Structural Plasticity of GABAergic Pallidothalamic Terminals in MPTP-Treated Parkinsonian Monkeys: A 3D Electron Microscopic Analysis.

The internal globus pallidus (GPi) is a major source of tonic GABAergic inhibition to the motor thalamus. In parkinsonism, the firing rate of GPi neurons is increased, and their pattern switches from a tonic to a burst mode, two pathophysiological changes associated with increased GABAergic pallidothalamic activity. In this study, we used high-resolution 3D electron microscopy to demonstrate that GPi terminals in the parvocellular ventral anterior nucleus (VApc) and the centromedian nucleus (CM), the two main GPi-recipient motor thalamic nuclei in monkeys, undergo significant morphometric changes in parkinsonian monkeys including (1) increased terminal volume in both nuclei; (2) increased surface area of synapses in both nuclei; (3) increased number of synapses/GPi terminals in the CM, but not VApc; and (4) increased total volume, but not number, of mitochondria/terminals in both nuclei. In contrast to GPi terminals, the ultrastructure of putative GABAergic nonpallidal terminals was not affected. Our results also revealed striking morphological differences in terminal volume, number/area of synapses, and volume/number of mitochondria between GPi terminals in VApc and CM of control monkeys. In conclusion, GABAergic pallidothalamic terminals are endowed with a high level of structural plasticity that may contribute to the development and maintenance of the abnormal increase in pallidal GABAergic outflow to the thalamus in the parkinsonian state. Furthermore, the evidence for ultrastructural differences between GPi terminals in VApc and CM suggests that morphologically distinct pallidothalamic terminals from single pallidal neurons may underlie specific physiological properties of pallidal inputs to VApc and CM in normal and diseased states.

Forest carbon sink neutralized by pervasive growth-lifespan trade-offs.

Land vegetation is currently taking up large amounts of atmospheric CO2, possibly due to tree growth stimulation. Extant models predict that this growth stimulation will continue to cause a net carbon uptake this century. However, there are indications that increased growth rates may shorten trees' lifespan and thus recent increases in forest carbon stocks may be transient due to lagged increases in mortality. Here we show that growth-lifespan trade-offs are indeed near universal, occurring across almost all species and climates. This trade-off is directly linked to faster growth reducing tree lifespan, and not due to covariance with climate or environment. Thus, current tree growth stimulation will, inevitably, result in a lagged increase in canopy tree mortality, as is indeed widely observed, and eventually neutralise carbon gains due to growth stimulation. Results from a strongly data-based forest simulator confirm these expectations. Extant Earth system model projections of global forest carbon sink persistence are likely too optimistic, increasing the need to curb greenhouse gas emissions.

Streamflow variations across the Andes (18°-55°S) during the instrumental era.

The rivers originating in the southern Andes (18°-55°S) support numerous ecosystems and a large number of human populations and socio-economic activities in the adjacent lowlands of Chile, Argentina and Bolivia. Here we show that ca. 75% of the total variance in the streamflow records from this extensive region can be explained by only eight spatially coherent patterns of variability. Five (three) of these Andean patterns exhibit extreme dry (wet) conditions in recent years, with strong interannual variations in northern Chile; long-term drying trends between 31° and 41°S; a transitional pattern in the central Patagonian Andes; and increasing trends in northwestern Argentina and southern Bolivia, the Fueguian Andes, and the eastern portion of the South Patagonian Icefield. Multivariate regression analyses show that large-scale indices of ENSO variability can predict 20% to 45% of annual runoff variability between 28° and 46°S. The influence of Antarctic and North Pacific indices becomes more relevant south of 43°S and in northwestern Argentina and southern Bolivia, respectively, but their overall skill as predictors of Andean streamflows is weak. The analyses provide relevant new information to improve understanding of the spatial coherence, the main temporal features, and the ocean-atmospheric forcings of surface runoff across the southern Andes.

