Search

Objetivo: El presente artículo presenta los resultados de un estudio que abordó la percepción de un grupo de profesores frente al Programa de Aceleración del Aprendizaje -en el marco de la pandemia- en una escuela rural de la zona norte de Colombia. Metodología: mediante una metodología cualitativa, a través de un diseño fenomenológico, en el que se analizaron 17 entrevistas. Resultados: los resultados permitieron establecer que los participantes tienen conocimiento sobre él programa, no obstante, evidencian particulares que indican dificultades en su desarrollo. Pese a que los participantes reconocen los criterios a tener en cuenta para llevar a cabo el programa, se determinó como un aspecto relevante la necesidad capacitación. Se evidenció que los participantes a lo largo de la pandemia no recibieron el seguimiento de los organismos gubernamentales. Las brechas digitales, que evidencian los estudiantes adheridos al programa, jugaron un papel importante en este desequilibrio.

Glioblastoma (GBM) is the most common primary brain cancer in adults where tumor cell heterogeneity and sex differences influence clinical outcomes. Here, we functionally characterize three male and three female patient-derived GBM cell lines, identify protumorigenic BTICs, and create novel male and female preclinical models of GBM. Cell lines were evaluated on the following features: proliferation, stemness, migration, tumorigenesis, clinical characteristics, and sensitivity to radiation, TMZ, rhTNFSF10 (rhTRAIL), and rhBMP4. All cell lines were classified as GBM according to epigenetic subtyping, were heterogenous and functionally distinct from one another, and re-capitulated features of the original patient tumor. In establishing male and female preclinical models, it was found that two male-derived GBM cell lines (QNS108 and QNS120) and one female-derived GBM cell line (QNS315) grew at a faster rate in female mice brains. One male-derived GBM cell line (QNS108) decreased survival in female mice in comparison with male mice. However, no survival differences were observed for mice injected with a female-derived cell line (QNS315). In summary, a panel of six GBM patient-derived cell lines were functionally characterized, and it was shown that BTIC lines can be used to construct sex-specific models with differential phenotypes for additional studies.

Early and accurate identification of cognitive and functional decline in bilingual Latino/a older adults with Alzheimer's disease and related dementias continues to be a substantial public health concern. This paper highlights the heterogeneity in the clinical expression of Alzheimer's disease among bilingual Latino/as, the clinical decisions leading to a culturally and linguistically congruent neuropsychological assessment, and the interdisciplinary, multi-setting partnerships needed to ensure a healthy longevity post-diagnosis for the patient, the caregiver, and the family. Psychologists play an important role in advocating for the best standard of care, as the patients and families endure the long journey of care with dignity and respect.

Objective Neurosurgical patients are at a higher risk of having a severe course of coronavirus disease 2019 (COVID-19). The objective of this study was to determine morbidity, hospital course, and mortality of neurosurgical patients during the coronavirus disease 2019 (COVID-19) pandemic in a multicenter health care system. Methods A retrospective observational study was conducted to identify all hospitalized neurosurgical patients positive for COVID-19 from March 11, 2020 to November 2, 2020 at Mayo Clinic and the Mayo Clinic Health System. Results Eleven hospitalized neurosurgical patients (0.68%) were positive for COVID-19. Four patients (36.6%) were men and 7 (63.3%) were women. The mean age was 65.7 years (range, 35–81 years). All patients had comorbidities. The mean length of stay was 13.4 days (range, 4–30 days). Seven patients had a central nervous system malignancy (4 metastases, 1 meningioma, 1 glioblastoma, and 1 schwannoma). Three patients presented with cerebrovascular complications, comprising 2 spontaneous intraparenchymal hemorrhages and 1 ischemic large-vessel stroke. One patient presented with an unstable traumatic spinal burst fracture. Four patients underwent neurosurgical/neuroendovascular interventions. Discharge disposition was to home in 5 patients, rehabilitation facility in 3, and hospice in 3. Five patients had died at follow-up, 3 within 30 days from COVID-19 complications and 2 from progression of their metastatic cancer. Conclusions COVID-19 is rare among the inpatient neurosurgical population. In all cases, patients had multiple comorbidities. All symptomatic patients from the respiratory standpoint had complications during their hospitalization. Deaths of 3 patients who died within 30 days of hospitalization were all related to COVID-19 complications. Neurosurgical procedures were performed only if deemed emergent.

