Micro-CT evaluation of the presence of voids in endodontic obturation.

Identifying the presence, size, type and location of voids in an endodontic obturation is of great clinical importance because it enables evaluation of the three-dimensionality of the sealing techniques, which can be related to the success of the endodontic treatment. AIM: To analyze by micro-CT the presence of voids in lower single-rooted premolar root canal obturations prepared using the single cone and ultrasound vibration technique. MATERIALS AND METHODS: Twenty extracted single-rooted lower premolars were selected, and the root canal prepared surgically and chemically. In GROUP 1 - Without Vibration, the canal was obturated with a single cone and bioceramic, without applying vibration. In GROUP 2 - With Vibration, the gutta-percha cone inside the root canal was held with a cotton plier to which ultrasound vibration was applied for 3 periods of 3 seconds each. A micro-CT scanner was used to acquire and reconstruct images for analysis. RESULTS: No significant difference was found between obturation techniques, though there were differences between thirds, with the cervical third having a higher percentage of voids than the middle and apical thirds. CONCLUSIONS: The results suggest that the volume of closed, open and total voids does not differ between treatments with and without ultrasound vibration. In the cervical third, the highest volume of voids was related to oval geometry in the teeth evaluated.

La presencia de vacíos en la obturación endodóntica, su tamaño y el tipo y localización tiene gran importancia clínica ya que permite evaluar la tridimensionalidad de las técnicas de sellado y relacionarlas con el éxito del tratamiento endodóntico. OBJETIVO: analizar mediante microtomografía la presencia de vacíos en la obturación del conducto radicular de premolares inferiores unirradiculares, utilizando la técnica de cono único y vibración con ultrasonido. MATERIALES Y MÉTODOS: se seleccionaron 20 premolares inferiores unirradiculares a los que se les realizó la preparación quirúrgica y química del conducto radicular. Se realizó la obturación con cono único y biocerámico GRUPO 1- sin vibración. En el GRUPO 2 - con vibración se aplicó vibración por ultrasonido, se tomó del cono de gutapercha colocado en el interior del conducto con pinza de algodón que fue vibrada durante 3 períodos de 3 segundos cada uno. Las mismas fueron adquiridas y reconstruidas en un microtomógrafo para posterior análisis de las imágenes obtenidas. RESULTADOS: No se evidenciaron diferencias significativas entre ambas técnicas de obturación comparadas, pero si entre los tercios analizados, siendo el cervical el que mayor porcentaje de vacíos presenta en comparación a los cortes correspondientes al tercio medio y apical. CONCLUSIONES: Los resultados sugieren que el volumen de vacíos cerrados, abiertos y total no varía en los tratamientos donde se aplica vibración por ultrasonido. En el tercio cervical, el mayor volumen de vacíos se relaciona con la geometría oval que presentaron las piezas dentarias evaluadas en este estudio.

Student training in administering inferior alveolar nerve block anesthesia with a simple manufactured simulation model.

OBJECTIVE: To compare the effectiveness of administering inferior alveolar nerve blocks (IANB) for the first time with or without a previous practical lesson using a simple manufactured simulator. METHODS: This was a study designed to compare students' first administration of IANB anesthesia during 2022, with or without a previous practical lesson. Students were randomized into two groups. The experimental group attended both theoretical lessons and a practical lesson with a simulator device, while the control group attended only theoretical lessons. The theoretical lesson included usual contents such as anatomy, physiology, technical maneuvers for administering anesthesia, tips, and complications, and the practical lesson consisted of the administration of anesthesia using a simple manufactured simulator. After students applied their first IANB, its efficacy, and their answers to a questionnaire on a 5-point Likert scale were recorded. Statistical analysis consisted of the Chi-square test (p < 0.05). RESULTS: The study recorded 60 anonymous surveys. The main difference observed was in instrument handing (p < 0.05), and there was a tendency in the ease of recognition of the anatomical marks used for the technique-pterygomandibular raphe and coronoid notch of the mandible (p = 0.08 and 0.11, respectively). No difference in success was observed (p > 0.05). Self-confidence and personal feelings did not differ statistically. All students agreed strongly or partially that training with the simulator model was helpful. CONCLUSION: Students who used simple manufactured simulators achieved better outcomes for instrument handling, and possibly for identification of anatomical landmarks, than those who received only theoretical lessons.

