Success rate of orthograde endodontic retreatment after failed apicectomy - A retrospective study.

AIM: Orthograde retreatment after failed apicectomy maybe a treatment alternative to endodontic resurgery. The purpose of this study was to examine the clinical outcome of orthograde endodontic retreatment after failed apicectomy. METHODOLOGY: Success was rated radiographically in 191 cases of orthograde retreatment after failed apicectomy that were treated in a private practice with a documented recall of at least 12 months. The radiographs were rated individually by two observers, in cases of disagreement a consensus was reached by joint discussion with a third observer. Success or failure were evaluated according to previously described criteria. The success rate and the median survival were calculated using the Kaplan-Meier survival analysis. The log rank test was used to evaluate the effect of prognostic factors/predictors. Hazard ratios of predictors were analysed using Univariate Cox Proportional Hazard regression analysis. RESULTS: The mean follow-up of the included 191 patients (124 females, 67 males) was 32.13 (±23.68) months and the median was 25 months. The overall recall rate was 54%. Cohen Kappa analysis revealed nearly perfect agreement between both observers (k = 0.81; p = 1.0). The overall percentage of success was 84.82% (complete healing 79.06%, incomplete healing 5.76%). The median survival was 86 months (95% CI: 56-86). None of the selected predictors had an influence on the treatment outcome (p > .05). CONCLUSIONS: Orthograde retreatment should be considered a valuable treatment option after failed apicectomy. A surgical endodontic retreatment can still be a treatment option after orthograde retreatment to obtain outcome for the patient.

Joint Trauma System Clinical Practice Guideline: Acute Coronary Syndrome (ACS). 14 May 2021.

Deployed medical providers at all roles of care must be prepared to recognize and manage acute coronary syndrome (ACS). Under optimal conditions, treatment is initiated with medical therapy and may be followed by prompt coronary angiography and revascularization. Emergent percutaneous coronary intervention (PCI) is not available in most deployed locations, however, and the time for such intervention is often dependent on long-range evacuation. This CPG provides guidance on best management for ACS patients in the deployed and resource-constrained environment.

PTSD and Depressive Symptoms as Potential Mediators of the Association between World Trade Center Exposure and Subjective Cognitive Concerns in Rescue/Recovery Workers.

We observed that World Trade Center (WTC) exposure, post-traumatic stress disorder (PTSD) symptoms and depressive symptoms were associated with subjective cognitive concerns in Fire Department of the City of New York (FDNY) rescue/recovery workers. This follow-up study examined whether PTSD symptoms and/or depressive symptoms mediate the observed association between WTC exposure and subjective cognitive concerns. We included WTC-exposed FDNY workers who completed the Cognitive Function Instrument (CFI), measuring self-perceived cognitive decline (N = 9516). PTSD symptoms and depressive symptoms were assessed using the PCL-S and CES-D, respectively. Multivariable linear regression estimated the association between WTC exposure and CFI score, adjusting for confounders. Mediation analyses followed the methods of Vanderweele (2014). Participants' average age at CFI assessment was 56.6 ± 7.6 years. Higher-intensity WTC exposure was associated with worse CFI score, an effect that was entirely mediated by PTSD symptoms (%mediated: 110.9%; 95%CI: 83.1-138.9). When substituting depressive symptoms for PTSD symptoms, the WTC exposure-CFI association was largely mediated (%mediated: 82.1%; 95%CI: 60.6-103.7). Our findings that PTSD symptoms and depressive symptoms mediate the association between WTC exposure and subjective cognitive concerns indicate that in the absence of these symptoms, WTC exposure in rescue/recovery workers would not be associated with subjective cognition. Interventions targeting PTSD and depression may have additional value in mitigating cognitive decline in WTC-exposed populations.

Complete genome sequence analysis of a genetic variant of grapevine virus L from the grapevine cultivar Blanc du Bois.

