Tumor-derived hypoxic small extracellular vesicles promote endothelial cell migration and tube formation via ALS2/Rab5/ß-catenin signaling.

Tumor hypoxia has been associated with cancer progression, angiogenesis, and metastasis via modifications in the release and cargo composition of extracellular vesicles secreted by tumor cells. Indeed, hypoxic extracellular vesicles are known to trigger a variety of angiogenic responses via different mechanisms. We recently showed that hypoxia promotes endosomal signaling in tumor cells via HIF-1α-dependent induction of the guanine exchange factor ALS2, which activates Rab5, leading to downstream events involved in cell migration and invasion. Since Rab5-dependent signaling is required for endothelial cell migration and angiogenesis, we explored the possibility that hypoxia promotes the release of small extracellular vesicles containing ALS2, which in turn activate Rab5 in recipient endothelial cells leading to pro-angiogenic properties. In doing so, we found that hypoxia promoted ALS2 expression and incorporation as cargo within small extracellular vesicles, leading to subsequent transfer to recipient endothelial cells and promoting cell migration, tube formation, and downstream Rab5 activation. Consequently, ALS2-containing small extracellular vesicles increased early endosome size and number in recipient endothelial cells, which was followed by subsequent sequestration of components of the ß-catenin destruction complex within endosomal compartments, leading to stabilization and nuclear localization of ß-catenin. These events converged in the expression of ß-catenin target genes involved in angiogenesis. Knockdown of ALS2 in donor tumor cells precluded its incorporation into small extracellular vesicles, preventing Rab5-downstream events and endothelial cell responses, which depended on Rab5 activity and guanine exchange factor activity of ALS2. These findings indicate that vesicular ALS2, secreted in hypoxia, promotes endothelial cell events leading to angiogenesis. Finally, these events might explain how tumor angiogenesis proceeds in hypoxic conditions.

Systematic review and meta-analysis of vaginal natural orifice transluminal endoscopic surgery hysterectomy versus vaginal hysterectomy for benign indications.

Objective: As the second most common surgery performed on women in the United States, hysterectomy techniques are constantly examined for validity and superiority. The vaginal natural orifice transluminal endoscopic surgery (vNOTES) has increased in popularity since the first vNOTES hysterectomy was performed in 2012. We sought out to evaluate the safety and effectiveness of hysterectomy by vNOTES compared to conventional vaginal hysterectomy for various benign indications. Data sources: We searched Scopus, Medline, PubMed, ClinicalTrials.Gov, and the Cochrane Library. Our search included all studies from each respective database's inception until September 1, 2023. Study eligibility criteria: We included eligible studies that compare vNOTES hysterectomy versus conventional vaginal hysterectomy for various benign indications, and included at least one of our preselected outcomes. The main outcomes were estimated blood loss (mL), operation time (min), length of hospital stay (d), Visual Analogue Scale pain score at Day 1, intraoperative complications, and postoperative complications. Study appraisal and synthesis methods: We analyzed data of our continuous outcomes using RevMan 5.4.1. Continuous outcomes were analyzed using mean difference (MD) and 95% confidence intervals (CIs) under the inverse variance analysis method. We assessed the quality of the studies using the ROBINS-I assessment tool. Results: We found 4 eligible studies to include in our analysis. Surgeon declared estimated blood loss was found to be similar in both groups (MD=-44.70 [-99.97, 10.57]; P=.11). Also, the total length of hospital stay (in days) was found to be comparable in both groups (MD=-0.16 [-1.62, 1.30]; P=.83). We also found no other statistically significant difference between hysterectomy by vNOTES and vaginal hysterectomy in other studied outcomes, including the duration of the operation, the Visual Analogue Scale Pain score after 1 day, intraoperative complications, and postoperative complications. Conclusion: vNOTES seems to be associated with a nonsignificant lower surgeon declared estimated blood loss. We found no other significant differences in hospital stay, intraoperative, or postoperative outcomes. Further studies may clarify if other differences in safety or efficacy exist.

Meta-analysis of residency program application and acceptance according to sex, race and ethnicity.

