Structural identification of the related substances in phloroglucinol injection by two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry / 药学学报

This study aimed to identify the related substances of phloroglucinol injection by two-dimensional liquid chromatography quadrupole time-of-flight mass spectrometry (2D-LC-Q-TOF/MS). The first-dimensional separation was carried out on an HSS T3 (250 mm × 4.6 mm, 5 μm) column by gradient elution using 1.36 g·L-1 potassium dihydrogen phosphate buffer solution (pH adjusted to 3.0 with diluted phosphoric acid) and acetonitrile as the mobile phases. The separated components were then trapped in switch valve tube lines respectively and delivered to the second-dimensional desalting gradient elution which was performed with a BDS C18 (100 mm × 4.6 mm, 2.4 μm) column using 0.1% formic acid and methanol as the mobile phases. After rapid desalting, electrospray-ionization quadrupole time-of-flight high resolution mass spectrometry was used for determining the accurate masses and elemental compositions of the parents and their product ions for both phloroglucinol and its related substance. Structures of the related substances were then figured out by mass spectrometry elucidation, organic reaction mechanism analysis, and/or comparison with reference substances. Under the established analytical conditions, phloroglucinol and its related substances were adequately separated, 17 main related substances were detected and identified in the injection and its stressed samples for the first time. The identification results can provide reference for the quality control of phloroglucinol injection.

Effect of Xiangsha Liu Junzitang Combined with Phlegm-removing and Detoxifying Traditional Chinese Medicine on Immune Escape in Lewis Lung Cancer Mice / 中国实验方剂学杂志

ObjectiveTo study the effect and mechanism of Xiangsha Liu Junzitang combined with phlegm-removing and detoxifying traditional Chinese medicine on immune escape in Lewis lung cancer mice. MethodA total of 60 specific-pathogen-free （SPF）-grade C57BL/6J male mice were injected subcutaneously with 0.2 mL of Lewis cell suspension （containing 2×106 cells·mL-1） in the right mid-axillary line. After 7 days， the mice that had been successfully modeled were randomly divided into six groups： the model group， the cisplatin group， the Xiangsha Liu Junzitang low-， medium-， and high-dose groups， and the combined group， with 10 mice in each group. The Xiangsha Liu Junzitang low-， medium- and high-dose groups were gavaged with 17.88， 35.75， 71.50 g·kg-1 Xiangsha Liu Junzitang solution once a day， respectively， and the dosage of cisplatin intraperitoneally injected into the mice was converted to 5 mg·kg-1 twice a week， and the tumour volumes of each group were measured every two days. The intervention lasted for 14 consecutive days. At the end of treatment， the tumour mass of mice in each group was weighed and the tumour inhibition rate was calculated. The morphological characteristics of tumours in each group were observed by hematoxylin-eosin （HE） staining. Fluorescent quantitative real-time polymerase chain reaction （Real-time PCR） assay was used to detect messenger ribonucleic acid （mRNA） contents of the natural killer group 2 member D （NKG2D） receptor， ribonucleic acid export-1 （RAE-1）， and γ interferon （IFN-γ） in the tumour tissues of each group. NKG2D， RAE-1， and IFN-γ mRNA in tumour tissues of each group. Immunohistochemistry （IHC） and Western blot were applied to detect the expressions of RAE-1， NKG2D， and IFN-γ in tumour tissues of each group， and Western blot was used to detect the expressions of interleukin-6 （IL-6）， Janus kinase 2 （JAK2）， p-JAK2， signal transducer and activator of transcription 3 （STAT3）， and p-STAT3 in tumour tissues of each group， as well as the protein levels of NKG2D， and RAE-1 in spleen tissues of each group. ResultCompared with that in the model group， the tumour mass decreased in all dose groups of Xiangsha Liu Junzitang， with no statistically significant difference. The tumour volume was reduced （P<0.05， P <0.01）. The pathological morphology was improved. The mRNA contents of NKG2D， RAE-1 and IFN-γ were increased in the medium-dose group （P<0.05， P<0.01）， and the protein expressions of NKG2D， RAE-1， and IFN-γ in tumour tissues were elevated （P<0.05， P<0.01）， and p-JAK2 and p-STAT3 protein expressions were decreased （P<0.05， P<0.01）. In spleen tissues， the protein expressions of NKG2D and RAE-1 in all dose groups of Xiangsha Liu Junzitang were significantly elevated （P<0.01）. Compared with those in the cisplatin group， NKG2D， RAE-1 and IFN-γ mRNA contents were elevated in the middle-dose group of Xiangsha Liu Junzitang， and the difference was not statistically significant. IHC showed that the protein expressions of NKG2D and IFN-γ in the combined group were significantly elevated （P<0.01）， and Western blot results showed that the protein expressions of RAE-1， NKG2D and IFN-γ were elevated （P<0.05， P<0.01）. p-JAK2 and p-STAT3 protein expressions were decreased in the combined group （P<0.05， P<0.01）. NKG2D and RAE-1 protein expressions were significantly increased in spleen tissues of the medium-dose groups and the combined group （P<0.01）. ConclusionXiangsha Liu Junzitang combined with phlegm-removing and detoxifying traditional Chinese medicine can inhibit the growth of tumours in Lewis lung cancer mice by up-regulating the expressions of RAE-1/NKG2D， promoting the activation of NK cells， and inhibiting immune escape， the mechanism of which may be related to down-regulation of the JAK2/STAT3 pathway.

