Case report: Bilateral optic nerve sheath meningocele: clinical aspects.

Optic nerve sheath meningocele is an enlargement of the sheath itself, consisting of a collection of cerebrospinal fluid along the perineural space. It should be considered primary if it is not associated with orbital-cerebral neoplasm or with cranio-orbital junction malformations. We report three cases of bilateral primary idiopathic optic nerve sheath meningocele, two of them with gradual vision loss. The first case presented a history of monocular blurred vision of the right eye and headache. It was initially treated with acetazolamide without any improvement, after which optic nerve sheath fenestration was required. The second case showed intermittent binocular diplopia with central 24-2 perimetry defects in the left eye. The third case was first presented as a subacute bilateral conjunctivitis with a suspected orbital pseudotumor. An incidental bilateral optic nerve sheath meningocele was found in the orbital imaging, being totally asymptomatic. In all the cases, orbital and cranial magnetic resonance with contrast and fat suppression was crucial in the diagnosis.

Older Adults with Cancer and Common Comorbidities-Challenges and Opportunities in Improving Their Cancer Treatment Outcomes.

The older American population is rapidly increasing, and millions of older adults will be cancer survivors with comorbidities. This population faces specific challenges regarding treatment and has unique clinical needs. Recognizing this need, the National Cancer Institute (NCI), in collaboration with the National Institute on Aging (NIA), hosted a webinar series, entitled "Cancer, Aging, and Comorbidities." This commentary provides a reflection of five thematic areas covered by the webinar series, which was focused on improving cancer treatment for older adults with cancer and comorbidities: i) the impact of comorbidities on treatment tolerability and patient outcomes; ii) the impact of comorbidities on cancer clinical trial design; iii) the development of wearable devices in measuring comorbidities in cancer treatment; iv) the effects of nutrition and the microbiome on cancer therapy and; v) the role of senescence and senotherapy in age-related diseases. While advances have been made in these areas, many gaps and challenges exist and are discussed in this commentary. To improve cancer survivorship in older populations with comorbidities, aging and comorbidities must be jointly considered and incorporated across the spectrum of cancer research. This includes more basic research of the mechanisms linking comorbidities and cancer development and treatment response, building critical resources and infrastructure (eg, preclinical models and patient samples), conducting clinical trials focused on the older population, integrating geriatric assessment into cancer treatment, and incorporating novel technologies, such as wearable devices into clinical trials and cancer care.

Chromosome-Level Assembly and Annotation of the Genome of the Endangered Giant Patagonian Bumble Bee Bombus dahlbomii.

This article describes a genome assembly and annotation for Bombus dahlbomii, the giant Patagonian bumble bee. DNA from a single, haploid male collected in Argentina was used for PacBio (HiFi) sequencing, and Hi-C technology was then used to map chromatin contacts. Using Juicer and manual curation, the genome was scaffolded into 18 main pseudomolecules, representing a high-quality, near chromosome-level assembly. The sequenced genome size is estimated at 265 Mb. The genome was annotated based on RNA sequencing data of another male from Argentina, and BRAKER3 produced 15,767 annotated genes. The genome and annotation show high completeness, with >95% BUSCO scores for both the genome and annotated genes (based on conserved genes from Hymenoptera). This genome provides a valuable resource for studying the biology of this iconic and endangered species, as well as for understanding the impacts of its decline and designing strategies for its preservation.

First large-scale study reveals important losses of managed honey bee and stingless bee colonies in Latin America.

Over the last quarter century, increasing honey bee colony losses motivated standardized large-scale surveys of managed honey bees (Apis mellifera), particularly in Europe and the United States. Here we present the first large-scale standardized survey of colony losses of managed honey bees and stingless bees across Latin America. Overall, 1736 beekeepers and 165 meliponiculturists participated in the 2-year survey (2016-2017 and 2017-2018). On average, 30.4% of honey bee colonies and 39.6% of stingless bee colonies were lost per year across the region. Summer losses were higher than winter losses in stingless bees (30.9% and 22.2%, respectively) but not in honey bees (18.8% and 20.6%, respectively). Colony loss increased with operation size during the summer in both honey bees and stingless bees and decreased with operation size during the winter in stingless bees. Furthermore, losses differed significantly between countries and across years for both beekeepers and meliponiculturists. Overall, winter losses of honey bee colonies in Latin America (20.6%) position this region between Europe (12.5%) and the United States (40.4%). These results highlight the magnitude of bee colony losses occurring in the region and suggest difficulties in maintaining overall colony health and economic survival for beekeepers and meliponiculturists.

