Differential effects of high-altitude exposure on markers of oxidative stress, antioxidant capacity, and iron profiles.

High-altitude (HA) exposure may stimulate significant physiological and molecular changes, resulting in HA-related illnesses. HA may impact oxidative stress, antioxidant capacity, and iron homeostasis, yet it is unclear how both repeated exposure and HA acclimatization may modulate such effects. Therefore, we assessed the effects of weeklong repeated daily HA exposure (2,900-5,050 m) in altitude-naïve individuals (n = 21 individuals, 13 females, mean ± SD, 25.3 ± 3.7 yr) to mirror the working schedule of HA workers (n = 19 individuals, all males, 41.1 ± 9.4 yr) at the Atacama Large Millimeter Array (ALMA) Observatory (San Pedro de Atacama, Chile). Markers of oxidative stress, antioxidant capacity, and iron homeostasis were measured in blood plasma. Levels of protein oxidation (P < 0.001) and catalase activity (P = 0.023) increased and serum iron (P < 0.001), serum ferritin (P < 0.001), and transferrin saturation (P < 0.001) levels decreased with HA exposure in both groups. HA workers had lower levels of oxidative stress, and higher levels of antioxidant capacity, iron supply, and hemoglobin concentration as compared with altitude-naïve individuals. On a second week of daily HA exposure, changes in levels of protein oxidation, glutathione peroxidase, and nitric oxide metabolites were lower as compared with the first week in altitude-naïve individuals. These results indicate that repeated exposure to HA may significantly alter oxidative stress and iron homeostasis, and the degree of such changes may be dependent on if HA is visited naïvely or routinely. Further studies are required to fully elucidate differences in HA-induced changes in oxidative stress and iron homeostasis profiles among visitors of HA.

Coccidioidomycosis mimicking testicular cancer: A case report.

We present the case of a 48 year-old man with a history of pulmonary tuberculosis who was brought to our centre with a progressively increasing left testicular mass. Radiological findings were not conclusive on whether the mass was neoplastic or infectious in nature. Therefore, an orchiectomy was performed. Pathology examination revealed coccidioidomycosis of the left testicle, highlighting an exceedingly rare presentation of disseminated genitourinary coccidioidomycosis.

2-AMINOETHYLDIPHENYLBORINATE MODIFIES THE PULMONARY CIRCULATION IN PULMONARY HYPERTENSIVE NEWBORN LAMBS WITH PARTIAL GESTATION AT HIGH ALTITUDE.

Calcium signaling through store operated channels (SOC) is involved in hypoxic pulmonary hypertension. We determined whether a treatment with 2-aminoethyldiphenylborinate (2-APB), a compound with SOC blocker activity, reduces pulmonary hypertension and vascular remodeling. Twelve newborn lambs exposed to perinatal chronic hypoxia were studied, 6 of them received a 2-APB treatment and the other 6 received vehicle treatment, for 10 days in both cases. Throughout this period, we recorded cardiopulmonary variables and on day 11 we evaluated the response to an acute hypoxic challenge. Additionally, we assessed the vasoconstrictor and vasodilator function in isolated pulmonary arteries as well as their remodeling in lung slices. 2-APB reduced pulmonary arterial pressure at the third and tenth days, cardiac output between the fourth and eighth days, and pulmonary vascular resistance at the tenth day of treatment. The pulmonary vasoconstrictor response to acute hypoxia was reduced by the end of treatment. 2-APB also decreased maximal vasoconstrictor response to the thromboxane mimetic U46619 and endothelin-1 and increased maximal relaxation to 8-Br-cGMP. The maximal relaxation and potency to phosphodiesterase-5 and Rho-kinase inhibition with sildenafil and fasudil respectively, were also increased. Finally, 2-APB reduced the medial and adventitial layers' thickness, the expression of α-actin and the percentage of Ki67+ nuclei of small pulmonary arteries. Taken together, our results indicate that 2-APB reduces pulmonary hypertension, vasoconstrictor responses and pathological remodeling in pulmonary hypertensive lambs. We conclude that SOC targeting may be a useful strategy for the treatment of neonatal pulmonary hypertension, however, further testing of specific blockers is needed.

Role of the RhoA/ROCK pathway in high-altitude associated neonatal pulmonary hypertension in lambs.