Asociación de fibrosis hepática mediante elastografía por shear wave 2D y score APRI

Introducción: Las hepatopatías son un problema prevalente a nivel mundial. La biopsia hepática ha sido hasta la fecha el gold standard para valorar el grado de fibrosis, sin embargo, con el advenimiento de nuevos métodos no invasivos, costo-efectivos para el sistema sanitario, cada vez recurrimos menos a esta. En nuestro medio se introdujo recientemente la elastografía por onda cizallamiento con imagen biplanar, lo que implica una curva de aprendizaje por parte de los técnicos. Objetivo: Valorar la asociación de los grados de fibrosis hepática determinado por la elastografía por onda de cizallamiento con imagen biplanar (2D-SWE) y el score APRI en pacientes portadores de enfermedad hepática asistidos en el servicio de hepatología del Hospital Pasteur.Médica 2. Metodología: Se incluyeron los pacientes con enfermedad hepática de cualquier etiología, asistidos entre el 01/10/21 al 31/08/22, mayores de 15 años, de ambos sexos y que han sido valorados con elastografía por onda de cizallamiento con imagen biplanar (2D-SWE) y analítica sanguínea realizado por el equipo médico del servicio mencionado en los últimos 6 meses. Resultados: Se incluyeron 158 pacientes. Se encontró mayor prevalencia de enfermedad hepática en mujeres, con predominio de la etiología de enfermedad por hígado graso no alcohólico (EHGNA) e infección por virus de hepatitis C (VHC). Se evidenció asociación positiva entre la elastografía (2D-SWE) y el score APRI para el diagnóstico o exclusión de enfermedad hepática avanzada, sin diferencia estadísticamente significativa entre los dos médicos hepatólogos. Conclusiones: Existe asociación entre la elastografía por SWE y el score APRI para el diagnóstico de enfermedad hepática avanzada en la población general y por etiología.

Introduction: Liver diseases are a prevalent problem worldwide. To date, liver biopsy has been the gold standard for assessing the degree of fibrosis; however, with the advent of new non-invasive, cost-effective methods for the healthcare system, we are resorting to it less and less. Shear wave elastography with biplanar imaging was recently introduced in our setting, which implies a learning curve for technicians. Objective: To assess the association of the degrees of liver fibrosis determined by shear wave elastography with biplanar imaging (2D-SWE) and the APRI score in patients with liver disease treated in the hepatology service of the Pasteur Hospital. Methodology: Patients with liver disease of any etiology, attended between 01/10/21 and 08/31/22, over 15 years of age, of both sexes and who have been evaluated with shear wave elastography with biplanar image were included. (2D-SWE) and blood analysis performed by the medical team of the aforementioned service in the last 6 months. Results: 158 patients were included. A higher prevalence of liver disease was found in women, with a predominance of the etiology of nonalcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV) infection. A positive association was evident between elastography (2D-SWE) and the APRI score for the diagnosis or exclusion of advanced liver disease, with no statistically significant difference between the two hepatologists. Conclusions: There is an association between SWE elastography and the APRI score for the diagnosis of advanced liver disease in the general population and by etiology.

Introdução: As doenças hepáticas são um problema prevalente em todo o mundo. Até o momento, a biópsia hepática tem sido o padrão ouro para avaliar o grau de fibrose, porém, com o advento de novos métodos não invasivos e de baixo custo para o sistema de saúde, recorremos cada vez menos a ela. A elastografia por onda de cisalhamento com imagem biplanar foi introduzida recentemente em nosso meio, o que implica uma curva de aprendizado para os técnicos. Objetivo: Avaliar a associação dos graus de fibrose hepática determinados pela elastografia por ondas de cisalhamento com imagem biplanar (2D-SWE) e o escore APRI em pacientes com hepatopatia atendidos no serviço de hepatologia do Hospital Pasteur. Metodologia: Foram incluídos pacientes portadores de doença hepática de qualquer etiologia, atendidos entre 10/01/21 e 31/08/22, maiores de 15 anos, de ambos os sexos e que foram avaliados com elastografia por onda de cisalhamento com imagem biplanar. ( 2D-SWE) e análises sanguíneas realizadas pela equipa médica do referido serviço nos últimos 6 meses. Resultados: foram incluídos 158 pacientes. Foi encontrada maior prevalência de doença hepática em mulheres, com predomínio da etiologia da doença hepática gordurosa não alcoólica (DHGNA) e da infecção pelo vírus da hepatite C (HCV). Foi evidente uma associação positiva entre a elastografia (2D-SWE) e o escore APRI para o diagnóstico ou exclusão de doença hepática avançada, sem diferença estatisticamente significativa entre os dois hepatologistas. Conclusões: Existe associação entre a elastografia SWE e o escore APRI para o diagnóstico de doença hepática avançada na população geral e por etiologia.

Can the Second and Fourth Finger (2D: 4D) Ratio Guide Physicians in Choosing Internal Medicine or Surgical Branch? / ¿Puede la proporción del Segundo y Cuarto Dedo (2D: 4D) Guiar a los Médicos en la Elección de Medicina Interna o Rama Quirúrgica?

SUMMARY: This study investigates the relationship between the second and fourth finger ratio (2D:4D), physicians' propensity to choose an internal or surgical branch, and sex differences. On a voluntary basis, 177 physicians working in Elazig, 122 men and 55 women were enrolled in the study. Their hands were measured for 2D and 4D lengths, and the 2D:4D ratio was computed. In female doctors, the left hand's 2D:4D ratio is 1.01, compared to the right hand's 1.00. Male doctors' right 2D:4D ratio is 0.99, while their left 2D:4D ratio is 1.00. Male physicians' 2D:4D ratios were different from those of men in the general population, whereas female physicians' 2D:4D ratios were comparable to those of women in the general population. As a result, this study was the first to examine the relationship between the ratio of the second and fourth fingers (2D:4D), physicians' tendency to choose an internal medicine or surgical branch, and sex differences. While the 2D:4D ratio was higher than 0.98 in all physicians, it was low in women who disliked their profession and branch. Since there aren't many studies on this subject, data from in-depth studies that will be conducted in the future will help physicians who choose internal medicine and surgery make more informed decisions.

Este estudio investiga la relación entre la proporción de los dedos segundo y cuarto (2D:4D), la propensión de los médicos a elegir una rama interna o quirúrgica y las diferencias de género. De forma voluntaria, se inscribieron en el estudio 177 médicos que trabajaban en Elazig, 122 hombres y 55 mujeres. Sus manos se midieron en longitudes 2D y 4D, y se calculó la relación 2D:4D. En las médicos mujeres, la relación 2D:4D de la mano izquierda es 1,01, en comparación con 1,00 de la mano derecha. La relación 2D:4D derecha de los médicos hombres fue 0,99, mientras que la relación 2D:4D izquierda fye 1,00. Las proporciones 2D:4D de los médicos hombres fueron diferentes de las de los hombres en la población general, mientras que las proporciones 2D:4D de las mujeres médicas fueron comparables a las de las mujeres en la población general. Como resultado, este estudio fue el primero en examinar la relación entre la proporción del segundo y cuarto dedo (2D:4D), la tendencia de los médicos a elegir una rama de medicina interna o quirúrgica y las diferencias de sexo. Mientras que la relación 2D:4D fue superior a 0,98 en todos los médicos, fue baja en las mujeres que no les gustaba su profesión y rama. Dado que no hay muchos estudios sobre este tema, los datos de estudios en profundidad que se realizarán en el futuro ayudarán a los médicos que eligen medicina interna y cirugía a tomar decisiones más informadas.

