Effects of continuous chelation on the instrumentation of curved canals with a martensitic NiTi file system: an ex vivo micro-CT evaluation.

This study aimed to evaluate the influence of continuous chelation on apical transportation and centrality in shaped curved canals prepared with a martensitic file system and evaluated by micro-CT. Twenty-four lower molar canals with a curvature of 25º-40º were scanned pre-operatively with micro-CT and divided into 2 groups according to two different irrigation regimens (n = 12). Group 1 was irrigated with NaOCl, group 2 with Dual Rinse. All canals were prepared with VDW.ROTATE system. The samples were scanned post-operatively and evaluated at 1, 3 and 5 mm from the apex to determine apical transportation and canal centrality using VG Studio software. Statistical analysis was performed with SPSS software using the non-parametric Mann-Whitney test. No statistically significant differences were found between the two groups for both apical transportation and canal centrality at any of the levels studied (p < 05). The use of continuous chelation during the instrumentation of the canals with martensitic alloy files does not produce greater transportation and does not generate changes in centralization compared to NaOCl-only irrigation. Combined chelation and disinfection while shaping with martensitic NiTi can simplify the irrigation regimen without inducing iatrogenic aberrations.

Birth interval and stunting in children under five years of age in Peru (1996-2014).

BACKGROUND: Examine the evolution of stunting in <5 years of age in Peru and its relationship with birth interval (BI), and associated factors from 1996 to 2014. METHODS: Data were extracted from the National Demographic and Health Survey of Peru (DHS) for the years 1996, 2000, 2005, 2010 and 2014 on children <5 years of age for stunting (height / age ≤ 2DS). The main independent variable of interest was BI dichotomized by interval between date of last and penultimate birth (≤24 months vs. >24 months) and others sociodemographic variables. Crude and adjusted odds ratios with 95% confidence intervals were estimated in logistic regression for the effect of BI and other variables on stunting by each survey year. RESULTS: Between 1996 and 2014, stunting declined in both BI groups: ≤24 months: 35.8% to 21.8%; >24 months: 29.5% to 14.3%. BI was associated with stunting after adjustment for other variables in each survey except 2005. Of the other factors, sex, birth order (fourth child or more), maternal education and poverty were independently associated with stunting in all survey years. Residence in rural areas and in Amazon forest and highland regions was associated with stunting 1996 and 2000. Maternal age was not independently associated with stunting. CONCLUSIONS: While stunting showed a decreasing trend from 1996 to 2014, birth interval exceeding 24 months exerted a protective effect on stunting across the years surveyed. Poverty, low maternal education and high birth order were associated with stunting in all survey years.

Antiallodynic Activity of Ceftriaxone and Clavulanic Acid in Acute Administration is Associated with Serum TNF-α Modulation and Activation of Dopaminergic and Opioidergic Systems.

Preclinical Research The aim of this study was to determine the antiallodynic effect of acute administration of the ß-lactam antimicrobials, ceftriaxone (CFX) and clavulanic acid (CLAV), for the control of established pain on a model of neuropathic pain (NP). We also investigated the involvement of dopaminergic and opioidergic pathways as well as alterations in serum concentrations of TNF-α in the antiallodynic actions of these drugs. CFX, CLAV, or gabapentin (GAP), a reference drug, were administered i.p. twelve days after constriction of the sciatic nerve in rats. Mechanic and cold allodynia were evaluated for 3 h and alterations in serum concentration of TNF-α determined. Both CFX and CLAV had antiallodynic effects in response to mechanical and cold stimulation, similar to GAP. The antiallodynic effects of CFX and CLAV were blocked by haloperidol (HAL), a D2 receptor antagonist, and by naloxone (NLX), an opioid receptor antagonist. Additionally, serum TNF-α levels were attenuated following CFX and CLAV administration. These results suggest that acute administration of CFX and CLAV may represent a promising approach for treating the acute allodynia of NP, and that the mechanisms involved in these effects involve activation of dopaminergic and opioidergic pathways as well as modulation of TNF-α production. Drug Dev Res 78 : 105-115, 2017. © 2017 Wiley Periodicals, Inc.

