The decline of measles antibody titers in previously vaccinated adults: a cross-sectional analysis

ABSTRACT The global reemergence of measles in 2018-2019 reinforces the relevance of high-coverage immunization to maintain the disease elimination. During an outbreak in the Sao Paulo State in 2019, several measles cases were reported in individuals who were adequately vaccinated according to the current immunization schedule recommends. This study aimed to assess measles IgG antibody seropositivity and titers in previously vaccinated adults. A cross-sectional study was conducted at CRIE-HC-FMUSP (Sao Paulo, Brazil) in 2019. It included healthy adults who had received two or more Measles-Mumps-Rubella vaccines (MMR) and excluded individuals with immunocompromising conditions. Measles IgG antibodies were measured and compared by ELISA (Euroimmun®) and chemiluminescence (LIASON®). The association of seropositivity and titers with variables of interest (age, sex, profession, previous measles, number of measles-containing vaccine doses, interval between MMR doses, and time elapsed since the last MMR dose) was analyzed. A total of 162 participants were evaluated, predominantly young (median age 30 years), women (69.8%) and healthcare professionals (61.7%). The median interval between MMR doses was 13.2 years, and the median time since the last dose was 10.4 years. The seropositivity rate was 32.7% by ELISA and 75.3% by CLIA, and a strong positive correlation was found between the tests. Multivariate analyses revealed that age and time since the last dose were independently associated with positivity. Despite being a single-center evaluation, our results suggest that measles seropositivity may be lower than expected in adequately immunized adults. Seropositivity was higher among older individuals and those with a shorter time since the last MMR vaccine dose.

Optimization of water extraction technology of Xiangqin jiere granules by orthogonal design based on G1-entropy weight compared with BP neural network / 中国药房

OBJECTIVE Optimizing the water extraction technology of Xiangqin jiere granules. METHODS The orthogonal test of 3 factors and 3 levels was designed， and comprehensive scoring was conducted for the above indexes by using G1-entropy weight to obtain the optimized water extraction technology of Xiangqin jiere granules with water addition ratio， extraction time and extraction times as factors， using the contents of forsythoside A， baicalin， phillyrin， oroxylin A-7-O-β-D-glycoside， wogonoside， baicalein and wogonin， and extraction rate as evaluation indexes. BP neural network modeling was used to optimize the network model and water extraction process using the results of 9 groups of orthogonal tests as test and training data， the water addition multiple， decocting time and extraction times as input nodes， and the comprehensive score as output nodes. Then the two analysis methods were compared by verification test to find the best water extraction process parameters. RESULTS The water extraction technology optimized by the orthogonal test was 8-fold water， extracting 3 times， extracting for 1 h each time. Comprehensive score was 96.84 （RSD＝0.90%）. The optimal water extraction technology obtained by BP neural network modeling included 12-fold water， extracting 4 times， extracting for 0.5 h each time. The comprehensive score was 92.72 （RSD＝0.77%）， which was slightly lower than that of the orthogonal test. CONCLUSIONS The water extraction technology of Xiangqin jiere granules is optimized successfully in the study， which includes adding 8-fold water， extracting 3 times， and extracting for 1 hour each time.

Effect of Zuogui Jiangtang Tongmai Prescription on Inflammatory Injury of Human Umbilical Vein Endothelial Cells Induced by High Glucose and LPS Based on GPR43/β-arrestin-2/IκBα/NF-κB Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects and mechanism of Zuogui Jiangtang Tongmai prescription （ZJTP） on human umbilical vein endothelial cells （HUVECs） damaged by high glucose combined with lipopolysaccharide （LPS）. MethodThe survival rate of cells was determined by cell counting kit-8 （CCK-8）， and the level of tumor necrosis factor-α （TNF-α） was determined by enzyme-linked immunosorbent assay （ELISA） to determine the optimal injury concentration and action time of LPS， as well as the optimal action concentration of ZJTP drug-containing serum. HUVECs were divided into a blank control group， a model group， a ZJTP drug-containing serum group， and an SCFA mixed liquid group. ELISA was used to detect the level of endothelin-1 （ET-1）， nitric oxide （NO）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and TNF-α. Western blot was performed to detect the protein expression of G protein-coupled receptor43 （GPR43）， β-suppressor protein-2 （β-arrestin-2）， nuclear factor-κB suppressor α （IκBα）， and nuclear factor κB p65 （NF-κB p65）. The nucleation of NF-κB p65 was observed by immunofluorescence staining （IF）. The role of GPR43 in the regulation of inflammatory injury was observed by means of small interfering ribonucleic acid （siRNA）. The cells after intervention were divided into an empty carrier group， a ZJTP drug-containing serum group， a Si-GPR43 group， and a Si-GPR43 + ZJTP drug-containing serum group. The content of IL-1β， IL-6， and TNF-α was detected by ELISA. The protein expression of pathways was detected by Western blot. IF was used to observe the nucleation of NF-κB p65. ResultThe optimal molding condition was 1 mg·L-1 LPS for 24 h. The optimal drug intervention condition was 5% ZJTP drug-containing serum for 24 h. Compared with the blank control group， the content of ET-1 in the model group was significantly increased， and the content of NO was significantly decreased （P<0.01）. The levels of inflammatory factors were significantly increased （P<0.01）. The expressions of GPR43 and IκBα were significantly decreased， while the protein expressions of β-arrestin-2 and NF-κB p65 were significantly increased （P<0.01）. NF-κB p65 protein was transferred from the extranuclear to the intranuclear （P<0.01）. Compared with the model group， the content of ET-1 in the ZJTP drug-containing serum group was decreased， and the content of NO was increased （P<0.05）. The levels of inflammatory factors decreased （P<0.05）. The protein expressions of GPR43 and IκBα were increased， while the expressions of β-arrestin-2 and NF-κB p65 were decreased （P<0.05）. The amount of NF-κB p65 transferred from the intranuclear to the extranuclear decreased （P<0.01）. The mechanism study showed that compared with the Si-GPR43 group， the content of IL-1β， IL-6， and TNF-α were significantly decreased after treatment with ZJTP drug-containing serum （P<0.01）. The protein expressions of GPR43 and IκBα were significantly increased （P<0.01）， while the protein expressions of β-arrestin-2 and NF-κB p65 were significantly decreased （P<0.01）. The amount of NF-κB p65 transferred from the extranuclear to the intranuclear decreased （P<0.01）. ConclusionZJTP has a protective effect on HUVECs with high glucose and LPS-induced inflammatory injury， which may be related to the regulation of GPR43/β-arrestin-2/IκBα/NF-κB pathway.