Type III aortic arch angulation increases aortic stiffness: Analysis from an ex vivo porcine model.

Objective: The relationship among increased aortic arch angulation, aortic flow dynamics, and vessel wall stiffness remains unclear. This experimental ex vivo study investigated how increased aortic arch angulation affects aortic stiffness and stent-graft induced aortic stiffening, assessed by pulse wave velocity (PWV). Methods: Porcine thoracic aortas were connected to a circulatory mock loop in a Type I and Type III aortic arch configuration. Baseline characteristics and blood pressures were measured. Proximal and distal flow curves were acquired to calculate PWV in both arch configurations. After that, a thoracic stent-graft (VAMF2626C100TU) was deployed in aortas with adequate proximal landing zone diameters to reach 10% t0 20% oversizing. Acquisitions were repeated for both arch configurations after stent-graft deployment. Results: Twenty-four aortas were harvested, surgically prepared, and mounted. Cardiac output was kept constant for both arch configurations (Type I: 4.74 ± 0.40 and Type III: 4.72 ± 0.38 L/minute; P = .703). Compared with a Type I arch, aortic PWV increased significantly in the Type III arch (3.53 ± 0.40 vs 3.83 ± 0.40 m/second; P < .001), as well as blood pressures. A stent-graft was deployed in 15 aortas. After deployment, Type I arch PWV increased (3.55 ± 0.39 vs 3.81 ± 0.44 m/second; P < .001) and Type III arch PWV increased although not significantly (3.86 ± 0.42 vs 4.03 ± 0.46 m/second; P = .094). Type III arch PWV resulted the highest and significantly higher compared with the Type I arch after stent-graft deployment (3.81 ± 0.44 vs 4.03 ± 0.46 m/second; P = .023). Conclusions: Increased aortic arch angulation-as in a Type III arch-is associated with higher aortic PWV and blood pressures and this may negatively influence cardiovascular health.

Paleoneurology and neuroanatomical notes on the South American "rauisuchian" Saurosuchus galilei from the Ischigualasto formation, San Juan, Argentina.

Non-crocodylomorph loricatans, traditionally known as "rauisuchians," are considered as the top predators of the Triassic continental faunas that reigned before the emergence of the well-known theropod dinosaurs. In particular, Saurosuchus galilei is a large quadrupedal prestosuchid loricatan found in the Ischigualasto Formation from northwestern Argentina. Here, we reevaluated the braincase of S. galilei and present the first paleoneurological study based on the partial natural casts of the holotype and the digital cranial endocast of the referred specimen PVSJ 32. The braincase of S. galilei was here reinterpreted, identifying the sutures of the supraoccipital, otoccipital, basioccipital, parabasisphenoid, prootic, and laterosphenoid. A unique feature identified in the braincase of S. galilei is the presence of deep paracondylar recesses associated with pharyngotympanic pneumaticity, which has not been identified in any other "rauisuchians" so far. Most of the structures of the encephalon were recognized in the cranial endocast and natural casts including cranial nerves V-XII, olfactory bulbs, main blood vessels and sinuses, and inner ear. These structures allowed us to quantify some of its sensorial capacities and recognize that S. galilei had an enhanced olfactory acuity, with coefficients higher than those expected for its body size, a condition previously observed in living crocodilians and tyrannosaurid dinosaurs. An improved sense of smell might have allowed Saurosuchus to track its prey from long distances and compensate for the poorer development of its other senses like vision and balance.

