Impact of Peptide Sequence on Functional siRNA Delivery and Gene Knockdown with Cyclic Amphipathic Peptide Delivery Agents.

Short-interfering RNA (siRNA) oligonucleotide therapeutics that modify gene expression by accessing RNA-interference (RNAi) pathways have great promise for the treatment of a range of disorders; however, their application in clinical settings has been limited by significant challenges in cellular delivery. Herein, we report a structure-function study using a series of modified cyclic amphipathic cell-penetrating peptides (CAPs) to determine the impact of peptide sequence on (1) siRNA-binding efficiency, (2) cellular delivery and knockdown efficiency, and (3) the endocytic uptake mechanism. Nine cyclic peptides of the general sequence Ac-C[XZ]4CG-NH2 in which X residues are hydrophobic/aromatic (Phe, Tyr, Trp, or Leu) and Z residues are charged/hydrophilic (Arg, Lys, Ser, or Glu) are assessed along with one acyclic peptide, Ac-(WR)4G-NH2. Cyclization is enforced by intramolecular disulfide bond formation between the flanking Cys residues. Binding analyses indicate that strong cationic character and the presence of aromatic residues that are competent to participate in CH-π interactions lead to CAP sequences that most effectively interact with siRNA. CAP-siRNA binding increases in the following order as a function of CAP hydrophobic/aromatic content: His < Phe < Tyr < Trp. Both cationic charge and disulfide-constrained cyclization of CAPs improve uptake of siRNA in vitro. Net neutral CAPs and an acyclic peptide demonstrate less-efficient siRNA translocation compared to the cyclic, cationic CAPs tested. All CAPs tested facilitated efficient siRNA target gene knockdown of at least 50% (as effective as a lipofectamine control), with the best CAPs enabling >80% knockdown. Significantly, gene knockdown efficiency does not strongly correlate with CAP-siRNA internalization efficiency but moderately correlates with CAP-siRNA-binding affinity. Finally, utilization of small-molecule inhibitors and targeted knockdown of essential endocytic pathway proteins indicate that most CAP-siRNA nanoparticles facilitate siRNA delivery through clathrin- and caveolin-mediated endocytosis. These results provide insight into the design principles for CAPs to facilitate siRNA delivery and the mechanisms by which these peptides translocate siRNA into cells. These studies also demonstrate the nature of the relationships between peptide-siRNA binding, cellular delivery of siRNA cargo, and functional gene knockdown. Strong correlations between these properties are not always observed, which illustrates the complexity in the design of optimal next-generation materials for oligonucleotide delivery.

Eventos de vida estresantes y su efecto en la conducta suicida en mujeres durante la pandemia por Covid-19 en México.

OBJETIVO: Analizar la estructura factorial, la validez convergente y divergente de la Escala Columbia de Severidad Suicida (CSSRS) y el Cuestionario de Eventos de Vida Estresantes (EVE) y medir la asociación entre EVE y conducta suicida (CS) en mujeres mexicanas durante la pandemia por Covid-19. Material y métodos. Se usaron datos de 2 398 mujeres que participaron en un estudio multicéntrico, realizado en México entre mayo y octubre de 2021. La información se recolectó mediante un cuestionario en línea que incluyó la CSSRS y el EVE. Se hizo un análisis factorial confirmatorio para valorar el ajuste de los modelos. RESULTADOS: El modelo final mostró asociación entre los EVE y la CS, y tuvo a la violencia como variable central. Dicho modelo presentó un ajuste adecuado (CFI = 0.950, IFI = 0.950, MFI = 0.975, RMSEA = 0.031, CI RMSEA = 0.026-0.036). CONCLUSIONES: La pandemia por Covid-19 evidenció la necesidad de crear e implementar estrategias que promuevan el cuidado de la salud mental, reduzcan la exposición a la violencia y faciliten los procesos de duelo para prevenir la CS en mujeres mexicanas.

Novel Francisella-like endosymbiont and Anaplasma species from Amblyomma nodosum hosted by the anteater Tamandua Mexicana in Mexico.