Objectives:We investigated the impact of culturally relevant social, educational, and language factors on cognitive test performance among Spanish speakers living near the US–Mexico border.Methods:Participants included 254 healthy native Spanish speakers from the Neuropsychological Norms for the US–Mexico Border Region in Spanish (NP-NUMBRS) project (Age: M = 37.3, SD = 10.4; Education: M = 10.7, SD = 4.3; 59% Female). A comprehensive neuropsychological battery was administered in Spanish. Individual test scaled scores and T-scores (based on region-specific norms adjusted for age, education, and sex) were averaged to create Global Mean Scaled and T-scores. Measures of culturally relevant factors included a self-reported indicator of educational quality/access (proportion of education in Spanish-speaking country, quality of school/classroom setting, stopped attending school to work), childhood socioeconomic environment (parental education, proportion of time living in Spanish-speaking country, childhood socioeconomic and health status, access to basic resources, work as a child), and Spanish/English language use and fluency.Results:Several culturally relevant variables were significantly associated with unadjusted Global Scaled Scores in univariable analyses. When using demographically adjusted T-scores, fewer culturally relevant characteristics were significant. In multivariable analyses, being bilingual (p = .04) and working as a child for one’s own benefit compared to not working as a child (p = .006) were significantly associated with higher Global Mean T-score, accounting for 9% of variance.Conclusions:Demographically adjusted normative data provide a useful tool for the identification of brain dysfunction, as these account for much of the variance of sociocultural factors on cognitive test performance. Yet, certain culturally relevant variables still contributed to cognitive test performance above and beyond basic demographics, warranting further investigation.

Background The coronavirus disease identified in 2019 (COVID-19) pandemic changed neurosurgery protocols to provide ongoing care for patients while ensuring the safety of health care workers. In Brazil, the rapid spread of the disease led to new challenges in the health system. Neurooncology practice was one of the most affected by the pandemic due to restricted elective procedures and new triage protocols. We aim to characterize the impact of the pandemic on neurosurgery in Brazil. Methods We analyzed 112 different types of neurosurgical procedures, with special detail in 11 neurooncology procedures, listed in the Brazilian Hospital Information System records in the DATASUS database between February and July 2019 and the same period in 2020. Linear regression and paired t-test analyses were performed and considered statistically significant at P < 0.05. Results There was an overall decrease of 21.5% (28,858 cases) in all neurosurgical procedures, impacting patients needing elective procedures (−42.46%) more than emergency surgery (−5.93%). Neurooncology procedures decreased by 14.89%. Nonetheless, the mortality rate during hospitalization increased by 21.26%. Linear regression analysis in hospitalizations (Slope = 0.9912 ± 0.07431; CI [95%] = 0.8231−1.159) and total cost (Slope = 1.03 ± 0.03501; CI [95%] = 0.9511−1.109) in the 11 different types of neurooncology procedures showed a P < 0.0001. The mean cost per type of procedure showed an 11.59% increase (P = 0.0172) between 2019 and 2020. Conclusions The COVID-19 pandemic has increased mortality, decreased hospitalizations, and therefore decreased overall costs, despite increased costs per procedure for a variety of neurosurgical procedures. Our study serves as a stark example of the effect of the pandemic on neurosurgical care in settings of limited resources and access to care.

Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults with a median overall survival of only 14.6 months despite aggressive treatment. While immunotherapy has been successful in other cancers, its benefit has been proven elusive in GBM, mainly due to a markedly immunosuppressive tumor microenvironment. SARS-CoV-2 has been associated with the development of a pronounced central nervous system (CNS) inflammatory response when infecting different cells including astrocytes, endothelial cells, and microglia. While SARS-CoV2 entry factors have been described in different tissues, their presence and implication on GBM aggressiveness or microenvironment has not been studied on appropriate preclinical models.We evaluated the presence of crucial SARS-CoV-2 entry factors: ACE2, TMPRSS2, and NRP1 in matched surgically-derived GBM tissue, cells lines, and organoids; as well as in human brain derived specimens using immunohistochemistry, confocal pixel line intensity quantification, and transcriptome analysis.We show that patient derived-GBM tissue and cell cultures express SARS-CoV2 entry factors, being NRP1 the most crucial facilitator of SARS-CoV-2 infection in GBM. Moreover, we demonstrate that, receptor expression remains present in our GBM organoids, making them an adequate model to study the effect of this virus in GBM for the potential development of viral therapies in the future.Our findings suggest that the SARS-CoV-2 virus entry factors are expressed in primary tissues and organoid models and could be potentially utilized to study the susceptibility of GBM to this virus to target or modulate the tumor microenviroment.

