Whole genome sequencing of nine Vibrio parahaemolyticus strains encoding (Pir) toxin-like genes from shrimp cultures in northern Peru using Oxford Nanopore technology.

Nine Peruvian isolates of Vibrio parahaemolyticus were characterized through sequencing, revealing the presence of simple sequence repeat, Pir toxin-like genes, and genes associated with antibiotic resistance, toxic components, and transposable elements. These findings expand our understanding of the genetic diversity, disease resistance, and virulence in cultivated shrimp populations in Peru.

Implantable SDF-1α-loaded silk fibroin hyaluronic acid aerogel sponges as an instructive component of the glioblastoma ecosystem: Between chemoattraction and tumor shaping into resection cavities.

In view of inevitable recurrences despite resection, glioblastoma (GB) is still an unmet clinical need. Dealing with the stromal-cell derived factor 1-alpha (SDF-1α)/CXCR4 axis as a hallmark of infiltrative GB tumors and with the resection cavity situation, the present study described the effects and relevance of a new engineered micro-nanostructured SF-HA-Hep aerogel sponges, made of silk fibroin (SF), hyaluronic acid (HA) and heparin (Hep) and loaded with SDF-1α, to interfere with the GB ecosystem and residual GB cells, attracting and confining them in a controlled area before elimination. 70 µm-pore sponges were designed as an implantable scaffold to trap GB cells. They presented shape memory and fit brain cavities. Histological results after implantation in brain immunocompetent Fischer rats revealed that SF-HA-Hep sponges are well tolerated for more than 3 months while moderately and reversibly colonized by immuno-inflammatory cells. The use of human U87MG GB cells overexpressing the CXCR4 receptor (U87MG-CXCR4+) and responding to SDF-1α allowed demonstrating directional GB cell attraction and colonization of the device in vitro and in vivo in orthotopic resection cavities in Nude rats. Not modifying global survival, aerogel sponge implantation strongly shaped U87MG-CXCR4+ tumors in cavities in contrast to random infiltrative growth in controls. Overall, those results support the interest of SF-HA-Hep sponges as modifiers of the GB ecosystem dynamics acting as "cell meeting rooms" and biocompatible niches whose properties deserve to be considered toward the development of new clinical procedures. STATEMENT OF SIGNIFICANCE: Brain tumor glioblastoma (GB) is one of the worst unmet clinical needs. To prevent the relapse in the resection cavity situation, new implantable biopolymer aerogel sponges loaded with a chemoattractant molecule were designed and preclinically tested as a prototype targeting the interaction between the initial tumor location and its attraction by the peritumoral environment. While not modifying global survival, biocompatible SDF1-loaded hyaluronic acid and silk fibroin sponges induce directional GB cell attraction and colonization in vitro and in rats in vivo. Interestingly, they strongly shaped GB tumors in contrast to random infiltrative growth in controls. These results provide original findings on application of exogenous engineered niches that shape tumors and serve as cell meeting rooms for further clinical developments.

Enduring association between irritable bowel syndrome and war trauma during the Nicaragua civil war period: A population-based study.

BACKGROUND: Psychosocial and physical trauma are known risk factors for irritable bowel syndrome (IBS), including in war veterans, whereas war exposure in civilians is unclear. Nicaragua experienced two wars, 1970-1990: The Sandinistas Revolution (1970s) and The Contra War (1980s). Our aim was to investigate the role of exposure to war trauma in the subsequent development of IBS in the context of an established health surveillance system (11000 households). AIM: To investigate in a civilian population the relationship between exposure to war trauma and events and the subsequent development of IBS in the context of an established public health and demographic surveillance system in western Nicaragua. METHODS: We conducted a nested population-based, cross-sectional study focused on functional gastrointestinal disorders based on Rome II criteria. 1617 adults were randomly selected. The Spanish Rome II Modular Questionnaire and Harvard Trauma Questionnaire were validated in Nicaragua. War exposure was assessed with 10 measures of direct and indirect war trauma and post-war effects. Multiple exposures were defined by ≥ 3 measures. RESULTS: The prevalence of IBS was 15.2% [Female (F) 17.1%, Male (M) 12.0%], war exposure 19.3% (F 9.3%, M 36.7%), and post-traumatic stress disorder (PTSD) 5.6% (F 6.4%, M 4.3%). Significant associations with IBS in the civilian population were observed (adjusted by gender, age, socioeconomic status, education): physical and psychological abuse [adjusted odds ratio (aOR): 2.25; 95% confidence interval: 1.1-4.5], witnessed execution (aOR: 2.4; 1.1-5.2), family member death (aOR: 2.2; 1.2-4.2), and multiple exposures (aOR: 2.7; 1.4-5.1). PTSD was independently associated with IBS (aOR: 2.6; 1.2-5.7). CONCLUSION: An enduring association was observed in the Nicaragua civilian population between specific civil war-related events and subsequent IBS. Civilian populations in regions with extended armed conflict may warrant provider education and targeted interventions for patients.

