Long-term annual estimation of forest above ground biomass, canopy cover, and height from airborne and spaceborne sensors synergies in the Iberian Peninsula.

The Mediterranean Basin has experienced substantial land use changes as traditional agriculture decreased and population migrated from rural to urban areas, which have resulted in a large forest cover increase. The combination of Landsat time series, providing spectral information, with lidar, offering three-dimensional insights, has emerged as a viable option for the large-scale cartography of forest structural attributes across large time spans. Here we develop and test a comprehensive framework to map forest above ground biomass, canopy cover and forest height in two regions spanning the most representative biomes in the peninsular Spain, Mediterranean (Madrid region) and temperate (Basque Country). As reference, we used lidar-based direct estimates of stand height and forest canopy cover. The reference biomass and volume were predicted from lidar metrics. Landsat time series predictors included annual temporal profiles of band reflectance and vegetation indices for the 1985-2023 period. Additional predictor variables including synthetic aperture radar, disturbance history, topography and forest type were also evaluated to optimize forest structural attributes retrieval. The estimates were independently validated at two temporal scales, i) the year of model calibration and ii) the year of the second lidar survey. The final models used as predictor variables only Landsat based metrics and topographic information, as the available SAR time-series were relatively short (1991-2011) and disturbance information did not decrease the estimation error. Model accuracies were higher in the Mediterranean forests when compared to the temperate forests (R2 = 0.6-0.8 vs. 0.4-0.5). Between the first (1985-1989) and the last (2020-2023) decades of the monitoring period the average forest cover increased from 21 ± 2% to 32 ± 1%, mean height increased from 6.6 ± 0.43 m to 7.9 ± 0.18 m and the mean biomass from 31.9 ± 3.6 t ha-1 to 50.4 ± 1 t ha-1 for the Mediterranean forests. In temperate forests, the average canopy cover increased from 55 ± 4% to 59 ± 3%, mean height increased from 15.8 ± 0.77 m to 17.3 ± 0.21m, while the growing stock volume increased from 137.8 ± 8.2 to 151.5 ± 3.8 m3 ha-1. Our results suggest that multispectral data can be successfully linked with lidar to provide continuous information on forest height, cover, and biomass trends.

Epidemiology of Non-Tuberculous Mycobacteria isolated from clinical specimens in Madrid, Spain, from 2013 to 2017.

The epidemiology of non-tuberculous mycobacteria (NTM) in Spain is largely unknown because systematic reporting is not compulsory. The aim of our study was to describe the frequency and diversity of NTM species in our region and their distribution according to the source sample, gender, and age of the patients. We performed a multicenter study of all NTM isolated in 24 public hospitals in Madrid from 2013 to 2017. A total of 6.923 mycobacteria were isolated: 4535 (65.5%) NTM, and 2.388 (34.5%) Mycobacterium tuberculosis complex (MTB). Overall, 61 different NTM species were identified. The most frequently isolated species were Mycobacterium avium complex (47.7%), M. lentiflavum (12.2%), M. gordonae (9.2%), M. fortuitum (8.9%), and M. abscessus (3.9%). Whereas MTB cases were stable during the study period, the number of NTM isolates increased considerably from 930 isolates in 2013 to 1012 in 2017; a sharp increase occurred in the last year. The rise in NTM isolates was mostly due to M. lentiflavum, M. kansasii, and M. abscessus mainly isolated from respiratory specimens in patients older than 60. The increase in isolation rate of NTM in our region is consistent with the increasing rates reported worldwide in the last decades. The rise in NTM isolates was mainly attributed to M. lentiflavum but it also should be noted the increasing of species with high pathogenic potential such as M. kansasii and M. abscessus.

Craniofacial and dental findings in cystinosis.

