New candidate SNPs for genetic association with Alzheimer's disease: a linkage disequilibrium analysis for the FCGRIIB and PILRA genes

Background Two new SNPs have been recently associated to Alzheimer's disease in African American populations: FCGRIIB rs1050501 C/T, and PILRA rs1859788 A/G. The risk of Alzheimer's disease in FCGRIIB C and PILRA A allele carriers is three times higher than in non-carriers. However, the association between these and other single nucleotide polymorphisms (SNPs) has not been assessed. Methods Linkage disequilibrium analysis, with r= 0.8 as a threshold value, was used to impute new candidate SNPs, on genomic data from both genes in 26 populations worldwide (n= 2504) from the 1000Genomes database. Results Four SNPs (rs13376485, rs3767640, rs3767639 and rs3767641) were linked to rs1050501 and one (rs2405442) to rs1859788 in the whole sample. Conclusions Five novel SNPs could be associated with Alzheimer's disease susceptibility and play a causal role, even if none of them are exon variants since their potential roles in the regulation of gene expression.

Antecedentes Recientemente se han asociado dos nuevos polimorfismos de un solo nucleótido (SNP) a la enfermedad de Alzheimer en poblaciones afroamericanas: FCGRIIB rs1050501 C/T, y PILRA rs1859788 A/G. El riesgo de enfermedad de Alzheimer en los portadores de los alelos FCGRIIB C y PILRA A es tres veces mayor que en los no portadores. Sin embargo, no se ha evaluado la asociación entre estos y otros SNP. Métodos Se utilizó el análisis de desequilibrio de ligamiento, con r2= 0,8 como valor umbral, para imputar nuevos SNPs candidatos, sobre datos genómicos de ambos genes en 26 poblaciones de todo el mundo (n= 2504) de la base de datos 1000Genomes. Resultados Cuatro SNPs (rs13376485, rs3767640, rs3767639 y rs3767641) se vincularon al rs1050501 y uno (rs2405442) al rs1859788 en toda la muestra. Conclusiones Cinco nuevos SNP podrían estar asociados con la susceptibilidad a la enfermedad de Alzheimer y desempeñar un papel causal, aunque ninguno de ellos sea una variante de exón, dado su papel potencial en la regulación de la expresión génica.

Review and Prospect of Development Status of Traditional Chinese Medicine Processing Technology from 1.0 to 4.0 / 中国实验方剂学杂志

The development and application of processing technology is closely related to the quality of Chinese medicine. Currently， Chinese medicine processing is still in the mechanization stage with limited processing equipment， low levels of automation and intelligence. As a result， the imprecise control of parameters during processing leads to unstable quality of Chinese herbal pieces. However， with the arrival of the big data era and the continuous development of "Internet+"， Chinese medicine processing technology and equipment have been continuously improved and updated， and gradually shifted to the development direction of automation and intelligence. The linkage production technology of Chinese herbal pieces optimizes the separate processing equipment coupling into the production line for continuous manufacture of Chinese herbal pieces， intending to improve production efficiency. The large-scale industrialized production of Chinese herbal pieces tends towards digital technology of processing experience and online inspection technology based on machine vision， electronic nose， and electronic tongue. These technologies are crucial prerequisites for standardizing the parameters of Chinese medicine processing. And further by docking the processing process and equipment with the internet， realizing the intelligent control of the production process is an important process for the transformation and upgrading of Chinese herbal piece industry in the future. In this paper， we summarized the development characteristics of different stages of Chinese medicine processing technology， combed application and development of processing theory， the evolution of processing equipment， and problems in the current industrial development stage of Chinese medicine processing， in order to provide ideas and methods for achieving digital and intelligent innovation of processing technology as well as high-efficient and high-quality production of Chinese herbal pieces.

Avaliação do sistema de vigilância em saúde do trabalhador relacionada aos acidentes de trabalho, antes e após a implantação do software de linkage Sentinela, em Porto Alegre, 2018-2021 / Evaluation of the occupational health surveillance system before and after the implementation of the Sentinela linkage software, in Porto Alegre, 2018-2021 / Evaluación del sistema de vigilancia de la salud del trabajador relacionada con los accidentes de trabajo, antes y después de la implementación del software de enlace Sentinela, en Porto Alegre, 2018-2021

O objetivo deste artigo é avaliar, segundo alguns atributos, o sistema de vigilância dos acidentes de trabalho antes e após a implantação do software Sentinela (2018-2021), com base em uma pesquisa descritiva de dados secundários, e efetuar recomendações. Foram analisadas variáveis da ficha de investigação, de acordo com os atributos qualidade dos dados (completitude e consistência), oportunidade e representatividade. Os resultados mostraram que, após o Sentinela, houve aumento da notificação de acidentes (66,16%), maior completitude das variáveis, com importante alteração na 'atividade econômica' (98,9%) e 'evolução' (96,3%), diminuição dos campos ignorados/em branco, com destaque para o campo 'evolução' (3,7%), e melhora na oportunidade de controle dos acidentes fatais (79 dias). Concluímos que a vigilância dos acidentes de trabalho tem excelente qualidade dos dados, é representativa, mas inoportuna. O Sentinela melhorou o sistema, tornando-o mais sensível na captação dos acidentes e permitindo-lhe ter informações de melhor qualidade. É necessária a avaliação rotineira dos atributos, para aprimoramento constante do sistema, assim como rever as rotinas das equipes de saúde, melhorando a oportunidade de controle por meio de suas ações

