REDEN: Interactive multi-fitting decomposition-based NMR peak picking assistant.

We present a new program REDEN (Residual Decomposition of NMR peaks) designed to perform identification of peaks in NMR spectra. This integrated, cross-platform, open-source software visually assists with explicit peak picking through decomposition of NMR peaks on the frequency domain data. It provides a distinctive interactive workflow with iPick due to its integration with the POKY suite, providing users with a seamless and efficient experience. The decomposition of peaks operates in a chosen region of an NMR spectrum by multi-fitting simulated peaks with four lineshape fitting options as support, Gaussian, Lorentzian, a fast/optimized Lorentzian, and Pseudo-Voigt. Furthermore, REDEN provides a way to fine-tune for the users in two operating modes (Basic and Advanced). REDEN is pre-built in the POKY suite, which is available from https://poky.clas.ucdenver.edu.

Breaking boundaries: TINTO in POKY for computer vision-based NMR walking strategies.

Nuclear magnetic resonance is a crucial technique for studying biological complexes, as it provides precise structural and dynamic information at the atomic level. However, the process of assigning resonances can be time-consuming and challenging, particularly in cases where peaks overlap, or the data quality is poor. In this paper, we present TINTO (Two and three-dimensional Imaging for NMR sTrip Operation via CV/ML), an advanced semiautomatic toolset for NMR resonance assignment. TINTO comprises two separate tools, each tailored for either two-dimensional or three-dimensional imaging. The toolset utilizes a computer-vision approach and a machine learning approach, specifically structural similarity index and principal components analysis, to perform visual similarity searches of resonances and quickly locate similar strips, and in that way overcome the challenges associated with peak overlap without requiring peak picking. Our tool offers a user-friendly interface and has the potential to enhance the efficiency and accuracy of NMR resonance assignment, particularly in complex cases. This advancement holds promising implications for furthering our understanding of biological systems at the molecular level. TINTO is pre-installed in the POKY suite, which is available at https://poky.clas.ucdenver.edu .

Mitigating First-Cycle Capacity Losses in NMC811 via Lithicone Layers Grown by Molecular Layer Deposition.

Nickel-rich LiNi1-x-yMnxCoyO2 (NMC, 1 - x - y ≥ 0.8) is currently considered one of the most promising cathode materials for high-energy-density automotive lithium-ion batteries. Here, we show that capacity losses occurring in balanced NMC811||graphite cells can be mitigated by lithicone layers grown by molecular layer deposition directly onto porous NMC811 particle electrodes. Lithicone layers with a stoichiometry of LiOC0.5H0.3 as determined by elastic recoil detection analysis and a nominal thickness of 20 nm determined by ellipsometry on a flat reference substrate improve the overall NMC811||graphite cell capacity by ∼5% without negatively affecting the rate capability and long-term cycling stability.

Beta-KTx14.3, a scorpion toxin, blocks the human potassium channel KCNQ1.

Potassium channels play a key role in regulating many physiological processes, thus, alterations in their proper functioning can lead to the development of several diseases. Hence, the search for compounds capable of regulating the activity of these channels constitutes an intense field of investigation. Potassium scorpion toxins are grouped into six subfamilies (α, ß, γ, κ, δ, and λ). However, experimental structures and functional analyses of the long chain ß-KTx subfamily are lacking. In this study, we recombinantly produced the toxins TcoKIK and beta-KTx14.3 present in the venom of Tityus costatus and Lychas mucronatus scorpions, respectively. The 3D structures of these ß-KTx toxins were determined by nuclear magnetic resonance. In both toxins, the N-terminal region is unstructured, while the C-terminal possesses the classic CSα/ß motif. TcoKIK did not show any clear activity against frog Shaker and human KCNQ1 potassium channels; however, beta-KTx14.3 was able to block the KCNQ1 channel. The toxin-channel interaction mode was investigated using molecular dynamics simulations. The results showed that this toxin could form a stable network of polar-to-polar and hydrophobic interactions with KCNQ1, involving key conserved residues in both molecular partners. The discovery and characterization of a toxin capable of inhibiting KCNQ1 pave the way for the future development of novel drugs for the treatment of human diseases caused by the malfunction of this potassium channel. STATEMENT OF SIGNIFICANCE: Scorpion toxins have been shown to rarely block human KCNQ1 channels, which participate in the regulation of cardiac processes. In this study, we obtained recombinant beta-KTx14.3 and TcoKIK toxins and determined their 3D structures by nuclear magnetic resonance. Electrophysiological studies and molecular dynamics models were employed to examine the interactions between these two toxins and the human KCNQ1, which is the major driver channel of cardiac repolarization; beta-KTx14.3 was found to block effectively this channel. Our findings provide insights for the development of novel toxin-based drugs for the treatment of cardiac channelopathies involving KCNQ1-like channels.