Assessment of Left Ventricular Diastolic Dysfunction in Cases with Liver Cirrhosis

Background: Cirrhosis is a long-term inflammatory process of hepatic tissue condition that mainly affects people aged 50 to 60. This study aims to assess Left ventricular diastolic dysfunction (LVDD) in cases with cirrhotic liver by conventional, tissue Doppler and two-dimensional speckle tracking echocardiography to clarify the correlation between the severity of cirrhotic liver and LVDD. Methods: A prospective case-control research involved 100 adult cases with confirmed HCV and HBV. Cases were divided into 4 equal group: Group A: Child A cases, group B: Child B cases, group C: Child C cases and group D (Controls): healthy non-hepatic subjects of the same age and sex who have normal blood pressure, nonsmoking participants with no further concomitant problems. Results: Number of cases with LVDD had a statistical noticeable increase in Child A, B, and C (p =0.004, <0.001, and <0.001 respectively. LAVi had a statistical noticeable increase in Child C / B (p =0.013 and p =0.014). Conclusion: Left atrial volume index (LAVi) had a statistical noticeable increase in Child C / B in comparison to the controls but E m, E l were statistical noticeable lower in Child C / B. /E had a statistical noticeable increase in Child C group, LVSRe had a statistical noticeable decrease in Child C group but it was insignificantly different across Child A / B/ C and controls and across Child B / C and controls.

Ultrasensitive quantification of trace amines based on N-phosphorylation labeling chip 2D LC-QQQ/MS / 药物分析学报

Trace amines(TAs)are metabolically related to catecholamine and associated with cancer and neuro-logical disorders.Comprehensive measurement of TAs is essential for understanding pathological pro-cesses and providing proper drug intervention.However,the trace amounts and chemical instability of TAs challenge quantification.Here,diisopropyl phosphite coupled with chip two-dimensional(2D)liquid chromatography tandem triple-quadrupole mass spectrometry(LC-QQQ/MS)was developed to simul-taneously determine TAs and associated metabolites.The results showed that the sensitivities of TAs increased up to 5520 times compared with those using nonderivatized LC-QQQ/MS.This sensitive method was utilized to investigate their alterations in hepatoma cells after treatment with sorafenib.The significantly altered TAs and associated metabolites suggested that phenylalanine and tyrosine metabolic pathways were related to sorafenib treatment in Hep3B cells.This sensitive method has great potential to elucidate the mechanism and diagnose diseases considering that an increasing number of physiological functions of TAs have been discovered in recent decades.

Expressions of programmed death 1 and its ligand in acute myeloid leukemia patients and their effect on anti-tumor effect of programmed death receptor 1-positive natural killer cells in vitro / 白血病·淋巴瘤

Objective:To investigate the expression of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway in patients with acute myeloid leukemia (AML) and its relationship with clinical features and prognosis, and to examine its effect on PD-1-positive natural killer (NK) cells against AML cells in vitro.Methods:The bone marrow samples of 65 AML patients and the peripheral blood of 32 AML patients diagnosed in Affiliated Cancer Hospital of Zhengzhou University from July 2019 to December 2020 were prospectively collected, and the peripheral blood of 24 healthy people was taken as healthy control. The expression level of PD-L1 in bone marrow tumor cells and expression level of PD-1 in peripheral blood NK cells were detected by flow cytometry. The correlations of PD-1 expression in bone marrow tumor cells and PD-1 expression in NK cells with the clinicopathological features, curative effect and prognosis of patients were analyzed. Flow cytometry was used to detect the expression level of PD-L1 in AML cell line THP-1 (target cells) and the expression level of PD-L1 in NK cell line NKL (effector cells). THP-1 cells treated with and without 25 μmol/L of PD-L1 inhibitor fraxinellone were used as experimental group and control group, and co-cultured with NKL cells at different effector-to-target ratios. The apoptosis of THP-1 cells and the expression of NKG2D in NKL cells were detected by flow cytometry, the cell proliferation status was detected by CCK-8 and the cell proliferation inhibition rate was calculated; the levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in the supernatant of co-culture system were detected by enzyme-linked immunosorbent assay (ELISA).Results:The proportion of AML patients with PD-L1-positive expression in bone marrow tumor cells was higher than that in the healthy control group [38.5% (25/65) vs. 8.3% (2/24), P = 0.029]. The proportion of AML patients with PD-1-positive expression in peripheral blood NK cells was higher than that in the healthy control group [40.6% (13/32) vs. 12.5% (3/24), P = 0.035]. There were no statistical differences in sex, age, hemogram, proportion of primordial cells, risk stratification, chromosomal karyotype, gene mutation (except NPM1 gene), fusion gene and French-American-British cooperative group (FAB) typing between patients with PD-L1 positive and negative in bone marrow tumor cells and between patients with PD-1 positive and negative in peripheral blood NK cells (all P > 0.05). In relapsed/refractory patients, the proportion of patients with PD-L1-positive expression in bone marrow tumor cells was higher than that in newly treated patients [58.8% (10/17) vs. 31.2% (15/48), P = 0.045]. There was no significant difference in the proportion of patients with PD-1-positive expression in peripheral blood NK cells between relapsed/refractory patients and newly treated patients [(38.5% (5/13) vs. 42.1% (8/19), P = 0.837]. There was no statistical difference in complete remission (CR) rate between PD-L1 positive and negative patients [69.6% (16/23) vs. 74.3% (26/35), P > 0.05]. There was no statistical difference in CR rate between PD-1 positive and negative patients [66.7% (8/12) vs. 70.6% (12/17), P > 0.05]. There was no statistical difference in recurrence rate after CR between PD-L1 positive and negative patients [12.5% (2/16) vs. 19.2% (5/26), P > 0.05]. There was no statistical difference in recurrence rate after CR between PD-1 positive and negative patients [25.0% (2/8) vs. 16.7% (2/12), P > 0.05]. Flow cytometry showed that the positive rate of PD-1 in NKL cells was (67±6)% and the positive rate of PD-L1 in THP-1 cells was (85±5)%. After co-culture with NKL cells, the apoptotic rate and proliferation inhibition rate of THP-1 cells were higher in the experimental group compared with the control group, the expression of NKG2D on the surface of NKL cells was elevated, and the levels of IFN-γ and TNF-α in the co-culture supernatant were increased. Conclusions:In AML patients, the expression of PD-L1 in bone marrow tumor cells is high, and the expression of PD-1 in peripheral blood NK cells is also high. The expression of PD-L1 in bone marrow tumor cells of relapsed/refractory AML patients is higher than that of newly treated patients. Inhibition of PD-L1 expression in THP-1 cells can enhance the tumor killing activity of NKL cells in vitro. The mechanism may be that inhibition of PD-L1 expression in THP-1 cells up-regulates the expression of NKL cell activated receptor NKG2D and promotes the secretion of IFN- γ and TNF- α.