OBJECTIVE: We aimed to investigate trends in residency program application and acceptance rates according to sex and race and ethnicity. METHODS: We collected data from the Journal of the American Medical Association Graduation Medical Education Reports. We extracted the data for 25 residency programs in the United States from 2005 to 2021 and conducted statistical analyses. RESULTS: Men were most matched for orthopedics (84.7%, 95% confidence interval [CI] 84.2%-85.1%), and women for oncology (78.7%, 95% CI 78.2%-79.2%). The most matched program was orthopedics for the White subgroup (43.5%, 95% CI 43.2%-43.9%), radiology for the Black subgroup (20%, 95% CI 18.9%-20.9%), general surgery for the Hispanic subgroup (11%, 95% CI 10.7%-11.2%), and internal medicine for the Asian subgroup (35.3%, 95% CI 34.9%-35.6%). CONCLUSION: Match rates for women were lower than those for men in all programs except psychiatry, pediatrics, obstetrics and gynecology, and dermatology. Match rates were significantly lower for Black, Hispanic, and Asian subgroups than the White subgroup in all programs except for internal medicine, with the Asian subgroup being higher. We observed a significant increase in both application and acceptance rates for women and racial and ethnic minorities over the past 40 years.

Systematic review and meta-analysis of vaginal natural orifice transluminal endoscopic surgery vs laparoscopic hysterectomy.

OBJECTIVE: Because vaginal natural orifice transluminal endoscopic surgery and laparoscopic hysterectomy techniques both aim to decrease tissue injury and postoperative morbidity and mortality and to improve a patient's quality of life, we sought to evaluate the safety and effectiveness of a hysterectomy by vaginal natural orifice transluminal endoscopic surgery and compared that with conventional laparoscopic hysterectomy among women with benign gynecologic diseases. DATA SOURCES: We used Scopus, Medline, ClinicalTrials.Gov, PubMed, and the Cochrane Library and searched from database inception to September 1, 2023. STUDY ELIGIBILITY CRITERIA: We included all eligible articles that compared vaginal natural orifice transluminal endoscopic surgery hysterectomy with any conventional laparoscopic hysterectomy technique without robotic assistance for women with benign gynecologic pathology and that included at least 1 of our main outcomes. These outcomes included estimated blood loss (in mL), operation time (in minutes), length of hospital stay (in days), decrease in hemoglobin level (g/dL), visual analog scale pain score on postoperative day 1, opioid analgesic dose required, rate of conversion to another surgical technique, intraoperative complications, postoperative complications, and requirements for blood transfusion. We included randomized controlled trials and observational studies. Ultimately, 14 studies met our criteria. METHODS: The study quality of the randomized controlled trials was assessed using the Cochrane assessment tool, and the quality of the observational studies was assessed using the ROBINS-I tool. We analyzed data using RevMan 5.4.1. Continuous outcomes were analyzed using the mean difference and 95% confidence intervals under the inverse variance analysis method. Dichotomous outcomes were analyzed using OpenMeta[Analyst] and odds ratios and 95% confidence intervals were reported. RESULTS: The operative time and length of hospitalization were shorter in the vaginal natural orifice transluminal endoscopic surgery cohort. We also found lower visual analog scale pain scores, fewer postoperative complications, and fewer blood transfusions in the vaginal natural orifice transluminal endoscopic surgery group. We found no difference in the estimated blood loss, decrease in hemoglobin levels, analgesic usage, conversion rates, or intraoperative complications. CONCLUSION: When evaluating the latest data, it seems that vaginal natural orifice transluminal endoscopic surgery techniques may have some advantages over conventional laparoscopic hysterectomy techniques.

Pupil size change in agricultural workers exposed to pesticides.

