Measurable Residual Disease by Mass Spectrometry and Next-Generation Flow to Assess Treatment Response in Myeloma.

Quantitative immuneprecipitation mass-spectrometry (QIP-MS) allows the identification of the M-protein in patients with multiple myeloma (MM) otherwise in complete response, and could be considered suitable for measurable residual disease (MRD) evaluation in peripheral blood. In the context of the GEM2012MENOS65 and GEM2014MAIN trials, we compared the performance of QIP-MS in serum with next-generation flow (NGF) cytometry in bone marrow to assess MRD in paired samples obtained post-induction, transplant, consolidation and after 24 cycles of maintenance. At each time point, both NGF and QIP-MS were able to segregate two groups of patients with significantly different progression-free survival (PFS); when the evolution of the results obtained with either method was considered, maintaining or converting to MRD negativity was associated with longer survival, significantly better when compared to sustaining or converting to MRD positivity. Of note, reemergence of MRD by QIP-MS was associated with high risk of imminent clinical progression. In conclusion, MRD evaluation by NGF and MS achieve similar prognostic value based in single time point assessments and kinetics. Thus, the minimally-invasive nature of MRD monitoring by MS represents a breakthrough in high-sensitive response assessment in MM. GEM2012MENOS65: #NCT01916252 and EudraCT as #2012-005683-10. GEM2014MAIN: #NCT02406144 and at EudraCT as 2014-00055410.

Single-point and kinetics of peripheral residual disease by mass spectrometry to predict outcome in patients with high risk smoldering multiple myeloma included in the GEM-CESAR trial.

The value of quantitative immunoprecipitation mass spectrometry (QIP-MS) to identify the M-protein is being investigated in patients with monoclonal gammopathies but no data are yet available in high-risk smoldering myeloma (HRsMM). We have therefore investigated QIP-MS to monitor peripheral residual disease (PRD) in 62 HRsMM patients enrolled in the GEM-CESAR trial. After 24 cycles of maintenance, detecting the M-protein by MS or clonal plasma cells by NGF identified cases with a significantly shorter median PFS (mPFS; MS: not reached vs 1,4 years, p=0.001; NGF: not reached vs 2 years, p=0.0002) but reaching CR+sCR did not discriminate patients with different outcome. With NGF as a reference, the combined results of NGF and MS showed a high negative predictive value (NPV) of MS: 81% overall and 73% at treatment completion. When sequential results were considered, sustained negativity by MS or NGF was associated with a very favorable outcome with a mPFS not yet reached vs 1.66 years and 2.18 years in cases never attaining PRD or minimal residual disease (MRD) negativity, respectively. We can thus conclude that 1) the standard response categories of the IMWG do not seem to be useful for treatment monitoring in HRsMM patients, 2) MS could be used as a non-invasive, clinical valuable tool with the capacity of guiding timely bone marrow evaluations (based on its high NPV with NGF as a reference) and 3) similarly to NGF, sequential results of MS are able identify a subgroup of HRsMM patients with long-term disease control. This study was registered at www.clinicaltrials.gov (ClinicalTrials.gov identifier: NCT02415413).

Optimizing herbicide selection for pre-emergence control of itchgrass and cypressvine morningglory in sugarcane.

The aim of this study was to assess the efficacy of herbicides in association to control Rottboellia exaltata and Ipomoea quamoclit during pre-emergence while also to evaluate the potential impact on the sugarcane. The experimental design employed a randomized block with seven treatments and four replications. The treatments were: 1 - no herbicide application; 2 - indaziflam + sulfentrazone; 3 - indaziflam + diclosulam; 4 - indaziflam + tebuthiuron; 5 - flumioxazin + diclosulam, 6 - flumioxazin + pyroxasulfone and 7 - clomazone + sulfentrazone. The evaluated parameters were: percentage of weeds control, green coverage percentage (Canopeo® system), weed biomass (g m-2), itchgrass height, and sugarcane tiller. Several herbicide associations have been proven effective alternatives for managing itchgrass and cypressvine morningglory. The most successful treatments for itchgrass control were indaziflam + tebuthiuron (100%) and indaziflam + diclosulam (97%), whereas for cypressvine morningglory, the betters were indaziflam + sulfentrazone (97%), indaziflam + diclosulam (98%), indaziflam + tebuthiuron (97%), flumioxazin + diclosulam (94%), and clomazone + sulfentrazone (96%). All treatments reduced the weed biomass, with indaziflam + tebuthiuron being the safest option for protecting sugarcane.