The microbiome represents a complex network among the various members of the community of microorganisms that are associated with a host. The composition of the bacterial community is essential to supplement multiple metabolic pathways that the host lacks, particularly in organisms with blood-sucking habits such as ticks. On the other hand, some endosymbionts showed some competence with potentially pathogenic microorganisms. Francisella-like endosymbionts (FLEs) encompass a group of gamma-proteobacterias that are closely related to Francisella tularensis, but are usually apathogenic, which brings nutrients like vitamin B and other cofactors to the tick. It has been postulated that the main route of transmission of FLE is vertical; however, evidence has accumulated regarding the possible mechanism of horizontal transmission. Despite growing interest in knowledge of endosymbionts in the Neotropical region, the efforts related to the establishment of their inventory for tick communities are concentrated in South and Central America, with an important gap in knowledge in Mesoamerican countries such as Mexico. For this reason, the aim of this work was to evaluate the presence and diversity of endosymbionts in the highly host-specialized tick Amblyomma nodosum collected from the anteater Tamandua mexicana in Mexico. We analysed 36 A. nodosum for the presence of DNA of endosymbiont (Coxiella and Francisella) and pathogenic (Anaplasma, Borrelia, Ehrlichia and Rickettsia) bacteria. The presence of a member of the genus Francisella and Candidatus Anaplasma brasiliensis was demonstrated. Our findings provide information on the composition of A. nodosum's microbiome, increasing the inventory of bacterial species associated with this hard tick on the American continent.

Morphological and molecular characteristics of hemoparasites in vaillant's frogs (Lithobates vaillanti).

Amphibian populations are declining around the world, and the main reasons are the environmental changes and pathogens. However, there are few studies addressing the interaction and impact of the different pathogens that affect amphibians, such as hemoparasites. These parasites had been described as common in some amphibian species, but unfortunately, their description and characterization are unclear and scarcely spread. The objective of the present study was to evaluate the morphological and molecular characterization of hemoparasites present in vaillant's frogs. Seven frogs of Lithobates vaillanti were captured at the biological station La Florida in Tabasco, Mexico. Blood smears were performed, and results show that 100% of the animals have hemoparasites. Three types of hemoparasites were found. Eighty-five percent of the frogs were positive to Hepatozoon sp., 57% to Lankesterella sp., and 28% to Trypanosoma sp. According to the molecular analysis of the obtained sequences of Trypanosoma sp. and Hepatozoon sp., both protozoans were positioned in between the clusters of parasites of different geographical regions. Nevertheless, no species names were assigned to any of these parasites because more sequences and analysis are needed.

Religious affiliation and major depressive episode in older adults: a cross-sectional study in six low- and middle- income countries.

BACKGROUND: The relationship of religious affiliation and mental health is complex, and being part of a minority religious group could have negative effects on mental health. In this study, we assessed the association between religious affiliation and major depressive episode (MDE) in older adults (> = 60 years) from China, Ghana, India, Mexico, Russia and South Africa. METHODS: We conducted a secondary analysis of data from the Study on global Ageing and adult health (SAGE), with six nationally-representative community-based samples (n = 21,410). Religious affiliation was self-reported by participants, and we defined MDE based on ICD-10 classification. We estimated the association of MDE with religious affiliation versus no religious affiliation, and minority versus majority affiliation. RESULTS: We observed no association between having a religious affiliation (vs. no affiliation) and the odds of MDE in older adults. In most cases minorities had higher odds of MDE as compared with the majority religion, but the associations were only significant for Muslims in Ghana and for Muslims, Hindus and Other in South Africa. CONCLUSIONS: While the results were significant only for two countries, we observed higher odds of MDE among minorities in most of them. Older adults who are members of religious minorities might be at risk for mental health problems, and there is a need for public health interventions aimed at them.

The role of sloths and anteaters as Leishmania spp. reservoirs: a review and a newly described natural infection of Leishmania mexicana in the northern anteater.

