Locomotion Outcome Improvement in Mice with Glioblastoma Multiforme after Treatment with Anastrozole.

Glioblastoma Multiforme (GBM) is a tumor that infiltrates several brain structures. GBM is associated with abnormal motor activities resulting in impaired mobility, producing a loss of functional motor independence. We used a GBM xenograft implanted in the striatum to analyze the changes in Y (vertical) and X (horizontal) axis displacement of the metatarsus, ankle, and knee. We analyzed the steps dissimilarity factor between control and GBM mice with and without anastrozole. The body weight of the untreated animals decreased compared to treated mice. Anastrozole reduced the malignant cells and decreased GPR30 and ERα receptor expression. In addition, we observed a partial recovery in metatarsus and knee joint displacement (dissimilarity factor). The vertical axis displacement of the GBM+anastrozole group showed a difference in the right metatarsus, right knee, and left ankle compared to the GBM group. In the horizontal axis displacement of the right metatarsus, ankle, and knee, the GBM+anastrozole group exhibited a difference at the last third of the step cycle compared to the GBM group. Thus, anastrozole partially modified joint displacement. The dissimilarity factor and the vertical and horizontal displacements study will be of interest in GBM patients with locomotion alterations. Hindlimb displacement and gait locomotion analysis could be a valuable methodological tool in experimental and clinical studies to help diagnose locomotive deficits related to GBM.

Risk Factors for Nontuberculous Mycobacteria Infections in Solid Organ Transplant Recipients: A Multinational Case-Control Study.

BACKGROUND: Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors. METHODS: Retrospective, multinational, 1:2 matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018. Controls were matched on transplanted organ, NTM treatment center, and post-transplant survival greater than or equal to the time to NTM diagnosis. Logistic regression on matched pairs was used to assess associations between risk factors and NTM infections. RESULTS: Analyses included 85 cases and 169 controls (59% male, 88% White, median age at time of SOT of 54 years [interquartile range {IQR} 40-62]). NTM infection occurred in kidney (42%), lung (35%), heart and liver (11% each), and pancreas transplant recipients (1%). Median time from transplant to infection was 21.6 months (IQR 5.3-55.2). Most underlying comorbidities were evenly distributed between groups; however, cases were older at the time of NTM diagnosis, more frequently on systemic corticosteroids and had a lower lymphocyte count (all P < .05). In the multivariable model, older age at transplant (adjusted odds ratio [aOR] 1.04; 95 confidence interval [CI], 1.01-1.07), hospital admission within 90 days (aOR, 3.14; 95% CI, 1.41-6.98), receipt of antifungals (aOR, 5.35; 95% CI, 1.7-16.91), and lymphocyte-specific antibodies (aOR, 7.73; 95% CI, 1.07-56.14), were associated with NTM infection. CONCLUSIONS: Risk of NTM infection in SOT recipients was associated with older age at SOT, prior hospital admission, receipt of antifungals or lymphocyte-specific antibodies. NTM infection should be considered in SOT patients with these risk factors.

Effect of goal-directed haemodynamic therapy guided by non-invasive monitoring on perioperative complications in elderly hip fracture patients within an enhanced recovery pathway.