Body composition in women with premature ovarian insufficiency using hormone therapy and the relation to cardiovascular risk markers: A case-control study.

OBJECTIVE: To compare body composition between women with premature ovarian insufficiency (POI) using hormone therapy and controls with normal ovarian function, and to correlate body composition with cardiovascular risk markers in the POI group. PATIENTS AND DESIGN: A case-control study of 70 women with POI matched by age and body mass index with 70 controls. MEASUREMENTS: All were submitted to whole-body dual-energy X-ray absorptiometry (DXA) to analyse body composition. In the POI group, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, triglycerides, glucose, insulin, transaminases and C-reactive protein levels were measured, as well as the thickness of the carotid artery intima-media complex. RESULTS: Total mass, fat mass, lean mass (total, percentage and index) and the android/gynoid (A/G) ratio were similar in both groups; however, bone mineral content was lower (P < .001) in the POI group. Lean and fat mass indexes were 14.19 ± 1.63 and 11.04 ± 3.58, respectively, and the percentage of gynoid to android fat was higher (51.17 ± 6.71% versus 47.74 ± 9.19%; A/G ratio = 0.93 ± 0.15) in the POI group. In addition, the increase in total mass correlated positively with glucose and ALT levels and negatively with HDL-cholesterol. Increased A/G ratio was the measurement most frequently associated with cardiovascular risk markers. CONCLUSION: The body composition of women with POI using hormone therapy is similar to that of women with normal ovarian function with regard to lean and fat mass content and fat distribution. In women with POI, the higher the A/G ratio, the worse the cardiovascular risk markers.

The three-dimensional structure of the toxic peptide Cl13 from the scorpion Centruroides limpidus.

Cl13 is a toxin purified previously from the venom of the Mexican scorpion Centruroides limpidus. This toxin affects the function of voltage gated Na+-channels, human subtypes Nav1.4, Nav1.5 and Nav1.6 in a similar manner as other known ß-toxins from scorpion venoms. Here, we report a correction of the primary structure of Cl13, previously published. The peptide does contain 66 amino acids, but residue 58 is a tryptophan and the last C-terminal amino acid is an amidated lysine, instead of arginine. The main contribution of this communication is the determination of the 3D-structure of Cl13, by solution NMR, showing that Cl13 has the classical cysteine-stabilized α/ß (CSα/ß) folding. It has a triple stranded antiparallel beta sheet commonly present in scorpion sodium channel ß-toxins. In addition, we report and discuss a comparison of Cl13 structure with two other toxins (Cn2 and Css2) from scorpions of the same genus Centruroides, which shows important surface similarities with the structure reported here. Finally, the lack of neutralization of Cl13 toxin by two single-chain antibody fragments (scFvs), named LR and 10FG2, which are capable of neutralizing various toxins from Mexican scorpions, is revised. In particular, 10FG2 is capable of neutralizing toxins Cll1 and Cll2 of the same scorpion C. limpidus. The reasons why LR and 10FG2 are unable of neutralizing Cl13 toxin are discussed.

Interferential current: a new option for the treatment of sexual complaints in women with premature ovarian insufficiency using systemic hormone therapy: a randomized clinical trial.

OBJECTIVE: The aim of the study was to evaluate the efficacy of interferential current (IC) in the sexual function of women with premature ovarian insufficiency (POI) using systemic hormone therapy (HT), compared to topical estriol. METHODS: A randomized clinical trial with 40 women with POI using systemic HT, who were sexually active and referred for dyspareunia and reduction of lubrication. The women were divided into two treatment groups for 4 weeks: IC group (eight electrotherapy sessions twice a week); or E group (estriol vaginal cream, daily application, 0.5 mg/d). The Female Sexual Function Index was used to evaluate pre-/posttreatment sexual function. RESULTS: Mean age was 37.13 ±â€Š7.27 years and mean treatment time with HT was 8.20 ±â€Š8.73 years, similar data for both groups. There was an improvement in global sexual function, lubrication, and pain domains for both treatments. The differences between the pre-/posttreatment lubrication scores were respectively 0.75 ±â€Š3.31 (P = 0.014) for IC and 1.16 ±â€Š1.22 (P < 0.001) for estriol, whereas for dyspareunia the differences were 1.00 ±â€Š1.47 (P = 0.005) for IC, and 0.68 ±â€Š1.30 (P = 0.006) for estriol. There was no pre-/posttreatment difference for the desire and arousal domains. Only in the IC group did orgasm (difference 0.90 ±â€Š1.42, P = 0.010) and satisfaction improve (difference 0.70 ±â€Š1.28, P = 0.021). CONCLUSION: The use of perineal IC seems to be a new option for women with POI using systemic HT and presenting with sexual complaints, leading to an improvement in pain, lubrication, satisfaction, and orgasm.

