Cholesterol-modified sphingomyelin chimeric lipid bilayer for improved therapeutic delivery.

Cholesterol (Chol) fortifies packing and reduces fluidity and permeability of the lipid bilayer in vesicles (liposomes)-mediated drug delivery. However, under the physiological environment, Chol is rapidly extracted from the lipid bilayer by biomembranes, which jeopardizes membrane stability and results in premature leakage for delivered payloads, yielding suboptimal clinic efficacy. Herein, we report a Chol-modified sphingomyelin (SM) lipid bilayer via covalently conjugating Chol to SM (SM-Chol), which retains membrane condensing ability of Chol. Systemic structure activity relationship screening demonstrates that SM-Chol with a disulfide bond and longer linker outperforms other counterparts and conventional phospholipids/Chol mixture systems on blocking Chol transfer and payload leakage, increases maximum tolerated dose of vincristine while reducing systemic toxicities, improves pharmacokinetics and tumor delivery efficiency, and enhances antitumor efficacy in SU-DHL-4 diffuse large B-cell lymphoma xenograft model in female mice. Furthermore, SM-Chol improves therapeutic delivery of structurally diversified therapeutic agents (irinotecan, doxorubicin, dexamethasone) or siRNA targeting multi-drug resistant gene (p-glycoprotein) in late-stage metastatic orthotopic KPC-Luc pancreas cancer, 4T1-Luc2 triple negative breast cancer, lung inflammation, and CT26 colorectal cancer animal models in female mice compared to respective FDA-approved nanotherapeutics or lipid compositions. Thus, SM-Chol represents a promising platform for universal and improved drug delivery.

A Spontaneous Renal Calyceal Rupture Mimicking Physiologic Changes of Pregnancy and Other Common Pathologies.

A spontaneous renal calyceal rupture in pregnancy is extremely rare and can be challenging to identify as its presentation can mimic other more common diagnoses, which can lead to a delay in management. Here, we describe an unusual case of renal calyceal rupture in a 24-year-old G2P0010 female with pregnancy at 26.5 weeks gestation age (WGA) who was admitted to the antepartum ward due to left flank pain and uterine contractions. A renal sonogram was performed, which revealed severe left hydronephrosis and the absence of the ipsilateral ureteral jet. Urinalysis was within normal limits, and her renal function was preserved. Laboratories were remarkable for elevated liver enzymes. Finally, an abdominopelvic MRI revealed the culprit, a calyceal rupture. Once the diagnosis was clear, a double J-stent was inserted using limited fluoroscopy with the goal of reducing intrarenal pressure and decreasing disease morbidity. The patient's symptoms significantly improved after double J-stent placement and resolved the following day. The patient further developed preeclampsia with severe features, which has previously been documented to occur in pregnant patients with renal tract ruptures. The diagnosis of a renal calyceal rupture in pregnancy is not straightforward, in part because of a lack of awareness of this pathology. Nevertheless, early identification can prevent unnecessary interventions and adverse outcomes. Its diagnosis can be made with MRI, and its management with ureteral stent placement shouldn't be delayed, and its association with preeclampsia should be further explored.

A Holistic and Community-Based Service Program Promoting Mental Health among Latina Breast Cancer Survivors and Informal Caregivers.

This report discusses the components and uptake of a holistic-health community-based service program designed to promote mental health among Latina breast cancer survivors and their caregivers. Salud Holística para la Mujer's (SAHOM) strategic plan tackled all phases of the mental health prevention continuum and of the cancer care continuum.

Nanotechnology-empowered therapeutics targeting neurodegenerative diseases.

Neurodegenerative diseases are posing pressing health issues due to the high prevalence among aging populations in the 21st century. They are evidenced by the progressive loss of neuronal function, often associated with neuronal necrosis and many related devastating complications. Nevertheless, effective therapeutical strategies to treat neurodegenerative diseases remain a tremendous challenge due to the multisystemic nature and limited drug delivery to the central nervous system. As a result, there is a pressing need to develop effective alternative therapeutics to manage the progression of neurodegenerative diseases. By utilizing the functional reconstructive materials and technologies with specific targeting ability at the nanoscale level, nanotechnology-empowered medicines can transform the therapeutic paradigms of neurodegenerative diseases with minimal systemic side effects. This review outlines the current applications and progresses of the nanotechnology-enabled drug delivery systems to enhance the therapeutic efficacy in treating neurodegenerative diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Nanotechnology-enabled gene delivery for cancer and other genetic diseases.

