Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.

Background: This guideline addresses the diagnosis of hypersensitivity pneumonitis (HP). It represents a collaborative effort among the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.Methods: Systematic reviews were performed for six questions. The evidence was discussed, and then recommendations were formulated by a multidisciplinary committee of experts in the field of interstitial lung disease and HP using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.Results: The guideline committee defined HP, and clinical, radiographic, and pathological features were described. HP was classified into nonfibrotic and fibrotic phenotypes. There was limited evidence that was directly applicable to all questions. The need for a thorough history and a validated questionnaire to identify potential exposures was agreed on. Serum IgG testing against potential antigens associated with HP was suggested to identify potential exposures. For patients with nonfibrotic HP, a recommendation was made in favor of obtaining bronchoalveolar lavage (BAL) fluid for lymphocyte cellular analysis, and suggestions for transbronchial lung biopsy and surgical lung biopsy were also made. For patients with fibrotic HP, suggestions were made in favor of obtaining BAL for lymphocyte cellular analysis, transbronchial lung cryobiopsy, and surgical lung biopsy. Diagnostic criteria were established, and a diagnostic algorithm was created by expert consensus. Knowledge gaps were identified as future research directions.Conclusions: The guideline committee developed a systematic approach to the diagnosis of HP. The approach should be reevaluated as new evidence accumulates.

One-session bilateral sequential whole lung lavage (OSBSWLL) for the management of pulmonary alveolar proteinosis.

BACKGROUND: Whole Lung Lavage (WLL) has been an important part in the management of Pulmonary Alveolar Proteinosis (PAP) since it improves radiologic and clinical parameters. Bilateral WLL is usually performed in two sessions on different days. Few case reports have described one-session bilateral sequential lung lavage (OSBSWLL), and none have described ambulatory management (same-day discharge). METHODS: Demographic characteristics, physiologic parameters, procedure details and outcomes were retrospectively collected on consecutive patients who underwent OSBSWLL for PAP following an ambulatory protocol stablished in our institution. RESULTS: A total of 13 patients underwent 30 OSBSWLL (61.5% male; mean age 40). The mean SpO2 was 90% (IQR 9) and 94% (IQR 6), before and after OSBSWLL respectively. In 63.3% of cases, patients were discharged home the same day of procedure. Only in two cases (6.6%), patients required post-procedure prolonged mechanical ventilation (> 4 h) due to persistent hypoxia. CONCLUSIONS: OSBSWLL can be performed with same-day discharge.

Shape-sensing robotic-assisted bronchoscopy for pulmonary nodules: initial multicenter experience using the Ion™ Endoluminal System.

BACKGROUND: Traditional bronchoscopy provides limited approach to peripheral nodules. Shape-sensing robotic-assisted bronchoscopy (SSRAB, Ion™ Endoluminal System) is a new tool for minimally invasive peripheral nodule biopsy. We sought to answer the research question: Does SSRAB facilitate sampling of pulmonary nodules during bronchoscopists' initial experience? METHODS: The lead-in stage of a multicenter, single-arm, prospective evaluation of the Ion Endoluminal System (PRECIsE) is described. Enrolled subjects ≥ 18 years old had recent computed tomography evidence of one or more solid or semi-solid pulmonary nodules ≥ 1.0 to ≤ 3.5 cm in greatest dimension and in any part of the lung. Subjects were followed at 10- and 30-days post-procedure. This stage provided investigators and staff their first human experience with the SSRAB system; safety and procedure outcomes were analyzed descriptively. Neither diagnostic yield nor sensitivity for malignancy were assessed in this stage. Categorical variables are summarized by percentage; continuous variables are summarized by median/interquartile range (IQR). RESULTS: Sixty subjects were enrolled across 6 hospitals; 67 nodules were targeted for biopsy. Median axial, coronal and sagittal diameters were < 18 mm with a largest cardinal diameter of 20.0 mm. Most nodules were extraluminal and distance from the outer edge of the nodule to the pleura or nearest fissure was 4.0 mm (IQR: 0.0, 15.0). Median bronchial generation count to the target location was 7.0 (IQR: 6.0, 8.0). Procedure duration (catheter-in to catheter-out) was 66.5 min (IQR: 50.0, 85.5). Distance from the catheter tip to the closest edge of the virtual nodule was 7.0 mm (IQR: 2.0, 12.0). Biopsy completion was 97.0%. No pneumothorax or airway bleeding of any grade was reported. CONCLUSIONS: Bronchoscopists leveraged the Ion SSRAB's functionality to drive the catheter safely in close proximity of the virtual target and to obtain biopsies. This initial, multicenter experience is encouraging, suggesting that SSRAB may play a role in the management of pulmonary nodules. Clinical Trial Registration identifier and date NCT03893539; 28/03/2019.

