[Recurring genital bleeding in an extreme premature infant]. / Sangrado genital recurrente en una lactante prematura extrema.

Mini-puberty refers to the transient activation of the hypothalamic-pituitary-gonadal axis during the first months of life. This activation in preterm infants could be more exaggerated and prolonged. Ob jective: To present a case of exaggerated mini-puberty in an extremely preterm infant, with recurrent genital bleeding. Clinical Case: A 25-week preterm newborn presented at 5 months old with breast buds, areolar pigmentation, and estrogenic effects on the vaginal mucosa, with recurrent genital blee ding in three consecutive months. Her laboratory evaluation showed elevated values of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2). An exaggerated mini-puber ty due to extreme prematurity was suspected, therefore a conservative approach was taken. During follow-up, the patient showed partial regression of breast buds and cessation of genital bleeding, and decreasing levels of gonadotropin and estradiol. Conclusion: Mini-puberty in preterm newborns can present exaggeratedly, simulating precocious puberty and even presenting, exceptionally, recurrent genital bleeding. Considering the increasing survival of extremely premature infants, it is important to know the spectrum of clinical and laboratory manifestations of this phenomenon, in order to carry out adequate management.

[Starting of a new pediatric palliative care program in a general hospital: characteristics of the population and use of resources].

This article sets out to describe the characteristics of patients at a second-level hospital who are likely to receive pedi-atric palliative care (PPC), the frequency of visits to the emergency room, admissions and technological devices used. A retrospective study was carried out of the patients who received care from the start of the PPC program (January 2017 to January 2020) at a secondary-level hospital. Twenty-nine patients were included, 58.6% male with mean age at entry into the study of 2.3 years (SD: 2.4); 44.8% of them were from rural areas. The prevalence of multimorbidity was 41%, with a higher frequency of neurological patholo-gy. Respiratory infection was the most frequent cause of emergency care (n = 360) and hospitalization (n=145). Half of patients (51.7%) depended on medical devices. Better knowledge of the resources used by this population can lead to more effective distribution/management that in turn can enable PPC to be offered regardless of the place of residence.

OLA strategy for ARDS: Its effect on mortality depends on achieved recruitment (PaO2/FiO2) and mechanical power. Systematic review and meta-analysis with meta-regression.

OBJECTIVE: The "Open Lung Approach" (OLA), that includes high levels of positive end-expiratory pressure coupled with limited tidal volumes, is considered optimal for adult patients with ARDS. However, many previous meta-analyses have shown only marginal benefits of OLA on mortality but with statistical heterogeneity. It is crucial to identify the most likely moderators of this effect. To determine the effect of OLA strategy on mortality of ventilated ARDS patients. We hypothesized that the degree of recruitment achieved in the control group (PaO2/FiO2 ratio on day 3 of ventilation), and the difference in Mechanical Power (MP) or Driving Pressure (DP) between experimental and control groups will be the most likely sources of heterogeneity. DESIGN: A Systematic Review and Meta-analysis was performed according to PRISMA statement and registered in PROSPERO database. We searched only for randomized controlled trials (RCTs). GRADE guidelines were used for rating the quality of evidence. Publication bias was assessed. For the Meta-analysis, we used a Random Effects Model. Sources of heterogeneity were explored with Meta-Regression, using a priori proposed set of possible moderators. For model comparison, Akaike's Information Criterion with the finite sample correction (AICc) was used. SETTING: Not applicable. PATIENTS: Fourteen RCTs were included in the study. INTERVENTIONS: Not applicable. MAIN VARIABLES OF INTEREST: Not applicable. RESULTS: Evidence of publication bias was detected, and quality of evidence was downgraded. Pooled analysis did not show a significant difference in the 28-day mortality between OLA strategy and control groups. Overall risk of bias was low. The analysis detected statistical heterogeneity. The two "best" explicative meta-regression models were those that used control PaO2/FiO2 on day 3 and difference in MP between experimental and control groups. The DP and MP models were highly correlated. CONCLUSIONS: There is no clear benefit of OLA strategy on mortality of ARDS patients, with significant heterogeneity among RCTs. Mortality effect of OLA is mediated by lung recruitment and mechanical power.

OLA strategy for ARDS: Its effect on mortality depends on achieved recruitment (PaO2/FiO2) and mechanical power. Systematic review and meta-analysis with meta-regression.