Engineering Mycoplasma pneumoniae to bypass the association with Guillain-Barré syndrome.

A non-pathogenic Mycoplasma pneumoniae-based chassis is leading the development of live biotherapeutic products (LBPs) for respiratory diseases. However, reports connecting Guillain-Barré syndrome (GBS) cases to prior M. pneumoniae infections represent a concern for exploiting such a chassis. Galactolipids, especially galactocerebroside (GalCer), are considered the most likely M. pneumoniae antigens triggering autoimmune responses associated with GBS development. In this work, we generated different strains lacking genes involved in galactolipids biosynthesis. Glycolipid profiling of the strains demonstrated that some mutants show a complete lack of galactolipids. Cross-reactivity assays with sera from GBS patients with prior M. pneumoniae infection showed that certain engineered strains exhibit reduced antibody recognition. However, correlation analyses of these results with the glycolipid profile of the engineered strains suggest that other factors different from GalCer contribute to sera recognition, including total ceramide levels, dihexosylceramide (DHCer), and diglycosyldiacylglycerol (DGDAG). Finally, we discuss the best candidate strains as potential GBS-free Mycoplasma chassis.

Niche analyses and the potential distribution of four invasive bumblebees worldwide.

The introduction of bees for agricultural production in distinct parts of the world and poor management have led to invasion processes that affect biodiversity, significantly impacting native species. Different Bombus species with invasive potential have been recorded spreading in different regions worldwide, generating ecological and economic losses. We applied environmental niche and potential distribution analyses to four species of the genus Bombus to evaluate the similarities and differences between their native and invaded ranges. We found that B. impatiens has an extended environmental niche, going from dry environmental conditions in the native range to warmer and wetter conditions in the invaded range. Bombus ruderatus also exhibited an extended environmental niche with drier and warmer conditions in the invaded range than in its native range. Bombus subterraneus expanded its environmental niche from cooler and wetter conditions in the native range to drier and warmer conditions in the invaded range. Finally, B. terrestris showed the most significant variation in the environmental niche, extending to areas with similar and different environmental conditions from its native range. The distribution models agreed with the known distributions for the four Bombus species, presenting geographic areas known to be occupied by each species in different regions worldwide. The niche analysis indicate shifts in the niches from the native to the invaded distribution area of the bee species. Still, niche similarities were observed in the areas of greatest suitability in the potential distribution for B. ruderatus, B. subterraneus, and B. terrestris, and to a lesser degree in the same areas with B. impatiens. These species require similar environmental conditions as in their native ranges to be established in their introduced ranges. Still, they can adapt to changes in temperature and humidity, allowing them to expand their ranges into new climatic conditions.

ProTInSeq: transposon insertion tracking by ultra-deep DNA sequencing to identify translated large and small ORFs.

Identifying open reading frames (ORFs) being translated is not a trivial task. ProTInSeq is a technique designed to characterize proteomes by sequencing transposon insertions engineered to express a selection marker when they occur in-frame within a protein-coding gene. In the bacterium Mycoplasma pneumoniae, ProTInSeq identifies 83% of its annotated proteins, along with 5 proteins and 153 small ORF-encoded proteins (SEPs; ≤100 aa) that were not previously annotated. Moreover, ProTInSeq can be utilized for detecting translational noise, as well as for relative quantification and transmembrane topology estimation of fitness and non-essential proteins. By integrating various identification approaches, the number of initially annotated SEPs in this bacterium increases from 27 to 329, with a quarter of them predicted to possess antimicrobial potential. Herein, we describe a methodology complementary to Ribo-Seq and mass spectroscopy that can identify SEPs while providing other insights in a proteome with a flexible and cost-effective DNA ultra-deep sequencing approach.

