Cystatin C and Creatinine Concentrations Are Uninformative Biomarkers of Sarcopenia: A Cross-Sectional NHANES Study.

OBJECTIVES: Differences in creatinine and cystatin C-based estimates of glomerular filtration rate (eGFRDiff = eGFRCr - eGFRCysC) may reflect differences in muscle mass. We sought to determine if eGFRDiff (1) reflects lean mass, (2) identifies sarcopenic individuals beyond estimates based on age, body mass index (BMI), and sex; and (3) demonstrates associations differently in those with and without chronic kidney disease (CKD). DESIGN AND METHODS: This cross-sectional study included 3,754 participants, ages 20-85 years, with creatinine and cystatin C concentration levels, and dual-energy X-ray absorptiometry scans from National Health and Nutrition Examination Survey data (1999-2006). Dual-energy X-ray absorptiometry-derived appendicular lean mass index (ALMI) estimated muscle mass. Non-race-based CKD Epidemiology Collaboration equations estimated glomerular filtration rate using eGFRCr, eGFRCysC, and both biomarkers (eGFRCysC&Cr). CKD was defined as eGFRCysC&Cr <60 mL/minute/1.73 m2. ALMI sex-specific T-scores (compared with young adult) < -2.0 defined sarcopenia. In estimating ALMI, we compared the coefficient of determination (R2) values from: 1) eGFRDiff, 2) clinical characteristics (age, BMI, and sex), and 3) clinical characteristics plus eGFRDiff. Using logistic regression, we evaluated each model's C-statistic to diagnose sarcopenia. RESULTS: eGFRDiff was negatively and weakly associated with ALMI (No CKD: R2 = 0.006, p-value 0.002; CKD: R2 = 0.001, P value .9). Clinical characteristics explained most of the variation in ALMI (No CKD: R2 = 0.851, CKD: R2 = 0.828), and provided strong discrimination of sarcopenia (No CKD C-statistic: 0.950; CKD C-statistic: 0.943). Adding eGFRDiff improved the R2 by 0.025, and the C-statistic by 0.003. Tests for interaction between eGFRDiff and CKD were not significant (all P values > .05). CONCLUSIONS: Although eGFRDiff has statistically significant associations with ALMI and sarcopenia in univariate analyses, multivariate analyses demonstrate that eGFRDiff does not capture more information beyond routine clinical characteristics (age, BMI, and sex).

Low variability of plant protein intake in the CKiD cohort does not demonstrate changes in estimated GFR nor electrolyte balance.

BACKGROUND: Vegetable or plant-based sources of protein may confer health benefits in children with progressive kidney disease. Our aims were to understand the effect of the proportion of vegetable protein intake on changes in estimated GFR and to understand the effect of the proportion of vegetable protein intake on serum levels of bicarbonate, phosphorus, and potassium. METHODS: Children with baseline eGFR between 30 and 90 mL/min/1.73 m2 were recruited from 59 centers across North America as part of the chronic kidney disease in children (CKiD) study. The percentage of dietary vegetable protein (VP%) was gathered from annual Food Frequency Questionnaires. We performed longitudinal linear mixed models to determine the effect of VP% on eGFR and longitudinal logistic mixed models to determine the effect of VP% on electrolyte balance (potassium, phosphorus, bicarbonate). RESULTS: Two thousand visits from 631 subjects. Across all dichotomized groups of children (sex, African American race, Hispanic ethnicity, glomerular etiology of CKD, hypertension, anemia, hyperkalemia, hyperphosphatemia, acidosis, BMI < 95th percentile), the median VP% was 32-35%. The longitudinal mixed model analysis did not show any effect of VP% on eGFR electrolyte (bicarbonate, phosphorus, and potassium) abnormalities (p > 0.1). CONCLUSIONS: A diverse cohort of children with CKD has a narrow and homogeneous intake of vegetable protein. Due to the low variability of plant-based protein in the cohort, there were no associations between the percentage of plant protein intake and changes in eGFR nor electrolyte balance. A higher resolution version of the Graphical abstract is available as Supplementary information.

Relaxation Dispersion NMR to Reveal Fast Dynamics in Brønsted Acid Catalysis: Influence of Sterics and H-Bond Strength on Conformations and Substrate Hopping.