Endoscopic reconstruction of large anterior skull base defects with opening of the sellar diaphragm. Experience at a tertiary level university hospital.

BACKGROUND: The indications for expanded endoscopic transnasal approaches continue to increase, with more complex skull base defects needing to be repaired. This study reviews the management of large anterior skull base defects with opening of the sellar diaphragm. METHOD: A prospective analysis of endonasal endoscopic surgery carried out at Son Espases University Hospital between January 2013 and December 2018 was performed. The analysis included only the cases with a significative intra-operative cerebrospinal fluid leak. In all cases, reconstruction was performed by combining the gasket seal technique with a pedicled mucosal endonasal flap. RESULTS: Twenty-eight patients were included. The mucoperiosteal nasoseptal flap, the lateral wall flap and the middle turbinate flap were used in 13, 8 and 7 patients, respectively, combined with the gasket seal technique. One case of post-operative cerebrospinal fluid leak was observed (3.57 per cent). CONCLUSION: The combination of a gasket seal with an endonasal mucosal flap is an excellent technique for repairing large anterior skull base defects.

Tree-ring correlations suggest links between moderate earthquakes and distant rockfalls in the Patagonian Cordillera.

Earthquakes with magnitudes M > 7 can trigger large landslides and rockfalls at epicenter distances of up to 400 km, whereas moderate shaking (M = 5-7) is generally thought to result in abundant co-seismic mass movements in the vicinity of the epicenter. Although one might anticipate that large magnitude earthquakes off the Chilean coast would result in abundant rockfall in the Patagonian Cordillera, only limited research has explored this hypothesis. Here, we use tree-ring records from 63 cross-sections of century-old (103.9 ± 40.1 yr) Nothofagus pumilio trees to develop a calendar-dated record of small rockfall events (101-102 m3) on a talus slope located next to Monte Fitz Roy (El Chaltén, Argentina; 49°4'S, 72°57'W). The resulting rockfall record is used to infer that subduction zone seismicity at the Triple Junction and intraplate shaking around Lago Argentino almost systematically caused rockfall activity at this site, even if seismicity occurred at large distances (up to 300 km away) and with moderate intensity (M = 5-7). About one third of the rockfalls are triggered by factors other than earthquakes, predominantly in spring when freeze-thaw cycles occur frequently at the site. Despite the fact that seismicity is not the only trigger of rockfall activity at Cerro Crestón, at the foot of Monte Vespignani, we conclude that, in regions where topographic amplification plays a role, small rockfalls can be triggered by earthquakes of moderate intensity at large distances from the epicenter.

Re-examining the role of the gut microbiota in the conversion of the lipid-lowering statin monacolin K (lovastatin) into its active ß-hydroxy acid metabolite.

Monacolin K (MK, lovastatin), a naturally occurring statin, only exerts lipid-lowering effects in its active ß-hydroxy acid form (MKA). This activation was thought to be mediated by the gut microbiota (GM). We report here for the first time that the GM does not convert MK into MKA (a spontaneous pH-dependent conversion) but catabolises MKA. The GM might hamper the lipid-lowering effects by degrading the active metabolite MKA.

The gut microbiota urolithin metabotypes revisited: the human metabolism of ellagic acid is mainly determined by aging.

Understanding individuals' response to dietary bioactives is crucial for personalized nutrition. We report here for the first time in a Caucasian cohort (5-90 years, n = 839) that aging is the main factor that determines the gut microbiota involved in the ellagic acid-ellagitannin metabolism (urolithin metabotypes), with potential consequences for human health.

Vasorelaxant activity of twenty-one physiologically relevant (poly)phenolic metabolites on isolated mouse arteries.

Polyphenols are beneficial for health, but are metabolised after consumption. We compared the vasorelaxant capacity of twenty-one physiologically relevant polyphenol metabolites in isolated mouse arteries. Hesperetin, urolithins and ferulic acid-4-O-sulfate - not their glucuronidated forms or ferulic acid - caused vasorelaxation. Therefore, we advise the use of relevant conjugates in future mechanistic research.