Enfermeros mexicanos en Alemania en tiempos de Covid-19.

Señor editor: La emigración de enfermeros mexicanos hacia el extranjero es un tema que cobra relevancia durante la pandemia por Covid-19, principalmente por la necesidad de contar con profesionales calificados que hagan frente a esta situación de emergencia sanitaria. Pero ¿por qué los enfermeros están emigrando cuando México también tiene escasez de estos profesionales?..

Selective Formation of S4- and T-Symmetric Supramolecular Tetrahedral Cages and Helicates in Polar Media Assembled via Cooperative Action of Coordination and Hydrogen Bonds.

We report on the synthesis and self-assembly study of novel supramolecular monomers encompassing quadruple hydrogen-bonding motifs and metal-coordinating 2,2'-bipyridine units. When mixed with metal ions such as Fe2+ or Zn2+, the tetrahedron cage complexes are formed in quantitative yields and full diastereoselectivity, even in highly polar acetonitrile or methanol solvents. The symmetry of the complexes obtained has been shown to depend critically on the flexibility of the ligand. Restriction of the rotation of the hydrogen-bonding unit with respect to the metal-coordinating site results in a T-symmetric cage, whereas introducing flexibility either through a methylene linker or rotating benzene ring allows the formation of S4-symmetric cages with self-filled interior. In addition, the possibility to select between tetrahedral cages or helicates and to control the dimensions of the aggregate has been demonstrated with a three-component assembly using external hydrogen-bonding molecular inserts or by varying the radius of the metal ion (Hg2+ vs Fe2+). Self-sorting studies of individual Fe2+ complexes with ligands of different sizes revealed their inertness toward ligand scrambling.

Malva parviflora extract ameliorates the deleterious effects of a high fat diet on the cognitive deficit in a mouse model of Alzheimer's disease by restoring microglial function via a PPAR-γ-dependent mechanism.

BACKGROUND: Alzheimer's disease (AD) is a neuropathology strongly associated with the activation of inflammatory pathways. Accordingly, inflammation resulting from obesity exacerbates learning and memory deficits in humans and in animal models of AD. Consequently, the long-term use of non-steroidal anti-inflammatory agents diminishes the risk for developing AD, but the side effects produced by these drugs limit their prophylactic use. Thus, plants natural products have become an excellent option for modern therapeutics. Malva parviflora is a plant well known for its anti-inflammatory properties. METHODS: The present study was aimed to determine the anti-inflammatory potential of M. parviflora leaf hydroalcoholic extract (MpHE) on AD pathology in lean and obese transgenic 5XFAD mice, a model of familial AD. The inflammatory response and Amyloid ß (Aß) plaque load in lean and obese 5XFAD mice untreated or treated with MpHE was evaluated by immunolocalization (Iba-1 and GFAP) and RT-qPCR (TNF) assays and thioflavin-S staining, respectively. Spatial learning memory was assessed by the Morris Water Maze behavioral test. Microglia phagocytosis capacity was analyzed in vivo and by ex vivo and in vitro assays, and its activation by morphological changes (phalloidin staining) and expression of CD86, Mgl1, and TREM-2 by RT-qPCR. The mechanism triggered by the MpHE was characterized in microglia primary cultures and ex vivo assays by immunoblot (PPAR-γ) and RT-qPCR (CD36) and in vivo by flow cytometry, using GW9662 (PPAR-γ inhibitor) and pioglitazone (PPAR-γ agonist). The presence of bioactive compounds in the MpHE was determined by HPLC. RESULTS: MpHE efficiently reduced astrogliosis, the presence of insoluble Aß peptides in the hippocampus and spatial learning impairments, of both, lean, and obese 5XFAD mice. This was accompanied by microglial cells accumulation around Aß plaques in the cortex and the hippocampus and decreased expression of M1 inflammatory markers. Consistent with the fact that the MpHE rescued microglia phagocytic capacity via a PPAR-γ/CD36-dependent mechanism, the MpHE possess oleanolic acid and scopoletin as active phytochemicals. CONCLUSIONS: M. parviflora suppresses neuroinflammation by inhibiting microglia pro-inflammatory M1 phenotype and promoting microglia phagocytosis. Therefore, M. parviflora phytochemicals represent an alternative to prevent cognitive impairment associated with a metabolic disorder as well as an effective prophylactic candidate for AD progression.

