Crisis en urgencias: una vista a las características clínicas y terapéuticas a través de 122 pacientes / Seizures in the emergency service: the clinical and therapeutic characteristics of 122 patients

Introducción Las crisis epilépticas son un motivo frecuente de consulta en los servicios de urgencias hospitalarias. Llegar al diagnóstico correcto puede ser complejo, y es fundamental decidir cuándo y qué medicamento anticrisis (MAC) pautar. Nuestro objetivo es detallar las características de los pacientes que consultaron por este motivo en un hospital mediano. Pacientes y métodos Estudio observacional retrospectivo de todos los pacientes mayores de edad que consultaron en el servicio de urgencias del Hospital Universitario Lucus Augusti entre enero de 2022 y enero de 2023 con diagnóstico al alta de crisis epiléptica. Se registraron variables demográficas, los antecedentes, si era una primera crisis, el número de éstas, si se inició un MAC y cuál, el diagnóstico, qué pruebas se realizaron y si se interconsultó con la guardia de neurología. Resultados Se diagnosticó a 122 pacientes de crisis epilépticas en urgencias. El 50,8% eran mujeres. La media de edad fue de 69,8 años. Se solicitó valoración por neurología en un 47,6%. El 50,8% presentó una primera crisis. No se llegó al diagnóstico en un 46% de los casos, de los cuales sólo 10 fueron valorados por neurología. La etiología más frecuente fue la vascular. Se realizó un electroencefalograma en un 41,8%. El levetiracetam fue prácticamente el único fármaco utilizado cuando no se consultó con neurología. Conclusiones La valoración precoz de los pacientes con una primera crisis en urgencias por un especialista en neurología es determinante para el diagnóstico de epilepsia. Cuando no se interconsulta, casi siempre se pauta el mismo MAC. (AU)

INTRODUCTION Epileptic seizures are a common cause of admission in emergency services at hospitals. Performing the correct diagnosis can be difficult, and deciding when and which anti-seizure medication (ASM) to prescribe is critical. Our objective is to detail the characteristics of patients treated in a medium-sized hospital for this reason. PATIENTS AND METHODS A retrospective observational study was performed, including all the adult patients treated by the emergency service of the Lucus Augusti University Hospital between January 2022 and January 2023 with a diagnosis of epileptic seizure on discharge. The study recorded their demographic variables, history, whether it was their first seizure, the number of seizures, whether an anti-seizure medication was administered and which one, the diagnosis, the tests performed, and whether the patient was referred to the neurology service. RESULTS A total of 122 patients were diagnosed with epileptic seizures in the emergency service. 50.8% of the patients were women. The mean age was 69.8 years. Neurological assessment was requested for 47.6%. 50.8% presented their first seizure. No diagnosis was performed in 46% of the cases, of which only 10 were evaluated by the neurology service. The most common etiology was vascular. An electroencephalogram was performed on 41.8%. Levetiracetam was practically the only drug administered when the neurology department was not consulted. CONCLUSIONS Early evaluation of patients with their first seizure in the emergency service by a neurological specialist is crucial for the diagnosis of epilepsy. The same anti-seizure medication is almost always prescribed when no cross-consultation takes place. (AU)

Bacterial diversity using metagenomics of 16s rDNA in water kefir, an innovative source of probiotics for bee nutrition.

Water kefir is a sparkling, slightly acidic fermented beverage made from sugar, water, and water kefir grains, which are a mixture of yeast and bacteria. These grains produce a variety of fermentation compounds such as lactic acid, acetaldehyde, acetoin, ethanol and carbon dioxide. In this study, a high-throughput sequencing technique was used to characterize the bacterial composition of the original water kefir from which potential probiotics were obtained. We studied the bacterial diversity of both water kefir grains and beverages. DNA was extracted from three replicate samples of both grains and beverages using the Powerlyzer Microbial Kit. The hypervariable V1-V2 region of the bacterial 16S ribosomal RNA gene was amplified to prepare six DNA libraries. Between 1.4M and 2.4M base-pairs were sequenced for the library. In total, 28721971 raw reads were obtained from all the samples. Estimated species richness was higher in kefir beverage samples compared to grain samples. Moreover, a higher level of microbial alpha diversity was observed in the beverage samples. Particularly, the predominant bacteria in beverages were Anaerocolumna and Ralstonia, while in grains Liquorilactobacillus dominated, with lower levels of Leuconostoc and Oenococcus. Although the bacterial diversity in kefir grains was low because only three genera were the most represented, all of them are LAB bacteria with the potential to serve as probiotics in the artificial feeding of bees.