Does water availability regulate biomass partitioning between trunk and branches?

The extent to which a vertical trunk is differentiated from its branches is a key trait for the architecture of trees and may affect interspecific relationships. In this study, we analysed the effect of soil water availability on biomass partitioning for Nothofagus pumilio by means of a nursery experiment. Juvenile trees were subject to three irrigation conditions: no irrigation, intermediate irrigation and high irrigation. Irrigation conditions emulated the mean precipitation of the most representative environments inhabited by N. pumilio. Changes in soil water availability modified the biomass partitioning patterns of trees. In comparison to the other two conditions, high irrigation caused: (i) a higher ratio of biomass partitioning to stems than roots; (ii) more trunk growth in relation to its branches; and (iii) more photosynthetic organs relative to the aboveground biomass. Trunk size relative to that of its most recent branches was not increased by water availability. Water availability may play a significant role in the capacity of N. pumilio for space occupation due to the effects on axis differentiation.

Effect of bovine ABCG2 polymorphism Y581S SNP on secretion into milk of enterolactone, riboflavin and uric acid.

The ATP-binding cassette transporter G2/breast cancer resistance protein (ABCG2/BCRP) is an efflux protein involved in the bioavailability and milk secretion of endogenous and exogenous compounds, actively affecting milk composition. A limited number of physiological substrates have been identified. However, no studies have reported the specific effect of this polymorphism on the secretion into milk of compounds implicated in milk quality such as vitamins or endogenous compounds. The bovine ABCG2 Y581S polymorphism is described as a gain-of-function polymorphism that increases milk secretion and decreases plasma levels of its substrates. This work aims to study the impact of Y581S polymorphism on plasma disposition and milk secretion of compounds such as riboflavin (vitamin B2), enterolactone, a microbiota-derived metabolite from the dietary lignan secoisolariciresinol and uric acid. In vitro transport of these compounds was assessed in MDCK-II cells overexpressing the bovine ABCG2 (WT-bABCG2) and its Y581S variant (Y581S-bABCG2). Plasma and milk levels were obtained from Y/Y homozygous and Y/S heterozygous cows. The results show that riboflavin was more efficiently transported in vitro by the Y581S variant, although no differences were noted in vivo. Both uric acid and enterolactone were substrates in vitro of the bovine ABCG2 variants and were actively secreted into milk with a two-fold increase in the milk/plasma ratio for Y/S with respect to Y/Y cows. The in vitro ABCG2-mediated transport of the drug mitoxantrone, as a model substrate, was inhibited by enterolactone in both variants, suggesting the possible in vivo use of this enterolignan to reduce ABCG2-mediated milk drug transfer in cows. The Y581S variant was inhibited to a lesser extent probably due to its higher transport capacity. All these findings point to a significant role of the ABCG2 Y581S polymorphism in the milk disposition of enterolactone and the endogenous molecules riboflavin and uric acid, which could affect both milk quality and functionality.

Tratamiento médico del embarazo ectópico en un centro de salud privado / Medical treatment ectopic pregnancy in a private health center

El tratamiento médico del embarazo ectópico está determinado en base a la correlación entre el diagnóstico clínico, ecográfico y laboratorial (B- hCG). Aunque el tratamiento médico es bastante difundido, no existe un consenso sobre la terapéutica adecuada en cuanto al uso del Methotrexate. El presente trabajo analiza el uso del Methotrexate (MTX) como terapia para el embarazo ectópico ilustrado en cuatro casos diagnosticados por ultrasonografía y laboratorio (B-hCG) tratados exitosamente con terapia sistémica de Methotrexate. Siendo el Methotrexate un quimioterápico que ha demostrado seguridad en su administración ofrece una alternativa efectiva no quirúrgica y a bajos costos comparados con el clásico tratamiento quirúrgico.

