Beliefs about raw milk production and consumption and their relationship with health in Miraflores, Boyacá, Colombia.

The consumption of raw milk in Colombia continues despite the regulations issued to standardize or prohibit it. In the municipality where this study was carried out, more than 90% of the population chooses to consume this product, being at potential risk of acquiring diseases. The objective of this study was to understand the beliefs surrounding the production and consumption of raw milk and its relationship with health. It was carried out in 2020. Ethnography was used as a method of data collection and analysis. It was found that this phenomenon is related to the economy, identity, and ecology and is a central axis and articulator of various socio-cultural activities. It is guided by traditional production practices that do not fully respect biosafety and hygiene. Furthermore, the consumption of raw milk is socially approved and is the result of a social construction that arose independently of the physicochemical and microbiological properties of raw milk. Furthermore, local and national government regulators are not interested in this productive sector or in the consequences that their practices may have on the health of consumers. Thus, the responsibility for the consumption of raw milk and the possible acquisition of diseases passes from the food industry to the consumer. It is up to each consumer to make raw milk a safe food.

Atypical Choroid Plexus Tumor of the Cauda Equina With Metastases to the Spinal Cord and Brain.

We report a case of a 57-year-old man with a tumor arising from the cauda equina with spinal cord and intracranial metastases in the basal cisterns and along the cranial nerves. He presented with severe lower back pain and mild gait imbalance. His imaging revealed a large mass in the lumbosacral region with involvement of the cauda equina, intradural extramedullary enhancing metastases in the thoracic spinal canal, and intracranial metastases in the suprasellar cistern and along both trigeminal and facial/vestibulocochlear nerve complexes. Pathological examination of the resected thoracic spinal cord mass showed an atypical papillary proliferation with moderate nuclear pleomorphism and rare mitotic figures. While the morphologic and immunophenotypic features were consistent with the diagnosis of a choroid plexus tumor, the atypical location for this entity required the exclusion of other epithelioid tumors with papillary architecture. Additional immunohistochemical markers were used to exclude a metastatic adenocarcinoma, a papillary variant of a meningioma, and a papillary variant of an ependymoma. Ultimately, methylation-based tumor profiling determined that the methylation class was a match for "plexus tumor" resulting in the integrated diagnosis of the tumor with features of choroid plexus papilloma. This is a unique presentation for both the location and the metastatic spread. The methylation profile was instrumental in establishing this diagnosis.

Defining the quality of interdisciplinary care for patients with brain metastases: modified Delphi panel recommendations.

The value of interdisciplinary teams in improving outcomes and quality of care of patients with brain metastases remains uncertain, partly due to the lack of consensus on key indicators to evaluate interprofessional care. We aimed to obtain expert consensus across disciplines on indicators that evaluate the quality and value of brain metastases care. A steering committee of key opinion leaders curated relevant outcomes and process indicators from a literature review and a stakeholder needs assessment, and an international panel of physicians rated the outcomes and process indicators using a modified Delphi method. After three rounds, a consensus was reached on 29 indicators encompassing brain-directed oncological treatment, surgery, whole-brain radiotherapy, stereotactic radiosurgery, supportive or palliative care, and interdisciplinary team care. The Brain Metastases Quality-of-Care measure reflects the value and quality of brain metastases team-based care according to treatment modality and provides a benchmark of care for this under-studied patient population. The adoption, implementation, and sustainability of this set of indicators could help address the need expressed by patients with cancer, caregivers, and clinicians for more coordinated care across inpatient, outpatient, home, community, and tertiary academic settings.

Genomic Analysis of Aedes aegypti in the Northern Chihuahuan Desert of Texas and Mexico.