OBJECTIVE: The "Open Lung Approach" (OLA), that includes high levels of positive end-expiratory pressure coupled with limited tidal volumes, is considered optimal for adult patients with ARDS. However, many previous meta-analyses have shown only marginal benefits of OLA on mortality but with statistical heterogeneity. It is crucial to identify the most likely moderators of this effect. To determine the effect of OLA strategy on mortality of ventilated ARDS patients. We hypothesized that the degree of recruitment achieved in the control group (PaO2/FiO2 ratio on day 3 of ventilation), and the difference in Mechanical Power (MP) or Driving Pressure (DP) between experimental and control groups will be the most likely sources of heterogeneity. DESIGN: A Systematic Review and Meta-analysis was performed according to PRISMA statement and registered in PROSPERO database. We searched only for randomized controlled trials (RCTs). GRADE guidelines were used for rating the quality of evidence. Publication bias was assessed. For the Meta-analysis, we used a Random Effects Model. Sources of heterogeneity were explored with Meta-Regression, using a priori proposed set of possible moderators. For model comparison, Akaike's Information Criterion with the finite sample correction (AICc) was used. SETTING: Not applicable. PATIENTS: Fourteen RCTs were included in the study. INTERVENTIONS: Not applicable. MAIN VARIABLES OF INTEREST: Not applicable. RESULTS: Evidence of publication bias was detected, and quality of evidence was downgraded. Pooled analysis did not show a significant difference in the 28-day mortality between OLA strategy and control groups. Overall risk of bias was low. The analysis detected statistical heterogeneity. The two "best" explicative meta-regression models were those that used control PaO2/FiO2 on day 3 and difference in MP between experimental and control groups. The DP and MP models were highly correlated. CONCLUSIONS: There is no clear benefit of OLA strategy on mortality of ARDS patients, with significant heterogeneity among RCTs. Mortality effect of OLA is mediated by lung recruitment and mechanical power.

Association of tyrosine hydroxylase expression in brain and tumor with increased tumor growth in sympathectomized mice.

OBJECTIVE: Lymphocytes express tyrosine hydroxylase (TH), the rate-limiting enzyme for the synthesis of dopamine, norepinephrine and epinephrine. This suggests a broader role for cathecholamines in lymphocyte function, as well as the potential secretion of catecholamines by tumors of lymphoid origin. Our aim was to evaluate the expression of Th by murine lymphoma cells in an in vivo mouse model. For this, L5178Y-R lymphoma cells were implanted in nerve-intact and sympathectomized male BALB/c mice. Relative Th gene expression in tumor and brain was determined by quantitative PCR. Body composition, tumor volume, and plasma TH1/TH2/TH17 cytokines were also evaluated as markers of tumor-host condition and anti-tumor immune response in absence of adrenergic innervation. RESULTS: We found a significant (p = 0.045) 3.3-fold decrease of Th gene expression in tumor and a non-significant (p = 0.60) 6.9-fold increase in brain after sympathectomy. Sympathectomized mice also showed a significant increase in tumor mass at days 18 (p = 0.032) and 28 (p = 0.022) and increased interscapular fat (p = 0.04). TH1/TH2 and TH17 cytokines levels in plasma from sympathectomized tumor-bearing mice were not different from control mice. CONCLUSION: The L5178Y-R lymphoma does not express Th during in vivo progression.

Covid-19 management by farmers and policymakers in Burkina Faso, Colombia and France: Lessons for climate action.

CONTEXT: During crises, adaptation or recovery measures or plans at local or national scales may not necessarily address longer-term or structural problems such as climate change mitigation. OBJECTIVE: This article describes farmers and policymakers' responses to mitigate the adverse effects of Covid-19 on the agricultural sector. We then assess the responses' possible effects on greenhouse gas (GHG) emissions. METHODS: The study is based on surveys conducted with farmers, traders, and extension staff in Burkina Faso, Colombia, and France, and literature. We used the Cool Farm Tool calculator to assess GHG emissions associated with fertilizer production, crop production and produce transportation to international markets for the three main cash crops in the three countries. RESULTS AND CONCLUSIONS: We identified contrasting responses by the agricultural sector mostly driven by changes in the consumption patterns at local or international levels. We also identified contrasting state responses to mitigate Covid-19. These responses at farm and policy scales led to similar trends in decreasing carbon dioxide (CO2) emissions across the studied countries. However, none of the studied countries linked Covid-19 response measures to long-term climate change mitigation actions. Therefore, an opportunity to sustain Covid-19 induced short-term decreases in GHG emissions was overlooked. SIGNIFICANCE: Analyzing the impacts that Covid-19 had on agricultural systems and the decision taken by policymakers to handle its direct and indirect effects can help society draw lessons on how to improve climate action.

