Bioprospecting of extremophilic perchlorate-reducing bacteria: report of promising Bacillus spp. isolated from sediments of the bay of Cartagena, Colombia.

Three extremophile bacterial strains (BBCOL-009, BBCOL-014 and BBCOL-015), capable of degrading high concentrations of perchlorate at a range of pH (6.5 to 10.0), were isolated from Colombian Caribbean Coast sediments. Morphological features included Gram negative strain bacilli with sizes averaged of 1.75 × 0.95, 2.32 × 0.65 and 3.08 × 0.70 µm, respectively. The reported strains tolerate a wide range of pH (6.5 to 10.0); concentrations of NaCl (3.5 to 7.5% w/v) and KClO4- (250 to 10000 mg/L), reduction of KClO4- from 10 to 25%. LB broth with NaCl (3.5-30% w/v) and KClO4- (250-10000 mg/L) were used in independent trials to evaluate susceptibility to salinity and perchlorate, respectively. Isolates increased their biomass at 7.5 % (w/v) NaCl with optimal development at 3.5 % NaCl. Subsequently, ClO4- reduction was assessed using LB medium with 3.5% NaCl and 10000 mg/L ClO4-. BBCOL-009, BBCOL-014 and BBCOL-015 achieved 10%, 17%, and 25% reduction of ClO4-, respectively. The 16 S rRNA gene sequence grouped them as Bacillus flexus T6186-2, Bacillus marisflavi TF-11 (T), and Bacillus vietnamensis 15 - 1 (T) respectively, with < 97.5% homology. In addition, antimicrobial resistance to ertapenem, vancomycine, amoxicillin clavulanate, penicillin, and erythromycin was present in all the isolates, indicating their high adaptability to stressful environments. The isolated strains from marine sediments in Cartagena Bay, Colombia are suitable candidates to reduce perchlorate contamination in different environments. Although the primary focus of the study of perchlorate-reducing and resistant bacteria is in the ecological and agricultural realms, from an astrobiological perspective, perchlorate-resistant bacteria serve as models for astrobiological investigations.

Left Atrial Appendage Aneurysm: A Case Report and Literature Review.

The left atrial appendage aneurysm is an uncommon condition that has garnered attention from the medical community due to its low incidence and varied clinical manifestations. The difficulty in identification is reflected in its incidental detection in imaging studies such as echocardiograms and tomographies, while symptoms range from mild to severe, including heart failure and thromboembolic events. The complex etiology includes congenital and acquired factors, and its management focuses on preventing complications through surgical resection, accompanied by medical strategies such as controlling heart rhythm and anticoagulation. The case of a 67-year-old woman with significant medical history illustrates these challenges. Despite an inconclusive initial diagnosis, a tomography revealed an aneurysm with an intracavitary thrombus, leading to successful surgical resection. However, subsequent infectious complications resulted in her death. The average age of diagnosis is around 30 years, and while it is more common in women, there are no significant gender differences. Surgical management remains the preferred option, especially in severe cases, although in some patients, a watchful waiting approach is chosen. In conclusion, the left atrial appendage aneurysm is a complex entity that requires a multidisciplinary approach to improve clinical outcomes. Early diagnosis and appropriate treatment are crucial to prevent serious complications and improve the quality of life of affected patients.

Occurrence and toxicological relevance of pesticides and trace metals in agricultural soils, sediments, and water of the Sogamoso River basin, Colombia.

Historical pesticide use in agriculture and trace metal accumulation have long term impact on soil, sediment, and water quality. This research quantifies legacy and current-use pesticides and trace metals, assessing their occurrence and toxicological implications on a watershed scale in the Sogamoso River basin, tributary of the Magdalena River in Colombia. Organochlorine pesticides (22), organophosphates (7), and azole fungicides (5), as well as trace metals cadmium (Cd), chromium (Cr), copper (Cu), mercury (Hg), nickel (Ni), lead (Pb), and zinc (Zn) were analyzed in croplands and along the river. Toxic units (TU) and hazard quotients (HQ) were calculated to assess the mixture toxicity. Organochlorines were detected in 84% of soils, 100% of sediments, and 80% of water samples. Organophosphates were found in 100% of soil and sediment samples, as well as in 70% of water samples. Azole fungicides were present in 79% of soils, 60% of sediments, and in 10% of water samples. Total pesticide concentrations ranged from 214.2 to 8497.7 µg/kg in soils, 569.6-12768.2 µg/kg in sediments, and 0.2-4.1 µg/L in water. In addition, the use of partition coefficient (Kd) and organic carbon fraction (foc) allowed the distribution analysis for most of the pesticides in sediments, suspended particulate matter (SPM), and water systems, but not for soils. Concentrations of trace metals Cu, Zn, Pb, and Zn exceeded international quality guidelines for agricultural soils in 16% of the samples. Furthermore, Cu and Zn concentrations exceeded sediment quality guidelines in 50 and 90% of the samples, respectively. These findings demonstrate the broad distribution of complex mixtures of trace metals, legacy organochlorines, and current-use pesticides across the basin, indicating that conventional agriculture is a significant source of diffuse pollution. Sustainable agricultural practices are needed to mitigate adverse impacts on ecosystems and human health.