Background: Aedes aegypti, is the primary vector of dengue, Chikungunya, Zika, and yellow fever viruses. Both natural and human-impacted landscapes have selective pressures on Ae. aegypti, resulting in strong genomic structure even within close geographical distances. Materials and Methods: We assess the genetic structure of this medically important mosquito species at the northern leading edge of their distribution in Southwestern USA. Ae. aegypti were collected during 2017 in the urban communities of El Paso and Sparks, Texas (USA) and in the city of Ciudad Juárez, Mexico. Results: Thousands of nuclear loci were sequenced across 260 captured Ae. aegypti. First, we recovered the genetic structure of Ae. aegypti following geography, with all four major collection communities being genetically distinct. Importantly, we found population structure and genetic diversity that suggest rapid expansion through active-short distance dispersals, with Anapra being the likely source for the others. Next, tests of selection recovered eight functional genes across six outliers: calmodulin with olfactory receptor function; the protein superfamily C-type lectin with function in mosquito immune system and development; and TATA box binding protein with function in gene regulation. Conclusion: Despite these populations being documented in the early 2000s, we find that selective pressures on specific genes have already occurred and likely facilitate Ae. aegypti range expansion.

Tiered Pricing and Alternative Mechanisms for Equitative Access to Vaccines in Latin America: A Narrative Review of the Literature.

OBJECTIVES: To review and describe alternative strategies for the supply of vaccines in Latin America. METHODS: We conducted a narrative review to explore and describe alternatives for equitable vaccine access in Latin America. We searched and considered the main access strategies reported in the literature through PubMed, Science Direct, and Google Scholar. Additionally, we reviewed the web sites of key stakeholders. The search was conducted using the following keywords: ("access" or "availability" or "acquisition" or "affordability" or "tiered pricing") and ("vaccine"). Subsequently, documents that met the inclusion criteria were selected. Finally, findings were grouped by means of a thematic analysis and an interpretative synthesis. RESULTS: Twenty-four publications were included. We identified 5 main topics: current supply strategies, challenges for the acquisition of vaccines, vaccine prices equity, alternative supply strategies, and the advantages and impact of a tiered pricing strategy. CONCLUSIONS: Our review suggests that tiered pricing can be an tool for accelerating the process of introducing vaccines in low-income countries at affordable prices and for countries that do not adhere to the current procurement mechanisms or are not eligible for Vaccine Alliance because giving countries prices for vaccines that reflect their ability to pay can result in better programmatic and financial planning for the purchase of these vaccines, and in return, vaccine manufacturers can gain access to wider markets However, this model has not been z improve access to vaccines that are aimed only at developing countries, mainly because the market in these countries is not profitable for producers.

Current progress in international pediatric emergency medicine.

PURPOSE OF REVIEW: Over the past four decades, pediatric emergency Medicine (PEM) has witnessed significant global development, with a notable increase in training programs and official recognition by regulatory bodies. However, disparities persist in the recognition of PEM as an independent subspecialty, availability of training programs on a global scale, academic recognition, and the ability to provide high-quality care to children worldwide. There is paucity of published literature regarding development of PEM globally. This review explores the current trends and challenges in international pediatric emergency medicine. RECENT FINDINGS: Current trends in international pediatric emergency medicine encompass the provision of training in pediatric-focused emergency and acute care, increased propagation of evidence-based guidelines specific to the care of children, the growth of collaborative research networks and interest groups within national and international societies. Simultaneously, the field continues to face challenges such as the lack of recognition, inequities in access, and a lack of dissemination of global PEM initiatives. SUMMARY: While recent advancements have significantly enhanced the state of international pediatric emergency medicine, including pediatric specific research networks and training programs, barriers still hinder its overall quality. Many of these obstacles are not unique to pediatric emergency medicine but are directly affected by financial disparities and lack of governmental and public recognition of the essential role of pediatric emergency care.

Dysgerminoma Probably Due to a Novel SOHLH1-pathogenic Variant Causing Familial Ovarian Dysgenesis.

Pathogenic variants of the SOHLH1 gene are responsible for an autosomal recessive form of ovarian dysgenesis; this gene encodes a transcription factor expressed early in spermatogonia and oocytes and contributes to folliculogenesis. Previously, four affected women from two unrelated families reported homozygous variants in the SOHLH1 gene, but none had a history of gonadal malignancy or a histologic description. We present two sisters and their paternal great-aunt with a history of primary amenorrhea, pubertal delay, and hypergonadotrophism who came from an inbred Mexican family. The proband was the younger sister who was referred for bilateral dysgerminoma. She had a normal blood karyotype, and whole-exome sequencing analysis revealed a novel homozygous missense variant, c.275C>T, in SOHLH1; several family members were also analyzed. In addition to pure dysgerminoma, histopathological analysis revealed an ovarian cortex with fibrosis and almost total absence of follicles. This work confirms the inheritance of ovarian dysgenesis 5, supports the occurrence of cell loss in mouse models, and suggests that affected women should undergo periodic imaging surveillance due to the likely risk of tumor development.