Chordoma is a rare but devastating tumor that arises in the cranial skull base or spine. There are currently no US Food and Drug Administration-approved targeted therapies for chordoma, and little understanding of whether using more than one therapy has benefit over monotherapy. The objective of this study was to systematically review the current status of clinical trials completed for patients with chordoma to determine if multimodal therapy offers a benefit in progression-free survival over monomodal therapy. We performed a systematic review of the literature according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to review the available clinical trials of targeted therapy for chordoma. We compiled the clinical data to determine if there is a benefit of multimodal therapy over monotherapy. Our search resulted in 11 clinical trials including 270 patients with advanced chordoma who were treated with targeted therapies. The most commonly employed targeted therapies acted within the following pathways: platelet-derived growth factor receptor (187 patients), vascular endothelial growth factor (66 patients), and mammalian target of rapamycin (43 patients). Reported progression-free survival for included studies ranged from 2.5 to 58 months, with the longest progression-free survival in a trial that included a platelet-derived growth factor receptor inhibitor, nilotinib, and concurrent radiotherapy (58.2 months). There was a higher range of progression-free survival for trials treating patients with multimodal therapy (10.2–14 months vs 2.5–9.2 months, except for a monotherapy trial published in 2020 with a progression-free survival of 18 months), and those published in 2018 or later (14–58.2 months vs 2.5–10.2 months). Only 23% of patients with chordoma in published clinical trials have been treated with multimodal therapy. Progression-free survival may be enhanced by the use of targeted therapy with concurrent radiotherapy, use of multimodal therapy, and use of newer targeted therapy. Future clinical trials should consider use of concurrent radiotherapy and multimodal therapy for patients with advanced chordoma.

OBJECTIVE The vertebral column is the most common site for skeletal metastasis, often leading to debilitating pain and weakness. Metastatic cancer has unique genetic drivers that potentiate tumorigenicity. There is an unmet need for novel targeted therapy in patients with spinal metastatic disease. METHODS The authors assessed the effect of verteporfin-induced yes-associated protein (YAP) inhibition on spine metastatic cell tumorigenicity and radiation sensitivity in vitro. Animal studies used a subcutaneous xenograft mouse model to assess the use of systemic intraperitoneal verteporfin (IP-VP) and intratumoral verteporfin microparticles (IT-VP) to inhibit the tumorigenicity of lung and breast spinal metastatic tumors from primary patient-derived tissue. RESULTS Verteporfin led to a dose-dependent decrease in migration, clonogenicity, and cell viability via inhibition of YAP and downstream effectors cyclin D1, CTGF, TOP2A, ANDRD1, MCL-1, FOSL2, KIF14, and KIF23. This was confirmed with knockdown of YAP. Verteporfin has an additive response when combined with radiation, and knockdown of YAP rendered cells more sensitive to radiation. The addition of verteporfin to YAP knockdown cells did not significantly alter migration, clonogenicity, or cell viability. IP-VP and IT-VP led to diminished tumor growth (p < 0.0001), especially when combined with radiation (p < 0.0001). Tissue analysis revealed diminished expression of YAP (p < 0.0001), MCL-1 (p < 0.0001), and Ki-67 (p < 0.0001) in tissue from verteporfin-treated tumors compared with vehicle-treated tumors. CONCLUSIONS This is the first study to demonstrate that verteporfin-mediated inhibition of YAP leads to diminished tumorigenicity in lung and breast spinal metastatic cancer cells. Targeting of YAP with verteporfin offers promising results that could be translated to human clinical trials.