Insights into Healthcare Professionals' Perceptions and Attitudes toward Nanotechnological Device Application: What Is the Current Situation in Glioblastoma Research?

Nanotechnology application in cancer treatment is promising and is likely to quickly spread worldwide in the near future. To date, most scientific studies on nanomaterial development have focused on deepening the attitudes of end users and experts, leaving clinical practice implications unexplored. Neuro-oncology might be a promising field for the application of nanotechnologies, especially for malignant brain tumors with a low-survival rate such as glioblastoma (GBM). As to improving patients' quality of life and life expectancy, innovative treatments are worth being explored. Indeed, it is important to explore clinicians' intention to use experimental technologies in clinical practice. In the present study, we conducted an exploratory review of the literature about healthcare workers' knowledge and personal opinions toward nanomedicine. Our search (i) gives evidence for disagreement between self-reported and factual knowledge about nanomedicine and (ii) suggests the internet and television as main sources of information about current trends in nanomedicine applications, over scientific journals and formal education. Current models of risk assessment suggest time-saving cognitive and affective shortcuts, i.e., heuristics support both laypeople and experts in the decision-making process under uncertainty, whereas they might be a source of error. Whether the knowledge is poor, heuristics are more likely to occur and thus clinicians' opinions and perspectives toward new technologies might be biased.

Near-Complete Genome Sequence of White Spot Syndrome Virus Infecting Cultivated Shrimp (Penaeus vannamei) in Peru.

White spot syndrome virus (WSSV) infects a broad range of aquatic animals, including the shrimp Penaeus vannamei. In this study, we report one genome sequence of WSSV present in shrimp on the north coast of Peru.

Hyaluronic Acid Scaffolds for Loco-Regional Therapy in Nervous System Related Disorders.

Hyaluronic acid (HA) is a Glycosaminoglycan made of disaccharide units containing N-acetyl-D-glucosamine and glucuronic acid. Its molecular mass can reach 10 MDa and its physiological properties depend on its polymeric property, polyelectrolyte feature and viscous nature. HA is a ubiquitous compound found in almost all biological tissues and fluids. So far, HA grades are produced by biotechnology processes, while in the human organism it is a major component of the extracellular matrix (ECM) in brain tissue, synovial fluid, vitreous humor, cartilage and skin. Indeed, HA is capable of forming hydrogels, polymer crosslinked networks that are very hygroscopic. Based on these considerations, we propose an overview of HA-based scaffolds developed for brain cancer treatment, central and peripheral nervous systems, discuss their relevance and identify the most successful developed systems.

Trends and factors related to adolescent pregnancies: an incidence trend and conditional inference trees analysis of northern Nicaragua demographic surveillance data.

BACKGROUND: We aimed to identify the 2001-2013 incidence trend, and characteristics associated with adolescent pregnancies reported by 20-24-year-old women. METHODS: A retrospective analysis of the Cuatro Santos Northern Nicaragua Health and Demographic Surveillance 2004-2014 data on women aged 15-19 and 20-24. To calculate adolescent birth and pregnancy rates, we used the first live birth at ages 10-14 and 15-19 years reported by women aged 15-19 and 20-24 years, respectively, along with estimates of annual incidence rates reported by women aged 20-24 years. We conducted conditional inference tree analyses using 52 variables to identify characteristics associated with adolescent pregnancies. RESULTS: The number of first live births reported by women aged 20-24 years was 361 during the study period. Adolescent pregnancies and live births decreased from 2004 to 2009 and thereafter increased up to 2014. The adolescent pregnancy incidence (persons-years) trend dropped from 2001 (75.1 per 1000) to 2007 (27.2 per 1000), followed by a steep upward trend from 2007 to 2008 (19.1 per 1000) that increased in 2013 (26.5 per 1000). Associated factors with adolescent pregnancy were living in low-education households, where most adults in the household were working, and high proportion of adolescent pregnancies in the local community. Wealth was not linked to teenage pregnancies. CONCLUSIONS: Interventions to prevent adolescent pregnancy are imperative and must bear into account the context that influences the culture of early motherhood and lead to socioeconomic and health gains in resource-poor settings.