The complete genome sequences of two grapevine virus L (GVL) isolates collected from the wine grape cultivar Blanc du Bois (Vitis spp.: 'Florida D 6-148'×'Cardinal') in Texas were determined. The two genome sequences (excluding the polyA tail) were each 7594 nucleotide long and 99.7% identical to each other, but they shared only ~74% identity with those of previously published GVL isolates. Further analysis showed that the two Texas GVL isolates also diverged significantly from previously published isolates of the virus in each of the five ORFs at both the nucleotide and amino acid level, indicating that they represent a new phylogroup of this virus.

System impacts of the COVID-19 pandemic on New York City's emergency medical services.

OBJECTIVES: To describe the impact of the COVID-19 pandemic on New York City's (NYC) 9-1-1 emergency medical services (EMS) system and assess the efficacy of pandemic planning to meet increased demands. METHODS: Longitudinal analysis of NYC 9-1-1 EMS system call volumes, call-types, and response times during the COVID-19 peak-period (March 16-April 15, 2020) and post-surge period (April 16-May 31, 2020) compared with the same 2019 periods. RESULTS: EMS system received 30,469 more calls from March 16-April 15, 2020 compared with March 16-April 15, 2019 (161,815 vs 127,962; P < 0.001). On March 30, 2020, call volume increased 60% compared with the same 2019 date. The majority were for respiratory (relative risk [RR] = 2.50; 95% confidence interval [CI] = 2.44-2.56) and cardiovascular (RR = 1.85; 95% CI = 1.82-1.89) call-types. The proportion of high-acuity, life-threatening call-types increased compared with 2019 (42.3% vs 36.4%). Planned interventions to prioritize high-acuity calls resulted in the average response time increasing by 3 minutes compared with an 11-minute increase for low low-acuity calls. Post-surge, EMS system received fewer calls compared with 2019 (154,310 vs 193,786; P < 0.001). CONCLUSIONS: COVID-19-associated NYC 9-1-1 EMS volume surge was primarily due to respiratory and cardiovascular call-types. As the pandemic stabilized, call volume declined to below pre-pandemic levels. Our results highlight the importance of EMS system-wide pandemic crisis planning.

Grapevine virus M, a novel vitivirus discovered in the American hybrid bunch grape cultivar Blanc du Bois in Texas.

A novel ssRNA (+) virus with molecular properties typical of members of the genus Vitivirus (family Betaflexiviridae; subfamily Trivirinae) was discovered by high-throughput sequencing in samples of the American hybrid bunch grape cultivar Blanc du Bois in Texas. The results were independently confirmed by Sanger sequencing of the virus isolate, whose genome length is 7,387 nt, excluding the polyA tail. The genome sequence contains five ORFs that are homologous and phylogenetically related to ORFs of grapevine-infecting vitiviruses. The name "grapevine virus M" is proposed for this new virus, whose sequence divergence exceeds the current ICTV species demarcation threshold for the genus Vitivirus.

Unusual Repair of Aortic Coarctation: Transcatheter Intervention Implications.

A 56-year old male was evaluated for exertional dyspnea. He had previously undergone mechanical aortic valve replacement and aortic coarctation repair. Following uncomplicated coronary angiography using Judkins left and right catheters, aortography revealed that the loud murmur was related to an unusual, extra-anatomic surgical repair: transverse aorta to descending aorta bypass. Recognition of an extra-anatomic surgical bypass of coarctation is important, as this repair would leave a continuous murmur on exam.

Possible Biases of Researchers' Attitudes Toward Video Games: Publication Trends Analysis of the Medical Literature (1980-2013).

BACKGROUND: The study of video games is expanding, and so is the debate regarding their possible positive and deleterious effects. As controversies continue, several researchers have expressed their concerns about substantial biases existing in the field, which might lead to the creation of a skewed picture, both in the professional and in the lay literature. However, no study has tried to examine this issue quantitatively. OBJECTIVE: The objective of our study was to examine possible systematic biases in the literature, by analyzing the publication trends of the medical and life sciences literature regarding video games. METHODS: We performed a complete and systematic PubMed search up to December 31, 2013. We assessed all 1927 articles deemed relevant for their attitude toward video games according to the focus, hypothesis, and authors' interpretation of the study results, using a 3-category outcome (positive, negative, and neutral). We assessed the prevalence of different attitudes for possible association with year of publication, location of researchers, academic discipline, methodological research, and centrality of the publishing journals. RESULTS: The attitude toward video games presented in publications varied by year of publication, location, academic discipline, and methodological research applied (P<.001 for all). Moreover, representation of different attitudes differed according to centrality of the journals, as measured by their impact factor (P<.001). CONCLUSIONS: The results suggest that context, whether scientific or social, is related to researchers' attitudes toward video games. Readers, both lay and professional, should weigh these contextual variables when interpreting studies' results, in light of the possible bias they carry. The results also support a need for a more balanced, open-minded approach toward video games, as it is likely that this complex phenomenon carries novel opportunities as well as new hazards.