OBJECTIVE We generated demographically adjusted norms for the Brief Visuospatial Memory Test-revised (BVMT-R) and the Hopkins Verbal Learning Test-revised (HVLT-R) for Spanish-speakers from the U.S.-Mexico border region as part of a larger normative project. Methods: Healthy native Spanish-speakers (n = 203; Age: 19-60 years; Education: 0-20 years, 59% women) living in Arizona (n = 63) and California (n = 140) completed the BVMT-R and the HVLT-R as part of the larger Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) project. Raw scores were converted to T-scores utilizing fractional polynomial equations, which considered linear and non-linear effects of demographic variables (age, education, sex). To demonstrate the benefit of employing our population-specific norms, we computed the proportion of our participants whose test performance fell below one standard deviation (T-score < 40) when applying published norms from non-Hispanic English-speakers, compared to the base rate derived from the new normative sample. Results: The resulting demographically adjusted T-scores showed the expected psychometric properties and corrected the misclassification in rates of impairment that were obtained when applying norms based on the English-speaking sample. Unexpectedly, participants in Arizona obtained slightly lower HVLT-R T-scores than those in California. This site effect was not explained by available sociodemographic or language factors. Supplementary formulas were computed adjusting for site in addition to demographics. Conclusions: These updated norms improve accuracy in identification of learning and memory impairment among Spanish-speaking adults living in the U.S.-Mexico border region. It will be important to generate additional data for elders, as the present norms are only applicable to adults age 60 and younger.

OBJECTIVE: We aimed to investigate whether or not demographically-corrected test scores derived from the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) would be less accurate if applied to Spanish-speakers with various degrees of English fluency. SPANISH-ENGLISH METHOD: One hundred and seventy primarily Spanish-speaking adults from the NP-NUMBRS project completed a comprehensive neuropsychological test battery. T-scores adjusted for age, education, and sex (but not degree of bilingualism), were derived for each test utilizing population-specific normative data. English fluency was assessed via the Controlled Oral Word Association Test in English (F-A-S), and Spanish fluency with “P-M-R,” and degree of relative English fluency was calculated as the ratio of English language words over total words produced in both languages. Effects of degree of bilingualism on the NUMBRS battery test scores (raw scores and T-scores) were examined via Pearson’s product moment correlation coefficients, and language groups (Spanish dominant vs. relative bilingual) were compared on demographically adjusted T-scores via independent samples t-tests. RESULTS: Higher Spanish-English bilingualism was associated with higher education and SES, and was significantly associated with higher raw scores on all tests, but only associated with higher T-scores on a limited number of tests (i.e., WAIS-III Digit Symbol, Symbol Search, Letter-Number Sequencing and Trails B). CONCLUSION: Degree of Spanish-English bilingualism generally did not account for significant variance in the normed tests beyond the standard demographic adjustments on most tests. Overall, the normative adjustments provided by the NP-NUMBRS project appear applicable to native Spanish speakers from the U.S.-Mexico border region with various degrees of Spanish-English bilingualism.

Background The primary goal of brain tumor surgery is maximal safe resection while avoiding iatrogenic injury. As surgical technology increases, it is becoming more possible to resect these lesions using minimally invasive approaches. While keyhole surgeries are being advocated, the lower limit of these approaches is unclear. Bur hole–based approaches may represent a standardized minimally invasive approach. The exoscope may provide increased visualization over standard microscopic visualization, making this approach possible. This approach has yet to be described strictly for intra-axial brain tumors.Material and Methods All patients who underwent a bur hole–based surgery of an intra-axial tumor with exoscopic visualization by the senior author from January 2018 to December 2019 were prospectively identified and patient information and outcomes were collected.Results Fifteen consecutive patients underwent surgical resection of an intrinsic brain tumor using a bur hole–based approach with exoscopic visualization. The average ± standard deviation age was 57.9 ± 24.2 years. The pathology was a metastatic brain tumor in eight patients (53%), low-grade glioma in four patients (27%), and high-grade glioma in three patients (20%). The average percent resection was 100 ± 1%, where 14 (93%) underwent gross total resection. Following surgery, the median (interquartile range) Karnofsky performance scale (KPS) score was 90 (90–90), where 11 (73%) and four patients (27%) had improved and stable KPS, respectively. Zero patients had complications. The average length of stay following surgery was 1.4 ± 0.5 days, where nine patients (60%) were discharged on postoperative day 1.Conclusion This study shows that intra-axial tumors can be resected through a bur hole–based approach with exoscopic visualization with extensive resection, minimal morbidity, and early discharge rates.