Frecuencia y detección molecular de Gardnerella vaginalis en una institución de tercer nivel / Frequency and molecular detection of Gardnerella vaginalis in a third level institute

Resumen Antecedentes: Los padecimientos vaginales son la razón más común para que las mujeres busquen atención médica, con una prevalencia global que oscila entre el 23 y el 29% en mujeres en edad reproductiva. La vaginosis bacteriana es una de las principales causas de estos padecimientos, y el agente etiológico más frecuentemente identificado es Gardnerella vaginalis, sin embargo su diagnóstico es difícil, ya que requiere de medios artificiales selectivos enriquecidos y diferenciales. Objetivo: Determinar la frecuencia de G. vaginalis mediante la amplificación de ácidos nucleicos empleando la reacción en cadena de la polimerasa (PCR) en muestras cervicovaginales de pacientes que asisten a un instituto de tercer nivel. Método: Se analizaron 121 muestras cervicovaginales para la detección molecular del ARN ribosomal 16S de G. vaginalis. Resultados: G. vaginalis. se detectó en 34 muestras, de estas, 23 fueron de mujeres embarazadas y 11 de no embarazadas. Conclusión: La PCR de punto final detectó tres veces más la presencia de G. vaginalis que el medio de cultivo artificial.

Abstract Background: Vaginal conditions are the most common reason for women to seek medical care, with an overall prevalence ranging from 23 to 29% in women of reproductive age. Bacterial vaginosis is one of the main causes of these conditions, and the most frequently identified etiological agent is Gardnerella vaginalis, however, its diagnosis is difficult since it requires enriched and artificial selective culture media. Objective: To determine the frequency of G. vaginalis by nucleic acid amplification using polymerase chain reaction (PCR) in cervicovaginal samples from patients attending a third level institute. Method: One hundred twenty-one cervicovaginal samples were analyzed for molecular detection of 16S ribosomal RNA from G. vaginalis. Results: G. vaginalis was detected in 34 samples, of these, 23 were from pregnant women and 11 from non-pregnant women. Conclusion: Endpoint PCR detected three times more the presence of G. vaginalis than artificial culture medium.

Immunoglobulin G4-Related Disease, A Diagnosis to Take into Account: About a Case

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated and multisystemic condition associated with developing fibroinflammatory lesions in any organ. The diagnosis is made based on the sum of clinical, serological, radiological, and histopathological criteria; however, this is often difficult due to its similarity to neoplasms, infections, or other immune-mediated diseases. Treatment is based on corticosteroids, in a possible combination with immunomodulators. The present case concerns a 59-year-old man with a history of jaundice syndrome and weight loss, admitted for suspected malignant neoplasia of the bile duct. Imaging revealed stricture with dilation of the intrahepatic bile ducts, prominent pancreas, pancreatic duct stricture, and nodular renal lesions. Due to the history of left submandibulectomy two years before the current disease and histology compatible with Küttner's tumor, plus the high IgG4 serum values, the diagnosis of IgG4-RD was established. He started treatment with corticosteroids and was asymptomatic during follow-up.

La enfermedad relacionada con inmunoglobulina G4 (ER-IgG4) es una condición inmunomediada y multisistémica asociada al desarrollo de lesiones fibroinflamatorias en cualquier órgano. El diagnóstico se realiza bajo la suma de criterios clínicos, serológicos, radiológicos e histopatológicos; sin embargo, este suele ser difícil debido a su similitud con neoplasias, infecciones u otras enfermedades inmunomediadas. El tratamiento se basa en corticosteroides, en una posible combinación con inmunomoduladores. El presente caso trata de un varón de 59 años con historia de síndrome ictérico y baja de peso, admitido por sospecha de neoplasia maligna de la vía biliar. Las imágenes revelaron estenosis con dilatación de las vías biliares intrahepáticas, páncreas prominente, estenosis del conducto pancreático y lesiones nodulares renales. Debido al antecedente de submandibulectomía izquierda 2 años antes de la enfermedad actual e histología compatible con tumor de Küttner, más los valores elevados de IgG4 sérico, se estableció el diagnóstico de ER-IgG4. Inició tratamiento con corticosteroides y cursó asintomático durante el seguimiento.