Sleep Apnea Is Associated with Hearing Impairment: The Hispanic Community Health Study/Study of Latinos.

STUDY OBJECTIVE: Sleep apnea (SA) may promote hearing impairment (HI) through ischemia and inflammation of the cochlea. Our objective was to assess an independent association between SA and HI in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants. METHODS: We used data from the HCHS/SOL, a multicenter population-based study of self- identifying Hispanic/Latinos 18- to 74-y-old adults from four US urban communities. We performed home SA testing and in-clinic audiometry testing in all participants. SA was defined as an apnea-hypopnea index (AHI) ≥ 15 events/h. HI was defined as a mean hearing threshold > 25 dB hearing level in either ear at the frequencies: 3,000 to 8,000 Hz for high-frequency HI (HF-HI) and 500 to 2,000 Hz for low-frequency HI (LF-HI). Combined-frequency HI (CF-HI) was defined as both conditions present, and Any-HI was considered as HI in either low or high frequencies. RESULTS: Of 13,967 participants, 9.9% had SA and 32.3% had Any-HI. Adjusted for risk factors for HI, those with SA had a 30% higher odds of Any-HI (95% confidence interval [CI] = 8% to 57%), 26% higher odds of HF-HI (CI = 3% to 55%), 127% higher odds of LF-HI (CI = 21% to 326%), and 29% higher odds of CF-HI (CI = 0% to 65%). A dose-response association was observed between AHI severity and Any-HI (versus no SA, OR for AHI ≥ 15 and < 30 = 1.22, CI = 0.96 to 1.54, and OR for AHI ≥ 30 = 1.46, CI = 1.11 to 1.91, p = 0.002). CONCLUSION: SA is associated with HF-HI and LF-HI, independent of snoring and other confounders. COMMENTARY: A commentary on this article appears in this issue on page 641.

Obstructive sleep apnea and World Trade Center exposure.

OBJECTIVES: To describe the proportion of at-risk World Trade Center (WTC)-exposed rescue/recovery workers with polysomnogram-confirmed obstructive sleep apnea (OSA) and examine the relationship between WTC exposure, physician-diagnosed gastroesophageal reflux disease (GERD), and rhinosinusitis and OSA. METHODS: A total of 636 male participants completed polysomnography from September 24, 2010, to September 23, 2012. Obstructive sleep apnea was classified as mild, moderate, or severe. Associations were tested using nominal polytomous logistic regression. RESULTS: Eighty-one percent of workers were diagnosed with OSA. Using logistic regression models, severe OSA was associated with WTC exposure on September 11, 2001 (odds ratio, 1.91; 95% confidence interval, 1.15 to 3.17), GERD (odds ratio, 2.75; 95% confidence interval, 1.33 to 5.70), and comorbid GERD/rhinosinusitis (odds ratio, 2.31; 95% confidence interval, 1.22 to 4.40). CONCLUSIONS: We found significant associations between severe OSA and WTC exposure, and with diseases prevalent in this population. Accordingly, we recommend clinical evaluation, including polysomnography, for patients with high WTC exposure, other OSA risk factors, and a physician diagnosis of GERD or comorbid GERD and rhinosinusitis.

Thermogenic supplement use does not alter characteristics of sudden death in the young.