OBJECTIVE: Despite the wide use of the Trail Making Test (TMT), there is a lack of normative data for Spanish-speakers living in the United States (US). Here we describe the development of regional norms for the TMT for native Spanish-speakers residing in the Southwest Mexico-Border Region of the US. METHOD: Participants were 252 healthy native Spanish-speakers, 58% women, between the ages of 19 and 60, and ranging in education from 0–20 years, recruited in San Diego, CA and Tucson, AZ. All completed the TMT in Spanish along with a comprehensive neuropsychological test battery as part of their participation in the Neuropsychological Norms for the US-Mexico Border Region in Spanish (NP-NUMBRS) project. Univariable and interactive effects of demographics on test performance were examined. T-scores were calculated using fractional polynomial equations to account for linear and any non-linear effects of age, education, and sex. RESULTS: Older age and lower education were associated with worse scores on both TMT A and B. The newly derived T-scores showed no association with demographic variables and displayed the expected 16% rates of impairment using a −1 SD cut point based on a normal distribution. By comparison, published norms for English-speaking non-Hispanic Whites applied to the current data yielded significantly higher impairment for both TMT A and B with more comparable rates using non-Hispanic African Americans norms. CONCLUSIONS: Population-specific, demographically adjusted regional norms improve the utility and diagnostic accuracy of the TMT for use with native Spanish-speakers in the US-Mexico Border region.

OBJECTIVE: This paper summarizes the findings of the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) Project and offers a roadmap for future research. METHODS: The NP-NUMBRS project represents the largest and most comprehensive co-normed neuropsychological battery to date for native Spanish-speaking healthy adults from the U.S. (California/Arizona)-Mexico borderland region (N = 254; ages 19–60 years). These norms provide demographic adjustments for tests across numerous domains (i.e., verbal fluency, processing speed, attention/working memory, executive function, episodic memory [learning and delayed recall], visuospatial, and fine motor skills). CONCLUSIONS: This project: 1) shows that the NP-NUMBRS norms consistently outperformed previously published norms for English-speaking non-Hispanic (White and African-American) adults in identifying impairment; 2) explores the role of Spanish-English bilingualism in test performance; and 3) provides support for the diagnostic validity of these norms in detecting HIV-associated neurocognitive impairment. Study limitations include the limited assessment of sociocultural variables and generalizability (e.g., other Latina/o populations, age limit [19–60 years]). Future research is needed to: 1) investigate these norms with U.S.-dwelling Spanish-speakers of non-Mexican heritage and other clinical subpopulations; 2) expand coverage of cognitive domains (e.g. language, visuospatial); 3) develop large normative datasets for children and older Latina/o populations; 4) examine how sociocultural factors impact performance (e.g., bilingualism, acculturation); 5) investigate these norms’ diagnostic and ecological validity; and 6) develop norms for neurocognitive change across time. It is hoped that the NP-NUMBRS norms will aid researchers and clinicians working with U.S.-dwelling Spanish-speakers from the U.S.-Mexico borderland to conduct research and evidence-based neuropsychological evaluations in a more culturally responsive and ethical manner.

Background Awake craniotomy (AC) with brain mapping has been successfully used for the resection of lesions located in or near eloquent areas of the brain. The selection process includes a thorough presurgical evaluation to determine candidates suitable for the procedure. Psychiatric disorders including post-traumatic stress disorder (PTSD) are considered potential contraindications for this type of surgery because these patients may be less cooperative to tolerate AC. Here we present the management of a patient with PTSD who underwent an AC using a multidisciplinary team for removal of a dominant hemisphere low-grade insular glioma with speech, motor, and cognitive mapping. Case Description A 34-year-old right-handed male military veteran with a previous history of PTSD was scheduled for a left AC for resection of a low-grade insular glioma. He underwent preoperative neurocognitive assessment with a neuropsychologist and clinic visit with a neurosurgeon to characterize his PTSD and potential triggers, explain the procedure in a stepwise fashion, and address any concerns. The intraoperative environment was modified to minimize triggering stimuli, and an asleep-awake-asleep anesthetic protocol was followed. The patient tolerated the procedure well without any postoperative neurologic deficits including cognitive deficits. At 1-month follow-up, he denied any worsening of his PTSD symptoms and recalls the AC as a positive experience. Conclusions With a multidisciplinary team, adequate preoperative education, detailed clinical interview to identify triggers, and a controlled intraoperative environment, awake surgery can be carried out safely in a patient with PTSD.

OBJECTIVE: The present introduction to the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) project aims to provide an overview of the conceptual framework and rationale that guided the development of this project. METHODS: We describe important aspects of our conceptual framework, which was guided by some of the main purposes of neuropsychological testing, including the identification of underlying brain dysfunction, and the characterization of cognitive strengths and weakness relevant to everyday functioning. We also provide our rationale for focusing this norm development project on Spanish-speakers in the United States, and provide an outline of the articles included in this Special Issue focused on the NP-NUMBRS project. CONCLUSIONS: The data presented in this Special Issue represent an important tool for clinicians and researchers working in the neuropsychological assessment of Spanish-speakers in the United States.