OBJECTIVES: Cystinosis is a rare autosomal recessive lysosomal storage disorder with developmental and mineralization anomalies as part of its clinical presentation. The objective of this study was to provide the first systematic assessment of the craniofacial and dental characteristics associated with cystinosis. STUDY DESIGN: Oral and radiographic evaluations were performed on 73 patients with cystinosis. Analyses of cephalometry (n = 20), taurodontism (n = 47), caries (n = 47), enamel defects (n = 48), soft tissue anomalies (n = 48), and dental age (n = 41) were performed on the cystinosis group, and compared with age- and sex-comparable controls or standards. RESULTS: Cystinosis patients manifested relative mandibular deficiency, an increased facial height, and a reduced airway space. Taurodontism and enamel defects were significantly more prevalent in cystinosis patients compared with controls (P < 0.0001 and P = 0.027, respectively). Children (aged <15 years) with cystinosis also demonstrated a significant delay, of almost 9 months, of their dental development (P < 0.001). CONCLUSION: Novel craniofacial and dental features are associated with cystinosis. Craniofacial deficiencies may influence the swallowing and respiratory complications seen in cystinosis. Renal pathology and associated mineral imbalance may explain the dental root and enamel anomalies found in cystinosis patients; the developmental delays in cystinosis include delayed dental formation.

Apical and basolateral endosomes of MDCK cells are interconnected and contain a polarized sorting mechanism.

We have evaluated transcytotic routes in MDCK cells for their ability to generate a polarized surface distribution of trafficking proteins by following the intracellular sorting of transferrin receptors (TRs). We find that the selective basolateral expression of TRs is maintained in the face of extensive trafficking between the apical and basolateral surfaces. Biochemical studies of receptors loaded with tracer under conditions approaching steady state indicate that TRs internalized from the two surfaces are extensively colocalized within MDCK cells and that both populations of receptors are selectively delivered to the basolateral surface. Tailless TRs in which the cytoplasmic domain has been deleted display an unpolarized cell surface distribution and recycle in an unpolarized fashion. We show by EM that wild-type receptors internalized from each surface are colocalized within endosomal elements distributed throughout the cytoplasm. By preloading endosomal elements directly accessible from the basolateral surface with transferrin (Tf)-HRP, we show that apically internalized TRs rapidly enter the same compartment. We also show that both transcytosing (apically internalized) and recycling (basolaterally internalized) TRs are delivered to the basolateral border by a distinctive subset of exocytotic, 60-nm-diam vesicles. Together, the biochemical and morphological data show that apical and basolateral endosomes of MDCK cells are interconnected and contain a signal-dependent polarized sorting mechanism. We propose a dynamic model of polarized sorting in MDCK cells in which a single endosome-based, signal-dependent sorting step is sufficient to maintain the polarized phenotype.

In polarized MDCK cells basolateral vesicles arise from clathrin-gamma-adaptin-coated domains on endosomal tubules.

Human transferrin receptors (TR) and receptors for polymeric immunoglobulins (pIgR) expressed in polarized MDCK cells maintain steady-state, asymmetric distributions on the separate basolateral and apical surfaces even though they are trafficking continuously into and across these cells. The intracellular mechanisms required to maintain these asymmetric distributions have not been located. Here we show that TR and pIgR internalize from both surfaces to a common interconnected endosome compartment that includes tubules with buds coated with clathrin lattices. These buds generate vesicles that carry TR to the basolateral border. The lattices contain gamma-adaptin and are dispersed by treatment with brefeldin A (BFA). Since BFA treatment abrogates the vectorial trafficking of TR in polarized MDCK cells, we propose that the clathrin-coated domains of the endosome tubules contain the polarized sorting mechanism responsible for their preferential basolateral distribution.

Sorting mechanisms regulating membrane protein traffic in the apical transcytotic pathway of polarized MDCK cells.