Influência de um programa de exercícios físicos no uso de serviços de saúde na Atenção Básica de Saúde do município de Rio Claro, SP / Influence of a physical activity program on the use of Primary Care services in the city of Rio Claro, SP

A prevenção e o controle das doenças crônicas não transmissíveis adquiridos com a prática regular de atividade física podem contribuir na melhoria da saúde dos indivíduos, o que pode reduzir o uso dos serviços de saúde e os gastos do governo. O objetivo do estudo foi verificar a influência da prática de exercícios físicos no uso dos serviços de saúde na Atenção Básica de Saúde (ABS). Participaram do estudo 26 mulheres de um programa de exercícios físicos em unidades de saúde da ABS do município de Rio Claro- SP. Foi aplicado um questionário com as participantes do programa de 2009 a 2011, contendo questões referentes à participação no programa, condições de saúde, percepção dos participantes em relação ao uso dos serviços de saúde sobre consultas médicas, medicamentos, doenças/queixas e internações, no momento anterior e posterior ao ingresso no programa. Foi realizada análise descritiva e de comparação, na qual foi utilizada a análise por intervalo de confiança para médias e frequências, sendo este de 95%. Após iniciar no programa, houve melhora da percepção de saúde das participantes, bem como relatos de diminuição do número de visitas à unidade de saúde, do número de medidas da pressão arterial, do descontrole da pressão arterial e da glicemia. Houve também manutenção do número e da dose de medicamentos, do número de doenças/queixas e do número de medidas da glicemia. A prática de exercícios físicos oferecida pelo programa contribuiu para melhora nos níveis de saúde percebida e para diminuição do uso dos serviços de saúde.

The prevention and control of chronic non-communicable diseases, promoted by the regular practice of physical activity, can improve the health status of individuals, and this can reduce government spending and the use of healthcare services. The aim of this study was to investigate the influence of physical activity practice on the use of Primary Care services. Twenty-six women enrolled in a physical activity program held in Primary Care units located in the city of Rio Claro, state of São Paulo, participated in this study. A questionnaire was administered to the women who participated in the program from 2009 to 2011, containing questions regarding participation in the program, health conditions, and participants? perceptions concerning the use of healthcare services related to medical appointments, medications, diseases/complaints and hospitalizations, in the moments before and after the enrolment in the program. A descriptive and comparative analysis was carried out, in which confidence interval analysis for means and frequencies was used, with 95% confidence intervals. After starting the program, there was an improvement in the participants? health perception, as well as reports of decrease in the number of visits to the healthcare unit, in the number of blood pressure measurements, in uncontrolled blood pressure and blood glucose. On the other hand, the number and dose of drugs remained the same, as well as the number of diseases/complaints and the number of blood glucose measurements. The practice of physical exercises offered by the program contributed to improve the levels of perceived health and to reduce the use of the healthcare services.

Niveles de 25 hidroxivitamina D y su correlación clínica con diferentes variables metabólicas y cardiovasculares en una población de mujeres posmenopáusicas / Levels of 25-hydroxyvitamin D and their clinical correlation with several metabolic and cardiovascular variables in a population of postmenopausal women