Tracheal tumors.

PURPOSE OF REVIEW: This article provides the most recent literature and experienced guidance about diagnosis and management of tracheal tumors, including future directions. RECENT FINDINGS: Tracheal tumors are challenging to diagnose given their nonspecific and late-onset symptoms. Critical airway obstruction is the most feared complication. The cornerstone in management of them is surgical resection whenever is possible. Different diagnostic tests (i.e., imaging and bronchoscopy) help in the assessment of resectability. Alternative management including interventional bronchoscopic techniques can be offered to patients who are not suitable for surgical resection. Radiation and chemotherapy can also be used as adjuvant, neoadjuvant or sole treatment in malignant tumors. Recent advances in tracheal transplantation and bioengineering with tracheal reconstruction have shown a new direction in the management of these tumors. All these topics will be discussed in this article. SUMMARY: Despite advances in diagnostic and therapeutic techniques, tracheal tumors are still a medical challenge. Although studies are still trying to find the best surgical techniques as well as the role for chemotherapy and radiation, most recent studies are addressing tracheal reconstruction and transplantation as the new horizon for management.

Risk factors for pleural effusion recurrence in patients with malignancy.

BACKGROUND AND OBJECTIVE: The main purpose of treatment in patients with malignant pleural effusion (MPE) is symptom palliation. Currently, patients undergo repeat thoracenteses prior to receiving a definitive procedure as clinicians are not aware of the risk factors associated with fluid recurrence. The primary objective of this study was to identify risk factors associated with recurrent symptomatic MPE. METHODS: Retrospective multicentre cohort study of patients who underwent first thoracentesis was performed. The primary outcome was time to fluid recurrence requiring intervention in patients with evidence of metastatic disease. We used a cause-specific hazard model to identify risk factors associated with fluid recurrence. We also developed a predictive model, utilizing Fine-Gray subdistribution hazard model, and externally validated the model. RESULTS: A total of 988 patients with diagnosed metastatic disease were included. Cumulative incidence of recurrence was high with 30% of patients recurring by day 15. On multivariate analysis, size of the effusion on chest X-ray (up to the top of the cardiac silhouette (hazard ratio (HR): 1.84, 95% CI: 1.21-2.80, P = 0.004) and above the cardiac silhouette (HR: 2.22, 95% CI: 1.43-3.46, P = 0.0004)), larger amount of pleural fluid drained (HR: 1.06, 95% CI: 1.04-1.07, P < 0.0001) and higher pleural fluid LDH (HR: 1.008, 95% CI: 1.004-1.011, P < 0.0001) were associated with increased hazard of recurrence. Negative cytology (HR: 0.52, 95% CI: 0.43-0.64, P < 0.0001) was associated with decreased hazard of recurrence. The model had low prediction accuracy. CONCLUSION: Pleural effusion size, amount of pleural fluid drained, LDH and pleural fluid cytology were found to be risk factors for recurrence.