Decreased levels of angiogenic growth factors in intracranial atherosclerotic disease despite severity-related increase in endothelial progenitor cell counts.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is an important cause of ischemic stroke (IS) and endothelial dysfunction plays a critical role in its onset and progression. Endothelial progenitor cells (EPCs) and endothelial production of angiogenic growth factors (AGFs) may play an essential role in this process. This study investigated the association of EPCs and AGFs with ICAD severity. METHODS: A total of 42 patients who had experienced a transient ischemic attack (TIA) or IS attributable to symptomatic ICAD were included. Clinical and neurosonological evaluations were conducted between 2.4 and 8.7 years after the initial cerebrovascular event. Severe ICAD was defined as the presence of at least 1 severe intracranial stenosis, and extensive ICAD as 3 or more intracranial stenoses. Blood samples were obtained to determine EPC levels using flow cytometry (CD34+KDR+ cells), and the plasma levels of several growth factors were assessed with a protein array (Searchlight(®)). Twenty-two individuals without cerebrovascular disease and with normal ultrasonographic examination were also included. RESULTS: No difference in the count of circulating EPCs was found between patients and controls, and a moderate increase in the number of EPCs/ml was noted in patients with extensive ICAD (p = 0.05). Patients presented decreased levels of fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-BB) compared with controls (p = 0.002, p = 0.079 and p = 0.061, respectively). Higher levels of FGF, VEGF and PDGF-BB were found in patients with severe ICAD (p = 0.007, p = 0.07 and p = 0.07, respectively), but there was no correlation between any AGFs and EPCs. CONCLUSIONS: Symptomatic ICAD patients have decreased levels of AGFs with no correlation to the number of circulating EPCs, while patients with severe ICAD have higher levels of EPCs, FGF, VEGF and PDGF-BBs. This suggests that reduced EPC and proangiogenic factor production capacity is implicated in ICAD pathogenesis, while the more severe forms of chronic brain hypoperfusion in ICAD patients might stimulate EPC mobilization and AGF production.

Leukoaraiosis is associated with genes regulating blood-brain barrier homeostasis in ischaemic stroke patients.

BACKGROUND: The biologic agents causing leukoaraiosis are unknown. Our aim was to study the genetic basis of leukoaraiosis. METHODS: We analyzed 212 single nucleotide polymorphisms (SNPs) in 142 patients with ischaemic stroke, generating a total of 30,104 genotypes. Seventy-nine subjects (55.6%) presented leukoaraiosis measured by the Fazekas scale and 69 (48.6%) by ARWMC scale. We analyzed the presence of synergic associations between SNPs using the hfcc software. Finally, functional studies were performed in 56 subjects. The Ingenuity Pathways software (ipa) was used to examine the role of the identified genes. RESULTS: Six SNPs were associated with leukoaraiosis using both measuring scales. After logistic regression adjusted for leukoaraiosis risk factors, the rs2252070 of MMP13 (OR = 4.9, 95%CI: 1.34-17.9, P = 0.016), rs662 of PON1 (OR = 0.37, 95%CI: 0.15-0.87, P = 0.024) and rs1800779 of NOS3 (OR = 3.9, 95%CI: 1.38-11.38, P = 0.01) were independently associated with leukoaraiosis under a dominant/recessive model and the rs2290608 of IL5RA (OR = 0.46, 95%CI: 0.25-0.85, P = 0.013) and rs669 of A2M (OR = 2.5, 95%CI: 1.36-4.83, P = 0.004) under an additive model. Computational analysis showed a synergic association of rs10497212-AA of ITGB6 and rs2290608-GG of IL5RA with leukoaraiosis using both scales. (i) ARWMC (P = 1.3 × 10(-4) ) and (ii) Fazekas (P = 4.5 × 10(-5) ). Functional studies showed that the rs669 SNP was associated with plasma levels of A2M (P = 0.012) and A2M levels with leukoaraiosis in Fazekas scale (P = 0.02). ipa analysis revealed that the genes associated with leukoaraiosis were involved in blood-brain barrier (BBB) homeostasis. CONCLUSIONS: Amongst patients with ischaemic stroke, several genes associated with BBB homeostasis could be involved with a higher risk of leukoaraiosis.