Patients with brain and spine tumors are at high risk of presenting cancer-related complications at disease presentation or during active treatment and are usually related to the type and location of the lesion. Here, we discuss presentation and management of the most common emergencies affecting patients with central nervous system neoplastic lesions.Tumor-related emergencies encompass complications in patients with central nervous system neoplasms, as well as neurologic complications in patients with systemic malignancies. Brain tumor patients are at high risk of developing multiple complications such as intracranial hypertension, brain herniation, intracranial bleeding, spinal cord compression, and others. Neuro-oncologic emergencies require immediate attention and multi-disciplinary care. These emergent situations usually need rapid decision-making and management on an inpatient basis.

A small population of self-renewing stem cells initiate tumors and maintain therapeutic resistance in glioblastoma (GBM). Given the limited treatment options and dismal prognosis for this disease, there is urgent need to identify drivers of stem cells that could be druggable targets. Previous work showed that the endosomal pH regulator NHE9 is upregulated in GBM and correlates with worse survival prognosis. Here, we probed for aberrant signaling pathways in patient-derived GBM cells and found that NHE9 increases cell surface expression and phosphorylation of multiple receptor tyrosine kinases (RTKs) by promoting their escape from lysosomal degradation. Downstream of NHE9-mediated receptor activation, oncogenic signaling pathways converged on the JAK2-STAT3 transduction axis to induce pluripotency genes Oct4 and Nanog and suppress markers of glial differentiation. We used both genetic and chemical approaches to query the role of endosomal pH in GBM phenotypes. Loss-of-function mutations in NHE9 that failed to alkalinize endosomal lumen did not increase self-renewal capacity of gliomaspheres in vitro. However, monensin, a chemical mimetic of Na+/H+ exchanger activity, and the H+ pump inhibitor bafilomycin bypassed NHE9 to directly alkalinize the endosomal lumen resulting in stabilization of RTKs and induction of Oct4 and Nanog. Using orthotopic models of primary GBM cells we found that NHE9 increased tumor initiation in vivo. We propose that NHE9 initiates inside-out signaling from the endosomal lumen, distinct from the established effects of cytosolic and extracellular pH on tumorigenesis. Endosomal pH may be an attractive therapeutic target that diminishes stemness in GBM, agnostic of specific receptor subtype.

A small population of self-renewing stem cells initiate tumors and maintain therapeutic resistance in glioblastoma. Given the limited treatment options and dismal prognosis for this disease there is urgent need to identify drivers of stem cells that could be druggable targets. Previous work showed that the endosomal pH regulator NHE9 is upregulated in glioblastoma and correlates with worse survival prognosis. Here, we probed for aberrant signaling pathways in patient-derived glioblastoma cells and found that NHE9 increases cell surface expression and phosphorylation of multiple receptor tyrosine kinases by promoting their escape from lysosomal degradation. Downstream of NHE9-mediated receptor activation, oncogenic signaling pathways converged on the JAK2-STAT3 transduction axis to induce pluripotency genes Oct4 and Nanog and suppress markers of glial differentiation. We used both genetic and chemical approaches to query the role of endosomal pH in glioblastoma phenotypes. Loss-of-function mutations in NHE9 that failed to alkalinize endosomal lumen did not increase self-renewal capacity of gliomaspheres in vitro. However, monensin, a chemical mimetic of Na+/H+ exchanger activity, and the H+ pump inhibitor bafilomycin bypassed NHE9 to directly alkalinize the endosomal lumen resulting in stabilization of receptor tyrosine kinases and induction of Oct4 and Nanog. Using orthotopic models of primary glioblastoma cells we found that NHE9 increased tumor initiation in vivo. We propose that NHE9 initiates inside-out signaling from the endosomal lumen, distinct from the established effects of cytoplasmic and extracellular pH on tumorigenesis. Endosomal pH may be an attractive therapeutic target that diminishes stemness in glioblastoma, agnostic of specific receptor subtype.SignificanceA well-known hallmark of cancer is excessive acidification of tumor microenvironment, caused by upregulation of Na+/H+ exchanger activity on the cancer cell membrane. However, the role of organellar pH in tumor biology has not been established. This study identifies a mechanistic link between upregulation of the endosomal Na+/H+ exchanger NHE9 and stemness properties in glioblastoma, the most malignant and common brain tumor in adults. By increasing pH of the recycling endosome, NHE9 exerts a broad effect on post-translational stability and activation of multiple receptor tyrosine kinases, leading to increased stem cell-like properties of self-renewal and tumor initiation in glioblastoma models. Our findings suggest that targeting NHE9 or endosomal pH could be an effective strategy for receptor agnostic glioblastoma treatment.