Oleuropein-driven reprogramming of the myeloid cell compartment to sensitise tumours to PD-1/PD-L1 blockade strategies.

BACKGROUND: Previous studies have shown that functional systemic immunity is required for the efficacy of PD-1/PD-L1 blockade immunotherapies in cancer. Hence, systemic reprogramming of immunosuppressive dysfunctional myeloid cells could overcome resistance to cancer immunotherapy. METHODS: Reprogramming of tumour-associated myeloid cells with oleuropein was studied by quantitative differential proteomics, phenotypic and functional assays in mice and lung cancer patients. Combinations of oleuropein and two different delivery methods of anti-PD-1 antibodies were tested in colorectal cancer tumour models and in immunotherapy-resistant lung cancer models. RESULTS: Oleuropein treatment reprogrammed monocytic and granulocytic myeloid-derived suppressor cells, and tumour-associated macrophages towards differentiation of immunostimulatory subsets. Oleuropein regulated major differentiation programmes associated to immune modulation in myeloid cells, which potentiated T cell responses and PD-1 blockade. PD-1 antibodies were delivered by two different strategies, either systemically or expressed within tumours using a self-amplifying RNA vector. Combination anti-PD-1 therapies with oleuropein increased tumour infiltration by immunostimulatory dendritic cells in draining lymph nodes, leading to systemic antitumour T cell responses. Potent therapeutic activities were achieved in colon cancer and lung cancer models resistant to immunotherapies, even leading to complete tumour regression. DISCUSSION: Oleuropein significantly improves the outcome of PD-1/PD-L1 blockade immunotherapy strategies by reprogramming myeloid cells.

Racial and Ethnic Disparities in Excess All-Cause Mortality in the First Year of the COVID-19 Pandemic.

Research on the COVID-19 pandemic in the United States has consistently found disproportionately high mortality among ethnoracial minorities, but reports differ with respect to the magnitude of mortality disparities and reach different conclusions regarding which groups were most impacted. We suggest that these variations stem from differences in the temporal scope of the mortality data used and difficulties inherent in measuring race and ethnicity. To circumvent these issues, we link Social Security Administration death records for 2010 through 2021 to decennial census and American Community Survey race and ethnicity responses. We use these linked data to estimate excess all-cause mortality for age-, sex-, race-, and ethnicity-specific subgroups and examine ethnoracial variation in excess mortality across states and over the course of the pandemic's first year. Results show that non-Hispanic American Indians and Alaska Natives experienced the highest excess mortality of any ethnoracial group in the first year of the pandemic, followed by Hispanics and non-Hispanic Blacks. Spatiotemporal and age-specific ethnoracial disparities suggest that the socioeconomic determinants driving health disparities prior to the pandemic were amplified and expressed in new ways in the pandemic's first year to disproportionately concentrate excess mortality among racial and ethnic minorities.

Probiotics and in-hive fermentation as a source of beneficial microbes to support the gut microbial health of honey bees.

Managed populations of honey bees (Apis mellifera Linnaeus; Hymenoptera: Apidae) are regularly exposed to infectious diseases. Good hive management including the occasional application of antibiotics can help mitigate infectious outbreaks, but new beekeeping tools and techniques that bolster immunity and help control disease transmission are welcome. In this review, we focus on the applications of beneficial microbes for disease management as well as to support hive health and sustainability within the apicultural industry. We draw attention to the latest advances in probiotic approaches as well as the integration of fermented foods (such as water kefir) with disease-fighting properties that might ultimately be delivered to hives as an alternative or partial antidote to antibiotics. There is substantial evidence from in vitro laboratory studies that suggest beneficial microbes could be an effective method for improving disease resistance in honey bees. However, colony level evidence is lacking and there is urgent need for further validation via controlled field trials experimentally designed to test defined microbial compositions against specific diseases of interest.

Plasma fractalkine contributes to systemic myeloid diversity and PD-L1/PD-1 blockade in lung cancer.