Selectivity and control of Euphorbia heterophylla in sugarcane by herbicide in post-emergence.

To obtain good control of wild poinsettia (Euphorbia heterophylla) in post-emergence in sugarcane crop, we evaluate the herbicides association on post-emergence of E. heterophylla and the ratoon cane selectivity. The experimental scheme was in randomized blocks with 6 treatments and 4 replications. The treatments were: control; ametryn + mesotrione + sulfentrazone (1,500 + 144 + 800 g i.a ha-1); ametryn + mesotrione + diclosulan (1,500 + 144 + 200 g i.a ha-1); ametryn + mesotrione (2,500 + 144 g i.a ha-1: Highest dose); ametryn + mesotrione (2,000 + 144 g i.a ha-1: Lowest dose) and ametryn + mesotrione + diuron (1,000 + 144 + 1,250 g i.a ha-1). The percentage of control, dry mass, height and percentage of germination of E. heterophylla and injury level, yield and technological quality of sugarcane were evaluated. The best control of E. heterophylla was: ametryn + mesotrione +sulfentrazone; ametryn + mesotrione + diclosulan and ametryn + mesotrione (Lowest dose). As for the ratoon cane selectivity the best yield was achieved with the association ametryn + mesotrione +diclosulan. An appropriate association of herbicide molecules provides successful control of E. heterophylla, especially the association of sulfentrazone or diclosulan together with ametryn and mesotrione.

Double stenting in T configuration with safety micro-guidewire technique in a complex middle cerebral artery stenosis.

Intracranial arterial stenosis is a frequently misdiagnosed cause of ischemic stroke, associated with high rates of recurrence under medical therapy alone. Endovascular intracranial angioplasty and stenting has increasingly been used worldwide for treatment of symptomatic intracranial stenoses, despite controversial results of the first randomized trials. Lesion morphology and etiology must be considered during endovascular treatment planning. Complex morphologies can lead to serious complications during the endovascular procedure. We present a case of a symptomatic complex middle cerebral artery stenosis that was successfully treated with a double stenting in T configuration, using a safety micro-guidewire technique. During follow-up, intracranial Doppler revealed a non-significant residual stenosis and the patient remained asymptomatic.

Perspectives, Experiences, and Practices in the Use of Digital Information Technologies in the Management of Depression and Alcohol Use Disorder in Health Care Systems in Colombia.

Digital information technologies are increasingly used in the treatment of mental health disorders. Through this qualitative study, researchers illuminated perspectives, experiences, and practices among diverse stakeholders in the use of digital information technologies in the management of depression and alcohol use disorders in Colombia. In-depth interviews and focus groups were conducted in five primary care institutions across Colombia. Thematic analysis was used to analyze the data. The use of technology in the treatment of mental health disorders can facilitate the evaluation and diagnosis, treatment, and promotion and prevention of mental health disorders, as well as multiple nonmental health applications in the primary care setting. Potential barriers to the use of technology in this setting include challenges of digital literacy, access to technology, confidentiality, and financing. This study can inform the implementation of digital information technologies in the care of depression and problematic alcohol use within health care systems in Colombia.

Mean platelet volume and mechanical thrombectomy.

BACKGROUND AND PURPOSE: Mean Platelet Volume (MPV) is a marker of platelet activity and it is an independent predictor for long-term outcome in stroke patients. The aim of this study was to evaluate the association between baseline MPV value and clinical outcome at 90-days in anterior circulation stroke and large vessel occlusion (LVO) patients submitted to mechanical thrombectomy (MT). METHODS: We conducted a prospective observational cohort study in acute ischemic stroke (AIS) patients submitted to MT between January 2017 and May 2018. MPV was measured at admission. Patients were initially stratified into two groups according to the mean MPV level. We also compared groups that were stratified according to the MPV cut-off obtained by Peng F et al (10,4 fL) and performed analyses among MPV terciles. RESULTS: A total of 129 patients were included. Mean level of MPV was 10,9 fL. Patients with embolic stroke of undetermined source (ESUS) had significantly higher rates of good outcome at 3 months compared with large-artery atherosclerotic disease and cardioembolism [(82,9%) vs (78,3%) vs (55,2%); p=0,009]. There were no statistically significant differences in the mean MPV value (p=0,222), successful recanalization (p=0,464) and mortality (p=0,343) when evaluated for all TOAST etiologies. There were no statistically significant differences between the two groups according to the MPV level (10,4 and 10,9 fL) or between the terciles (lowest tertile <10,3 fL, median 10,3 - 11,3 fL, highest >11,3fL) concerning functional outcome at 3 months (p=0,357; p=0,24 and p=0,558, respectively), successful recanalization (p=0,108; p=0,582 and p=0,899, respectively) or mortality at 3 months (p=0,465; p=0,061 and p=0,484, respectively). CONCLUSION: Our study did not find an association between elevated MPV and worse outcome at 3 months in patients with acute anterior circulation stroke and LVO treated with MT. Since ischemic strokes have different pathophysiologic mechanisms, MPV may have distinct prognostic value according to each stroke etiology.

