HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study.

HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively. The effect of HMGA1 silencing on trabectedin activity and gene expression profiling was measured in leiomyosarcoma cells. The effect of combining mTOR inhibitors with trabectedin was assessed on cell viability in vitro studies, whereas in vivo studies tested the activity of this combination. HMGA1 mRNA and protein expression were significantly associated with worse progression-free survival of trabectedin and worse overall survival in STS. HMGA1 silencing sensitized leiomyosarcoma cells for trabectedin treatment, reducing the spheroid area and increasing cell death. The downregulation of HGMA1 significantly decreased the enrichment of some specific gene sets, including the PI3K/AKT/mTOR pathway. The inhibition of mTOR, sensitized leiomyosarcoma cultures for trabectedin treatment, increasing cell death. In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 is an adverse prognostic factor for trabectedin treatment in advanced STS. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growth.

Mitochondrial health, physical functioning, and daily affect: Bioenergetic mechanisms of dementia caregiver well-being.

OBJECTIVE: Chronic stress adversely affects mental and physical well-being. However, health outcomes vary among people experiencing the same stressor. Individual differences in physical and emotional well-being may depend on mitochondrial biology, as energy production is crucial for stress regulation. This study investigated whether mitochondrial respiratory capacity corresponds to individual differences in dementia spousal caregivers' mental and physical health. METHODS: Spousal caregivers of individuals with Alzheimer's disease and related dementias (N = 102, mean age = 71, 78% female, 83% White) provided peripheral blood samples and completed self-report questionnaires on quality of life, caregiver burden, and a 7-day affect scale. Multiple and mixed linear regression were used to test the relationship between mitochondrial biology and well-being. RESULTS: Spare respiratory capacity (b = 12.76, CI[5.23, 20.28 ], p = .001), maximum respiratory capacity (b = 8.45, CI [4.54, 12.35], p < .0001), and ATP-linked respiration (b = 10.11, CI [5.05, 15.18], p = .0001) were positively associated with physical functioning. At average (b = -2.23, CI [-3.64, -.82], p = .002) and below average (b = -4.96, CI [-7.22, 2.70], p < .0001) levels of spare respiratory capacity, caregiver burden was negatively associated with daily positive affect. At above average levels of spare respiratory capacity, caregiver burden was not associated with positive affect (p = .65). CONCLUSIONS: Findings suggest that better mitochondrial health is associated with better psychological and physical health - a pattern consistent with related research. These findings provide some of the earliest evidence that cellular bioenergetics are related to well-being.

The Relationship Between Apathy and Cognitive Impairment Among Hispanic/Latin Americans: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses Systematic Review.

OBJECTIVES: The primary aim was to evaluate apathy assessment measures in relation to cognitive impairment among Hispanic/Latin Americans. METHODS: A systematic review on the relationship between apathy and cognitive impairment among Hispanic/Latin Americans across normal aging and neurocognitive disorders was conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and using APA PsycInfo, Embase, and PubMed databases. Inclusion criteria required (1) a sample of English or Spanish-speaking adults ages 18 years and older, (2) with measures of apathy, (3) assessment of cognitive functioning or diagnosis of neurocognitive disorder, (4) with at least 18.5% Hispanic/Latin American represented in the sample. RESULTS: Only 14 papers met criteria to be included in this review. Of the 12 cross-sectional studies, 9 demonstrated significant associations between increased apathy and cognitive impairment, 1 demonstrated a descriptive difference between apathy and cognitive status (ie, no hypothesis test conducted), while 2 demonstrated null effects. These cross-sectional studies consisted of community and clinic samples of participants across North and South America. Two longitudinal studies conducted in North America demonstrated non-significant associations of apathy with cognitive status. CONCLUSIONS: The Neuropsychiatric Inventory (NPI) and Neuropsychiatric Inventory Questionnaire (NPI-Q) apathy subscales were the most used measures for apathy in this review (85.7% of included studies). However, validity evidence from a review of apathy measures has warranted caution against the use of the NPI outside the context of screening for apathy. This potential measurement bias with Hispanic/Latin Americans apathy research limits conclusions drawn from the present review.

Molecular Classifications in Gastric Cancer: A Call for Interdisciplinary Collaboration.