Recent studies highlight the importance of baseline functional immunity for immune checkpoint blockade therapies. High-dimensional systemic immune profiling is performed in a cohort of non-small-cell lung cancer patients undergoing PD-L1/PD-1 blockade immunotherapy. Responders show high baseline myeloid phenotypic diversity in peripheral blood. To quantify it, we define a diversity index as a potential biomarker of response. This parameter correlates with elevated activated monocytic cells and decreased granulocytic phenotypes. High-throughput profiling of soluble factors in plasma identifies fractalkine (FKN), a chemokine involved in immune chemotaxis and adhesion, as a biomarker of response to immunotherapy that also correlates with myeloid cell diversity in human patients and murine models. Secreted FKN inhibits lung adenocarcinoma growth in vivo through a prominent contribution of systemic effector NK cells and increased tumor immune infiltration. FKN sensitizes murine lung cancer models refractory to anti-PD-1 treatment to immune checkpoint blockade immunotherapy. Importantly, recombinant FKN and tumor-expressed FKN are efficacious in delaying tumor growth in vivo locally and systemically, indicating a potential therapeutic use of FKN in combination with immunotherapy.

Microbiological and Chemical characterization of water kefir: An innovative source of potential probiotics for bee nutrition / Caracterización microbiológica y química del kéfir de agua: una fuente innovadora de potenciales probióticos para la nutrición de las abejas

Abstract We evaluated the microbial composition of water kefir grains and beverage overthe course of one year to determine whether the number and type of microorganisms changedover the time. Bacteria and yeast colonies with different morphologies were isolated fromwater kefir and their antimicrobial activity was evaluated against Paenibacillus larvae andAscosphaera apis. A chemical characterization of kefir was also carried out. Our results con-firmed that bacteria and yeasts were more numerous in kefir grains compared with those in thebeverage. The counts of microorganisms declined, although an important microbial community was still present in kefir after the long storage period. Eleven strains which inhibited bee pathogens were isolated from kefir. Genotypic results demonstrated that these isolates included Lentilactobacillus hilgardii, Lentilactobacillus buchneri and Saccharomyces cerevisiae. Thus, water kefir may be an innovative source of potential probiotic strains for bee nutrition in order to control honeybee diseases.

Resumen Evaluamos la composición microbiana del kéfir de agua durante un ano para determinar si la cantidad y el tipo de microorganismos cambiaban con el tiempo. Se aislaron colonias de bacterias y de levaduras con diferentes morfologías, y su actividad antimicrobiana se evaluó frente a Paenibacillus larvaey Ascosphaeraapis. También se realizó una caracterización química del kéfir. Nuestros resultados confirmaron que las bacterias y las levaduras eran más numerosas en los gránulos de kéfir en comparación con la parte líquida. Los recuentos de microorganismos disminuyeron, aunque una cantidad igualmente importante se encontró en el kéfir después de un año. Se aislaron del kéfir once cepas que inhibieron los mencionados patógenos de abejas. Los resultados genotípicos demostraron que estos aislamientos eran Lentilactobacillus hilgardii, Lentilactobacillus buchneri y Saccharomyces cerevisiae. Por lo tanto, el kéfir de agua podría ser una fuente innovadora de potenciales cepas probióticas para contribuir a la nutrición y sanidad de las abejas.

Microbiological and chemical characterization of water kefir: An innovative source of potential probiotics for bee nutrition.

We evaluated the microbial composition of water kefir grains and beverage over the course of one year to determine whether the number and type of microorganisms changed over the time. Bacteria and yeast colonies with different morphologies were isolated from water kefir and their antimicrobial activity was evaluated against Paenibacillus larvae and Ascosphaera apis. A chemical characterization of kefir was also carried out. Our results confirmed that bacteria and yeasts were more numerous in kefir grains compared with those in the beverage. The counts of microorganisms declined, although an important microbial community was still present in kefir after the long storage period. Eleven strains which inhibited bee pathogens were isolated from kefir. Genotypic results demonstrated that these isolates included Lentilactobacillus hilgardii, Lentilactobacillus buchneri and Saccharomyces cerevisiae. Thus, water kefir may be an innovative source of potential probiotic strains for bee nutrition in order to control honeybee diseases.

Risk factors for head and neck cancer in more and less developed countries: Analysis from the INHANCE consortium.