NUAK1 coordinates growth factor-dependent activation of mTORC2 and Akt signaling.

BACKGROUND: mTORC2 is a critical regulator of cytoskeleton organization, cell proliferation, and cancer cell survival. Activated mTORC2 induces maximal activation of Akt by phosphorylation of Ser-473, but regulation of Akt activity and signaling crosstalk upon growth factor stimulation are still unclear. RESULTS: We identified that NUAK1 regulates growth factor-dependent activation of Akt by two mechanisms. NUAK1 interacts with mTORC2 components and regulates mTORC2-dependent activation of Akt by controlling lysosome positioning and mTOR association with this organelle. A second mechanism involves NUAK1 directly phosphorylating Akt at Ser-473. The effect of NUAK1 correlated with a growth factor-dependent activation of specific Akt substrates. NUAK1 induced the Akt-dependent phosphorylation of FOXO1/3a (Thr-24/Thr-32) but not of TSC2 (Thr-1462). According to a subcellular compartmentalization that could explain NUAK1's differential effect on the Akt substrates, we found that NUAK1 is associated with early endosomes but not with plasma membrane, late endosomes, or lysosomes. NUAK1 was required for the Akt/FOXO1/3a axis, regulating p21CIP1, p27KIP1, and FoxM1 expression and cancer cell survival upon EGFR stimulation. Pharmacological inhibition of NUAK1 potentiated the cell death effect induced by Akt or mTOR pharmacological blockage. Analysis of human tissue data revealed that NUAK1 expression positively correlates with EGFR expression and Akt Ser-473 phosphorylation in several human cancers. CONCLUSIONS: Our results showed that NUAK1 kinase controls mTOR subcellular localization and induces Akt phosphorylation, demonstrating that NUAK1 regulates the growth factor-dependent activation of Akt signaling. Therefore, targeting NUAK1, or co-targeting it with Akt or mTOR inhibitors, may be effective in cancers with hyperactivated Akt signaling.

Lumped-parameter model as a non-invasive tool to assess coronary blood flow in AAOCA patients.

Anomalous aortic origin of the coronary artery (AAOCA) is a rare disease associated with sudden cardiac death, usually related to physical effort in young people. Clinical routine tests fail to assess the ischemic risk, calling for novel diagnostic approaches. To this aim, some recent studies propose to assess the coronary blood flow (CBF) in AAOCA by computational simulations but they are limited by the use of data from literature retrieved from normal subjects. To overcome this limitation and obtain a reliable assessment of CBF, we developed a fully patient-specific lumped parameter model based on clinical imaging and in-vivo data retrieved during invasive coronary functional assessment of subjects with AAOCA. In such a way, we can estimate the CBF replicating the two hemodynamic conditions in-vivo analyzed. The model can mimic the effective coronary behavior with high accuracy and could be a valuable tool to quantify CBF in AAOCA. It represents the first step required to move toward a future clinical application with the aim of improving patient care. The study was registered at Clinicaltrial.gov with (ID: NCT05159791, date 2021-12-16).

Unveiling the Configurational Landscape of Carbamate: Paving the Way for Designing Functional Sequence-Defined Polymers.

Carbamate is an emerging class of a polymer backbone for constructing sequence-defined, abiotic polymers. It is expected that new functional materials can be de novo designed by controlling the primary polycarbamate sequence. While amino acids have been actively studied as building blocks for protein folding and peptide self-assembly, carbamates have not been widely investigated from this perspective. Here, we combined infrared (IR), vibrational circular dichroism (VCD), and nuclear magnetic resonance (NMR) spectroscopy with density functional theory (DFT) calculations to understand the conformation of carbamate monomer units in a nonpolar, aprotic environment (chloroform). Compared with amino acid building blocks, carbamates are more rigid, presumably due to the extended delocalization of π-electrons on the backbones. Cis configurations of the amide bond can be energetically stable in carbamates, whereas peptides often assume trans configurations at low energies. This study lays an essential foundation for future developments of carbamate-based sequence-defined polymer material design.