Central CO2 chemosensitivity and CO2 controller gain independently contribute to daytime Pco2 in young subjects with congenital central hypoventilation syndrome.

Whether peripheral chemoreceptor response is altered in congenital central hypoventilation syndrome (CCHS) remains debated. Our aim was to prospectively evaluate both peripheral and central CO2 chemosensitivity and to evaluate their correlations with daytime Pco2 and arterial desaturation during exercise in CCHS. To this end, tidal breathing was recorded in patients with CCHS allowing the calculation of loop gain and its components {steady-state controller (assumed to mainly be peripheral chemosensitivity) and plant gains using a bivariate [end-tidal Pco2 ([Formula: see text]) and ventilation] constrained model}, a hyperoxic, hypercapnic ventilatory response test (central chemosensitivity), and a 6-min walk test (arterial desaturation). The results of loop gain were compared with those previously obtained in a healthy group of similar age. The study prospectively included 23 subjects with CCHS, without daytime ventilatory support; the subjects had a median age of 10 (5.6 to 27.4) yr (15 females) with moderate polyalanine repeat mutation (PARM: 20/25, 20/26, n = 11), severe PARM (20/27, 20/33, n = 8), or non-PARM (n = 4). As compared with 23 healthy subjects (4.9-27.0 yr), the subjects with CCHS had a decreased controller gain and an increased plant gain. Mean daytime [Formula: see text] level of subjects with CCHS correlated negatively to both Log(controller gain) and the slope of CO2 response. Genotype was not related to chemosensitivity. Arterial desaturation on exercise correlated negatively with Log(controller) gain but not with the slope of the CO2 response. In conclusion, we demonstrate that peripheral CO2 chemosensitivity is altered in some patients with CCHS and that the daytime [Formula: see text] depends on central and peripheral chemoreceptor responses.NEW & NOTEWORTHY Altered central CO2 chemosensitivity is a hallmark of congenital central hypoventilation syndrome (CCHS). Peripheral CO2 chemosensitivity can be partly assessed by controller gain measurement obtained from tidal breathing recording. In young subjects with CCHS, this study shows that both central and peripheral CO2 sensitivities independently contribute to daytime Pco2. Hypocapnia during nighttime-assisted ventilation is associated with higher peripheral chemosensitivity that is further associated with lesser arterial desaturation at walk.

Marine Pollution and Advances in Biomonitoring in Cartagena Bay in the Colombian Caribbean.

Coastal zones sustain extensive biodiversity, support key processes for ocean dynamics, and influence the balance of the global environment. They also provide resources and services to communities, determine their culture, and are the basis for their economic growth. Cartagena Bay in the Colombian Caribbean is the place of the establishment of one of the country's main cities, which has a great historical and tourist attraction, and it is also the location of the main commercial port and a great variety of industries. Historically, it has been affected by several environmental impacts and intense pollution. This situation has gained the attention of different researchers, so herein is presented a literature review with a systematic approach using RStudio's bibliometrix on the presence of pollutants and the impact on biodiversity in recent decades, providing a critical analysis of the state of Cartagena Bay and its future needs to ensure its recovery and conservation. In addition, the socioeconomic dynamics related to the environmental state of Cartagena Bay are presented from the framework drivers, pressures, status, impacts, and responses (DPSIR). The update and critical understanding of the sources, fate, and effects of pollution are important not only for the knowledge of the status of this singular ecosystem but also to encourage future research and entrench evidence to support decision makers' actions. This review highlights that several pollutants that have been detected exceeding sediment quality guidelines, like As, Cd, Hg, and PAH, are also reported to bioaccumulate and cause damage throughout the trophic levels of the coastal environment. In addition, the potential use of sentinel species and biomarkers for their monitoring is discussed. Finally, the factors that cause pollution and threaten the state of the bay continue to exert pressure and impact; thus, there is a call for the further monitoring of this ecosystem and the strengthening of policies and regulations.

A decrease in plant gain, namely CO2 stores, characterizes dysfunctional breathing whatever its subtype in children.

Background: Whether dysfunctional breathing (DB) subtype classification is useful remains undetermined. The hyperventilation provocation test (HVPT) is used to diagnose DB. This test begins with a 3-min phase of hyperventilation during which fractional end-tidal CO2 (FETCO2) decreases that could be an assessment of plant gain, which relies on CO2 stores. Our aim was to assess 1) whether the children suffering from different subtypes of DB exhibit decreased plant gain and 2) the relationships between HVPT characteristics and plant gain. Methods: We retrospectively selected 48 children (median age 13.5 years, 36 females, 12 males) who exhibited during a cardiopulmonary exercise test either alveolar hyperventilation (transcutaneous PCO2 < 30 mmHg, n = 6) or inappropriate hyperventilation (increased VE'/V'CO2 slope) without hypocapnia (n = 18) or dyspnea without hyperventilation (n = 18) compared to children exhibiting physiological breathlessness (dyspnea for sports only, n = 6). These children underwent tidal-breathing recording (ventilation and FETCO2 allowing the calculation of plant gain) and a HVPT. Results: The plant gain was significantly higher in the physiological group as compared to the dyspnea without hyperventilation group, p = 0.024 and hyperventilation without hypocapnia group, p = 0.008 (trend for the hyperventilation with hypocapnia group, p = 0.078). The slope of linear decrease in FETCO2 during hyperventilation was significantly more negative in physiological breathlessness group as compared to hyperventilation without hypocapnia group (p = 0.005) and dyspnea without hyperventilation group (p = 0.049). Conclusion: The children with DB, regardless of their subtype, deplete their CO2 stores (decreased plant gain), which may be due to intermittent alveolar hyperventilation, suggesting the futility of our subtype classification.