Assessment of humoral immune response to different COVID-19 vaccines in patients undergoing maintenance hemodialysis / Avaliação da resposta imune humoral a diferentes vacinas contra a COVID-19 em pacientes submetidos à hemodiálise de manutenção

ABSTRACT Introduction: The immune response to different Coronavirus Disease 2019 (COVID-19) vaccines is under-investigated in end-stage kidney disease (ESKD) patients, especially in the Middle East and North Africa. We carried out this research to estimate the effectiveness of COVID-19 immunization in ESKD patients on regular hemodialysis (HD). Methods: In this prospective observational study, we enrolled 60 ESKD patients on regular HD who had completed COVID-19 vaccination and 30 vaccinated healthy participants. Serum levels of severe acute respiratory syndrome coronavirus 2 immunoglobulin G (SARS-COV2 IgG) were quantified 1 month after completing the vaccination schedule, and all participants were followed up from October 2021 to March 2022. The vaccines used in the study were from Pfizer-BioNTech, AstraZeneca, and Sinopharm. Results: The median level of SARS-COV2 IgG was lower in HD patients than in healthy participants (p < 0.001). Regarding the type of COVID-19 vaccination, there was no statistical difference in SARS-COV2 IgG levels among HD patients. During the observation period, none of the HD patients had COVID-19. Conclusion: COVID-19 vaccination appeared to be protective in HD patients for 6 months and the side effects of vaccines were tolerable.

RESUMO Introdução: A resposta imune a diferentes vacinas contra a doença do coronavírus 2019 (COVID-19) é pouco investigada em pacientes com doença renal em estágio terminal (DRET), especialmente no Oriente Médio e norte da África. Realizamos esta pesquisa para estimar a eficácia da imunização contra a COVID-19 em pacientes com DRET em hemodiálise regular (HD). Métodos: Nesse estudo observacional prospectivo, inscrevemos 60 pacientes com DRET em HD regular que haviam concluído o esquema de vacinação contra a COVID-19 e 30 participantes saudáveis vacinados. Os níveis séricos de imunoglobulina G da síndrome respiratória aguda grave do coronavírus 2 (SARS-COV2 IgG) foram quantificados um mês após a conclusão do esquema vacinal, e todos os participantes foram acompanhados de outubro de 2021 a março de 2022. As vacinas utilizadas no estudo eram da Pfizer-BioNTech, AstraZeneca e Sinopharm. Resultados: O nível mediano de SARS-COV2 IgG foi menor em pacientes em HD do que em participantes saudáveis (p < 0,001). Com relação ao tipo de vacinação contra a COVID-19, não houve diferença estatística nos níveis de SARS-COV2 IgG entre pacientes em HD. Durante o período de observação, nenhum dos pacientes em HD teve COVID-19. Conclusão: A vacinação contra a COVID-19 pareceu ser eficaz na proteção de pacientes em HD por 6 meses e os efeitos colaterais das vacinas foram toleráveis.

A conexão entre ácidos biliares e diabetes mellitus tipo 2 - Uma revisão / The connection between bile acids and type 2 diabetes mellitus - a review

ABSTRACT Background: Bile acids (BAs) are steroid molecules synthesized exclusively in the liver, being end products of cholesterol catabolism. BAs are known to be involved in several metabolic alterations, including metabolic syndrome and type 2 diabetes mellitus (DM2). DM2 is a chronic degenerative disease characterized by insulin resistance, insulin deficiency due to insufficient production of pancreatic ß-cells, and elevated serum glucose levels leading to multiple complications. Objective: The objective of this study is to investigate the role of BAs in the pathophysiology of DM2, highlighting the possibilities in the development of therapeutic procedures targeting BAs as an optional pathway in the treatment of DM2. Methods: The research was carried out through narrative review and publications on the relationship between BAs and DM2. The databases used for the search include PubMed, Scopus, and Web of Science. The keywords used for the search include bile acids, type 2 diabetes mellitus, metabolic syndrome, and metabolic disorders. Results: The studies have reported the involvement of BAs in the pathophysiology of DM2. BAs act as a ligand for the nuclear farnesoid X receptor, regulating glucose metabolism, lipid metabolism, and cellular energy production. Additionally, BAs modulate the production, elimination, and mobilization of BAs through the farnesoid X receptor. BAs also act as a signaling pathway through Takeda G protein-coupled receptor 5, further contributing to metabolic regulation. These findings suggest that targeting BAs may offer a novel therapeutic approach in the treatment of DM2. Conclusion: This study highlights the important role of BAs in DM2, specifically through their interactions with key metabolic pathways. Targeting BAs may represent an innovative and effective approach to the treatment of DM2.