Gastric cancer (GC) is a heterogeneous disease, often diagnosed at advanced stages, with a 5-year survival rate of approximately 20%. Despite notable technological advancements in cancer research over the past decades, their impact on GC management and outcomes has been limited. Numerous molecular alterations have been identified in GC, leading to various molecular classifications, such as those developed by The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG). Other authors have proposed alternative perspectives, including immune, proteomic, or epigenetic-based classifications. However, molecular stratification has not yet transitioned into clinical practice for GC, and little attention has been paid to alternative molecular classifications. In this review, we explore diverse molecular classifications in GC from a practical point of view, emphasizing their relationships with clinicopathological factors, prognosis, and therapeutic approaches. We have focused on classifications beyond those of TCGA and the ACRG, which have been less extensively reviewed previously. Additionally, we discuss the challenges that must be overcome to ensure their impact on patient treatment and prognosis. This review aims to serve as a practical framework to understand the molecular landscape of GC, facilitate the development of consensus molecular categories, and guide the design of innovative molecular studies in the field.

Hippocampal, basal ganglia and olfactory connectivity contribute to cognitive impairments in Parkinson's disease.

Cognitive impairment is increasingly recognized as a characteristic feature of Parkinson's disease (PD), yet relatively little is known about its underlying neurobiology. Previous investigations suggest that dementia in PD is associated with subcortical atrophy, but similar studies in PD with mild cognitive impairment have been mixed. Variability in cognitive phenotypes and diversity of PD symptoms suggest that a common neuropathological origin results in a multitude of impacts within the brain. These direct and indirect impacts of disease pathology can be investigated using network analysis. Functional connectivity, for instance, may be more sensitive than atrophy to decline in specific cognitive domains in the PD population. Fifty-eight participants with PD underwent a neuropsychological test battery and scanning with structural and resting state functional MRI in a comprehensive whole-brain association analysis. To investigate atrophy as a potential marker of impairment, structural gray matter atrophy was associated with cognitive scores in each cognitive domain using voxel-based morphometry. To investigate connectivity, large-scale networks were correlated with voxel time series and associated with cognitive scores using distance covariance. Structural atrophy was not associated with any cognitive domain, with the exception of visuospatial measures in primary sensory and motor cortices. In contrast, functional connectivity was associated with attention, executive function, language, learning and memory, visuospatial, and global cognition in the bilateral hippocampus, left putamen, olfactory cortex, and bilateral anterior temporal poles. These preliminary results suggest that cognitive domain-specific networks in PD are distinct from each other and could provide a network signature for different cognitive phenotypes.

Severity Grading Systems for Intraoperative Adverse Events. A Systematic Review of the Literature and Citation Analysis.

INTRODUCTION: The accurate assessment and grading of adverse events (AE) is essential to ensure comparisons between surgical procedures and outcomes. The current lack of a standardized severity grading system may limit our understanding of the true morbidity attributed to AEs in surgery. The aim of this study is to review the prevalence in which intraoperative adverse event (iAE) severity grading systems are used in the literature, evaluate the strengths and limitations of these systems, and appraise their applicability in clinical studies. METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. PubMed, Web of Science, and Scopus were queried to yield all clinical studies reporting the proposal and/or the validation of iAE severity grading systems. Google Scholar, Web of Science, and Scopus were searched separately to identify the articles citing the systems to grade iAEs identified in the first search. RESULTS: Our search yielded 2957 studies, with 7 studies considered for the qualitative synthesis. Five studies considered only surgical/interventional iAEs, while 2 considered both surgical/interventional and anesthesiologic iAEs. Two included studies validated the iAE severity grading system prospectively. A total of 357 citations were retrieved, with an overall self/nonself-citation ratio of 0.17 (53/304). The majority of citing articles were clinical studies (44.1%). The average number of citations per year was 6.7 citations for each classification/severity system, with only 2.05 citations/year for clinical studies. Of the 158 clinical studies citing the severity grading systems, only 90 (56.9%) used them to grade the iAEs. The appraisal of applicability (mean%/median%) was below the 70% threshold in 3 domains: stakeholder involvement (46/47), clarity of presentation (65/67), and applicability (57/56). CONCLUSION: Seven severity grading systems for iAEs have been published in the last decade. Despite the importance of collecting and grading the iAEs, these systems are poorly adopted, with only a few studies per year using them. A uniform globally implemented severity grading system is needed to produce comparable data across studies and develop strategies to decrease iAEs, further improving patient safety.