OBJECTIVE: We analyzed the pooled case-control data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium to compare cigarette smoking and alcohol consumption risk factors for head and neck cancer between less developed and more developed countries. SUBJECTS AND METHODS: The location of each study was categorized as either a less developed or more developed country. We compared the risk of overall head and neck cancer and cancer of specific anatomic subsites associated with cigarette smoking and alcohol consumption. Additionally, age and sex distribution between categories was compared. RESULTS: The odds ratios for head and neck cancer sites associated with smoking duration differed between less developed and more developed countries. Smoking greater than 20 years conferred a higher risk for oral cavity and laryngeal cancer in more developed countries, whereas the risk was greater for oropharynx and hypopharynx cancer in less developed countries. Alcohol consumed for more than 20 years conferred a higher risk for oropharynx, hypopharynx, and larynx cancer in less developed countries. The proportion of cases that were young (<45 years) or female differed by country type for some HNC subsites. CONCLUSION: These findings suggest the degree of industrialization and economic development affects the relationship between smoking and alcohol with head and neck cancer.

Immune Profiling Uncovers Memory T-Cell Responses with a Th17 Signature in Cancer Patients with Previous SARS-CoV-2 Infection Followed by mRNA Vaccination.

It is unclear whether patients with cancer present inherently impaired responses to COVID-19 and vaccination due to their treatments, neoplastic diseases or both. To address this question, immune profiling was performed in three cohorts of healthy donors and oncologic patients: infected with SARS-CoV-2, BNT162b2-vaccinated, and with previous COVID-19 disease and subsequently vaccinated. Cancer patients showed good antibody responses to vaccination, but poor induction of T-cell responses towards the S protein when compared to infection. Following natural infection, the major targets for T-cells were the SARS-CoV-2 structural proteins M and S, but not the N protein. Similar to antibody titers, the T-cell responses quickly decayed after six months post-vaccination. Significant memory T-cell expansion was observed in vaccinated donors only if previously diagnosed with COVID-19 before undergoing vaccination. Oncologic patients with previous COVID-19 followed by vaccination exhibited potent IL-17+ CD4 and CD8 T-cell responses and elevated numbers of circulating neutrophils in peripheral blood.

Long-Term Intracoronary Structural and Vasomotor Assessment of the ABSORB Bioresorbable Vascular Scaffold.

We systematically categorized the longer-term (≥3 years) structural and functional characteristics of the ABSORB bioresorbable vascular scaffold (BVS) using optical coherence tomography imaging and coronary vasomotor reactivity testing and further compared the functional characteristics of BVS stented versus remote coronary segments. A total of 92 patients (mean age 56.4 ± 9.7 years, 22.8% women) who underwent percutaneous coronary intervention (76% with acute coronary syndrome) using the ABSORB BVS (112 lesions) were included. Optical coherence tomography analysis (38,790 visible struts) comprised in-segment quantitative lumen/plaque and semiquantitative plaque composition analysis of the neointimal pattern. Epicardial endothelium-dependent and-independent vasomotion was defined as any vasodilatation at low/intermediate intracoronary dose of acetylcholine (ACh) and nitroglycerine, assessed using quantitative coronary angiography. At a median time of 3.2 years follow-up, 79.8% of BVS segments still demonstrated visible struts with a predominant neointimal fibrotic healing pattern in 84% of BVS segments, with 99.5% of struts demonstrating coverage with apposition. Compared with remote segments, BVS segments demonstrated less endothelium-dependent vasodilatation at low (p = 0.06) and intermediate ACh doses (p = 0.04). Hypertension, longer time interval from index percutaneous coronary intervention, and the degree of in-BVS segment neointimal volume (p <0.03 for all) were each independently associated with abnormal BVS endothelium-dependent vasomotor function. Endothelium-independent function was more likely preserved in non-BVS (remote) segments compared with BVS segments (p = 0.06). In conclusion, at 3+ years post-ABSORB BVS insertion, the rate of complete scaffold resorption was low and residual strut presence was high, with a dominant fibrous healing response contributing toward neointimal hyperplasia and endothelium-dependent and-independent vasomotor dysfunction.