This article aims to evaluate the occupational health surveillance system before and after the implementa-tion of the Sentinela software (2018-2021), according to some attributes and based on descriptive research using secondary data, and to make recommendations. Variables of the accident investigation report were analysed, according to the attributes of data quality (completeness and consistency), opportunity and rep-resentativeness. The results have revealed that after Sentinela, there was an increase in the notification of accidents (66.16%), greater completeness of the variables, with an important change in 'economic activity' (98.9%) and 'evolution' (96.3%), a decreased in blank fields/information missing, with emphasis on the 'evolution' field (3.7%), and an improvement in the opportunity to control fatal accidents (79 days). We have concluded that the surveillance of the occupational accidents has excellent data quality, is representative, but inopportune. The Sentinela has improved the system, making it more sensitive in capturing accidents, allowing it to provide better quality of information. An evaluation of the attributes is routinely necessary to constantly improve the system, as well as reviewing the routines of health professionals, improving the opportunity to control by their actions

El objetivo de este artículo es evaluar, según algunos atributos, el sistema de vigilancia de los accidentes de trabajo antes y después de la implementación del software Sentinela (2018-2021), por medio de una investigación descriptiva de datos secundarios, y hacer recomendaciones. Fueron analizadas variables de la ficha de investigación de accidentes, de acuerdo con los atributos de calidad de los datos (completitud y consistencia), oportunidad y representatividad. Los resultados demostraron que, después del Sentinela, ha habido un aumento de la notificación de accidentes (66,16 %), una mayor completitud de las variables, con un cambio importante en 'actividad económica' (98,9 %) y 'evolución' (96,3 %), una disminución de campos ignorados/en blanco, con énfasis en el campo 'evolución' (3,7%), y mejora en la probabilidad de control de los accidentes mortales (79 días). Concluimos que la vigilancia de los accidentes de trabajo tiene excelente calidad de datos, es representativa, pero inoportuna. El Sentinela ha mejorado el sistema, haciéndolo más sensible en la captación de los accidentes y permitiéndole tener informaciones de mejor calidad. La evaluación de los atributos con regularidad es necesaria para el perfeccionamiento constante del sistema, así como la revisión de las rutinas de los equipos de salud, mejorando la oportunidad de control a través de sus acciones

population analysis of the CLOCK rs3749474T-rs4864548A haplotype and its relationship with obesity / Análisis poblacional in silico del haplotipo CLOCK rs3749474T-rs4864548A y su relación con obesidad

Se ha sugerido que el haplotipo rs3749474T/rs4864548A del gen CLOCK aumentaría el riesgo de obesidad, pero se desconoce el patrón de variabilidad poblacional de estos alelos y del haplotipo. El objetivo de este estudio es determinar el nivel de ligamiento entre los alelos de riesgo rs3749474T y rs4864548A a partir de la base de datos 1000Genomes para confirmar la existencia del haplotipo TA de los polimorfismos rs3749474-rs4864548 del gen CLOCK y su frecuencia cinco macro poblaciones. Se analizó el desequilibrio de ligamiento y las frecuencias haplotípicas para 2504 individuos, de 26 poblaciones, utilizando el estadístico r y la prueba exacta de Fisher. Existe una alta frecuencia del haplotipo TA en Latinoamérica (44,8%), un alto desequilibrio de ligamiento (r= 0,92) a nivel mundial entre esos alelos, una alta diferenciación entre macro poblaciones y una alta homogeneidad al interior de ellas. La evidencia presentada permite sugerir la realización de posteriores estudios de asociación entre este haplotipo y el nivel de riesgo de obesidad y sobrepeso en poblaciones latinoamericanas.

It has been suggested that the rs3749474T/rs4864548A haplotype of the CLOCK gene increases the risk of obesity, but the population variability of these alleles and the haplotype is unknown. This research aims to determine the linkage between the rs3749474T and rs4864548A alleles from the database of 1000Genomes to confirm the existence of the TA haplotype polymorphisms of these alleles and their frequency in five macro populations. Linkage disequilibrium and haplotype frequencies for 2504 individuals from 26 populations were analyzed using the r statistic and Fisher's exact test. There is a high frequency of the TA haplotype in Latin America (44.8%), a high linkage disequilibrium (r2= 0.92) worldwide between these alleles, a high differentiation between macro populations, and a high homogeneity. The evidence warrants further studies on the association between this haplotype and the risk of obesity and overweight in Latin American populations.