The transcytotic pathway followed by the polymeric IgA receptor (pIgR) carrying its bound ligand (dIgA) from the basolateral to the apical surface of polarized MDCK cells has been mapped using morphological tracers. At 20 degreesC dIgA-pIgR internalize to interconnected groups of vacuoles and tubules that comprise the endosomal compartment and in which they codistribute with internalized transferrin receptors (TR) and epidermal growth factor receptors (EGFR). Upon transfer to 37 degreesC the endosome vacuoles develop long tubules that give rise to a distinctive population of 100-nm-diam cup-shaped vesicles containing pIgR. At the same time, the endosome gives rise to multivesicular endosomes (MVB) enriched in EGFR and to 60-nm-diam basolateral vesicles. The cup-shaped vesicles carry the dIgA/pIgR complexes to the apical surface where they exocytose. Using video microscopy and correlative electron microscopy to study cells grown thin and flat we show that endosome vacuoles tubulate in response to dIgA/pIgR but that the tubules contain TR as well as pIgR. However, we show that TR are removed from these dIgA-induced tubules via clathrin-coated buds and, as a result, the cup-shaped vesicles to which the tubules give rise become enriched in dIgA/pIgR. Taken together with the published information available on pIgR trafficking signals, our observations suggest that the steady-state concentrations of TR and unoccupied pIgR on the basolateral surface of polarized MDCK cells are maintained by a signal-dependent, clathrin-based sorting mechanism that operates along the length of the transcytotic pathway. We propose that the differential sorting of occupied receptors within the MDCK endosome is achieved by this clathrin-based mechanism continuously retrieving receptors like TR from the pathways that deliver pIgR to the apical surface and EGFR to the lysosome.

Hyper IgE (Job's) syndrome: a primary immune deficiency with oral manifestations.

Autosomal dominant hyper IgE (HIES or Job's) syndrome is a rare primary immune deficiency characterized by eczema, recurrent skin and lung infections, extremely elevated serum IgE, and a variety of connective tissue and skeletal abnormalities. Individuals with HIES share a characteristic facial appearance and many oral manifestations including retained primary dentition, a high arched palate, variations of the oral mucosa and gingiva, and recurrent oral candidiasis. Mutations in STAT3 account for the majority, if not all, of the cases of autosomal dominant HIES, but the pathogenesis of the many varied features remains poorly understood. In this review, we discuss the clinical phenotype of HIES including immunologic and non-immunologic features, the genetics of HIES, and treatment.

Hutchinson-Gilford progeria syndrome: oral and craniofacial phenotypes.

OBJECTIVE: Hutchinson-Gilford progeria syndrome (HGPS) is a rare early-onset accelerated senescence syndrome. In HGPS, a recently identified de novo dominant mutation of the lamin A gene (LMNA) produces abnormal lamin A, resulting in compromised nuclear membrane integrity. Clinical features include sclerotic skin, cardiovascular and bone abnormalities, and marked growth retardation. Craniofacial features include 'bird-like' facies, alopecia, craniofacial disproportion, and dental crowding. Our prospective study describes dental, oral soft tissue, and craniofacial bone features in HGPS. METHODS: Fifteen patients with confirmed p.G608G LMNA mutation (1-17 years, seven males, eight females) received comprehensive oral evaluations. Anomalies of oral soft tissue, gnathic bones, and dentition were identified. RESULTS: Radiographic findings included hypodontia (n = 7), dysmorphic teeth (n = 5), steep mandibular angles (n = 11), and thin basal bone (n = 11). Soft tissue findings included ogival palatal arch (n = 8), median sagittal palatal fissure (n = 7), and ankyloglossia (n = 7). Calculated dental ages (9 months to 11 years 2 months) were significantly lower than chronological ages (1 year 6 months to 17 years 8 months) (P = 0.002). Eleven children manifested a shorter mandibular body, anterior/posterior cranial base and ramus, but a larger gonial angle, compared to age/gender/race norms. CONCLUSION: Novel oral-craniofacial phenotypes and quantification of previously reported features are presented. Our findings expand the HGPS phenotype and provide additional insight into the complex pathogenesis of HGPS.

Enamel defects and salivary methylmalonate in methylmalonic acidemia.