INTRODUCTION: Despite gene therapy is ideal for genetic abnormality-related diseases, the easy degradation, poor targeting, and inefficiency in entering targeted cells are plaguing the effective delivery of gene therapy. Viral and non-viral vectors have been used for delivering gene therapeutics in vivo by safeguarding nucleic acid agents to target cells and to reach the specific intracellular location. A variety of nanotechnology-enabled safe and efficient systems have been successfully developed to improve the targeting ability for effective therapeutic delivery of genetic drugs. AREAS COVERED: In this review, we outline the multiple biological barriers associated with gene delivery process, and highlight recent advances to gene therapy strategy in vivo, including gene correction, gene silencing, gene activation and genome editing. We point out current developments and challenges exist of non-viral and viral vector systems in association with chemical and physical gene delivery technologies and their potential for the future. EXPERT OPINION: This review focuses on the opportunities and challenges to various gene therapy strategy, with specific emphasis on overcoming the challenges through the development of biocompatibility and smart gene vectors for potential clinical application.

Modernization, collectivism, and gender equality predict love experiences in 45 countries.

Recent cross-cultural and neuro-hormonal investigations have suggested that love is a near universal phenomenon that has a biological background. Therefore, the remaining important question is not whether love exists worldwide but which cultural, social, or environmental factors influence experiences and expressions of love. In the present study, we explored whether countries' modernization indexes are related to love experiences measured by three subscales (passion, intimacy, commitment) of the Triangular Love Scale. Analyzing data from 9474 individuals from 45 countries, we tested for relationships with country-level predictors, namely, modernization proxies (i.e., Human Development Index, World Modernization Index, Gender Inequality Index), collectivism, and average annual temperatures. We found that mean levels of love (especially intimacy) were higher in countries with higher modernization proxies, collectivism, and average annual temperatures. In conclusion, our results grant some support to the hypothesis that modernization processes might influence love experiences.

Flow cytometry: a tool for understanding the behaviour of polyhydroxyalkanoate accumulators.

The use of mixed microbial cultures (MMCs) is seen as an attractive strategy for polyhydroxyalkanoate (PHA) production. In order to optimize the MMC-PHA production process, tools are required to improve our understanding of the physiological state of the PHA-storing microorganisms within the MMC. In the present study, we explored the use of flow cytometry to analyse the metabolic state and polyhydroxybutyrate (PHB) content of the microorganisms from an MMC-PHA production process. A sequencing batch reactor under a feast and famine regime was used to enrich an MMC with PHB-storing microorganisms. Interestingly, once the PHB-storing microorganisms are selected, the level of PHB accumulation depends largely on the metabolic state of these microorganisms and not exclusively on the consortium composition. These results demonstrate that flow cytometry is a powerful tool to help to understand the PHA storage response of an MMC-PHA production process. KEY POINTS: • Flow cytometry allows to measure PHB content and metabolic activity over time. • Microorganisms showing high PHB content also have high metabolic activity. • PHB producers with low metabolic activity show low PHB content.

Surface-modified nanotherapeutics targeting atherosclerosis.

Atherosclerosis is a chronic and metabolic-related disease that is a serious threat to human health. Currently available diagnostic and therapeutic measures for atherosclerosis lack adequate efficiency which requires promising alternative approaches. Nanotechnology-based nano-delivery systems allow for new perspectives for atherosclerosis therapy. Surface-modified nanoparticles could achieve highly effective therapeutic effects by binding to specific receptors that are abnormally overexpressed in atherosclerosis, with less adverse effects on non-target tissues. The main purpose of this review is to summarize the research progress and design ideas to target atherosclerosis using a variety of ligand-modified nanoparticle systems, discuss the shortcomings of current vector design, and look at future development directions. We hope that this review will provide novel research strategies for the design and development of nanotherapeutics targeting atherosclerosis.

Camptothesome elicits immunogenic cell death to boost colorectal cancer immune checkpoint blockade.