Tendência temporal da prevalência e mortalidade infantil das anomalias congênitas no Brasil, de 2001 a 2018 / Temporal trends in prevalence and infant mortality of birth defects in Brazil, from 2001 to 2018

Resumo As anomalias congênitas (AC) configuram um relevante problema para a saúde pública global, afetando em média de 3% a 6% dos recém-nascidos em todo o mundo. No Brasil, ocupam a segunda posição entre os principais grupos de causas de óbito infantil. Assim, estudos amplos são necessários para mostrar o impacto das AC na saúde infantil. O presente estudo descreve a tendência temporal da prevalência e da mortalidade infantil por AC entre nascidos vivos (NV) no Brasil e em suas cinco regiões de 2001 a 2018, utilizando dados vinculados entre as bases de dados do Sistema de Informações sobre Nascidos Vivos (SINASC) e do Sistema de Informações sobre Mortalidade (SIM). A prevalência e mortalidade infantil por AC mostrou-se crescente no Brasil na maioria das regiões, principalmente no Norte e no Nordeste. Aquelas do aparelho osteomuscular foram as mais prevalentes ao nascimento (29,8/10.000 NV); as do aparelho circulatório passaram para a segunda posição (12,7/10.000 NV) após a vinculação das bases e representam a primeira causa de morte desse grupo. A técnica de vinculação de dados aplicada corrigiu a prevalência nacional das AC em 17,9% no período analisado, após serem recuperadas as AC notificadas no SIM, mostrando ser uma boa ferramenta para melhorar a qualidade das informações das AC.

Abstract Congenital anomalies (CA) are a relevant problem for global public health, affecting about 3% to 6% of newborns worldwide. In Brazil, these are the second main cause of infant mortality. Thus, extensive studies are needed to demonstrate the impact of these anomalies on births and deaths. The present study describes the temporal trends of prevalence and infant mortality due to CA among live births in Brazil and regions, from 2001 to 2018, using the related data between the Live Birth Information System (SINASC, acronym in Portuguese) and the Mortality Information System (SIM, acronym in Portuguese). The prevalence and infant mortality due to CA has increased in Brazil and in most regions, especially in the Northeast and North. CAs in the musculoskeletal system were the most frequent at birth (29.8/10,000 live births), followed by those in the circulatory system (12.7/10,000 live births), which represented the primary cause of death in this group. The applied linkage technique made it possible to correct the national prevalence of CA by 17.9% during the analyzed period, after retrieving the anomalies reported in SIM, thereby proving to be a good tool to improve the quality of information on anomalies in Brazil.

Exploration on multifunctional linkage and scientific use of medical colleges psychological experimental teaching center based on the network background / 中华医学教育探索杂志

The experimental teaching of psychology is not only an important course in the undergraduate and graduate education of applied psychology, but also can assist the practical teaching of quite a few other subjects. It clearly divides three basic functions of experimental psychology teaching center: teaching, scientific research and service, which play an important role in facilitating teachers and students to understand corresponding courses. At the same time, it is discussed and proposed to strengthen the internal and external scientific linkage of the experimental center under the network background, and put forward the use of Internet technology, in order to improve the scientific use of the experimental teaching center, and reflect its maximum value, thereby achieving the purpose of university laboratory joint construction and serve the university to cultivate innovative and compound personnels.

Fragmentation stability and retention time-shift obtained by LC-MS/MS to distinguish sialylated N-glycan linkage isomers in therapeutic glycoproteins / 药物分析学报

Sialylated N-glycan isomers with α2-3 or 42-6 linkage(s)have distinctive roles in glycoproteins,but are difficult to distinguish.Wild-type(WT)and glycoengineered(mutant)therapeutic glycoproteins,cyto-toxic T lymphocyte-associated antigen-4-immunoglobulin(CTLA4-Ig),were produced in Chinese ham-ster ovary cell lines:however,their linkage isomers have not been reported.In this study,N-glycans of CTLA4-Igs were released,labeled with procainamide,and analyzed by liquid chromatography-tandem mass spectrometry(MS/MS)to identify and quantify sialylated N-glycan linkage isomers.The linkage isomers were distinguished by comparison of 1)intensity of the N-acetylglucosamine ion to the sialic acid ion(Ln/Nn)using different fragmentation stability in MS/MS spectra and 2)retention time-shift for a selective m/z value in the extracted ion chromatogram.Each isomer was distinctively identified,and each quantity(＞0.1％)was obtained relative to the total N-glycans(100％)for all observed ionization states.Twenty sialylated N-glycan isomers with only α2-3 linkage(s)in WT were identified,and each isomer's sum of quantities was 50.4％.Furthermore,39 sialylated N-glycan isomers(58.8％)in mono-(3 N-glycans;0.9％),bi-(18;48.3％),tri-(14;8.9％),and tetra-(4;0.7％)antennary structures of mutant were obtained,which comprised mono-(15 N-glycans;25.4％),di-(15;28.4％),tri-(8;4.8％),and tetra-(1;0.2％)sialy-lation,respectively,with only α2-3(10 N-glycans;4.8％),both α2-3 and α2-6(14;18.4％),and only α2-6(15;35.6％)linkage(s).These results are consistent with those for α2-3 neuraminidase-treated N-glycans.This study generated a novel plot of Ln/Nn versus retention time to distinguish sialylated N-glycan linkage isomers in glycoprotein.