INTRODUCTION AND OBJECTIVE: To characterize enamel defects in patients with methylmalonic acidemia (MMA) and cobalamin (cbl) metabolic disorders and to examine salivary methylmalonate levels in MMA. SUBJECTS AND METHODS: Teeth from patients (n = 32) were evaluated for enamel defects and compared with age- and gender-matched controls (n = 55). Complementation class (mut, cblA, cblB and cblC) and serum methylmalonate levels were examined. Primary teeth from two patients were examined by light and scanning electron microscopy and salivary methylmalonate levels from two patients were analyzed. RESULTS: Enamel defects were significantly more prevalent per tooth in the affected group than the control group, across complementation types (P < 0.0001). The mut MMA subgroup had a significantly higher prevalence per individual of severe enamel defects than controls (P = 0.021), and those with enamel defects exhibited higher serum methylmalonate levels than those without (P = 0.017). Salivary methylmalonate levels were extremely elevated and were significantly higher than controls (P = 0.002). Primary teeth were free of enamel defects except for two cblC patients who exhibited severe enamel hypoplasia. One primary tooth from a cblC patient manifested markedly altered crystal microstructure. CONCLUSION: Enamel anomalies represent a phenotypic manifestation of MMA and cbl metabolic disorders. These findings suggest an association between enamel developmental pathology and disordered metabolism.

Staphylococcus aureus meningitis in adults: A comparative cohort study of infections caused by meticillin-resistant and meticillin-susceptible strains.

BACKGROUND: Staphylococcus aureus meningitis is an uncommon nosocomial infection usually associated with neurosurgical procedures, but spontaneous infections may occasionally appear. AIMS: To compare the features of meningitis caused by meticillin-resistant (MRSA) and meticillin-susceptible (MSSA) S. aureus and examine the prognostic factors for mortality, including MRSA infection and combined antimicrobial therapy. METHODS: Retrospective cohort study of 350 adults with S. aureus meningitis admitted to 11 hospitals in Spain (1981-2015). Logistic regression and propensity score matching were used to analyse prognostic factors. RESULTS: There were 118 patients (34%) with MRSA and 232 (66%) with MSSA. Postoperative infection (91% vs 73%) and nosocomial acquisition (93% vs 74%) were significantly more frequent in MRSA than in MSSA meningitis (P < 0.001). Combined therapy was given to 118 (34%) patients. Overall 30-day mortality rate was 23%. On multivariate analysis, mortality was associated with severe sepsis or shock (odds ratio (OR) 9.9, 95% confidence interval (CI) 4.5-22.0, P < 0.001), spontaneous meningitis (OR 4.2, 95% CI 1.9-9.1, P < 0.001), McCabe-Jackson score rapidly or ultimately fatal (OR 2.8, 95% CI 1.4-5.4, P = 0.002), MRSA infection (OR 2.6, 95% CI 1.3-5.3, P = 0.006), and coma (OR 2.6, 95% CI 1.1-6.1, P < 0.029). In postoperative cases, mortality was related to retention of cerebrospinal devices (OR 7.9, 95% CI 3.1-20.3, P < 0.001). CONCLUSIONS: Clinical and epidemiological differences between MRSA and MSSA meningitis may be explained by the different pathogenesis of postoperative and spontaneous infection. In addition to the severity of meningitis and underlying diseases, MRSA infection was associated with increased mortality. Combined antimicrobial therapy was not associated with increased survival.

[Susceptibility of 36 Helicobacter pylori clinical isolates to four first-line antibiotics and virulence factors]. / Sensibilidad de 36 aislamientos de Helicobacter pylori a cuatro antibióticos de primera línea y características de virulencia.

Helicobacter pylori possess various virulence factors, including cagA and vacA genes, that are associated with more aggressive symptoms such as bleed-ing ulcer and gastric cancer. Although there are different treatment regimens, there is still a failure rate of up to 20% due to antibiotic resistance, among other causes. In our country resistance to metronidazole and clarithromycin is increasing, especially in children, although they are still susceptible to amoxicillin and tetracycline. In order to determine the susceptibility pattern to these antibiotics 36 H. pylori clinical isolates were studied. MIC was determined by agar diffusion and agar dilution, and vacA and cagA genes were detected by conventional PCR. All isolates were susceptible to amoxicillin and tetracycline. Resistance to metronidazole by diffusion or dilution tests was 35.7% and 36.1%, respectively, and to clarithromycin, 21.4% and 22.3%, respectively. There was one strain that showed intermediate resistance to clarithromycin (MIC 0.38 mg/l), using agar diffusion, and that was included among the resistant strains. Three discrepancies were observed between the diffusion and dilution methods. The vacA s1 allele was detected in 17.2% of the strains, and vacA s2 in 82.8%; 51.7% of the total were cagA+. In conclusion, all strains tested in our study were susceptible to amoxicillin and tetracycline, allowing them to be considered as first-line antibiotics, while clarithromycin and metronidazole maintain a slight increase in their resistance level. The cagA+ strains were detected in expected quantities, while the s1 allele of the vacA gene was detected in lower quantities.