RESUMO Contexto: Os ácidos biliares (ABs) são moléculas esteróides sintetizadas exclusivamente no fígado, sendo produtos finais do catabolismo do colesterol. Os ABs são conhecidos por estarem envolvidos em várias alterações metabólicas, incluindo a síndrome metabólica e o diabetes mellitus tipo 2 (DM2). A DM2 é uma doença crônica degenerativa caracterizada pela resistência insulínica, deficiência de insulina devido à produção insuficiente de células ß pancreáticas e hiperglicemia levando a múltiplas complicações. Objetivo: O objetivo deste estudo é investigar o papel dos ABs na fisiopatologia da DM2, destacando as possibilidades no desenvolvimento de procedimentos terapêuticos visando os ABs como uma via opcional no tratamento da DM2. Métodos: A pesquisa foi realizada por meio de revisão narrativa e publicações sobre a relação entre ABs e DM2. As bases de dados usadas para a pesquisa incluem PubMed, Scopus e Web of Science. As palavras-chave usadas para a pesquisa incluíram: ácidos biliares, diabetes mellitus tipo 2, síndrome metabólica e distúrbios metabólicos. Resultados: Os estudos relataram o envolvimento dos ABs na fisiopatologia da DM2. Os ABs atuam como ligantes para o receptor nuclear farnesoide X, regulando o metabolismo da glicose, metabolismo lipídico e produção de energia celular. Além disso, os ABs regulam a produção, eliminação e mobilização de ABs através do receptor farnesoide X. Os ABs também atuam como uma via de sinalização através do receptor acoplado à proteína G Takeda 5, contribuindo ainda mais para a regulação metabólica. Esses achados sugerem que o ABs pode oferecer uma nova abordagem terapêutica no tratamento da DM2. Conclusão: Este estudo destaca o papel importante do ABs na DM2, especificamente por meio de suas interações com vias metabólicas-chave. O redirecionamento ao ABs pode representar uma abordagem inovadora e eficaz para o tratamento da DM2.

Seropositividad de Chlamydia psittaci en trabajadores expuestos a aves y revisión de la literatura: evidencia de circulación en Antioquia / Chlamydia psittaci seropositivity in workers exposed to birds and review of the literature: Evidence of circulation in Antioquia

Introducción. La psitacosis es una enfermedad zoonótica causada por Chlamydia psittaci. Esta bacteria es catalogada como un agente con potencial bioterrorista y ha causado múltiples brotes en trabajadores con exposición laboral a aves en diferentes lugares del mundo. En Colombia, no se hace seguimiento epidemiológico de la infección y existe una gran brecha en el conocimiento. Objetivos. Determinar la frecuencia de anticuerpos contra C. psittaci en trabajadores con exposición laboral a aves y sus factores asociados. Además, revisar la literatura en relación con los estudios sobre el tema realizados en Colombia. Materiales y métodos. Se llevó a cabo un estudio descriptivo, transversal, con intención analítica, en trabajadores en contacto con aves y se revisó la literatura científica relacionada en Colombia. Se detectaron anticuerpos IgM e IgG contra C. psittaci en suero por microinmunofluorescencia. La descripción de las características sociodemográficas y de exposición se hizo con frecuencias y medidas de resumen. Se exploraron factores asociados por análisis bivariados y multivariados. La revisión de la literatura científica y gris se hizo con búsqueda estructurada. Resultados. Se analizaron 54 trabajadores en contacto con aves y se encontró una prevalencia de anticuerpos del 31,5 %. El ejercer funciones de sacrificio y faenado de las aves sin ser médico veterinario fue un factor de riesgo para la presencia de anticuerpos. Solo se encontraron cuatro estudios previos sobre C. psittaci hechos en Colombia. Conclusiones. Este estudio constituye la primera evidencia de la circulación de C. psittaci en trabajadores en contacto con aves en Antioquia y el segundo reporte en el país. Estos hallazgos aportan desde la salud pública a la estrategia One Health.

Introduction. Psittacosis is a zoonotic disease caused by Chlamydia psittaci, a bacterium classified as an agent with bioterrorist potential. It has caused multiple outbreaks in exposed poultry workers around the world. Colombia has no epidemiological follow-up of the infection and a big knowledge gap. Objectives. To determine the antibodies' frequency against C. psittaci in workers with occupational exposure to birds and to review the literature on studies conducted in Colombia. Materials and methods. We conducted a cross-sectional descriptive study with analytical intent on workers in contact with birds and reviewed the related literature in Colombia. IgM and IgG serum antibodies against C. psittaci were detected by microimmunofluorescence. The sociodemographic and exposure characteristics were expressed as frequencies and summary measures. Associated factors were explored by bivariate and multivariate analysis. The scientific and gray literature review was done with a structured search. Results. We analyzed 54 workers in contact with birds. Antibody prevalence was 31.5%. Slaughtering and evisceration by non-veterinarians was a risk factor for antibody presence. There are only four previous studies on C. psittaci in Colombia. Conclusions. Here, we present the first evidence of C. psittaci circulation among workers exposed to birds in Antioquia and the second report in the country. These findings contribute to the "One Health" public health strategy.

