Association of the rs1126616 and rs9138 Variants in the SPP1 Gene among Mexican Patients with Systemic Lupus Erythematosus and Lupus Nephritis.

Systemic lupus erythematosus (SLE) is a multisystem disease considered a prototype of the main autoimmune disease and presents serious complications, such as lupus nephritis (LN), which generates a significant impact on morbidity and mortality. The SPP1 gene encodes the osteopontin (OPN) protein, which plays a crucial role in the regulation of inflammation and immunity. The variants rs1126616 and rs9138 of this gene have been associated with the inflammatory response. The study aims to analyze the association of the rs1126616 and rs9138 variants of the SPP1 gene in SLE Mexican-Mestizo patients without LN (SLE-LN). In this cross-sectional study, a total of 171 genomic DNA samples from SLE patients were clinically confirmed, of which 111 were SLE without LN, 60 were SLE with LN, and 100 healthy individuals were included as reference group. The rs1126616 variant was genotyped using PCR-RFLPs, and the rs9138 variant was genotyped using qPCR TaqMan. The TT genotype, the recessive model [OR 2.76 (95% CI 1.31-5.82), p = 0.011], and the T allele [OR 2.0 (95% CI 1.26-3.16), p = 0.003] of the rs1126616 variant are risk factors for SLE with LN. By contrast, the rs9138 variant did not show statistically significant differences among SLE patients stratified by LN. In our study of SLE Mexican-Mestizo patients with and without NL, demographic and clinical characteristics do not differ from other SLE populations, and the TT genotype of the rs1126616 variant of the SPP1 gene confers a risk factor for the presentation of LN. Otherwise, the rs9138 variant did not show association with NL.

3,3'-Diindolylmethane and indole-3-carbinol: potential therapeutic molecules for cancer chemoprevention and treatment via regulating cellular signaling pathways.

Dietary compounds in cancer prevention have gained significant consideration as a viable method. Indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) are heterocyclic and bioactive chemicals found in cruciferous vegetables like broccoli, cauliflower, cabbage, and brussels sprouts. They are synthesized after glycolysis from the glucosinolate structure. Clinical and preclinical trials have evaluated the pharmacokinetic/pharmacodynamic, effectiveness, antioxidant, cancer-preventing (cervical dysplasia, prostate cancer, breast cancer), and anti-tumor activities of I3C and DIM involved with polyphenolic derivatives created in the digestion showing promising results. However, the exact mechanism by which they exert anti-cancer and apoptosis-inducing properties has yet to be entirely understood. Via this study, we update the existing knowledge of the state of anti-cancer investigation concerning I3C and DIM chemicals. We have also summarized; (i) the recent advancements in the use of I3C/DIM as therapeutic molecules since they represent potentially appealing anti-cancer agents, (ii) the available literature on the I3C and DIM characterization, and the challenges related to pharmacologic properties such as low solubility, and poor bioavailability, (iii) the synthesis and semi-synthetic derivatives, (iv) the mechanism of anti-tumor action in vitro/in vivo, (v) the action in cellular signaling pathways related to the regulation of apoptosis and anoikis as well as the cell cycle progression and cell proliferation such as peroxisome proliferator-activated receptor and PPARγ agonists; SR13668, Akt inhibitor, cyclins regulation, ER-dependent-independent pathways, and their current medical applications, to recognize research opportunities to potentially use these compounds instead chemotherapeutic synthetic drugs.

Current Status of the Therapeutic Approach for Dysmenorrhea.

Dysmenorrhea is the combination of cramps and pain associated with the menstrual period, and the symptoms affect at least 30% of women worldwide. Tolerance to symptoms depends on each person's pain threshold; however, dysmenorrhea seriously affects daily activities and chronically reduces the quality of life. Some dysmenorrhea cases even require hospitalization due to unbearable symptoms of severe pain. Dysmenorrhea is an underestimated affectation and remains even in different first-world countries as a taboo subject, promoted by the establishment of an apparent policy of gender equality. A person with primary or secondary dysmenorrhea requires medical assistance in choosing the best treatment and an integral approach. This review intends to demonstrate the impact of dysmenorrhea on quality of life. We describe the pathophysiology of this disorder from a molecular point of view and perform a comprehensive compilation and analysis of the most critical findings in the therapeutic management of dysmenorrhea. Likewise, we propose an interdisciplinary approach to the phenomenon of dysmenorrhea at the cellular level in a concise way and the botanical, pharmacological, and medical applications for its management. Since dysmenorrhea symptoms can vary between individuals, medical treatment cannot be generalized and depends on each patient. Therefore, we hypothesized that a suitable strategy could result from the combination of pharmacological therapy aided by a non-pharmacological approach.

Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain.

BACKGROUND AND OBJECTIVES: Chronic widespread musculoskeletal pain (CWP) is a symptom of fibromyalgia and a complex trait with poorly understood pathogenesis. CWP is heritable (48%-54%), but its genetic architecture is unknown and candidate gene studies have produced inconsistent results. We conducted a genome-wide association study to get insight into the genetic background of CWP. METHODS: Northern Europeans from UK Biobank comprising 6914 cases reporting pain all over the body lasting >3 months and 242 929 controls were studied. Replication of three independent genome-wide significant single nucleotide polymorphisms was attempted in six independent European cohorts (n=43 080; cases=14 177). Genetic correlations with risk factors, tissue specificity and colocalisation were examined. RESULTS: Three genome-wide significant loci were identified (rs1491985, rs10490825, rs165599) residing within the genes Ring Finger Protein 123 (RNF123), ATPase secretory pathway Ca2+transporting 1 (ATP2C1) and catechol-O-methyltransferase (COMT). The RNF123 locus was replicated (meta-analysis p=0.0002), the ATP2C1 locus showed suggestive association (p=0.0227) and the COMT locus was not replicated. Partial genetic correlation between CWP and depressive symptoms, body mass index, age of first birth and years of schooling were identified. Tissue specificity and colocalisation analysis highlight the relevance of skeletal muscle in CWP. CONCLUSIONS: We report a novel association of RNF123 locus and a suggestive association of ATP2C1 locus with CWP. Both loci are consistent with a role of calcium regulation in CWP. The association with COMT, one of the most studied genes in chronic pain field, was not confirmed in the replication analysis.

Development of films from natural sources for infections during wound healing.

The skin is the largest organ in the human body, and due to its barrier function, it is susceptible to multiple injuries. The appearance of infections during the wound healing process is a complication that represents a formidable hospital challenge. The presence of opportunistic bacteria with sophisticated resistance mechanisms is difficult to eradicate and compromises patients' lives. Therefore, the search for new efficacious treatments from natural sources that prevent and counteract infections, in addition to promoting the healing process, has increased in recent years. In this respect, films with the capability to protect wounds and release drugs are the presentation that predominates commercially in the hospital environment. Those films can offer several mechanical advantages such as physical protection to prevent opportunistic bacteria's entry, regulation of gas exchange, and capture of exudate through a swelling process. Wound dressings are generally curative materials easily adaptable to different anatomical regions, with high strength and elasticity, and some are even bioabsorbable. Additionally, the components of the films can actively participate in promoting the healing process. Even more, the film can be made up of carriers with other active participants to prevent and eradicate infections. Therefore, the extensive versatility, practicality, and usefulness of films from natural sources to address infectious processes during wound healing are relevant and recurrent themes. This work presents an analysis of the state-of-the-art of films with natural products focused on preventing and eradicating infections in wound healing.

Insights into Terminal Sterilization Processes of Nanoparticles for Biomedical Applications.

Nanoparticles possess a huge potential to be employed in numerous biomedical purposes; their applications may include drug delivery systems, gene therapy, and tissue engineering. However, the in vivo use in biomedical applications requires that nanoparticles exhibit sterility. Thus, diverse sterilization techniques have been developed to remove or destroy microbial contamination. The main sterilization methods include sterile filtration, autoclaving, ionizing radiation, and nonionizing radiation. Nonetheless, the sterilization processes can alter the stability, zeta potential, average particle size, and polydispersity index of diverse types of nanoparticles, depending on their composition. Thus, these methods may produce unwanted effects on the nanoparticles' characteristics, affecting their safety and efficacy. Moreover, each sterilization method possesses advantages and drawbacks; thus, the suitable method's choice depends on diverse factors such as the formulation's characteristics, batch volume, available methods, and desired application. In this article, we describe the current sterilization methods of nanoparticles. Moreover, we discuss the advantages and drawbacks of these methods, pointing out the changes in nanoparticles' biological and physicochemical characteristics after sterilization. Our main objective was to offer a comprehensive overview of terminal sterilization processes of nanoparticles for biomedical applications.

Implications of Social and Legal Status on Immigrants' Health in Disaster Zones.

This commentary highlights how immigrants who are linguistically isolated, have limited social networks, and lack legal immigration status experience unique health risks in disaster zones. Research on immigrants and disasters tends to focus on immigrants with these characteristics who are residents of disaster-affected areas, disaster recovery workers, or both. We review the sparse research literature and provide examples of innovative but underresourced programs that reduce immigrants' exposure to disaster-related health hazards and economic exploitation in the recovery. We conclude with recommendations for advancing these initiatives while, simultaneously, addressing the anti-immigrant policies that contribute to these disaster-related inequities.