Recent Advances in Neuropsychological Test Interpretation for Clinical Practice.

Much attention in the field of clinical neuropsychology has focused on adapting to the modern healthcare environment by advancing telehealth and promoting technological innovation in assessment. Perhaps as important (but less discussed) are advances in the development and interpretation of normative neuropsychological test data. These techniques can yield improvement in diagnostic decision-making and treatment planning with little additional cost. Brooks and colleagues (Can Psychol 50: 196-209, 2009) eloquently summarized best practices in normative data creation and interpretation, providing a practical overview of norm development, measurement error, the base rates of low scores, and methods for assessing change. Since the publication of this seminal work, there have been several important advances in research on development and interpretation of normative neuropsychological test data, which may be less familiar to the practicing clinician. Specifically, we provide a review of the literature on regression-based normed scores, item response theory, multivariate base rates, summary/factor scores, cognitive intraindividual variability, and measuring change over time. For each topic, we include (1) an overview of the method, (2) a rapid review of the recent literature, (3) a relevant case example, and (4) a discussion of limitations and controversies. Our goal was to provide a primer for use of normative neuropsychological test data in neuropsychological practice.

Does neurocognition contribute to age-related deficits in the online navigation of electronic patient health portals?

OBJECTIVE: The internet serves an increasingly critical role in how older adults manage their personal health. Electronic patient portals, for example, provide a centralized platform for older adults to access lab results, manage prescriptions and appointments, and communicate with providers. This study examined whether neurocognition mediates the effect of older age on electronic patient portal navigation. METHOD: Forty-nine younger (18-35 years) and 35 older adults (50-75 years) completed the Test of Online Health Records Navigation (TOHRN), which is an experimenter-controlled website on which participants were asked to log-in, review laboratory results, read provider messages, and schedule an appointment. Participants also completed a neuropsychological battery, self-report questionnaires, and measures of health literacy and functional capacity. RESULTS: Mediation analyses revealed a significant indirect effect of older age on lower TOHRN accuracy, which was fully mediated by the total cognitive composite. CONCLUSIONS: Findings indicate that neurocognition may help explain some of the variance in age-related difficulties navigating electronic patient health portals. Future studies might examine the possible benefits of both structural (e.g., human factors web design enhancement) and individual (e.g., training and compensation) cognitive supports to improve the navigability of electronic patient health portals for older adults.

Assessment and Reporting of Perioperative Adverse Events and Complications in Patients Undergoing Inguinal Lymphadenectomy for Melanoma, Vulvar Cancer, and Penile Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Inguinal lymph node dissection (ILND) plays a crucial role in the oncological management of patients with melanoma, penile, and vulvar cancer. This study aims to systematically evaluate perioperative adverse events (AEs) in patients undergoing ILND and its reporting. METHODS: A systematic review was conducted according to PRISMA. PubMed, MEDLINE, Scopus, and Embase were queried to identify studies discussing perioperative AEs in patients with melanoma, penile, and vulvar cancer following ILND. RESULTS: Our search generated 3.469 publications, with 296 studies meeting the inclusion criteria. Details of 14.421 patients were analyzed. Of these studies, 58 (19.5%) described intraoperative AEs (iAEs) as an outcome of interest. Overall, 68 (2.9%) patients reported at least one iAE. Postoperative AEs were reported in 278 studies, combining data on 10.898 patients. Overall, 5.748 (52.7%) patients documented ≥1 postoperative AEs. The most reported ILND-related AEs were lymphatic AEs, with a total of 4.055 (38.8%) events. The pooled meta-analysis confirmed that high BMI (RR 1.09; p = 0.006), ≥1 comorbidities (RR 1.79; p = 0.01), and diabetes (RR 1.81; p = < 0.00001) are independent predictors for any AEs after ILND. When assessing the quality of the AEs reporting, we found 25% of studies reported at least 50% of the required criteria. CONCLUSION: ILND performed in melanoma, penile, and vulvar cancer patients is a morbid procedure. The quality of the AEs reporting is suboptimal. A more standardized AEs reporting system is needed to produce comparable data across studies for furthering the development of strategies to decrease AEs.