Heart rate variability in congenital central hypoventilation syndrome: relationships with hypertension and sinus pauses.

BACKGROUND: Autonomic nervous system (ANS) dysregulation has been described in congenital central hypoventilation syndrome (CCHS). The objectives were to describe heart rate variability (HRV) analyses in children suffering from CCHS both while awake and asleep and their relationships with both ambulatory blood pressure (BP) and ECG monitoring results. METHODS: This retrospective study enrolled children with CCHS (n = 33, median age 8.4 years, 18 girls) who had BP and ECG monitored during the same 24 h. From the latter, HRV analyses were obtained during daytime and nighttime. RESULTS: The prevalences of hypertension and sinus pauses were 33% (95% confidence interval [CI]: 18-52) and 18% (95% CI: 7-35), respectively. The decrease in systolic BP at night negatively correlated with an increase in very low frequency (VLF) and LF powers at night, and the longest RR interval positively correlated with daytime VLF and LF powers. Among the three groups of children (polyalanine repeat expansion mutation [PARM], moderate [20/25 and 20/26], severe [20/27 and 20/33], and non-PARMs), the prevalence of elevated BP or hypertension was different: in PARM subjects: 6/18 moderate, 7/9 severe versus 0/6 in non-PARM (p = 0.002). CONCLUSION: Modifications of cardiac ANS are associated with systemic hypertension and the occurrence of sinus pauses in CCHS. IMPACT: Children with congenital central hypoventilation syndrome (CCHS) exhibit an increased prevalence of hypertension and sinus pauses that are linked to cardiac autonomic nervous system dysfunction. Sinus pauses are the main manifestation of sinus nodal dysfunction in children with CCHS. The increased prevalence of hypertension, especially at nighttime, is a new finding in CCHS. Sinus nodal dysfunction can be due to the sole impairment of the cardiac autonomic nervous system. Ambulatory blood pressure and ECG monitoring are mandatory in patients with CCHS.

Oropharyngeal obstruction and respiratory system compliance are linked to ventilatory control parameters in pediatric obstructive sleep apnea syndrome.

Instable ventilatory control is an endotypic trait of obstructive sleep apnea syndrome (OSAS). This study aimed to evaluate the relationships between the anatomical compromise of the upper (oro- and naso-pharynx) and lower airways and ventilatory control (measured by chemical loop gain) in otherwise healthy children suffering from moderate to severe OSAS (apnea hypopnea index ≥ 5/hour). The children underwent ear, nose and throat examination, measurement of impedance of the respiratory system that allowed characterizing peripheral lung mechanics using the extended Resistance-Inertance-Compliance model. Physiologically constrained analytical model based on tidal breathing analysis allowed for the computation of steady-state plant gain, steady-state controller gain (CG0) and steady-state loop gain (LG0). Medium-frequency components of the feedback control system were then deduced. Fifty children (median age 11.2 years) were enrolled. Oropharyngeal obstruction was associated with decreased CG0 (0.6 [0.2; 1.0] vs 1.5 [0.5; 6.6] L.s- 1.mmHg- 1, p = 0.038) and LG0 (0.4 [0.2; 1.1] vs 1.2 [0.4; 9.3], p = 0.027), while nasal obstruction did not modify ventilatory control parameters. In a multivariate analysis Medium-Frequency PG was negatively related to minute ventilation and respiratory system compliance. Both upper (tonsil hypertrophy) and lower (compliance of respiratory system) airways are linked to ventilatory control in children with moderate to severe OSAS.

Obstructive Apneas in a Mouse Model of Congenital Central Hypoventilation Syndrome.