Application of Internet-based hospital-institution linkage care management model in elderly care for elderly people with dementia / 中国实用护理杂志

Objective:To explore the application effect of Internet-based hospital-institution linkage care management model in elderly care for the elderly of dementia.Methods:The research was a quasi-experiment study. A total of 80 elderly people of dementia from three combined medical and nursing institutions, Beijing Fangshan District Mental Health Care Hospital, Beijing Jinhai Hospital of Traditional Chinese Medicine, and Beijing Yiciyuan Nursing Care Center, were selected as the research objects by convenient sampling. The elderly people of dementia enrolled from May to August 2021 served as the control group, and elderly people of dementia enrolled from September to December 2021 served as the experimental group, with 40 cases in each group. Conventional management methods were taken in the control group, while Internet-based hospital-institution linkage care management model was taken in the experimental group. Before the intervention, at 3 months of intervention, the Mini-Mental State Examination (MMSE), Barthel index (BI) and Cohen Mansfield agitation behavior inventory (CMAI) were used to evaluate the cognitive function, activities of daily living and agitation behavior of two groups.Results:A total of 78 cases were included, including 39 cases in the experimental group and 39 cases in the control group, respectively. Before intervention, there was no significant difference in scores of MMSE, BI, and CMAI in the two groups of elderly people with dementia ( P>0.05). After 3 months of intervention, the score of MMSE in the experimental group was (17.36±5.67) points, which was higher than (15.05 ± 2.70) points of the control group, and the difference was statistically significant ( t=2.13, P<0.05). The score of CMAI in the experimental group was (34.18 ± 4.37) points, which was lower than (37.13 ± 5.06) points of the control group, and the difference was statistically significant ( t=2.76, P<0.05). There was no significant difference in BI scores ( t=0.13, P>0.05). Conclusions:The Internet-based hospital-institution linkage care management model improves the cognitive function and agitated behavior of the elderly with dementia in medical-nursing institutions.

Study on essential medicine system from the perspective of coordinated with centralized volume-based procurement policy / 中国药房

OBJECTIVE To provide a reference for further improvement of the essential medicine system. METHODS Statistical analysis method and comparative analysis method were used to explain the necessity of coordination between the two systems from the direct correlation and indirect impact of centralized volume-based procurement on the essential medicine system at the present stage. The relevant suggestions were put forward for the development of the essential medicine system in the new era from the perspective of improving institutional synergy. RESULTS & CONCLUSIONS There was a direct correlation between the policy of centralized procurement and the essential medicine system in terms of policy objectives and medicines selection. However， it also indirectly affects the use of essential medicines in medical institutions through production and supply， coincidence degree between the essential medicine list and the selected variety， and the consistency evaluation of generic drugs. It is suggested that in the selection of essential medicine list in the future， priority should be given to the selection of varieties through centralized procurement， and improve the drug supply guarantee capacity under the dual policy linkage； at the same time， incentive assessments for the allocation and use of essential medicines by various entities should be further strengthened to promote the further improvement and development of the essential medicine system.

Research progress on linear ubiquitin chain assembly complex and OTU deubiquitinase with linear linkage specificity in tumor / 药学实践杂志

Linear ubiquitination is an important post-translational modification that has been discovered in recent years. The linear ubiquitin chain is formed by the linkage of glycine residue of one ubiquitin protein to the methionine residue of another ubiquitin. This process is regulated by the linear ubiquitin chain assembly complex (LUBAC) and the OTU deubiquitinase with linear linkage specificity (OTULIN). Linear ubiquitination is involved in various biological processes, including immune response, inflammation, and cell apoptosis. Recent studies have shown that linear ubiquitination is closely related to the occurrence, development, and drug resistance of tumors by affecting signaling pathways such as NF-κB and Wnt/β-catenin. The research progress on the function of LUBAC and OTULIN in tumors was reviewed in this paper.

Integración de la vinculación-investigación en la carrera de Medicina de la Universidad Regional Autónoma de Los Andes

Introducción: La integración de la investigación científica y la vinculación es clave para la contribución de las universidades a la solución de los problemas de la sociedad mediante la transferencia de conocimientos y la innovación. Objetivo: Caracterizar el proceso de integración entre vinculación e investigación en la carrera de Medicina de UNIANDES. Método: Se realizó una investigación predominantemente cualitativa y descriptiva con la utilización del análisis documental y la entrevista. Se revisaron documentos rectores, lineamientos, y políticas, aplicadas en la carrera de Medicina. Se aplicaron entrevistas a los coordinadores en la carrera para buscar volumen informativo acerca de estas dos actividades y las proyecciones concretas de transversalización. Resultados: Se denotó una debilidad en cuanto a la gestión de la vinculación con la sociedad, ausencia de una visión más amplia de una gestión integral donde no solo se imbrique vinculación con docencia en las prácticas preprofesionales sino en los proyectos integradores y la existencia de la voluntad de los directivos institucionales en gestar desde la investigación una verdadera vinculación universidad-sociedad. Conclusiones: Falta una visión más amplia de la integración entre los tres procesos claves universitarios, se evidencia solo la relación entre docencia y vinculación a partir de las prácticas preprofesionales, dejando fuera la base y génesis que deben ser los proyectos integradores de saberes. En aras del perfeccionamiento de esta integración se deben proponer proyectos de innovación social donde se unan vinculación e investigación, garantizar la publicación de los resultados de los proyectos de innovación social en las revistas internas de UNIANDES y en otras de impacto regional o mundial.