BACKGROUND: Goal-directed haemodynamic therapy (GDHT) has been shown to reduce morbidity and mortality in high-risk surgical patients. However, there is little evidence of its efficacy in patients undergoing hip fracture surgery. This study aims to evaluate the effect of GDHT guided by non-invasive haemodynamic monitoring on perioperative complications in patients undergoing hip fracture surgery. METHODS: Patients > 64 years undergoing hip fracture surgery within an enhanced recovery pathway (ERP) were enrolled in this single-centre, non-randomized, intervention study with a historical control group and 12-month follow-up. Exclusion criteria were patients with pathological fractures, traffic-related fractures and refractures. Control group (CG) patients received standard care treatment. Intervention group (IG) patients received a GDHT protocol based on achieving an optimal stroke volume, in addition to a systolic blood pressure > 90 mmHg and an individualized cardiac index. No changes were made between groups in the ERP during the study period. Primary outcome was percentage of patients who developed intraoperative haemodynamic instability. Secondary outcomes were intraoperative arrhythmias, postoperative complications (cardiovascular, respiratory, infectious and renal complications), administered fluids, vasopressor requirements, perioperative transfusion, length of hospital stay, readmission and 1-year survival. RESULTS: In total, 551 patients (CG=272; IG=279) were included. Intraoperative haemodynamic instability was lower in the IG (37.5% vs 28.0%; p=0.017). GDHT patients had fewer postoperative cardiovascular (18.8% vs 7.2%; p < 0.001), respiratory (15.1% vs 3.6%; p<0.001) and infectious complications (21% vs 3.9%; p<0.001) but not renal (12.1% vs 33.7%; p<0.001). IG patients had less vasopressor requirements (25.5% vs 39.7%; p<0.001) and received less fluids [2.600 ml (IQR 1700 to 2700) vs 850 ml (IQR 750 to 1050); p=0.001] than control group. Fewer patients required transfusion in GDHT group (73.5% vs 44.4%; p<0.001). For IG patients, median length of hospital stay was shorter [11 days (IQR 8 to 16) vs 8 days; (IQR 6 to 11) p < 0.001] and 1-year survival higher [73.4% (95%CI 67.7 to 78.3 vs 83.8% (95%CI 78.8 to 87.7) p<0.003]. CONCLUSIONS: The use of GDHT decreases intraoperative complications and postoperative cardiovascular, respiratory and infectious but not postoperative renal complications. This strategy was associated with a shorter hospital stay and increased 1-year survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT02479321 .

Neonatal Mice Spinal Cord Interneurons Send Axons through the Dorsal Roots.

Spontaneous interneuron activity plays a critical role in developing neuronal networks. Discharges conducted antidromically along the dorsal root (DR) precede those from the ventral root's (VR) motoneurons. This work studied whether spinal interneurons project axons into the neonate's dorsal roots. Experiments were carried out in postnatal Swiss-Webster mice. We utilized a staining technique and found that interneurons in the spinal cord's dorsal horn send axons through the dorsal roots. In vitro electrophysiological recordings showed antidromic action potentials (dorsal root reflex; DRR) produced by depolarizing the primary afferent terminals. These reflexes appeared by stimulating the adjacent dorsal roots. We found that bicuculline reduced the DRR evoked by L5 dorsal root stimulation when recording from the L4 dorsal root. Simultaneously, the monosynaptic reflex (MR) in the L5 ventral root was not affected; nevertheless, a long-lasting after-discharge appeared. The addition of 2-amino-5 phosphonovaleric acid (AP5), an NMDA receptor antagonist, abolished the MR without changing the after-discharge. The absence of DRR and MR facilitated single action potentials in the dorsal and ventral roots that persisted even in low Ca2+ concentrations. The results suggest that firing interneurons could send their axons through the dorsal roots. These interneurons could activate motoneurons producing individual spikes recorded in the ventral roots. Identifying these interneurons and the persistence of their neuronal connectivity in adulthood remains to be established.

Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2015 and GOLD 2019 staging: a pooled analysis of individual patient data.

In 2019, The Global Initiative for Chronic Obstructive Lung Disease (GOLD) modified the grading system for patients with COPD, creating 16 subgroups (1A-4D). As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aim to compare the mortality prediction of the 2015 and 2019 COPD GOLD staging systems. We studied 17 139 COPD patients from the 3CIA study, selecting those with complete data. Patients were classified by the 2015 and 2019 GOLD ABCD systems, and we compared the predictive ability for 5-year mortality of both classifications. In total, 17 139 patients with COPD were enrolled in 22 cohorts from 11 countries between 2003 and 2017; 8823 of them had complete data and were analysed. Mean±sd age was 63.9±9.8 years and 62.9% were male. GOLD 2019 classified the patients in milder degrees of COPD. For both classifications, group D had higher mortality. 5-year mortality did not differ between groups B and C in GOLD 2015; in GOLD 2019, mortality was greater for group B than C. Patients classified as group A and B had better sensitivity and positive predictive value with the GOLD 2019 classification than GOLD 2015. GOLD 2015 had better sensitivity for group C and D than GOLD 2019. The area under the curve values for 5-year mortality were only 0.67 (95% CI 0.66-0.68) for GOLD 2015 and 0.65 (95% CI 0.63-0.66) for GOLD 2019. The new GOLD 2019 classification does not predict mortality better than the previous GOLD 2015 system.