Progress of tumor suppressor genes MLL3 in leukemia / 白血病·淋巴瘤

MLL3 is also known as lysine methyltransferase 2C (KMT2C). The mutation of MLL3 can occur in a variety of human cancers, including leukemia, liver cancer, and stomach cancer. The effect of MLL3 in different cancers is also different, for example, MLL3 is carcinogenic in pancreatic and liver cancer, while it acts as a tumor suppressor in acute myeloid leukemia and esophageal squamous cell carcinoma. The effects of genes in tumors depend on certain environment and conditions, and the mechanism of the suppressive effect of MLL3 in leukemia is still not clear. This paper reviews the research progress of the antitumor mechanism of MLL3 in leukemia.

Gabapentin effectively alleviates pain sensitization and regulates CACNA2D1 expression in postherpetic neuralgia rats / 中国药理学通报

Aim To identify the molecular target of gabapentin in the treatment of postherpetic neuralgia(PHN). Methods The molecular target of gabapentin for PHN was analyzed by network pharmacology and molecular docking and confirmed by coprecipitation test. Rats were randomly divided into control group, model group, model+50 mg·kg-1 gabapentin group, model+100 mg·kg-1 gabapentin group, and model+200 mg·kg-1 gabapentin group, with nine rats in each group. The pain-related behaviors of the rats were measured at different time points. The mRNA and protein expressions of CACNA2D1, Bax, and Bcl-2 in rat spinal cord were determined by immunofluorescence, Western blot, and qPCR. Results CACNA2D1 was the target gene of gabapentin that determined via network pharmacology, molecular docking, and co-precipitation tests. After modeling, mechanical pain threshold and thermal pain threshold significantly decreased, and the number of apoptotic GABA cells significantly increased. However, after intraperitoneal injection of 50, 100, and 200 mg·kg-1 gabapentin, mechanical pain threshold and thermal pain threshold significantly increased(P<0.05), and the number of apoptotic GABA cells significantly decreased(P<0.01). Immunofluorescence and Western blot results showed that compared with the model group, with the increase of gabapentin concentration, the positive expression rate of Bax significantly decreased, and the positive expression rate of Bcl-2 and CACNA2D1 significantly increased. The mRNA expression levels of Bax, Bcl-2 and CACNA2D1 detected by qPCR were consistent with the results of immunofluorescence and Western blot. Conclusions Gabapentin up-regulates the expression of target protein CACNA2D1, inhibits the proapoptotic protein Bax, and promotes the expression of apoptotic inhibitor Bcl-2.

A precision medication study of atomoxetine in children with attention deficit hyperactivity disorder: CYP2D6 genetic testing and therapeutic drug monitoring / 中国当代儿科杂志

Atomoxetine is the first non-stimulant drug for the treatment of children and adults with attention deficit hyperactivity disorder (ADHD), and its safety and efficacy show significant differences in the pediatric population. This article reviews the genetic factors influencing the pharmacokinetic differences of atomoxetine from the aspect of the gene polymorphisms of the major metabolizing enzyme CYP2D6 of atomoxetine, and then from the perspective of therapeutic drug monitoring, this article summarizes the reference ranges of the effective concentration of atomoxetine in children with ADHD proposed by several studies. In general, there is an association between the peak plasma concentration of atomoxetine and clinical efficacy, but with a lack of data from the Chinese pediatric population. Therefore, it is necessary to establish related clinical indicators for atomoxetine exposure, define the therapeutic exposure range of children with ADHD in China, and combine CYP2D6 genotyping to provide support for the precision medication of atomoxetine.

Une double discordance cardiaque complexe décompensée, à propos d'un cas et revue de la littérature / A double cardiac discordance decompensated, about a case and review of the literature

La double discordance est une cardiopathie congénitale complexe extrêmement rare, elle se caractérise par une discordance auriculo-ventriculaire suivie d'une autre discordance ventriculo-artérielle. Son diagnostic est posé généralement à l'âge adulte par des examens d'imagerie. Son pronostic dépend essentiellement des autres malformations congénitales cardiaques associées, des arythmies et des troubles de la conduction, ainsi que de la fonction systolique du ventricule droit en position systémique. Nous rapportons le cas d'un patient âgé de 23 ans, porteur d'une cardiopathie congénitale complexe cyanogène. Il s'agit d'une double discordance associée à une large communication interventriculaire sous aortique avec un shunt inversé et une hypoplasie de l'artère pulmonaire. Ce diagnostic a été confirmé par l'imagerie multimodale. Non opéré, le patient a vu son stade fonctionnel s'aggraver rapidement avec une dyspnée qui est passée d'un stade I à un stade III-IV de la New York Heart Association (NYHA), et apparition de signes hypoxiques et congestifs. A travers cette observation, nous avons précisé les caractéristiques anatomocliniques de cette cardiopathie congénitale complexe cyanogène, son exploration, ses options thérapeutiques, ainsi que le rôle péjoratif de son association avec d'autres malformations congénitales.

Double discordance is an extremely rare complex congenital heart disease; It is characterized by atrioventricular discordance followed by another ventriculo-arterial discordance. Its diagnosis is usually made in adulthood by imaging examinations. Its prognosis depends mainly on other associated congenital heart defects, arrhythmias and disorders of the conduction, as well as systolic function of the right ventricle in the systemic position. We report the case of a 23-year-old patient with a complex cyanogen heart disease.It is a double discordance associated to an interventricular communication with reverse shunt and an hypoplasia of the pulmonary artery.This Diagnosis was confirmed in multimodal imaging. Non-operated, the patient saw his functional status worsen rapidly with dyspnea which went from stage I to stage III-IV of the New York Heart Association (NYHA), and appearance of hypoxic and congestive signs. Through this observation, we have clarified the anatomoclinical characteristics of this complex congenital cyanogens heart disease, the necessary explorations and the different therapeutic options, as well as the pejorative role of its association with other congenital malformations.