For years, mammals of the order Pilosa have been considered Leishmania reservoirs. But while most studies have focused on sloth species, anteaters have been overlooked, and in many Leishmania endemic countries like Mexico, no studies have been carried out. The aims of this work were to identify the presence of Leishmania spp. in tissue samples from road-killed northern tamanduas (Tamandua mexicana), using PCR amplification and sequencing of ITS1 DNA, and to discuss the role of Pilosa mammals as reservoirs of Leishmania based on available scientific records. This is the first study that identifies Leishmania in T. mexicana, from 1 of 16 individuals analyzed, so the estimated prevalence (CI 95%) of infection was 6.3% (0.3-27.2). Amplified sequence exhibited a 98.9% (727/735) similarity with L. mexicana, and phylogenetic analysis grouped the species in the L. mexicana-amazonensis cluster. The literature review revealed 241 cases of Leishmania spp. infection among 1219 Pilosa mammals evaluated, with prevalence between studies ranging from 3.5% in the brown-throated three-toed sloth (Bradypus variegatus) to 78% in the Hoffman's two-toed sloth (Choloepus hoffmanni). Current scientific information indicates that C. hoffmanni sloths are reservoirs of Leishmania, and further studies are needed in order to clarify if other Pilosa species play a role in Leishmania transmission.

New insights into the clinico-histopathological and molecular features of Pelecitus (Filarioidea: Onchocercidae) from a raptor bird.

Some Onchocercidae nematodes such as Pelecitus are parasites of medical and veterinary importance. The adult stage of Pelecitus has been reported infecting birds, and the microfilaria has been associated to human blindness. However, in some of these cases, the nematode was incompletely identified at the species level due to the scarcity of morphological taxonomic keys and, also, to the lack of molecular diagnostic analysis. Here, we report a new Pelecitus species in a crested caracara (Caracara cheriway) producing a severe tenosynovitis and microfilarial dermatitis. It is also the first record of Pelecitus in an American bird of prey. Clinical and histopathological features are described, contributing towards our understanding of the pathogenesis of Pelecitus and the health and conservation of wild bird populations. Our study also provides new information on the molecular diagnosis of this parasite and highlights the potential role of wild birds as Pelecitus reservoirs, and health risk for humans and wildlife.

Effect of host species diversity on multiparasite systems in rodent communities.

Reduced species diversity has been suggested to increase transmission rates and prevalence of infectious diseases. While this theory has been studied mostly in single pathogen systems, little is known regarding multiple pathogens systems in vertebrates at the community level. The aim of this study was to evaluate the effect of host richness and diversity on multiple parasite systems on a local scale. We captured small rodents and collected feces in three different vegetation types in a natural protected area in Janos, Chihuahua, Mexico. The flotation technique was used to identify parasite eggs or oocysts. Analysis of linear correlations was conducted between parasite prevalence and host and parasite diversity and richness. Negative correlation was detected between parasite prevalence and host diversity (p = 0.02 r(2) =-0.86), but no significant correlations was detected between parasite prevalence and host richness or parasite diversity or richness. Our study shows that at local scale, host diversity could affect multiple parasite systems in the same way that single pathogens do. Further studies should be performed on larger temporal and spatial scales to more thoroughly investigate the correlation observed in our analysis.

The role of interpersonal stressors and connectedness in acute suicide risk and the suicide crisis syndrome during the COVID-19 pandemic.

BACKGROUND: The global COVID-19 pandemic rapidly and drastically impacted everyday life and relationships. Fear of contracting and spreading the virus brought governments and individuals to adopt strict social distancing measures. These changes have had a significant negative impact on mental health, including a suggested increase in suicidal behaviors. The present study examined the role of interpersonal stress and connectedness in suicidal ideation, deliberate self-harm, suicide attempts, and the suicide crisis syndrome during the COVID-19 pandemic. METHODS: An international sample of 7837 adult participants was recruited across ten participating countries to complete an anonymous online battery of self-report questionnaires. Questionnaires assessed suicide-related outcomes, stressful life events (SLE), and connectedness. Multilevel regression analyses were used to examine the associations between SLE and connectedness on suicide-related outcomes within the past month. RESULTS: Interpersonal SLEs and low connectedness were associated with an increased likelihood of suicide-related outcomes and increased severity of suicide crisis syndrome. Specifically, higher rates of SLEs and lower levels of connectedness were associated with more suicide-related outcomes. LIMITATIONS: The use of a cross-sectional design and snowball sampling method may restrict the ability to establish causal relationships and limit the representativeness of the findings. CONCLUSIONS: Our findings suggest elevated suicide-related outcomes during the COVID-19 pandemic among individuals experiencing multiple interpersonal stressful life events and low connectedness with others. The circumstances of social life during the COVID-19 pandemic highlight the urgency of implementing preventive programs aimed at mitigating potential suicide risks that may arise in the aftermath of public stress situations.

