Usefulness of the N-Terminal Fraction of Brain Natriuretic Peptide for Deciding When to Refer Patients With Sleep Apnea-Hypopnea Syndrome to the Cardiologist

Introduction and objectiveWhen sleep apnea-hypopnea syndrome (SAHS) and cardiovascular disease occur concurrently, prognosis is affected. Echocardiography can detect structural cardiac abnormalities but using this technique in all patients would place a heavy burden on resources. The objective of this study was to investigate whether the N-terminal fraction of brain natriuretic peptide (NT-proBNP) can be used as a marker for silent heart disease.Patients and methodsNT-proBNP concentration was measured in the 114 consecutive patients with SAHS who underwent echocardiography before starting treatment. Left and right ventricular systolic and diastolic function, as well as structural abnormalities, were studied. Correlations between NT-proBNP concentration and the abnormalities detected were investigated. A receiver operating characteristics (ROC) curve was plotted for NT-proBNP concentration and cardiac abnormalities.ResultsData for 98 patients were finally analyzed. NT-proBNP concentration was significantly correlated with ventricular septal thickness (r=0.63), posterior wall thickness (r=0.45), and left ventricular enddiastolic diameter (r=0.51) (P<.0001 for all correlations). The area under the ROC curve was significant (0.870; 95% confidence interval, 0.801-0.939; P<.0001). Assuming that specificity would be more useful for clinical practice, we calculated that NT-proBNP concentrations below 100 and 200 pg/mL could rule out structural abnormalities with a reliability of 90% and 100%, respectively.ConclusionsNT-proBNP concentration was strongly correlated with echocardiographic abnormalities and so could be a useful tool for identifying patients who should be referred to the cardiologist.     

Multidimensional approach to the differences between muscular and articular temporomandibular patients: coping, distress, and pain characteristics.

OBJECTIVE: This study analyzes the differences in psychological variables and symptomatology between temporomandibular disorder diagnosis subgroups. STUDY DESIGN: The sample included 114 temporomandibular disorder patients that were evaluated in coping, distress, and temporomandibular characteristics. Diagnostic muscular (n = 58) and articular (n = 56) subgroups were compared in these variables through a MANCOVA. RESULTS: Muscular patients show a higher level of general distress, specifically in the anxiety and somatization subscales and a more active coping style, with a tendency of a minor use of humor and a higher number of parafunctional habits, specifically, biting nails, hangnails, and lips. CONCLUSION: We discuss the differences found in order to design the targets of the psychological intervention of temporomandibular patients.     

Mature eosinophils stimulated to develop in human-cord blood mononuclear cell cultures supplemented with recombinant human interleukin-5. II. Vesicular transport of specific granule matrix peroxidase, a mechanism for effecting piecemeal degranulation.

The mechanism of piecemeal degranulation by human eosinophils was investigated. Mature eosinophils that developed in rhIL-5-containing conditioned media from cultured human cord blood mononuclear cells were prepared for ultrastructural studies using a combined technique to image eosinophil peroxidase by cytochemistry in the same sections on which postembedding immunogold was used to demonstrate Charcot-Leyden crystal protein. Vesicular transport of eosinophil peroxidase from the specific granule matrix compartment to the cell surface was associated with piecemeal degranulation. This process involved budding of eosinophil peroxidase-loaded vesicles and tubules from specific granules. Some eosinophil peroxidase that was released from eosinophils remained bound to the cell surface; some was free among the cultured cells. Macrophages and basophils bound the released eosinophil peroxidase to their plasma membranes, internalized it in endocytotic vesicles, and stored it in their respective phagolysosomes and secretory granules. Charcot-Leyden crystal protein was diffusely present in the nucleus and cytoplasm of IL-5-stimulated mature eosinophils. Extensive amounts were generally present in granule-poor and subplasma membrane areas of the cytoplasm in contrast to eosinophil peroxidase, which was secreted and bound to the external surface of eosinophil plasma membranes. These studies establish vesicular transport as a mechanism for emptying the specific eosinophil granule matrix compartment during IL-5-associated piecemeal degranulation.     