BACKGROUND: To evaluate supplement use, most notably ephedra, which has been temporally associated with sudden death. Animal models suggest increased myocardial irritability may predispose to primary arrhythmic death. METHODS: Clinical, pathological, and investigative records from the Office of the Armed Forces Medical Examiner's Cardiovascular Death Registry were reviewed. Forty-eight cases of those with known supplement use were compared to 144 age-, gender-, and socioeconomic-matched controls in a 1:3 case:control manner. RESULTS: Of the 48 sudden deaths temporally associated with supplement use, the mean age was 34.2 ± 10.0 years and predominantly male (n = 44, 91.7%). The underlying cause of death was fatal atherosclerotic coronary disease in 18 (37.5%), sudden unexplained death in 16 (33.3%), and hypertrophic cardiomyopathy in six (12.5%). Compared with controls, there were no statistically significant differences in adjudicated cause of death. On autopsy, there were no differences in cardiac mass, ventricular wall thickness, or presence of atherosclerosis in those known to be taking identified supplements compared to a control population. In the subject ≥35 years, and known to be taking supplements, there was a significant increase in causality of death as due to sudden unexplained death (relative risk = 5.1 [95% confidence interval, 1.4-18.7]). CONCLUSIONS: Active surveillance of mortality in an autopsy-derived series of young adults finds atherosclerotic coronary disease and idiopathic sudden death are common etiologies of death when taking supplements, but no cardiac structural or histologic mechanism to suggest different pathologic process than a matched control population.

Evaluation of organic cation transporter 3 (SLC22A3) inhibition as a potential mechanism of antidepressant action.

Organic cation transporter 3 (OCT3, SLC22A3) is a low-affinity, high-capacity transporter widely expressed in the central nervous system (CNS) and other major organs in both humans and rodents. It is postulated that OCT3 has a role in the overall regulation of neurotransmission and maintenance of homeostasis within the CNS. It is generally believed that all antidepressant drugs in current clinical use exert their primary therapeutic effects through inhibition of one or more of the high-affinity neuronal plasma membrane monoamine transporters, such as the norepinephrine transporter and the serotonin transporter. In the present study, we investigated the inhibitory effects of selected antidepressants on OCT3 activity in OCT3-transfected cells to evaluate whether OCT3 inhibition may at least in part contribute to the pharmacological effects of tested antidepressants. The studies demonstrated that all examined antidepressants inhibited OCT3-mediated uptake of the established OCT3 substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (4-Di-1-ASP) in a concentration-dependent manner. The IC(50) values were determined to be 4.7 µM, 7.4 µM, 12.0 µM, 18.6 µM, 11.2 µM, and 21.9 µM for desipramine, sertraline, paroxetine, amitriptyline, imipramine, and fluoxetine, respectively. Additionally, desipramine had an IC(50) value of 0.7 µM for the uptake of NE by OCT3, while the IC(50) value of sertraline was 2.3 µM for 5-HT uptake. Both desipramine and sertraline appeared to inhibit OCT3 activity via a non-competitive mechanism. In vivo studies are warranted to determine whether such effects on OCT3 inhibition are of sufficient magnitude to contribute to the overall therapeutic effects of antidepressants.

A liquid chromatography/tandem mass spectrometry assay for the analysis of atomoxetine in human plasma and in vitro cellular samples.

A simple, rapid and sensitive method for quantification of atomoxetine by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. This assay represents the first LC-MS/MS quantification method for atomoxetine utilizing electrospray ionization. Deuterated atomoxetine (d3-atomoxetine) was adopted as the internal standard. Direct protein precipitation was utilized for sample preparation. This method was validated for both human plasma and in vitro cellular samples. The lower limit of quantification was 3 ng/mL and 10 nm for human plasma and cellular samples, respectively. The calibration curves were linear within the ranges of 3-900 ng/mL and 10 nm to 10 µm for human plasma and cellular samples, respectively (r(2) >0.999). The intra- and inter-day assay accuracy and precision were evaluated using quality control samples at three different concentrations in both human plasma and cellular lysate. Sample run stability, assay selectivity, matrix effect and recovery were also successfully demonstrated. The present assay is superior to previously published LC-MS and LC-MS/MS methods in terms of sensitivity or the simplicity of sample preparation. This assay is applicable to the analysis of atomoxetine in both human plasma and in vitro cellular samples.