A Clinicodemographic Study of Leprosy in Elderly: 8-Year Data from a Tertiary Care Centre in North India

The changing demographics of India due to better life expectancy has led to significant increase in the geriatric population. Physiological changes due to aging lead to altered biological response to disease as well as coping with it. There are very few published studies that have addressed the issue of geriatric leprosy. This was a retrospective record review of 8-year data from a tertiary care centre in North India of leprosy patients aged 60 years or more. Clinical and demographic details were noted. Data was compared with 154 other leprosy patients aged 18-59 years. Out of 1083 leprosy cases, 80 (7.4%) were elderly and 67.5% of these were males. Majority (92.5%) were in the multibacillary (MB) spectrum. Type 2 reactions were more commonly seen than type 1 reactions in this age group. Pre-existing co-morbidities were present in 52.5% of patients. Grade 2 disability (G2D) was noted in 13.8% of cases, all of whom were in MB spectrum. Comorbidities were significantly higher amongst the elders whereas nerve involvement and G2D rates were higher amongst other leprosy patients (18-59 years). The prevalence of geriatric leprosy is on the rise due to better life expectancy. The high MB rate and G2D rate in geriatric population is a cause of concern for ongoing disease transmission and leprosy control programs. Due to a higher proportion of patients having pre-existing co-morbid conditions and polypharmacy, this sub-group needs special attention and care after release from treatment

2D Echocardiographic Findings, NT-ProBNP Levels, and Outcomes in Dyspnoeic Patients: Results from the Pro-BNP Investigation of Dyspnoea in the Emergency Department- a Single Centre Experience

Background: Dyspnoeic in the emergency department with multiple co-morbidities is a diagnostic challenge. Approximately 15-20% of acute dyspneic in the Emergency Department due to ADHF (acute decompensated heart failure) are misdiagnosed. B-type peptide (BNP) and its amino-terminal fragment (NT-proBNP) accurately identify HF in dyspnoeic patients. In the general population with dyspnoea, plasma pro-BNP concentrations are increased in left ventricular dilatation, hypertrophy, systolic dysfunction, or diastolic dysfunction but are unaffected by pulmonary dysfunction. Aims and Objectives: To study the relation between NT pro-BNP & echocardiographic findings in acute dyspnoeic patients, and the relation between NT pro-BNP and In-hospital Mortality. Materials and Methods: Source of data- Patients admitted to the Emergency Room or cardiac intensive care unit with a history of acute dyspnea in a tertiary cardiac care center in south India, meeting inclusion & exclusion criteria, were studied. Results: The study population is predominantly constituted of the elderly population. The most common co-morbid condition was hypertension. The present study uses an NT pro BNP level of 900pg/ml as the cut-off level. 78 patients were positive for the test. Echocardiography showed that 58% had LV systolic dysfunction, 60% had diastolic dysfunction. 42 patients had EF >55%, 10 patients between 55-45%, 33 patients between 44-30% and 15 patients had EF < 30%. Mortality rate was 6% in the whole study population. However, Mortality was seen in only NT pro-BNP positive group it was not statistically significant (p=0.46). Conclusions: NT pro-BNP correlates well with the worsening of LV systolic function; as the EF decreases, NT pro-BNP increases. Increase in NT pro-BNP levels has to be interpreted in the clinical context, and it is not a substitute for echocardiography for assessing cardiac abnormalities and dysfunction.

Enantiomeric characteristics of non-synthetic cannabidiol by two-dimensional nuclear magnetic resonance

SUMMARY Introduction: Cannabidiol (CBD) has become a promising bioactive for the next decades after the recent recognition of the medical potential of Cannabis derivatives by United Nations member countries, as it has no psychotropic potential as your isomer A9-tetrahydrocannabinol (Δ9-THC). The differentiation of these isomers has been studied for decades. Recent studies demonstrate that even with more subtle chemical characteristics, such as those of the CBD enantiomers, there are considerable bioactive differences. However, there are still not many studies on their chemical structures. Aim: This work aims to present experimental data obtained by Nuclear Magnetic Resonance (NMR) to better elucidate the three-dimensional structure of this enantiomeric bioactive. Materials and methods: For this, a sample of non-synthetic high purity CBD was subjected to different one-dimensional (1D-NMR) and two-dimensional (2D-NMR) analyses related to the hydrogen (1H) and carbon (13C) nuclei. Results and discussion: The 1D-NMR techniques used are sufficient to distinguish the CBD and Δ 9-THC isomers, but not to identify the enantiomeric characteristics of the non-synthetic CBD. Conclusions: It is concluded that the two-dimensional homonuclear (1H,1H) and heteronuclear (1H,13C) techniques analyzed are suitable to help distinguish CBD enantiomers.

Introducción: El cannabidiol (CBD) se ha convertido en un bioactivo prometedor para las próximas décadas tras el reciente reconocimiento del potencial medicinal de los derivados del Cannabis por parte de los países miembros de las Naciones Unidas, ya que no tiene potencial psicotrópico como su isómero Δ9-tetrahidrocannabinol (Δ 9-THC). La diferenciación de estos isómeros se ha estudiado durante décadas. Estudios recientes demuestran que incluso con características químicas más sutiles, como las de los enan-tiómeros del CBD, existen diferencias bioactivas considerables. Sin embargo, no existen muchos estudios sobre sus estructuras químicas. Objetivo: Este trabajo tiene como objetivo presentar datos experimentales obtenidos por Resonancia magnética nuclear (RMN) para dilucidar mejor la estructura tridimensional de este bioactivo enantiomérico. Materiales y métodos: Para ello, una muestra de CBD no sintético de alta pureza se sometió a diferentes análisis unidimensionales (RMN-1D) y bidimensionales (RMN-2D) relacionados con los núcleos del hidrógeno (1H) y carbono (13C). Resultados y discusión: Las técnicas de RMN-1D utilizadas son suficientes para distinguir los isómeros de CBD y Δ 9-THC, pero no para identificar las características enantioméricas del CBD no sintético. Conclusiones: Se concluye que las técnicas bidimensionales homonucleares (1H,1H) y heteronucleares (1H,13C) analizadas son adecuadas para ayudar a distinguir los enantiómeros del CBD.

