) that potently directs the lysis of SIV-infected cells by NK cells but poorly neutralizes SIV infectivity. To determine if ADCC is sufficient for protection, separate groups of six rhesus macaques were treated with PGT145 or a control antibody (DEN3) by intravenous infusion followed five days later by intrarectal challenge with SIVmac239. Despite high concentrations of PGT145 and potent ADCC activity in plasma on the day of challenge, all animals became infected and viral loads did not differ between the PGT145- and DEN3-treated animals. To determine if PGT145 can protect against a neutralization-sensitive virus, two additional groups of six macaques were treated with PGT145 and DEN3 and challenged with an SIVmac239 variant with a single amino acid change in Env (K180S) that increases PGT145 binding and renders the virus susceptible to neutralization by this antibody. Although there was no difference in virus acquisition, peak and chronic phase viral loads were significantly lower and time to peak viremia was significantly delayed in the PGT145-treated animals compared to the DEN3-treated control animals. Env changes were also selected in the PGT145-treated animals that confer resistance to both neutralization and ADCC. These results show that ADCC is not sufficient for protection by this V2-specific antibody. However, protection may be achieved by increasing the affinity of antibody binding to Env above the threshold required for neutralization.

Phylogenetic congruence of Plasmodium spp. and wild ungulate hosts in the Peruvian Amazon.

Malaria parasites are known to infect a variety of vertebrate hosts, including ungulates. However, ungulates of Amazonia have not been investigated. We report for the first time, the presence of parasite lineages closely related to Plasmodium odocoilei clade 1 and clade 2 in free-ranging South American red-brocket deer (Mazama americana; 44.4%, 4/9) and gray-brocket deer (Mazama nemorivaga; 50.0%, 1/2). We performed PCR-based analysis of blood samples from 47 ungulates of five different species collected during subsistence hunting by an indigenous community in the Peruvian Amazon. We detected Plasmodium malariae/brasilianum lineage in a sample from red-brocket deer. However, no parasite DNA was detected in collared peccary (Pecari tajacu; 0.0%, 0/10), white-lipped peccary (Tayassu pecari; 0.0%, 0/15), and tapir (Tapirus terrestris; 0.0%, 0/11). Concordant phylogenetic analyses suggested a possible co-evolutionary relationship between the Plasmodium lineages found in American deer and their hosts.

A Preliminary Investigation of Prenatal Anxiety Sensitivity and Postpartum Distress.

INTRODUCTION: Distress during pregnancy and postpartum is common and contributes to poor infant and maternal outcomes, such as developmental delays and mental health disorders, respectively. Anxiety sensitivity, or fear of the symptoms of anxiety (eg, palpitations, confusion), is a risk factor known to increase distress across psychological and health-related conditions. Given the physiologic and emotional changes that occur during the perinatal period, anxiety sensitivity may be a salient risk factor for maternal distress. In this pilot study, we aimed to understand the unique role of prenatal anxiety sensitivity in postpartum psychological and parenting distress. METHODS: Twenty-eight pregnant women (mean age, 30.86 years) were recruited from the community in a Southeastern metropolitan area of the United States. Participants completed self-report measures during their third trimester of pregnancy and again within 10 weeks postpartum. The Depression Anxiety and Stress Scales-21 and the Parenting Distress subscale of the Parenting Stress Index-4-Short Form were the primary postpartum outcome measures. RESULTS: Prenatal anxiety sensitivity was elevated in this sample relative to convenience samples. Prenatal anxiety sensitivity uniquely contributed to postpartum psychological (b, 1.01; P < .001) and parenting distress (b, 0.62; P = .008), after accounting for age, gravidity, and gestation. DISCUSSION: Albeit preliminary, results suggest prenatal anxiety sensitivity may be an important and malleable risk factor associated with several mental health concerns common in the perinatal period. Anxiety sensitivity may be targeted with brief interventions to prevent or reduce postpartum distress. Reducing prenatal anxiety sensitivity has the potential prevent the onset or worsening of psychological disorders among women and, in turn, may improve infant and child outcomes. Future studies should replicate these findings in a larger sample.

Complexation of the Antihypertensive Drug Olmesartan with Zn: In Vivo Antihypertensive and Cardiac Effects.

This study is based on the premise that the application of chemical synthesis strategies to structurally modify commercial drugs by complexation with biometals is a valid procedure to improve their biological effects. Our purpose is to synthesize a compound with greater efficacy than the original drug, able to enhance its antihypertensive and cardiac pharmacological activity. Herein, the structure of the coordination compound of Zn(II) and the antihypertensive drug olmesartan, [Zn(Olme)(H2O)2] (ZnOlme), is presented. After 8 weeks of treatment in SHR male rats, ZnOlme displayed a better blood pressure-lowering activity compared with olmesartan, with a noticeable effect even in the first weeks of treatment, while ZnCl2 showed similar results than the control. ZnOlme also reduced left ventricle (LV) weight and left ventricle/tibia length ratio (LV/TL), posterior wall thickness (PWT), and intraventricular septum in diastole (IVSd) suggesting its potential to prevent LV hypertrophy. Besides, ZnOlme reduced interstitial fibrosis (contents of collagen types I and III, responsible for giving rigidity and promoting vascular elasticity, respectively). The recovery of heart function was also evidenced by fractional shortening (diastolic left ventricular/systolic left ventricular) diameter determinations. Furthermore, ZnOlme increased the antioxidant capacity and prevented cardiac oxidative stress: it enhanced the reduction of reactive oxygen species generation, exerted a significant decrease in lipid peroxidation and enhanced glutathione contents in heart tissues compared to the control, Zn, and olmesartan treatments. Our results demonstrate that continuous oral administration of ZnOlme causes a better antihypertensive effect and grants enhancement of cardioprotection through antioxidant activity, in combination with hemodynamic improvement.