Subtle hydrogen bond preference and dual Franck-Condon activity - the interesting pairing of 2-naphthol with anisole.

The hydrogen-bonded complexes between 2-naphthol (or ß-naphthol) and anisole are explored by detecting their IR absorption in the OH stretching range as well as their UV absorption by means of laser-induced fluorescence and resonance-enhanced two-photon UV ionisation. For the more stable cis and the metastable trans conformations of the OH group in 2-naphthol, hydrogen bonding to the oxygen atom of anisole is consistently detected in different supersonic jet expansions. Alternative hydrogen bonding to the aromatic ring of anisole remains elusive, although the majority of state-of-the-art hybrid DFT functionals with London dispersion correction and - less surprisingly - MP2 wavefunction theory predict it to be slightly more stable at zero-point level, unless three-body dispersion correction is added to the B3LYP-D3(BJ) approach. This changes at the CCSD(T) level, which forecasts an energy advantage of 1-3 kJ mol-1 for the classical hydrogen bond arrangement even after including (DFT) zero-point energy contributions. The UV and IR spectra of the cis complex exhibit clear evidence for intensity redistribution of the primary OH stretch oscillator to combination states with the same low-frequency intermolecular bending mode by Franck-Condon-type vertical excitation mechanisms. This rare case of dual (vibronic and vibrational) Franck-Condon activity of a low-frequency mode invites future studies of homologues where aromatic ring docking of the OH group may be further stabilised, e.g. through anisole ring methylation.

To care for them, we need to take care of ourselves: A qualitative study on the health of home health aides.

OBJECTIVE: To understand the perspectives of home health aides (HHAs) toward their own health and health behaviors, and how their job impacts both. DATA SOURCES AND STUDY SETTING: Interviews were conducted with 28 HHAs from 16 unique home care agencies from August 2021 to January 2022. The study was conducted in partnership with the 1199SEIU Training and Employment Fund, a labor-management fund of the largest health care union in the US. STUDY DESIGN: A qualitative study with English and Spanish-speaking HHAs. Interviews were conducted using a semi-structured topic guide, informed by Pender's Health Promotion Model and the National Institute for Occupational Safety and Health's Total Worker Health Model. To be eligible, HHAs had to be currently employed by a home care agency in New York, NY. DATA COLLECTION/EXTRACTION METHODS: Interviews were recorded, professionally transcribed, and analyzed thematically. PRINCIPAL FINDINGS: The 28 HHAs had a mean age of 47.6 years (SD 11.1), 39% were non-Hispanic Black, 43% were Hispanic, and they had a mean of 14.1 years (SD 7.8) of job experience. Five themes emerged; HHAs were: (1) Healthy enough to work, but were managing their own chronic conditions while working; (2) Motivated to be healthy, in part driven by their desire to care for others; (3) Worked closely with sick patients, which influenced their perceptions of health; (4) Experienced occupational and patient-level barriers to practicing healthy behaviors; (5) Sought support and resources to improve their health and wellbeing. CONCLUSIONS: HHAs have numerous health challenges, many of which are influenced by their job. Culturally and occupationally tailored interventions may mitigate the barriers that HHAs experience to achieve optimal health.

C-shaped Canal System in Maxillary Molars Evaluated by Cone- Beam Computed Tomography in an Argentine subpopulation / Conductos en C en molares superiores evaluados mediante tomografía cone-beam en una sub-población Argentina