30G needle aspiration - A modified technique of capsulorhexis in pediatric cataract with high intra-lenticular pressure

This surgical technique describes a modification of the continuous curvilinear capsulorhexis (CCC) to achieve an adequate-sized capsulorhexis in pediatric cataracts with high intralenticular pressure. Performing CCC in pediatric cataracts is challenging, especially when the intralenticular pressure is high. This technique involves 30 G needle decompression of the lens to reduce positive intralenticular pressure and subsequent flattening of the anterior capsule. This minimizes the chances of extension of CCC without using any special equipment. This technique was used in two eyes of two patients (age 8 and 10 years) with unilateral developmental cataracts. Both surgeries were performed by a single surgeon (PKM). In both eyes, a well-centered CCC was achieved with no extension, and a posterior chamber intraocular lens (IOL) was placed in the capsular bag. Thus, our technique of 30 G needle aspiration could be extremely useful to achieve an adequately sized CCC in pediatric cataracts with high intralenticular pressure, especially for beginner surgeons.

Myosin 1g as a high-risk biomarker in a pediatric patient with lineage switch from acute lymphoblastic leukemia to myeloid phenotype / Miosina 1g como un marcador de alto riesgo en una paciente pediátrica con cambio de linaje de leucemia linfoblástica aguda a fenotipo mieloide

Abstract Background: Myosin 1g (Myo1g) has recently been identified as a potential diagnostic biomarker in childhood acute lymphocytic leukemia (ALL). Case report: We describe the case of a 1-year-old Mexican female patient. Although initially studied for hepatomegaly, an infectious or genetic etiology was excluded. Liver biopsy showed infiltration by neoplastic B-cell precursors (BCPs), and bone marrow (BM) aspirate showed 14.5% of BCPs. In a joint session of the oncology, hematology, and pathology departments, low-risk (LR) BCP-ALL of hepatic origin with aberrant myeloid markers was diagnosed. Although treatment was initiated, the patient presented early with BM relapse. Modest overexpression of Myo1g was observed from the onset. However, at the end of the steroid window, expression increased significantly and remained elevated during this first relapse to BM. The parents refused hematopoietic stem cell transplantation, but she continued chemotherapy. After a second BM relapse at 5 years of age, the phenotype switched to myeloid. Her parents then opted for palliative care, and the patient died two months later at home. Conclusions: This case shows the potential use of Myo1g in clinical practice as a high-risk indicator. Myo1g monitoring may reveal a high risk and relapse trend, even when typical parameter values are not altered: Myo1g could be used to classify patients from low to high risk from diagnosis, allowing patients to promptly receive the best treatment and potentially modifying prognosis and survival.

Resumen Introducción: Recientemente se ha identificado a miosina 1g (Myo1g) como un potencial biomarcador de diagnóstico en la leucemia linfoblástica aguda (LLA) infantil. Caso clínico: Se describe el caso de una paciente mexicana de 1 año de edad. Aunque inicialmente se estudió por hepatomegalia, se descartó una etiología infecciosa o genética. La biopsia hepática mostró infiltración por precursores de células B neoplásicas (PCB) y un aspirado de médula ósea (MO) mostró 14.5% de PCB. En una sesión conjunta de los departamentos de oncología, hematología y patología, se diagnosticó PCB-LLA de bajo riesgo de origen hepático con marcadores mieloides aberrantes. Aunque se inició tratamiento, la paciente presentó tempranamente recaída de MO. Se observó una modesta sobreexpresión de Myo1g. Sin embargo, al final de la ventana de esteroides, la expresión aumentó considerablemente y permaneció elevada durante esta primera recaída a MO. El trasplante de células madre hematopoyéticas fue rechazado por los padres, pero se continuó con la quimioterapia. Tras una segunda recaída de MO a los 5 años, el fenotipo cambió a mieloide. Sus padres optaron entonces por cuidados paliativos y la paciente falleció dos meses después en su domicilio. Conclusiones: Este caso muestra el potencial uso de Myo1g como indicador de alto riesgo en la práctica clínica. El seguimiento de Myo1g puede revelar una tendencia de alto riesgo y recaídas, incluso cuando los valores de los parámetros rutinarios son aparentemente normales; Myo1g podría utilizarse para clasificar a los pacientes de bajo a alto riesgo desde el diagnóstico, lo que permitiría que los pacientes reciban el mejor tratamiento de manera oportuna, modificando potencialmente el pronóstico y la supervivencia.

Effects of cloperastine, a non-narcotic antitussive, on the expression of GIRK channels in the brain of methamphetamine-induced hyperactive mice

Objectives: Centrally-acting antitussives with inhibitory effects on G protein-coupled inwardly rectifying potassium (GIRK) channels have been shown to also inhibit methamphetamine-induced hyperactivity in mice. In this study, we examined if cloperastine, which is the most potent inhibitor of the GIRK channels among antitussives, is sensitive to the expression levels of GIRK channels in the brain of methamphetaminetreated mice. Materials and Methods: The brain tissues have been removed and the total RNA has been extracted from tissues. The mRNA levels were evaluated using semiquantitative reverse transcription-polymerase chain reaction. Results: The concentration levels of the mRNA of GIRK channels within the ventral midbrain of methamphetamine-treated mice increased as compared with that in control and cloperastine reduced an upregulation in GIRK2, one of the subunits of the GIRK channels, by the injection of methamphetamine. Conclusion: These findings suggest that cloperastine might ameliorate hyperactivity by inhibiting the GIRK channels in the brain.