Insuficiencia suprarrenal secundaria persistente tras tratamiento prolongado con corticoides / Chronic secondary suprarrenal failure after prolonged corticosteroid treatment

Los glucocorticoides son fármacos frecuentemente usados de forma crónica para el tratamiento de enfermedades autoinmunes, hematológicas y neoplasias avanzadas. Sin embargo, representan una causa común de insuficiencia suprarrenal terciaria. Por lo tanto, la terapia de reemplazo corticoidea puede ser frecuente tras la administración crónica de glucocorticoides. Presentamos el caso clínico de una paciente de 65 años en tratamiento crónico con glucocorticoides debido a una sarcoidosis pulmonar diagnosticada en 2012. A pesar de la reducción gradual del tratamiento, una vez que la patología estaba en remisión, la paciente es diagnosticada de insuficiencia suprarrenal ante la persistencia de clínica de astenia intensa y sudoración profusa y haber descartado una reactivación de su proceso. Se debe sospechar Insuficiencia suprarrenal en todo paciente que ha estado en tratamiento crónico con tratamiento glucocorticoideo. La retirada gradual del tratamiento con glucocorticoides a lo largo de las semanas es una práctica comúnmente extendida que minimiza el riesgo de Insuficiencia suprarrenal pero no lo anula. La determinación del cortisol basal al menos 18 horas de la última dosis de glucocorticoides puede ser útil para evaluar el eje hipofisario-adrenal y retirar con seguridad el tratamiento con glucocorticoides.(AU)

Glucocorticoids are drugs widely used chronically to treat various autoimmune, haematological conditions and advanced malignancies. Nevertheless, glucocorticoids are considered a common cause of tertiary adrenal insufficiency. Therefore, patients may require glucocorticoid replacement therapy after chronic use of glucocorticoids. We report the clinical case of a 65-year-old patient on chronic glucocorticoid treatment due to pulmonary sarcoidosis diagnosed in 2012. Despite gradual tapering of treatment once the main disease was in remission, the patient was diagnosed with adrenal insufficiency due to persistent clinical symptoms of intense asthenia and profuse sweating once reactivation of her disease was ruled out. Adrenal insufficiency should be suspected in every patient on chronic glucocorticoid treatment. Gradual tapering of glucocorticoid treatment over weeks is a common clinical practice that minimizes the risk of adrenal insufficiency but does not eliminate it completely. Determination of basal cortisol at least 18 hours after the last dose of glucocorticoid may be useful to evaluate the pituitary-adrenal axis and safely withdraw glucocorticoid treatment.(AU)

Transopercular Insular Approach, Overcoming the Training Curve Using a Cadaveric Simulation Model: 2-Dimensional Operative Video.

Transopercular approach to the insula is indicated for resection of insular low-grade gliomas, particularly for Yasargil's 3B, 5A, and 5B types. Nevertheless, the infrequent location and its challenging approach make it difficult to master the surgery. Consequently, a realistic laboratory training model might help to acquire key surgical skills. In this video, we describe a cadaveric-based model simulating the resection of a temporo-insular low-grade glioma. Kingler's fixation technique was used to fix the cadaver head before injecting red and blue colorants for a realistic vascular appearance. Hemisphere was frozen for white matter tract dissection. Tractography and intraoperative eloquent areas were extrapolated from a glioma patient by using a neuronavigation system. Then, a fronto-temporal craniotomy was performed through a question mark incision, exposing from inferior temporal gyrus up to middle frontal gyrus. After cortical anatomic landmark identification, eloquent areas were extrapolated creating a simulated functional cortical map. Then, transopercular noneloquent frontal and temporal corticectomies were performed, followed by subpial resection. Detailed identification of Sylvian vessels and insular cortex was demonstrated. Anatomic resection limits were exposed, and implicated white matter bundles, uncinate and fronto-occipital fascicles, were identified running through the temporal isthmus. Finally, a temporo-mesial resection was performed. In summary, this model provides a simple, cost-effective, and very realistic simulation of a transopercular approach to the insula, allowing the development of surgical skills needed to treat insular tumors in a safe environment. Besides, the integration of simulated navigation has proven useful in better understanding the complex white matter anatomy involved. Cadaver donation, subject or relatives, includes full consent for publication of the images. For the purpose of this video, no ethics committee approval was needed. Images correspond to a cadaver head donation. Cadaver donation, subject or relatives, includes full consent for any scientific purposes involving the corpse. The consent includes image or video recording. Regarding the intraoperative surgical video and tractography, the patient gave written consent for scientific divulgation prior to surgery.