Prognostic role of the number of resected and negative lymph nodes in Spanish patients with gastric cancer.

INTRODUCTION: Lymph node (LN) involvement is one of the most critical prognostic factors in resected gastric cancer (GC). Some analyses, mainly conducted in Asian populations, have found that patients with a higher number of total lymph nodes (NTLN) and/or negative lymph nodes (NNLN) have a better prognosis, although other authors have failed to confirm these results. MATERIALS AND METHODS: Retrospective study including all patients with GC resected in a tertiary hospital in Spain between 2001 and 2019 (n = 315). Clinicopathological features were collected and patients were categorized according to the NTLN and the NNLN. Statistical analyses were performed. RESULTS: Mean NNLN was 17. The NNLN was significantly related to multiple clinicopathological variables, including recurrence and tumor-related death. The classification based on the NNLN (N1: ≥16, N2: 8-15, N3: ≤7) effectively stratified the entire cohort into three distinct prognostic groups and maintained its prognostic value within both the pN0 and pN+ patient subsets. Furthermore, it was an independent prognostic indicator for both overall and disease-free survival. Conversely, the mean NTLN was 21.9. Patients with ≤16 LN retrieved exhibited distinct clinicopathological features compared to those with >16 LN, but no significant differences were observed in terms of recurrence or disease-associated death. The application of alternative cut-off points for NTLN (10, 20, 25, 30, and 40) showed no prognostic significance. CONCLUSIONS: In Spanish patients with resected GC the NNLN hold prognostic significance, while the NTLN does not appear to be prognostically significant. Incorporating the NNLN into GC staging may enhance the accuracy of the TNM system.

Characterization of the Key Compounds of Bell Pepper by Spectrophotometry and Gas Chromatography on the Effects of Induced Stress on the Concentration of Secondary Metabolite.

Sweet peppers are consumed worldwide, and traditional uses have sparked interest in their applications as dietary antioxidants, which can be enhanced in plants using elicitors. These are endowed with phytochemicals with potential health benefits such as antioxidants, bioavailability, and bioaccessibility. The trend in metabolomics shows us chemical fingerprints linking metabolomics, innovative analytical form, and bioinformatics tools. The objective was to evaluate the impact of multiple stress interactions, elicitor concentrations, and electrical conductivity on the concentration of secondary metabolites to relate their response to metabolic pathways through the foliar application of a cocktail of said elicitors in pepper crops under greenhouse conditions. The extracts were analyzed by spectrophotometry and gas chromatography, and it was shown that the PCA analysis identified phenolic compounds and low molecular weight metabolites, confirming this as a metabolomic fingerprint in the hierarchical analysis. These compounds were also integrated by simultaneous gene and metabolite simulants to obtain effect information on different metabolic pathways. Showing changes in metabolite levels at T6 (36 mM H2O2 and 3.6 dS/m) and T7 (0.1 mM SA and 3.6 dS/m) but showing statistically significant changes at T5 (3.6 dS/m) and T8 (0.1 mM SA, 36 mM H2O2, and 3.6 dS/m) compared to T1 (32 dS/m) or control. Six pathways changed significantly (p < 0.05) in stress-induced treatments: aminoacyl t-RNA and valine-leucine-isoleucine biosynthesis, and alanine-aspartate-glutamate metabolism, glycoxylate-dicarboxylate cycle, arginine-proline, and citrate. This research provided a complete profile for the characterization of metabolomic fingerprint of bell pepper under multiple stress conditions.

Long-term oncological and surgical outcomes after Video Endoscopic Inguinal Lymphadenectomy (VEIL) in patients with penile cancer.