Rationale: Congenital central hypoventilation syndrome (CCHS) is characterized by life-threatening sleep hypoventilation and is caused by PHOX2B gene mutations, most frequently the PHOX2B27Ala/+ mutation, with patients requiring lifelong ventilatory support. It is unclear whether obstructive apneas are part of the syndrome. Objectives: To determine if Phox2b27Ala/+ mice, which present the main symptoms of CCHS and die within hours after birth, also express obstructive apneas, and to investigate potential underlying mechanisms. Methods: Apneas were classified as central, obstructive, or mixed by using a novel system combining pneumotachography and laser detection of abdominal movement immediately after birth. Several respiratory nuclei involved in airway patency were examined by immunohistochemistry and electrophysiology in brainstem-spinal cord preparations. Measurements and Main Results: The median (interquartile range) of obstructive apnea frequency was 2.3 (1.5-3.3)/min in Phox2b27Ala/+ pups versus 0.6 (0.4-1.0)/min in wild types (P < 0.0001). Obstructive apnea duration was 2.7 seconds (2.3-3.9) in Phox2b27Ala/+ pups versus 1.7 seconds (1.1-1.9) in wild types (P < 0.0001). Central and mixed apneas presented similar significant differences. In Phox2b27Ala/+ preparations, the hypoglossal nucleus had fewer (P < 0.05) and smaller (P < 0.01) neurons, compared with wild-type preparations. Importantly, coordination of phrenic and hypoglossal motor activities was disrupted, as evidenced by the longer and variable delay of hypoglossal activity with respect to phrenic activity onset (P < 0.001). Conclusions: The Phox2b27Ala/+ mutation predisposed pups not only to hypoventilation and central apneas, but also to obstructive and mixed apneas, likely because of hypoglossal dysgenesis. These results thus demand attention toward obstructive events in infants with CCHS.

Determinación de los factores predictivos para complicaciones en cirugía electiva de pacientes con cáncer colorrectal. Experiencia del Instituto de Cancerología Las Américas Auna (Colombia, 2016-2019) / Determination of predictive factors for complications in elective surgeryof colorectal cancer patients. Experience of the Instituto de CancerologíaLas Américas Auna (Colombia, 2016-2019)

Introducción. El pilar fundamental del tratamiento del cáncer colorrectal es la cirugía, situación que expone a los pacientes a la posible presentación de complicaciones, morbimortalidad, pobre calidad de vida, recurrencia tumoral o la muerte. El objetivo de este estudio fue determinar las variables clínicas y quirúrgicas que inciden en el riesgo de la aparición de complicaciones en los pacientes con cáncer colorrectal llevados a cirugía electiva entre los años 2016 y 2019. Métodos. Estudio observacional, descriptivo, transversal y retrospectivo. Se incluyeron pacientes mayores de 18 años con cáncer colorrectal sometidos a cirugía electiva. Se realizó un análisis multivariado para determinar los factores que se relacionan con las complicaciones postquirúrgicas. Resultados. Se incluyeron 298 pacientes, 68 % mayores de 60 años, 52,3 % mujeres, 74,2 % presentaban comorbilidades y 48,3 % fueron diagnosticados en estadio III. El 48,3 % presentó complicaciones postoperatorias. De ellos, el 68,1 % no tenía tamización nutricional y el 61,8 % no tenía preparación del colon; un 55 % fueron cirugías del recto, 69,1 % de las cirugías fueron por vía laparoscópica y 71,8 % presentaron sangrado inferior a 500 ml. La mayoría de las complicaciones fueron clasificadas como Clavien-Dindo I-III. Discusión. Las características de los pacientes fueron similares a los presentados en otros estudios, aunque hubo mayor incidencia de íleo postoperatorio. El análisis multivariado mostró una mayor probabilidad de presentar una complicación en pacientes con diabetes mellitus, hipertensión arterial, falta de tamización nutricional o preparación de colon, cirugía de recto y el sangrado mayor a 500 ml

Introduction. The fundamental pillar of colorectal cancer treatment is surgery, a situation that exposes patients to the possible presentation of complications, morbidity and mortality, poor quality of life, tumor recurrence or death. The objective of this study was to determine the clinical and surgical variables that affect the risk of the appearance of complications in colorectal cancer patients taken to elective surgery between 2016 and 2019.Methods. Observational, descriptive, cross-sectional and retrospective study. Patients over the age of 18 with colorectal cancer undergoing elective surgery were included. A multivariate analysis was performed to determine the factors related to postsurgical complications. Results. We included 298 patients, 68% over 60 years of age, 52.3% women, 74.2% had comorbidities and 48.3% were diagnosed in stage III. 48.3% presented postoperative complications; of these, 68.1% had no nutritional screening, and 61.8% had no colon preparation; 55% were rectal cancer surgeries, 69.1% underwent laparoscopic surgeries, and 71.8% had bleeding less than 500 ml. Most complications were classified as Clavien Dindo I-III. Discussion. The characteristic of the patients was similar to those presented in other studies, even though we had more incidence of postoperative ileus. The multivariate analysis showed a higher probability of complications in patients with: diabetes, hypertension, lack of nutritional screening, bleeding over 500cc, lack of colon mechanical preparation and rectal cancer surgery.Patient characteristics were similar to those presented in other studies, although there was a higher incidence of postoperative ileus. The multivariate analysis showed a greater probability of presenting a complication in patients with diabetes mellitus, arterial hypertension, lack of nutritional screening, colon preparation, rectal cancer surgery, and bleeding greater than 500 ml

Gene expression and morphological responses of Lolium perenne L. exposed to cadmium (Cd2+) and mercury (Hg2+).