Exposure to high-altitude chronic hypoxia during pregnancy may cause pulmonary hypertension in neonates, as a result of vasoconstriction and vascular remodeling. We hypothesized that susceptibility to pulmonary hypertension, due to an augmented expression and activity of the RhoA/Rho-kinase (ROCK) pathway in these neonates, can be reduced by daily administration of fasudil, a ROCK inhibitor. We studied 10 highland newborn lambs with conception, gestation, and birth at 3,600 m in Putre, Chile. Five highland controls (HLC) were compared with 5 highland lambs treated with fasudil (HL-FAS; 3 mg·kg(-1)·day(-1) iv for 10 days). Ten lowland controls were studied in Lluta (50 m; LLC). During the 10 days of fasudil daily administration, the drug decreased pulmonary arterial pressure (PAP) and resistance (PVR), basally and during a superimposed episode of acute hypoxia. HL-FAS small pulmonary arteries showed diminished muscular area and a reduced contractile response to the thromboxane analog U46619 compared with HLC. Hypoxia, but not fasudil, changed the protein expression pattern of the RhoA/ROCKII pathway. Moreover, HL-FAS lungs expressed less pMYPT1(T850) and pMYPT1T(696) than HLC, with a potential increase of the myosin light chain phosphatase activity. Finally, hypoxia induced RhoA, ROCKII, and PKG mRNA expression in PASMCs of HLC, but fasudil reduced them (HL-FAS) similarly to LLC. We conclude that fasudil decreases the function of the RhoA/ROCK pathway, reducing the PAP and PVR in chronically hypoxic highland neonatal lambs. The inhibition of ROCKs by fasudil may offer a possible therapeutic tool for the pulmonary hypertension of the neonates.

[Pneumococcal vaccination coverage in at-risk children in Catalonia]. / Cobertura de vacunación antineumocócica en niños con condiciones de riesgo en Cataluña.

INTRODUCTION: The public health system in Catalonia only funds pneumococcal vaccination in paediatrics for children at-risk. The aim of this study was to determine pneumococcal vaccination coverage and its association with age, sociodemographic factors and other variables. MATERIAL AND METHOD: Descriptive cross-sectional study of children aged between 2 months and 15 years old assigned to primary care centres in Catalonia and with diseases that are included for pneumococcal vaccine in the official vaccination program. The information on vaccination status and study variables were obtained from data registered in the electronic medical records in the primary care centres. An analysis was made of the association between pneumococcal vaccination and demographic and medical variables using bivariate analysis and a multiple logistic regression model. The adjusted odds ratio (aOR), with a confidence interval of 95%, was used to measure the relationships. RESULTS: Pneumococcal vaccination coverage was 47.7%. Variables which predicted pneumococcal vaccination were: age (aOR: 9.2 [7.9-10.7] in children 2 months-2 years old; aOR 8.1 [7.0-9.3] in children 3-5 years; aOR: 4.6 [4.0-5.2] in children 6-10 years), Spanish nationality (aOR: 3.9 [3.5-4.3]), correct immunisation according to systematic immunisation schedule (aOR: 2.5 [2.1-3.0]), and number of risk conditions (aOR: 3.2 [2.5-4.1] in children with 2 or more conditions). CONCLUSIONS: Pneumococcal vaccination coverage in children with risk conditions is low in Catalonia. Strategies need to be implemented to increase coverage.

VR-assisted aggression treatment in forensic psychiatry: a qualitative study in patients with severe mental disorders.

Introduction: Improvements in virtual reality (VR) have made it possible to create realistic, virtual settings for behavioral assessment and skills training that cannot otherwise be accessed in a safe way in forensic psychiatric settings. VR interventions are under development but little is known how forensic psychiatric patients with severe mental disorders experience VR-assisted assessments or treatments. Methods: The present study aimed to help fill this knowledge gap via qualitative interviews with seven patients with severe mental disorders at a high-security forensic psychiatric clinic who had completed the newly revised Virtual Reality Aggression Prevention Training (VRAPT). All participants were interviewed 12 weeks after the VRAPT intervention, and interview data analyzed with manifest inductive content analysis. Results: Six manifest content categories were identified: 1. Therapeutic process, 2. VRAPT method, 3. VR technology, 4. Previous treatment experiences, 5. Challenges to treatment of aggression, and 6. Unexpected experiences. The participants had diverse experiences related to both the VRAPT intervention and forensic psychiatric care. Participants described a mixture of positive experiences in relation to VR-assisted role-plays, and less positive in relation to motivation for aggression-focused treatment and technological limitations. Discussion: The present findings suggest further studies are needed on how to best implement VR-assisted treatments for aggression in forensic settings, and potentially further modification of treatment content in interventions like VRAPT.