NMR provides both structural and dynamic information, which is key to connecting intermediates and to understanding reaction pathways. However, fast exchanging catalytic intermediates are often inaccessible by conventional NMR due its limited time resolution. Here, we show the combined application of the 1H off-resonance R1ρ NMR method and low temperature (185-175 K) to resolve intermediates exchanging on a µs time scale (ns at room temperature). The potential of the approach is demonstrated on chiral phosphoric acid (CPA) catalysts in their complexes with imines. The otherwise inaccessible exchange kinetics of the E-I ⇌ E-II imine conformations and thermodynamic E-I:E-II imine ratios inside the catalyst pocket are experimentally determined and corroborated by calculations. The E-I ⇌ E-II exchange rate constants (kex185 K) for different catalyst-substrate binary complexes varied between 2500 and 19 000 s-1 (τex = 500-50 µs). Theoretical analysis of these exchange rate constants revealed the involvement of an intermediary tilted conformation E-III, which structurally resembles the hydride transfer transition state. The main E-I and E-II exchange pathway is a hydrogen bond strength dependent tilting-switching-tilting mechanism via a bifurcated hydrogen bond as a transition state. The reduction in the sterics of the catalyst showed an accelerated switching process by at least an order of magnitude and enabled an additional rotational pathway. Hence, the exchange process is mainly a function of the intrinsic properties of the 3,3'-substituents of the catalyst. Overall, we believe that the present study opens a new dimension in catalysis via experimental access to structures, populations, and kinetics of catalyst-substrate complexes on the µs time scale by the 1H off-resonance R1ρ method.

Chemical Exchange Saturation Transfer in Chemical Reactions: A Mechanistic Tool for NMR Detection and Characterization of Transient Intermediates.

The low sensitivity of NMR and transient key intermediates below detection limit are the central problems studying reaction mechanisms by NMR. Sensitivity can be enhanced by hyperpolarization techniques such as dynamic nuclear polarization or the incorporation/interaction of special hyperpolarized molecules. However, all of these techniques require special equipment, are restricted to selective reactions, or undesirably influence the reaction pathways. Here, we apply the chemical exchange saturation transfer (CEST) technique for the first time to NMR detect and characterize previously unobserved transient reaction intermediates in organocatalysis. The higher sensitivity of CEST and chemical equilibria present in the reaction pathway are exploited to access population and kinetics information on low populated intermediates. The potential of the method is demonstrated on the proline-catalyzed enamine formation for unprecedented in situ detection of a DPU stabilized zwitterionic iminium species, the elusive key intermediate between enamine and oxazolidinones. The quantitative analysis of CEST data at 250 K revealed the population ratio of [Z-iminium]/[exo-oxazolidinone] 0.02, relative free energy +8.1 kJ/mol (calculated +7.3 kJ/mol), and free energy barrier of +45.9 kJ/mol (ΔG⧧calc.(268 K) = +42.2 kJ/mol) for Z-iminium → exo-oxazolidinone. The findings underpin the iminium ion participation in enamine formation pathway corroborating our earlier theoretical prediction and help in better understanding. The reliability of CEST is validated using 1D EXSY-build-up techniques at low temperature (213 K). The CEST method thus serves as a new tool for mechanistic investigations in organocatalysis to access key information, such as chemical shifts, populations, and reaction kinetics of intermediates below the standard NMR detection limit.

The Structure of [HSi9 ]3- in the Solid State and Its Unexpected Highly Dynamic Behavior in Solution.

We report on the first unambiguous detection of the elusive [HSi9 ]3- anion in solutions of liquid ammonia by various 29 Si and 1 H NMR experiments including chemical exchange saturation transfer (CEST). The characteristic multiplicity patterns of both the 29 Si and 1 H resonances together with CEST and a partially reduced 1 H,29 Si coupling constant indicate the presence of a highly dynamic Si8 entity and a Si-H moiety with slow proton hopping. Theoretical calculations corroborate both reorganization of Si8 on the picosecond timescale via low vibrational modes and proton hopping. In addition, in a single-crystal X-ray study of (K(DB[18]crown-6))(K([2.2.2]crypt))2 [HSi9 ]⋅8.5 NH3 , the H atom was unequivocally localized at one vertex of the basal square of the monocapped square-antiprismatic cluster. Thus experimental studies and theoretical considerations provide unprecedented insight into both the structure and the dynamic behavior of these cluster anions, which hitherto had been considered to be rigid.