Introdução: O canabidiol (CBD) se tornou um bioativo promissor para as próximas décadas após o recente reconhecimento do potencial medicinal dos derivados da Cannabis pelos países membros das Nações Unidas, uma vez que não tem potencial psicotrópico como seu isômero Δ 9-tetrahidrocanabinol (A9-THC). A diferenciação desses isômeros é estudada há décadas. Estudos recentes demonstram que mesmo com características químicas mais sutis, como as dos enantiômeros do CBD, há consideráveis diferenças bioativas. Todavia, ainda não há muitos estudos sobre suas estruturas químicas. Objetivo: Este trabalho tem como objetivo apresentar dados experimentais obtidos por Ressonância magnética nuclear (RMN) para melhor elucidar a estrutura tridimensional deste bioativo enantiomérico. Materiais e métodos: Para isso, uma amostra de CBD não sintético de alta pureza foi submetida a diferentes análises unidimensionais (RMN-1D) e bidimensionais (RMN-2D) relacionadas aos núcleos de hidrogênio (1H) e carbono (13C). Resultados e discussão: As técnicas de RMN-1D usadas são suficientes para distinguir os isômeros CBD e Δ 9-THC, mas não para identificar as características enantioméricas do CBD não sintético. Conclusões: Conclui-se que as técnicas bidimensionais homonucleares (1H,1H) e heteronucleares (1H,13C) analisadas são adequadas para auxiliar na distinção dos enantiômeros do CBD.

La relación entre el biomarcador índice digital D2:D4 y el diagnóstico psicopedagógico de TDAH. Datos de un estudio / The relationship between the biomarker ratio D2:D4 and the psycho-pedagogical diagnosis of ADHD. Data from a study

Resumen La hipótesis organizacional sostiene que el índice digital D2:D4 (obtenido de la división entre la longitud de los dedos índice y anular) es un biomarcador que informa de la sobreexposición a la testosterona a nivel prenatal (Myers et al., 2018). El objetivo del presente trabajo fue determinar si el índice digital podría ser útil en el diagnóstico psicopedagógico del trastorno por déficit de atención con hiperactividad (TDAH), dado que los trabajos previos no son concluyentes en este punto (Stevenson et al., 2007; Wang et al., 2017). La muestra estudiada estuvo conformada por 82 estudiantes de ambos sexos (Medad = 11.77 años, DE = 2.97) de la región de Andalucía (España), igualada en edad, sexo y nivel cognitivo. La mitad de los participantes tenía diagnóstico de TDAH, la otra mitad, no. Los resultados reflejan menor índice digital en participantes del grupo con diagnóstico de TDAH (.945) versus el grupo control (.995), y estas diferencias son significativas (p = .000), independientemente del sexo. Además, la presencia de determinados comportamientos en el entorno doméstico (medidos con la Escala Conners) correlaciona positivamente con un bajo valor del índice digital (r = .47; p = .001) y con el diagnóstico psicopedagógico de TDAH.

Abstract The digital ratio D2:D4 (length of the index finger between the length of the ring finger) is a biomarker that reports the presence of high levels of testosterone during the prenatal period. A differential digital pattern (D2 < D4) has been found in several disorders (ASD or Klinefelter's syndrome) although data for Attention Deficit Hyperactivity Disorder (ADHD) are not conclusive (Stevenson et al., 2007; Wang et al., 2017). The aim of this paper was to determine whether digital ratio can be used as an indicator in the psychoeducational diagnosis of ADHD. A sample of 82 students of both sexes aged between 6 and 16 years (M = 11.77, SD = 2.97) from the Andalusian Community was taken. Among the members of the sample there were no differences in terms of sex, age, or cognitive level. The sample was divided into two groups, the group with a psycho-pedagogical diagnosis of ADHD and the control or undiagnosed group. The group with ADHD consisted of 42 subjects and the control group consisted of 46 subjects. All sessions were conducted individually for each of the subjects and their families following these guidelines: the session began with the parent signing a consent form that allowed the therapist to proceed with the intervention. After that, the TONI-2 non-verbal intelligence test was given to the child by the therapist in a quiet room. At the same time, the parents responded to the Conners Scale questions on behaviour at home to verify the existence or not of behavioural symptoms compatible with the presence of ADHD. For parents of children with ADHD diagnosis, an interview was conducted to learn about the course of the disease to have a general profile of the patient and his or her disorder. Finally, the participants' right hand was scanned at the same school with an HP DeskJet 2630 scanner printer. Using the scanner and the Adobe Photoshop® tool, the length of the index and ring fingers was measured [(from proximal line of the finger to the end of the distal phalanx of the index (D2) and ring (D4) fingers]. The digital measurements from the scanned images were taken by the two researchers who signed the work, and there was more than 90 % agreement on the measurements. The results show a lower digital index in participants in the ADHD group (.945) versus the control group (.995), these differences being significant (p = 0.000), regardless of gender. In addition, the presence of certain behaviours in the home environment (measured with the Conners Scale) correlates positively with a low value of the digital index (r = .47; p = .001) and with the psycho-pedagogical diagnosis of ADHD. Significant differences have been shown in this study. Subjects with a psychopedagogical diagnosis of ADHD have been exposed to higher levels of testosterone during pregnancy since they present a lower D2:D4 ratio compared to the participants in the control group (without a diagnosis of ADHD), in line with the work of Martel et al. (2008) and Wang et al. (2017). In addition, this study has found that the group with psychopedagogical diagnosis of ADHD has a shorter index finger than the ring finger in both boys and girls, while for the control group the digital pattern is reversed or there is no difference between the two fingers. Therefore, we consider that the digital ratio biomarker (D2:D4) may be an additional useful criterion for the psychopedagogical diagnosis of ADHD or at least as a screening method.