Pharmacophore Selection and Redesign of Non-nucleotide Inhibitors of Anthrax Edema Factor

Antibiotic treatment may fail to protect individuals, if not started early enough, after infection with Bacillus anthracis, due to the continuing activity of toxins that the bacterium produces. Stable and easily stored inhibitors of the edema factor toxin (EF), an adenylyl cyclase, could save lives in the event of an outbreak, due to natural causes or a bioweapon attack. The toxin’s basic activity is to convert ATP to cAMP, and it is thus in principle a simple phosphatase, which means that many mammalian enzymes, including intracellular adenylcyclases, may have a similar activity. While nucleotide based inhibitors, similar to its natural substrate, ATP, were identified early, these compounds had low activity and specificity for EF. We used a combined structural and computational approach to choose small organic molecules in large, web-based compound libraries that would, based on docking scores, bind to residues within the substrate binding pocket of EF. A family of fluorenone-based inhibitors was identified that inhibited the release of cAMP from cells treated with EF. The lead inhibitor was also shown to inhibit the diarrhea caused by enterotoxigenic E. coli (ETEC) in a murine model, perhaps by serving as a quorum sensor. These inhibitors are now being tested for their ability to inhibit Anthrax infection in animal models and may have use against other pathogens that produce toxins similar to EF, such as Bordetella pertussis or Vibrio cholera.     

A phase 1/2 trial of ibrutinib in combination with pembrolizumab in patients with mismatch repair proficient metastatic colorectal cancer

Background MMR proficient (pMMR) colorectal cancer (CRC) is usually unresponsive to immunotherapy. Recent data suggest that ibrutinib may enhance the anti-tumour activity of anti-PD-1 immunotherapy. In this study, we evaluated the safety and efficacy of ibrutinib plus pembrolizumab in refractory metastatic CRC.Methods This was a phase 1/2 study in patients with refractory metastatic pMMR CRC. The primary endpoints for phases 1 and 2 were maximum tolerated dose (MTD) and disease control rate, respectively. The secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS).Results A total of 40 patients were enrolled. No dose-limiting toxicity was observed, and MTD was not identified. The highest tested dose of ibrutinib, 560 mg once daily, was combined with a fixed dose of pembrolizumab 200 mg every 3 weeks for the phase 2 portion. The most common grade 3/4 treatment-related adverse events were anaemia (21%), fatigue (8%) and elevated alkaline phosphatase (8%). Among 31 evaluable patients, 8 (26%) achieved stable disease, and no objective response was observed. The median PFS and OS were 1.4 and 6.6 months, respectively.Conclusion Ibrutinib 560 mg daily plus pembrolizumab 200 mg every 3 weeks appears to be well tolerated with limited anti-cancer activity in metastatic CRC.ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT03332498","term_id":"NCT03332498"}}NCT03332498.Subject terms: Cancer immunotherapy, Colorectal cancer     

Bonding efficacy of an acetone/based etch-and-rinse adhesive after dentin deproteinization

Objectives: to evaluate the effect of sodium hypochlorite (NaOCl) treatment on dentin bonding by means of shear bond strength (SBS) measurements when using Prime&Bond NT (PB NT) adhesive. Ultrastructure of the interfaces was examined by scanning electron microscopy (SEM). Study design: Extracted human third molars were sectioned and ground to expose flat surfaces of superficial or deep dentin. Specimens were randomly assigned to two equal groups, and bonded as follows: (1) according to the manufacturers’ directions, after 35% H3PO4 etching, (2) 5% NaOCl treated for 2 minutes, after 35% H3PO4 etching. Each sample was embedded in a Watanabe shear test assembly for a single plane lap shear. After PB NT bonding, specimens were stored in water for 24 h at 37ºC and thermocycled (500x). Samples were tested in shear to failure using a universal testing machine at 0.75 mm/min. Data were analyzed with ANOVA and Newman-Keuls multiple comparison test procedures. Two samples of each group were randomly selected to investigate the morphologic aspect of the resin/dentin interface with SEM. Results: After etching and after aqueous sodium hypochlorite (NaOClaq) application, SBS values were similar on superficial than deep dentin (p>0.05). SEM findings shows for H3PO4 etching conditioned samples a detectable hybrid layer and long resin tags; for NaOCl treated specimens, it may be observed a non apparent hybrid layer, and the adhesive contact directly with the neck of the cylindrical resin tags. Conclusions: The use of 5% NaOCl for 2 min after dentin demineralization when PB NT was employed did not improve the bond strength to dentin, probably due to nanofiller content and/or oxidative changes on collagen-depleted dentin. Key words:Sodium hypochlorite, shear bond strength, SEM, Prime&Bond NT, superficial dentin, deep dentin.     