Effects of Ornamental Plant Density and Mineral/Plastic Media on the Removal of Domestic Wastewater Pollutants by Home Wetlands Technology.

Wastewater treatment (WWT) is a priority around the world; conventional treatments are not widely used in rural areas owing to the high operating and maintenance costs. In Mexico, for instance, only 40% of wastewater is treated. One sustainable option for WWT is through the use of constructed wetlands (CWs) technology, which may remove pollutants using cells filled with porous material and vegetation that works as a natural filter. Knowing the optimal material and density of plants used per square meter in CWs would allow improving their WWT effect. In this study, the effect of material media (plastic/mineral) and plant density on the removal of organic/inorganic pollutants was evaluated. Low (three plants), medium (six plants) and high (nine plants) densities were compared in a surface area of 0.3 m2 of ornamental plants (Alpinia purpurata, Canna hybrids and Hedychium coronarium) used in polycultures at the mesocosm level of household wetlands, planted on the two different substrates. Regarding the removal of contaminants, no significant differences were found between substrates (p ≥ 0.05), indicating the use of plastic residues (reusable) is an economical option compared to typical mineral materials. However, differences (p = 0.001) in removal of pollutants were found between different plant densities. For both substrates, the high density planted CWs were able to remove COD in a range of 86-90%, PO4-P 22-33%, NH4-N in 84-90%, NO3-N 25-28% and NO2-N 38-42%. At medium density, removals of 79-81%, 26-32, 80-82%, 24-26%, and 39-41%, were observed, whereas in CWs with low density, the detected removals were 65-68%, 20-26%, 79-80%, 24-26% and 31-40%, respectively. These results revealed that higher COD and ammonia were removed at high plant density than at medium or low densities. Other pollutants were removed similarly in all plant densities (22-42%), indicating the necessity of hybrid CWs to increase the elimination of PO4-P, NO3-N and NO2-N. Moreover, high density favored 10 to 20% more the removal of pollutants than other plant densities. In addition, in cells with high density of plants and smaller planting distance, the development of new plant shoots was limited. Thus, it is suggested that the appropriate distance for this type of polyculture plants should be from 40 to 50 cm in expansion to real-scale systems in order to take advantage of the harvesting of species in these and allow species of greater foliage, favoring its growth and new shoots with the appropriate distance to compensate, in the short time, the removal of nutrients.

Assessing the Integration of Behavioral Health Services in Primary Care in Colombia.

Integration of behavioral health care into primary care can improve health and economic outcomes. This study adapted the Behavioral Health Integration in Medical Care (BHIMC) index to the Colombian context and assessed the baseline level of behavioral health integration in a sample of primary care organizations. The BHIMC was able to detect the capacity to provide integrated behavioral care in Colombian settings. Results indicate a minimal to partial integration level across all sites, and that it is possible to measure the degree of integrated care capacity and identify improvement areas for better behavioral health care provision.

Germination and seedling growth of the Chilean native grass Polypogon australis in soil polluted with diesel oil.

The purpose of this study was to evaluate the ability of Polypogon australis, a Chilean native grass that colonizes copper polluted sites, to germinate and grow in soil contaminated with diesel oil. The effect of increasing proportions of diesel in soil (0.5%, 1%, 2%, and 5%) on the cumulative germination and growth of plants was measured. The relative seed germination (RSG), relative root growth (RRG), germination index (GI), and the effective concentration (EC50) were calculated. The cumulative germination in soil polluted with 0%, 0.5%, 1%, and 2% of diesel oil in soil was 93.3%, 85.5%, 99%, and 78.5%, respectively, showing no significant differences between the treatments (p > 0.05). A proportion of 5% of diesel in the soil reduced the germination of P. australis by 50%, compared to the control. The growth of leaves and roots of the plants germinated in 5% of diesel was reduced by 30% compared to the control, with a 34% survival rate observed on day 40. The calculated EC50 of diesel for P. australis was 4.5%. P. australis germinated and grew on all diesel concentration used in the experiments. The species was classified as a tolerant to diesel oil.