Introduction/Purpose: There is a general lack of consensus onboth the anatomic definition and function of Broca’s area. Given the belief that this region plays a critical role in expressive language, resective surgery is often avoided topreserve function. However, the putative role of Broca’s area in speech production has been recently challenged.The current study aims to investigatethe feasibilityof glioma resection and neurological outcomes in “Broca’s area” in 15 patients.Methods: We report a feasibility study describing the resection of gliomas within the IFG. Awake brain surgery for resection with mapping and intraoperative neuropsychological evaluation was carried out in all individuals. Results: All included patientshad tumors located in traditional “Broca’s area” and eight patients (53.33%) had tumors that additionally extendedinto the insula and subinsular regions. During stimulation, positive speech-language sites within the IFG were identified in ten patients. Two patients (13.33%) experienced a declinein naming during intraoperative cognitive monitoring and thirteen (86.66%) had a stable performance throughout surgery. With all patients had recovery of language functions at a two-week follow up. Extent of resection was stratified in anatomical regions within the IFG, being the pOr the area with the greatest EOR (97.4%), followed by the pT (84.1%), pOp (83.8%), and vPMC (80%).Conclusion: The belief that Broca’s area is not safe to resect is challenged. Adequate mapping and careful patient selection allow maximum safe resection of tumors located in thetraditional “Broca’s area”,with low risk of postoperative morbidity.

Acquired Reactive Perforating Collagenosis (ARPC) is a rare condition that belongs to a larger group of diseases: The Perforating Dermatoses (1). ARPC is usually refractory to treatment; thus, many treatments have been reported, including topical and systemic corticosteroids, retinoids, doxycycline, allopurinol and narrowband ultraviolet B (NBUVB) phototherapy (1). The aim of this manuscript is to present a case successfully treated with NBUVB phototherapy after 96 sessions and describe the treatment protocol used, as well as the utilized in currently reports as well.

OBJECTIVE: The present study aimed to develop norms applicable to Spanish-speakers living in the US- Mexico border region for the Halstead Category Test (HCT), a test of executive function. METHODS: Healthy native Spanish-speakers (N=252; Age: range 19-60 years, M=37.28, SD=10.24; Education: range 0-20 years; M=10.65, SD=4.33; 58.33% female) living in the US-Mexico border region of California and Arizona completed the HCT as part of a comprehensive neuropsychological test battery. The univariable and interactive effects of demographic variables on HCT raw scores were examined. Total scores were normed using fractional polynomial equations, which adjusted for linear and nonlinear effects of age, education, and gender. T-scores were also computed for HCT scores of the current Spanish-speaking normative sample using published, demographically-adjusted norms for English-speaking non-Hispanic Whites and Blacks. Impairment rates (T-Scores

Background: Obesity is common among children and teenagers and is associated with cardiometabolic risk factors in the adult age. The objective of this paper was to evaluate the association between the percentage of body fat and cardiometabolic risk factors in children and adolescents in the city of Bucaramanga, Colombia. Material and Methods: About 494 children and adolescents aged 10–20 years were studied. Laboratory tests were made for analyzing cardiovascular risk factors and anthropometric measurements. Percentage body fat was determined with Slaughter equation. Lineal regression analyses were conducted to evaluate the association between cardiometabolic risk factors and the percentage body fat. Results: Prevalence of percentage body fat (>26%) was 46.1%. Variables associated with percentage body fat were HOMA-IR – insulin resistance, HDL, LDL, triglycerides, and total cholesterol levels, and high blood pressure. Conclusions: Increase in percentage body fat is significantly associated with cardiometabolic risk factors in children and adolescents in Bucaramanga. Early identification and intervention of this population at risk is fundamental. Keywords: Skinfold thickness, Risk factors, Cardiovascular disease, Insulin resistance