Medical treatment of ectopic pregnancy is determined based on the correlation between clinical, ultrasound and laboratory diagnosis (B- hCG). Although medical treatment is fairly widespread, there is no consensus on the appropriate treatment in the use of methotrexate. This paper analyzes the use of Methotrexate (MTX) therapy for ectopic pregnancy illustrated in four cases diagnosed by ultrasonography and laboratory (B-hCG) successfully treated with systemic therapy Methotrexate. Being a chemotherapeutic methotrexate has demonstrated safety in its administration provides an effective non-surgical and at low cost alternative compared to the classical surgical treatment.

Manejo del vértigo posicional paroxístico benigno en atención primaria / Management of benign paroxysmal positional vertigo in first care centers

El vértigo posicional paroxístico benigno es la entidad más frecuente dentro de los vértigos de origen periférico. Se caracteriza por crisis de vértigo desencadenadas por cambios posicionales de la cabeza y de corta duración. Suele presentarse en los mayores de 40-50 años, y hasta el 50% de los casos no se deben a una causa conocida, por lo que se habla de vértigo posicional paroxístico benigno idiopático. Debido a la alta incidencia del vértigo posicional paroxístico benigno, consideramos de especial trascendencia poseer los conocimientos necesarios para poder diagnosticar y tratar con eficacia esta afección en el ámbito de la medicina de atención primaria, ya que en la mayoría de los casos se obtienen excelentes resultados a través de unas maniobras específicas y fáciles de realizar (AU)

The benign paroxysmal positional vertigo is the most common disease in the group of peripheral vertigo. It's characterized by vertiginous sensation triggered by the positional changes of the head and usually lasts less than one minute. It is most frequently seen in middle-aged patients (40-50 years old) and in up 50% of cases we do not know the cause, so we refer to them as idiopathic benign paroxysmal positional vertigo. Because of the high incidence of benign paroxysmal positional vertigo in general population, it is of utmost importance to be aware of the differential diagnosis and to be able to treat this pathology with efficacy, because in most cases we can achieve excellent results performing specific and simple maneuvers (AU)

[Management of benign paroxysmal positional vertigo in first care centers]. / Manejo del vértigo posicional paroxístico benigno en atención primaria.

The benign paroxysmal positional vertigo is the most common disease in the group of peripheral vertigo. It's characterized by vertiginous sensation triggered by the positional changes of the head and usually lasts less than one minute. It is most frequently seen in middle-aged patients (40-50 years old) and in up 50% of cases we do not know the cause, so we refer to them as idiopathic benign paroxysmal positional vertigo. Because of the high incidence of benign paroxysmal positional vertigo in general population, it is of utmost importance to be aware of the differential diagnosis and to be able to treat this pathology with efficacy, because in most cases we can achieve excellent results performing specific and simple maneuvers.

Flex center method versus center method for endothelial corneal evaluation in eye banking: a comparative analysis.

Specular microscopy can provide a non-invasive morphological analysis of the cornea endothelial cell layer. A variety of analysis programs are available to determine corneal endothelial quality. The flex-center endothelial analysis method (Konan Inc) is a newer technique including the outermost digitized cells and thus increases the number of cells for analysis. The aim of this study is to analyze whether the new flex-center method, increases the possibilities of corneal endothelium evaluation before implants. For this purpose 67 corneas were studied by both methods at the Eye Bank of the Tissue Establishment of Córdoba. Although we have found differences in the resulting of number of cells in the area analysed, no significant differences were found with respect to the endothelial cell count, coefficient of variation cell area, and the percentage of hexagonal cells recorded. Based on this data, both methods can be used satisfactorily in eye banking.

Bioavailability of phenolics from an oleuropein-rich olive (Olea europaea) leaf extract and its acute effect on plasma antioxidant status: comparison between pre- and postmenopausal women.