Prediction and in vitro evaluation of selected protease inhibitor antiviral drugs as inhibitors of carboxylesterase 1: a potential source of drug-drug interactions.

PURPOSE: To predict and determine whether the protease inhibitors (PIs) nelfinavir, amprenavir, atazanavir, ritonavir, and saquinavir could serve as metabolic inhibitors of the human CES1 (hCES1) using both molecular modeling techniques and in vitro inhibition assays. METHODS: Initially, a molecular modeling approach was utilized to predict whether the selected PIs could serve as hCES1 inhibitors. The inhibitory effects of these PIs on hCES1 activity were then further evaluated utilizing previously established in vitro assay. RESULTS: Pharmacophore and 2D-QSAR modeling predicted that nelfinavir would serve as a potent hCES1 inhibitor. This hypothesis was validated by in vitro hCES1 inhibition studies. Other PIs (amprenavir, atazanavir, ritonavir, saquinavir) were evaluated and also shown to be hCES1 inhibitors in vitro, although substantially less potent relative to nelfinavir. CONCLUSION: Computational molecular modeling is a valid approach to identify potential hCES1 inhibitors as candidates for further assessment using validated in vitro techniques. DDIs could occur when nelfinavir is co-administered with drugs metabolized by hCES1.

Sudden death in young adults: an autopsy-based series of a population undergoing active surveillance.

OBJECTIVES: The purpose of this study was to define the incidence and characterization of cardiovascular cause of sudden death in the young. BACKGROUND: The epidemiology of sudden cardiac death (SCD) in young adults is based on small studies and uncontrolled observations. Identifying causes of sudden death in this population is important for guiding approaches to prevention. METHODS: We performed a retrospective cohort study using demographic and autopsy data from the Department of Defense Cardiovascular Death Registry over a 10-year period comprising 15.2 million person-years of active surveillance. RESULTS: We reviewed all nontraumatic sudden deaths in persons 18 years of age and over. We identified 902 subjects in whom the adjudicated cause of death was of potential cardiac etiology, with a mean age of 38 ± 11 years. The mortality rate for SCD per 100,000 person-years for the study period was 6.7 for males and 1.4 for females (p < 0.0001). Sudden death was attributed to a cardiac condition in 715 (79.3%) and was unexplained in 187 (20.7%). The incidence of sudden unexplained death (SUD) was 1.2 per 100,000 person-years for persons <35 years of age, and 2.0 per 100,000 person-years for those ≥ 35 years of age (p < 0.001). The incidence of fatal atherosclerotic coronary artery disease was 0.7 per 100,000 person-years for those <35 years of age, and 13.7 per 100,000 person-years for those ≥ 35 years of age (p < 0.001). CONCLUSIONS: Prevention of sudden death in the young adult should focus on evaluation for causes known to be associated with SUD (e.g., primary arrhythmia) among persons <35 years of age, with an emphasis on atherosclerotic coronary disease in those ≥ 35 years of age.

Anemia of aging and obstructive sleep apnea.