Artificial intelligence-based fluid quantification and associated visual outcomes in a real-world, multicentre neovascular age-related macular degeneration national database.

AIM: To explore associations between artificial intelligence (AI)-based fluid compartment quantifications and 12 months visual outcomes in OCT images from a real-world, multicentre, national cohort of naïve neovascular age-related macular degeneration (nAMD) treated eyes. METHODS: Demographics, visual acuity (VA), drug and number of injections data were collected using a validated web-based tool. Fluid compartment quantifications including intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED) in the fovea (1 mm), parafovea (3 mm) and perifovea (6 mm) were measured in nanoliters (nL) using a validated AI-tool. RESULTS: 452 naïve nAMD eyes presented a mean VA gain of +5.5 letters with a median of 7 injections over 12 months. Baseline foveal IRF associated poorer baseline (44.7 vs 63.4 letters) and final VA (52.1 vs 69.1), SRF better final VA (67.1 vs 59.0) and greater VA gains (+7.1 vs +1.9), and PED poorer baseline (48.8 vs 57.3) and final VA (55.1 vs 64.1). Predicted VA gains were greater for foveal SRF (+6.2 vs +0.6), parafoveal SRF (+6.9 vs +1.3), perifoveal SRF (+6.2 vs -0.1) and parafoveal IRF (+7.4 vs +3.6, all p<0.05). Fluid dynamics analysis revealed the greatest relative volume reduction for foveal SRF (-16.4 nL, -86.8%), followed by IRF (-17.2 nL, -84.7%) and PED (-19.1 nL, -28.6%). Subgroup analysis showed greater reductions in eyes with higher number of injections. CONCLUSION: This real-world study describes an AI-based analysis of fluid dynamics and defines baseline OCT-based patient profiles that associate 12-month visual outcomes in a large cohort of treated naïve nAMD eyes nationwide.

Current landscape of treating different cancers using nanomedicines: Trends and perspectives.

The efforts to use novel nanotechnologies in medicine and cancer have been widespread. In order to understand better the focus areas of cancer nanomedicine research to date, we conducted a survey of nanomedicine developmental and clinical research in conjunction with treatment of various cancers. The survey has been performed based on number of publications, rate of citations, entry into clinical trials, and funding rates by the National Cancer Institute. Our survey indicates that breast and brain cancers are the most and one of the least studied by nanotechnology researchers, respectively. Breast cancer nano-therapies seem to also be most likely to achieve clinical translation as the number of publications produced, amount of funding, total citations, and clinical trials (active and completed) are the highest when compared with research in other cancers. Brain cancer, despite its low survival, has capture much less attention of nanomedicine research community as survey indicated, although nanotechnology can offer novel approaches which can address brain cancer challenges. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Macular Neovascularization Type Influence on Anti-VEGF Intravitreal Therapy Outcomes in Age-Related Macular Degeneration.

PURPOSE: To evaluate the influence of macular neovascularization (MNV) lesion type on 12-month clinical outcomes in treatment-naive eyes with neovascular age-related macular degeneration (nAMD) treated with anti-VEGF drugs nationwide. DESIGN: Multicenter national nAMD database observational study. SUBJECTS: One thousand six hundred six treatment-naive nAMD eyes (1330 patients) undergoing anti-VEGF therapy for 12 months nationwide. METHODS: Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution letters, number of injections and visits were was collected using a validated web-based tool. Neovascular lesion phenotype was classified as type 1 (T1, n = 711), type 2 (T2, n = 505), type 3 (T3, n = 315), and aneurysmal type 1 (A-T1, n = 75), according to the new proposed consensus classification. MAIN OUTCOME MEASURES: Mean VA change at 12 months, final VA at 12 months, number of injections, time to lesion inactivation. RESULTS: A total of 1606 treatment-naive nAMD eyes (1330 patients) received a median of 7 injections over 12 months. Mean (± standard deviation) baseline VA was significantly lower for T2 (49.4 ± 23.5 letters) compared with T1 (57.8 ± 20.8) and T3 (58.2 ± 19.4) (both P < 0.05) lesions. Mean VA change at 12 months was significantly greater for A-T1 (+9.5 letters) compared with T3 (+3.1 letters, P < 0.05). Patients with T3 lesions had fewer active visits (24.9%) than those with other lesion types (T1, 30.5%; T2, 32.6%; A-T1, 27.5%; all P < 0.05). Aflibercept was the most used drug in A-T1 lesions (70.1%) and ranibizumab in T1 (40.7%), T2 (57.7%), and T3 (47.6%) lesions. CONCLUSIONS: This study highlights the relevance of MNV type on clinical outcomes in nAMD and reports significant differences in baseline VA, VA change, and lesion activity at 12 months. This report provides data about lesion-specific clinical features, which may guide the management of nAMD cases and potentially support personalized clinical decision making for these patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Independencia del perfil antropométrico, atención e inteligencia en estudiantes de educación superior en el ámbito de actividad física de Chile / Independence of the anthropometric profile, attention and intelligence in higher education students in the field of physical activity in Chile