Detection of Antibodies to Lokern, Main Drain, St. Louis Encephalitis, and West Nile Viruses in Vertebrate Animals in Chihuahua, Guerrero, and Michoacán, Mexico.

We conducted serologic surveillance for flaviviruses and orthobunyaviruses in vertebrate animals in Mexico in 2018-2019. Sera were collected from 856 vertebrate animals, including 323 dogs, 223 horses, and 121 cows, from 16 species. The animals were from 3 states: Chihuahua in northwest Mexico (704 animals) and Guerrero and Michoacán on the Pacific Coast (27 and 125 animals, respectively). Sera were assayed by plaque reduction neutralization test using four flaviviruses (dengue type 2, St. Louis encephalitis, West Nile, and Zika viruses) and six orthobunyaviruses from the Bunyamwera (BUN) serogroup (Cache Valley, Lokern, Main Drain, Northway, Potosi, and Tensaw viruses). Antibodies to West Nile virus (WNV) were detected in 154 animals of 9 species, including 89 (39.9%) horses, 3 (21.4%) Indian peafowl, and 41 (12.7%) dogs. Antibodies to St. Louis encephalitis virus (SLEV) were detected in seven animals, including three (0.9%) dogs. Antibodies to Lokern virus (LOKV) were detected in 22 animals: 19 (8.5%) horses, 2 (1.7%) cows, and a dog (0.3%). Antibodies to Main Drain virus (MDV) were detected in three (1.3%) horses. WNV and LOKV activity was detected in all three states, SLEV activity was detected in Chihuahua and Michoacán, and MDV activity was detected in Chihuahua. None of the animals was seropositive for Cache Valley virus, the most common and widely distributed BUN serogroup virus in North America. In conclusion, we provide serologic evidence that select flaviviruses and BUN serogroup viruses infect vertebrate animals in Chihuahua, Guerrero, and Michoacán. We also provide the first evidence of LOKV and MDV activity in Mexico.

Nanoparticle-containing electrospun nanofibrous scaffolds for sustained release of SDF-1α.

Chemokines such as stromal cell-derived factor-1α (SDF-1α) regulate the migration of cancer cells that can spread from their primary tumor site by migrating up an SDF-1α concentration gradient, facilitating their local invasion and metastasis. Therefore, the implantation of SDF-1α-releasing scaffolds can be a useful strategy to trap cancer cells expressing the CXCR4 receptor. In this work, SDF-1α was encapsulated into poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles and subsequently electrospun with chitosan to produce nanofibrous scaffolds of average fiber diameter of 261 ± 45 nm, intended for trapping glioblastoma (GBM) cells. The encapsulated SDF-1α maintained its biological activity after the electrospinning process as assessed by its capacity to induce the migration of cancer cells. The scaffolds could also provide sustained release of SDF-1α for at least 5 weeks. Using NIH3T3 mouse fibroblasts, human Thp-1 macrophages, and rat primary astrocytes we showed that the scaffolds possessed high cytocompatibility in vitro. Furthermore, a 7-day follow-up of Fischer rats bearing implanted scaffolds demonstrated the absence of adverse effects in vivo. In addition, the nanofibrous structure of the scaffolds provided excellent anchoring sites to support the adhesion of human GBM cells by extension of their pseudopodia. The scaffolds also demonstrated slow degradation kinetics, which may be useful in maximizing the time window for trapping GBM cells. As surgical resection does not permit a complete removal of GBM tumors, our results support the future implantation of these scaffolds into the walls of the resection cavity to evaluate their capacity to attract and trap the residual GBM cells in the brain.

Near-Complete Genome Sequences of 12 Peruvian Strains of Infectious Hypodermal and Hematopoietic Necrosis Virus Infecting the Shrimp Penaeus vannamei.