CLINICAL RELEVANCE: Pupil size evaluation using clinical examination may be important for detecting and monitoring individuals at risk of neurotoxic effects from chemical exposure, as it may enable early intervention and the implementation of preventive measures. BACKGROUND: This work aimed to investigate the association between pesticide exposure and pupil size. Pupil size is regulated by muscarinic and nicotinic receptors, and it is well-established that common pesticide chemicals disrupt this regulation. METHODS: Twenty agricultural workers exposed to pesticides, and twenty participants not exposed, underwent visual screening, and pupil size evaluation under mesopic and photopic conditions. Additionally, signs of neurotoxicity and pesticide exposure in both groups were evaluated using the modified version of the neurotoxic symptoms questionnaire (Q16) and measuring cholinesterase (AChE) levels in blood, respectively. RESULTS: Agricultural workers exposed to pesticides had a score indicating medium-high level of neurotoxicity (49.85 (SD ± 8.94)) which was significantly higher (t (36) = 7.659, p ≤ 0.0001) than non-exposed participants who had low levels of neurotoxicity (27.25 SD ± 8.86). There was a significant difference in pupil size (mm) under mesopic (t (19) 4.42 p = 0.003) and scotopic (t (19) 4.63, p = 0.0002) conditions between the two groups. Additionally, there was a significant difference in AChE blood levels (t (19) 2.94 p = 0.008) between exposed and non-exposed participants, indicating that exposed workers had low levels of this enzyme (average exposed group 3381 U/L (SD ± 1306)) compared to the non-exposed group (average non-exposed group 4765 U/L (SD ± 1300)). A significant negative correlation between AChE levels, years of exposure, and pupil size was found. The latter finding importantly showed that smaller pupils are associated with the accumulation of acetylcholine or a decrease in the activity of the enzyme AChE. CONCLUSION: Pupil size of agricultural workers exposed to pesticides can be abnormal and is associated with neurotoxicity as indicated by symptomatology and cholinesterase levels. Evaluation of pupil size may be useful for clinically detecting neurotoxicity.

Targeting the Endothelin-1 pathway to reduce invasion and chemoresistance in gallbladder cancer cells.

BACKGROUND: Gallbladder cancer (GBC) is a prevalent and deadly biliary tract carcinoma, often diagnosed at advanced stages with limited treatment options. The 5-year survival rate varies widely from 4 to 60%, mainly due to differences in disease stage detection. With only a small fraction of patients having resectable tumors and a high incidence of metastasis, advanced GBC stages are characterized by significant chemoresistance. Identification of new therapeutic targets is crucial, and recent studies have shown that the Endothelin-1 (ET-1) signaling pathway, involving ETAR and/or ETBR receptors (ETRs), plays a crucial role in promoting tumor aggressiveness in various cancer models. Blocking one or both receptors has been reported to reduce invasiveness and chemoresistance in cancers like ovarian, prostate, and colon. Furthermore, transcriptomic studies have associated ET-1 levels with late stages of GBC; however, it remains unclear whether its signaling or its inhibition has implications for its aggressiveness. Although the role of ET-1 signaling in gallbladder physiology is minimally understood, its significance in other tumor models leads us to hypothesize its involvement in GBC malignancy. RESULTS: In this study, we investigated the expression of ET-1 pathway proteins in three GBC cell lines and a primary GBC culture. Our findings demonstrated that both ETAR and ETBR receptors are expressed in GBC cells and tumor samples. Moreover, we successfully down-regulated ET-1 signaling using a non-selective ETR antagonist, Macitentan, which resulted in reduced migratory and invasive capacities of GBC cells. Additionally, Macitentan treatment chemosensitized the cells to Gemcitabine, a commonly used therapy for GBC. CONCLUSION: For the first time, we reveal the role of the ET-1 pathway in GBC cells, providing insight into the potential therapeutic targeting of its receptors to mitigate invasion and chemoresistance in this cancer with limited treatment options. These findings pave the way for further exploration of Macitentan or other ETR antagonists as potential therapeutic strategies for GBC management. In summary, our study represents a groundbreaking contribution to the field by providing the first evidence of the ET 1 pathway's pivotal role in modulating the behavior and aggressiveness of GBC cells, shedding new light on potential therapeutic targets.

Lipopolysaccharides from Porphyromonas endodontalis and Porphyromonas gingivalis promote angiogenesis via Toll-like-receptors 2 and 4 pathways in vitro.