Introduction: The integration of scientific research and linkage is key for the contribution of universities to the solution of society's problems through the transfer of knowledge and innovation. Objective: Characterize the integration process between linkage and research in the UNIANDES Medicine degree. Method: A predominantly qualitative and descriptive research was carried out with the use of documentary analysis and interviews. Governing documents, guidelines, and policies applied in the Medicine career were reviewed. Interviews were carried out with the coordinators in the program to search for volume of information about these two activities and the specific projections of mainstreaming. Results: A weakness was noted in terms of the management of the link with society, absence of a broader vision of comprehensive management where not only linkage with teaching is intertwined in pre-professional practices but also in integrative projects and the existence of will of institutional directors to create a true university-society link through research. Conclusions: A broader vision of the integration between the three key university processes is missing, only the relationship between teaching and connection is evident from pre-professional practices, leaving out the basis and genesis that knowledge-integrating projects should be. In order to perfect this integration, social innovation projects must be proposed where linkage and research come together, guaranteeing the publication of the results of social innovation projects in the internal journals of UNIANDES and in others with regional or global impact.

Introdução: A integração e articulação da investigação científica é fundamental para a contribuição das universidades na solução dos problemas da sociedade através da transferência de conhecimento e inovação. Objetivo: Caracterizar o processo de integração entre vinculação e pesquisa na graduação em Medicina da UNIANDES. Método: Foi realizada uma pesquisa predominantemente qualitativa e descritiva com utilização de análise documental e entrevistas. Foram revisados documentos normativos, diretrizes e políticas aplicadas à carreira de Medicina. Foram realizadas entrevistas com os coordenadores do programa para buscar volume de informações sobre essas duas atividades e as projeções específicas de mainstreaming. Resultados: Constatou-se uma fragilidade na gestão do vínculo com a sociedade, ausência de uma visão mais ampla de uma gestão integral onde não só o vínculo com o ensino esteja entrelaçado nas práticas pré-profissionais, mas também nos projetos integradores e na existência de vontade de instituições diretores para criar um verdadeiro vínculo universidade-sociedade através da pesquisa. Conclusões: Falta uma visão mais ampla da integração entre os três principais processos universitários, apenas a relação entre ensino e conexão é evidente nas práticas pré-profissionais, deixando de fora a base e a gênese que os projetos integradores de conhecimento deveriam ser. Para aperfeiçoar esta integração, devem ser propostos projetos de inovação social onde a articulação e a investigação se unam, garantindo a publicação dos resultados dos projetos de inovação social nas revistas internas da UNIANDES e em outras com impacto regional ou global.

Multi-link Linkage Research on Medical Humanistic Education by Integrating Narrative Medical Materials / 中国医学伦理学

Taking the current situation and problems of medical humanities education as the background, the concept of narrative medicine was used to sort out and integrate various course materials of medical humanities, explore the multi-link linkage mode of medical humanities education, and organically integrate medical humanities courses scattered in medical education activities such as medical ethics, health law, doctor-patient communication, and health policy science with teaching stages, teaching resources, and teaching methods, forming vivid narrative medical materials throughout the entire process of medical humanities education, and improving teaching efficiency by sharing and optimizing resources. Through questionnaire analysis, it was found that there are many unsatisfactory aspects of medical humanities education. Further analysis of the issues focuses on the contradiction between learning willingness and time allocation, the lack of synchronization between teaching and social development, the lack of integration between courses, and insufficient innovation in teaching methods. Based on these, countermeasures were put forward to integrate narrative medical materials of medical humanities courses and build a platform for the application and communication of narrative medical materials.

Strong Linkage Disequilibrium and Haplotype Association of Neovascular Age-related Macular Degeneration in Indonesian Patients

@#Introduction: The aim of this study was to investigate the linkage disequilibrium (LD) and haplotype of three most associated SNP with nAMD of 80 patients in Indonesia. Methods: All patients underwent standard ophthalmic tests including fundoscopy and optical coherence tomography. Genomic DNA was extracted using commercially available DNA isolation kits. Genotyping of rs11200638, rs1061170 and del443ins54 used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. The acquired genotype data were analyzed using Haploview and R package software. Results: Linkage Disequilibrium analyses showed high LD value in the 10q26 region of 80 patients with AMD and 85 controls. The PCR-RFLP showed TTA was the most frequent haplotype while GTG was the most associated haplotype in the study sample. Conclusion: There was a high LD in the 10q26 region and strong association in GTG haplotype of Indonesian patients with AMD.

Analysis of the incentive effect of the patent linkage system on the application of generic drugs in China and suggestions for countermeasures / 中国药房

OBJECTIVE To optimize the system of patent linkage system and provide a reference for encouraging generic drugs to apply for listing. METHODS On the basis of literature research， combined with the author’s work experience， the situation of generic drug application and patent challenge were analyzed comparatively after the implementation of the patent linkage system in China. Based on the patent linkage system， the reasons for the insufficient incentive for the challenge of generic drug patents in China were analyzed； corresponding countermeasures and suggestions were proposed. RESULTS & CONCLUSIONS The patent linkage system in China was implemented in 2021， but due to the implementation of the system being still in its initial stage， the relevant documents for practical guidance are not yet complete， and the supporting incentive mechanism is not yet sound， resulting in a weak willingness of generic pharmaceutical enterprises to initiate patent challenges. It is suggested that China can further improve the patent linkage system by improving the patent information registration platform of generic drugs， developing professional drug patent agencies， and establishing the patent common challenges platform of the first generic drug， in order to incentivize Chinese generic drug enterprises to increase innovation motivation， challenge original research drug patents， and apply for listing， achieving the effect of suppressing drug prices and benefiting the people through full competition.