PURPOSE: Preclinical studies suggest a potential protective effect of oleuropein in osteoporosis, and one of the proposed mechanisms is the modulation of the oxidative stress. Oleuropein bioavailability and its effect on antioxidant status in pre- and postmenopausal women are unknown. The aim of the present study was to investigate the oral bioavailability of an olive leaf extract rich in oleuropein (40 %) and its effect on antioxidant status in postmenopausal women compared to premenopausal women. METHODS: Premenopausal (n = 8) and postmenopausal women (n = 8) received 250 mg of olive leaf extract, blood samples (t = 0, 1, 2, 3, 4, 6, 8, 12, 16 and 24 h) were taken, and 24-h urine divided into five fractions was collected. Olive-leaf-extract-derived metabolites were analyzed in plasma and urine by HPLC-ESI-QTOF and UPLC-ESI-QqQ, and pharmacokinetics parameters were determined. Ferric reducing antioxidant ability and malondialdehyde levels were measured in plasma. RESULTS: Plasma levels of hydroxytyrosol glucuronide, hydroxytyrosol sulfate, oleuropein aglycon glucuronide and oleuropein aglycon derivative 1 were higher in postmenopausal women. MDA levels were significantly decreased (32%) in postmenopausal women and inversely correlated with hydroxytyrosol sulfate levels. Postmenopausal women excreted less sulfated metabolites in urine than premenopausal women. CONCLUSIONS: Our results suggest that postmenopausal women could be a target population for the intake of olive phenolics in order to prevent age-related and oxidative stress-related processes such as osteoporosis.

Neuronal loss in the caudal intralaminar thalamic nuclei in a primate model of Parkinson's disease.

In light of postmortem human studies showing extensive degeneration of the center median (CM) and parafascicular (Pf) thalamic nuclei in Parkinson's disease patients, the present study assessed the extent of neuronal loss in CM/Pf of non-human primates that were rendered parkinsonian by repeated injections of low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In order to determine the course of CM/Pf degeneration during the MPTP intoxication, motor-asymptomatic animals with partial striatal dopamine denervation were also used. The Cavalieri's principle for volume estimation and the unbiased stereological cell count method with the optical dissector technique were used to estimate the total number of neurons in the CM/Pf. We found substantial neurons loss in the CM/Pf in both, motor-symptomatic MPTP-treated monkeys in which the striatal dopamine innervation was reduced by more than 80%, and in motor-asymptomatic MPTP-treated animals with 40-50% striatal dopamine loss. In MPTP-treated parkinsonian monkeys, 60 and 62% neurons loss was found in CM and Pf, respectively, while partially dopamine-depleted asymptomatic animals displayed 59 and 52% neurons loss in the CM and Pf, respectively. Thus, our study demonstrates that the CM/Pf neurons loss is an early phenomenon that occurs prior to the development of parkinsonian motor symptoms in these animals. In contrast, the neighboring mediodorsal nucleus of the thalamus was only mildly affected (18% neurons loss) in the parkinsonian monkeys. Together with recent findings about the possible role of the CM/Pf-striatal system in cognition, our findings suggest that the pathology of the thalamostriatal system may precede the development of motor symptoms in PD, and may account for some of the cognitive deficits in attentional set-shifting often seen in these patients. Future studies in this animal model, and in monkeys with selective lesion of CM or Pf, are needed to further elucidate the role of the CM/Pf-striatal system in normal and parkinsonian conditions.