Infectious hypodermal and hematopoietic necrosis virus (IHHNV) is a shrimp virus listed by the World Organisation for Animal Health (OIE). In this study, we report the genomic sequences of 12 IHHNV strains obtained from shrimp samples from aquaculture cultures from the Tumbes region of Peru.

Curdlan-Chitosan Electrospun Fibers as Potential Scaffolds for Bone Regeneration.

Polysaccharides have received a lot of attention in biomedical research for their high potential as scaffolds owing to their unique biological properties. Fibrillar scaffolds made of chitosan demonstrated high promise in tissue engineering, especially for skin. As far as bone regeneration is concerned, curdlan (1,3-ß-glucan) is particularly interesting as it enhances bone growth by helping mesenchymal stem cell adhesion, by favoring their differentiation into osteoblasts and by limiting the osteoclastic activity. Therefore, we aim to combine both chitosan and curdlan polysaccharides in a new scaffold for bone regeneration. For that purpose, curdlan was electrospun as a blend with chitosan into a fibrillar scaffold. We show that this novel scaffold is biodegradable (8% at two weeks), exhibits a good swelling behavior (350%) and is non-cytotoxic in vitro. In addition, the benefit of incorporating curdlan in the scaffold was demonstrated in a scratch assay that evidences the ability of curdlan to express its immunomodulatory properties by enhancing cell migration. Thus, these innovative electrospun curdlan-chitosan scaffolds show great potential for bone tissue engineering.

A Mathematical Model of Average Dynamics in a Stem Cell Hierarchy Suggests the Combinatorial Targeting of Cancer Stem Cells and Progenitor Cells as a Potential Strategy against Tumor Growth.

The cancer stem cell hypothesis states that tumors are maintained by a small subpopulation of stem-like cells, often called cancer stem cells (CSCs) or tumor initiating cells. CSCs can self-renew and give rise to more differentiated cells, which comprise the bulk of the tumor. In addition, CSCs are resistant to conventional therapy, which suggests that they are responsible for tumor relapse. This has led researchers to increase efforts to develop directed therapies against CSCs. However, some experiments in mice have shown that the elimination of CSCs might not ensure tumor eradication. This may be due to different events, such as residual CSCs after treatment, the plasticity of cells within the tumor, the presence of different CSCs having their own hierarchy within the same tumor, and the ability of more differentiated cells to maintain the disease, among others. Trying to decipher this complexity may benefit from dissecting the whole in its parts. Here, we hypothesize that tumor relapse after the selective targeting of CSCs may be due to intermediate progenitor (P) cells that can maintain the tumor volume. In order to support the hypothesis, we implemented a mathematical model derived using pseudo-reactions representing the events of each cell subpopulation within the tumor. We aimed to test if a minimal unidirectional hierarchical model consisting of CSCs, P, and terminally differentiated (D) cells could be adjusted to experimental data for selective CSC targeting. We further evaluated therapies ranging from nonselective to specifically directed and combination therapy. We found that selective killing of the CSC compartment has a delaying effect on the overall exponential tumor growth, but was not able to eliminate the disease. We show that therapy that targets both CSCs and intermediate progenitor (P) cells with a sufficient capacity to proliferate and differentiate could represent a more efficient treatment option for tumor depletion. Testing this hypothesis in vivo may allow us to discriminate within the array of possibilities of tumor relapse, and further open the idea of combination therapy against different subpopulations of tumor cells instead of segregating CSCs and bulk tumor cells.

Aerogel sponges of silk fibroin, hyaluronic acid and heparin for soft tissue engineering: Composition-properties relationship.

This work aims to design biocompatible aerogel sponges that can host and control the release of stromal cell-derived factor-1α (SDF-1α or CXCL12), a key protein for applications ranging from regenerative medicine to cancer therapy (notably for neural tissues). Miscibility of silk fibroin (SF) and hyaluronic acid (HA) was investigated by means of fluorescence and scanning electron microscopy to identify processing conditions. Series of freeze-dried sponges were prepared by associating and cross-linking within the same 3D structure, HA, SF, poly-l-lysine (PLL) and heparin (hep). Aerogel sponges presented high swelling degree and porosity (∼90 %), adequate mean pore diameter (ca. 60 µm) and connectivity for welcoming cells, and a soft texture close to that of the brain (6-13 kPa Young's Modulus). Addition of SF yielded sponges with slower biodegradation. SF-HA and SF-HA-hep sponges retained 75 % and 93 % of the SDF-1α respectively after 7 days and were found to be cytocompatible in vitro.