Communication flows and the durability of a transnational social field.

We draw on unique data on communication flows between migrants and non-migrants in a bi-national, cross-border social network to test competing theories of the process of social incorporation. While advocates of the assimilation perspective argue that social incorporation is largely a one-way street, a recent literature on immigrant transnationalism challenges this view by arguing that changes in communication technologies and reductions in travel costs have made it possible for migrants to retain meaningful connections to their origin communities. In the context of this debate, we argue that communication flows-as measured by a combination of the number of social ties and the frequency of communication with them-provide an empirical test of the potential durability of cross-border networks. In our analysis, we find mixed support for both transnationalism and assimilation: while the classic assimilation perspective is correct that the strength of migrants' ties to origin attenuates as time in the destination increases, we also find evidence of a striking persistence in cross-border communication that is reinvigorated by migrant return visits, consistent with an attenuated view of transnationalism.

Gender, migration and perceptions of HIV risk in Mexico.

This study examines the role that duty plays in men's and women's perceptions of HIV-related risk in Mexico, and how gender and migration influence these perceptions. We draw on qualitative data from the 2014 Study of Health and Migration in Mexico (SHMM), which included 24 in-depth interviews with migrant men and non-migrant women living in a medium-sized city in Guanajuato, Mexico. While men report migrating out of responsibility to provide for their families, this sense of duty also had implications for their sexual health behaviours. Duty permeates how residents in this migrant-sending community described their perceptions of HIV risk, with men and women drawing consistently on three aspects of duty: fidelity, gendered sexual expectations, and the burden of HIV prevention. We argue that a strong sense of duty can prompt gender role expansion for migrant men and limit gender role expansion for non-migrant women.

High altitude agriculture in the Titicaca basin (800 BCE-200 CE): Impacts on nutrition and disease load.

OBJECTIVES: This study investigates the biological impacts of sedentism and agriculture on humans living in the high altitude landscape of the Titicaca Basin between 800 BCE and CE 200. The transition to agriculture in other global areas resulted in increases in disease and malnutrition; the high altitude of the Titicaca Basin could have exacerbated this. Our objective is to test whether the high altitude of the Titicaca Basin created a marginal environment for early agriculturalists living there, reflected through elevated rates of malnutrition and/or disease. METHODS: To test this, we analyzed human remains excavated from seven archaeological sites on the Copacabana Peninsula for markers of diet and disease. These markers included dental caries, dental abscesses, cribra orbitalia, porotic hyperostosis, periosteal reactions, osteomyelitis, and linear enamel hypoplasia. RESULTS: Results showed that markers of diet did not support malnutrition or micronutrient deficiencies but instead, indicated a relatively diverse diet for all individuals. Markers of disease also did not vary significantly but were common, indicating circulation of pathogens or chronic bodily stress. CONCLUSIONS: We interpret these results as an indication that while diets remained nutritious, investment in the landscape exposed populations to issues of sanitation and disease. The high-altitude of the Titicaca Basin did not exacerbate the biological impacts of agriculture in terms of increased malnutrition. Additionally, disease load was likely related to problems faced by many sedentary groups as opposed to unique challenges posed by high altitude. In sum, despite the high elevation, the Titicaca Basin is not truly a marginal environment for humans.

Gambling with life: Masculinity, risk, and danger in the lives of unauthorized migrant roofers.

BACKGROUND: This paper examines the occupational experiences of unauthorized immigrants employed in one of the most dangerous occupations in the United States: roofing. METHODS: We draw on 40 in-depth interviews with return migrants in Guanajuato, Mexico, to examine how the adoption of masculinity, dangerous working conditions, the labor market structure, and absence of legal status exacerbates injuries for unauthorized roofers. FINDINGS: Undocumented men return to Mexico injured with chronic pain, health complications, and trauma. We find that men "do gender" that is adopt masculine beliefs, when they skirt safety practices, police each other's behaviors, withhold their emotions, experience heightened stress, and engage in poor health behaviors. It is a combination of dangerous working conditions, economic insecurity, and men seeking to fulfill their masculine roles that all combine to create unsafe working conditions and lead to injuries.

Adaptive filtering for hidden node detection and tracking in networks.