OBJECTIVE: To report outcomes from the largest multicenter series of penile cancer patients undergoing video endoscopic inguinal lymphadenectomy (VEIL). MATERIALS AND METHODS: Retrospective multicenter analysis. Authors of 21 centers from the Penile Cancer Collaborative Coalition-Latin America (PeC-LA) were included. All centers performed the procedure following the same previously described standardized technique. Inclusion criteria included penile cancer patients with no palpable lymph nodes and intermediate/high-risk disease and those with non-fixed palpable lymph nodes less than 4 cm in diameter. Categorical variables are shown as percentages and frequencies whereas continuous variables as mean and range. RESULTS: From 2006 to 2020, 210 VEIL procedures were performed in 105 patients. Mean age was 58 (45-68) years old. Mean operative time was 90 minutes (60-120). Mean lymph node yield was 10 nodes (6-16). Complication rate was 15.7%, including severe complications in 1.9% of procedures. Lymphatic and skin complications were noted in 8.6 and 4.8% of patients, respectively. Histopathological analysis revealed lymph node involvement in 26.7% of patients with non-palpable nodes. Inguinal recurrence was observed in 2.8% of patients. 10y- overall survival was 74.2% and 10-y cancer specific survival was 84.8%. CSS for pN0, pN1, pN2 and pN3 were 100%, 82.4%, 72.7% and 9.1%, respectively. CONCLUSION: VEIL seems to offer appropriate long term oncological control with minimal morbidity. In the absence of non-invasive stratification measures such as dynamic sentinel node biopsy, VEIL emerged as the alternative for the management of non-bulky lymph nodes in penile cancer.

Are accuracy discernment and sharing of COVID-19 misinformation associated with older age and lower neurocognitive functioning?

The online proliferation of COVID-19 misinformation led to adverse health and societal consequences. This study investigated possible differences in COVID-19 headline accuracy discernment and online sharing of COVID-19 misinformation between older and younger adults, as well as the role of individual differences in global cognition, health literacy and verbal IQ. Fifty-two younger (18-35 years old) and fifty older adults (age 50 and older) completed a neurocognitive battery, health literacy and numeracy measures, and self-report questionnaires via telephone. Participants also completed a social media headline-sharing experiment (Pennycook et al., Psychological science, 31(7), 770-780, 2020) in which they were presented with true and false COVID-19 headlines about which they indicated: 1) the likelihood that they would share the story on social media; and 2) the factual accuracy of the story. A repeated measures multivariate analysis of variance controlling for gender and race/ethnicity showed no effects of age (p = .099) but a significant interaction between actual COVID-19 headline accuracy and the likelihood of sharing (p < .001), such that accuracy was more strongly related to sharing false headlines (r = -.64) versus true headlines (r = -.43). Moreover, a higher likelihood of sharing false COVID-19 headlines was associated with lower verbal IQ and numeracy skills in older adults (rs = -.51--.40) and with lower verbal IQ, numeracy, and global cognition in younger adults (rs = -.66--.60). Findings indicate that headline accuracy judgements, numeracy, and verbal IQ are important contributors to sharing COVID-19 misinformation in both older and younger adults. Future work might examine the benefits of psychoeducation for improving health and science literacy for COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-023-04464-w.

Primary central nervous system sarcoma with DICER1 mutation-treatment results of a novel molecular entity in pediatric Peruvian patients.

BACKGROUND: A high frequency of primary central nervous system (CNS) sarcomas was observed in Peru. This article describes the clinical characteristics, biological characteristics, and outcome of 70 pediatric patients. METHODS: Data from 70 pediatric patients with primary CNS sarcomas diagnosed between January 2005 and June 2018 were analyzed. DNA methylation profiling from 28 tumors and gene panel sequencing from 27 tumors were available. RESULTS: The median age of the patients was 6 years (range, 2-17.5 years), and 66 of 70 patients had supratentorial tumors. DNA methylation profiling classified 28 of 28 tumors as primary CNS sarcoma, DICER1 mutant. DICER1 mutations were found in 26 of 27 cases, TP53 mutations were found in 22 of 27 cases, and RAS-pathway gene mutations (NF1, KRAS, and NRAS) were found in 19 of 27 tumors, all of which were somatic (germline control available in 19 cases). The estimated incidence in Peru was 0.19 cases per 100,000 children (<18 years old) per year, which is significantly higher than the estimated incidence in Germany (0.007 cases per 100,000 children [<18 years] per year; P < .001). Patients with nonmetastatic disease (n = 46) that were treated with a combination therapy had a 2-year progression-free survival (PFS) rate of 58% (95% CI, 44%-76%) and a 2-year overall survival rate of 71% (95% CI, 57%-87%). PFS was the highest in patients treated with chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) after upfront surgery followed by radiotherapy and ICE (2-year PFS, 79% [59%-100%], n = 18). CONCLUSIONS: Primary CNS sarcoma with DICER1 mutation has an aggressive clinical course. A combination of surgery, chemotherapy, and radiotherapy seems beneficial. An underlying cancer predisposition syndrome explaining the increased incidence in Peruvian patients has not been identified so far. LAY SUMMARY: A high incidence of primary pediatric central nervous system sarcomas in the Peruvian population is described. Using sequencing technologies and DNA methylation profiling, it is confirmed that these tumors molecularly belong to the recently proposed entity "primary central nervous system sarcomas, DICER1 mutant." Unexpectedly, DICER1 mutations as well as all other defining tumor mutations (TP53 mutations and RAS-pathway mutations) were not inherited in all 19 patients where analyzation was possible. These tumors have an aggressive clinical course. Multimodal combination therapy based on surgery, ifosfamide, carboplatin, and etoposide chemotherapy, and local radiotherapy leads to superior outcomes.