Mandibular Myxoid Liposarcoma: a Case Study.

Liposarcomas are described as soft tissue sarcomas derived from adipose tissue. The finding of this tumor in the mandibular region is exceedingly rare. As of now, it has been described mainly in case reports and small series. A multidisciplinary approach is required to offer optimal treatment and may involve surgery, radiation and systemic therapies. Surgical repair of these defects represents a major challenge in oral and maxillofacial reconstructive surgery. We present the case of a 54-year-old man referred to our center with a progressively increasing mass in the anterior portion of the mandible. Biopsy revealed a well-differentiated myxoid liposarcoma. Resection of the tumor was performed with an additional primary reconstruction.

Store-operated channels in the pulmonary circulation of high- and low-altitude neonatal lambs.

We determined whether store-operated channels (SOC) are involved in neonatal pulmonary artery function under conditions of acute and chronic hypoxia, using newborn sheep gestated and born either at high altitude (HA, 3,600 m) or low altitude (LA, 520 m). Cardiopulmonary variables were recorded in vivo, with and without SOC blockade by 2-aminoethyldiphenylborinate (2-APB), during basal or acute hypoxic conditions. 2-APB did not have effects on basal mean pulmonary arterial pressure (mPAP), cardiac output, systemic arterial blood pressure, or systemic vascular resistance in both groups of neonates. During acute hypoxia 2-APB reduced mPAP and pulmonary vascular resistance in LA and HA, but this reduction was greater in HA. In addition, isolated pulmonary arteries mounted in a wire myograph were assessed for vascular reactivity. HA arteries showed a greater relaxation and sensitivity to SOC blockers than LA arteries. The pulmonary expression of two SOC-forming subunits, TRPC4 and STIM1, was upregulated in HA. Taken together, our results show that SOC contribute to hypoxic pulmonary vasoconstriction in newborn sheep and that SOC are upregulated by chronic hypoxia. Therefore, SOC may contribute to the development of neonatal pulmonary hypertension. We propose SOC channels could be potential targets to treat neonatal pulmonary hypertension.

Salmonella paratyphi B and Salmonella litchfield outbreaks associated with pet turtle exposure in Spain.

INTRODUCTION: Salmonellosis is an important public health problem. Turtles are increasingly involved in the role of transmitters of this infection to humans. METHODS: Salmonella cases are reported to the local Surveillance Agency where interviews are carried out to address possible exposures. Molecular epidemiology techniques were used to identify species. RESULTS: In this article we report two examples of this type of infection in two places, 300 km apart in Spain. In Barcelona a turtle transmitted the disease to a small baby via her mother, and in Castellón 5 related cases of Salmonella infections were detected, and all were transmitted by imported turtles. Molecular epidemiology techniques confirmed the turtle-person transmissions and showed strong relationships between cases in Castellón and Barcelona. DISCUSSION: These examples represent the tip of the iceberg of what is happening with pet reptiles as regards transmission of this infection. We believe that it is important to assess the impact of this type of infection in each country, in order to subsequently promote prevention strategies such as: regulations for pet shops, and educating/informing families who buy reptiles as pets.

Post-intubation double tracheal stenosis.

Post-intubation tracheal stenosis is a condition that can occur as a consequence of tracheostomy or prolonged intubation. The development of two levels of airway narrowing is rare. We present the case of a 43-year-old male with a history of prolonged mechanical ventilation, who presented to our center with progressive respiratory impairment. Computed tomography with three-dimensional reconstruction demonstrated complex tracheal anatomy with double-level stenosis. The patient underwent successful endoscopic procedure. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-022-01426-y.