Construction on the integrated management information platform of urban medical alliances and county medical communities in Hainan province / 中华医院管理杂志

In order to achieve the goal of integration, homogeneity, a net and a center of medical groups in Hainan province, Hainan province built an integrated management information platform of urban medical alliances and county medical communities based on projects such as the provincial three medical linkage information platform in February 2022. The overall architecture of the medical alliance and medical community platform was divided into system integration layer, data center layer, service layer and application layer. The service layer included four major systems: unified operation management platform, business center, performance evaluation management platform and comprehensive supervision subsystem, which was the core hub connecting the data center layer and application layer, and also was the unified operation and closed-loop management platform of the medical alliance and medical community. As of November 2022, the platform had covered 31 medical alliances or medical communities in 19 cities and counties of Hainan province, achieving information exchange, personnel interaction, resource sharing, business collaboration, and data integration among member units, narrowing the gap between urban and rural medical and health services, which had preliminarily achieved homogeneous management of the medical alliances and medical communities throughout the province, for a reference for the integrated management of medical alliances and medical communities within the regional scope of China.

ADAM10 gene mutations caused familial progressive hyperpigmentation / 中华皮肤科杂志

Objective:To identify the causative gene in patients with familial progressive hyperpigmentation (FPH) .Methods:Two families with FPH were collected in March 2005 and March 2015 respectively, and their phenotypes were observed and recorded. The causative gene was investigated by single nucleotide polymorphism (SNP) -based genome-wide linkage analysis and exome sequencing, and verified by Sanger sequencing. The candidate gene expression was determined in FPH lesions and normal skin tissues by using immunohistochemical techniques.Results:The genome-wide linkage analysis showed that the causative gene in FPH family 1 was mapped to the loci of rs1026369-rs11857925 on chromosome 15q21.1 - q22.2; a disintegrin and metalloproteinase 10 (ADAM10) gene was identified as the possible causative gene by exome sequencing; Sanger sequencing showed that a splice-site mutation c.1511+1G>A in the ADAM10 gene was co-segregated with the disease phenotype in the FPH family 1. Immunohistochemical staining demonstrated that ADAM10 was expressed in both the FPH lesions and normal skin tissues of the proband in the FPH family 1. A missense mutation c.1172C>T (p.Ser319Phe) was identified by further ADAM10 mutation analysis in another 3-generation family with FPH (family 2). Both the above mutations were not detected in 300 local healthy controls.Conclusion:ADAM10 was identified as a novel causative gene responsible for FPH.

Curious Case of Alagille Syndrome: Case Report with NANDANIC-NOC Linkage in Care Plan

Alagille syndrome is a rare and complex multisystem disorder caused by an autosomal dominant genetic mutation of JAG1 (90% cases) and NOTCH2 (1-2% cases) genes located on the short arm of chromosome 20. This case is reported as per the CARE (for Case Reports, 2013) guidelines. A 14-year old male, known case of chronic cholestatic liver disease of neonatal onset, diagnosed with Alagille syndrome as evident from NOTCH 2 mutation in genetic analysis and paucity of intrahepatic bile ducts on biopsy presented with portal hypertension, growth failure and persistent hyperbilirubinemia.

Interaction analysis of FTO and IRX3 genes with obesity and related metabolic disorders in an admixed Latin American population: a possible risk increases of body weight excess / Análisis de la interacción entre los genes FTO e IRX3 con obesidad y desórdenes metabólicos relacionados en una población mixta de América Latina: un posible aumento del riesgo de exceso de peso

Abstract Background: Fat Mass and Obesity-related (FTO) has been one of the genes consistently related to common obesity. Single nucleotide polymorphisms (SNPs) in FTO have been linked with the IRX3 gene. Aim: This study was designed by testing the hypothesis that: i) common SNPs in FTO and IRX3 are associated with obesity and related disorders; ii) there is significant linkage disequilibrium between both genes. Methods: A cross-sectional study was carried out on the Colombian Caribbean Coast. Anthropometric and biochemical variables were measured, and obesity and metabolic disorders were diagnosed. Four SNPs were genotyped: 3 at FTO locus (rs17817449, rs8050136, rs9939609) and one at IRX3 locus (rs3751723). LD between these SNPs was estimated. A logistic regression model was applied to estimate associations. Results: A total of 792 subjects were included. FTO and IRX3 were not in LD (D'≤ 0.03; R2≤ 0.03). TT genotype (rs9939609) was found to be associated with waist circumference (p= 0.04; adj-p= 0.01), and IRX3 SNP with Body Weight Excess (BWE) (OR= 1.06, adj-p= 0.03). One FTO-IRX3 haplotype was associated with BWE (G-A-A-T, rs17817449-rs8050136-rs9939609-rs3751723; OR= 0.67, p= 0.04). The statistical significance of these relations continued after admixture adjustment for a three-hybrid population (p= 0.03). Conclusions: FTO was related to waist circumference, and IRX3 was associated with BWE in Latin American adults. This relation remained statistically significant after an adjustment for sex, age, and genetic ancestry was performed. Despite that these genes were not in LD, findings of a haplotype involving FTO-IRX3 suggest a gene-gene interaction associated with an increased risk of BWE.