Soil contamination with heavy metals is a major problem worldwide, due to the increasing impact mainly caused by anthropogenic activities. This research evaluated the phytoremediation capacity of, Lolium perenne for heavy metals such as cadmium (Cd2+) and mercury (Hg2+), and the effects of these metals on morphology, biomass production, and the changes on gene expression. Seeds of L. perenne were exposed to six concentrations of Cd2+ and Hg2+ in the range of 0 to 25 mg L-1, and two mixtures of Cd2+-Hg2. The Non-Observed Effect Level (NOEL) was established with dose response curves and the expression of specific genes was evaluated applying a commercially available quantitative reverse transcription (RT-qPCR) assay. There was no significant effect when exposing the seeds to Hg2+, for Cd2+ the maximum concentration was established in 0.1 mg L-1, and for the two concentrations of mixtures, there was a negative effect. An increase of expression of genes that regulate antioxidant activity and stress was found when the plant was exposed to heavy metals. Given the high tolerance to metals analyzed that was reflected both, the development of the plant and in its molecular response, these results highlight that L. perenne is a plant with phytoremediator potential.

Cross-sectional case-control study of the relationships between pharyngeal compliance and heart rate variability indices in childhood obstructive sleep apnoea.

A combination of noradrenergic and antimuscarinic agents reduces the apnea-hypopnea index (AHI) in adult patients with obstructive sleep apnoea (OSA) via reduced upper airway collapsibility, suggesting that a shift in the sympathovagal balance improves OSA. The objectives of our present case-control study were to assess heart rate variability (HRV) indices in the stages of sleep in children with and without OSA to evaluate OSA-induced sleep HRV modifications and to assess whether increased collapsibility measured during wakefulness is associated with reduced sympathetic activity during non-rapid eye movement (NREM) sleep. Three groups of 15 children were matched by sex, age, z-score of body mass index and ethnicity: non-OSA (obstructive AHI [OAHI] <2 events/hr), mild (OAHI ≥2 to <5 events/hr) or moderate-severe (OAHI ≥5 events/hr) OSA. Pharyngeal compliance was measured during wakefulness using acoustic pharyngometry. HRV indices (time and frequency domain variables) were calculated on 5-min electrocardiography recordings from polysomnography during wakefulness, NREM and REM sleep in periods free of any event. As compared to children without OSA, those with OSA (n = 30) were characterised by increased compliance and no physiological parasympathetic tone increase in REM sleep. Children with increased pharyngeal compliance (n = 21) had a higher OAHI due to higher AHI in NREM sleep, whereas their sympathetic tone was lower than that of those with normal compliance (n = 24). In conclusion, children with increased pharyngeal compliance exhibit decreased sympathetic tone associated with increased AHI in NREM sleep. Therapeutics directed at sympathovagal balance modifications should be tested in childhood OSA.

Cytogenetic toxicity from pesticide and trace element mixtures in soils used for conventional and organic crops of Allium cepa L.

Pesticides and trace elements occur in complex mixtures in agroecosystems, affecting soil health and food security. Hence, it is necessary to determine their toxicity in field conditions and to develop monitoring approaches to assess conventional and organic agriculture. The aim of this research was to evaluate the associations between Allium cepa L. cytogenetic biomarkers and the realistic mixture of pesticides and trace elements found in soils of conventional, conversion, and organic crops in an intensive agricultural region in Colombia. Pesticide screening was conducted using GC-MS/MS and LC-MS/MS methods. Arsenic, cadmium, lead, and zinc were analyzed by ICP-MS; chromium, copper, nickel, and selenium by ICP-OES; and mercury by a direct analyzer. The meristematic cells in roots of Allium cepa L. were analyzed through microscopic observations to quantify cytogenetic effects. In conventional crops, 26 pesticides were detected in the soil samples, and those were below the limit of quantification in organic crops. The mean levels of As, Cd, Cr, Ni, Pb, and Se were also greater in soils of conventional crops compared to the organics. In addition, the biomarkers of cytotoxicity and genotoxicity appeared augmented in conventional samples, and those were correlated with pesticide and trace element concentrations, pollution indices, and hazard quotients. Subsequently, a discriminant function based on the mitotic index, chromosomal aberrations, and nuclear abnormalities was suitable to classify the samples by crop type. These results demonstrate the sensitivity of Allium cepa L. to the toxicity of complex mixtures in field crops and its potential as an in-situ approach for soil health monitoring in organic and conventional crop systems.

Preventing rather than punishing: An early warning model of malfeasance in public procurement.

Is it possible to predict malfeasance in public procurement? With the proliferation of e-procurement systems in the public sector, anti-corruption agencies and watchdog organizations have access to valuable sources of information with which to identify transactions that are likely to become troublesome and why. In this article, we discuss the promises and challenges of using machine learning models to predict inefficiency and corruption in public procurement. We illustrate this approach with a dataset with more than two million public procurement contracts in Colombia. We trained machine learning models to predict which of them will result in corruption investigations, a breach of contract, or implementation inefficiencies. We then discuss how our models can help practitioners better understand the drivers of corruption and inefficiency in public procurement. Our approach will be useful to governments interested in exploiting large administrative datasets to improve the provision of public goods, and it highlights some of the tradeoffs and challenges that they might face throughout this process.