Children hospitalized for myiasis in a reference center in Uruguay / Niños hospitalizados por miasis en un centro de referencia de Uruguay

Abstract Background: Myiasis is an emerging disease caused by tissue invasion of dipteran larvae. In Uruguay, Cochliomyia hominivorax and Dermatobia hominis are the most frequent species. This study aimed to describe the epidemiological and clinical characteristics and the follow-up of children < 15 years hospitalized for myiasis in a reference center in Uruguay between 2010 and 2019. Methods: We conducted a descriptive and retrospective study by reviewing medical records. We analyzed the following variables: age, sex, comorbidities, origin, the month at admission, clinical manifestations, other parasitoses, treatments, complications, and larva species identified. Results: We found 63 hospitalized children: median age of 7 years (1 month-14 years), 68% of females. We detected risk comorbidities for myiasis (33%), of which chronic malnutrition was the most frequent (n = 6); 84% were from the south of the country; 76% were hospitalized during the summer. Superficial and multiple cutaneous involvements were found in 86%: of the scalp 50, furunculoid type 51, secondary to C. hominivorax 98.4%, and to D. hominis in 1.6%. As treatments, larval extraction was detected in all of them, surgical in 22%. Asphyctic products for parasites were applied in 94%, ether in 49. Antimicrobials were prescribed in 95%; cephradine and ivermectin were the most frequent. About 51% presented infectious complications: impetigo was found in 29, cellulitis in 2, and abscess in 1. Conclusions: Myiasis predominantly affected healthy schoolchildren during the summer months and was frequently associated with ectoparasites. Superficial infestation of the furuncle-like scalp by C. hominivorax was the most frequent form. Infectious complications motivated hospitalizations.

Resumen Introducción: La miasis es una enfermedad emergente producida por la invasión tisular por larvas de dípteros. En Uruguay, Cochliomyia hominivorax y Dermatobia hominis son las especies más frecuentes. El objetivo de este estudio fue describir las características epidemiológicas y clínicas, y el seguimiento, de niños menores de 15 años hospitalizados por miasis en un centro de referencia del Uruguay entre 2010 y 2019. Métodos: Se llevó a cabo un estudio descriptivo y retrospectivo mediante la revisión de las historias clínicas. Se analizaron las siguientes variables: edad, sexo, comorbilidad, procedencia, mes al ingreso, cuadro clínico, otras parasitosis, tratamientos, complicaciones y especie de larva identificada. Resultados: Se encontraron 63 casos de niños hospitalizados, con una mediana de edad de 7 años (rango: 1 mes a 14 años) y el 68% de sexo femenino. Se identificó comorbilidad de riesgo para miasis (33%), siendo la desnutrición crónica la más frecuente (n = 6). El 84% eran procedentes del sur del país y el 76% fueron hospitalizados en los meses estivales. Se encontró afectación cutánea superficial y múltiple en el 86%: de cuero cabelludo en 50, de tipo forunculoide en 51, secundaria a C. hominivorax en el 98.4% y a D. hominis en el 1.6%. Se realizó extracción larvaria en todos los casos, que fue quirúrgica en el 22%. Se aplicaron productos asfícticos para parásitos en el 94%, con éter en 49 niños. Se prescribieron antimicrobianos en el 95%; los más usados fueron cefradina e ivermectina. El 51% presentaron complicaciones infecciosas: 29 impétigo, 2 celulitis y 1 absceso. Conclusiones: La miasis afectó predominantemente a escolares sanos y durante los meses estivales, y se encontró frecuentemente asociada con ectoparasitosis. La infestación superficial del cuero cabelludo de tipo forunculoide por C. hominivorax fue la forma más frecuente. Las complicaciones infecciosas motivaron las hospitalizaciones.

A Proteomic Atlas of Lineage and Cancer-Polarized Expression Modules in Myeloid Cells Modeling Immunosuppressive Tumor-Infiltrating Subsets.