First report of Cassava Bacterial Blight caused by Xanthomonas phaseoli pv. manihotis in the Amazonian forest of Ecuador.

Xanthomonas phaseoli pv. manihotis (Xpm) is a plant pathogenic bacterium known as the causal agent of cassava bacterial blight (CBB). CBB is the most limiting bacterial disease affecting cassava (Manihot esculenta Crantz), characterized by diverse symptoms including angular water-soaked leaf lesions, blight, wilting, stem exudates, stem cankers and dieback. CBB has been reported in most cassava-growing regions around the world, and, under conducive conditions, crop yield losses can reach up to 100% (Zárate-Chaves et al. 2021). While Xpm genetic diversity is remarkably high in South America (Bart et al. 2012) and cassava originates and was domesticated in the Amazon basin (Allem 2002), reports of CBB in the Amazonian region are missing. To fill this gap, in October 2018 we surveyed for CBB symptoms in cassava fields of the Orellana Province, located in the Amazon forest of the Republic of Ecuador. Adult cassava plants exhibiting typical angular, water-soaked leaf lesions were found in polyculture plots, i.e. intercrops of cassava with other species such as plantains and fruit trees (a.k.a. chakras). After surface disinfection with 5% sodium hypochlorite followed by 70% ethanol, white Xpm-like colonies were isolated from diseased leaf tissues of four plants on YPGA medium (yeast extract, 5 g/l; peptone, 5 g/l; glucose, 5 g/l; agar-agar, 15 g/l) supplemented with cephalexin (40 mg/l) and cycloheximide (50 mg/l). Pathogenicity tests were performed on peat-potted, 2-month-old cassava plants of the cultivar 60444. Bacterial suspensions were adjusted to an OD600 of 0.2 (2 × 108 CFU/ml) in sterile 10-mM MgCl2 and syringe infiltrated in fully-expanded leaves. In parallel, 20 µl of each bacterial suspension adjusted to an OD600 of 0.02 (2 × 107 CFU/ml) were inoculated on stems inside a hole previously punched with a sterile needle in the junction of the third-top petiole. Sterile 10-mM MgCl2 was used for mock inoculations in both leaves and stems, and experiments were replicated in three plants. Plants were incubated in a greenhouse at 28 ± 1°C with a 12-h photoperiod. Infiltrated leaves developed watersoaking 3 days post inoculation, while wilted leaves, stem exudates, and dieback were observed 21 days after stem inoculation. Control plants remained symptomless. White Xpm-like colonies were re-isolated from symptomatic leaves (Fig S1). One colony of each of the four Xpm isolates (before and after re-isolation) was assessed using diagnostic PCRs (Bernal-Galeano et al. 2018; Flores et al. 2019), using strain Xam668 as positive control. All four candidates were positive for both diagnostic tools. The sequences of the housekeeping genes atpD, dnaK, efp, glnA, gyrB and rpoD of our isolates were extracted from full genome sequences obtained through Oxford Nanopore Technologies (ONT) (GenBank OR288194 to OR288217) and compared to their homologs in four close Xanthomonas species and a reference Xpm strain (Table S1). The sequences of the tested strains aligned with that of Xpm CIO151 (GCA_004025275.1) (Arrieta-Ortiz et al. 2013) with nucleotide identity above 99.92% (Fig S2). The four strains were named CIX4169, CIX4170, CIX4171 and CIX4172, stored in the IRD Collection of Xanthomonas, where they are available upon request. To our knowledge, this is the first report of CBB in the Amazonian region and in Ecuador, where cassava is a central element for local culture and economy. Further surveys will be necessary to evaluate the distribution and prevalence of CBB in other ecozones of Ecuador where cassava is cultivated.

Phase I study targeting newly diagnosed grade 4 astrocytoma with bispecific antibody armed T cells (EGFR BATs) in combination with radiation and temozolomide.