Camptothesome is an innovative nanovesicle therapeutic comprising the sphingomyelin-derived camptothecin (CPT) lipid bilayer. In this work, we deciphered that Camptothesome was taken up by colorectal cancer (CRC) cells through primarily the clathrin-mediated endocytotic pathway and displayed the potential of eliciting robust immunogenic cancer cell death (ICD) via upregulating calreticulin, high mobility group box 1 protein (HMGB-1), and adenosine triphosphate (ATP), three hallmarks involved in the induction of ICD. In addition, use of dying MC38 tumor cells treated with Camptothesome as vaccine prevented tumor growth in 60% mice that received subsequent injection of live MC38 cells on the contralateral flank, validating Camptothesome was a legitimate ICD inducer in vivo. Camptothesome markedly reduced the acute bone marrow toxicity and gastrointestinal mucositis associated with free CPT and beat free CPT and Onivyde on anti-CRC efficacy and immune responses in a partially interferon gamma (IFN-γ)-dependent manner. Furthermore, Camptothesome enhanced the efficacy of immune checkpoint inhibitors to shrink late-stage orthotopic MC38 CRC tumors with diminished tumor metastasis and markedly prolonged mice survival.

Afrontamiento a la muerte en estudiantes de medicina del Paraguay en agosto 2021: estudio multicéntrico / Coping with death in Paraguayan medical students in August 2021: a multicenter study

RESUMEN Introducción: el afrontamiento a la muerte constituye una de las situaciones más difíciles y estresantes a las que se tienen que enfrentar los estudiantes de medicina por el contacto cercano a pacientes en riesgo vital. Objetivos: determinar el nivel de afrontamiento a la muerte en estudiantes de medicina. Metodología: se aplicó diseño con enfoque cuantitativo, de tipo observacional, transversal, multicéntrico. Se incluyó a estudiantes de medicina del Paraguay, de ambos sexos, en agosto 2021, que aceptaban participar del estudio. Se utilizó un cuestionario telemático. Se midieron variables sociodemográficas. El nivel de afrontamiento se determinó con la escala de Bugen. La investigación fue aprobada por Comité de Ética de la Universidad Privada del Este, Asunción. Resultados: se incluyeron 504 estudiantes, siendo del sexo femenino en 74 % y con edad media 22 ± 4 años. El 88 % de los encuestados eran de nacionalidad paraguaya (88 %) y 73 % de religión católica. La mayoría nació en Paraguay (88 %), era católica (73 %), se hallaba inscripta como donante de órganos (60 %) y tenía antecedente reciente de muerte de un familiar o amigo (76 %). La escala de Bugen detectó bajo nivel de afrontamiento a la muerte en 50 %, siendo 52 % en las mujeres y 42 % en los varones (p <0,05). Conclusión: el afrontamiento a la muerte en estudiantes de medicina fue bajo. Se sugiere incluir cursos, talleres y planes formativos dentro de las asignaturas o como actividades de extensión para mejorar ese aspecto en el currículo de las facultades de medicina del Paraguay.

ABSTRACT Introduction: coping with death is one of the most difficult tasks that medical students have to face. Objectives: to determine the level of coping with death in medical students. Methodology: we conducted an observational, cross-sectional, multicenter study. We included men and women, medical students from public and private universities from Paraguay in 2021, who agreed to participate in the study. A telematic questionnaire was used. Sociodemographic variables were measured. The level of coping was determined with the Bugen scale. The research was approved by the Comité de Ética of the Universidad Privada del Este, Asunción. Results: 504 students were included, 74 % being female and with a mean age of 22 ± 4 years. Most were born in Paraguay (88 %), were Catholic (73 %), registered as an organ donor (60 %), and had a recent history of the death of a family member or friend (76 %). The Bugen scale detected a low level of coping with death in 52 % of the women and 42 % of the men (p <0.05). Conclusion: coping with death in medical students was low. It is suggested to include courses or workshops to improve this aspect in the curriculum of the medical schools of Paraguay.

Determinant Factors in Personal Decision-Making to Adopt COVID-19 Prevention Measures in Chile.

The pandemic has challenged countries to develop stringent measures to reduce infections and keep the population healthy. However, the greatest challenge is understanding the process of adopting self-care measures by individuals in different countries. In this research, we sought to understand the behavior of individuals who take self-protective action. We selected the risk homeostasis approach to identify relevant variables associated with the risk of contagion and the Protective Action Decision Model to understand protective decision-making in the pandemic. Subsequently, we conducted an exploratory survey to identify whether the same factors, as indicated in the literature, impact Chile's adoption of prevention measures. The variables gender, age, and trust in authority behave similarly to those found in the literature. However, socioeconomic level, education, and media do not impact the protection behaviors adopted to avoid contagion. Furthermore, the application of the Protective Action Decision Model is adequate to understand the protective measures in the case of a pandemic. Finally, women have a higher risk perception and adopt more protective measures, and in contrast, young people between 18 and 30 years of age are the least concerned about COVID-19 infection.

Sex differences in human mate preferences vary across sex ratios.