Intentions to use mental health and suicide prevention resources among individuals with symptoms of the suicide crisis syndrome and/or suicidal ideation.

INTRODUCTION: The suicide crisis syndrome (SCS) has demonstrated efficacy in predicting suicide attempts, showing potential utility in detecting at-risk individuals who may not be willing to disclose suicidal ideation (SI). The present international study examined differences in intentions to utilize mental health and suicide prevention resources among community-based adults with varying suicide risk (i.e., presence/absence of SCS and/or SI). METHODS: A sample of 16,934 community-based adults from 13 countries completed measures about the SCS and SI. Mental health and suicide prevention resources were provided to all participants, who indicated their intentions to use these resources. RESULTS: Individuals with SCS (55.7%) were just as likely as those with SI alone (54.0%), and more likely than those with no suicide-related symptoms (45.7%), to report willingness to utilize mental health resources. Those with SI (both with and without SCS) were more likely to seek suicide prevention resources (52.6% and 50.5%, respectively) than those without SI (41.7% and 41.8%); however, when examining endorsements for personal use, those with SCS (21.6%) were more likely to use resources than individuals not at risk (15.1%). CONCLUSIONS: These findings provide insight into individuals' willingness to use resources across configurations of explicitly disclosed (SI) and indirect (SCS) suicide risk.

Cross transmission of gastrointestinal nematodes between captive neotropical felids and feral cats.

Pathogen cross transmission between wildlife and domestic animals represents an extinction risk for wildlife; however, reliable verification is difficult to perform, and in some cases, it is even considered unlikely to be conducted. The aim of this work was to identify cross transmission of helminths between feral cats and captive wild felids at a zoological park in southeastern Mexico. Feces were collected from jaguars (Panthera onca), cougars (Puma concolor), ocelots (Leopardus pardalis), margays (Leopardus wiedii), and jaguarundis (Puma yagouaroundi). A flotation technique and macroscopic sieving were performed on the feces. Additionally, as part of the noxious fauna control program of the park, feral cats were captured and euthanized. To perform parasitologic studies, helminths from these animals were recovered. Toxocara cati and Trichuris campanula were shared by jaguarundis and feral cats. Ancylostoma sp. was found in jaguar and ocelot and Ancylostoma tubaeforme in feral cats. Additionally, during this study, a couple of jaguarundis died with clinical signs of trichuriasis. This is the first report of T. campanula in jaguarundi. Because feral cats roam freely in the park, transmission could occur from these vertebrates to wild felids. This study shows the risk that parasites represent to wild felids; a similar situation could be found in free-living species, especially in fragmented habitats that favor contact with domestic animals.

Health and Social Care System Preparedness for Dementia Care in Mexico: Current Status and Recommendations to Achieve Optimal Care.

In this article, we summarise the findings of the situational analysis of dementia care generated as part of the STRiDE: Strengthening responses to dementia care in developing countries project, including a desk review, a SWOT analysis and views from relevant stakeholders. In addition, the article incorporates the experience of 4 years of work within the STRiDE project of FEDMA, Mexico's Federation of Alzheimer's and other dementias and its allied Associations in presenting specific recommendations to optimise dementia care in the country. All the information gathered brings together a detailed understanding of the current dementia care systems of diagnosis, treatment, and support in general and what is lacking, allowing for the generation of general recommendations to enhance the isolated efforts currently available and amplify their impact, as well as strategies to generate new services currently unavailable, but urgently needed.

3D wildlife skull models for wildlife veterinary training.