PURPOSE: The purpose of this study was to determine the safety, feasibility, and immunologic responses of treating grade 4 astrocytomas with multiple infusions of anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed T cells (EGFR BATs) in combination with radiation and chemotherapy. METHODS: This phase I study used a 3 + 3 dose escalation design to test the safety and feasibility of intravenously infused EGFR BATs in combination with radiation and temozolomide (TMZ) in patients with newly diagnosed grade 4 astrocytomas (AG4). After finding the feasible dose, an expansion cohort with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) tumors received weekly EGFR BATs without TMZ. RESULTS: The highest feasible dose was 80 × 109 EGFR BATs without dose-limiting toxicities (DLTs) in seven patients. We could not escalate the dose because of the limited T-cell expansion. There were no DLTs in the additional cohort of three patients with unmethylated MGMT tumors who received eight weekly infusions of EGFR BATs without TMZ. EGFR BATs infusions induced increases in glioma specific anti-tumor cytotoxicity by peripheral blood mononuclear cells (p < 0.03) and NK cell activity (p < 0.002) ex vivo, and increased serum concentrations of IFN-γ (p < 0.03), IL-2 (p < 0.007), and GM-CSF (p < 0.009). CONCLUSION: Targeting AG4 with EGFR BATs at the maximum feasible dose of 80 × 109, with or without TMZ was safe and induced significant anti-tumor-specific immune responses. These results support further clinical trials to examine the efficacy of this adoptive cell therapy in patients with MGMT-unmethylated GBM. CLINICALTRIALS: gov Identifier: NCT03344250.

Identifying relevant asymmetry features of EEG for emotion processing.

The left and right hemispheres of the brain process emotion differently. Neuroscientists have proposed two models to explain this difference. The first model states that the right hemisphere is dominant over the left to process all emotions. In contrast, the second model states that the left hemisphere processes positive emotions, whereas the right hemisphere processes negative emotions. Previous studies have used these asymmetry models to enhance the classification of emotions in machine learning models. However, little research has been conducted to explore how machine learning models can help identify associations between hemisphere asymmetries and emotion processing. To address this gap, we conducted two experiments using a subject-independent approach to explore how the asymmetry of the brain hemispheres is involved in processing happiness, sadness, fear, and neutral emotions. We analyzed electroencephalogram (EEG) signals from 15 subjects collected while they watched video clips evoking these four emotions. We derived asymmetry features from the recorded EEG signals by calculating the log ratio between the relative energy of symmetrical left and right nodes. Using the asymmetry features, we trained four binary logistic regressions, one for each emotion, to identify which features were more relevant to the predictions. The average AUC-ROC across the 15 subjects was 56.2, 54.6, 51.6, and 58.4% for neutral, sad, fear, and happy, respectively. We validated these results with an independent dataset, achieving comparable AUC-ROC values. Our results showed that brain lateralization was observed primarily in the alpha frequency bands, whereas for the other frequency bands, both hemispheres were involved in emotion processing. Furthermore, the logistic regression analysis indicated that the gamma and alpha bands were the most relevant for predicting emotional states, particularly for the lateral frontal, parietal, and temporal EEG pairs, such as FT7-FT8, T7-T8, and TP7-TP8. These findings provide valuable insights into which brain areas and frequency bands need to be considered when developing predictive models for emotion recognition.

Relevance of the Updated Recursive Partitioning Analysis (U-RPA) Classification in the Contemporary Care of Patients with Brain Metastases.

Patients with brain metastases (BMETS) need information about the prognosis and potential value of treatment options to make informed therapeutic decisions, but tools to predict survival in contemporary practice are scarce. We propose an Updated Recursive Partitioning Analysis (U-RPA) instrument to predict survival and benefit from brain-directed treatment (BDT) of contemporary patients. This was a retrospective analysis of patients with BMETS treated between 2017 and 2019. With survival as the primary endpoint, we calculated the U-RPA and generated estimates using Kaplan-Meier curves and hazard ratios. Of 862 eligible patients, 752 received BDT and 110 received best supportive care (BSC). Median overall survival with BDT and BSC was 9.3 and 1.3 months, respectively. Patients in RPA class 1, 2A, 2B and 3 who underwent BDT had median survival of 28.1, 14.7, 7.6 and 3.3 months, respectively. The median survival for patients in RPA 3 who received BDT (n = 147), WBRT (n = 79) and SRS (n = 54) was 3.3, 2.9 and 4.1 months, respectively. The U-RPA defines prognosis estimates, independent of tumor type and treatment modality, which can assist to make value-based care treatment decisions. The prognosis for patients in U-RPA class 2B and 3 remains poor, with consideration for early palliative care involvement in these cases.