Cierre de defecto tóraco-lumbar mediante colgajo de dorsal ancho reverso: a propósito de un caso / Closure of thoracolumbar defect with reverse latissimus muscle flap: case report

Para la reconstrucción de grandes defectos tóracolumbares, ya sean congénitos o adquiridos, se utilizan diversas técnicas quirúrgicas como injertos de piel, colgajos locales, colgajos loco-regionales, colgajos a distancia y colgajos libres, cada una con sus ventajas e inconvenientes dependiendo no solo del defecto a cubrir sino también de la disponibilidad para realizarlos. Presentamos el caso de una mujer de 56 años de edad con patología discal, intervenida quirúrgicamente para artrodesis póstero-lateral L1-L5 que requirió varias intervenciones con desbridamiento de la musculatura paravertebral tras infección y hematoma, quedando como secuela de las mismas un defecto de aproximadamente 20 x 5 cm que tras un intento fallido de cicatrización dirigida tuvo que ser reconstruido mediante colgajo de dorsal ancho reverso. Tras 2 años de seguimiento postoperatorio, la paciente presenta una evolución satisfactoria con cierre total del defecto y sin secuelas (AU)

For the reconstruction of large thoracolumbar defects, whether congenital or acquired, have been used several surgical techniques such as skin grafts, local flaps, locoregional flaps, distant flaps and free flaps, each one showing its advantages and disadvantages depending not only to cover the defect but the availability of achieving them. A case of a woman of 56-year-old, disc pathology, operated from L1-L5 posterolateral arthrodesis requiring several interventions in the area with debridement of the paraspinal muscles after infection and hematoma, leaving a defect of about 20 x 5 cm that after the failed attempt to heal addressed, is reconstructed by a reverse latissimus dorsi flap. After 2 years of follow-up period has developed well, with complete closure of the defect and without sequels (AU)

Differential striatal spine pathology in Parkinson's disease and cocaine addiction: a key role of dopamine?

In the striatum, the dendritic tree of the two main populations of projection neurons, called "medium spiny neurons (MSNs)", are covered with spines that receive glutamatergic inputs from the cerebral cortex and thalamus. In Parkinson's disease (PD), striatal MSNs undergo an important loss of dendritic spines, whereas aberrant overgrowth of striatal spines occurs following chronic cocaine exposure. This review examines the possibility that opposite dopamine dysregulation is one of the key factors that underlies these structural changes. In PD, nigrostriatal dopamine degeneration results in a significant loss of dendritic spines in the dorsal striatum, while rodents chronically exposed to cocaine and other psychostimulants, display an increase in the density of "thin and immature" spines in the nucleus accumbens (NAc). In rodent models of PD, there is evidence that D2 dopamine receptor-containing MSNs are preferentially affected, while D1-positive cells are the main targets of increased spine density in models of addiction. However, such specificity remains to be established in primates. Although the link between the extent of striatal spine changes and the behavioral deficits associated with these disorders remains controversial, there is unequivocal evidence that glutamatergic synaptic transmission is significantly altered in both diseased conditions. Recent studies have suggested that opposite calcium-mediated regulation of the transcription factor myocyte enhancer factor 2 (MEF2) function induces these structural defects. In conclusion, there is strong evidence that dopamine is a major, but not the sole, regulator of striatal spine pathology in PD and addiction to psychostimulants. Further studies of the role of glutamate and other genes associated with spine plasticity in mediating these effects are warranted.

In vitro susceptibility of high virulence microorganisms isolated in heart valve banking.

Storage preparation of human heart valves for implants generally includes incubation in an antimicrobial disinfection solution and cryopreservation. Changes in patterns of microorganisms susceptibility to antibiotics is a variable process of that promote its inefficiency. The aim of this study has been an evaluation of in vitro susceptibility of high virulence microorganisms isolated in our tissue bank for 14 years in order to evaluate the efficiency, and to promote changes for further antibiotics mixtures as well. Data presented in this study show that microorganisms isolates in valve banking display susceptibility patterns similar to those shown in other clinical circumstances, and the most commonly used antibiotics regimes are useful to date. An antibiotic cocktail containing aminoglicoside in addition to ciprofloxacin and vancomycin is an efficient mixture to be used in valve banking. Further studies will be necessary for monitoring patterns changes of in vitro susceptibility of microbiological isolates in tissue banking.