AIM: Angiogenesis contributes to the development of apical periodontitis, periodontitis, and other oral pathologies; however, it remains unclear how this process is triggered. The aim was to evaluate whether lipopolysaccharide (LPS) from Porphyromonas endodontalis and Porphyromonas gingivalis induced angiogenesis-related effects in vitro via TLR2 and TLR4. METHODOLOGY: Porphyromonas endodontalis LPS (ATCC 35406 and clinical isolate) was purified with TRIzol, whereas P. gingivalis LPS was obtained commercially. The effects of the different LPS (24 h) in endothelial cell migration were analysed by Transwell assays, following quantification in an optical microscope (40×). The effects of LPS on FAK Y397 phosphorylation were assessed by Western blotting. Angiogenesis in vitro was determined in an endothelial tube formation assay (14 h) in Matrigel in the absence or presence of either LPS. IL-6 and VEGF-A levels were determined in cell supernatants, following 24 h treatment with LPS, and measured in multiplex bead immunoassay. The involvement of TLR2 and TLR4 was assessed with blocking antibodies. The statistical analysis was performed using STATA 12® (StataCorp LP). RESULTS: The results revealed that P. endodontalis LPS, but not P. gingivalis LPS, stimulated endothelial cell migration. Pre-treatment with anti-TLR2 and anti-TLR4 antibodies prevented P. endodontalis LPS-induced cell migration. P. endodontalis LPS promoted FAK phosphorylation on Y397, as observed by an increased p-FAK/FAK ratio. Both P. gingivalis and P. endodontalis LPS (ATCC 35406) induced endothelial tube formation in a TLR-2 and -4-dependent manner, as shown by using blocking antibodies, however, only TLR2 blocking decreased tube formation induced by P. endodontalis (clinical isolate). Moreover, all LPS induced IL-6 and VEGF-A synthesis in endothelial cells. TLR2 and TLR4 were required for IL-6 induction by P. endodontalis LPS (ATCC 35406), while only TLR4 was involved in IL-6 secretion by the other LPS. Finally, VEGF-A synthesis did not require TLR signalling. CONCLUSION: Porphyromonas endodontalis and P. gingivalis LPS induced angiogenesis via TLR2 and TLR4. Collectively, these data contribute to understanding the role of LPS from Porphyromonas spp. in angiogenesis and TLR involvement.

Biochar addition reduces non-CO2 greenhouse gas emissions during composting of human excreta and cattle manure.

Ecological sanitation combined with thermophilic composting is a viable option to transform human excreta into a stabilized, pathogen-free, and nutrient-rich fertilizer. In combination with suitable bulking materials such as sawdust and straw, and additives such as biochar, this could also be a suitable waste management strategy for reducing greenhouse gas (GHG) emissions. In this study, we conducted a 143-days thermophilic composting of human excreta or cattle manure together with teff straw, organic waste, and biochar to investigate the effect that biochar has on GHG (CO2 , N2 O, and CH4 ) and NH3 emissions. The composting was performed in wooden boxes (1.5 × 1.5 × 1.4 m3 ), GHG were measured by using a portable FTIR gas analyzer and NH3 was sampled as ammonium in an H2 SO4 trap. We found that the addition of biochar significantly reduced CH4 emissions by 91% in the cattle manure compost, and N2 O emissions by 56%-57% in both humanure and cattle manure composts. Overall, non-CO2 GHG emissions were reduced by 51%-71%. In contrast, we did not observe a significant biochar effect on CO2 and NH3 emissions. Previous data already showed that it is possible to sanitize human fecal material when using this composting method. Our results suggest that thermophilic composting with biochar addition is a safe and cost-effective waste management practice for producing a nutrient-rich fertilizer from human excreta, while reducing GHG emissions at the same time.

MRI and Targeted Biopsy Essential Tools for an Accurate Diagnosis and Treatment Decision Making in Prostate Cancer.

Prostate cancer (PCa) is one of the most frequent causes of cancer death worldwide. Historically, diagnosis was based on physical examination, transrectal (TRUS) images, and TRUS biopsy resulting in overdiagnosis and overtreatment. Recently magnetic resonance imaging (MRI) has been identified as an evolving tool in terms of diagnosis, staging, treatment decision, and follow-up. In this review we provide the key studies and concepts of MRI as a promising tool in the diagnosis and management of prostate cancer in the general population and in challenging scenarios, such as anteriorly located lesions, enlarged prostates determining extracapsular extension and seminal vesicle invasion, and prior negative biopsy and the future role of MRI in association with artificial intelligence (AI).

Endothelin-1 induces changes in the expression levels of steroidogenic enzymes and increases androgen receptor and testosterone production in the PC3 prostate cancer cell line.