Introducción: la osteoporosis es la enfermedad ósea metabólica más común. Entre sus causas secundarias se encuentra la deficiencia de vitamina D (VD), la cual predispone además a fracturas por fragilidad e incrementa el riesgo de caídas. También confiere un riesgo incrementado de desarrollar enfermedad cardiovascular, diabetes mellitus tipo 1 y 2. Objetivo: el objetivo principal del estudio fue determinar los niveles de vitamina D en la población y correlacionarlos con diferentes variables clínicas, de laboratorio y densitométricas. Métodos: se realizó un estudio descriptivo de corte transversal, de una cohorte de pacientes donde se analizaron datos secundarios de mujeres posmenopáusicas colombianas con diagnóstico de osteoporosis y osteopenia (N=205). Se analizaron 46 variables donde se calcularon estadísticos descriptivos y regresiones lineales múltiples para determinar correlaciones. Resultados: la prevalencia de niveles insuficientes de vitamina D fue 55.1%, (n=113), deficientes 16.6% (n=34), y adecuados sólo 28.29% (n=58). Al comparar los pacientes con niveles deficientes e insuficientes, se encontró que los pacientes con niveles de vitamina D deficientes fue un factor de riesgo para la presencia de fracturas vertebrales, RR de 1.02 (IC: 0.96 a 1.06) y para la hipertensión arterial RR de 1.47 (IC: 1.36 a 1.58). Conclusión: dos terceras partes de nuestra población de pacientes tienen niveles inadecuados de vitamina D, y se encontró correlación con fracturas vertebrales e hipertensión arterial (Acta Med Colomb 2011; 36: 18-23).

Introduction: osteoporosis is the most common metabolic bone disease. Vitamin D deficiency is an important cause of secondary osteopenia and osteoporosis. It predisposes to fragility fractures and increases the risk of falling, while augmenting the risk of developing cardiovascular disease and diabetes mellitus type 1 and 2. Objective: the objective of this study was to determine the levels of vitamin D in our population study and to correlate them with bone density, vertebral fractures, and other cardiovascular and laboratory variables. Methods: we conducted a cross-sectional study of a cohort (n=205) of postmenopausal Colombian women diagnosed with osteoporosis and osteopenia. We analyzed 46 variables. Descriptive statistics were used, and multiple linear regressions were analyzed in order to determine correlations. Results: it was found that the prevalence of insufficient levels of vitamin D was 55.1% (n=113), deficient levels 16.6% (n=34), and adequate levels in only 28.29% (n=58) of patients. Comparing poor and inadequate levels, we found that deficient levels of vitamin D are a risk factor for vertebral fractures, with an RR of 1.02 (IC: 0,96 a 1.06) and for high blood pressure. with an RR of 1.47 (IC: 1.36 a 1.58). Conclusions: our study shows that inadequate levels of vitamin D are common in our population. This is associated with low bone mass, vertebral fractures, and hypertension. Further studies are needed in our country to confirm our findings (Acta Med Colomb 2011; 36: 18-23).

The "perfusion map" of the unipedicled TRAM flap to reduce postoperative partial necrosis.

The unipedicled transverse rectus abdominis musculocutaneous (TRAM) flap is a well-known technique for breast reconstruction. However, it is clinically difficult to evaluate the blood perfusion of the flap in the operating room. A new technique of blood supply evaluation, employing indocyanine green dye (ICG) fluorescence videoangiography has been performed in 10 cases of unipedicled TRAM flap breast reconstruction. In our series, the ICG measurement was demonstrated to be a safe, quick, and accurate technique of flap perfusion analysis. We confirmed the presence of individual pattern ("perfusion map") of the flap perfusion, zone II sometimes not being as well perfused as zone III. In this paper, we present our descriptive findings, and the ICG analysis seems to have a predictive value of unipedicled TRAM flap viability.

The nipple-sparing mastectomy: early results of a feasibility study of a new application of perioperative radiotherapy (ELIOT) in the treatment of breast cancer when mastectomy is indicated.

BACKGROUND: Breast cancer surgery has become less and less mutilating, however a mastectomy is required in the case of multicentric, large tumors or recurrences after conservative treatment. The removal of the nipple areola complex during the mastectomy dramatically increases the feeling of mutilation. To reduce this negative psychological impact, in cancers located outside of the central area of the breast, we propose a new type of nipple-sparing mastectomy associated with intraoperative electron beam radiotherapy (ELIOT) delivered on the region of the areola. The nipple-sparing mastectomy is performed leaving 5 mm of glandular tissue behind the nipple areola complex to preserve its blood supply. The reconstruction is immediately performed with a prosthesis or an autologous flap. PATIENTS AND METHODS: Twenty-five patients were included in the study; two of them had a bilateral nipple-sparing mastectomy. RESULTS: Pathological examinations demonstrated the presence of 19 infiltrating carcinomas and 8 ductal carcinoma in situ. Two patients had a superficial skin areolar slough followed by spontaneous healing. One necrosis of the areola occurred due to extensive retroareolar dissection. In the early follow-up, the color of the areola was preserved. All patients except one expressed their satisfaction of having kept their areola. CONCLUSIONS: These preliminary results are encouraging but they require further studies to evaluate the long-term results, the local recurrence rate and the psychological impact.