Introducción: la cineantropometría es la ciencia actual que estudia los parámetros corporales en relación con su funcionamiento (por ejemplo, composición corporal, proporcionalidad, somatotipo, etc.), con normas, técnicas y criterios establecidos. Objetivo: relacionar el perfil antropométrico, la atención y la resolución de problemas en estudiantes de educación superior en el ámbito de actividad física de Chile. Método: enfoque cuantitativo-correlacional, diseño no experimental y de corte transversal. Resultados: no existe una relación significativa entre la composición corporal (masas corporales) y las pruebas cognitivas (atención y Raven). En relación con los datos antropométricos (composición corporal), no se observaron diferencias significativas entre ambos sexos para ningún parámetro. Conclusión: se deduce que los resultados de los factores cognitivos pueden estar asociados a otras variables, y no específicamente a las variables que pueden afectar los parámetros antropométricos. Estos temas son muy interesantes para próximos estudios, por lo que se sugiere seguir estudiando las habilidades cognitivas con otras variables. (AU)

Introduction: kinanthropometry is the current science that studies body parameters in relation to its functioning (such as body composition, proportionality, somatotype, etc.), with established norms, techniques and criteria. Objective: to relate anthropometric profile, attention and problem solving in higher education students in the field of physical activity in Chile. Method: quantitative-correlational approach, with non-experimental and cross-sectional design. Results: there is no significant relationship between body composition (body masses) and cognitive tests (attention and Raven). Regarding anthropometric data (body composition), no significant differences were observed between the sexes for any parameter. Conclusion: it can be deduced that the results of the cognitive factors may be associated with other variables, and not specifically with the variables that may affect anthropometric parameters. These are very interesting topics for future studies, so it is suggested to continue studying cognitive abilities with other variables. (AU)

[Independence of the anthropometric profile, attention and intelligence in higher education students in the field of physical activity in Chile]. / Independencia del perfil antropométrico, atención e inteligencia en estudiantes de educación superior en el ámbito de actividad física de Chile.

Introduction: Introduction: kinanthropometry is the current science that studies body parameters in relation to its functioning (such as body composition, proportionality, somatotype, etc.), with established norms, techniques and criteria. Objective: to relate anthropometric profile, attention and problem solving in higher education students in the field of physical activity in Chile. Method: quantitative-correlational approach, with non-experimental and cross-sectional design. Results: there is no significant relationship between body composition (body masses) and cognitive tests (attention and Raven). Regarding anthropometric data (body composition), no significant differences were observed between the sexes for any parameter. Conclusion: it can be deduced that the results of the cognitive factors may be associated with other variables, and not specifically with the variables that may affect anthropometric parameters. These are very interesting topics for future studies, so it is suggested to continue studying cognitive abilities with other variables.