A wide range of literature connects sex ratio and mating behaviours in non-human animals. However, research examining sex ratio and human mating is limited in scope. Prior work has examined the relationship between sex ratio and desire for short-term, uncommitted mating as well as outcomes such as marriage and divorce rates. Less empirical attention has been directed towards the relationship between sex ratio and mate preferences, despite the importance of mate preferences in the human mating literature. To address this gap, we examined sex ratio's relationship to the variation in preferences for attractiveness, resources, kindness, intelligence and health in a long-term mate across 45 countries (n = 14 487). We predicted that mate preferences would vary according to relative power of choice on the mating market, with increased power derived from having relatively few competitors and numerous potential mates. We found that each sex tended to report more demanding preferences for attractiveness and resources where the opposite sex was abundant, compared to where the opposite sex was scarce. This pattern dovetails with those found for mating strategies in humans and mate preferences across species, highlighting the importance of sex ratio for understanding variation in human mate preferences.

Are Juglans neotropica Plantations Useful as a Refuge of Bryophytes Diversity in Tropical Areas?

Neotropical montane forests are considered biodiversity hotspots, where epiphytic bryophytes are an important component of the diversity, biomass and functioning of these ecosystems. We evaluated the richness and composition of bryophytes in secondary successional forests and mixed plantations of Juglans neotropica. In each forest type, the presence and cover of epiphytic bryophytes was registered in 400 quadrats of 20 cm × 30 cm. We analyzed the effects of canopy openness, diameter at breast height (DBH) and forest type on bryophyte richness, using a generalized linear model (GLM), as well as the changes in species composition using multivariate analysis. Fifty-five bryophyte species were recorded, of which 42 species were in secondary forests and 40 were in mixed plantations. Bryophyte richness did not change at forest level; however, at tree level, richness was higher in the mixed plantation of J. neotropica compared to the secondary forests, due to the presence of species adapted to high light conditions. On the other hand, bryophyte communities were negatively affected by the more open canopy in the mixed plantation of J. neotropica, species adapted to more humid conditions being less abundant. We conclude that species with narrow microclimatic niches are threatened by deforestation, and J. neotropica plantations do not act as refuge for drought-sensitive forest species present in secondary forests.

The Mediating Role of Organizational Identification in the Relation between Organizational Social Capital, Perceived Organizational Prestige, Perceived Employability and Career Satisfaction.

In career development, a variety of personal, organizational and labor market variables challenge employees and organizations, in particular those in dynamic working environments, such as higher education (HE) institutions. This study examines the association between work history, organizational social capital (OSC) and perceived organizational prestige (POP) as antecedent variables, and perceived employability (PE) and career satisfaction (CS) as outcome variables, as well as the mediating role of organizational identification (OI) in these relations. A sample of 283 workers in Chilean HE institutions filled out an on-line questionnaire, and hypotheses were tested using a mediation model. Results indicated a significant mediation effect of OI, abt = 0.363, 95% CI [0.181, 0.576] abt/c = 31.98%, to explain the relationship between internal perceived employability (IPE) and its predictor variables POP, abpo = 0.102, 95% CI [0.056, 0.160], abpo/c = 9.01%, and OSC, abcsoc = 0.101, 95% CI [0.053, 0.183, abcsoc/c = 8.89%. Promoting a positive image of the organization and its social capital, strengthened by OI, emerge as strategies for HR management oriented toward workers' career development, with consequent implications for commitment, intention to leave and ultimately for organizational results. The study provides a deeper understanding of the complexity of careers and explains the importance of identification with the organization when the impact of organizational attributes on one's career is analyzed.

Getting by with a Little Help from Our Friends: The Role of Social Support in Addressing HIV-related Mental Health Disparities among Sexual Minorities in the Lower Rio Grande Valley.

This study examines how social support and perceived discrimination influence depressive symptoms of sexual minorities (including, lesbian, gay, bisexual-identifying individuals, and others with same-sex sexual partners) relative to heterosexual peers, while considering the role of HIV-positive status. We surveyed low-income, predominantly Hispanic/Latino/as residents receiving STI-testing and/or HIV/AIDS care in the lower Rio Grande Valley of southernmost Texas. Respondents aged 18+ took a self-administered survey in English or Spanish in a clinic waiting room (N= 273). Based on OLS regression, HIV-positive status (OLS coefficient = 2.54, p< .01) and social support (OLS coefficient = -0.17, p< .001) were significant predictors of depressive symptoms among sexual minorities, but not those who identified as heterosexual. Perceived discrimination was uniquely associated with increased depressive symptoms among sexual minorities (interaction coefficient = 0.21, p< .05). Clinicians treating sexual minority patients for depression should consider developing and applying resources tailored to individuals' level of social support and ongoing experiences of social discrimination.