Is digit ratio (2D:4D) different between sexual and non-sexual offenders, and non-offending men: study of a Colombian sample / Existen diferencias en la ratio 2D:4D entre delincuentes sexuales y no sexuales, y hombres no delincuentes? Un estudio en una muestra colombiana

Abstract One research line in criminal behavior studies 2D:4D ratio as predictor of aggression and violent behavior has been established, given that there are sexually dimorphic behaviors associated with the influence of testosterone on brain organization. However, results have been mixed. The aim of this study was to explore the differences in the 2D:4D ratio among offending and non-offending Colombian men in four groups (N = 139). A comparative study was conducted with three groups of offenders sentenced in a Colombian penitentiary: (1) sexual offenders against children (n = 34), (2) sexual offenders against adult women (n = 31), and (3) non-sexual violent offenders (n = 26); as well as one group (4) men with no criminal record (n = 48). The 2D:4D ratio was measured using the hand scanning technique and three digital measurements were analyzed with the Autometric software: right hand ratio, left hand ratio, and difference between the right and left hand ratios (Dr - Iz). Although, in all groups, right-digit ratio was lower that left-digit ratio (negative Dr-l ratio) and, in non-offending men this difference was not significant, no strong significant differences were found between groups in any measure of 2D:4D ratio used (right hand, left hand or Dr−l). The results support the idea that these associations are too weak to consider them predictors of sexual or non-sexual criminal behavior. The risk factors determining sexual or non-sexual criminal behavior, seems to go beyond intra-uterine effects and involve complex interactions between heritability, epigenetics, and pre-natal and post-natal life events.

Resumen Una de las líneas de investigación de la conducta criminal estudia la relación 2D:4D como predictor de agresión y comportamiento violento, dada la conexión de este marcador biológico con la influencia de la testosterona en la organización del cerebro y los comportamientos sexualmente dimórficos más prevalentes en hombres. Los resultados han sido mixtos y, en general, se han encontrado tamaños de efecto débiles, aunque significativos, en la relación entre proporción 2D:4D y el comportamiento agresivo, con escasos estudios comparativos y con muestras forenses. El objetivo de este estudio fue explorar las diferencias en la relación 2D:4D entre hombres colombianos (N = 139) con y sin delitos en cuatro grupos. Para ello, .e realizó un estudio comparativo con tres grupos de delincuentes condenados en una cárcel de Colombia: (1) agresores sexuales de menores (n = 34); (2) agresores sexuales de mujeres adultas (n = 31); (3) delincuentes violentos no sexuales (n = 26), y uno de (4) hombres sin antecedentes delictivos (n = 48). Se midió la proporción 2D:4D usando la técnica de escaneo de las manos y se analizaron tres medidas digitales con el software Autometric: proporción de la mano derecha, mano izquierda y diferencia entre la proporción de las manos derecha e izquierda (Dr - Iz). Se encontraron diferencias significativas entre la diferencia de la proporción Dr-Iz en todos los grupos, en la que la 2D:4D de la mano derecha fue menor que la de la mano izquierda en todos los grupos. Sólo en los hombres sin antecedentes delictivos esta diferencia no fue significativa. Para evaluar las diferencias grupales en las relaciones 2D:4D, se ajustaron modelos tipo a ANOVA unidireccional con un solo grupo como predictor, seguidos de contrastes de Helmert para comparar las diferencias entre todos los grupos. El grupo predijo sólo la diferencia de las proporciones Dr - Iz, pero no las proporciones de la mano derecha o izquierda por separado. El grupo de hombres sin antecedentes delictivos, mostró una proporción 2D:4D de la mano izquierda significativamente menor (masculinizada) y una menor diferencia (más cercana a cero) entre las proporciones Dr-Iz comparado con los grupos de delincuentes. Sin embargo, los contrastes con cada grupo, mostraron que la diferencia sólo fue significativa con el grupo de delincuentes violentos no sexuales, pero no con los grupos de agresores sexuales. Se concluyó que no hubo diferencias significativas importantes y concluyentes entre los grupos en ninguna medida de la proporción 2D:4D utilizada (mano derecha, mano izquierda o Dr − Iz). Estos resultados respaldan la idea de que estas asociaciones son demasiado débiles para considerarlas predictores de conductas criminales sexuales o no sexuales. Los factores de riesgo que determinan el comportamiento delictivo sexual o no sexual parecen ir más allá de los efectos intrauterinos reflejados por el biomarcador 2D:4D y, posiblemente, involucrar interacciones complejas entre heredabilidad, epigenética y eventos de la vida prenatal y postnatal. Si la relación 2D:4D es un marcador indirecto válido y confiable de androgenización prenatal, no es algo que se pueda discutir con los datos aquí obtenidos. Sin embargo, si tiene más que un simple efecto detectado por casualidad en el comportamiento delictivo, esto también debería explorarse más a fondo no sólo en la mano derecha, como la mayoría de la investigación disponible lo ha hecho, sino en la mano izquierda y en la diferencia entre las proporciones 2D:4D Dr-Iz, para evaluar si su poder explicativo se mantiene bajo como hasta ahora o incluso inexistente.

Ortodoncia estética. Tratamientos híbridos o combinados: ortodoncia lingual y vestibular / Aesthetic orthodontics. Hybrid or combined treatments: lingual and vestibular orthodontics

La ortodoncia lingual ha acercado a la consulta ortodóncica a pacientes que nunca antes hubie- ran aceptado un tratamiento ortodóncico. Los tratamientos estéticos son una de las opciones más solicitadas en este siglo por los pacientes adultos, que no solo desean un resultado estético sino que solicitan, también, aparatología estética. Se presenta el caso de una paciente adulta para el que se eligió un tratamiento híbrido: aparatología superior lingual (brackets linguales 2D) y apara- tología inferior vestibular (brackets autoligables, prescripción Roth pasiva-activa). Los brackets 2D son de autoligado, por lo que se utilizan fuerzas biológicas, suaves, constantes y continuas. Es importante en estos casos que ambos maxilares se trabajen con el mismo tipo de fuerzas.

Lingual orthodontics has brought to the orthodontic consultation patients who would never have accepted orthodontic treatment before. In this century, aesthetic treatments are one of the most requested options by adult patients who not only want an aesthetic result but also aesthetic appliances. It is presented the case of an adult patient to which a hybrid treatment was chosen: upper lingual appliances (2D lingual brackets) and lower vestibular appliances (self-ligating brackets, passive-active Roth prescription). 2D brackets are self-ligating, so constant and continuous biological gentle forces are used. In these cases, it is important that both jaws are worked with the same type of forces.