Combined effects of older age and HIV disease on changes in everyday functioning over one year.

Older age and HIV disease are independent risk factors for problems in many aspects of everyday functioning. However, less is known about how these risk factors may combine to influence everyday functioning over time. The current study examined the possible combined effects of age and HIV serostatus on change in everyday functioning over a 1-year period and its specific associations with changes in neurocognition. A repeated measures factorial design was employed. Participants included 77 older persons with HIV (PWH), 35 younger PWH, 44 older HIV-, and 27 younger HIV-adults who each completed baseline and follow-up visits approximately 14 months apart. Everyday functioning was assessed using a standardized self-report measure of activities of daily living (ADLs) at each visit. A comprehensive clinical battery assessed six domains of neurocognition. Raw scores on each neurocognitive measure were converted to sample-based z-scores, from which a global neurocognitive z-score was derived. Older PWH reported the poorest everyday functioning at baseline and follow-up visits at medium-to-large effect sizes. However, these ADL disruptions among older PWH were relatively stable over time, differing significantly from younger PWH who evidenced mild ADL improvements from baseline to follow-up. Within the entire sample, everyday functioning at baseline predicted neurocognitive performance at follow-up, but the reciprocal relationship was not significant. Older adults with HIV have high rates of ADL problems, which appear stable over 1 year, the trajectory of which differed from younger adults with HIV for whom mild improvements were observed. Importantly, the results also suggest that problems with ADLs may sometimes precede neurocognitive declines. Further examination of longitudinal data is needed to elucidate the long-term trajectory of neurocognitive and functional changes in older PWH to support early detection and proper management of clinical care.

The Emergence of Hepatitis C Virus Genotype 4d Among Human Immunodeficiency Virus-Infected Patients in Mexico City: A Molecular Epidemiological Study.

ABSTRACT: The recent detection of hepatitis C virus genotype 4 infection in human immunodeficiency virus-infected patients prompted performing molecular characterization of these isolates. All the Mexican isolates belonged to a subcluster within the 4d group and shared a common ancestor with a French isolate. The estimated timing of introduction in Mexico City was as recent as December 2015.

Living in honey: bacterial and fungal communities in honey of sympatric populations of Apis mellifera and the stingless bee Melipona beecheii, in Yucatan, Mexico.

Bacterial and fungal communities in the honey of sympatric populations of the bee species Apis mellifera and Melipona beecheii were profiled by amplicon sequencing of the 16S gene and the ITS of the ribosomal DNA. Results showed that the structure of the honey microbiota of these two bee species was very different from each other. Both the bacterial and fungal species in A. mellifera honey were more similar to those of A. mellifera honey reported for other parts of the world than to those in M. beecheii honey. Nevertheless, in both, the most abundant bacterial species belonged to the family Lactobacillaeae.

Factors influencing outcomes of older children with medulloblastoma over 15 years in Peru, a resource-limited setting.