Increased phagocytosis and growth inhibition of Encephalitozoon cuniculi by LPS-activated J774A.1 murine macrophages.

Encephalitozoon cuniculi is an obligate macrophage parasite of vertebrates that commonly infects rodents, monkeys, dogs, birds, and humans. In the present study, we aimed to assess the phagocytosis and intracellular survival of E. cuniculi spores using untreated and lipopolysaccharide (LPS)-activated J774A.1 murine macrophages and assess the macrophage viability. The experimental groups comprised untreated spores, spores killed by heat treatment at 90 °C, and spores killed by treatment with 10% formalin. LPS-activated macrophages significantly increased the phagocytosis of spores and reduced their intracellular growth after 24 and 48 h (P < 0.01); however, after 72 h, we observed an increase in spore replication but no detectable microbicidal activity. These results indicate that LPS activation enhanced E. cuniculi phagocytosis between 24 and 48 h of treatment, but the effect was lost after 72 h, enabling parasitic growth. This study contributes to the understanding of the phagocytosis and survival of E. cuniculi in murine macrophages.

[Boussignac continuous positive airway pressure device during inter-hospital transportation in infants aged less than three months]. / Dispositivo de presión positiva continua en la vía aérea de Boussignac durante el transporte interhospitalario en lactantes menores de tres meses.

BACKGROUND: The present study aims to evaluate the safety and effectiveness of the Boussignac continuous positive airway pressure device (CPAPB) when used during the transportation of infants under three months of age with bronchiolitis. METHODS: Transversal analytical observational study of four years duration. Data was collected on 25 infants who needed inter-hospital transportation to the reference Paediatric Intensive Care Unit (PICU), with CPAPB and Helmet interface. The epidemiological characteristics of the transportation and evolution in the PICU were registered, as well as the cardiorespiratory gastronomic parameters prior to transfer and on arrival at the PICU. RESULTS: The median level of continuous airway pressure (CPAP) used during the transfer was 7 cm H2O (6-7.25). No patient required endotracheal intubation during transportation, while one patient required this during the first six hours of admission in the PICU. The following cardiorespiratory parameters presented a statistically significant improvement on arrival at the PICU: modified Wood-Downes score [8.40 (2.1) vs 5.29 (1.68)], respiratory frequency [60.72 (12.73) vs 47.28 (10.31)], cardiac frequency [167.28 (22.60) vs 154.48 (24.83)] and oxygen saturation [92.08 (5.63) vs 97.64 (2.27)]. CONCLUSIONS: Application of CPAPB proved to be a safe method of respiratory support in infants under three months of age. Its use during transportation brought an improvement in cardiorespiratory parameters.

Fast optimized Monte Carlo phase-space generation and dose prediction for low energy x-ray intra-operative radiation therapy.

Low energy x-ray intra-operative radiation therapy (IORT) is used mostly for breast cancer treatment with spherical applicators. X-ray IORT treatment delivered during surgery (ex: INTRABEAM®, Carl Zeiss) can benefit from accurate and fast dose prediction in a patient 3D volume. However, full Monte Carlo (MC) simulations are time-consuming and no commercial treatment planning system (TPS) was available for this treatment delivery technique. Therefore, the aim of this work is to develop a dose computation tool based on MC phase space information, which computes fast and accurate dose distributions for spherical and needle INTRABEAM® applicators. First, a database of monoenergetic phase-space (PHSP) files and depth dose profiles (DDPs) in water for each applicator is generated at factory and stored for on-site use. During commissioning of a given INTRABEAM® unit, the proposed fast and optimized phase-space (FOPS) generation process creates a phase-space at the exit of the applicator considered, by fitting the energy spectrum of the source to a combination of the monoenergetic precomputed phase-spaces, by means of a genetic algorithm, with simple experimental data of DDPs in water provided by the user. An in-house hybrid MC (HMC) algorithm which takes into account condensed history simulations of photoelectric, Rayleigh and Compton interactions for x-rays up to 1 MeV computes the dose from the optimized phase-space file. The whole process has been validated against radiochromic films in water as well as reference MC simulations performed with penEasy in heterogeneous phantoms. From the pre-computed monoenergetic PHSP files and DDPs, building the PHSP file optimized to a particular depth-dose curve in water only takes a few minutes in a single core (i7@2.5 GHz), for all the applicators considered in this work, and this needs to be done only when the x-ray source (XRS) is replaced. Once the phase-space file is ready, the HMC code is able to compute dose distributions within 10 min. For all the applicators, more than 95% of voxels from dose distributions computed with the FOPS+hybrid code agreed within 7%-0.5 mm with both reference MC simulations and measurements. The method proposed has been fully validated and it is now implemented into radiance (GMV SA, Spain), the first commercial IORT TPS.