Primary Thrombectomy Versus Combined Mechanical Thrombectomy and Intravenous Thrombolysis in Large Vessel Occlusion Acute Ischemic Stroke.

Mechanical thrombectomy (MT) in combination with intravenous thrombolysis (IVT) is the standard of care for patients with acute ischemic stroke with anterior circulation large vessel occlusion. The particular benefit of IVT in these patients is unknown. We performed a retrospective analysis of patients submitted to MT at our center between January 2015 and June 2017. Functional outcome was prospectively assessed using modified Rankin scale (mRS) at 3 months. A total of 234 patients were enrolled, 152 (65%) in the combined treatment group and 82 (35%) in the direct MT group. Patients receiving combined treatment had a higher frequency of intracranial internal carotid artery occlusion (48 [31.6%] versus 16 [19.5%], P = .048) and significantly less strokes of cardioembolic etiology (72 [47.4%] versus 57 [69.5%], P = .01). Other baseline characteristics did not differ between the 2 groups. Good functional outcome at 3 months (mRS 0-2) was trending toward being higher in patients in the combined treatment group (98 [64.9%] versus 42 [52.5%], P = .066). Rates of symptomatic intracranial hemorrhage (5 [3.3%] versus 4 [4.9%], P = .723) and mortality (15 [9.9%] versus 14 [17.5%], P = .099) did not differ between groups. In multivariate logistic regression analysis, we did not find a statistically significant association between the use of IVT and any of the outcomes studied. Our results suggest that combined treatment carries similar effectiveness and safety than direct MT. Randomized controlled trials regarding this subject are warranted.

Time to Reset the Definition of Successful Revascularization in Endovascular Treatment of Acute Ischemic Stroke.

BACKGROUND: A 2013 consensus statement recommended the use of the modified Treatment In Cerebral Ischemia (mTICI) scale to evaluate angiographic revascularization after endovascular treatment (EVT) of acute ischemic stroke due to its higher inter-rater agreement and capacity of clinical outcome prediction. The current definition of successful revascularization includes the achievement of grades mTICI 2b or 3. However, mTICI 2b grade encompasses a large heterogeneity of revascularization states, and prior studies suggested that the magnitude of benefit derived from mTICI 2b and mTICI 3 does not seem to be equivalent. In a way to restrain the referred heterogeneity, Goyal et al. [J Neurointerv Surg 2014; 6: 83-86] proposed a revised mTICI scale that includes a 2c grade (rTICI). METHODS: Retrospective analysis of prospectively collected data from consecutive cases of EVT for anterior circulation large-vessel occlusion, performed between January 2015 and July 2017. Patients with mTICI 2b or 3 grades were reclassified according to the rTICI scale, and the outcomes between the 3 revascularization grades (rTICI 2b, 2c, 3) compared. RESULTS: Our study population of 226 patients (64 rTICI 2b, 30 rTICI 2c, 132 rTICI 3) has a mean age of 71 years, 48.2% males, median baseline NIHSS of 16 (13-19) and ASPECTS of 8 (7-9). The 3 revascularization grades are represented by homogeneous populations. Logistic regression analysis showed statistically significant higher rates of functional independence at 3 months (65.9 vs. 50.0%; adjusted OR 0.39, 95% CI 0.18-0.86), with lower rates of mortality (8.3 vs. 15.6%; adjusted OR 3.54, 95% CI 1.14-10.97) and intracranial hemorrhage (ICH) in rTICI 3 than 2b groups. When comparing rTICI 3 with 2c groups, there were only statistically significant differences in the total ICH rate (8.3 vs. 26.7%; adjusted OR 7.08, 95% CI 1.80-27.82) but not in symptomatic ICH. CONCLUSIONS: These results corroborate the scarce prior findings suggesting that patients with rTICI 2c grade should be reported separately, since they have similar outcomes to rTICI 3, and better than rTICI 2b patients. Therefore, we suggest resetting the angiographic revascularization endpoint to perfect revascularization (rTICI 2c or 3 grades), a target that neurointerventionalists should strive to achieve.