[Prevalence of lymph node involvement in patients with endometrial cancer, Colombia 2009-2016: Exploratory analysis of associated factors].

OBJECTIVE: To determine the prevalence of lymph node involvement in patients with endometrial cancer and to explore factors associated with lymph node invasion. METHODS: Prevalence study with exploratory analysis. The study included patients with endometrial cancer who underwent total abdominal hysterectomy plus bilateral salpyingooophorectomy and pelvic lymphadenectomy with or without para-aortic lymphadenectomy in seven oncology centers in Colombia between 2009 and 2016. Patients who had received prior radiotherapy or chemotherapy, with a histological diagnosis of neuroendocrine tumors, carcinosarcomas or synchronous or metachronous lesions were excluded. Non-probabilistic sampling. Sample size n=290. Measured variables: sociodemographic, clinical and histopathological, and pelvic or para-aortic lymph node involvement. The prevalence for the period is presented. The exploratory analysis was conducted using crude odds ratio (OR) and adjusted OR by means of a multivariate model (unconditional logistic regression). RESULTS: Overall, 467 cases were retrieved. Of them, 163 were excluded because of non-availability of all the variables. In total, 304 patients were studied. The prevalence of lymph node involvement was 15.8 % (48/304). In the crude and adjusted analysis, factors associated with lymph node involvement were lymphovascular invasion (adjusted OR: 9.32; 95 % CI 4.27-21.15) and myometrial invasion (adjusted OR: 3.95; 95 % CI 1.29-14.98). CONCLUSIONS: Of the patients undergoing lymphadenectomy, 15 % have lymph node involvement. Less invasive diagnostic options than radical surgery to ascertain lymph node invasion should be assessed.

TITULO: PREVALENCIA DEL COMPROMISO GANGLIONAR EN PACIENTES CON CÁNCER DE ENDOMETRIO, COLOMBIA 2009-2016: ANÁLISIS EXPLORATORIO DE FACTORES ASOCIADOS. OBJETIVO: Determinar la prevalencia del compro miso ganglionar de pacientes con cáncer de endometrio y hacer una exploración de los factores asociados a la invasión ganglionar. METODOS: Estudio de prevalencia con análisis exploratorio. Se incluyeron pacientes con cáncer de endometrio llevadas a histerectomía abdominal total más salpingooforectomía bilateral y linfadenectomía pélvica, con o sin linfadenectomía paraaórtica en siete centros de oncología de Colombia, en el periodo 2009-2016. Se excluyeron pacientes con radioterapia o quimioterapia previa, diagnóstico histológico de tumores neuroendocrinos, carcinosarcomas, tumores sincrónicos o metacrónicos. Muestreo no probabilístico. Tamaño muestral n = 290. Variables medidas: sociodemográficas, clínicas e histopatológicas y compromiso ganglionar pélvico o paraaórtico. Se presenta la prevalencia de periodo; el análisis exploratorio se realizó por medio de odds ratio (OR) crudo y el ajustado mediante un modelo multivariado (regresión logística no condicional). RESULTADOS: Se obtuvieron 467 casos de los cuales se excluyeron 163 por no presentar la totalidad de las variables, se estudiaron 304 pacientes. La prevalencia del compromiso ganglionar fue del 15,8 % (48/304). Los factores asociados al compromiso ganglionar en el análisis crudo y ajustado fueron la invasión linfovascular (OR ajustado = 9,32; IC 95 %: 4,27-21,15) e invasión miometrial (OR ajustado = 3.95; IC 95 %: 1,29-14,98). CONCLUSIONES: El 15 % de las pacientes sometidas a linfadenectomía tienen compromiso ganglionar. Se deben evaluar alternativas diagnósticas menos invasivas que la cirugía radical para establecer la invasión ganglionar.

Prevalence of lymph node involvement in patients with endometrial cancer, Colombia 2009-2016: Exploratory analysis of associated factors / Prevalencia del compromiso ganglionar en pacientes con cáncer de endometrio, colombia 2009-2016: análisis exploratorio de factores asociados