Antibody Response to SARS-COV-2 Vaccination in Healthcare Workers of Uttarakhand: A Prospective Follow-up Study

Background: Countries around the world are now racing to vaccinate people against SARS-CoV-2, the virus that causes COVID-19. The Government of India also rolled out its vaccination drive from 16th January ‘2021. Aims: To estimate the antibody response of the COVID-19 vaccine in the form of SARS-COV-2 IgG antibodies in vaccinated healthcare workers. Methods: Prospective follow-up was study conducted on healthcare workers (HCWs) of a Medical college in Dehradun, Uttarakhand. Healthcare workers who have been vaccinated for COVID-19 were tested for SARS-CoV-2-IgG antibodies at regular intervals i.e at 4 weeks after the 1st dose and then again at 4 weeks after the 2nd dose. The third sample was taken 6 months after the 2nd dose. Results: A total of 302 HCWs were enrolled in the study who gave their samples for IgG antibody estimation after the Covishield vaccine. After 4 weeks of completion of both doses, 96% HCWs formed SARS-COV-2 IgG antibodies, whereas 4% didn’t. Then after 6 months of follow-up, 14% HCWs have become negative for antibodies and better immunity is seen in people who also got infected with COVID-19 during this time. Conclusion: This study concludes that the immunity gained after vaccination is waning off in around 6 months and there is a need for a booster dose, especially for people at high risk. The infection control practices still play a crucial role in the prevention of this deadly disease.

Hypophysitis an uncommon manifestation of IgG4-related disease: Case report

IgG4-related disease is a recently described disease that can involve various organs and systems. Single organ involvement is the exception to the rule, it is generally a multi-system entity. We present a 36-year-old woman, with no previous pathological history or autoimmune disease, with headache caused by cystic macroadenoma. A transsphenoidal resection was performed and pathology documented areas of fibrosis with a predominantly plasmolymphocytic infíltrate and positive IgG4 staining in more than 20 cells per high-power field, meeting diagnostic criteria for IgG4-related sclerosing disease. Involvement of other organs was ruled out, and the patient improved clinically after management.

La enfermedad relacionada con IgG4 es una entidad recientemente descrita, capaz de involucrar diversos órganos y sistemas. El compromiso de órganos aislados es la excepción a la regla, dado que generalmente se trata de una entidad multisistémica. Se presenta el caso de una mujer de 36 años, sin antecedentes patológicos previos, en quien como causa de cefalea se documenta un macroadenoma quístico llevado a resección transesfenoidal, cuyo resultado de patología documenta zonas de fibrosis con infiltrado de predominio plasmo-linfocitario y la tinción para IgG4 positiva en más de 20 células por campo de alto poder, lo que configura criterios diagnósticos para enfermedad esclerosante relacionada con IgG4; se descartó compromiso de otros órganos y hubo mejoría clínica posterior al manejo.

Systemic disease in leukocytoclastic vasculitis: a focus on direct immunofluorescence findings

Abstract Background Direct immunofluorescence (DIF) panels are usually ordered for clinically suspected cutaneous vasculitis, but their positivity rate is variable, and their prognostic significance is not clear to date. Objective The study aims to investigate the systemic involvement rate in leukocytoclastic vasculitis (LCV) patients and the potential clinical and laboratory associations with systemic involvement, including DIF findings. Methods A retrospective study of patients with histopathologically proven cutaneous LCV examined in the dermatology department between 2013 and 2017 was performed. Results Of the 81 patients (mean age, 50.6 years), 42 (52%) were male. The mean time between the appearance of skin lesions and biopsy was 23.1 days, ranging from 2 to 180 days. DIF showed overall positivity of 90.1%, and C3 was the most frequent immunoreactant (82.7%). Any kind of extracutaneous involvement was present in 47 (58%) of patients, with renal involvement being the most frequent (53.1%), followed by articular (18.5%) and gastrointestinal (11.1%) involvement. The presence of renal disease was associated with the detection of IgG in the lesional skin (p = 0.017), and with the absence of IgM in the lesional skin (p = 0.032). There was a significant association between C3 deposition and joint involvement (p = 0.05). Study limitations This is a single-center study with a retrospective design. Conclusion DIF seems to be a useful ancillary diagnostic tool in the evaluation of cutaneous vasculitis, but the relationship between DIF findings and systemic involvement needs to be further elucidated due to contradictory data in the current literature.

A permanência dos símbolos teriomórficos na arte e na psique / The permanence of sybols in artand in the psyque / La permanencia de los simlolos del teriomorfismo en elarte yen la psique

O artigo trata de símbolos teriomórficos­referidos a animais. A importância que exercem pode ser atestada pela permanência na arte (pinturas parietais até os grafites contemporâneos) e na psique. A perpetuação de símbolos e temas é tratada por estudos como os de Aby Warburg em história da arte, com as noções de Kulturgeschichte, Pathosformele Mnemosyne: a recorrência de temas, emoções e comportamentos revela a perpetuação de símbolos interligados à cultura. Essa recorrência simbólica, em termos psíquicos é entendida por C.G. Jung mediante as noções de arquétipo e inconsciente coletivo. Autores contemporâneos a Warburg e a Jung e seus respectivos conceitos, bem como a apresentação de algumas obras de arte, ilustram a importância dos símbolos teriomórficos .Aventa-se a hipótese de que seja uma necessidade psíquica de reunir a natureza biológica, sua força desejante instintiva com a esfera da mente e do sentido de ser constantemente renovada (AU).