Assessing the Multiple Dimensions of Poverty. Data Mining Approaches to the 2004-14 Health and Demographic Surveillance System in Cuatro Santos, Nicaragua.

We identified clusters of multiple dimensions of poverty according to the capability approach theory by applying data mining approaches to the Cuatro Santos Health and Demographic Surveillance database, Nicaragua. Four municipalities in northern Nicaragua constitute the Cuatro Santos area, with 25,893 inhabitants in 5,966 households (2014). A local process analyzing poverty-related problems, prioritizing suggested actions, was initiated in 1997 and generated a community action plan 2002-2015. Interventions were school breakfasts, environmental protection, water and sanitation, preventive healthcare, home gardening, microcredit, technical training, university education stipends, and use of the Internet. In 2004, a survey of basic health and demographic information was performed in the whole population, followed by surveillance updates in 2007, 2009, and 2014 linking households and individuals. Information included the house material (floor, walls) and services (water, sanitation, electricity) as well as demographic data (birth, deaths, migration). Data on participation in interventions, food security, household assets, and women's self-rated health were collected in 2014. A K-means algorithm was used to cluster the household data (56 variables) in six clusters. The poverty ranking of household clusters using the unsatisfied basic needs index variables changed when including variables describing basic capabilities. The households in the fairly rich cluster with assets such as motorbikes and computers were described as modern. Those in the fairly poor cluster, having different degrees of food insecurity, were labeled vulnerable. Poor and poorest clusters of households were traditional, e.g., in using horses for transport. Results displayed a society transforming from traditional to modern, where the forerunners were not the richest but educated, had more working members in household, had fewer children, and were food secure. Those lagging were the poor, traditional, and food insecure. The approach may be useful for an improved understanding of poverty and to direct local policy and interventions.

Ultrasound molecular imaging as a non-invasive companion diagnostic for netrin-1 interference therapy in breast cancer.

In ultrasound molecular imaging (USMI), ligand-functionalized microbubbles (MBs) are used to visualize vascular endothelial targets. Netrin-1 is upregulated in 60% of metastatic breast cancers and promotes tumor progression. A novel netrin-1 interference therapy requires the assessment of netrin-1 expression prior to treatment. In this study, we studied netrin-1 as a target for USMI and its potential as a companion diagnostic in breast cancer models. Methods: To verify netrin-1 expression and localization, an in vivo immuno-localization approach was applied, in which anti-netrin-1 antibody was injected into living mice 24 h before tumor collection, and revealed with secondary fluorescent antibody for immunofluorescence analysis. Netrin-1 interactions with the cell surface were studied by flow cytometry. Netrin-1-targeted MBs were prepared using MicroMarker Target-Ready (VisualSonics), and validated in in vitro binding assays in static conditions or in a flow chamber using purified netrin-1 protein or netrin-1-expressing cancer cells. In vivo USMI of netrin-1 was validated in nude mice bearing human netrin-1-positive SKBR7 tumors or weakly netrin-1-expressing MDA-MB-231 tumors using the Vevo 2100 small animal imaging device (VisualSonics). USMI feasibility was further tested in transgenic murine FVB/N Tg(MMTV/PyMT634Mul) (MMTV-PyMT) mammary tumors. Results: Netrin-1 co-localized with endothelial CD31 in netrin-1-positive breast tumors. Netrin-1 binding to the surface of endothelial HUVEC and cancer cells was partially mediated by heparan sulfate proteoglycans. MBs targeted with humanized monoclonal anti-netrin-1 antibody bound to netrin-1-expressing cancer cells in static and dynamic conditions. USMI signal was significantly increased with anti-netrin-1 MBs in human SKBR7 breast tumors and transgenic murine MMTV-PyMT mammary tumors compared to signals recorded with either isotype control MBs or after blocking of netrin-1 with humanized monoclonal anti-netrin-1 antibody. In weakly netrin-1-expressing human tumors and normal mammary glands, no difference in imaging signal was observed with anti-netrin-1- and isotype control MBs. Ex vivo analysis confirmed netrin-1 expression in MMTV-PyMT tumors. Conclusions: These results show that USMI allowed reliable detection of netrin-1 on the endothelium of netrin-1-positive human and murine tumors. Significant differences in USMI signal for netrin-1 reflected the significant differences in netrin-1 mRNA & protein expression observed between different breast tumor models. The imaging approach was non-invasive and safe, and provided the netrin-1 expression status in near real-time. Thus, USMI of netrin-1 has the potential to become a companion diagnostic for the stratification of patients for netrin-1 interference therapy in future clinical trials.