Seasonal and dietary effects on Vitamin D deficiencies detected in wild boar from mid-western Spain.

Vitamin D (VitD) is involved in important mammalian physiological mechanisms, such as Ca-P metabolism, bone development and immunological response. VitD deficiencies are frequently detected in domestic animals and related to various health problems (e.g., rickets, bone deformation). However, knowledge about the status of VitD in wildlife species, such as the wild boar, is scarce. The aims of this work were to explore VitD status in wild boar populations from mid-western Spain and to elucidate the influence of daylight exposure and food supplementation in levels of VitD. Serum concentration of VitD (measured as 25-hydroxivitaminD) was assessed in 276 wild boar from 27 game estates located in mid-western Spain using a commercial ELISA kit. In 19 out of 27 estates, the staff supplied a specific VitD-enriched food (2,000 UI/Kg) ad libitum throughout the year, while in the remaining estates (8), no food was supplied. Blood samples were extracted from hunted animals (198) between October and February of hunting seasons 2016/2017 and 2017/2018, and from live wild boar (78) that were captured, sampled and released (March-September of 2017). The percentage of animals with VitD deficiency (<20 ng/ml), VitD insufficiency (20-30 ng/ml) and VitD sufficiency (>30 ng/ml) was estimated, and the relationship of these levels to factors like sex, age and season was assessed using chi-square tests. Furthermore, associations between daylight exposure and supplemental food with VitD levels were explored using linear models. Of the studied wild boar population, 82.2% showed a VitD deficiency or insufficiency. VitD deficiencies were more frequent in animals sampled in winter and spring. Furthermore, levels of VitD positively correlated with daylight exposure and supplemental food intake. Ad libitum supplementation with VitD-enriched food was insufficient to prevent VitD deficiencies in wild boar from November to April, probably because food consumption is lower during this period.

Autophagy impairment by caspase-1-dependent inflammation mediates memory loss in response to ß-Amyloid peptide accumulation.

ß-Amyloid peptide accumulation in the cortex and in the hippocampus results in neurodegeneration and memory loss. Recently, it became evident that the inflammatory response triggered by ß-Amyloid peptides promotes neuronal cell death and degeneration. In addition to inflammation, ß-Amyloid peptides also induce alterations in neuronal autophagy, eventually leading to neuronal cell death. Thus, here we evaluated whether the inflammatory response induced by the ß-Amyloid peptides impairs memory via disrupting the autophagic flux. We show that male mice overexpressing ß-Amyloid peptides (5XFAD) but lacking caspase-1, presented reduced ß-Amyloid plaques in the cortex and in the hippocampus; restored brain autophagic flux and improved learning and memory capacity. At the molecular level, inhibition of the inflammatory response in the 5XFAD mice restored LC3-II levels and prevented the accumulation of oligomeric p62 and ubiquitylated proteins. Furthermore, caspase-1 deficiency reinstates activation of the AMPK/Raptor pathway while down-regulating AKT/mTOR pathway. Consistent with this, we found an inverse correlation between the increase of autophagolysosomes in the cortex of 5XFAD mice lacking caspase-1 and the presence of mitochondria with altered morphology. Together our results indicate that ß-Amyloid peptide-induced caspase-1 activation, disrupts autophagy in the cortex and in the hippocampus resulting in neurodegeneration and memory loss.

Rigid Bronchoscopy.

Rigid bronchoscopy is one of the oldest medical techniques used in the respiratory and thoracic fields. Even though its use declined after the development of flexible bronchoscopy, it has again gained importance with the growth of interventional pulmonology, becoming a critical technique taught as part of the training in this subspecialty. The therapeutic advantages compared to other approaches of thoracic pathologies makes rigid bronchoscopy a primary component in the present and future of interventional pulmonary medicine.

A Prediction Model to Help with the Assessment of Adenopathy in Lung Cancer: HAL.