2009 H1N1: risk factors for hospitalization in a matched case-control study.

In order to compare sociodemographical data and preexisting risk medical conditions in patients requiring hospital admission for 2009 pandemic influenza A (H1N1) virus infection and those managed on an outpatient basis, a prospective observational, matched case-control study in 36 hospitals of the Spanish National Health Service was conducted from July 2009 to February 2010. Cases were patients aged 6 months to 18 years hospitalized for influenza syndrome, in whom 2009 influenza A (H1N1) virus infection was confirmed using real-time reverse-transcription polymerase chain reaction. Controls were patients aged 6 months to 18 years with confirmed 2009 influenza A (H1N1) infection managed on an outpatient basis. There were 195 cases and 184 controls. In a multivariate model, hospitalization was more frequent in children aged <2 years (odds ratio (OR), 13.8; 95% confidence interval (CI), 1.7-106.4), those with neurological and/or neuromuscular diseases (OR, 3.0; 95% CI, 1.1-8.2), and those whose parents had less than a secondary educational level (OR, 2.7; 95% CI, 1.4-5.2). Children aged <2 years, children with neurological diseases, and children from families with a lower educational status had a higher risk of hospitalization due to influenza A (H1N1) 2009 infection.

Cinaciguat (BAY-582667) Modifies Cardiopulmonary and Systemic Circulation in Chronically Hypoxic and Pulmonary Hypertensive Neonatal Lambs in the Alto Andino.

Neonatal pulmonary hypertension (NPHT) is produced by sustained pulmonary vasoconstriction and increased vascular remodeling. Soluble guanylyl cyclase (sGC) participates in signaling pathways that induce vascular vasodilation and reduce vascular remodeling. However, when sGC is oxidized and/or loses its heme group, it does not respond to nitric oxide (NO), losing its vasodilating effects. sGC protein expression and function is reduced in hypertensive neonatal lambs. Currently, NPHT is treated with NO inhalation therapy; however, new treatments are needed for improved outcomes. We used Cinaciguat (BAY-582667), which activates oxidized and/or without heme group sGC in pulmonary hypertensive lambs studied at 3,600 m. Our study included 6 Cinaciguat-treated (35 ug kg-1 day-1 x 7 days) and 6 Control neonates. We measured acute and chronic basal cardiovascular variables in pulmonary and systemic circulation, cardiovascular variables during a superimposed episode of acute hypoxia, remodeling of pulmonary arteries and changes in the right ventricle weight, vasoactive functions in small pulmonary arteries, and expression of NO-sGC-cGMP signaling pathway proteins involved in vasodilation. We observed a decrease in pulmonary arterial pressure and vascular resistance during the acute treatment. In contrast, the pulmonary pressure did not change in the chronic study due to increased cardiac output, resulting in lower pulmonary vascular resistance in the last 2 days of chronic study. The latter may have had a role in decreasing right ventricular hypertrophy, although the direct effect of Cinaciguat on the heart should also be considered. During acute hypoxia, the pulmonary vascular resistance remained low compared to the Control lambs. We observed a higher lung artery density, accompanied by reduced smooth muscle and adventitia layers in the pulmonary arteries. Additionally, vasodilator function was increased, and vasoconstrictor function was decreased, with modifications in the expression of proteins linked to pulmonary vasodilation, consistent with low pulmonary vascular resistance. In summary, Cinaciguat, an activator of sGC, induces cardiopulmonary modifications in chronically hypoxic and pulmonary hypertensive newborn lambs. Therefore, Cinaciguat is a potential therapeutic tool for reducing pulmonary vascular remodeling and/or right ventricular hypertrophy in pulmonary arterial hypertension syndrome.

Massive hemoptysis as a complication of pulmonary actinomycosis: a case report.

Massive hemoptysis is a rare life-threatening complication of pulmonary actinomycosis that should be treated promptly due to the risk of asphyxiation and hemodynamic instability. We present the case of a 57-year-old female who was presented to our center with massive hemoptysis. Thoracic computed tomography scan revealed a cavitated lesion with perilesional ground-glass opacity. Right lower lobectomy was then performed using uniportal video-assisted thoracic surgery, excising a 13 × 12 × 8 cm cavitated lung fragment. The pathology service reported the presence of microscopical evidence of filamentous gram positive bacterial colonies, showing compatible features of pulmonary actinomycosis. The patient was discharged with oral penicillin with an uneventful post-operative course.