ABSTRACT The aim of the present study was to evaluate the presence of maxillary first and second molars with a C-shaped canal system in an Argentine subpopulation, and to classify them. Materials and Method: Of the 332 CBCTs initially evaluated, 120 met the selection criteria. Once the presence of a C-shaped canal system had been established, the teeth were classified following Martins et al. Data were expressed as absolute frequencies, percentages with of 95% confidence intervals, according to the score test. Comparisons were analyzed by Chi-square test and Fisher' exact test, with 5% significance level. Results: It was found that 5 out of 120 first molars (4%) and 17 out of 152 second molars (11%) had a C-shaped canal system. Regarding the classification applied, of 5 C-shaped first molars, 2 corresponded to type E2 (40%), 2 corresponded to type C (40%), and 1 corresponded to type B1 (20%). Of 17 C-shaped second molars, 4 resembled a type A (24%), 7 resembled a type B1 (41%), 5 resembled a type B2 (29%), and 1 resembled a type C (6%). UC1 and UC2 configurations were the most common at all levels except apical level. Conclusion: The prevalence of C-shaped canal system pattern in maxillary first and second molars was estimated for the first time in an Argentine subpopulation, in vivo. Knowledge of these data should help clinicians during endodontic treatment.

RESUMEN El objetivo del presente estudio fue evaluar la presencia de conductos en C en primeros y segundos molares superiores, en una subpoblación de Argentina. Materiales y Método: Se observaron 332 CBCTs, de las cuales 120 cumplieron los criterios de selección. Una vez determinada la presencia de conducto en C se clasificaron según Martins et al. Los datos fueron descriptos mediante frecuencias absolutas y porcentajes, con intervalos de confianza al 95% (IC95), según método score. Las comparaciones fueron analizadas mediante la prueba de Chi-cuadrado o exacta de Fisher con un nivel de significación del 5%. Resultados: De 120 primeros molares, 5 presentaron conductos en C, es decir un 4% y de 152 segundos molares, 17 presentaron conductos en C, es decir un 11%. Según la clasificación aplicada, de 5 primeros molares en C, 2 correspondieron al tipo E2 (40%), 2 al tipo C (40%) y 1 al tipo B1 (20%). De 17 segundos molares en C, 4 pertenecieron al tipo A (24%), 7 al tipo B1 (41%), 5 al tipo B2 (29%) y 1 al tipo C (6%). Las clasificaciones UC1 y UC2 fueron las más representativas en todos los niveles, excluyendo el tercio apical. Conclusión: La prevalencia de conductos en C en primeros y segundos molares superiores, fue estimada por primera vez en una subpoblación Argentina, in vivo. Los datos obtenidos en el presente estudio, resultan de interés para el abordaje de los tratamientos endodónticos.

Resource-dependent investment in male sexual traits in a viviparous fish.

Exaggerated and conspicuous sexually selected traits are often costly to produce and maintain. Costly traits are expected to show resource-dependent expression, since limited resources prevent animals from investing maximally in multiple traits simultaneously. However, there may be critical periods during an individual's life where the expression of traits is altered if resources are limited. Moreover, costly sexual traits may arise from sexual selection acting both before (pre-copulatory) and after mating (post-copulatory). Gaining a robust understanding of resource-dependent trait expression therefore requires an approach that examines both episodes of sexual selection after resource limitation during different times in an individual's life. Yet few studies have taken such an approach. Here, we examine how resource restriction influences a set of pre- and post-copulatory traits in male pygmy halfbeaks (Dermogenys collettei), which invest in sexual ornaments and routinely engage in male-male contests and sperm competition. Critically, we examined responses in males when resources were restricted during development and after reaching sexual maturity. Both pre- and post-copulatory traits are resource-dependent in male halfbeaks. Body size, beak size, courtship behavior, and testes size were reduced by diet restriction, while, unexpectedly, the restricted-diet group had a larger area of red color on the beak and fins after diet treatment. These patterns were generally consistent when resources were restricted during development and after reaching sexual maturity. The study reinforces the role of resource acquisition in maintaining variation among sexual traits.

Development and Piloting of a Community-Partnered Heart Failure Training Course for Home Health Care Workers.