Food insecurity and self-rated health in rural Nicaraguan women of reproductive age: a cross-sectional study.

BACKGROUND: Access to food is a basic necessity, and food insecurity may impair the individual's well-being and health. Self-rated health measurements have frequently been used to assess population health. Little is known, however, as to whether food security is associated with self-rated health in low- and middle-income settings. This study aims at analyzing the association between food security and self-rated health among non-pregnant women of reproductive age in a rural Nicaraguan setting. METHODS: Data was taken from the 2014 update of a health and demographic surveillance system in the municipalities of Los Cuatro Santos in northwestern Nicaragua. Fieldworkers interviewed women about their self-rated health using a 5-point Likert scale. Food insecurity was assessed by the household food insecurity access (HFIAS) scale. A multilevel Poisson random-intercept model was used to calculate the prevalence ratio. RESULTS: The survey included 5866 women. In total, 89% were food insecure, and 48% had poor self-rated health. Food insecurity was associated with poor self-rated health, and remained so after adjustment for potential confounders and accounting for community dependency. CONCLUSION: In this Nicaraguan resource-limited setting, there was an association between food insecurity and poor self-rated health. Food insecurity is a facet of poverty and measures an important missing capability directly related to health.

Child survival revolutions revisited - lessons learned from Bangladesh, Nicaragua, Rwanda and Vietnam.

Analysing child mortality may enhance our perspective on global achievements in child survival. We used data from surveillance sites in Bangladesh, Nicaragua and Vietnam and Demographic Health Surveys in Rwanda to explore the development of neonatal and under-five mortality. The mortality curves showed dramatic reductions over time, but child mortality in the four countries peaked during wars and catastrophes and was rapidly reduced by targeted interventions, multisectorial development efforts and community engagement. CONCLUSION: Lessons learned from these countries may be useful when tackling future challenges, including persistent neonatal deaths, survival inequalities and the consequences of climate change and migration.

Breaking the cycles of poverty: Strategies, achievements, and lessons learned in Los Cuatro Santos, Nicaragua, 1990-2014.

BACKGROUND: In a post-war frontier area in north-western Nicaragua that was severely hit by Hurricane Mitch in 1998, local stakeholders embarked on and facilitated multi-dimensional development initiatives to break the cycles of poverty. OBJECTIVE: The aim of this paper is to describe the process of priority-setting, and the strategies, guiding principles, activities, achievements, and lessons learned in these local development efforts from 1990 to 2014 in the Cuatro Santos area, Nicaragua. METHODS: Data were derived from project records and a Health and Demographic Surveillance System that was initiated in 2004. The area had 25,893 inhabitants living in 5,966 households in 2014. RESULTS: A participatory process with local stakeholders and community representatives resulted in a long-term strategic plan. Guiding principles were local ownership, political reconciliation, consensus decision-making, social and gender equity, an environmental and public health perspective, and sustainability. Local data were used in workshops with communities to re-prioritise and formulate new goals. The interventions included water and sanitation, house construction, microcredits, environmental protection, school breakfasts, technical training, university scholarships, home gardening, breastfeeding promotion, and maternity waiting homes. During the last decade, the proportion of individuals living in poverty was reduced from 79 to 47%. Primary school enrolment increased from 70 to 98% after the start of the school breakfast program. Under-five mortality was around 50 per 1,000 live births in 1990 and again peaked after Hurricane Mitch and was approaching 20 per 1,000 in 2014. Several of the interventions have been scaled up as national programs. CONCLUSIONS: The lessons learned from the Cuatro Santos initiative underline the importance of a bottom-up approach and local ownership of the development process, the value of local data for monitoring and evaluation, and the need for multi-dimensional local interventions to break the cycles of poverty and gain better health and welfare.