Introducción: Introducción: la cineantropometría es la ciencia actual que estudia los parámetros corporales en relación con su funcionamiento (por ejemplo, composición corporal, proporcionalidad, somatotipo, etc.), con normas, técnicas y criterios establecidos. Objetivo: relacionar el perfil antropométrico, la atención y la resolución de problemas en estudiantes de educación superior en el ámbito de actividad física de Chile. Método: enfoque cuantitativo-correlacional, diseño no experimental y de corte transversal. Resultados: no existe una relación significativa entre la composición corporal (masas corporales) y las pruebas cognitivas (atención y Raven). En relación con los datos antropométricos (composición corporal), no se observaron diferencias significativas entre ambos sexos para ningún parámetro. Conclusión: se deduce que los resultados de los factores cognitivos pueden estar asociados a otras variables, y no específicamente a las variables que pueden afectar los parámetros antropométricos. Estos temas son muy interesantes para próximos estudios, por lo que se sugiere seguir estudiando las habilidades cognitivas con otras variables.

Relationship of vitamin D with the anthropometric indicators and lifestyle of adults. Medellín. Colombia

Introduction: Serum vitamin D levels depend on sunlight, diet, and other factors. Objective: We aimed to determine serum vitamin D levels and evaluate their relationship with anthropometric indicators and lifestyle habits in apparently healthy volunteers. Materials and Methods: In this cross-sectional study (n=75), socio-demographic, anthropometric, and lifestyle habit-related data were collected. Serum vitamin D levels were determined with high performance liquid chromatography, food intake was measured by semiquantitative frequency and nutritional status was assessed by anthropometry. Chi-square test and also principal component analysis were used to analyze the relationship between some variables and vitamin D status. Spearman's test was used to determine correlations between quantitative variables. Results: 73% were women and 61% belonged to medium socio-economic level. Median vitamin D intake was 137 (83.1­227.3) IU/day. Based on body mass index (BMI), 44% individuals had overweight/obesity. The 68% exhibited deficient/insufficient vitamin D levels (Hypovitaminosis D). BMI classification and waist circumference (CW) were not related with vitamin D status; however, activities with higher sun exposure were highly related (p = 0.013). Sun exposure time explained variation in component 2 (16.60%), where most of the individuals with normal level were grouped. Sun exposure time was positively correlated with vitamin D status (r = 0.263; p = 0.023). Discussion: Excess weight and abdominal obesity are not always associated with hypovitaminosis D. Conclusions: The majority of individuals showed hypovitaminosis D but their status was not related with anthropometric indicators. A Sun exposure time was the only factor positively correlated with vitamin D status.

Introducción: Los niveles séricos de vitamina D dependen de la luz solar, la dieta y otros factores. Objetivo: Nuestro objetivo fue determinar los niveles séricos de vitamina D y evaluar su relación con indicadores antropométricos y estilos de vida en voluntarios aparentemente sanos. Materiales y métodos: En este estudio trasversal (n=75) se recogieron datos sociodemográficos, antropométricos y aquellos relacionados con hábitos y estilos de vida. La vitamina D se determinó por cromatografía liquida de alta eficiencia; la ingesta de alimentos, mediante frecuencia semicuantitativa, y el estado nutricional por antropometría. Para analizar la relación entre algunas variables y el estado de la vitamina D se usó la prueba de Chi cuadrado y también el análisis de componentes principales. Se empleó la prueba de Spearman para determinar la correlación entre variables cuantitativas. Resultados: El 73% eran mujeres y el 61% pertenecían a un estrato socioeconómico medio. La mediana de la ingesta de vitamina D fue de 137 (83,1­227,3) UI/día. Según el índice de masa corporal (IMC), el 44% de los individuos tenían sobrepeso/obesidad. El 68% mostro deficiencia/insuficiencia de vitamina D (hipovitaminosis D). La clasificación del IMC y la circunferencia abdominal no se relacionaron con el estado de la vitamina D; sin embargo, las actividades con una mayor exposición solar estuvieron altamente relacionadas (p=0,013). El tiempo de exposición solar explico la variación en el componente 2 (16,60%) donde se agruparon la mayoría de los individuos con niveles normales. El tiempo de exposición solar tuvo una correlación positiva con el estado de la vitamina D (r = 0,263; p = 0,023). Discusión: El exceso de peso y la obesidad abdominal no siempre se relacionan con la hipovitaminosis D. Conclusiones: La mayoría de los individuos presentaron hipovitaminosis D, pero su estado no se relacionó con los indicadores antropométricos. El tiempo de exposición al sol fue el único factor que se correlaciono positivamente con el estado de la vitamina D.