Wildlife veterinarians are necessary for zoonotic diseases and species loss management, and there is a rising interest to enroll at veterinary schools with the wish to work in zoo and wildlife medicine. However, teaching wildlife is challenging due to the difficulty faced by universities to work with wild animal specimens. The aim of the present was to evaluate the understanding efficiency of some anatomical and behavioral aspects using 3D printed models of four wildlife species skulls, the kinkaju (Potos flavus), the white-nosed coati (Nasua narica), the northern anteater (Tamandua mexicana), and the nine-banded armadillo (Dasypus novemcinctus). This study was performed on 85 third-year veterinary students, divided into an experimental and a control group, who used and not used 3D printed skulls, respectively. Results show that the experimental group shows higher scores, in three of the four variables evaluated, than the control group. Then, 3D wildlife printed skulls constitute a promising teaching tool for veterinary students. In fact, it may be as good as real skulls, since new 3D printers can print on high endurance and firmness stock with high accuracy at reduced costs. In this context, it is important to encourage its use for the training of new generations and keep professionals up to date.

Violence against Women during the COVID-19 Pandemic in Mexico.

This study measured the prevalence of cases of domestic violence against women and some associated factors during the COVID-19 pandemic in Mexico. Data were collected through a remote survey during 2020. The sample included 47,819 women aged 15 years and older. Jointpoint regression and logistic regression models were used. The prevalence of violence was 11.5%, which decreased in July and subsequently increased. The associated factors were being unemployed (OR = 2.01; 95%CI 1.89-2.16); being partially and totally quarantined (OR = 1.58; 95%CI 1.43-1.75 and OR = 1.47; 95%CI 1.32-1.63); being a caregiver of children; being a caregiver of elderly and/or suffering from a chronic illness (OR = 1.27; 95%CI 1.19-1.36; OR = 1.42; 95%CI 1.33-1.53; OR = 1.59; 95%CI 1.47-1.73); losing a family member to COVID-19 (OR = 1.26; 95%CI 1.13-1.41); and binge drinking (OR = 1.94; 95%CI 1.78-2.12). The confinement measures increased gender inequalities, economic problems and workload which further evidenced violence against women.

Transforming dementia research into policy change: A case study of the multi-country STRiDE project.

STRiDE was an ambitious four-year project in seven countries aiming to build capacity around generating and using research to support the development of policies to improve quality of life of people with dementia and their carers. The project's innovative approach combined rigorous academic research and hands-on civil society advocacy. This paper explores the project's unique strategy for policy change and compiles case-studies from several of the STRiDE countries. Finally, we share lessons learned and next steps to keep momentum for policy change going in each of these countries - and beyond.

Sociodemographic and Personal Predictors of Exclusive Breastfeeding in Pregnant Mexican Women Using Public Health Services.

Exclusive breastfeeding (EBF) is a cost-effective healthy behavior for the mother-child dyad. Globally, rates of EBF are low. Little research has been conducted on the joint role of modifiable and nonmodifiable variables in pregnant women's decision-making. The aim was to develop and test a model that used personal and sociodemographic factors to predict whether pregnant women who use public healthcare services plan to breastfeed. In a nonprobabilistic sample of 728 pregnant Mexican women, self-efficacy, the planned behavior theory constructs, and the intention to breastfeed (BFI) were measured. A total 60% of the sample was randomly chosen to develop a predictive multivariate logistic regression model. The model was validated in the remaining 40%. Women in the highest tertiles of attitudes and self-efficacy had fourfold increased chances of having a high BFI (OR 4.2, 95% CI [2.4, 7.4]). Working was associated with a decreased intention to exclusively breastfeed (OR 0.61, 95% CI [0.37, 0.98]). The model predicted BFI with a sensitivity of 38.3% and specificity of 82.2%. While personal variables predict the BFI, working decreases women's chances of breastfeeding. The results can be utilized to develop primary prevention strategies to help mothers who use public health services to breastfeed.

Measurement invariance of the GAD-5 Generalized Anxiety Disorder Scale in a Mexican general population sample.