RESUMEN Objetivo: determinar la prevalencia del compro miso ganglionar de pacientes con cáncer de endometrio y hacer una exploración de los factores asociados a la invasión ganglionar. Materiales y métodos: estudio de prevalencia con análisis exploratorio. Se incluyeron pacientes con cáncer de endometrio llevadas a histerectomía abdominal total más salpingooforectomía bilateral y linfadenectomía pélvica, con o sin linfadenectomía paraaórtica en siete centros de oncología de Colombia, en el periodo 2009-2016. Se excluyeron pacientes con radioterapia o quimioterapia previa, diagnóstico histológico de tumores neuroendocrinos, carcinosarcomas, tumores sincrónicos o metacrónicos. Muestreo no probabilístico. Tamaño muestral n = 290. Variables medidas: sociodemográficas, clínicas e histopatológicas y compromiso ganglionar pélvico o paraaórtico. Se presenta la prevalencia de periodo; el análisis exploratorio se realizó por medio de odds ratio (OR) crudo y el ajustado mediante un modelo multivariado (regresión logística no condicional). Resultados: se obtuvieron 467 casos de los cuales se excluyeron 163 por no presentar la totalidad de las variables, se estudiaron 304 pacientes. La prevalencia del compromiso ganglionar fue del 15,8 % (48/304). Los factores asociados al compromiso ganglionar en el análisis crudo y ajustado fueron la invasión linfovascular (OR ajustado = 9,32; IC 95 %: 4,27-21,15) e invasión miometrial (OR ajustado = 3.95; IC 95 %: 1,29-14,98). Conclusión: el 15 % de las pacientes sometidas a linfadenectomía tienen compromiso ganglionar. Se deben evaluar alternativas diagnósticas menos invasivas que la cirugía radical para establecer la invasión ganglionar.

ABSTRACT Objective: To determine the prevalence of lymph node involvement in patients with endometrial cancer and to explore factors associated with lymph node invasion. Materials and methods: Prevalence study with exploratory analysis. The study included patients with endometrial cancer who underwent total abdominal hysterectomy plus bilateral salpyingooophorectomy and pelvic lymphadenectomy with or without para-aortic lymphadenectomy in seven oncology centers in Colombia between 2009 and 2016. Patients who had received prior radiotherapy or chemotherapy, with a histological diagnosis of neuroendocrine tumors, carcinosarcomas or synchronous or metachronous lesions were excluded. Non-probabilistic sampling. Sample size n=290. Measured variables: sociodemographic, clinical and histopathological, and pelvic or para-aortic lymph node involvement. The prevalence for the period is presented. The exploratory analysis was conducted using crude odds ratio (OR) and adjusted OR by means of a multivariate model (unconditional logistic regression). Results: Overall, 467 cases were retrieved. Of them, 163 were excluded because of non-availability of all the variables. In total, 304 patients were studied. The prevalence of lymph node involvement was 15.8 % (48/304). In the crude and adjusted analysis, factors associated with lymph node involvement were lymphovascular invasion (adjusted OR: 9.32; 95 % CI 4.27-21.15) and myometrial invasion (adjusted OR: 3.95; 95 % CI 1.29-14.98). Conclusion: Of the patients undergoing lymphadenectomy, 15 % have lymph node involvement. Less invasive diagnostic options than radical surgery to ascertain lymph node invasion should be assessed.

Cross-sectional study of loop gain abnormalities in childhood obstructive sleep apnea syndrome.

STUDY OBJECTIVES: We aimed to assess ventilatory control in typically developing children with and without obstructive sleep apnea (OSA). METHODS: Otherwise healthy children referred for suspicion of OSA were recruited. In addition to polysomnography, we analyzed loop, controller and plant gains (ie, LG, CG, and PG), which reflect the stability of control, chemoreceptor sensitivity and the pulmonary control of blood gases in response to changes in ventilation, respectively, from tidal breathing recordings during wakefulness. Two bivariate (ventilation, end-tidal CO2: one unconstrained and one constrained) and one trivariate (plus end-tidal oxygen) unconstrained model were used to assess model consistency and oxygen chemosensitivity. RESULTS: In sum, 54 children (median age 11.6 years) were included. Children with OSA (n = 19, [obstructive apnea-hypopnea index] OAHI ≥2.h-1) had a higher plant gain compared with those without OSA (n = 35), and it was positively correlated with apnea hypopnea index (AHI) (r2 = 0.10, p < 0.020). The two models showed consistent results. The bivariate constrained model showed that children with OAHI ≥5.h-1 showed an increased steady-state plant gain compared with children with OAHI <5.h-1. The trivariate model did not show evidence of any abnormality of oxygen chemosensitivity. CONCLUSION: Plant gain may contribute to OSA pathophysiology in children, and therapies directed at its reduction should be tested.

Breathing under Anesthesia: A Key Role for the Retrotrapezoid Nucleus Revealed by Conditional Phox2b Mutant Mice.