La hemoptisis masiva es una complicación poco frecuente de la actinomicosis pulmonar que pone en peligro la vida del paciente y que debe ser tratada con prontitud debido al riesgo de asfixia e inestabilidad hemodinámica. Presentamos una mujer de 57 años que acudió a nuestro centro con hemoptisis masiva. La tomografía reveló una cavitación con opacidad perilesional en vidrio deslustrado. Realizamos lobectomía mediante cirugía uniportal, extirpando un fragmento de lesión. Patología informó de la presencia de colonias bacterianas filamentosas grampositivas, mostrando características compatibles con actinomicosis pulmonar. El paciente fue dado de alta con penicilina oral, con un curso postoperatorio sin incidentes.

Role of the α-adrenergic system in femoral vascular reactivity in neonatal llamas and sheep: a comparative study between highland and lowland species.

Using an integrative approach at the whole animal, isolated vessels, and molecular levels, we tested the hypothesis that the llama, a species that undergoes pregnancy under the influence of the chronic hypoxia of high altitude, delivers offspring with an increased α-adrenergic peripheral vascular reactivity compared with neonates from lowland species. We studied the femoral vascular response to acute hypoxia in vivo, the reactivity of femoral vessels ex vivo, and the expression of femoral α(1)-adrenergic receptor subtypes using RT-PCR in vitro. The increase in femoral resistance during hypoxia was 3.6 times greater in newborn llamas than newborn sheep (P < 0.05). The sensitivity of the contractile response to noradrenaline (pD(2) = 5.18 ± 0.06 vs. 4.84 ± 0.05, P < 0.05) and the maximal response (R(max) = 101.3 ± 1.4 vs. 52.4 ± 1.4% K(+)(max), P < 0.05) and sensitivity (pD(2) = 5.47 ± 0.03 vs. 4.57 ± 0.05, P < 0.05) to phenylephrine were higher in femoral vessels from newborn llamas than newborn sheep. Competitive inhibition with prazosin of noradrenaline-induced contraction followed by Schild analysis showed higher affinity in the llama than the sheep (pA(2) = 10.08 ± 0.093 vs. 8.98 ± 0.263, respectively, P < 0.05), consistent with greater α(1B)-adrenergic receptor transcript expression observed in small femoral arteries from neonatal llama. The llama newborn demonstrates significantly greater α-adrenergic peripheral vascular reactivity compared with neonates from lowland species that could be partially explained by preferential expression of α(1B)-adrenergic receptor subtype.

Clinical and epidemiological characteristics of patients with influenza A (H1N1) 2009 attended to at the emergency room of a children's hospital.

In June 2009, the first influenza pandemic of the twenty-first century, due to the swine origin influenza A (H1N1) 2009 virus, was declared. This study aimed to describe the epidemiological and clinical features, complications, lethality and risk factors for hospital admission of microbiologically confirmed cases of influenza A (H1N1) 2009 infection seen at the emergency department of a children's hospital. All cases of children with influenza A (H1N1) 2009 viral infection, confirmed microbiologically by real-time reverse transcription polymerase chain reactions and treated in the emergency room between July and December 2009, were prospectively included. Patients were compared according to admission requirement to study variables associated with the risk of hospitalisation. Oseltamivir was the antiviral used for the treatment and its safety was analysed. Four hundred and twelve patients with influenza A (H1N1) 2009 infection were included. The most frequent symptoms were: fever (96%), cough (95%) and coryza (90%). Eighty-five patients (20.6%) were admitted: three to the paediatric intensive care unit and two died. Hospitalised children were younger than those not admitted (median age 5 vs 8 years; p = 0.001). Age under 1 year (OR 6.01; CI 95% 2.77-13.05), pneumonia (OR 7.99; CI 95% 3.50-18.22) and haemoglobinopathy or underlying blood disorders (OR 5.99; CI 95% 1.32-27.30) were statistically significant risk factors for admission. No differences were observed regarding onset of antiviral treatment among admitted and non-admitted patients. Treatment with oseltamivir was well tolerated. In conclusion, the incidence of severe cases and lethality of influenza A (H1N1) 2009 infection were low in our setting, even in a population with risk factors for developing complications.