Endothelin­1 (ET­1) is involved in the regulation of steroidogenesis. Additionally, patients with castration­resistant prostate cancer (PCa) have a higher ET­1 plasma concentration than those with localized PCa and healthy individuals. The aim of the present study was to evaluate the effect of ET­1 on steroidogenesis enzymes, androgen receptor (AR) and testosterone (T) production in PCa cells. The expression levels of endothelin receptors in prostate tissue from patients with localized PCa by immunohistochemistry, and those in LNCaP and PC3 cells were determined reverse transcription­quantitative PCR (RT­qPCR) and western blotting. Furthermore, the expression levels of ET­1 were determined in LNCaP and PC3 cells by RT­qPCR and western blotting. The ET­1 receptor activation was evaluated by intracellular calcium measurement, the expression levels of AR and enzymes participating in steroidogenesis [cytochrome P450 family 11 subfamily A member 1 (CyP11A1), cytochrome P450 family 17 subfamily A member 1, aldo­keto reductase family member C2 and 3ß­hydroxysteroid dehydrogenase/isomerase 2 (3ß HSD2)] were determined by western blotting and T concentration was determined by ELISA using PC3 cells. The present results revealed higher expression levels of endothelin A receptor (ETAR) in tissues obtained from samples of patients with PCa with a low Gleason Score. No changes were identified for endothelin B receptor (ETBR). PC3 cells expressed higher levels of ET­1 and ETAR, while LNCaP cells exhibited higher expression levels of ETBR. Blocking of ETAR and endothelin B receptor decreased the expression levels of CyP11A1 and 3ß HSD2 enzymes and AR in PC3 cells, as well as T secretion. These findings suggested that ET­1 has a potential role in modulating the intratumoral steroidogenesis pathway and might have relevance as a possible therapeutic target.

Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development.

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

Gamma knife stereotactic radiosurgery as an effective tool in primary CNS lymphoma: Evaluation of stereotactic radiosurgery and methotrexate treatment in a prospective and observational clinical research study.

OBJECTIVE: The purpose of this study was to compare the progression of Primary Central Nervous System Lymphoma (PCNSL) in patients treated with methotrexate (MTX) versus those treated with a combination of Stereotactic Radiosurgery (SRS) and MTX. Progression was measured via brain lesion count and tumor volume. METHODS: This observational and prospective cohort study evaluated the outcome of SRS treatment of PCNSL in one hundred twenty-eight subjects. We analyzed baseline, prospective, and retrospective data of patients enrolled in the brain tumor registry between June 2010 and August 2017. Seventy-three patients were treated exclusively with MTX while the remaining fifty-five patients received a combination of SRS and MTX. Strict inclusion and exclusion criteria were established. RESULTS: Mean survival rate for patients receiving combined SRS and MTX treatment was significantly higher (52.6 months) compared to the MTX group (19.8 months); p = 0.0029. At the 36 months follow-up, patients treated with SRS and MTX also had a lower rate of tumor progression (32.7 %) than the MTX group (95.9 %); p = 0.00192. Local tumor control was achieved in all patients treated with SRS. No clinical toxicity was observed in this group. CONCLUSIONS: Clinical results obtained from this observational study highlight the potential effectiveness of SRS in the treatment of PCNSL. Although treatment outcomes have improved in the past years, additional evidence in the clinical design of randomized trials is needed to evaluate the strength of this treatment in specific situations.

Tuberculosis diseminada en una adolescente con diabetes mellitus tipo 1: un caso inusual que imita una enfermedad autoinmune / Disseminated Tuberculosis in a girl with Type 1 Diabetes Mellitus: An unusual case mimicking an autoimmune disease usage: case report

RESUMEN La tuberculosis es una de las principales causas de mortalidad en el mundo, a pesar de los múltiples controles y estrategias del tratamiento. La forma diseminada corresponde al 5 % de las presentaciones. Reportamos el primer caso en la literatura de una paciente adolescente con diabetes mellitus tipo 1 y tuberculosis diseminada quien presentó síntomas constitucionales asociados con un dolor lumbar, inicialmente interpretado como sacroileítis no infecciosa y una probable enfermedad inflamatoria intestinal.

SUMMARY Tuberculosis is one of the leading causes of mortality in the world despite multiple control and treatment strategies. Disseminated tuberculosis corresponds to 5% of cases. We report the first case in literature of an adolescent patient with type 1 diabetes mellitus and disseminated tuberculosis, who had constitutional symptoms associated with low back pain and was initially, interpreted initially as noninfectious sacroiliitis and a probable inflammatory bowel disease.

Characteristics of hypoparathyroidism in Colombia: data from a single center in the city of Medellín.