Study of cardiac function in adults with dengue

Background: Medical literature has reports of isolated cases of atrioventricular conduction disorders, supraventricular arrhythmias, and myocarditis in dengue fever (DF).There is a paucity of data available in the published literature on the cardiac manifestations of DF from India. The aim of the present study was to assess the cardiac manifestations of DF. Methods: The140 patients aged ?18 years with DF confirmed with a serology-dengue non-structural protein 1 antigen-positivewere included for this prospective observational study. Three serial ECGs were taken on day one, day three and day seven or day of discharge. All the patients were evaluated using 2D echo on day one, day seven or day of discharge. The primary outcome measures were to find the incidence and type of echocardiographic abnormalities and electrocardiographic changes in dengue.Results: The incidence of cardiac abnormalities on ECG and 2D echo was 30 (21.4%), and 5 (7.0%) respectively. On ECG, 14 (10%) 9 (6.4%) 3 (2.1%) 3 (2.1%) and 1 (0.7%) patients had sinus bradycardia, sinus tachycardia, non-specific ST-T changes, right bundle branch block and atrio-ventricular block respectively. On 2D echo, 7 (5.0%), 5 (3.6%) and 1 (0.7%) patient had systolic dysfunction, ejection fraction (<45.0%) and diastolic dysfunctionrespectively. Conclusions: The incidence of cardiac abnormalities on ECG and 2D ECHO in dengue patients was considerable. ECG and 2 D echo should be undertaken in patients with DF.

A comparative study of visual assessment between dry bone, 2-dimensional photograph, and deep learning methods in sex classification on the auricular area of the os coxae in a Thai population / Un estudio comparativo de la evaluación visual entre el hueso seco, la fotografía bidimensional y los métodos de aprendizaje profundo en la clasificación del sexo en el área auricular del hueso coxal en una población tailandesa

SUMMARY: Sex assessment is an important process in forensic identification. A pelvis is the best skeletal element for identifying sexes due to its sexually dimorphic morphology. This study aimed to compare the accuracy of the visual assessment in dry bones as well as 2D images and to test the accuracy of using a deep convolutional neural network (GoogLeNet) for increasing the performance of a sex determination tool in a Thai population. The total samples consisted of 250 left os coxa that were divided into 200 as a 'training' group (100 females, 100 males) and 50 as a 'test' group. In this study, we observed the auricular area, both hands-on and photographically, for visual assessment and classified the images using GoogLeNet. The intra-inter observer reliabilities were tested for each visual assessment method. Additionally, the validation and test accuracies were 85, 72 percent and 79.5, 60 percent, for dry bone and 2D image methods, respectively. The intra- and inter-observer reliabilities showed moderate agreement (Kappa = 0.54 - 0.67) for both visual assessments. The deep convolutional neural network method showed high accuracy for both validation and test sets (93.33 percent and 88 percent, respectively). Deep learning performed better in classifying sexes from auricular area images than other visual assessment methods. This study suggests that deep learning has advantages in terms of sex classification in Thai samples.

RESUMEN: La evaluación del sexo es un proceso importante en la identificación forense. La pelvis es el mejor elemento esquelético para identificar sexos debido a su morfología sexualmente dimórfica. Este estudio tuvo como objetivo comparar la precisión de la evaluación visual en huesos secos, así como imágenes 2D y probar la precisión del uso de una red neuronal convolucional profunda (GoogLeNet) para aumentar el rendimiento de una herramienta de determinación de sexo en una población tailandesa. Las muestras consistieron en 250 huesos coxales izquierdos, los que fueron dividi- das de la siguiente manera: 200 como un grupo de "entrenamiento" (100 mujeres, 100 hombres) y 50 como un grupo de "prueba". En este estudio, observamos el área auricular, tanto de forma práctica como fotográfica, para una evaluación visual y clasificamos las imágenes utilizando GoogLeNet. Se analizó la confiabilidad intra-interobservador para cada método de evaluación visual. Además, las precisiones de validación y prueba fueron del 85, 72 por ciento y 79,5, 60 por ciento, para los métodos de hueso seco y de imágenes 2D, respectivamente. Las confiabilidades intra e interobservador mostraron un acuerdo moderado (Kappa = 0.54 - 0.67) para ambas evaluaciones visuales. El método de red neuronal convolucional profunda mostró una alta precisión tanto para la validación como para los conjuntos de prueba (93,33 por ciento y 88 por ciento, respectivamente). El aprendizaje se desempeñó mejor en la clasificación de sexos a partir de imágenes del área auricular que otros métodos de evaluación visual. Este estudio sugiere que el aprendizaje profundo tiene ventajas en términos de clasificación por sexo en muestras tailandesas.

Left ventricular global longitudinal strain imaging in identifying subclinical myocardial dysfunction among covid-19 survivors

Background: Covid-19 is multi-system viral infection caused by SARS-CoV-2 virus. Apart from having acute severe respiratory illness causing high mortality, the disease also has a variety of cardiovascular manifestations contributing to morbidity as well as mortality. Cardiac dysfunction and myocarditis are well established complications of Covid-19 as evident in multiple studies after the Covid-19 pandemic. However it is not sufficiently studied in Indian patients either by Echocardiography or by any other imaging modalities like cardiac magnetic resonance imaging (MRI). Methodology: In this study, we analysed the severity of Left ventricular(LV) dysfunction in Covid-19 survivors. A total of 100 consecutive patients of Covid-19 after one month of discharge who had no underlying cardiovascular diseases underwent echocardiography and global longitudinal strain (GLS) imaging. This study cohort included patients with mild 42 (42%),moderate 46(46%) and severe 12(12%) Covid-19 disease as defined by computerised tomography (CT) severity score. Result: We observed that total 36(36%) patients had reduced ejection fraction(EF) which included 11 patients having EF <40% and remaining 25(25%) having EF 40e50% (p<0.002). Also 22 (22%) patients had abnormal global longitudinal strain (GLS) values with normal ejection fraction which is suggestive of subclinical myocarditis. We observed LV dysfunction in 7(19.5%) patients who had severe Covid-19 while mild to moderate LV dysfunction observed in 29(80.5%) non critical patients. Conclusion: In conclusion our study demonstrates that myocardial dysfunction is common in covid-19 regardless of disease severity. 2D-echocardiography with GLS is likely to detect early LV dysfunction among these patients.