Introdução: Os níveis séricos de vitamina D dependem da luz solar, da dieta e de outros fatores. Objetivo: Nosso objetivo foi determinar os níveis séricos de vitamina D e avaliar sua relação com indicadores antropométricos e hábitos de vida em voluntários aparentemente saudáveis. Materiais e métodos: Neste estudo transversal (n=75), foram coletados dados sociodemográficos, antropométricos e relacionados a hábitos de vida. Os níveis séricos de vitamina D foram determinados por cromatografia liquida de alto desempenho, a ingestão de alimentos foi medida por frequência semiquantitativa e o estado nutricional foi avaliado por antropometria. O teste do qui-quadrado e a análise de componentes principais foram utilizados para analisar a relação entre algumas variáveis e o estado da vitamina D. O teste de Spearman foi usado para determinar as correlações entre as variáveis quantitativas. Resultados: 73% eram mulheres e 61% pertenciam a um nível socioeconômico médio. A ingestão media de vitamina D foi de 137 (83,1-227,3) UI/dia. Com base no índice de massa corporal (IMC), 44% dos indivíduos tinham sobrepeso/obesidade. Os 68% apresentaram níveis deficientes/insuficientes de vitamina D (hipovitaminose D). A classificação do IMC e a circunferência da cintura (CW) não foram relacionadas ao status da vitamina D; entretanto, as atividades com maior exposição ao sol foram altamente relacionadas (p = 0,013). O tempo de exposição ao sol explicou a variação no componente 2 (16,60%), onde a maioria dos indivíduos com nível normal foi agrupada. O tempo de exposição ao sol foi positivamente correlacionado com o status de vitamina D (r = 0,263; p = 0,023). Discussão: O excesso de peso e a obesidade abdominal nem sempre estão associados com a hipovitaminose D. Conclusões: A maioria dos indivíduos apresentou hipovitaminose D, mas seu status não foi relacionado com indicadores antropométricos. O tempo de exposição ao sol foi o único fator positivamente correlacionado com o status da vitamina D.

Persistent high levels of carcinoembryonic antigen after tumor resection are associated with poorer survival outcomes in patients with resected colon cancer.

BACKGROUND: Interindividual survival and recurrence rates in cases of locoregional colon cancer following surgical resection are highly variable. The aim of the present study was to determine whether elevated pre-operative and post-operative CEA values are useful prognostic biomarkers for patients with stage I-III colon cancer who underwent surgery with curative intent. METHODS: We conducted a retrospective study in patients with histologically confirmed stage I-III primary colonic adenocarcinoma who underwent radical surgical resection at Mexico's National Cancer Institute, between January 2008 and January 2020. We determined pre-operative and post-operative CEA and analyzed the association of scores with poorer survival outcomes in patients with resected colon cancer, considering overall survival (OS) and disease-free survival (DFS). RESULTS: We included 640 patients with stage I-III colon cancer. Pre-operative CEA levels were in the normal range in 460 patients (group A) and above the reference value in the other 180. Of the latter, 134 presented normalized CEA levels after surgery, but 46 (group C) continued to show CEA levels above the reference values after surgery. Therefore, propensity score matching (PSM) was carried out to reduce the bias. Patients were adjusted at a 1:1:1 ratio with 46 in each group, to match the number in the smallest group. Median follow- up was 46.4 months (range, 4.9-147.4 months). Median DFS was significantly shorter in Group C: 55.5 months (95% CI 39.6-71.3) than in the other two groups [Group A: 77.1 months (95% CI 72.6-81.6). Group B: 75.7 months (95% CI 66.8-84.5) (p-value < 0.001)]. Overall survival was also significantly worse in group C [57.1 (95% CI 37.8-76.3) months] than in group A [82.8 (95% CI 78.6-86.9 months] and group B [87.1 (95% CI 79.6-94.5 months] (p-value = 0.002). To identify whether change in CEA levels operative and post-surgery was an independent prognostic factor for survival outcomes, a Cox proportional hazard model was applied. In multivariate analysis, change in CEA level was a statistically significant, independent prognostic factor for overall survival (p-value = 0.031). CONCLUSIONS: When assessed collectively, pre-operative and post-operative CEA values are useful biomarkers for predicting survival outcomes in patients with resected colon cancer. Prognoses are worse for patients with elevated pre-operative and post-surgical CEA values, but similar in patients with normal post-surgical values, regardless of their pre-surgery values.