Pharmacometabolomics applied to zonisamide pharmacokinetic parameter prediction.

INTRODUCTION: Zonisamide is a new-generation anticonvulsant antiepileptic drug metabolized primarily in the liver, with subsequent elimination via the renal route. OBJECTIVES: Our objective was to evaluate the utility of pharmacometabolomics in the detection of zonisamide metabolites that could be related to its disposition and therefore, to its efficacy and toxicity. METHODS: This study was nested to a bioequivalence clinical trial with 28 healthy volunteers. Each participant received a single dose of zonisamide on two separate occasions (period 1 and period 2), with a washout period between them. Blood samples of zonisamide were obtained from all patients at baseline for each period, before volunteers were administered any medication, for metabolomics analysis. RESULTS: After a Lasso regression was applied, age, height, branched-chain amino acids, steroids, triacylglycerols, diacyl glycerophosphoethanolamine, glycerophospholipids susceptible to methylation, phosphatidylcholines with 20:4 FA (arachidonic acid) and cholesterol ester and lysophosphatidylcholine were obtained in both periods. CONCLUSION: To our knowledge, this is the only research study to date that has attempted to link basal metabolomic status with pharmacokinetic parameters of zonisamide.

Correction to: Pharmacometabolomics applied to zonisamide pharmacokinetic parameter prediction.

The original version of this article contains a mistake.

Alterations of antitumor and metabolic responses in L5178Y-R lymphoma-bearing mice after only 30-minute daily chronic stress exposure.

AIM: In stress research, reducing times of stress induction may contribute to improving the well-being of experimental animals, especially in cancer models, already under physiological distress. To support this idea, we evaluated the effects of a short-timed stress protocol on endocrine, metabolic and immune indicators in mice bearing the L5178Y-R lymphoma. MATERIALS AND METHODS: A 30-minute daily stress protocol was applied for 28 days to healthy and lymphoma-bearing BALB/c mice; body weight, plasma levels of corticosterone, norepinephrine, Th1/Th2 cytokines, insulin, and leptin, were measured. RESULTS: We found a 12% significant decrease in body weight in non-tumor bearing mice under stress (p < 0.007). The disruption of weight evolution was accompanied by a stress induced 85% decrease in plasmatic leptin (p < 0.01) and total reduction of insulin. Tumor burden alone was associated to an increase in more than two-fold of plasmatic levels of norepinephrine (p < 0.008). Neither stress nor tumor or their combination, resulted in an elevation of systemic IL-6. IFN-γ levels were 20 times higher in lymphoma-bearing animals when compared with non-tumor bearing mice (p < 0.01); however, under stress, this response was reduced by half, indicating a suppressing effect of chronic stress on the antitumor immune response. CONCLUSION: A short-timed stress induction is enough to cause significant alterations in the metabolism and immunity of healthy and tumor-bearing mice, supporting the use of short-timed protocols as an efficient way to induce chronic stress that also considers concerns regarding the well-being of experimental animals in biomedical research.

Sugars and char formation on subcritical water hydrolysis of sugarcane straw.

Subcritical water has potential as an environmentally friendly solvent for applications including hydrolysis, liquefaction, extraction, and carbonization. Here, we report hydrolysis of sugarcane straw, an abundant byproduct of sugar production, in a semi-continuous reactor at reaction temperatures ranging from 190 to 260°C and at operating pressures of 9 and 16MPa. The target hydrolysis products were total reducing sugars. The main products of sugarcane straw hydrolysis were glucose, xylose, arabinose, and galactose in addition to 5- hydroxymethylfurfural and furfural as minor byproducts. Fourier transform infrared spectroscopy and thermogravimetric analysis provided additional information on the surface and bulk composition of the residual biomass. Char was present on samples treated at temperatures equal to and greater than 190°C. Samples treated at 260°C contained approximately 20wt% char, yet retained substantial hemicellulose and cellulose content. Hydrolysis temperature of 200°C provided the greatest TRS yield while minimizing char formation.

Organogenesis and foetal haemodynamics during the normal gestation of healthy black-rumped agoutis (Dasyprocta prymnolopha, Wagler, 1831) bred in captivity.