Neuroimmunological interactions in stroke. / Interacciones neuroinmunológicas en el ictus.

INTRODUCTION: Stroke is one of the leading causes of death in the world; its incidence is increasing due to increased life expectancy. However, treatment options for these patients are limited since no clinically effective drugs have been developed to date. DEVELOPMENT: According to clinical evidence, a number of neurochemical changes take place after stroke, including energy depletion, increased free radical synthesis, calcium accumulation, neurotransmitter imbalance, excitotoxicity, and, at a later stage, immune system activation leading to inflammation. Immune response has been shown to be a major factor in disease progression. The release of proinflammatory cytokines such as TNF increase brain damage secondary to excitotoxicity and calcium accumulation, and promote free radical synthesis and cell death through various mechanisms. On the other hand, certain anti-inflammatory cytokines, such as IL-10 and IL-4, have been shown to have a neuroprotective effect and even promote neurogenesis and synapse remodeling, which makes immune modulation a promising treatment approach. CONCLUSIONS: Understanding the relationship between the immune system and the nervous system not only deepens our knowledge of stroke but also provides new diagnostic, prognostic, and therapeutic strategies that may increase the quality of life of stroke patients.

Carga y profilaxis de la enfermedad meningocócica invasiva: actualización sobre la vacunación frente al serogrupo B / Invasive meningococcal disease burden and prophylaxis: update on serogroup B vaccination

La enfermedad meningocócica invasiva (EMI) es una infección bacteriana grave que suele presentarsecomo meningitis o sepsis. Se transmite por las secreciones de nariz y boca, cursa con síntomas de evolución rápida que, si no se tratan, causan la muerte en 24-48 horas y puede acarrear secuelas devastadoras,como amputación de miembros, convulsiones, ictus y deterioro de la visión, habla y audición. El serogrupo(Men) B es el patógeno responsable de la mayoría de las EMI en Europa, América y Australia.La Organización Mundial de la Salud considera que la vacunación es el método más efectivopara combatir la meningitis meningocócica. Hasta la fecha no existe ninguna vacuna que protejade manera conjunta frente a todos los serogrupos causantes de EMI. Las vacunas de polisacáridosconjugados frente a MenACWY se han utilizado durante años, mientras que las dos vacunas frente aMenB han sido desarrollas recientemente. La vacuna MenACWY está incluida en el programa nacionalde inmunización español para adolescentes de 12 años. La Asociación Española de Pediatría proponeincluir también la vacuna MenB de manera sistemática para lactantes, ya que es el serogrupo másprevalente en España. Los farmacéuticos cumplen, como agentes sanitarios, una misión cotidianaesencial de asesoramiento y dispensación en las farmacias. Esta revisión ofrece información a losfarmacéuticos para ayudarles a resolver preguntas sobre la EMI, así como de su profilaxis con vacunasy así, puedan explicar a los padres la importancia de administrar las dosis de recuerdo para completarla pauta de vacunación. (AU)