Co-Plasticization of Starch with Glycerol and Isosorbide: Effect on Retrogradation in Thermo-Plastic Cassava Starch Films.

Thermoplastic starch (TPS) has emerged as an essential alternative to produce environmentally friendly packaging; however, retrogradation is a disadvantage that affects its shelf life. This study analyzed the co-plasticizing effect of isosorbide on the mechanical, thermal, physicochemical, and microstructural properties and the retrogradation of films obtained by blown film extrusion from thermoplasticized starch with mixtures of glycerol and isosorbide in different ratios (3:0, 2:1, 1:2, and 0:3, respectively). The results showed that the higher concentration of isosorbide significantly increased the tensile strength; however, it reduced the elongation. Retrogradation modeled using the Avrami equation showed that the presence of isosorbide reduced the retrogradation rate (k) and modified the recrystallization mechanism (n). The relative crystallinity in the plasticized TPS films was reduced to 89%, and the adsorption significantly decreased. Isosorbide was very important in reducing the retrogradation of TPS. The best performance was obtained with the 2:1 ratio of glycerol/isosorbide due to the synergistic effect between the plasticizers. The results would allow tuning the properties of TPS films by combining glycerol/isosorbide in different ratios, which enables the design of materials tailored to potential application requirements.

First Report of Mexican Patients with PACS1-Related Neurodevelopmental Disorder and Review of the PACS1-, PACS2-, and WDR37-Related Ophthalmological Manifestations.

Introduction: PACS1-related neurodevelopmental disorder (PACS1-related NDD) is caused by pathogenic variants in the PACS1 gene and is characterized by a distinctive facial appearance, intellectual disability, speech delay, seizures, feeding difficulties, cryptorchidism, hernias, and structural anomalies of the brain, heart, eye, and kidney. There is a marked facial resemblance and a common multisystem affectation with patients carrying pathogenic variants in the WDR37 and PACS2 genes, although they vary in terms of severity and eye involvement. Case Presentation: Here, we describe 4 individuals with PACS1-related NDD from Mexico, all of them carrying a de novo PACS1 variant c.607C>T; p.(Arg203Trp) identified by exome sequencing. In addition to eye colobomata, this report identified corneal leukoma, cataracts, and tortuosity of retinal vessels as ophthalmic manifestations not previously reported in patients with PACS1-related NDD. Discussion: We reviewed the ocular phenotypes reported in 74 individuals with PACS1-related NDD and the overlaps with WDR37- and PACS2-related syndromes. We found that the 3 syndromes have in common the presence of colobomata, ptosis, nystagmus, strabismus, and refractive errors, whereas microphthalmia, microcornea, and Peters anomaly are found only among individuals with PACS1-related NDD and WDR37 syndrome, being more severe in the latter. This supports the previous statement that the so-called WDR37-PACS1-PACS2 axis might have an important role in ocular development and also that the specific ocular findings could be useful in the clinical differentiation between these related syndromes.

Identifying factors that shape whether digital food marketing appeals to children.

OBJECTIVE: Children are frequently exposed to unhealthy food marketing on digital media. This marketing contains features that often appeal to children, such as cartoons or bold colours. Additional factors can also shape whether marketing appeals to children. In this study, in order to assess the most important predictors of child appeal in digital food marketing, we used machine learning to examine how marketing techniques and children's socio-demographic characteristics, weight, height, BMI, frequency of screen use and dietary intake influence whether marketing instances appeal to children. DESIGN: We conducted a pilot study with thirty-nine children. Children were divided into thirteen groups, in which they evaluated whether food marketing instances appealed to them. Children's agreement was measured using Fleiss' kappa and the S score. Text, labels, objects and logos extracted from the ads were combined with children's variables to build four machine-learning models to identify the most important predictors of child appeal. SETTING: Households in Calgary, Alberta, Canada. PARTICIPANTS: 39 children aged 6-12 years. RESULTS: Agreement between children was low. The models indicated that the most important predictors of child appeal were the text and logos embedded in the food marketing instances. Other important predictors included children's consumption of vegetables and soda, sex and weekly hours of television. CONCLUSIONS: Text and logos embedded in the food marketing instances were the most important predictors of child appeal. The low agreement among children shows that the extent to which different marketing strategies appeal to children varies.