Innovation Strategies of the Spanish Agri-Food Sector in Response to the Black Swan COVID-19 Pandemic.

Health, financial, and social crises cause variations in the buying behaviour of food consumers as well as in the value they assign to food attributes and the place of purchase, leading to consumers with profiles that are more susceptible to these changes than others. Thus, it was observed that 61.4% of consumers modified their buying behaviour at the onset of the COVID-19 pandemic, with those who modified it the most being the people who stockpiled the most food and went panic buying more often. This has made it possible to establish the profile of different significant consumer segments, and as a response, food production/distribution companies can implement different innovative strategies aimed at decreasing the impact of stockpiling and, therefore, the shortage of food. The possible strategies that companies can put into effect are creating a stock of non-perishable foods, increasing production capabilities in a sustainable way and, especially in light of the results obtained, boost the online sale and distribution of foods, with the goal of decreasing the amount of people in shops (which decreases the spreading of the pandemic and favours health) and preventing consumers from observing possible circumstantial shortages that would only encourage stockpiling and panic buying, even among consumers who have not changed their buying behaviour.

Differences in Consumer Preferences for Lamb Meat before and duriang the Economic Crisis in Spain. Analysis and Perspectives.

Determining the preferences of food consumers is key for adapting supply and demand. This adaptation of supply is dynamic rather than static, given that it develops over time and is influenced by both social and economic factors. This work presents an analysis of the development of lamb meat consumption at two points in time, 2004 and 2014, before and in the midst of the economic crisis in Spain (2007-2017). Our findings show that together with the external appearance and against the backdrop of an economic recession, price has a greater impact on consumers' purchasing decisions than origin and quality seals, despite these being attributes that are traditionally used as a guarantee of food safety and traceability. This suggests that in times of economic crisis consumer preferences shift towards attributes that are less related to product quality. Nonetheless, the comparison of the consumer segments for each of the years under study revealed that age and level of education are the socioeconomic factors that most influence the preferences of lamb meat consumers.

Fictive Scratching Patterns in Brain Cortex-Ablated, Midcollicular Decerebrate, and Spinal Cats.

Background: The spinal cord's central pattern generators (CPGs) have been explained by the symmetrical half-center hypothesis, the bursts generator, computational models, and more recently by connectome circuits. Asymmetrical models, at odds with the half-center paradigm, are composed of extensor and flexor CPG modules. Other models include not only flexor and extensor motoneurons but also motoneuron pools controlling biarticular muscles. It is unknown whether a preferred model can explain some particularities that fictive scratching (FS) in the cat presents. The first aim of this study was to investigate FS patterns considering the aiming and the rhythmic periods, and second, to examine the effects of serotonin (5HT) on and segmental inputs to FS. Methods: The experiments were carried out first in brain cortex-ablated cats (BCAC), then spinalized (SC), and for the midcollicular (MCC) preparation. Subjects were immobilized and the peripheral nerves were used to elicit the Monosynaptic reflex (MR), to modify the scratching patterns and for electroneurogram recordings. Results: In BCAC, FS was produced by pinna stimulation and, in some cases, by serotonin. The scratching aiming phase (AP) initiates with the activation of either flexor or extensor motoneurons. Serotonin application during the AP produced simultaneous extensor and flexor bursts. Furthermore, WAY 100635 (5HT1A antagonist) produced a brief burst in the tibialis anterior (TA) nerve, followed by a reduction in its electroneurogram (ENG), while the soleus ENG remained silent. In SC, rhythmic phase (RP) activity was recorded in the soleus motoneurons. Serotonin or WAY produced FS bouts. The electrical stimulation of Ia afferent fibers produced heteronymous MRes waxing and waning during the scratch cycle. In MCC, FS began with flexor activity. Electrical stimulation of either deep peroneus (DP) or superficial peroneus (SP) nerves increased the duration of the TA electroneurogram. Medial gastrocnemius (MG) stretching or MG nerve electrical stimulation produced a reduction in the TA electroneurogram and an initial MG extensor burst. MRes waxed and waned during the scratch cycle. Conclusion: Descending pathways and segmental afferent fibers, as well as 5-HT and WAY, can change the FS pattern. To our understanding, the half-center hypothesis is the most suitable for explaining the AP in MCC.