Automated annotation and classification of BI-RADS assessment from radiology reports.

The Breast Imaging Reporting and Data System (BI-RADS) was developed to reduce variation in the descriptions of findings. Manual analysis of breast radiology report data is challenging but is necessary for clinical and healthcare quality assurance activities. The objective of this study is to develop a natural language processing (NLP) system for automated BI-RADS categories extraction from breast radiology reports. We evaluated an existing rule-based NLP algorithm, and then we developed and evaluated our own method using a supervised machine learning approach. We divided the BI-RADS category extraction task into two specific tasks: (1) annotation of all BI-RADS category values within a report, (2) classification of the laterality of each BI-RADS category value. We used one algorithm for task 1 and evaluated three algorithms for task 2. Across all evaluations and model training, we used a total of 2159 radiology reports from 18 hospitals, from 2003 to 2015. Performance with the existing rule-based algorithm was not satisfactory. Conditional random fields showed a high performance for task 1 with an F-1 measure of 0.95. Rules from partial decision trees (PART) algorithm showed the best performance across classes for task 2 with a weighted F-1 measure of 0.91 for BIRADS 0-6, and 0.93 for BIRADS 3-5. Classification performance by class showed that performance improved for all classes from Naïve Bayes to Support Vector Machine (SVM), and also from SVM to PART. Our system is able to annotate and classify all BI-RADS mentions present in a single radiology report and can serve as the foundation for future studies that will leverage automated BI-RADS annotation, to provide feedback to radiologists as part of a learning health system loop.

Performance of a Mobile Phone App-Based Participatory Syndromic Surveillance System for Acute Febrile Illness and Acute Gastroenteritis in Rural Guatemala.

BACKGROUND: With their increasing availability in resource-limited settings, mobile phones may provide an important tool for participatory syndromic surveillance, in which users provide symptom data directly into a centralized database. OBJECTIVE: We studied the performance of a mobile phone app-based participatory syndromic surveillance system for collecting syndromic data (acute febrile illness and acute gastroenteritis) to detect dengue virus and norovirus on a cohort of children living in a low-resource and rural area of Guatemala. METHODS: Randomized households were provided with a mobile phone and asked to submit weekly reports using a symptom diary app (Vigilant-e). Participants reporting acute febrile illness or acute gastroenteritis answered additional questions using a decision-tree algorithm and were subsequently visited at home by a study nurse who performed a second interview and collected samples for dengue virus if confirmed acute febrile illness and norovirus if acute gastroenteritis. We analyzed risk factors associated with decreased self-reporting of syndromic data using the Vigilant-e app and evaluated strategies to improve self-reporting. We also assessed agreement between self-report and nurse-collected data obtained during home visits. RESULTS: From April 2015 to June 2016, 469 children in 207 households provided 471 person-years of observation. Mean weekly symptom reporting rate was 78% (range 58%-89%). Households with a poor (<70%) weekly reporting rate using the Vigilant-e app during the first 25 weeks of observation (n=57) had a greater number of children (mean 2.8, SD 1.5 vs mean 2.5, SD 1.3; risk ratio [RR] 1.2, 95% CI 1.1-1.4), were less likely to have used mobile phones for text messaging at study enrollment (61%, 35/57 vs 76.7%, 115/150; RR 0.6, 95% CI 0.4-0.9), and were less likely to access care at the local public clinic (35%, 20/57 vs 67.3%, 101/150; RR 0.4, 95% CI 0.2-0.6). Parents of female enrolled participants were more likely to have low response rate (57.1%, 84/147 vs 43.8%, 141/322; RR 1.4, 95% CI 1.1-1.9). Several external factors (cellular tower collapse, contentious elections) were associated with periods of decreased reporting. Poor response rate (<70%) was associated with lower case reporting of acute gastroenteritis, norovirus-associated acute gastroenteritis, acute febrile illness, and dengue virus-associated acute febrile illness (P<.001). Parent-reported syndromic data on the Vigilant-e app demonstrated agreement with nurse-collected data for fever (kappa=.57, P<.001), vomiting (kappa=.63, P<.001), and diarrhea (kappa=.61, P<.001), with decreased agreement as the time interval between parental report and nurse home visit increased (<1 day: kappa=.65-.70; ≥2 days: kappa=.08-.29). CONCLUSIONS: In a resource-limited area of rural Guatemala, a mobile phone app-based participatory syndromic surveillance system demonstrated a high reporting rate and good agreement between parental reported data and nurse-reported data during home visits. Several household-level and external factors were associated with decreased syndromic reporting. Poor reporting rate was associated with decreased syndromic and pathogen-specific case ascertainment.