Invasive meningococcal disease (IMD) is a serious bacterial infection commonly presenting as meningitisor sepsis. Transmitted through the mouth and nose secretions, it has rapidly evolving symptoms thatcan cause death in 24-48 hours if untreated and may also have devastating consequences, such as lossof limbs, seizures, stroke, as well as impairment of vision, speech, and hearing. Serogroup (Men) B is thepathogen responsible for most of cases of IMD in Europe, America, and Australia. The World Health Organization considers that vaccination is the most effective approach to defeatmeningococcal meningitis. For now, there is no single vaccine that protects against all serogroupscausing IMD. Conjugate polysaccharide vaccines against MenACWY have been available for years, andonly recently two MenB vaccines have been developed. MenACWY vaccination for adolescents aged12 years is included in the Spanish National Immunization Program and the Spanish Association ofPaediatrics suggests the systematic inclusion of the MenB vaccine as well for infants, as it is the mostprevalent serogroup in Spain. Pharmacists play an essential role as healthcare agents, advising anddispensing every day to patients who visit the pharmacy. This review provides information that willhelp pharmacists to answer questions relevant to IMD and prophylaxis with the available vaccines,so that they can explain to parents the importance of booster doses and vaccination schedulecompletion. (AU)

Use of antibodies neutralizing epithelial cell infection to diagnose patients at risk for CMV Disease after transplantation.

OBJECTIVES: Although a CMV-specific T-cell response is associated with reduced risk for infection after transplantation, some patients still develop CMV disease. Thus, the characterization of additional parameters of the CMV-specific immune response that correlate with the control of CMV infection and disease and their use in defining thresholds that can be applied to clinical practice is of interest. METHODS: In a cohort of high risk solid organ transplant recipients we characterized CMV-specific T-cell responses using intracellular cytokine staining upon stimulation with pp65 and IE-1 peptides, and levels of CMV-specific antibodies neutralizing infection in fibroblast (MRC-5) and epithelial (ARPE-19) cells using microneutralization assays. RESULTS: Although patients with a positive (≥0.25%CD8(+)CD69(+)IFN-γ+) T-cell response were 6.4 fold more protected (OR 6.4, 95% CI 1.6-25.3; p < 0.001) from CMV infection than patients without a response, 2 (4.2%) patients developed disease. We defined a cut-off titer for epithelial cell neutralizing antibodies of ≥480 that correlated with disease protection. Thus, patients with a CMV-specific T-cell response and titers ≥480 were 14.2 fold more protected from CMV infection (OR 14.2, 95% CI 5-40.2; p < 0.001) and had no episodes of CMV disease. CONCLUSIONS: Our results indicate that antibodies neutralizing epithelial cell infection may have an important role in long-term protection. Quantification of antibodies neutralizing epithelial cells, in addition to the T-cell response, may be useful for identifying patients with lower risk for CMV disease.

Cheilitis associated with sensitization to penicillium notatum in a clarinetist

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The long-term benefit of surgery on health-related quality of life in patients with inflammatory bowel disease.

HYPOTHESES: Health-related quality of life (HRQL) has been shown to improve dramatically shortly after surgery in patients with inflammatory bowel disease (IBD). Our hypotheses were that (1) improved HRQL would be maintained long term in patients after surgery for ulcerative colitis and (2) the improved HRQL in patients with Crohn disease would decline with long-term follow-up. DESIGN: Consecutive series of patients undergoing surgery for IBD between June 1994 and January 2000 prospectively investigated as a cohort outcomes study. PATIENTS: Data were obtained in 139 patients. The diagnoses were Crohn disease (n = 56) and ulcerative colitis (n = 83). INTERVENTION: Patients with Crohn disease underwent resections with or without stricturoplasties; all but 5 patients with ulcerative colitis underwent ileal pouch-anal anastomoses. MAIN OUTCOME MEASURE: Health status was measured using the Health Status Questionnaire (HSQ) preoperatively and then every 3 months postoperatively. RESULTS: Preoperative HSQ scores were very low in all 8 scales of the HSQ. Postoperatively, HRQL measures improved significantly (P<.05) both in patients with Crohn disease and ulcerative colitis, with scores equal to or better than published scores in the general population. In patients with Crohn disease, the scores improved significantly after surgical resection and steadily increased despite disease recurrence and reoperations. The HRQL at last follow-up was equivalent to the general population. The improvements were statistically significant in patients followed up for more than 1 year in 7 of 8 scales of the HSQ. CONCLUSIONS: These results confirm that HRQL is poor in patients with IBD referred for possible operation. Surgical resection resulted in significant improvement in HRQL. More important, the results were durable. With follow-up up to 6 years, the HRQL in this cohort was equal to or better than norms for the general population both in patients with ulcerative colitis and with Crohn disease. We believe these data justify aggressive surgical intervention in many patients with IBD and support the prospective study of HRQL by surgeons treating patients with chronic diseases.