Monocytic and granulocytic myeloid-derived suppressor cells together with tumor-infiltrating macrophages constitute the main tumor-infiltrating immunosuppressive myeloid populations. Due to the phenotypic resemblance to conventional myeloid cells, their identification and purification from within the tumors is technically difficult and makes their study a challenge. We differentiated myeloid cells modeling the three main tumor-infiltrating types together with uncommitted macrophages, using ex vivo differentiation methods resembling the tumor microenvironment. The phenotype and proteome of these cells was compared to identify linage-dependent relationships and cancer-specific interactome expression modules. The relationships between monocytic MDSCs and TAMs, monocytic MDSCs and granulocytic MDSCs, and hierarchical relationships of expression networks and transcription factors due to lineage and cancer polarization were mapped. Highly purified immunosuppressive myeloid cell populations that model tumor-infiltrating counterparts were systematically analyzed by quantitative proteomics. Full functional interactome maps have been generated to characterize at high resolution the relationships between the three main myeloid tumor-infiltrating cell types. Our data highlights the biological processes related to each cell type, and uncover novel shared and differential molecular targets. Moreover, the high numbers and fidelity of ex vivo-generated subsets to their natural tumor-shaped counterparts enable their use for validation of new treatments in high-throughput experiments.

Hemorrhagic colloid cyst of the third ventricle: A rare cause of colloid cyst growth and progressive hydrocephalus. Case report / Quiste coloide hemorrágico del tercer ventrículo: una causa rara de crecimiento de los quistes coloides e hidrocefalia progresiva. Reporte de un caso

Introduction Acute spontaneous bleeding within a colloid cyst of the third ventricle is extremely rare. Accordingly, is difficult to establish reliable prognostic factors, risk factors for obstructive hydrocephalus remain poorly defined, and there are no standard management strategies. Case presentation 19-Year-old man with a colloid cyst of the third ventricle causing obstructive hydrocephalus is described, initially treated with partial endoscopic removal and ventriculo-peritoneal shunt placement. Serial neuroimaging follow-up showed gradual growth of the cyst due to clinically silent intracystic recurrent hemorrhage. Microsurgical transcallosal approach was performed and the cyst was totally resected. Pathological examination demonstrated hemorrhages of varying ages within the tumor. Conclusion Bleeding within a colloid cyst must be considered when neuroimaging follow-up shows cyst growth, even with no clinical events associated. Hemorrhagic changes within the colloid cyst should be considered in the surgical indication and approach. Resumen Introducción El sangrado espontáneo agudo en un quiste coloide del tercer ventrículo es extremadamente raro. En consecuencia, es difícil establecer factores pronósticos fiables, los factores de riesgo asociados a hidrocefalia obstructiva permanecen mal definidos y no existen estrategias de manejo estandarizadas. Presentación del caso Varón de 19 años con un quiste coloide del tercer ventrículo e hidrocefalia obstructiva, inicialmente tratado mediante extirpación endoscópica parcial y derivación ventriculoperitoneal. Posteriormente se demostró el crecimiento gradual del quiste debido a hemorragias intraquísticas recurrentes, clínicamente silentes. Se realizó un abordaje microquirúrgico transcalloso con resección completa. El examen anatomopatológico demostró la presencia de hemorragias en diferentes estadios dentro del tumor (AU)

Colloid cysts are rare and benign intracranial tumors located in the third ventricle. Reliably defining the natural history of colloid cysts has been challenging due to their low incidence and the small number of cases in most reported series. They are a well-known cause of obstructive hydrocephalus, with occasional rapid clinical deterioration, and even sudden death.1 Acute spontaneous bleeding within a colloid cyst of the third ventricle is a rare event usually causing a sudden increase of the cyst size, that results in obstructive hydrocephalus and clinical deterioration. This complication has only been reported in a few cases of the scientific literature.2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 For these reasons, risk factors for obstructive hydrocephalus in the setting of hemorrhagic colloid cysts remain poorly defined, there are no grading scales on which to develop standardized management strategies and is difficult to establish the reliable prognostic factors and surgical indications. We report a case of a colloid cyst of the third ventricle, that, after partial endoscopic removal developed progressive gradual growth due to recurrent and initially silent intracystic hemorrhages. The literature of this rare entity has been revised (AU)

Hyperprogressive Disease: Main Features and Key Controversies.