Resumen Introducción: FTO (Fat Mass and Obesity-related) se ha relacionado de manera consistente con la obesidad. Recientemente, Polimorfismos de Nucleótido Único (SNP) en este gen se han relacionado con el gen IRX3. Objetivo: Probar la hipótesis de que: i) SNPs en FTO e IRX3 están asociados con la obesidad y trastornos relacionados; ii) existe desequilibrio de ligamiento (LD) significativo entre ambos genes. Métodos: se realizó un estudio transversal en la costa caribe colombiana. Se valoraron variables antropométricas y bioquímicas, la obesidad y trastornos metabólicos. Se genotipificaron 4 SNPs: 3 en FTO (rs17817449, rs8050136, rs9939609) y uno en IRX3 (rs3751723). Se estimó el LD entre estos SNPs. Se aplicó un modelo de regresión logística para estimar asociaciones. Resultados: Se incluyeron 792 sujetos. FTO e IRX3 no se encontraron en LD (D' ≤0.03; R2 ≤0.03). El genotipo TT (rs9939609) se encontró asociado con la circunferencia de la cintura (p= 0.04; adj-p= 0.01), y el SNP IRX3 con el Exceso de Peso (EP) (OR= 1.06, adj-p= 0.03). Se encontró un haplotipo FTO-IRX3 asociado con EP (G-A-A-T, rs17817449-rs8050136-rs9939609-rs3751723; OR= 0.67, p= 0.04). Esta asociación persistió después del ajuste para una población mixta (p= 0.03). Conclusiones: FTO se encontró asociado con la circunferencia de la cintura e IRX3 con EP en adultos latinoamericanos. Estas asociaciones persistieron tras el ajuste por sexo, edad y ascendencia genética. Aunque estos genes no estaban en LD, los hallazgos de un haplotipo entre FTO-IRX3 sugieren una interacción gen-gen asociada con un mayor riesgo de EP.

Avaliação do grau da implementação do Programa Vida no Trânsito em municípios brasileiros e verificação do desempenho do Record Linkage da "Plataforma Digital do PVT" / Avaliação do grau da implementação do Programa Vida no Trânsito em municípios brasileiros e verificação do desempenho do Record Linkage da "Plataforma Digital do PVT"

Introdução: Em 2020, conclui-se o ciclo da Década de Ações para a Segurança no Trânsito proposto pela Organização das Nações Unidas. Para atingir a meta de redução das mortes estabelecida pela ONU, em 2010, teve início o Programa Vida no Trânsito (PVT), cuja implementação está organizada em quatro etapas: articulação intersetorial; qualificação e integração dos dados; ações integradas de segurança no trânsito; e monitoramento das ações. Considera-se importante identificar quais etapas não estão implementadas e apontar possíveis estratégias para o ajuste do programa, de modo a atingir suas metas. A possibilidade de se obter uma plataforma web capaz de vincular bases epidemiológicas de dados consolidados, permitindo o amplo uso desses na vigilância para a produção de informação sobre os acidentes de trânsito, faz-se oportuna à avaliação do desempenho dessa ferramenta digital. Objetivo: Avaliar o grau da implementação do PVT em 31 municípios, a confiabilidade e a validade no pareamento probabilístico de bases de dados (record linkage) realizado na plataforma digital especialmente desenvolvida para a o PVT. Método: foi realizada uma avaliação formal e normativa, composta de duas fases: a) validação de conteúdo de 28 indicadores da implementação do PVT e b) a avaliação do grau da implementação, a partir de dois inquéritos (2015 e 2017) numa amostra de 30 municípios. Em seguida, Record Linkage (RL) probabilístico foi realizado com uso do software Reclink e da plataforma digital PD-PVT. Estes estudos utilizaram registros disponíveis na base de dados de vítimas do trânsito (VIT), no Sistema de Internação Hospitalar (SIH) e no Sistema de Informação de Mortalidade (SIM), referentes ao segundo trimestre de 2016 de um município participante do PVT. Foi então verificado o desempenho do RL na PD-PVT, por meio da análise das medidas de concordância e validade comparadas à rotina do RL realizado no Reclink. Resultados: O PVT encontra-se parcial ou totalmente implementado em 84,61% dos municípios. Observou-se um aumento no número de municípios implementados, passando de oito para dez, nos anos de 2015 a 2017. Entre as quatro etapas da metodologia do PVT, apenas a primeira, encontra-se implementada. Acerca do desempenho do RL na PD-PVT, a integração entre as bases SIH-VIT e SIM-VIT mostraram uma excelente confiabilidade entre os avaliadores (Kappa 0,95-0,98). Para validade, os resultados do PD-PVT foram: Precision 1,00 (IC 1,00-1,00) para o SIM-VIT; Recall 1,00 (CI 1,00-1,00) para SIH-VIT; e AUCPR 0,99 (CI 0,99-1,00) para SIH-VIT. Conclusão: Este estudo encontrou avanços no processo de implementação do programa nos anos avaliados, no entanto, apenas a primeira etapa apresenta-se implementada nos municípios avaliados. A técnica de RL realizada na PD-PVT mostrou excelente desempenho. É relevante destacar que uma das grandes vantagens desse sistema web está no processo automatizado de pareamento probabilístico. Diante disso, acredita-se que a redução dos passos torne o processo de RL mais ágil e mais simples, possibilitando, dessa forma a incorporação da técnica de RL, na rotina do serviço dos profissionais envolvidos, o que deverá contribuir para o andamento das atividades seguintes à etapa de qualificação da informação.