NMR Spectroscopic Characterization of Charge Assisted Strong Hydrogen Bonds in Brønsted Acid Catalysis.

Hydrogen bonding plays a crucial role in Brønsted acid catalysis. However, the hydrogen bond properties responsible for the activation of the substrate are still under debate. Here, we report an in depth study of the properties and geometries of the hydrogen bonds in (R)-TRIP imine complexes (TRIP: 3,3'-Bis(2,4,6-triisopropylphenyl)-1,1'-binaphthyl-2,2'-diylhydrogen phosphate). From NMR spectroscopic investigations 1H and 15N chemical shifts, a Steiner-Limbach correlation, a deuterium isotope effect as well as quantitative values of 1JNH,2hJPH and 3hJPN were used to determine atomic distances (rOH, rNH, rNO) and geometry information. Calculations at SCS-MP2/CBS//TPSS-D3/def2-SVP-level of theory provided potential surfaces, atomic distances and angles. In addition, scalar coupling constants were computed at TPSS-D3/IGLO-III. The combined experimental and theoretical data reveal mainly ion pair complexes providing strong hydrogen bonds with an asymmetric single well potential. The geometries of the hydrogen bonds are not affected by varying the steric or electronic properties of the aromatic imines. Hence, the strong hydrogen bond reduces the degree of freedom of the substrate and acts as a structural anchor in the (R)-TRIP imine complex.

RNA nucleosides as chiral sensing agents in NMR spectroscopy.

The study reports chiral sensing properties of RNA nucleosides. Adenosine, guanosine, uridine and cytidine are used as chiral derivatizing agents to differentiate chiral 1°-amines. A three component protocol has been adopted for complexation of nucleosides and amines. The chiral differentiating ability of nucleosides is examined for different amines based on the (1)H NMR chemical shift differences of diastereomers (Δδ(R,S)). Enantiomeric differentiation has been observed at multiple chemically distinct proton sites. Adenosine and guanosine exhibit large chiral differentiation (Δδ(R,S)) due to the presence of a purine ring. The diastereomeric excess (de) measured by using adenosine is in good agreement with the gravimetric values.

Cephalometric assessment of effect of head rotation toward focal spot on lateral cephalometric radiographs.

INTRODUCTION: The patient's head can be slightly rotated sagittally vertically or transversely with the head holding device. Because of such improper positions due to head rotation, an error can occur in cephalometric measurements. The purpose of this study was to identify the projection errors of lateral cephalometric radiograph due to head rotation in the vertical Z-axis toward the focal spot. MATERIALS AND METHODS: Ten human dry skulls with permanent dentition were collected. Each dry skull was rotated from 0° to +20° at 5° intervals. A vertical axis, the Z-axis, was used as a rotational axis to have 50 lateral cephalometric radiographs exposed. Four linear (S-N, Go-Me, N-Me, S-Go) and six angular measurements (SNA, SNB, N-S-Ar, S-Ar-Go, Ar-Go-Me, AB-mandibular plane angle) were calculated manually. RESULTS: The findings were that: (1) Angular measurements have fewer projection errors than linear measurements. (2) The greater the number of landmarks on the midsagittal plane that are included in angular measurements, the fewer the projection errors occurring. (3) Horizontal linear measurements have more projection errors than vertical linear measurements. CONCLUSION: The angular measurements of lateral cephalometric radiographs are more useful than linear measurements in minimizing the projection errors associated with head rotation on a vertical axis toward the focal spot.

Biomechanical characteristics of microimplant for anchorage in orthodontics: a 3D finite element model study.

In orthodontic treatment, anchorage control is essential for success. A recent development, stationary anchorage (micro- implants) eliminates one of the uncertainties of orthodontic tooth movement by offering absolute control over potentially undesirable counter movements. The objective of this study was to establish a 3D finite element model for microimplant and to analyze the influence of different angulations to the long axis of the teeth (30-90°) on the biomechanical characteristics of orthodontic anchorage implant-bone interface. Results of this study showed that largest stress and deformation was seen in the cortical bone and upper region of trabecular bone. Stress and deformation increased as the angulations of the implant to the long axis of the tooth increased. As the angulation of the implant to the long axis of maxillary 1st molar increased, stress and deformation also decreased. Maximum stress and displacement were recorded when implant was placed perpendicular to the long axis of maxillary 1st molar.