The identification of network connectivity from noisy time series is of great interest in the study of network dynamics. This connectivity estimation problem becomes more complicated when we consider the possibility of hidden nodes within the network. These hidden nodes act as unknown drivers on our network and their presence can lead to the identification of false connections, resulting in incorrect network inference. Detecting the parts of the network they are acting on is thus critical. Here, we propose a novel method for hidden node detection based on an adaptive filtering framework with specific application to neuronal networks. We consider the hidden node as a problem of missing variables when model fitting and show that the estimated system noise covariance provided by the adaptive filter can be used to localize the influence of the hidden nodes and distinguish the effects of different hidden nodes. Additionally, we show that the sequential nature of our algorithm allows for tracking changes in the hidden node influence over time.

Alkylglycerol Derivatives, a New Class of Skin Penetration Modulators.

The absorption modulating activity of two alkylglycerol derivatives (batyl and chimyl alcohol) on skin barrier properties was evaluated. Biophysical tests such as transepidermal water loss (TEWL) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, as well as in vitro skin permeation studies, were performed in order to determine the effect of these compounds as chemical absorption modulators. Four drugs were used as models: three NSAIDS (diclofenac, naproxen, and piroxicam) and glycyrrhizic acid. The results showed that treatment of the skin with alkylglycerols caused (i) a reduction on the amount of drug permeated; (ii) a reduction in TEWL; and (iii) changes in the ATR-FTIR peaks of stratum corneum lipids, indicative of a more ordered structure. All of these findings confirm that alkyl glycerols have an absorption retarding effect on the drugs tested. Such effects are expected to give rise to important applications in the pharmaceutical and cosmetic sectors, in cases where it is desirable for the drug to remain in the superficial layers of the skin to achieve a local effect.

Bi-national Social Networks and Assimilation: A Test of the Importance of Transnationalism.

While the concept of transnationalism has gained widespread popularity among scholars as a way to describe immigrants' long-term maintenance of cross-border ties to their origin communities, critics have argued that the overall proportion of immigrants who engage in transnational behavior is low and that, as a result, transnationalism has little sustained effect on the process of immigrant adaptation and assimilation. In this paper, we argue that a key shortcoming in the current empirical debate on transnationalism is the lack of data on the social networks that connect migrants to each other and to non-migrants in communities of origin. To address this shortcoming, our analysis uses unique bi-national data on the social network connecting an immigrant sending community in Guanajuato, Mexico, to two destination areas in the United States. We test for the effect of respondents' positions in cross-border networks on their migration intentions and attitudes towards the United States using data on the opinions of their peers, their participation in cross border and local communication networks, and their structural position in the network. The results indicate qualified empirical support for a network-based model of transnationalism; in the U.S. sample we find evidence of network clustering consistent with peer effects, while in the Mexican sample we find evidence of the importance of cross-border communication with friends.

How Housing, Employment, and Legal Precarity Affect the Sleep of Migrant Workers: A Mixed-Methods Study.

In the United States, natural disasters have increased in frequency and intensity, causing significant damage to communities, infrastructure, and human life. Migrant workers form part of a growing occupational group that rebuilds in the aftermath of natural disasters like hurricanes and tornadoes. The work these migrant workers perform is essential but also unstable, exploitative, and dangerous, which stresses their health and well-being. This study focuses on the health and well-being of migrant roofers, a precarious occupational group who restores communities and helps the U.S. population adjust to a climate-changed world. Using surveys (N = 359) and in-depth interviews (n = 58) from a convenience sample of migrant roofers, we examine how precarity in terms of employment, housing, and legal status affect the sleep outcomes of these workers, who derive their income from an industry where instability is the norm, live in substandard and irregular housing, and lack workplace protections given their legal status.

Novel ultra-stretchable and self-healing crosslinked poly (ethylene oxide)-cationic guar gum hydrogel.

Hydrogels are three-dimensional structures with specific features that render them useful for biomedical applications, such as tissue engineering scaffolds, drug delivery systems, and wound dressings. In recent years, there has been a significant increase in the search for improved mechanical properties of hydrogels derived from natural products to extend their applications in various fields, and there are different methods to obtain strengthened hydrogels. Cationic guar gum has physicochemical properties that allow it to interact with other polymers and generate hydrogels. This study aimed to develop an ultra-stretchable and self-healing hydrogel, evaluating the influence of adding PolyOX [poly(ethylene oxide)] on the mechanical properties and the interaction with cationic guar gum for potential tissue engineering applications. We found that variations in PolyOX concentrations and pH changes influenced the mechanical properties of cationic guar gum hydrogels. After optimization experiments, we obtained a novel hydrogel, which was semi-crystalline, highly stretchable, and with an extensibility area of approximately 400 cm2, representing a 33-fold increase compared to the hydrogel before being extended. Moreover, the hydrogel presented a recovery of 96.8% after the self-healing process and a viscosity of 153,347 ± 4,662 cP. Therefore, this novel hydrogel exhibited optimal mechanical and chemical properties and could be suitable for a broad range of applications in different fields, such as tissue engineering, drug delivery, or food storage.