RATIONALE: Estimating the probability of finding N2 or N3 (prN2/3) malignant nodal disease on endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with non-small cell lung cancer (NSCLC) can facilitate the selection of subsequent management strategies. OBJECTIVES: To develop a clinical prediction model for estimating the prN2/3. METHODS: We used the AQuIRE (American College of Chest Physicians Quality Improvement Registry, Evaluation, and Education) registry to identify patients with NSCLC with clinical radiographic stage T1-3, N0-3, M0 disease that had EBUS-TBNA for staging. The dependent variable was the presence of N2 or N3 disease (vs. N0 or N1) as assessed by EBUS-TBNA. Univariate followed by multivariable logistic regression analysis was used to develop a parsimonious clinical prediction model to estimate prN2/3. External validation was performed using data from three other hospitals. MEASUREMENTS AND MAIN RESULTS: The model derivation cohort (n = 633) had a 25% prevalence of malignant N2 or N3 disease. Younger age, central location, adenocarcinoma histology, and higher positron emission tomography-computed tomography N stage were associated with a higher prN2/3. Area under the receiver operating characteristic curve was 0.85 (95% confidence interval, 0.82-0.89), model fit was acceptable (Hosmer-Lemeshow, P = 0.62; Brier score, 0.125). We externally validated the model in 722 patients. Area under the receiver operating characteristic curve was 0.88 (95% confidence interval, 0.85-0.90). Calibration using the general calibration model method resulted in acceptable goodness of fit (Hosmer-Lemeshow test, P = 0.54; Brier score, 0.132). CONCLUSIONS: Our prediction rule can be used to estimate prN2/3 in patients with NSCLC. The model has the potential to facilitate clinical decision making in the staging of NSCLC.

Diagnostic Yield and Complications of Bronchoscopy for Peripheral Lung Lesions. Results of the AQuIRE Registry.

RATIONALE: Advanced bronchoscopy techniques such as electromagnetic navigation (EMN) have been studied in clinical trials, but there are no randomized studies comparing EMN with standard bronchoscopy. OBJECTIVES: To measure and identify the determinants of diagnostic yield for bronchoscopy in patients with peripheral lung lesions. Secondary outcomes included diagnostic yield of different sampling techniques, complications, and practice pattern variations. METHODS: We used the AQuIRE (ACCP Quality Improvement Registry, Evaluation, and Education) registry to conduct a multicenter study of consecutive patients who underwent transbronchial biopsy (TBBx) for evaluation of peripheral lesions. MEASUREMENTS AND MAIN RESULTS: Fifteen centers with 22 physicians enrolled 581 patients. Of the 581 patients, 312 (53.7%) had a diagnostic bronchoscopy. Unadjusted for other factors, the diagnostic yield was 63.7% when no radial endobronchial ultrasound (r-EBUS) and no EMN were used, 57.0% with r-EBUS alone, 38.5% with EMN alone, and 47.1% with EMN combined with r-EBUS. In multivariate analysis, peripheral transbronchial needle aspiration (TBNA), larger lesion size, nonupper lobe location, and tobacco use were associated with increased diagnostic yield, whereas EMN was associated with lower diagnostic yield. Peripheral TBNA was used in 16.4% of cases. TBNA was diagnostic, whereas TBBx was nondiagnostic in 9.5% of cases in which both were performed. Complications occurred in 13 (2.2%) patients, and pneumothorax occurred in 10 (1.7%) patients. There were significant differences between centers and physicians in terms of case selection, sampling methods, and anesthesia. Medical center diagnostic yields ranged from 33 to 73% (P = 0.16). CONCLUSIONS: Peripheral TBNA improved diagnostic yield for peripheral lesions but was underused. The diagnostic yields of EMN and r-EBUS were lower than expected, even after adjustment.

Can We Improve the Outcomes of Multivessel Disease Using Modified SYNTAX and Residual SYNTAX Scores?