Benzodiazepine types in high versus therapeutic dose dependence.

Two types of benzodiazepine dependence have been described: high vs. therapeutic dose dependence. So far, no systematic research has been conducted regarding the frequency with which the various benzodiazepines are represented in one type or the other. In this study, 153 dependent patients using 14 different benzodiazepines were evaluated to assess the prevalence of their use among high vs. therapeutic dose dependents. Triazolam was the single drug most frequently used by high-dose dependents, followed by Lorazepam. No significant differences were found among benzodiazepines regarding their use by therapeutic dose dependents. Our data shows that pharmacokinetic and pharmacodynamic factors appear to be related to the frequency with which the different benzodiazepines are used by high and therapeutic dose dependents.

The long-term follow-up of patients with positive intraoperative cholangiograms during laparoscopic cholecystectomy.

BACKGROUND: The routine use of laparoscopic common bile duct exploration (LCBDE) for common bile duct (CBD) stones discovered during cholecystectomy would be further supported if the long-term outcomes were similar to those for endoscopic retrograde cholangiopancreatography with endoscopic papillotomy (ERCP/EP). METHODS: A retrospective review was completed of 151 patients who had a positive intraoperative cholangiogram (IOC) during laparoscopic cholecystectomy (LC). A "positive" IOC was defined as a filling defect or lack of contrast flow into the duodenum. A "successful" CBDE was defined as a negative IOC after completion of CBDE. Long-term follow-up was obtained using a standardized questionnaire to determine the incidence of recurrent biliary pain or need for subsequent ERCP/EP. RESULTS: CBD exploration was attempted in 142 patients (transcystic LCBDE 126 and open CBDE 16) and was successful in 107 of 142 (75%). Transcystic LCBDE was successful in 90 of 126 (71%). ERCP/EP was used in 41 patients; 35 of these cases were for failed LCBDE. Pancreatitis was not observed in any patient after CBDE but was observed in 3 of 41 patients (7.3%) after ERCP/EP. Long-term follow-up of the LCBDE versus ERCP/EP patients revealed no difference in the incidence of recurrent biliary pain or need for subsequent ERCP (mean follow-up time of 61 months). CONCLUSION: LCBDE is safe and effective in the majority of cases when an attempt at transcystic LCBDE was made. In addition, after long-term follow-up of >5 years, the outcomes were similar if the stones were removed by intraoperative laparoscopic methods versus postoperative ERCP. LCBDE seems worthy of pursuing when an intraoperative CBD stone is discovered.

Naphthoquinone spiroketals and organic extracts from the endophytic fungus Edenia gomezpompae as potential herbicides.

From the fermentation mycelium of the endophytic fungus Edenia gomezpompae were obtained several phytotoxic compounds including two new members of the naphthoquinone spiroketal family, namely, palmarumycin EG1 (1) and preussomerin EG4 (4). In addition, preussomerins EG1-EG3 (7-9) and palmarumycins CP19 (2), CP17 (3), and CP2 (6), as well as ergosta-4,6,8(14),22-tetraen-3-one (5), were obtained. Compounds 2, 3, and 5 are new to this species. The structures of palmarumycins CP19 (2) and CP17 (3) were unambiguously determined by X-ray analysis. The isolates and mycelium organic extracts from four morphological variants of E. gomezpompae caused significant inhibition of seed germination, root elongation, and seedling respiration of Amaranthus hypochondriacus, Solanum lycopersicum, and Echinochloa crus-galli. The treatments also affected respiration on intact mitochondria isolated from spinach.