A Community-Based Mindfulness Intervention Among Latino Adolescents and Their Parents: A Qualitative Feasibility and Acceptability Study.

Few studies have evaluated the effectiveness of mindfulness-based meditation interventions (MBMIs) among Latino youth. Furthermore, joint parent-child participation in such programs is rare. Utilizing a community-based participatory research approach, this study evaluated the feasibility of a pilot bilingual MBMI among Latino adolescents and their parents in Los Angeles. Qualitative interviews were conducted to assess the practicality, implementation, and acceptability of the program. Challenges to attendance included health issues or conflicts with work. Several adolescents struggled with distractions from peers. However, overall responses suggest that parents and children found the program convenient and enjoyable, and perceived benefits from the curriculum. This study supports the feasibility of a MBMI among Latino family dyads.

Elaboration of reference material for cadmium and arsenic in hydrobiological products, for the purpose of being used in a laboratory intercomparation program / Elaboración de un material de referencia para cadmio y arsénico en productos hidrobiológicos, para propósito de ser utilizado en un programa de intercomparación de laboratorios

Reference materials (RM) are tools used in the comparability and traceability of measurements. They are widely used by laboratories for method validation and quality control of assay. Chile must evaluate theperformance of laboratories that analyzing metals in fishery products, despite RM have high prices and are scarce. For that reason, a RM in a hydrobiological product was developed. Reference values for arsenic and cadmium elements for a fishmeal were assigned. The measurement methods for characterization of the material were Inductively Coupled Plasma Mass Spectrometry, Atomic Absorption Spectrometry and Neutron Activation Analysis. Reference values with their expanded uncertainty (U) were established for arsenic 2.64 ± 0.42 mg/kg (U; k = 2) and for cadmium 0.86 ± 0.16 mg/kg (U; k = 2). Homogeneity and stability of the RM allowed its use in a proficiency test for eleven food control laboratories. Results for median were 2.114 mg/kg for arsenic, and 0.863 mg/kg for cadmium. The performance values of the participants were evaluated with a z score obtaining 60% satisfaction for arsenic and 73% for cadmium.The material demonstrated to be suitable for use in interlaboratory proficiency assay. (AU)

Materiales de referencia (MR) son herramientas utilizadas en la comparabilidad y trazabilidad entre mediciones. Laboratorios los utilizan ampliamente en validación de métodos y control de calidad. Chile debe evaluar el desempeño de los laboratorios que analizan metales en productos pesqueros, a pesar de los altos precios y escasez del MR. Por esa razón, se desarrolló un MR en producto hidrobiológico. Se asignaron valores de referencia para arsénico y cadmio en harina de pescado. Los métodos de medición para la caracterización del material fueron Espectrometría de Masas de Plasma Acoplado Inductivamente, Espectrometría de Absorción Atómica y Análisis de Activación de Neutrones. Se establecieron valores de referencia con su incertidumbre (U) para arsénico 2.64 ± 0.42 mg/kg (U; k = 2) y para cadmio 0.86 ± 0.16 mg/kg (U; k = 2). La homogeneidad y estabilidad del MR permitieron su uso en una prueba de aptitud para once laboratorios de control de alimentos. Las medianas fueron 2,114 mg/kg para arsénico y 0,863 mg/kg para cadmio. Se evaluaron los rendimientos de los participantes con un estadístico de puntaje z satisfactorio del 60% para el arsénico y 73% para el cadmio. El material demostró ser adecuado para uso en ensayo de aptitud de intercomparación. (AU)

High prevalence of human papillomavirus type 66 in low-grade cervical lesions of Mexican women.

Our aim was to analyze the prevalence of high-risk human papillomavirus (HR-HPV) and its association with risk factors related to cervical lesions. We used 362 cervical samples from a transversal study to detect nineteen types from the high-risk HPV clade by highly sensitive PCR. Unexpectedly, we found a very high prevalence of HPV type 66 (32.8%), particularly in low-grade squamous intraepithelial lesions. A significant association of HPV66 with previously sexually transmitted disease was observed (p < 0.05). Our results strongly suggest that HPV66 might be indicative of cervical lesions that will not progress to cancer. HPV genotyping by methods that grouped type 66 with other HR-HPV clade types should be interpreted with caution.