Endovascular Stroke Treatment of Patients Over 80 Years Old: Cumulative Evidence from the "Real World".

BACKGROUND: Evidence on stent retriever-based thrombectomy (SRT) efficacy in elderly patients is controversial. This study aimed to analyze safety and efficacy outcomes in octogenarians submitted to SRT. METHODS: Analysis was based on a prospective observational registry of patients with stroke because of anterior circulation large-vessel occlusion treated with SRT at our center between January 2015 and September 2016. Patients were dichotomized into 2 age groups: ≤80 and >80 years old. Outcomes at 90 days were assessed: "excellent outcome" (a modified Rankin scale [mRs] score of 0-1) and "good outcome" (a mRs score of 0-2). RESULTS: A total of 141 patients were included: 35 (24.8%) >80 years old and 106 (71.2%) ≤80 years old; 43.4% of patients in the younger group and 25.7% of patients in the older group achieved an "excellent outcome." A "good outcome" was achieved in 65.1% of patients in the younger group, and 60% of patients in the older group; crude odds ratio (OR) for "excellent outcome" was 0.452 (P = .067). Crude OR for "good outcome" was 0.804 (P = .587). After adjusting for gender, National Institutes of Health Stroke Scale score at admission, Alberta Stroke Program Early CT Score, and thrombolysis, the OR was 0.450 (P = .100) and 1.217 (P = .686) for "excellent" and "good" outcomes, respectively. CONCLUSIONS: In this cohort, 60% of elderly patients regained functional independence at 3 months after SRT. Although age may be a prognostic factor, patients should not be excluded from SRT based on age criteria.

Mechanical Thrombectomy in Acute Ischemic Stroke: Initial Single-Center Experience and Comparison with Randomized Controlled Trials.

BACKGROUND: Until recently, intravenous thrombolysis was the only reperfusion therapy with proven efficacy in patients with acute ischemic stroke. However, this treatment option has low recanalization rates in large-vessel occlusions. The search for additional treatments continued until 5 randomized trials (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, and REVASCAT) revealed the superiority of mechanical thrombectomy for anterior circulation large-vessel occlusion. After 1 year of performing thrombectomy with stent retrievers in our tertiary hospital, we intended to answer the question: is it possible to achieve similar results in a "real-world" setting? METHODS: We analyzed data from our prospective observational registry, compared it with the trials aforementioned, and concluded that the answer is affirmative. RESULTS: Our study population of 77 patients, with a mean age of 68,2 years and 48,1% men, is comparable with these trials in much of selection criteria, baseline characteristics, and rate of previous intravenous thrombolysis (72,7%). Recovery of functional independence at 90 days was achieved in almost two thirds of patients, similarly to the referred trials. We devoted special emphasis on fast recanalization, keeping a simple image selection protocol (based on non-enhanced and computed tomography angiography) and not waiting for clinical response to thrombolysis in patients eligible for mechanical thrombectomy. We emphasize a successful recanalization rate of 87% and only 2,6% symptomatic intracranial hemorrhage. CONCLUSION: In summary, mechanical thrombectomy seems to be a safe and effective treatment option in a "real-world" scenario, with results similar to those of the recent randomized controlled trials.

Molecular organization of the 5S rDNA gene type II in elasmobranchs.

The 5S rDNA gene is a non-coding RNA that can be found in 2 copies (type I and type II) in bony and cartilaginous fish. Previous studies have pointed out that type II gene is a paralog derived from type I. We analyzed the molecular organization of 5S rDNA type II in elasmobranchs. Although the structure of the 5S rDNA is supposed to be highly conserved, our results show that the secondary structure in this group possesses some variability and is different than the consensus secondary structure. One of these differences in Selachii is an internal loop at nucleotides 7 and 112. These mutations observed in the transcribed region suggest an independent origin of the gene among Batoids and Selachii. All promoters were highly conserved with the exception of BoxA, possibly due to its affinity to polymerase III. This latter enzyme recognizes a dT4 sequence as stop signal, however in Rajiformes this signal was doubled in length to dT8. This could be an adaptation toward a higher efficiency in the termination process. Our results suggest that there is no TATA box in elasmobranchs in the NTS region. We also provide some evidence suggesting that the complexity of the microsatellites present in the NTS region play an important role in the 5S rRNA gene since it is significantly correlated with the length of the NTS.