BACKGROUND: Despite their unique contributions to heart failure (HF) care, home healthcare workers (HHWs) have unmet educational needs and many lack HF caregiving self-efficacy. To address this, we used a community-partnered approach to develop and pilot a HF training course for HHWs. METHODS: We partnered with the Training and Employment Fund, a benefit fund of the largest healthcare union in the United States, to develop a 2-hour virtual HF training course that met HHWs' job-specific needs. English and Spanish-speaking HHWs interested in HF training, with access to Zoom, were eligible. We used a mixed methods design with pre/postsurveys and semi-structured interviews to evaluate the course: (a) feasibility, (b) acceptability, and (c) effectiveness (change in knowledge [Dutch Heart Failure Knowledge Scale range 0-15] and caregiving self-efficacy [HF Caregiver Self-efficacy Scale range 0-100]). RESULTS: Of the 210 HHWs approached, 100 were eligible and agreed, and 70 enrolled. Of them, 53 (employed by 15 different home care agencies) participated. Posttraining data showed significant improvements (pretraining mean [SD] versus posttraining mean [SD]; P value) in HF knowledge (11.21 [1.90] versus 12.21 [1.85]; P=0.0000) and HF caregiving self-efficacy (75.21 [16.57] versus 82.29 [16.49]; P=0.0017); the greatest gains occurred among those with the lowest pre-training scores. Participants found the course engaging, technically feasible, and highly relevant to their scope of care. CONCLUSIONS: We developed and piloted the first HF training course for HHWs, which was feasible, acceptable, and improved their HF knowledge and caregiving self-efficacy. Our findings warrant scalability to the workforce at large with a train-the-trainer model.

The Sall2 transcription factor promotes cell migration regulating focal adhesion turnover and integrin ß1 expression.

SALL2/Sall2 is a transcription factor associated with development, neuronal differentiation, and cancer. Interestingly, SALL2/Sall2 deficiency leads to failure of the optic fissure closure and neurite outgrowth, suggesting a positive role for SALL2/Sall2 in cell migration. However, in some cancer cells, SALL2 deficiency is associated with increased cell migration. To further investigate the role of Sall2 in the cell migration process, we used immortalized Sall2 knockout (Sall2 -/- ) and Sall2 wild-type (Sall2 +/+ ) mouse embryonic fibroblasts (iMEFs). Our results indicated that Sall2 positively regulates cell migration, promoting cell detachment and focal adhesions turnover. Sall2 deficiency decreased cell motility and altered focal adhesion dynamics. Accordingly, restoring Sall2 expression in the Sall2 -/- iMEFs by using a doxycycline-inducible Tet-On system recovered cell migratory capabilities and focal adhesion dynamics. In addition, Sall2 promoted the autophosphorylation of Focal Adhesion Kinase (FAK) at Y397 and increased integrin ß1 mRNA and its protein expression at the cell surface. We demonstrated that SALL2 increases ITGB1 promoter activity and binds to conserved SALL2-binding sites at the proximal region of the ITGB1 promoter, validated by ChIP experiments. Furthermore, the overexpression of integrin ß1 or its blockade generates a cell migration phenotype similar to that of Sall2 +/+ or Sall2 -/- cells, respectively. Altogether, our data showed that Sall2 promotes cell migration by modulating focal adhesion dynamics, and this phenotype is associated with SALL2/Sall2-transcriptional regulation of integrin ß1 expression and FAK autophosphorylation. Since deregulation of cell migration promotes congenital abnormalities, tumor formation, and spread to other tissues, our findings suggest that the SALL2/Sall2-integrin ß1 axis could be relevant for those processes.

Fertilization mode differentially impacts the evolution of vertebrate sperm components.