A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles.

The mechanisms underlying neoplastic epithelial cell killing by ionizing radiation are largely unknown. We discovered a novel response to radiation manifested by autophagy and the development of acidic vesicular organelles (AVO). Acidification of AVO was mediated by the vacuolar H+-ATPase. Staining with the lysosomotropic agent acridine orange enabled us to quantify AVO accumulation and to demonstrate their time- and dose-dependent appearance. The appearance of AVO occurred in the presence of the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethyl ketone, but was inhibited by 3-methyladenine, an inhibitor of autophagy. The accretion of AVO in surviving progenies of irradiated cells, and the increased incidence of clonogenic death after inhibition of vacuolar H+-ATPase suggest that formation of acidic organelles represents a novel defense mechanism against radiation damage.

[Resistance of Mycobacterium tuberculosis in a four-year period in a Madrid hospital]. / Resistencia en Mycobacterium tuberculosis durante un periodo de cuatro años en un hospital de Madrid.

Tuberculosis is considered a serious public health problem. Some factors, such as HIV infection and immigration, have had a major impact on the epidemiology of this illness in Spain. The problem has worsened in recent years due to the dissemination of multiresistant strains. Therefore, a periodic surveillance should be established with respect to the incidence and the resistances observed. In this study we collect M. tuberculosis isolates carried out in the years 2001, 2002, 2003 and 2004, and their susceptibility characteristics in patients from Area 2 in Madrid. To evaluate the isolates' susceptibilities, the MGIT 960 system was used. Of a total of 244 isolates, 15.2% were resistant to at least one antibiotic (different to streptomycin), and 29.9% of the isolates were obtained in samples from immigrant patients. In addition, the immigrant population affected showed a greater percentage of resistances (p <0.01) and a younger mean age (p <0.01) than the indigenous population.

[In vitro activity of furazolidone and nitrofurantoin in Helicobacter pylori clinical isolates and study of mutation rate]. / Actividad in vitro de la furazolidona y la nitrofurantoína en aislamientos clínicos de Helicobacter pylori y estudio de la tasa de mutación.

Clarithromycin, amoxicillin, tetracycline and metronidazole are the most frequently used antimicrobials for Helicobacter pylori infection treatment. While tetracycline and amoxicillin resistance are rare, clarithromycin and metronidazole resistance vary in different populations and are considered factors for treatment failure. The aim of this study was to determine the in vitro activity of furazolidone and nitrofurantoin in 164 H. pylori clinical isolates by agar dilution and to determine the spontaneous mutation rate. Metronidazole and clarithromycin resistance were 23.77% (CI95%: 18.96-29.14) and 16.78% (CI95%: 12.64-21.62), respectively; moreover, 1.4% (CI95%: 0.38-3.54) were intermediate to clarithromycin. All the isolates were susceptible to amoxicillin and tetracycline. Furazolidone and nitrofurantoin resistance rates were 1.82% (CI95%: 0.37-5.25) and 0.6% (CI95%: 0-3.35), respectively. The three furazolidone-resistant strains were nitrofurantoine-susceptible (MIC 4 mg/l for furazolidone and 2 mg/l for nitrofurantoin) and the nitrofurantoin-resistant strains were furazolidone-susceptible (MIC 4 mg/l for nitrofurantoin and 1 mg/l for furazolidone). These four strains were metronidazole-resistant (MIC 16 mg/l). Furazolidone or nitrofurantoin spontaneous mutants were not detected in the eight H. pylori strains tested. However, mutants with resistance to metronidazole were found with all the strains with a mutation rate of 7.4 x 10(-10) to 9.4 x 10(-10). Furazolidone and nitrofurantoin showed an excellent in vitro activity against the H. pylori clinical isolates included herein, supporting the usefulness of furazolidone as second-line antimicrobial after treatment failure or as first-line therapy in populations with low economical resources.