Teriomorphicsymbols refer to animals. The importance they exercise can be demonstrated by the permanence of these symbols both in art (parietal paintings to contemporary graffiti) and in the psyche. The perpetuation of symbols and themes is dealt with by studies suchas those by Aby Warburg in art history: Kulturgeschichte, Pathosformel and Mnemosyne. The recurrence of themes, emotions and behaviors reveals the perpetuation of symbols intertwined with culture. This symbolic recurrence, in psychic terms, is understood by C.G. Jung through the notions of archetype and collective unconscious. Contemporary authors of Warburg and Jungand their respective concepts, as well as the presentation of some works of artillustratethe importance of teriomorphic symbols. It is hypothesized that it is a psychic need to unite the biological nature, its instinctive desiring force with the sphere of the mind and the sense of being constantly renewed (AU).

Los símbolos teriomorfosse refieren a los animales. La importancia que ejercen puede ser atestiguada por su permanencia en el arte (pinturas parietales hasta grafitis contemporáneos) y en la psiquis. La perpetuación de símbolos y temas es abordada por estudios como los de Aby Warburg en historia del arte: Kulturgeschichte, Pathosformel y Mnemosyne: la recurrencia de temas, emociones y comportamientos revela la perpetuación de símbolos entrelazados con la cultura. Esta recurrencia simbólica, en términos psíquicos, es comprendida por C.G. por Jung a través de las nociones de arquetipo e inconsciente colectivo. Autores contemporáneos de Warburg y Jungy sus respectivos conceptos,así como la presentación de algunas obras de arte, ilustran la importancia de los símbolos teriomorfos. Se plantea la hipótesis de que se trata de una necesidad psíquica de unir la naturaleza biológica, su fuerza instintiva deseante con la esfera de la mente y el sentido de renovarse constantemente (AU).

Correction of the pathogenic mutation in the G6PC3 gene by adenine base editing in mutant embryos / 中华血液学杂志

Objective: To determine whether the adenine base editor (ABE7.10) can be used to fix harmful mutations in the human G6PC3 gene. Methods: To investigate the safety of base-edited embryos, off-target analysis by deep sequencing was used to examine the feasibility and editing efficiency of various sgRNA expression vectors. The human HEK293T mutation models and human embryos were also used to test the feasibility and editing efficiency of correction. Results: ①The G6PC3(C295T) mutant cell model was successfully created. ②In the G6PC3(C295T) mutant cell model, three distinct Re-sgRNAs were created and corrected, with base correction efficiency ranging from 8.79% to 19.56% . ③ ABE7.10 could successfully fix mutant bases in the human pathogenic embryo test; however, base editing events had also happened in other locations. ④ With the exception of one noncoding site, which had a high safety rate, deep sequencing analysis revealed that the detection of 32 probable off-target sites was <0.5% . Conclusion: This study proposes a new base correction strategy based on human pathogenic embryos; however, it also produces a certain nontarget site editing, which needs to be further analyzed on the PAM site or editor window.

Analysis of psychological crisis vulnerability among rural college students and its related factors / 中国学校卫生

Objective@#To understand vulnerability to psychological crisis among rural college students and its related factors, so as to provide reference for the prevention or intervention of psychological crisis among rural college students.@*Methods@#A total of 3 560 rural college students from grade one to grade three from five universities were selected using convenient cluster sampling method from January to September 2022 in Nanyang City. General information, vulnerability to psychological crisis, parenting style and Scale of Perceived Social Self efficacy (PSSE) were collected and analyzed through questionnaire.@*Results@#Among the investigated rule college students, the score of psychological crisis vulnerability and spoiling dimension of parenting style were (10.76± 3.46 ) points and (2.68±0.55) points, while the score of trust encouragement dimension of parenting style and PSSE were (2.52± 0.62 ) points and (3.29±0.61) points. Pearson correlation analysis showed that vulnerability to psychological crisis of rural students was positively correlated with spoiling and neglect ( r =0.32, 0.49), and was negatively correlated with trust encouragement, emotional warmth and PSSE ( r =-0.38, -0.53, -0.51)( P <0.05). Multiple linear regression analysis revealed that single parent family or other families, poor students, left behind experience, high score of spoiling and high score of neglect revealed high psychological crisis vulnerability ( P <0.05). High score of trust encouragement, high score of emotional warmth and PSSE were associated with low vulnerability to psychological crisis ( P <0.05).@*Conclusion@#Vulnerability to psychological crisis among rural college students is higher, which is related to the family structure, students whether they are poor, leftover experience, parenting style and PSSE. Mental health among rural college students should be promoted by strengthening communication with students parents and cultivating students social self efficacy.