Environmental change frequently drives morphological diversification, including at the cellular level. Transitions in the environment where fertilization occurs (i.e., fertilization mode) are hypothesized to be a driver of the extreme diversity in sperm morphology observed in animals. Yet how fertilization mode impacts the evolution of sperm components-head, midpiece, and flagellum-each with different functional roles that must act as an integrated unit remains unclear. Here, we test this hypothesis by examining the evolution of sperm component lengths across 1103 species of vertebrates varying in fertilization mode (external vs. internal fertilization). Sperm component length is explained in part by fertilization mode across vertebrates, but how fertilization mode influences sperm evolution varies among sperm components and vertebrate clades. We also identify evolutionary responses not influenced by fertilization mode: midpieces evolve rapidly in both external and internal fertilizers. Fertilization mode thus influences vertebrate sperm evolution through complex component- and clade-specific evolutionary responses.

Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma.

Idecabtagene vicleucel (ide-cel) was FDA-approved in March 2021 for the treatment of relapsed/refractory multiple myeloma after 4 lines of therapy. On the KarMMa trial, grade ≥ 3 cytopenias and infections were common. We sought to characterize cytopenias and infections within 100 days after ide-cel in the standard-of-care (SOC) setting. This multi-center retrospective study included 52 patients who received SOC ide-cel; 47 reached day-90 follow-up. Data were censored at day 100. Grade ≥ 3 cytopenia was present among 65% of patients at day 30 and 40% of patients at day 90. Granulocyte colony stimulating factor (G-CSF) was administered to 88%, packed red blood cell transfusions to 63%, platelet transfusions to 42%, thrombopoietin (TPO) agonists to 21%, intravenous immunoglobulin to 13%, and CD34+ stem cell boosts to 8%. At day 100, 19% and 13% of patients had ongoing use of TPO agonists and G-CSF, respectively. Infections occurred in 54% of patients and were grade ≥ 3 in 23%. Earlier infections in the first 30 days were typically bacterial (68%) and severe (50%). Later infections between days 31 and 100 were 50% bacterial and 42% viral; only 13% were grade ≥ 3. On univariate analysis, high pre-CAR-T marrow myeloma burden (≥ 50%), circulating plasma cells at pre-lymphodepletion (LD), and grade ≥ 3 anemia at pre-LD were associated with grade ≥ 3 cytopenia at both days 30 and 90. Longer time from last bridging treatment to LD was the only significant risk factor for infection.

Echocardiographic Measurements of Left Heart Chamber Size in a Large Cohort of Subjects: Comparison of Body Surface Area and Height Indexing to Account for Effects of Obesity.

BACKGROUND: The assessment of cardiac chamber size in the obese population is a challenging subject. Values usually indexed to body surface area (BSA) are smaller in obese subjects and prone to overcorrection. The aims of this study were to find reference thresholds to account for the effects of obesity among a large cohort of patients and to evaluate indexing to height as an alternative to BSA. METHODS: The past 10 years of records from a single echocardiography unit were retrospectively analyzed, and 14,007 subjects without known cardiac disease were included (mean age, 45 ± 15 years; 54% women; 20% obese). Measurements included left atrial diameter, area, and volume, left ventricular (LV) end-diastolic and end-systolic diameters, aortic root diameter, and LV mass. Absolute, BSA-indexed, and height-indexed maximum thresholds (mean + 1.96 SDs) were calculated. Allometric indexing of the form variable/heightß was tested. Correlation coefficients between indexed and absolute values were calculated to evaluate their proportional association (ideally r = 1). Correlations between indexed values and body size represented residual associations to be minimized (ideally r = 0). RESULTS: The strongest association of echocardiographic measurements with body size was observed for BSA (r = 0.36-0.63), whereas the isometric and allometric height models showed lower comparable values (r = 0.28-0.48). Positive correlations with body mass index were mostly observed for left atrial size (r ≈ 0.36) and LV mass (r ≈ 0.36) measurements. Values of the scaling exponent ß for allometric height indexing were 1.72 for left atrial volume and 2.33 for LV mass. Correlations between indexed and absolute values were higher for height than BSA (0.80-0.98 vs 0.44-0.92). Correlations between indexed values and height were closer to 0 than for BSA, particularly using the allometric model. The overcorrection observed with increasing obesity class after BSA indexing was avoided after height indexing. CONCLUSIONS: Unlike BSA, height indexing provided adequate body size scaling of left heart chamber size, avoiding overcorrection using allometric models in particular.