Flow cytometry "Ogata score" for the diagnosis of myelodysplastic syndromes in a real-life setting. A Latin American experience.

INTRODUCTION: Flow cytometry (FC) is a helpful tool for the diagnosis of myelodysplastic syndrome (MDS). Different FC score systems have been developed. The "Ogata score" is a simple diagnostic score that has been validated having a sensitivity of 69% and a specificity of 92% in low-risk MDS. We aimed to study the feasibility and the utility of the "Ogata score" for the diagnosis of MDS among Latin America (LA) Laboratories. METHODS: This is a case and control study conducted in LA institutions members of Grupo Latinoamericano de Mielodisplasia (GLAM). A total of 146 MDS patients and 57 control patients were included. "Ogata score" was calculated. RESULTS: The sensitivity of "Ogata score" was 75.6% (95% CI, 66.8-81.3), specificity was 91.2% (95% CI, 79.7-96.7), PPV was 95.6% (95% CI, 88.5-98.3), and NPV was 65.4% (95% CI, 49.1-71.9). In low/intermediate-1 IPSS patients group, the sensitivity was 70.1% (95% CI, 60.2-78.2), specificity was 91.2% (CI-95%, 79.7-96.7), PPV was 94.2% (95% CI, 86.4-97.8), and NPV was 62.1% (95% CI, 53.0-78.7). In the group of patients "without MDS specific markers" (patients without ring sideroblasts, blast excess, or chromosomal abnormalities), the sensitivity was 66.7% (CI-95%, 55.8-76.0), specificity was 91.2% (95% CI, 79.7-96.7), PPV was 92.3% (95% CI, 82.2-97.1), and NPV was 63.5% (95% CI, 51.9-73.5). CONCLUSIONS: The diagnostic power found in this study was similar to the reported by Della-Porta et al. Also in LA, the analysis was made in modern equipment with acquisition of at least 100 000 events which permits a good reproducibility of the results.

Tamoxifen Promotes Axonal Preservation and Gait Locomotion Recovery after Spinal Cord Injury in Cats.

We performed experiments in cats with a spinal cord penetrating hemisection at T13-L1 level, with and without tamoxifen treatment. The results showed that the numbers of the ipsilateral and contralateral ventral horn neurons were reduced to less than half in the nontreated animals compared with the treated ones. Also, axons myelin sheet was preserved to almost normal values in treated cats. On the contrary, in the untreated animals, their myelin sheet was reduced to 28% at 30 days after injury (DAI), in both the ipsilateral and contralateral regions of the spinal cord. Additionally, we made hindlimb kinematics experiments to study the effects of tamoxifen on cat locomotion after the injury: at 4, 16, and 30 DAI. We observed that the ipsilateral hindlimb angular displacement (AD) of the pendulum-like movements (PLM) during gait locomotion was recovered to almost normal values in treated cats. Contralateral PLM acquired similar values to those obtained in intact cats. At 4 DAI, untreated animals showed a compensatory increment of PLM occurring in the contralateral hindlimb, which was partially recovered at 30 DAI. Our findings indicate that tamoxifen exerts a neuroprotective effect and preserves or produces myelinated axons, which could benefit the locomotion recovery in injured cats.

Aberrant gastrocnemius muscle innervation by tibial nerve afferents after implantation of chitosan tubes impregnated with progesterone favored locomotion recovery in rats with transected sciatic nerve.