Films for Wound Healing Fabricated Using a Solvent Casting Technique.

Wound healing is a complex process that involves restoring the structure of damaged tissues through four phases: hemostasis, inflammation, proliferation, and remodeling. Wound dressings are the most common treatment used to cover wounds, reduce infection risk and the loss of physiological fluids, and enhance wound healing. Despite there being several types of wound dressings based on different materials and fabricated through various techniques, polymeric films have been widely employed due to their biocompatibility and low immunogenicity. Furthermore, they are non-invasive, easy to apply, allow gas exchange, and can be transparent. Among different methods for designing polymeric films, solvent casting represents a reliable, preferable, and highly used technique due to its easygoing and relatively low-cost procedure compared to sophisticated methods such as spin coating, microfluidic spinning, or 3D printing. Therefore, this review focuses on the polymeric dressings obtained using this technique, emphasizing the critical manufacturing factors related to pharmaceuticals, specifically discussing the formulation variables necessary to create wound dressings that demonstrate effective performance.

Enhancing chemical and physical stability of pharmaceuticals using freeze-thaw method: challenges and opportunities for process optimization through quality by design approach.

The freeze-thaw (F/T) method is commonly employed during the processing and handling of drug substances to enhance their chemical and physical stability and obtain pharmaceutical applications such as hydrogels, emulsions, and nanosystems (e.g., supramolecular complexes of cyclodextrins and liposomes). Using F/T in manufacturing hydrogels successfully prevents the need for toxic cross-linking agents; moreover, their use promotes a concentrated product and better stability in emulsions. However, the use of F/T in these applications is limited by their characteristics (e.g., porosity, flexibility, swelling capacity, drug loading, and drug release capacity), which depend on the optimization of process conditions and the kind and ratio of polymers, temperature, time, and the number of cycles that involve high physical stress that could change properties associated to quality attributes. Therefore, is necessary the optimization of F/T conditions and variables. The current research regarding F/T is focused on enhancing the formulations, the process, and the use of this method in pharmaceutical, clinical, and biological areas. The present review aims to discuss different studies related to the impact and effects of the F/T process on the physical, mechanical, and chemical properties (porosity, swelling capacity) of diverse pharmaceutical applications with an emphasis on their formulation properties, the method and variables used, as well as challenges and opportunities in developing. Finally, we review the experimental approach for choosing the standard variables studied in the F/T method applying the systematic methodology of quality by design.

Neopeltolide and its synthetic derivatives: a promising new class of anticancer agents.

Being the first or second cause of death worldwide, cancer represents the most significant clinical, social, and financial burden of any human illness. Despite recent progresses in cancer diagnosis and management, traditional cancer chemotherapies have shown several adverse side effects and loss of potency due to increased resistance. As a result, one of the current approaches is on with the search of bioactive anticancer compounds from natural sources. Neopeltolide is a marine-derived macrolide isolated from deep-water sponges collected off Jamaica's north coast. Its mechanism of action is still under research but represents a potentially promising novel drug for cancer therapy. In this review, we first illustrate the general structural characterization of neopeltolide, the semi-synthetic derivatives, and current medical applications. In addition, we reviewed its anticancer properties, primarily based on in vitro studies, and the possible clinical trials. Finally, we summarize the recent progress in the mechanism of antitumor action of neopeltolide. According to the information presented, we identified two principal challenges in the research, i) the effective dose which acts neopeltolide as an anticancer compound, and ii) to unequivocally establish the mechanism of action by which the compound exerts its antiproliferative effect.

Atraumatic Acromioclavicular Joint Dislocation: A Case Report Treated with Excision of the Distal Clavicle Margin and Button Slide System with Allograft Tendon Reinforcement at Coracoclavicular and Acromioclavicular Joint.

Although acromioclavicular joint (ACJ) dislocation is a common injury following trauma involving the shoulder, it is rare in the absence of trauma. In this manuscript, we describe a case of ACJ in a 15-year-old girl who presented a painful dislocation with spontaneous shortening of the right acromioclavicular joint that forced her to temporarily abandon her sports career. After failure of conservative physiotherapy treatment, surgical intervention was proposed by performing an arthroscopic-assisted button slide combined with augmented hamstring allograft reconstruction. After the intervention and the subsequent recovery period, the athlete was able to return to her semi-professional training. The follow-up of the patient is 5.5 years post-surgery. The result obtained could help in planning the treatment of future cases.