[Nontuberculous mycobacteria in patients with cystic fibrosis]. / Micobacterias ambientales en pacientes adultos con fibrosis quística.

OBJECTIVE: Patients with cystic fibrosis are at great risk of infection by nontuberculous mycobacteria from the environment because of certain predisposing factors such as bronchiectasis, malnutrition, and diabetes. The aim of this study was to analyze the mycobacterial content of sputum smears and cultures from adult patients with cystic fibrosis attended at a specialized unit for adults from March 1997 through December 2001. PATIENTS AND METHODS: Sputum samples were collected prospectively according to a protocol applied at each visit, and during most exacerbations staining and culture for mycobacteria were ordered in addition to the usual cultures for bacteria and fungi. A tuberculin test was performed at the end of the study. RESULTS: Twenty-eight patients (16 men) with cystic fibrosis were enrolled. The mean (SD) age was 25.3 (6.7) years. A total of 251 samples were cultured (range in number of samples per patient, 1-31). The mean period of follow up was 40.3 (22.1) months. The sputum smear was positive in 29 cases (4 patients); the culture was positive in 7 patients. More than 3 samples were positive in only 4 patients. Mycobacterium abscessus was isolated in 3 cases, Mycobacterium avium complex in 2 and Mycobacterium simiae in 1 and other an unidentified rapid growth Mycobacterium species. The Mantoux test was positive in 5 patients. Two of the 4 patients in whose samples mycobacteria were isolated repeatedly required treatment. CONCLUSIONS: The prevalence of nontuberculous mycobacterial infection is high in patients with cystic fibrosis. Staining and culture for mycobacteria should be carried out regularly and whenever exacerbation of pulmonary symptoms cannot be attributed to bacteria usually found in such patients. Patients with recurrent isolations of mycobacteria should be monitored closely.

A withdrawal syndrome after abrupt discontinuation of alprazolam.

A patient who received therapeutic doses of alprazolam for 8 weeks experienced a withdrawal syndrome beginning 18 hours after its abrupt discontinuation. Short-acting and minimally sedating benzodiazepines may have increased potential for withdrawal reactions.

Role of NF-kappaB in the control of apoptotic and proliferative responses in IL-2-responsive T cells.

The NF-kappaB/Rel/IkappaB family of transcription factors regulates a number of genes involved in a wide variety of biological processes. The activation of p53, c-myc and Ras genes suggests a role for NF-kappaB in cell proliferation; NF-kappaB is also important in immune and inflammatory responses. By virtue of its role in apoptosis, NF-kappaB participates in the thymus as well as in embryonic development. The NF-kappaB family of transcription factors is also involved in viral transcription, transformation and in the development of some types of human cancers. Given the pivotal role of NF-kappaB, clarification is needed of the mechanisms through which its deregulation contributes to disease. Several aspects of NF-kappaB regulation, such as phosphatase involvement, the mechanism of IkappaB ubiquitination and the regulation of nuclear translocation, remain obscure. Here, we review and discuss the function of NF-kappaB activation in IL-2-stimulation and in apoptosis induced by IL-2 deprivation in T cells.

Pharmacologic treatment of phobic disorders.

Pharmacologic treatment of phobic disorders, in particular agoraphobia, has been proved to be effective, especially when used in combination with behavior therapy. Favorable responses to tricyclic antidepressants, monoamine oxidase inhibitors, and benzodiazepines have been reported. The limitations of drug therapy for phobias include high dropout rates and the tendency to relapse after discontinuation of therapy. Successful treatment depends on the careful selection of patients and medications and on coordination of drug and behavior therapies.

Apoptosis as a scaffold for building up the B cell repertoire.

Control of cell number is determined by a balance between cell proliferation and cell death, both of which are highly regulated processes, with numerous checks and balances. Cells control their own death through activation of an internally coded suicide program that, when activated, initiates a characteristic form of cell death called apoptosis. This type of regulation allows elimination of cells that have been produced in excess, that have developed improperly, or that have sustained genetic damage. Apoptosis is, therefore, the most common physiological form of cell death and occurs during embryonic development, tissue remodeling, immune regulation, cell activation and tumor regression.