OBJECT: Transection of peripheral nerves produces loss of sensory and/or motor function. After complete nerve cutting, the distal and proximal segment ends retract, but if both ends are bridged with unaltered chitosan, progesterone-impregnated chitosan, or silicone tubes, an axonal repair process begins. Progesterone promotes nerve repair and has neuroprotective effects thwarting regulation of neuron survival, inflammation, and edema. It also modulates aberrant axonal sprouting and demyelination. The authors compared the efficacy of nerve recovery after implantation of progesterone-loaded chitosan, unaltered chitosan, or silicone tubes after sciatic nerve transection in rats. METHODS: After surgical removal of a 5-mm segment of the proximal sciatic nerve, rats were implanted with progesterone-loaded chitosan, unaltered chitosan, or silicone tubes in the transected nerve for evaluating progesterone and chitosan effects on sciatic nerve repair and ipsilateral hindlimb kinematic function, as well as on gastrocnemius electro-myographic responses. In some experiments, tube implantation was performed 90 minutes after nerve transection. RESULTS: At 90 days after sciatic nerve transection and tube implantation, rats with progesterone-loaded chitosan tubes showed knee angular displacement recovery and better outcomes for step length, velocity of locomotion, and normal hindlimb raising above the ground. In contrast, rats with chitosan-only tubes showed reduced normal raising and pendulum-like hindlimb movements. Aberrant fibers coming from the tibial nerve innervated the gastrocnemius muscle, producing electromyographic responses. Electrical responses in the gastrocnemius muscle produced by sciatic nerve stimulation occurred only when the distal nerve segment was stimulated; they were absent when the proximal or intratubular segment was stimulated. A clear sciatic nerve morphology with some myelinated fiber fascicles appeared in the tube section in rats with progesterone-impregnated chitosan tubes. Some gastrocnemius efferent fibers were partially repaired 90 days after nerve resection. The better outcome in knee angle displacement may be partially attributable to the aberrant neuromuscular synaptic effects, since nerve conduction in the gastrocnemius muscle could be blocked in the progesterone-impregnated chitosan tubes. In addition, in the region of the gap produced by the nerve resection, the number of axons and amount of myelination were reduced in the sciatic nerve implanted with chitosan, progesterone-loaded chitosan, and silicone tubes. At 180 days after sciatic nerve sectioning, the knee kinematic function recovered to a level observed in control rats of a similar age. In rats with progesterone-loaded chitosan tubes, stimulation of the proximal and intratubular sciatic nerve segments produced an electromyographic response. The axon morphology of the proximal and intratubular segments of the sciatic nerve resembled that of the contralateral nontransected nerve. CONCLUSIONS: Progesterone-impregnated chitosan tubes produced aberrant innervation of the gastrocnemius muscle, which allowed partial recovery of gait locomotion and could be adequate for reinnervating synergistic denervated muscles while a parent innervation is reestablished. Hindlimb kinematic parameters differed between younger (those at 90 days) and older (those at 180 days) rats.

[Health impact evaluation of particle air pollution in five Spanish cities. European APHEIS project]. / Evaluación en cinco ciudades españolas del impacto en salud de la contaminación atmosférica por partículas. Proyecto europeo APHEIS.

BACKGROUND: The health effects of air pollution have been analyzed in numerous studies over recent years, thus having made it possible to quantify the relationship between the two. This study is aimed at analyzing the theoretical benefits which would be achieved by meeting the air quality objectives set forth under EC Directive 1999/30/EC with regard to suspended particles. METHODS: The exposure measurement was taken for Black Smoke (Barcelona, Bilbao, Valencia) and suspended particles under 10 microm (PM10) (Bilbao, Madrid y Sevilla). The health indicators calculated were the mortality due to all causes and respiratory and cardiovascular causes, and emergency hospital admissions and mortality due to respiratory and cardiovascular causes. In the case of PM10 the impact has been calculated because its effects to short-term, within a period of up to 40 days following exposure, and to long-term. For Black Smoke the effects only has been calculated to short-term. RESULTS: The daily levels of PM10 from exceeding 50 microg/m3 in Bilbao, Madrid and Sevilla cause the earlier death of 1.4/100,000 individuals per year because its effects. The effect within a period of up to 40 days following exposure is of 2.8 deaths/100,000. The total number of deaths per year which may be later due to long-term exposure if the yearly average is lowered to 20 microg/m3 is 68/100,000. CONCLUSIONS: The health impact of the current air pollution levels is quantifiable and is not insignificant. APHEIS and the impact evaluations may be of aid in healthcare planning and environmental policies.