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. While survival has improved in high-income countries (HIC), the outcomes for patients in low-to-middle-income countries (LMIC) are unclear. Therefore, we sought to determine the survival of children with medulloblastoma at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 1997 and 2013 in Peru. METHODS: Between 1997 and 2013, data from 103 children older than 3 years with medulloblastoma were analyzed. Fourteen patients were excluded. The patients were split into two distinct cohorts, 1997-2008 and 2009-2013, corresponding with chemotherapy regimen changes. Event-free (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method, whereas prognostic factors were determined by univariate analysis (log-rank test). RESULTS: Eighty-nine patients were included; median age was 8.1 years (range: 3-13.9 years). The 5-year OS was 62% (95% CI: 53%-74%), while EFS was 57% (95% CI: 48%-69%). The variables adversely affecting survival were anaplastic histology (compared to desmoplastic; OS: HR = 3.4, p = .03), metastasis (OS: HR = 3.5, p = .01; EFS: HR = 4.3, p = .004), delay in radiation therapy of 31-60 days (compared to ≤30 days; EFS: HR = 2.1, p = .04), and treatment 2009-2013 cohort (OS: HR = 2.2, p = .02; EFS: HR = 2.0, p = .03). CONCLUSIONS: Outcomes for medulloblastoma at INEN were low compared with HIC. Anaplastic subtype, metastasis at diagnosis, delay in radiation therapy, and treatment in the period 2009-2013 negatively affected the outcomes in our study. Multidisciplinary teamwork, timely delivery of treatment, and partnerships with loco-regional groups and colleagues in HIC is likely beneficial.

Robotic-assisted vesicovaginal fistula repair using a vaginal cuff flap.

INTRODUCTION AND HYPOTHESIS: Vesicovaginal fistula (VVF) is an abnormal communication between the bladder and the vagina. Complex fistulae include those after failed repair attempts, radiotherapy, measuring ≥ 2 cm, located in the trigone, or with concomitant ureteric strictures or fistulae. We aimed to describe a technique for the robotic repair of a complex VVF using a vaginal cuff flap. METHODS: A 56-year-old woman with a history of ovarian debulking surgery and radiotherapy underwent repair for VVF and rectovaginal fistula. In lithotomy, cystoscopy was performed for fistulous tract cannulation. Port placement, extensive adhesiolysis, and robot docking followed. The vaginal apex was dissected, the VVF excised, and the bladder closed. The rectum was separated from the posterior vaginal wall, the rectovaginal fistula excised, and the rectum closed. A vaginal cuff flap was harvested and interposed between the bladder and the vagina. RESULTS: Operative time was 9 h, estimated blood loss was 300 cc, and no intraoperative complications occurred. The patient was discharged on postoperative day 8. Further management included 37 sessions in a hyperbaric chamber and a transvesical endoluminal bladder closure 10 months after the initial surgery. Follow-up at 30 months shows no fistula recurrence. CONCLUSIONS: Vaginal cuff flaps represent a feasible interposition tissue in patients with hysterectomy for managing complex VVF in the case of omentum unavailability.

Over 55 years of critical power: Fact or artifact?

This report aims to generate an evidence-based debate of the Critical Power (CP), or its analogous Critical Speed (CS), concept. Race times of top Spanish runners were utilized to calculate CS based on three (1500-m to 5000-m; CS1.5-5km ) and four (1500-m to 10000-m; CS1.5-10km ) distance performances. Male running world records from 1000 to 5000-m (CS1-5km ), 1000 to 10,000-m (CS1-10km ), 1000-m to half marathon (CS1km-half marathon ), and 1000-m to marathon (CS1km-marathon ) distance races were also utilized for CS calculations. CS1.5-5km (19.62 km h-1 ) and CS1.5-10km (18.68 km h-1 ) were different (p < 0.01), but both approached the average race speed of the longest distance chosen in the model, and were remarkably homogeneous among subjects (97% ±1% and 98% ±1%, respectively). Similar results were obtained using the world records. CS values progressively declined, until reaching a CS1km-marathon value of 20.77 km h-1 (10% lower than CS1-5km ). Each CS value approached the average speed of the longest distance chosen in the model (96.4%-99.8%). A power function better fitted the speed-time relationship compared with the standardized hyperbolic function. However, the horizontal asymptote of a power function is zero. This better approaches the classical definition of CP: the power output that can be maintained almost indefinitely without exhaustion. Beyond any sophisticated mathematical calculation, CS corresponds to 95%-99% of the average speed of the longest distance chosen as an exercise trial. CP could be considered a mathematical artifact rather than an important endurance performance marker. In such a case, the consideration of CP as a physiological "gold-standard" should be reevaluated.