The prevalence and phenotypic range associated with biallelic PKDCC variants.

PKDCC encodes a component of Hedgehog signalling required for normal chondrogenesis and skeletal development. Although biallelic PKDCC variants have been implicated in rhizomelic shortening of limbs with variable dysmorphic features, this association was based on just two patients. In this study, data from the 100 000 Genomes Project was used in conjunction with exome sequencing and panel-testing results accessed via international collaboration to assemble a cohort of eight individuals from seven independent families with biallelic PKDCC variants. The allelic series included six frameshifts, a previously described splice-donor site variant and a likely pathogenic missense variant observed in two families that was supported by in silico structural modelling. Database queries suggested that the prevalence of this condition is between 1 of 127 and 1 of 721 in clinical cohorts with skeletal dysplasia of unknown aetiology. Clinical assessments, combined with data from previously published cases, indicate a predominantly upper limb involvement. Micrognathia, hypertelorism and hearing loss appear to be commonly co-occurring features. In conclusion, this study strengthens the link between biallelic inactivation of PKDCC and rhizomelic limb-shortening and will enable clinical testing laboratories to better interpret variants in this gene.

Systematic review of the management of brain metastases from hormone receptor positive breast cancer.

INTRODUCTION: Brain metastases are a common cause of morbidity and mortality in patients with breast cancer. Local central nervous system (CNS) directed therapies are usually the first line treatment for breast cancer brain metastases (BCBM), but those must be followed by systemic therapies to achieve long-term benefit. Systemic therapy for hormone receptor (HR+) breast cancer has evolved in the last 10 years, but their role when brain metastases occur is uncertain. METHODS: We performed a systematic review of the literature focused on management of HR+ BCBM by searching Medline/PubMed, EBSCO, and Cochrane databases. The PRISMA guidelines were used for systematic review. RESULTS: Out of 807 articles identified, 98 fulfilled the inclusion criteria in their relevance to the management of HR+ BCBM. CONCLUSIONS: Similar to brain metastases from other neoplasms, local CNS directed therapies are the first line treatment for HR+ BCBM. Although the quality of evidence is low, after local therapies, our review supports the combination of targeted and endocrine therapies for both CNS and systemic management. Upon exhaustion of targeted/endocrine therapies, case series and retrospective reports suggest that certain chemotherapy agents are active against HR+ BCBM. Early phase clinical trials for HR+ BCBM are ongoing, but there is a need for prospective randomized trials to guide management and improve patients' outcome.

CRISPRi in Xanthomonas demonstrates functional convergence of transcription activator-like effectors in two divergent pathogens.

Functional analysis of large gene families in plant pathogens can be cumbersome using classical insertional mutagenesis. Additionally, Cas9 toxicity has limited the application of CRISPR-Cas9 for directed mutagenesis in bacteria. Here, we successfully applied a CRISPR interference strategy to investigate the cryptic role of the transcription activator-like effector (tale) multigene family in several plant-pathogenic Xanthomonas bacterial species, owing to their contribution to pathogen virulence. Single guide RNAs (sgRNAs) designed against Xanthomonas phaseoli pv manihotis tale conserved gene sequences efficiently silenced expression of all tales, with concomitant decrease in virulence and TALE-induced host gene expression. The system is readily translatable to other Xanthomonas species infecting rice, citrus, Brassica, and cassava, silencing up to 16 tales in a given strain using a single sgRNA. Complementation with plasmid-borne designer tales lacking the sgRNA-targeted sequence restored molecular and virulence phenotypes in all pathosystems. Our results evidenced that X. campestris pv campestris CN08 tales are relevant for symptom development in cauliflower. They also show that the MeSWEET10a sugar transporter is surprisingly targeted by the nonvascular cassava pathogen X. cassavae, highlighting a new example of TALE functional convergence between phylogenetically distant Xanthomonas. Overall, this novel technology provides a platform for discovery and rapid functional understanding of highly conserved gene families.