Predictive value of ankle-brachial index and PAI-1 in symptomatic intracranial atherosclerotic disease recurrence.

BACKGROUND AND PURPOSE: We prospectively examine the single and combined predictive value of biological and clinical markers in recurrent strokes related to intracranial atherosclerotic disease (ICAD). METHODS: In 73 ICAD first-ever stroke patients, ankle-brachial index (ABI) was assessed three months after TIA or stroke together with CRP, Lp-PLA2, ICAM-1, E-selectin and PAI-1 measurements. Appearance of new TIA/stroke was assessed every 6 months. RESULTS: After a median follow-up of 22.4 months, 13 patients (17.8%) suffered a new stroke or TIA. Risk of new cerebrovascular events (CVEs) was associated with lowered ABI (p=0.011), baseline PAI-1>22.52 ng/ml (<0.001), E-selectin>24.75 ng/ml (p = 0.008) and ICAM-1>205 ng/ml (p = 0.029). The combination of PAI-1 with ABI or ESRS reclassified 55.4% (p<0.005) and 48.3% (p<0.05) of patients between low, high and very high-risk categories. CONCLUSIONS: This tentative study shows that ABI and PAI-1 are associated with the risk of new CVEs in symptomatic ICAD patients, and their combination might improve identification of patients at higher risk.

Determination, validation and standardization of a CMV DNA cut-off value in plasma for preemptive treatment of CMV infection in solid organ transplant recipients at lower risk for CMV infection.

BACKGROUND: Valganciclovir preemptive therapy guided by the viral load is the current strategy recommended for preventing CMV disease in CMV-seropositive Solid Organ Transplant Recipients (SOTR) at lower risk for developing CMV infection. However, universal viral load cut-off has not been established for initiating therapy. OBJECTIVES: Our goal was to define and validate a standardized cut-off determined in plasma by real-time PCR assay for initiating preemptive therapy in this population. STUDY DESIGN: A prospective cohort study of consecutive cases of CMV-seropositive SOTR was carried out. The cut-off value was determined in a derivation cohort and was validated in the validation cohort. Viral loads were determined using the Quant CMV LightCycler 2.0 real-time PCR System (Roche Applied Science) and results were standardized using the WHO International Standard for human CMV. RESULTS: A viral load of 3983 IU/ml (2600 copies/ml) was established as the optimal cut-off for initiating preemptive therapy in a cohort of 141 patients with 982 tests and validated in a cohort of 252 recipients with a total of 2022 test. This cut-off had a 99.6% NPV indicating that the great majority of patients at lower risk will not develop CMV disease without specific antiviral therapy. The high sensitivity and specificity (89.9% and 88.9%, respectively) and the relatively small numbers of patients with CMV disease confirm that real-time PCR was optimal. CONCLUSIONS: We have established a cut-off viral load for starting preemptive therapy for CMV-seropositive SOT recipients. Our results emphasized the importance of a mandatory follow-up protocol for CMV-seropositive patients receiving preemptive treatment.

Andalusian registry of heart transplantation: first official adult heart transplant report 2010.

This is the first official report of the Andalusian Registry of Heart Transplantation. Since 1986, two centers in the community have been authorized to perform adult heart transplantation. Until 2010, 854 adult heart transplantation procedures were performed, which constitute the basis of the present report. Clinical features and survival are analyzed. The leading reason for heart transplantation was ischemic cardiomyopathy (34%) and nonischemic dilated cardiomyopathy (34%). The mean age of the recipients was 46 ± 16 years and the mean age of the donors was 29 ± 13 years. After a median follow-up of 106 months, the mean survival was 13.4 ± 0.6 years.