Impact of ileostomy in the adjuvant treatment and outcome of colon cancer.

BACKGROUND: After tumor resection, a preventive diverting loop ileostomy creation is a routine surgical procedure to prevent anastomotic leakage and infections and to preclude secondary surgeries. Despite its benefits, several studies have proposed potential complications that extend the disease course by impairing the feasibility of adjuvant chemotherapy and adherence. PURPOSE: The aim of this study was to evaluate the impact of ileostomy complications on the adherence to adjuvant treatment and overall survival (OS) of colon cancer (CC) patients. METHODS: Retrospective, observational study. Patients diagnosed with colon adenocarcinoma were treated between January 2010 and December 2020 at the National Cancer Institute in Mexico. STATISTICAL ANALYSIS: χ2 and t-test, Kaplan-Meier, log-rank, and Cox regression. Statistical significance differences were assessed when p was bilaterally < 0.05. RESULTS: The most frequent complications of loop-derived ileostomy were hydro-electrolytic dehydration (50%), acute kidney injury (AKI) (26%), grade 1-2 diarrhea (28%), and grade 3-4 diarrhea (21%) (p = 0.001). Patients with complete chemotherapy did not reach the median OS. In contrast, the median OS for patients with non-complete chemotherapy was 56 months (p = 0.023). Additionally, 5-year OS reached to 100% in the early restitution group, 85% in the late restitution group, and 60% in the non-restitution group (p = 0.016). Finally, AKI (p = 0.029; 95% confidence interval (CI) 3.348 [1.133-9.895]), complete chemotherapy (p = 0.028; 95% CI 0.376 [0.105-0.940]), and reversed ileostomy (p = 0.001; 95% CI 0.125 [0.038-0.407]) remained as predictors of overall survival for patients with CC treated with a loop ileostomy. CONCLUSIONS: Our results emphasize the early stoma reversal restitution as a safe and feasible alternative to prevent severe complications related to ileostomies which improve chemotherapy adherence and overall survival of colon cancer patients. This is one of the pioneer studies analyzing the impact of ileostomy on treatment adherence and outcome of Latin American patients with colon cancer. TRIAL REGISTRATION: Retrospective study No. 2021/045, in April 2021.

Ursodeoxycholic Acid Binds PERK and Ameliorates Neurite Atrophy in a Cellular Model of GM2 Gangliosidosis.

The Unfolded protein response (UPR), triggered by stress in the endoplasmic reticulum (ER), is a key driver of neurodegenerative diseases. GM2 gangliosidosis, which includes Tay-Sachs and Sandhoff disease, is caused by an accumulation of GM2, mainly in the brain, that leads to progressive neurodegeneration. Previously, we demonstrated in a cellular model of GM2 gangliosidosis that PERK, a UPR sensor, contributes to neuronal death. There is currently no approved treatment for these disorders. Chemical chaperones, such as ursodeoxycholic acid (UDCA), have been found to alleviate ER stress in cell and animal models. UDCA's ability to move across the blood-brain barrier makes it interesting as a therapeutic tool. Here, we found that UDCA significantly diminished the neurite atrophy induced by GM2 accumulation in primary neuron cultures. It also decreased the up-regulation of pro-apoptotic CHOP, a downstream PERK-signaling component. To explore its potential mechanisms of action, in vitro kinase assays and crosslinking experiments were performed with different variants of recombinant protein PERK, either in solution or in reconstituted liposomes. The results suggest a direct interaction between UDCA and the cytosolic domain of PERK, which promotes kinase phosphorylation and dimerization.