Status of Substance use among Undergraduate Medical Students in a Selected Government Medical College in Puducherry - An Explanatory Mixed Method Study.

Background: Studies have shown increase in health-risking behavior and a decline in health-promoting behavior among medical students during their stay in medical school. This study aims to determine the prevalence and reason for substance abuse among the undergraduate medical students in a selected medical college in Puducherry. Material and Methods: This was a facility-based explanatory mixed method study conducted from May 2019 to July 2019. Assessment of their substance abuse was done using ASSIST questionnaire. Substance use was summarized as proportions with 95% CI. Results: A total of 379 participants were included in the study. The mean age of the study participants was 20 years (± 1.34). The most prevalent substance use was alcohol (10.8%). About 1.9% and 1.6% of students surveyed consume tobacco and cannabis, respectively. Conclusion: Facilitating factors for substance use as perceived by the participants were stress, peer pressure, easy availability of substances, socialization, curiosity, and awareness knowledge about safe limits of alcohol and tobacco.

Deep learning image segmentation approaches for malignant bone lesions: a systematic review and meta-analysis.

Introduction: Image segmentation is an important process for quantifying characteristics of malignant bone lesions, but this task is challenging and laborious for radiologists. Deep learning has shown promise in automating image segmentation in radiology, including for malignant bone lesions. The purpose of this review is to investigate deep learning-based image segmentation methods for malignant bone lesions on Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Positron-Emission Tomography/CT (PET/CT). Method: The literature search of deep learning-based image segmentation of malignant bony lesions on CT and MRI was conducted in PubMed, Embase, Web of Science, and Scopus electronic databases following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of 41 original articles published between February 2017 and March 2023 were included in the review. Results: The majority of papers studied MRI, followed by CT, PET/CT, and PET/MRI. There was relatively even distribution of papers studying primary vs. secondary malignancies, as well as utilizing 3-dimensional vs. 2-dimensional data. Many papers utilize custom built models as a modification or variation of U-Net. The most common metric for evaluation was the dice similarity coefficient (DSC). Most models achieved a DSC above 0.6, with medians for all imaging modalities between 0.85-0.9. Discussion: Deep learning methods show promising ability to segment malignant osseous lesions on CT, MRI, and PET/CT. Some strategies which are commonly applied to help improve performance include data augmentation, utilization of large public datasets, preprocessing including denoising and cropping, and U-Net architecture modification. Future directions include overcoming dataset and annotation homogeneity and generalizing for clinical applicability.

A Study to Compare and Correlate the Status of Maturation in Growing Individuals Using Chronological Age Dental Maturation and Cervical Vertebrae Maturation.

AIM AND OBJECTIVE: To compare and correlate the status of maturation in growing individuals using orthopantomograph (OPG) and lateral cephalogram to establish a reliable relationship between chronological age (CA) and dental maturation (DM) with cervical vertebrae maturation index (CVMI). MATERIALS AND METHODS: Lateral cephalometric radiographs and OPGs of 50 children within the circumpubertal period were collected (male n = 25, age 12-17 years, female n = 25, age 10-15 years) and evaluated for the status of maturation using CA, DM (of mandibular left canine and second molar using Demirjian Index-DI), and CVMI stages. RESULTS: Chronological age shows a positive correlation with CVMI stages in both groups. Gender-based association and distribution between DI stages of canine and CVMI stages shows that in both male and female sample groups DI G correlates with CVMI stage 1 and 2, DI H correlates with CVMI stage 3. Gender-based association and distribution between DI stages of 2nd molar and CVMI stages show that in the male sample group DI E shows a higher correlation with CVMI stage 1, DI F shows a higher correlation with CVMI stage 1 and 2. DI G shows a higher correlation with CVMI stages 2 and 3. DI H shows a higher correlation with CVMI stage 3. In the female sample group, DI F shows a higher correlation between CVMI stage 1 and 2, DI G and F show a higher correlation with CVMI stage 3. CONCLUSION: Mandibular canine, second molar calcification stages, and CA show a positive correlation with CVMI stages in the present study, hence, this can be considered as a reliable indicator in skeletal maturity assessment. HOW TO CITE THIS ARTICLE: Pooja U, Lokesh NK, Alle RS, et al. A Study to Compare and Correlate the Status of Maturation in Growing Individuals Using Chronological Age Dental Maturation and Cervical Vertebrae Maturation. Int J Clin Pediatr Dent 2021;14(S-1):S50-S53.