OBJECTIVE: Hypoparathyroidism is a rare condition, whose most common etiology is complications of neck surgery. The aim of the study was to identify the clinical and biochemical profile of the patients with diagnosis of hypoparathyroidism, including the frequency of symptoms, clinical signs, long-term complications and disease control. Additionally, the study sought to know what the medication profile was, and the doses required by the patients. SUBJECTS AND METHOD: A retrospective cohort study was conducted wherein all patients with ICD-10 codes associated with hypoparathyroidism between 2011 and 2018 at the Hospital Universitario San Vicente Fundación were included. We investigated the etiology of the disease; biochemical profile including lowest serum calcium, highest serum phosphorus, 25OHD levels, calciuria and calcium/phosphorus product; medication doses, disease control, and presence of complications, especially renal and neurologic complications were also evaluated. RESULTS: The cohort included 108 patients (99 women/9 men) with a mean age of 51.6 ± 15.6 years. The main etiology was postoperative (93.5%), the dose of elemental calcium received was relatively low (mean 1,164 mg/day), and in only 9.2% of cases more than 2,500 mg/day of elemental calcium was necessary. We were able to evaluate the follow-up in 89 patients, and found that only 57.3% met the criteria for controlled disease. CONCLUSION: The clinical profile of patients with hypoparathyroidism in our cohort is similar to that described in other international studies, with predominantly postoperative etiology. With standard therapy, only adequate control is achieved in a little more than half of patients. Arch Endocrinol Metab. 2020;64(3):282-9.

Characteristics of hypoparathyroidism in Colombia: data from a single center in the city of Medellín

ABSTRACT Objective Hypoparathyroidism is a rare condition, whose most common etiology is complications of neck surgery. The aim of the study was to identify the clinical and biochemical profile of the patients with diagnosis of hypoparathyroidism, including the frequency of symptoms, clinical signs, long-term complications and disease control. Additionally, the study sought to know what the medication profile was, and the doses required by the patients. Subjects and method A retrospective cohort study was conducted wherein all patients with ICD-10 codes associated with hypoparathyroidism between 2011 and 2018 at the Hospital Universitario San Vicente Fundación were included. We investigated the etiology of the disease; biochemical profile including lowest serum calcium, highest serum phosphorus, 25OHD levels, calciuria and calcium/phosphorus product; medication doses, disease control, and presence of complications, especially renal and neurologic complications were also evaluated. Results The cohort included 108 patients (99 women/9 men) with a mean age of 51.6 ± 15.6 years. The main etiology was postoperative (93.5%), the dose of elemental calcium received was relatively low (mean 1,164 mg/day), and in only 9.2% of cases more than 2,500 mg/day of elemental calcium was necessary. We were able to evaluate the follow-up in 89 patients, and found that only 57.3% met the criteria for controlled disease. Conclusion The clinical profile of patients with hypoparathyroidism in our cohort is similar to that described in other international studies, with predominantly postoperative etiology. With standard therapy, only adequate control is achieved in a little more than half of patients. Arch Endocrinol Metab. 2020;64(3):282-9

SNAIL expression correlates with the translocation of syndecan­1 intracellular domain into the nucleus in prostate cancer cell lines.

Zinc finger protein SNAI1 (SNAIL) and zinc finger protein SNAI2 (SLUG) transcription factors promote epithelial­mesenchymal transition, a process through which epithelial cells acquire a mesenchymal phenotype, increasing their migratory and invasive properties. In prostate cancer (PCa) progression, increased expression levels of SNAIL and SLUG have been described. In advanced PCa, a decrease in the cell surface proteoglycan syndecan­1 (SDC­1), which has a role in cell­to­extracellular matrix adhesion, has been observed. Notably, SDC­1 nuclear location has been observed in mesenchymal cancers. The present study aimed to determine if SNAIL and SLUG may be associated with the nuclear location of SDC­1 in PCa. To determine the location of SDC­1, antibodies against its intracellular domain (ID) or extracellular domain (ED) were used in benign prostatic hyperplasia (BPH) and PCa samples with high Gleason scores. Only ID­SDC­1 was located in the cell nuclei in advanced PCa samples, but not in the BPH samples. ED­SDC­1 was located in the cell membrane and cytoplasm, exhibiting decreased levels in PCa in comparison with those in BPH. Furthermore, LNCaP and PC3 PCa cell lines with ectopic SNAIL expression exhibited nuclear ID­SDC­1. No change was observed in the ED­SDC­1 levels, and maintained its location in the cell membrane and cytoplasm. SLUG induced no change in ID­SDC­1 location. At the protein level, an association between SNAIL and nuclear ID­SDC­1 was observed. In conclusion, the results of the present study demonstrated that nuclear ID­SDC­1 localization was associated with SNAIL expression in PCa cell lines.