BACKGROUND: Optimal management of anesthesia-induced respiratory depression requires identification of the neural pathways that are most effective in maintaining breathing during anesthesia. Lesion studies point to the brainstem retrotrapezoid nucleus. We therefore examined the respiratory effects of common anesthetic/analgesic agents in mice with selective genetic loss of retrotrapezoid nucleus neurons (Phox2b mice, hereafter designated "mutants"). METHODS: All mice received intraperitoneal ketamine doses ranging from 100 mg/kg at postnatal day (P) 8 to 250 mg/kg at P60 to P62. Anesthesia effects in P8 and P14 to P16 mice were then analyzed by administering propofol (100 and 150 mg/kg at P8 and P14 to P16, respectively) and fentanyl at an anesthetic dose (1 mg/kg at P8 and P14 to P16). RESULTS: Most mutant mice died of respiratory arrest within 13 min of ketamine injection at P8 (12 of 13, 92% vs. 0 of 8, 0% wild type; Fisher exact test, P < 0.001) and P14 to P16 (32 of 42, 76% vs. 0 of 59, 0% wild type; P < 0.001). Cardiac activity continued after terminal apnea, and mortality was prevented by mechanical ventilation, supporting respiratory arrest as the cause of death in the mutants. Ketamine-induced mortality in mutants compared to wild types was confirmed at P29 to P31 (24 of 36, 67% vs. 9 of 45, 20%; P < 0.001) and P60 to P62 (8 of 19, 42% vs. 0 of 12, 0%; P = 0.011). Anesthesia-induced mortality in mutants compared to wild types was also observed with propofol at P8 (7 of 7, 100% vs. 0 of 17,7/7, 100% vs. 0/17, 0%; P < 0.001) and P14 to P16 (8 of 10, 80% vs. 0 of 10, 0%; P < 0.001) and with fentanyl at P8 (15 of 16, 94% vs. 0 of 13, 0%; P < 0.001) and P14 to P16 (5 of 7, 71% vs. 0 of 11, 0%; P = 0.002). CONCLUSIONS: Ketamine, propofol, and fentanyl caused death by respiratory arrest in most mice with selective loss of retrotrapezoid nucleus neurons, in doses that were safe in their wild type littermates. The retrotrapezoid nucleus is critical to sustain breathing during deep anesthesia and may prove to be a pharmacologic target for this purpose.

Comparison of methods of chemical loop gain measurement during tidal ventilation in awake healthy subjects.

The loop gain (LG) is defined as the ratio of a ventilatory response over the perturbation in ventilation, and it is used to analyze ventilatory control stability. The LG can be derived from minute ventilation (V̇e), end-tidal Pco2 ([Formula: see text]), and end-tidal Po2 ([Formula: see text]) values. Several methods of LG assessment have been developed, which have never been compared. We evaluated the computability, the short-term repeatability, and the agreement of six published (or slightly modified) models for LG determination. These models included three unconstrained autoregressive models, univariate (V̇e), bivariate (V̇e, [Formula: see text]), and trivariate (V̇e, [Formula: see text], and [Formula: see text]), and three analytical transfer function constrained models based on V̇e, V̇e and CO2-sensitivity, and V̇e and central and peripheral CO2 sensitivities, respectively. The models were tested with tidal breathing data in 37 awake healthy subjects (median age 35 yr; 23 women, 14 men). Modeling failed in 11, 0, and 0 subjects for the three unconstrained models, respectively, and 4, 1, and 9 subjects for the three constrained models, respectively. Bland and Altman analyses of the LG values in the medium frequency range of two separate recordings demonstrated good repeatability for four models, excluding univariate and trivariate unconstrained models. The four repeatable models gave LG values that were in agreement (medium frequency LG, median 0.100-0.210), although the constrained model based on V̇e systematically overestimated LG values. The variances explained by these models were ∼20%. In conclusion, model-based analyses of tidal breathing were performed with different approaches that gave comparable results for chemical LG and explained variance.NEW & NOTEWORTHY Several methods of chemical loop gain measurement have been published but never compared. We show that a better repeatability is obtained with analytical constrained models compared with autoregressive unconstrained models and that the repeatable models gave comparable results of loop gain, even if the calculation based on ventilation-only recording gave higher values than those obtained with both ventilation and end-tidal Pco2 recording. The explained variance of ventilation was similar whatever the model.

Acetylcholine Modulates the Hormones of the Growth Hormone/Insulinlike Growth Factor-1 Axis During Development in Mice.

Pituitary growth hormone (GH) and insulinlike growth factor (IGF)-1 are anabolic hormones whose physiological roles are particularly important during development. The activity of the GH/IGF-1 axis is controlled by complex neuroendocrine systems including two hypothalamic neuropeptides, GH-releasing hormone (GHRH) and somatostatin (SRIF), and a gastrointestinal hormone, ghrelin. The neurotransmitter acetylcholine (ACh) is involved in tuning GH secretion, and its GH-stimulatory action has mainly been shown in adults but is not clearly documented during development. ACh, together with these hormones and their receptors, is expressed before birth, and somatotroph cells are already responsive to GHRH, SRIF, and ghrelin. We thus hypothesized that ACh could contribute to the modulation of the main components of the somatotropic axis during development. In this study, we generated a choline acetyltransferase knockout mouse line and showed that heterozygous mice display a transient deficit in ACh from embryonic day 18.5 to postnatal day 10, and they recover normal ACh levels from the second postnatal week. This developmental ACh deficiency had no major impact on weight gain and cardiorespiratory status of newborn mice. Using this mouse model, we found that endogenous ACh levels determined the concentrations of circulating GH and IGF-1 at embryonic and postnatal stages. In particular, serum GH level was correlated with brain ACh content. ACh also modulated the levels of GHRH and SRIF in the hypothalamus and ghrelin in the stomach, and it affected the levels of these hormones in the circulation. This study identifies ACh as a potential regulator of the somatotropic axis during the developmental period.