Secondary structure prediction of long noncoding RNA: review and experimental comparison of existing approaches.

MOTIVATION: In contrast to messenger RNAs, the function of the wide range of existing long noncoding RNAs (lncRNAs) largely depends on their structure, which determines interactions with partner molecules. Thus, the determination or prediction of the secondary structure of lncRNAs is critical to uncover their function. Classical approaches for predicting RNA secondary structure have been based on dynamic programming and thermodynamic calculations. In the last 4 years, a growing number of machine learning (ML)-based models, including deep learning (DL), have achieved breakthrough performance in structure prediction of biomolecules such as proteins and have outperformed classical methods in short transcripts folding. Nevertheless, the accurate prediction for lncRNA still remains far from being effectively solved. Notably, the myriad of new proposals has not been systematically and experimentally evaluated. RESULTS: In this work, we compare the performance of the classical methods as well as the most recently proposed approaches for secondary structure prediction of RNA sequences using a unified and consistent experimental setup. We use the publicly available structural profiles for 3023 yeast RNA sequences, and a novel benchmark of well-characterized lncRNA structures from different species. Moreover, we propose a novel metric to assess the predictive performance of methods, exclusively based on the chemical probing data commonly used for profiling RNA structures, avoiding any potential bias incorporated by computational predictions when using dot-bracket references. Our results provide a comprehensive comparative assessment of existing methodologies, and a novel and public benchmark resource to aid in the development and comparison of future approaches. AVAILABILITY: Full source code and benchmark datasets are available at: https://github.com/sinc-lab/lncRNA-folding. CONTACT: lbugnon@sinc.unl.edu.ar.

Detection by multiplex PCR of Mycoplasma species associated with dairy cattle in Argentina / Detección por PCR multiplex de especies de Mycoplasma asociadas a ganado lecheroen Argentina

Abstract There is scarce information about the frequency and epidemiological and clinicalfeatures associated with the presence of Mycoplasma spp. in Argentine dairy herds. The objec-tives of this study were to develop a multiplex PCR for identifying M. bovis and M. canadenseand to describe the frequency of Mycoplasma spp. isolated from clinical samples submitted to adiagnostic laboratory. Of a total of 1548 samples from intramammary infections, bulk tank milkand biological fluids, 38 Mycoplasma isolates were obtained. M. bovis, M. canadense, M. cali-fornicum and M. leachii were detected by using two multiplex PCRs, confirming their presencein clinical conditions in dairy cattle. The techniques used in the present study can be usefulto broaden the knowledge about Mycoplasma infections in cattle, since the search for theseorganisms is not usually included in routine diagnoses.

Resumen Existe poca información sobre la frecuencia, así como las características epidemi-ológicas y clínicas asociadas con la presencia de Mycoplasma en los rodeos lecheros argentinos.Los objetivos de este estudio fueron desarrollar una PCR multiplex para identificar M. bovis yM. canadense y describir la frecuencia de especies de Mycoplasma aisladas de muestras clíni-cas enviadas a un laboratorio de diagnóstico. De un total de 1.548 muestras de infeccionesintramamarias, leche de tanque de frío y fluidos biológicos, se obtuvieron 38 aislamientos de Mycoplasma. Mediante 2 PCR multiplex se detectaron M. bovis, M. canadense, M. californicumy M. leachii, confirmando su presencia en síndromes clínicos en ganado lechero. Las técnicasutilizadas en el presente estudio pueden ser útiles para ampliar el conocimiento sobre las infec-ciones por Mycoplasma en bovinos, ya que la búsqueda de estos organismos no suele incluirseen los diagnósticos de rutina.