Alimentación y crecimiento de infantes de 0-2 años hijos de madres adolescentes de Dosquebradas, Colombia, año 2018 / Feeding and growth of infants from 0-2 years old children of adolescent mothers

Objetivo El presente artículo pretende describir el crecimiento y alimentación de un grupo de niños hijos de madres adolescentes en el rango de edad de 0-2 años. Metodología Se realizó un estudio cuantitativo, descriptivo, transversal, desarrollado a partir de la información recolectada por aplicación de dos instrumentos. La muestra fue determinada por muestreo no probabilístico a conveniencia, conformada por 100 infantes en el rango de edad de 0 a 2 años. Resultados El 93% de los infantes recibieron lactancia materna por lo menos la primera semanade vida, un 7% inició su alimentación con leche de fórmula, el 27% recibieron lactancia materna exclusiva durante los primeros 6 meses. Se observó que 18% de las madres abandonaron la lactancia materna, refiriendo como principal causa baja producción de leche. De las madres que dieron lactancia materna exclusiva 62,9% pertenecían al rango de edad entre los 20 y 21 años. Con respecto al crecimiento, el 75% de los infantes estaban en rango de normalidad, 10% presentaron riesgo de desnutrición, 1% se encontrada en desnutrición y 14% en riesgo de sobrepeso, se evidenció un porcentaje superior del IMC en rangos de normalidad y otros en riesgo de sobrepeso. Conclusiones Se evidenció la necesidad de educación con respecto a introducción adecuada de alimentos en la dieta infantil, así como el trabajo continuo de las pautas de crianza y dinámicas familiares saludables. La promoción de la salud en el área materno-infantil debe ser considerada en políticas implementadas por planes de gobierno a nivel local.

Objective To describe the growth and nutrition of a group of children of teenage mothers in the age range of 0-2 years old. Methodology A quantitative, descriptive, cross-sectional study was performed, developed from the information collected by applying two instruments. The sample was determined by non-probability sampling at convenience, made up of 100 infants in the age range of 0 to 2 years. Results 93% of infants were breastfed for at least the first week of life, 7% started formula feeding, 27% exclusively breastfed for the first 6 months. It was observed that 18% of the mothers abandoned breastfeeding, referring to low milk production as the main cause. Of the mothers who exclusively breastfed, 62.9% belonged to the age range between 20 and 21 years. Regarding growth, 75% of infants were in the normal range, 10% were at risk of malnutrition, 1% were undernourished and 14% at risk of overweight, a higher percentage of BMI was evident in normal ranges and others at risk of being overweight. Conclusions The need for education regarding the adequate introduction of food in the children's diet was evident, as well as the continuous work on parenting guidelines and healthy family dynamics. Health promotion in the mother-child area must be considered in policies implemented by government plans at the local level.

Neumonía a repetición en un paciente con deformidades óseas: a propósito de un caso de raquitismo / Recurrent pneumonia in a patient with bone deformity: a case report of ricketts

El raquitismo es una enfermedad ósea infrecuente asociada a la disminución de niveles séricos de calcio o fosfato, la mayoría de los casos como consecuencia de déficit nutricional, aunque puede presentarse por mutaciones genéticas o defectos adquiridos del metabolismo. El cuadro clínico es heterogéneo y depende de la edad de presentación; manifestándose con ensanchamiento y retraso de la mineralización de la placa de crecimiento ósea. Se presenta el caso de un niño indígena de 11 meses de edad con historia de neumonía recurrente, al examen físico, presentaba hipotonía muscular generalizada, tórax con rosario costal y deformidad en extremidades, con paraclínicos: hipocalcemia e hipofosfatemia, fosfatasa alcalina y hormona paratiroidea elevadas, niveles de 25-hidroxi-vitamina normales-altos y con valor de 1,25-dihidroxi-vitamina D muy bajo, se sugirió el diagnóstico de raquitismo dependiente de vitamina D tipo 1A severo, una forma infrecuente de esta patología.