Resistance to bond degradation between dual-cure resin cements and pre-treated sintered CAD-CAM dental ceramics

Objective: To evaluate the bond stability of resin cements when luted to glass-reinforced alumina and zirconia CAD/CAM dental ceramics. Study design: Eighteen glass-infiltrated alumina and eighteen densely sintered zirconia blocks were randomly conditioned as follows: Group 1: No treatment; Group 2: Sandblasting (125 µm Al2O3-particles); and Group 3: Silica-coating (50 µm silica-modified Al2O3-particles). Composite samples were randomly bonded to the pre-treated ceramic surfaces using different resin cements: Subgroup 1: Clearfil Esthetic Cement (CEC); Subgroup 2: RelyX Unicem (RXU); and Subgroup 3: Calibra (CAL). After 24 h, bonded specimens were cut into 1 ± 0.1 mm2 sticks. One-half of the beams were tested for microtensile bond strength (MTBS). The remaining one-half was immersed in 10 % NaOCl aqueous solution (NaOClaq) for 5 h before testing. The fracture pattern and morphology of the debonded surfaces were assessed with a field emission gun scanning electron microscope (FEG-SEM). A multiple ANOVA was conducted to analyze the contributions of ceramic composition, surface treatment, resin cement type, and chemical challenging to MTBS. The Tukey test was run for multiple comparisons (p < 0.05). Results: After 24 h, CEC luted to pre-treated zirconia achieved the highest MTBS. Using RXU, alumina and zirconia registered comparable MTBS. CAL failed prematurely, except when luted to sandblasted zirconia. After NaOClaq storage, CEC significantly lowered MTBS when luted to zirconia or alumina. RXU decreased MTBS only when bonded to silica-coated alumina. CAL recorded 100 % of pre-testing failures. Micromorphological alterations were evident after NaOClaq immersion. Conclusions: Resin-ceramic interfacial longevity depended on cement selection rather than on surface pre-treatments. The MDP-containing and the self-adhesive resin cements were both suitable for luting CAD/CAM ceramics. Despite both cements being prone to degradation, RXU luted to zirconia or untreated or sandblasted alumina showed the most stable interfaces. CAL experimented spontaneous debonding in all tested groups. Key words:CAD/CAM ceramic, alumina, zirconia, resin cement, surface pre-treatment, sandblasting, silica-coating, chemical aging, bond degradation, microtensile bond strength.     

Disseminated adiaspiromycosis: case report of a liver transplant patient with human immunodeficiency infection,and literature review

I. Pelegrín, J. Ayats, X. Xiol, M. Cuenca‐Estrella, A. Jucglà, S. Boluda, N. Fernàndez‐Sabé, A. Rafecas, F. Gudiol, C. Cabellos. Disseminated adiaspiromycosis: case report of a liver transplant patient with human immunodeficiency infection, and literature review.
Transpl Infect Dis 2011: 13: 507–514. All rights reserved Abstract: Disseminated adiaspiromycosis is a rare infection that is sometimes associated with immunocompromised situations. We report the case of a patient, infected with human immunodeficiency virus and receiving highly active antiretroviral therapy, who had a liver transplant for hepatocellular carcinoma. The patient presented skin and pulmonary lesions due to adiaspiromycosis during immunosuppressive therapy. A review of >60 cases in the literature shows that adiaspiromycosis is a rare infection and Emmonsia is a dimorphic fungus that is difficult to grow. It should be considered a possible diagnosis in case of fungal infection and pulmonary granulomatosis. We should be aware of emerging adiaspiromycosis in patients with risk factors of immunosuppression, particularly transplant recipients. In these patients in particular, liposomal amphotericin B therapy should be considered.     

A Web-Based Survey of Oculoplastic Surgeons Regarding the Management of Lower Lid Retraction

Purpose: To survey the opinion of oculoplastic surgeons on the assessment and management of lower eyelid retraction (LLR).

Methods: A web-based survey queried oculoplastic surgeon members of Ojoplast, Spanish and Brazilian Oculoplastic Societies on the management of LLR. The frequency and percentage proportions of the responses were analyzed.

Results: One hundred ninety-six oculoplastic surgeons participated in the survey. The main cause of LLR is post-blepharoplasty (62;31.6%). The most used sign to detect LLR is scleral show. The most common approaches to managing LLR are lateral canthal surgery (164/593;27.6%), autogenous spacers (148/593; 24.9%) and retractor release (131/593;22.1%). The preferred autogenous graft material includes ear cartilage (102/260;39.2%). The majority of surgeons (161/314; 51.3%) recommend massage or steroids injection (80/314;25.5%) for early post-blepharoplasty LLR, while, 54.1% (106/196) of participants suggested waiting for at least six months prior to surgical intervention. Frost suture is used after most LLR surgeries (154/196;91.1%). Incomplete correction is the main complication (111/310;35.8%) of LLR surgery. For mild LLR, 48% of the responders prefer clinical treatment; conversely, severe cases routinely require combined surgical techniques.

Conclusions: Oculoplastic surgeons frequently diagnose LLR based on scleral show. LLR management depends on the cause and severity of lid retraction. Mild cases, in general, receive clinical treatment and severe cases need a combination of surgical techniques and grafts.