Detection of clinically relevant epidermal growth factor receptor pathway mutations in circulating cell-free tumor DNA using next generation sequencing in squamous cell carcinoma lung.

BACKGROUND: Limited repertoires of targets are available in the management of squamous cell carcinoma lung. In this study, we analyzed epidermal growth factor receptor (EGFR), RAS, BRAF mutations in lung cancer patients of squamous cell histology using next-generation sequencing (NGS) on the circulating cell-free DNA (cf-DNA). MATERIALS AND METHODS: In this prospective observational study, patients with squamous cell carcinoma lung, either newly diagnosed or having a progressive disease on prior therapy were eligible. Cf-DNA was extracted from peripheral blood and analyzed for EGFR, KRAS, NRAS, and BRAF mutations using NGS. RESULTS: Sixteen patients were enrolled over a period of 1 month. The mean cf-DNA quantity extracted from the plasma was 96.5 ng (range, 15-200 ng). Eight clinically relevant mutations in the EGFR pathway were identified. These include Exon 21 mutations in 4 patients, Exon 20 mutation in onepatient, complex mutations with coexisting Exon 21 and Exon18 in one patient and KRAS Exon 2 mutations in two patients. CONCLUSION: cf-DNA is a minimally invasive technique for detection of clinically relevant mutations in lung cancer patients. The use of novel advanced techniques such as NGS may help in detecting EGFR pathway mutations in patients with squamous cell carcinoma lung.

Prognostic and predictive implications of Sokal, Euro and EUTOS scores in chronic myeloid leukaemia in the imatinib era-experience from a tertiary oncology centre in Southern India.

Chronic myeloid leukaemia (CML) is a myeloproliferative disorder. Over the years many prognostic models have been developed to better risk stratify this disease at baseline. Sokal, Euro, and EUTOS scores were developed in varied populations initially receiving various therapies. Here we try to identify their predictive and prognostic implication in a larger population of Indian patients with CML-CP (chronic phase) in the imatinib era.

Assessment of Image Distortion from Head Rotation in Lateral Cephalometry.

BACKGROUND: The patient's head can be slightly rotated sagitally vertically or transversely within the head holding device. Because of such improper positions due to the head rotation, an error can occur in cephalometric measurements. The purpose of this study was to identify the potential projection errors of lateral cephalometric radiograph due to head rotation toward X-ray film in the vertical Z-axis. MATERIALS AND METHODS: Totally, 10 human dry skulls with permanent dentition were collected from the Department of Anatomy, J.J.M.C. Medical College, Davanagere. Each dry skull was rotated from 0° to -20° at 5° intervals. A vertical axis, the Z-axis, was used as a rotational axis to have 100 lateral cephalometric radiographs exposed. Four linear (S-N, Go-Me, N-Me, S-Go) and six angular measurements (SNA, SNB, N-S-Ar, S-Ar-Go, Ar-Go-Me, AB-Mandibular plane angle) were calculated manually. RESULTS: The findings were that: (1) Angular measurements have fewer projection errors than linear measurements; (2) the greater the number of landmarks on the midsagittal plane that are included in angular measurements, the fewer the projection errors occurring; (3) the horizontal linear measurements have more projection errors than vertical linear measurements according to head rotation. CONCLUSION: In summary the angular measurements of lateral cephalometric radiographs are more useful than linear measurements in minimizing the projection errors associated with head rotation on a vertical axis.

Quick re-introduction of selective scalar interactions in a pure-shift NMR spectrum.

A new 1D NMR experiment cited as 'Quick G-SERF', which re-introduces selective proton-proton scalar interactions in a pure shift spectrum during real time data acquisition, is reported. The method provides information on multiple proton-proton couplings from a single experiment, analogous to the 2D G-SERF technique, while significantly shortening the experimental time by 1-2 orders of magnitude due to reduced dimension and enhanced sensitivity.