Introduction: In 2020, the cycle of the Decade of Actions for Traffic Safety proposed by the United Nations Organization ends. In order to reach the goal of reducing deaths caused by the UN, in 2010, the Program Vida no Trânsito (PVT) was started, whose implementation is organized in four stages: intersectoral articulation; qualification and integration of data; integrated traffic safety actions; and monitoring of actions. It is considered important to identify which steps are not implemented and point out possible adjustments to the program in order to achieve its goals. The possibility of obtaining a web platform capable of linking epidemiological databases of consolidated data, allowing wide use in surveillance for the production of information on traffic accidents, makes the performance evaluation of this digital tool opportune. Objective: To evaluate the degree of implementation of the PVT in 31 municipalities, the reliability and validation of the probabilistic pairing of databases (record linkage) carried out on the digital platform specially developed for the PVT. Method: a formal and normative one was carried out, consisting of two phases: a) content validation of 28 indicators of the PVT implementation and b) the evaluation of the degree of implementation, based on two surveys (2015 and 2017) in a sample of 30 municipalities. Then, probabilistic Record Linkage (RL) was performed using the Reclink software and the PD-PVT digital platform. These studies use records available in the traffic death database (VIT), in the Hospital Admission System (SIH) and in the Mortality Information System (SIM), referring to the second quarter of 2016 of a municipality participating in the PVT. The performance of the RL in the PD-PVT was then verified, through the analysis of the measures of agreement and validated to the routine of the RL performed in the Reclink. Results: The PVT is partially or fully implemented in 84.61% of the municipalities. There was an increase in the number of implemented municipalities, from eight to ten, in the years 2015 to 2017. Among the four stages of the PVT methodology, only the first is implemented. Regarding the performance of the RL in the PD-PVT, an integration between the SIH-VIT and permanent SIM-VIT bases and an excellent reliability among the evaluators (Kappa 0.95-0.98). For validation, the PD-PVT results were: Precision 1.00 (CI 1.00-1.00) for SIM-VIT; Remember 1.00 (CI 1.00-1.00) for SIH-VIT; and AUCPR 0.99 (CI 0.99-1.00) for SIH-VIT. Conclusion: This study found advances in the process of implementing the program in the years obtained, however, only the first stage is implemented in the recovered municipalities. The RL technique performed on the PD-PVT revealed excellent performance. It is worth noting that one of the great advantages of this web system is not the automated process of probabilistic matching. Therefore, it is believed that the reduction of steps makes the RL process more agile and simpler, thus enabling an incorporation of the RL technique in the service routine of the professionals involved, which should contribute to the progress of activities following the information qualification stage.

Point-of-care hepatitis C screening with direct access referral to improve linkage to care among halfway house residents: a pilot randomised study

INTRODUCTION@#Linkage to care among individuals with substance misuse remains a barrier to the elimination of the hepatitis C virus (HCV). We aimed to determine whether point-of-care (PoC) education, screening and staging for liver disease with direct access to hospitals would improve linkage to care among this group. @*METHODS@#All participants were offered PoC education and HCV screening. HCV-positive participants were randomised to standard care (controls) or direct access, which provided a direct pathway to hospitals. Linkage to care was determined by reviewing electronic medical records. Linkage of care cascade was defined as attendance at the specialist clinic, confirmation of viraemia by HCV RNA testing, discussion about HCV treatment and initiation of treatment. @*RESULTS@#351 halfway house residents were screened. The overall HCV prevalence was 30.5% (n = 107), with 69 residents in the control group and 38 in the direct access group. The direct access group had a significantly higher percentage of cases linked to specialist review for confirmatory RNA testing (63.2% vs. 40.6%, p = 0.025), HCV treatment discussion (p = 0.009) and treatment initiation (p = 0.01) compared to the controls. Overall, only 12.6% (n = 13) had treatment initiation during follow-up. PoC HCV screening with direct access referral had significantly higher linkage to HCV treatment initiation (adjusted odds ratio 9.13, p = 0.005) in multivariate analysis. @*CONCLUSION@#PoC HCV screening with direct access improves linkage to care and simplifies the HCV care cascade, leading to improved treatment uptake. PoC education, screening, diagnosis and treatment may be an effective strategy to achieving HCV micro-elimination in this population.