Extensive Mandibular Ameloblastic Fibro-Odontoma.

Ameloblastic fibro-odontoma (AFO) is a mixed odontogenic tumor that presents epithelial and mesenchymal components. Ameloblastic fibro-odontoma is generally diagnosed between the first and second decades of life and normally shows a slow clinical growth in the posterior portion of the maxilla or mandible, being mostly associated with 1 or more impacted teeth. Radiographic features of AFO show a radiolucent well-defined, uni, or multilocular defect due to containing variable amounts of calcified material. The enucleation of the tumor is the usual conduct and should be followed up for a long period of time. Here, the authors report the case of 17-year-old male patient who presented an extensive AFO on the right posterior side of the mandible. The panoramic radiograph and the tomographic examination revealed a multilocular radiolucent lesion with impacted teeth. Histological examination revealed connective tissue resembling the dental papilla along with epithelial strands or islands, as well as dental hard tissue such enamel and dentin. Enucleation and curettage was performed and led to good outcome. There was no recurrence after an 8-year follow-up, and oral rehabilitation was performed with dental implants.

Amantadine as an Aid to Extubation in Severe Acute Brain Injury: A Case Series.

For a subset of patients with severe acute brain injury (SABI) undergoing invasive mechanical ventilation, the primary barrier to successful extubation is depressed mental status. Amantadine is a neurostimulant that has been demonstrated to increase arousal and improve functional outcomes in patients with SABI. In this case series, we describe 5 patients with SABI and invasive mechanical ventilation who received amantadine as an agent to improve mental status to allow extubation. The primary barrier to extubation for all patients was depressed mental status. Median age was 77 (range 32 to 82). Primary diagnoses were ischemic stroke (n = 1), subdural hemorrhage (n = 2), intracerebral hemorrhage (n = 1), and traumatic brain injury (n = 1). Median Glasgow Coma Score was 7T prior to administration of amantadine and 10T on the day after amantadine was initiated, with improvements in eye-opening and motor response. Four patients displayed improvement in arousal and attention and were successfully extubated 1 to 4 days after initiation of amantadine (median 2 days). The fifth patient only displayed marginal improvement in mental status after starting amantadine, but was ultimately able to be extubated 7 days later. Amantadine may improve the likelihood of or reduce the time to successful extubation in patients with SABI.

Mass Spectrometry as Alternative Method to Identify and Monitor Non-Secretory Progressive Disease in Patients with Multiple Myeloma.

INTRODUCTION: After receiving different lines of treatment, multiple myeloma patients tend to present with less secretory and more frequent extramedullary disease. These features make treatment monitoring and follow-up very complex since they have to be based on the use of imaging methods and/or bone marrow aspirations or biopsies. OBJECTIVE: To present the case of a patient with myeloma progressing with non-secretory bone disease and to discuss the potential impact of mass spectrometry as a new highly sensitive method able to identify the monoclonal protein (MP) in the serum of these types of patients. MATERIALS AND METHODS: Informed consent was signed by the patient prior to receiving each line of treatment. The clinical information and images were obtained from anonymized electronic files. The mass spectrometry was performed with the Immunoglobulin Isotypes (GAM) assay for the mass spectrometry EXENT® Analyser Technology from Binding Site, part of Thermofisher. RESULTS: A 73-year-old male with IgG kappa multiple myeloma progressing with a new lytic lesion after receiving 14 cycles of Talquetamab as a third line of therapy who, due to the non-secretory nature of the disease at this point, could not be enrolled in a clinical trial, thus limiting his therapeutic options. The mass spectrometry was able to identify and quantify the presence of the patient's MP when the serum protein electrophoresis and immunofixation were still negative and therefore could have been used to confirm the progression, to permit the inclusion of the patient in a clinical trial and to further monitor the disease response. CONCLUSIONS: The higher sensitivity of the mass spectrometry methods to detect the MP in patients with myeloma and other monoclonal gammopathies translates into better identification of the disease progression, permits the inclusion of more patients in clinical trials and facilitates treatment monitoring.