PURPOSE OF REVIEW: In spite of the benefits of drug eluting (DES), these advantages were not translated to better outcome when percutaneous coronary interventions (PCI) were compared with coronary artery bypass surgery. PCI strategy allowing stent deployment in all intermediate lesions including small vessels together with DES design may be the reasons of these findings. RECENT FINDINGS: Recently randomized and observational studies demonstrated using functional flow reserve analysis, residual Syntax score risk, or residual ERACI score after PCI that a reasonably incomplete revascularization was associated with good long-term outcome and low events rate at follow-up. In the ERACI IV study, which included patients with multiple vessel disease and left main, all intermediate lesions and severe lesions in small vessels were excluded from the revascularization strategy, and the 3-year follow-up results showed a remarkable low incidence of death/MI and stroke. Intermediate stenosis or severe lesions in small vessels should not be incorporated in the PCI strategy in order to define patient clinical cardiac prognosis or completeness of revascularization.

Double gastroepiploic vascularized lymph node tranfers to middle and distal limb for the treatment of lymphedema.

BACKGROUND: Vascularized lymph node (VLN) transfer for lymphedema treatment has shown promising results. Optimal donor and recipient sites remain a matter of debate. We describe the technique and outcomes of a laparoscopically harvested extended gastroepiploic VLN flap with two levels of inset. PATIENTS AND METHODS: Between 2014 and 2015, four-patients with upper limb breast cancer-related lymphedema and three-patients with lower limb pelvic cancer-related lymphedema who underwent VLN transfers were included. After harvest, the gastroepiploic VLN flap was divided into two halves that were separately inset at the level of elbow and wrist (upper limb) or knee and ankle (lower limb). The mean patient age was 53.1 years (range, 42-65 years). RESULTS: The average flap size after division was 6.3 cm in length (range, 5-7 cm) and 3.4 cm in width (range, 3-4 cm). The mean pedicle length was 3.2 cm (range, 2.5-4 cm). All flaps survived completely. No donor or recepient site complication was noted. At a mean follow-up of 9.7 months (range, 8-11 months), the mean circumference reduction rate was 43.7 ± 2.5% along the entire limb (P < 0.05). No episode of infection was noted postoperatively. CONCLUSIONS: Double gastroepiploic VLN transfers to middle and distal limb are a safe approach with very promising results. This technique may be used to improve clinical outcomes by enhancing the lymphatic drainage of the entire affected limb in a uniform fashion. In addition, the laparoscopic harvest can provide decreased donor site morbidity with a faster recovery.

Molecular Basis for the Recognition of Higher Fullerenes into Ureidopyrimidinone-Cyclotriveratrylene Self-Assembled Capsules.

Fullerenes C60 , C70 , and C84 may be readily encaged within a hydrogen-bonded dimeric capsule, based on two concave cyclotriveratrylene (CTV) scaffolds, each containing three self-complementary 2-ureido-4-[1H]-pyrimidinone (UPy) subunits. NMR spectroscopy and circular dichroism studies, complemented by dispersion-corrected DFT calculations, are reported with the aim of characterizing such capsule-fullerene complexes both structurally and energetically. Six fullerenes are considered: in agreement with experiments, calculations find that encapsulation is most favorable for C84 (on a par with C90 ), and follows the trend C60

Spoligotype diversity and 5-year trends of bovine tuberculosis in Extremadura, southern Spain.