Evaluación en cinco ciudades españolas del impacto en salud de la contaminación atmosférica por partículas. Proyecto europeo APHEIS / Health impact evaluation of particle air pollution in five spanish cities. European APHEIS project

Fundamento: Los efectos de la contaminación atmosféricasobre la salud han sido objeto en los últimos años de numerosos estudiosque han permitido cuantificar la asociación entre ambas El objetivode este trabajo es llevar a cabo la Evaluación del Impacto enSalud (EIS) calculando los beneficios que se obtendrían al cumplirlos objetivos establecidos por la Directiva 1999/30/CE en relacióncon las partículas en suspensión.Métodos: Se ha valorado el impacto en salud de la contaminación atmosférica por partículas en suspensión, para lo que se han utilizadodos indicadores distintos: Humos Negros (HN) (Barcelona,Bilbao, Valencia) y partículas en suspensión menores de 10 mm(PM10) (Bilbao, Madrid y Sevilla). Los indicadores de salud fueronla mortalidad por todas las causas, por causa respiratoria y por causacardiovascular, e ingresos hospitalarios urgentes por causa respiratoriay cardiovascular. El EIS se ha realizado mediante el cálculo de lafracción atribuible a la contaminación por partículas. En el caso dePM10 se ha calculado el impacto debido a efectos de la contaminación a corto plazo, los acumulados hasta 40 días después, y a largoplazo. Para HN únicamente se han calculado efectos a corto plazo.Resultados: Los niveles diarios de PM10 por encima de 50µg/m3 en Bilbao, Madrid y Sevilla son responsables de 1,4 muertesprematuras por 100.000 habitantes y año debido a sus efectos a cortoplazo y de 2,8 muertes/100.000 en un periodo de hasta 40 días trasla exposición. A largo plazo, el número de muertes prematuras atribuiblesa la contaminación media anual de PM10 por encima de 20µg/m3 es 68/100.000.Conclusiones: El impacto en salud de los niveles actuales decontaminación atmosférica es cuantificable y no despreciable.APHEIS y las evaluaciones de impacto pueden ayudar a la planificación sanitaria y a las políticas medioambientales

Background: The health effects of air pollution have beenanalyzed in numerous studies over recent years, thus having madeit possible to quantify the relationship between the two. This studyis aimed at analyzing the theoretical benefits which would be achievedby meeting the air quality objectives set forth under EC Directive1999/30/EC with regard to suspended particles.Methods: The exposure measurement was taken for Black Smoke(Barcelona, Bilbao, Valencia) and suspended particles under 10mm (PM10) (Bilbao, Madrid y Sevilla). The health indicators calculatedwere the mortality due to all causes and respiratory and cardiovascularcauses, and emergency hospital admissions and mortalitydue to respiratory and cardiovascular causes. In the case of PM10 theimpact has been calculated because its effects to short-term, within aperiod of up to 40 days following exposure, and to long-term. ForBlack Smoke the effects only has been calculated to short-term.Results: The daily levels of PM10 from exceeding 50 µg/m3 inBilbao, Madrid and Sevilla cause the earlier death of 1.4/100,000individuals per year because its effects. The effect within a period ofup to 40 days following exposure is of 2.8 deaths/100,000. The totalnumber of deaths per year which may be later due to long-term exposureif the yearly average is lowered to 20 µg/m3 is 68/100,000.Conclusions: The health impact of the current air pollutionlevels is quantifiable and is not insignificant. APHEIS and theimpact evaluations may be of aid in healthcare planning and environmentalpolicies

Hepatotoxicidad por clopidogrel / Clopidogrel-induced hepatoxicity

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