Ricketts is a rare bone disease associated with low serum levels of calcium and phosphate. Most of the cases occur as a consequence of nutritional deficits, but genetic mutations or acquired metabolic defects may account for it. Clinical presentation is heterogenous depending on age at presentation, manifesting as widening and retardation of mineralization of the growing bone plate. We present the case of a 11 month of age child with a history of recurrent pneumonia presenting with generalized muscle hypotonia, deformed chest and bowed extremities with hypocalcemia and hypophosphatemia, elevated levels of alkaline phosphatase and parathyroid hormone, high levels of 25-hidroxy-vitamine D3 and very low levels of 1,25-dihidroxy-vitamine D3 suggesting the diagnosis of severe vitamin D type 1A rickets, a rare form of this disease.

Presentación atípica anogenital de virus herpes simple en un adulto VIH positivo, manejo exitoso con foscarnet: reporte de caso / Atypical anogenital herpes simple virus infection in an hiv patient, successfully treatment with foscarnet: a case report

Las lesiones anogenitales hipertróficas, pseudotumorales y similares a placas, son presentaciones atípicas del virus herpes simple (VHS). Estas lesiones desarrollan resistencia a los tratamientos y se presentan en inmunocomprometidos, especialmente aquellos con infección por el virus de inmunodeficiencia humana (VIH). Presentamos el caso de un paciente masculino de 38 años de edad, VIH/SIDA, con antecedente de carcinoma escamocelular infiltrante de canal anal, con lesiones múltiples hipertróficas anogenitales y exudativas, a quien se le confirma infección por VHS-1, sin respuesta a aciclovir ni valaciclovir a dosis óptimas, el cual resuelve con 21 días de foscarnet intravenoso. Nuestro caso muestra la importancia de considerar el uso de foscarnet en adultos con infección de VIH y del VHS, que no respondan a tratamiento de primera línea, en un país donde no hay esquemas establecidos de manejo para este tipo de presentaciones y donde existe la limitante de no haber disponibilidad en pruebas para resistencia a antivirales.

Pseudotumoral, hypertrophic, plaque-like anogenital ulcers are atypical features of herpes simplex infection. These ulcers develop treatment resistance and they appear in immunocompromised mainly those infected by human immunodeficiency virus. We present a 38 years-old man with AIDS and personal history of infiltrative squamous carcinoma of anal canal with multiple hypertrophic and exudative ulcers secondary to VHS-1 etiology without response to acyclovir neither valacyclovir at optimal doses but complete answer with 21 days of foscarnet treatment. Our case highlights the role of foscarnet in adults with HIV-HSV coinfection that don't respond to frst line treatment in a country that doesn't have clear treatment recommendations in these cases and with the limitations of absence of antiviral resistance test.

The transcription factor ZEB1 promotes chemoresistance in prostate cancer cell lines.

One of the factors promoting tumoral progress is the abnormal activation of the epithelial-mesenchymal transition (EMT) program which has been associated with chemoresistance in tumoral cells. The transcription factor zinc finger E-box-binding homeobox 1 (ZEB1), a key EMT activator, has recently been related to docetaxel resistance, the main chemotherapeutic used in advanced prostate cancer treatment. The mechanisms involved in this protective effect are still unclear. In a previous work, we demonstrated that ZEB1 expression induced an EMT-like phenotype in prostate cancer cell lines. In this work, we used prostate cancer cell lines 22Rv1 and DU145 to study the effect of ZEB1 modulation on docetaxel resistance and its possible mechanisms. The results showed that ZEB1 overexpression conferred to 22Rv1 cell resistance to docetaxel while its silencing made DU145 cells more sensitive to it. Analysis of resistance markers showed no presence of ATP-binding cassette subfamily B member 1 (MDR1) and no changes in breast cancer resistance protein (BCRP) or ATP-binding cassette subfamily C member 10 (MRP7). However, a correlation between ZEB1, multidrug resistance-associated protein 1 (MRP1), and ATP-binding cassette subfamily C member 4 (MRP4) expression was observed. MRP4 inhibition, using MK571, resensitized cells with ZEB1 overexpression to docetaxel treatment. In addition, modulation of ZEB1 and subsequent change in MRP4 expression correlated with a lower apoptotic response to docetaxel, characterized by lower B-cell lymphoma 2 (Bcl2), high BCL2-associated X protein (Bax), and high active caspase 3 expression. The response to docetaxel in our model seems to be mediated mainly by activation of the apoptotic death program. Our results showed that modulation of MRP4 could be a mediator of ZEB1-related resistance to docetaxel in prostate cancer, making it a possible marker for chemotherapy response in patients who do not express MDR1.