Bovine tuberculosis (bTB) causes significant losses to farming economies worldwide. A better understanding on the epidemiology of this disease and the role that the different hosts develop in the maintenance and spread of bTB is vital to control this zoonotic disease. This study reports the spoligotype diversity and temporal evolution of Mycobacterium tuberculosis Complex (MTBC) isolates obtained from Extremadura (southern Spain). Genotyping data of Mycobacterium bovis (n = 2102) and Mycobacterium caprae (n = 96) isolates from cattle and wildlife species, collected between 2008 and 2012, were used in this study. The isolates resulted clustered into 88 spoligotypes which varied largely in frequency and occurrence in the three hosts. The 20 most frequent patterns represented 91.99 % of the isolates, the spoligotype SB0121 being the clearly predominant and most widely dispersed geographically. The major variety of the spoligotype patterns (78 out of 88) was isolated from the cattle, in fact 50 (56.83 %) of the patterns were found only in this species. Within the spoligotypes shared between the cattle and wildlife species, 17 patterns (1747 isolates) were shared with wild boar and Iberian red deer, 10 patterns (308 isolates) were exclusively shared with wild boar, and only one pattern (two isolates) was shared exclusively with Iberian red deer. The significant number of spoligotypes shared between the three hosts (79.49 %) highlights the components of the multi-host system that allows the bTB maintenance in our study area. The greater percentage of isolates shared by the wild boar and cattle (93.50 %) supports the role of wild boar as main maintenance host for bTB in cattle. These results could be extrapolated to areas with a similar epidemiological scenario and could be helpful for other countries where wild reservoirs represent a handicap for the successful eradication of bTB from livestock.

Cellular Antisense Activity of PNA-Oligo(bicycloguanidinium) Conjugates Forming Self-Assembled Nanoaggregates.

A series of peptide nucleic acid-oligo(bicycloguanidinium) (PNA-BGn ) conjugates were synthesized and characterized in terms of cellular antisense activity by using the pLuc750HeLa cell splice correction assay. PNA-BG4 conjugates exhibited low micromolar antisense activity, and their cellular activity required the presence of a hydrophobic silyl terminal protecting group on the oligo(BG) ligand and a minimum of four guanidinium units. Surprisingly, a nonlinear dose-response with an activity threshold around 3-4 µM, indicative of large cooperativity, was observed. Supported by light scattering and electron microscopy analyses, we propose that the activity, and thus cellular delivery, of these lipo-PNA-BG4 conjugates is dependent on self-assembled nanoaggregates. Finally, cellular activity was enhanced by the presence of serum. Therefore we conclude that the lipo-BG-PNA conjugates exhibit an unexpected mechanism for cell delivery and are of interest for further in vivo studies.

FATAL CASE OF STREPTOCOCCUS SUIS INFECTION IN A YOUNG WILD BOAR (SUS SCROFA) FROM SOUTHWESTERN SPAIN.

Streptococcus suis is a recognized pathogen that may cause important diseases in pigs and humans. This microorganism has been repeatedly isolated from wild boar (Sus scrofa). However, its health implications for this wild species are still unknown. This article reports a detailed description of a fatal case of septicemia by S. suis affecting a young wild boar. The affected animal, about 15 days old, was found near death and exhibiting neurologic signs at a wild boar estate in southwestern Spain. Postmortem examination showed generalized congestion, brain hemorrhages and lobular pneumonia. Histopathological evaluation demonstrated the presence of meningitis and encephalitis with marked congestion and suppurative bronchopneumonia. Streptococcus suis serotype 2 isolates exhibiting important virulence factors (extracellular factor, muramidase-released protein, and suylisin) were isolated from the affected animal. This study confirms the presence of potentially virulent and zoonotic strains of S. suis in wild boar from Spain.

Enhancing molecular recognition in electron donor-acceptor hybrids via cooperativity.

Herein, we report the synthesis of guanidinium bis-porphyrin tweezers 1 and fullerene carboxylate 3, their assembly into a novel supramolecular 1@3 electron donor-acceptor hybrid, and its characterization. In solution, the binding constant affording 1@3 is exceptionally high. 1@3, which features a highly confined topography, builds up from a combination of guanidinium-carboxylate hydrogen bonding and π-π stacking/charge-transfer motifs. The latter is governed by interactions between the electron-donating porphyrin and the electron-accepting fullerene. Importantly, positive cooperativity between the applied binding motifs is corroborated by a number of experimental techniques, such as NMR, absorption, fluorescence, etc. In addition, transient absorption experiments shed light onto electron-transfer processes taking place in the ground state and upon photoexcitation. In fact, porphyrin excitation powers an electron transfer to the fullerene yielding charge separated state lifetimes in the nanosecond regime.