The objective of this study was to define the patterns of organogenesis and foetal haemodynamics during the normal gestation of healthy agoutis (Dasyprocta prymnolopha) kept in captivity. Thirty pregnant agoutis that ranged in size from small to medium and weighed between 2.5 and 3 kg underwent B-mode and Doppler ultrasonography for the biometric evaluation of the foetal organs. The foetal aortic blood flow proved to be predominantly systolic, and the measured flow velocity was 78.89 ± 2.95 cm/s, with a maximum pressure gradient of 2.12 ± 0.27 mmHg. The liver was characterized by its large volume, occupying the entire cranial aspect of the abdominal cavity, and it was associated cranially with the diaphragm and caudally with the stomach. The flow velocity in the portal vein was estimated to equal 12.17 ± 2.37 cm/s, with a resistivity index of 0.82 ± 0.05. The gallbladder was centrally located and protruded cranially towards the diaphragm. The spleen was visualized as an elongated structure with tapered cranial and caudal extremities, and the foetal kidneys were visualized bilaterally in the retroperitoneal region, with the right kidney positioned slightly more cranially than the left. The morphological characterization and hemodynamic analysis of the foetal organs of black-rumped agoutis via B-mode and Doppler ultrasonography allow determination of the vascular network and of reference values for the blood flow required for perfusing the anatomical elements essential for maintaining the viability of foetuses at different gestational ages.

Reducing Staphylococcus aureus bloodstream infections associated with peripheral intravenous cannulae: successful implementation of a care bundle at a large Australian health service.

BACKGROUND: Healthcare-associated Staphylococcus aureus bacteraemia (HA-SAB) results in morbidity, mortality, and increased healthcare costs, and these infections are frequently regarded as preventable. AIM: To implement a multi-modal prevention programme for improved processes regarding peripheral intravenous cannula (PIVC) insertion and maintenance, in order to reduce PIVC-associated HA-SAB events in a large Australian health service. METHODS: Baseline clinical practice was evaluated for a 12-month pre-intervention period. Measures to reduce HA-SAB risk were introduced between January and September 2013: staff education, improved documentation (including phlebitis scoring), and availability of standardized equipment. Post-intervention auditing was performed during the 27 months following intervention. Baseline and post-intervention HA-SAB and PIVC-associated infection rates were compared. Interrupted time-series and Bayesian change-point analyses were applied to determine the impact of interventions and timing of change. FINDINGS: Significantly improved documentation regarding PIVC insertion and management was observed in the post-intervention period, with fewer PIVCs left in situ for ≥4 days (2.6 vs 6.9%, P<0.05). During the baseline period a total of 68 HA-SAB events occurred [1.01/10,000 occupied bed-days (OBDs)] and 24 were PIVC-associated (35% of total, rate 0.39 per 10,000 OBDs). In the post-intervention period, a total of 83 HA-SAB events occurred (0.99 per 10,000 OBDs) and 12 were PIVC-associated (14.4% of total, rate 0.14 per 10,000 OBDs). PIVC-associated SAB rates were 63% lower in the post-intervention period compared to baseline (P=0.018) with a change point observed following full bundle implementation in October 2013. CONCLUSION: A successful multi-modal hospital-wide campaign was introduced to reduce PIVC-associated SAB rates. Evaluation of cost-effectiveness and sustainability is required.

Detection of emerging rotavirus G12P[8] in Sonora, México.

Rotavirus is the most common cause of gastroenteritis in children up to five years of age worldwide. The aim of the present study was to analyze the genotypes of rotavirus strains isolated from children with gastroenteritis, after the introduction of the rotavirus vaccine in México. Rotavirus was detected in 14/100 (14%) fecal samples from children with gastroenteritis, using a commercial test kit. The viral genome was purified from these samples and used as a template in RT-PCR amplification of the VP4 and VP7 genes, followed by gene cloning and sequencing. Among the rotavirus strains, 4/14 (28.5%) were characterized as G12P[8], 2/14 (14.3%), as G12P (not typed), and 3/14 (21.42%) as G (not typed) P[8]. Phylogenetic analysis of the VP7 gene showed that G12 genotypes clustered in lineage III. Phylogenetic analysis revealed that VP4 genotype P[8] sequences clustered in lineage V, whereas other P[8] sequences previously reported in Mexico (2005-2008) clustered in different lineages. Rotavirus genotype G12 is currently recognized as a globally emerging rotavirus. To our knowledge, this is the first report of this emerging rotavirus strain G12P[8] in México. Ongoing surveillance is recommended to monitor the distribution of rotavirus genotypes and to continually reassess the suitability of currently available rotavirus vaccines.