Along with the positioning of immunotherapy as a preferential treatment for a wide variety of neoplasms, a new pattern of response consisting in a sudden acceleration of tumor growth has been described. This phenomenon has received the name of "hyperprogressive disease", and several definitions have been proposed for its identification, most of them relying on radiological criteria. However, due to the fact that the cellular and molecular mechanisms have not been elucidated yet, there is still some debate regarding whether this fast progression is induced by immunotherapy or only reflects the natural course of some highly aggressive neoplasms. Moreover, contradictory results of trials including patients with different cancer types suggest that both the incidence, the associated factors and the implications regarding prognosis might differ depending on tumor histology. This article intends to review the main publications regarding this matter and critically approach the most controversial aspects.

Effectiveness and tolerability of a squalane and dimethicone-based treatment for head lice.

Head lice (Pediculus humanus capitis) are worldwide obligate human ectoparasites, with high implications in pediatrics. In Europe, first-line topical neurotoxic insecticidal therapeutic strategies are being replaced by topical physically acting agents as the first-choice treatment. Safety of the active ingredients and high efficacy in a one-time single-dose treatment with a brief treatment application time are key issues for consumer use and effective compliance. The aim of this study was to assess the in vitro efficacy of a newly developed squalane and dimethicone-based pediculicidal formula, against motile head lice and eggs after 2 and 5 min immersion in the product, as well as its skin tolerance and acceptability under dermatological and pediatric expert control in children with atopic skin. The results indicate that at both time points, 100% mortality rate of head lice crawling stages and late-stage eggs was achieved. The formula was well tolerated and suitable for children with atopic skin from 12 months of age. Showing high in vitro efficacy and good skin acceptability, this solution is presented as a new safe alternative therapy for treatment of head lice infestations.

Occupational socioeconomic risk associations for head and neck cancer in Europe and South America: individual participant data analysis of pooled case-control studies within the INHANCE Consortium.

BACKGROUND: The association between socioeconomic disadvantage (low education and/or income) and head and neck cancer is well established, with smoking and alcohol consumption explaining up to three-quarters of the risk. We aimed to investigate the nature of and explanations for head and neck cancer risk associated with occupational socioeconomic prestige (a perceptual measure of psychosocial status), occupational socioeconomic position and manual-work experience, and to assess the potential explanatory role of occupational exposures. METHODS: Pooled analysis included 5818 patients with head and neck cancer (and 7326 control participants) from five studies in Europe and South America. Lifetime job histories were coded to: (1) occupational social prestige-Treiman's Standard International Occupational Prestige Scale (SIOPS); (2) occupational socioeconomic position-International Socio-Economic Index (ISEI); and (3) manual/non-manual jobs. RESULTS: For the longest held job, adjusting for smoking, alcohol and nature of occupation, increased head and neck cancer risk estimates were observed for low SIOPS OR=1.88 (95% CI: 1.64 to 2.17), low ISEI OR=1.74 (95% CI: 1.51 to 1.99) and manual occupations OR=1.49 (95% CI: 1.35 to 1.64). Following mutual adjustment by socioeconomic exposures, risk associated with low SIOPS remained OR=1.59 (95% CI: 1.30 to 1.94). CONCLUSIONS: These findings indicate that low occupational socioeconomic prestige, position and manual work are associated with head and neck cancer, and such risks are only partly explained by smoking, alcohol and occupational exposures. Perceptual occupational psychosocial status (SIOPS) appears to be the strongest socioeconomic factor, relative to socioeconomic position and manual/non-manual work.

Pharmacological inactivation of the prion protein by targeting a folding intermediate.

Recent computational advancements in the simulation of biochemical processes allow investigating the mechanisms involved in protein regulation with realistic physics-based models, at an atomistic level of resolution. These techniques allowed us to design a drug discovery approach, named Pharmacological Protein Inactivation by Folding Intermediate Targeting (PPI-FIT), based on the rationale of negatively regulating protein levels by targeting folding intermediates. Here, PPI-FIT was tested for the first time on the cellular prion protein (PrP), a cell surface glycoprotein playing a key role in fatal and transmissible neurodegenerative pathologies known as prion diseases. We predicted the all-atom structure of an intermediate appearing along the folding pathway of PrP and identified four different small molecule ligands for this conformer, all capable of selectively lowering the load of the protein by promoting its degradation. Our data support the notion that the level of target proteins could be modulated by acting on their folding pathways, implying a previously unappreciated role for folding intermediates in the biological regulation of protein expression.