INTRODUCTION: World Health Organization defined anemia of aging (AOA) when men and women greater than 65 years, respectively, have unexplained hemoglobin (Hgb) less than 13 and 12 g/dl. Recent evidence suggests that this is likely a chronic inflammatory process involving interleukins (IL) 6, 12, and C-reactive protein. Among elderly with obstructive sleep apnea (OSA), hypoxic stimulation of erythropoiesis may obscure AOA. Treatment of OSA may paradoxically restore AOA. We sought to identify OSA and AOA coexistence and OSA treatment AOA interaction. METHODS: Records of 101 successive patients older than 65 years and with OSA who were treated with continuous positive airway pressure were analyzed retrospectively. Differences among pre/post-treatment of OSA hemograms were assessed using paired two-tailed Student's t test. Hemogram changes were compared to apnea-hypopnea index (AHI), respiratory effort related arousals (RERA), and duration patients slept with oxyhemoglobin saturation <89% (hypoxic time (HT)) and were assessed for correlative significance using Pearson coefficient correlation. RESULTS: Eighty-two of one hundred one patients (27 men, 55 women; average age 71 years) had charted all the study data variables cited above. Mean pre-treatment and mean 1-year post-treatment of OSA Hgb/hematocrit (Hct) for men and women, respectively, were 13 g/dl/40.7% to 12.7 g/dl/39.1% and 12.1 g/dl/38.1% to 11.9 g/dl/37.6%. Hct changed significantly among both men and women (p < 0.05). Among 56% and 30% of the 82 patient study cohort, 1-year post-treatment of OSA, Hct declined (mean 4.8%) and increased (mean 3.7%), respectively; both changes were statistically significant (p < 0.01). These changes did not correlate significantly with AHI, RERA, or HT. DISCUSSION: Among the entire cohort for both men and women, we did not see AOA before OSA treatment and we did see AOA 1 year after OSA treatment. However, post-treatment of OSA Hct distributed bimodally, with significant increases and declines of Hct. While these Hct changes did not correlate significantly with selected sleep-breathing variables, we remain intrigued by a possible AOA-OSA interaction. AOA and OSA share common inflammatory processes. We believe OSA inflammatory processes interact with OSA hypoxia-induced erythropoiesis. The balance of these sets of processes determines the effect of OSA and OSA treatment on AOA.

Xylella fastidiosa: a model for analyzing agricultural biosecurity.

The threat to national security posed by the hostile release of human pathogens has been extensively documented. However, conclusions regarding the menace that plant pests and pathogens pose to the national economy and food supply are less developed. Here we present a risk analysis for the arrival and spread of foreign plant pathogens into the U.S. agricultural system. Xylella fastidiosa Citrus Variegated Chlorosis strain, an exotic plant pathogenic bacterium listed as a regulated biological agent under the Agricultural Bioterrorism Protection Act of 2002, serves as a model to evaluate the threat that plant diseases pose to crops and agriculture-dependent industries. We assess the nation's capacity to detect, contain, and manage newly introduced plant pathogens, exposing areas that need improvement and limitations of the system. This analysis provides a framework for understanding the risk that exotic plant diseases pose to U.S. agricultural biosecurity and a reference to continue preparing for the possible arrival of these threats.

Interaction of organic cation transporter 3 (SLC22A3) and amphetamine.

The organic cation transporter (OCT) 3 is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission. Relative to wild-type (WT) animals, Oct3 knockout (KO) mice have displayed altered behavioral and neurochemical responses to psychostimulants such as amphetamine (AMPH) and methamphetamine. In the present study, both in vitro and in vivo approaches were utilized to explore potential mechanisms underlying the disparate neuropharmacological effects observed following AMPH exposure in Oct3 KO mice. In vitro uptake studies conducted in OCT3 transfected cells indicated that dextroamphetamine (d-AMPH) is not a substrate of OCT3. However, OCT3 was determined to be a high-capacity and low-affinity transporter for the neurotransmitters dopamine (DA), norepinephrine (NE), and serotonin (5-HT). Inhibition studies demonstrated that d-AMPH exerts relatively weak inhibitory effects on the OCT3-mediated uptake of DA, NE, 5-HT, and the model OCT3 substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide. The IC(50) values were determined to be 41.5 +/- 7.5 and 24.1 +/- 7.0 microM for inhibiting DA and 5-HT uptake, respectively, while 50% inhibition of NE and 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide uptake was not achieved by even the highest concentration of d-AMPH applied (100 microM). Furthermore, the disposition of d-AMPH in various tissues including the brain, liver, heart, kidney, muscle, intestine, spleen, testis, uterus, and plasma were determined in both male and female Oct3 KO and WT mice. No significant difference was observed between either genotypes or sex in all tested organs and tissues. Our findings suggest that OCT3 is not a prominent factor influencing the disposition of d-AMPH. Additionally, based upon the inhibitory potency observed in vitro, d-AMPH is unlikely to inhibit the uptake of monoamines mediated by OCT3 in the brain. Differentiated neuropharmacological effects of AMPHs noted between Oct3 KO and WT mice appear to be due to the absence of Oct3 mediated uptake of neurotransmitters in the KO mice.