Peritoneal carcinomatosis index and overall survival in patients taken to cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

BACKGROUND: The peritoneal carcinomatosis (PC) secondary to gastrointestinal or gynecological cancer has increased its incidence. It has a worse prognosis compared to other sites of metastasis. The peritoneal carcinomatosis index (PCI) establishes overall survival in patients with gastrointestinal or gynecological tumors and carcinomatosis. OBJECTIVE: To evaluate the relationship of PCI to overall survival (OS) and recurrence-free survival (RFS) in patients treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHOD: A descriptive, retrolective study of 80 charts of patients with CP was conducted. We included patients with colon, ovarian, appendicular, pseudomyxoma and gastric tumors with CP treated with CRS plus HIPEC. The OS and RFS were determined according to the type of adenocarcinoma and the degree of differentiation. The OS and RFS were determined in months in patients with PCI > 15 PCI as well as in patients with PCI < 15 considering the tumor of origin. RESULTS: Patients with ovarian tumors and pseudomyxoma with PCI < 15 presented OS > 70 months, compared to patients with gastric tumors (4 months). CONCLUSIONS: The PCI and histology are predictors of OS. Patients with ovarian tumors and PCI < 15 have higher OS, similar to pseudomyxomas. RFS was also higher in patients with PCI < 15.

ANTECEDENTES: La incidencia de carcinomatosis peritoneal (CP) secundaria a cáncer gastrointestinal o ginecológico ha aumentado y tiene peor pronóstico en comparación con otros sitios de metástasis. El índice de carcinomatosis peritoneal (ICP) establece la supervivencia global en pacientes con tumores gastrointestinales o ginecológicos y carcinomatosis. OBJETIVO: Evaluar la relación del ICP con la supervivencia global (SG) y la supervivencia libre de recurrencia (SLR) en pacientes tratados con cirugía citorreductora (CCR) más quimioterapia intraperitoneal e hipertemia (HIPEC). MÉTODO: Estudio descriptivo, retrolectivo, de 80 expedientes de pacientes con CP. Se incluyeron tumores de colon, ovario, apendicular, pseudomixomas y gástricos con CP tratados con CCR + HIPEC. Se determinaron la SG y la SLR de acuerdo con el tipo de adenocarcinoma y el grado de diferenciación, en meses, en pacientes con ICP > 15 y con ICP < 15 considerando el tumor de origen. RESULTADOS: Los pacientes con tumores de ovario y pseudomixoma con ICP < 15 tenían una SG > 70 meses, frente a 4 meses con tumores gástricos. CONCLUSIONES: El ICP y la histología son predictores de la SG. Las pacientes con tumores ováricos con ICP < 15 tienen mayor SG, igual que los pseudomixomas. La SLR fue mayor en los pacientes con ICP < 15.

Rootstocks Comparison in Grafted Watermelon under Water Deficit: Effects on the Fruit Quality and Yield.

Drought is widely recognized as one of the most significant agricultural constraints worldwide. A strategy to avoid the adverse effects of drought on crops is to cultivate high-yielding varieties by grafting them onto drought-tolerant rootstocks with a differentiated root system. Thus, the objective of this study was to evaluate fruit yield and quality, root system architecture, and water productivity of watermelon grafted onto Lagenaria siceraria rootstocks. To do so, a commercial watermelon cultivar "Santa Amelia" [Citrullus lanatus (Thunb.)] was grafted onto five L. siceraria rootstocks: 'Illapel', 'Osorno', 'BG-48', 'GC', and 'Philippines', which were grown under three irrigation treatments (100%, 75%, and 50% of evapotranspiration). The comparison of the L. siceraria rootstocks in the irrigation treatments demonstrated no significant effect on watermelon fruit quality parameters. The rootstocks 'Illapel', 'Osorno', and 'GC' significantly improved the fruit number and yield (total fruit weight) under water deficit. Similarly, 'Illapel', 'Osorno', and 'GC' consistently showed statistical differences for root system architecture traits compared to 'BG-48' and 'Philippines'. Based on these results, we concluded that the used L. siceraria rootstocks did not affect the fruit yield and quality of grafted watermelon under water deficit. This study may help adjust the amount of applied water for watermelon production where L. siceraria rootstocks are utilized.