The primary objective of this study was to evaluate the measurement of invariance by sex, age, and educational level of an online version of the Generalized Anxiety Disorder Scale in a five-item version (GAD-5). Configural, metric, scalar, and strict invariance were evaluated using data from 79,473 respondents who answered a mental health questionnaire during the COVID-19 pandemic in Mexico. The sex variable was classified as male or female; age was categorized as minors, youth, young adults, adults, and older adults; and educational level was divided into basic, upper secondary, higher, and graduate education. To test for configural invariance, confirmatory factor models were constructed. For metric invariance, equality restrictions were established for the factor loadings between the construct and its items; for scalar invariance, equality restrictions were established between the intercepts; strict variance implied the additional restriction of the residuals. Statistical analysis was performed in R software with the lavaan package. The results show that with respect to sex, age, and educational level, configural and metric measurement invariance was confirmed (ΔCFI < 0.002; ΔRMSEA < 0.015). However, with respect to scalar and strict invariance, the results showed significant differences regarding the fit model (ΔCFI > 0.002; ΔRMSEA > 0.015). We conclude that the GAD-5 presents configural and metric invariance for sex, age, and educational level, and scalar invariance for sex and age groups. However, the scale does not demonstrate strict invariance. We discuss the implications and suggest that this result could be related to the evaluation of sociodemographic variables.

Medical outcomes study social support survey (MOS-SSS) in patients with chronic disease: A psychometric assessment.

Purpose: Currently, information on the psychometric properties of the Medical outcomes study-social support survey (MOS-SSS) for patients with chronic disease in primary health care, suggests problems in the dimensionality, specifically predominant unidimensionality in a multidimensional measure. The aim of this study was to determine the internal structure (dimensionality, measurement invariance and reliability) and association with other variables. Methods: A total of 470 patients with chronic disease from a Family Medicine Unit at the Instituto Mexicano del Seguro Social, IMSS, with a mean age of 51.51 years were included. Participants responded to the Questionnaire of Sociodemographic Variables (Q-SV), SF-36 Health-Related Quality of Life Scale-version 1.1, and MOS-SSS. Results: Non-parametric (Mokken scaling analysis) and parametric (confirmatory factor analysis) analyses indicated unidimensionality, and three-factor model was not representative. A new 8-item version (MOS-S) was developed, where measurement invariance, equivalence with the long version, reliability, and relationship with the SF-36 were satisfactory. Conclusion: The MOS-SSS scale is unidimensional, and the shortened version yields valid and reliable scores for measuring social support in patients with chronic disease at the primary health care.

Identification of a unique endoplasmic retention motif in the Xenopus GIRK5 channel and its contribution to oocyte maturation.

G protein-activated inward-rectifying potassium (K+ ) channels (Kir3/GIRK) participate in cell excitability. The GIRK5 channel is present in Xenopus laevis oocytes. In an attempt to investigate the physiological role of GIRK5, we identified a noncanonical di-arginine endoplasmic reticulum (ER) retention motif (KRXY). This retention motif is located at the N-terminal region of GIRK5, coded by two small exons found only in X. laevis and X. tropicalis. These novel exons are expressed through use of an alternative transcription start site. Mutations in the sequence KRXY produced functional channels and induced progesterone-independent oocyte meiotic progression. The chimeric proteins enhanced green fluorescent protein (EGFP)-GIRK5-WT and the EGFP-GIRK5K13AR14A double mutant, were localized to the ER and the plasma membrane of the vegetal pole of the oocyte, respectively. Silencing of GIRK5 or blocking of this channel by external barium prevented progesterone-induced meiotic progression. The endogenous level of GIRK5 protein decreased through oocyte stages in prophase I augmenting by progesterone. In conclusion, we have identified a unique mechanism by which the expression pattern of a K+ channel evolved to control Xenopus oocyte maturation.

The genus Rickettsia in Mexico: Current knowledge and perspectives.

The genus Rickettsia encompasses 35 valid species of intracellular, coccobacilli bacteria that can infect several eukaryotic taxa, causing multiple emerging and re-emerging diseases worldwide. This work aimed to gather and summarise the current knowledge about the genus Rickettsia in Mexico, updating the taxonomy of the bacteria and their hosts by including all the records available until 2020, to elucidate host-parasite relationships and determine the geographical distribution of each Rickettsia species present in the country. Until now, 14 species of Rickettsia belonging to four groups have been recorded in Mexico. These species have been associated with 26 arthropod species (14 hard ticks, three soft ticks, two sucking lice, and seven fleas) and 17 mammal species distributed over 30 states in Mexico. This work highlights the high biological inventory of rickettsias for Mexico and reinforces the need to approach the study of this group from a One Health perspective.