Effect of radiofrequency radiation from 5G mobile phone on blood-brain barrier in mice / 中华放射医学与防护杂志

Objective:To investigate the effect of radiofrequency radiation (RF) from 5G mobile phone communication frequency bands (3.5 GHz and 4.9 GHz) on the permeability of the blood-brain barrier (BBB) in mice.Methods:A total of 24 healthy adult male C57BL/6 mice (6-8 weeks old) were randomly divided into Sham, 3.5 GHz RF and 4.9 GHz RF groups, and 8 mice in each group. Mice in the RF groups were systemically exposed to 5G cell phone radiation for consecutive 35 d(1 h/d) with 50 W/m 2 power density. The BBB permeability of mice was detected by Evans Blue (EB) fluorescence experiment. The expression levels of the BBB tight junction-related proteins (ZO-1, occludin and claudin-11) and the gap junction-related protein Connexin 43 were determined by Western blot. Results:The number of spots, fluorescence intensity and comprehensive score of EB were significantly increased in 3.5 GHz RF group and 4.9 GHz RF group compared with the Sham group ( t=12.98, 17.82, P<0.001). Compared with the Sham group, the content of S100B in mouse serum was significantly increased in 3.5 GHz RF group and 4.9 GHz RF group ( t=19.34, 14.68, P<0.001). The BBB permeability was increased in the RF group. The expression level of occludin protein was significantly reduced in the 3.5 GHz RF group ( t=-3.13, P<0.05), and this decrease was much profound in the 4.9 GHz RF group ( t=-6.55, P<0.01). But the protein levels of ZO-1, Claudin-11 and Connexin 43 in the cerebral cortex of the RF groups had no significantly difference in comparison with the Sham group( P>0.05). Conclusions:The continuous exposure of mobile phone RF at 3.5 GHz or 4.9 GHz for 35 d (1 h/d) induces an increase of BBB permeability in the mouse cerebral cortex, perhaps by reducing the expression of occludin protein.

Lipid-lowering effect of atorvastatin on patients with acute cerebral infarction with different genotypes of ATP-binding cassette subfamily B member 1 G2677T / 中华行为医学与脑科学杂志

Objective:To observe the lipid-lowering effect of atorvastatin on patients with acute cerebral infarction with different ATP-binding cassette subfamily B member 1(ABCB1) genotypes, and thus to provide clinical research evidence for individual application of atorvastatin in patients with acute cerebral infarction.Methods:From March 2021 to December 2021, 131 patients with acute cerebral infarction admitted to the Department of Neurology of Xuchang Central Hospital were included. The ABCB1 G2677T gene polymorphism rs2032582 of patients was detected by fluorescence staining in situ hybridization.Based on the detection results, patients were divided into GG group, GT group and TT group.All patients were given atorvastatin (20 mg/d) for lipid-lowering treatment.The levels of low density lipoprotein cholesterol(HDL-C), high density lipoprotein cholesterol(HDL-C), total cholesterol(TC)and triglyceride(TG) in serum of patients in the three groups before and 2 months after treatment were recorded and analyzed.The adverse drug reactions in the three groups were recorded. When the serum LDL-C level was less than 1.8 mmol/L, it was considered that the lipid-lowering treatment was effective.The binary Logistic regression analysis was used to explore the influencing factors of atorvastatin lipid lowering therapy.The software of SPSS 25.0 was used for statistical analysis.Results:There were 50 (38.17%), 49 (37.40%) and 32 (24.43%) patients in GG group, GT group and TT group, respectively. The serum TC levels of patients in GG group, GT group and TT group after treatment were (3.47±0.70) mmol/L, (3.59±1.09) mmol/L and (3.48±1.02) mmol/L, respectively, which were lower than those before treatment ((4.27± 0.99) mmol/L, (4.02±0.98) mmol/L and (4.03±1.31) mmol/L), all of which were statistically significant ( t=7.652, 3.092, 5.593, all P<0.01). The serum LDL-C levels in GG group, GT group and TT group after treatment were (1.89±0.53) mmol/L, (2.07±0.92) mmol/L and (1.96±0.79) mmol/L, respectively, which were lower than those before treatment ((2.87±0.92) mmol/L, (2.56±0.89) mmol/L and (2.55±1.11) mmol/L) ( t=9.896, 4.055, 5.980, all P<0.001). The differences of serum LDL-C level before and after treatment in GG group, GT group and TT group were (-0.97±0.69) mmol/L, (-0.50±0.86) mmol/L and (-0.59±0.56) mmol/L, respectively. The difference of serum LDL-C level before and after treatment in the three groups was statistically significant ( F=5.614, P=0.005). The difference of TC, TG and HDL-C before and after treatment was not statistically significant( F=2.783, 0.490, 1.677, all P>0.05). The binary Logistic regression analysis showed that ABCB1 G2677T gene type and staying up late were independent influencing factors for atorvastatin lipid-lowering therapy. The probability of effective lipid-lowering in GT patients with ABCB1 G2677T gene was 27.9% of that in GG patients ( OR=0.279, 95% CI: 0.110-0.709, P=0.007), and the probability of TT type patients was 33.8% of GG type patients ( OR=0.338, 95% CI: 0.121-0.943, P=0.038). The probability of effective lipid-lowering in patients who had the habit of staying up late was 26.4% of the patients who did not stay up late ( OR=0.264, 95% CI: 0.118-0.591, P=0.001). There was no significant difference in the total incidence of adverse drug reactions among the three groups( χ2=0.868, P=0.648). Conclusion:The lipid-lowering effect in patients with GG type of ABCB1 G2677T is better than that of GT type and TT type when atorvastatin is used to treat patients with acute cerebral infarction.

Value of serum IgG4 and IgG4/IgG ratio in differential diagnosis of autoimmune diseases / 中国基层医药

Objective:To investigate the value of immunoglobulin G4 (IgG4) and IgG4/ immunoglobulin G (IgG) ratio in the differential diagnosis of IgG4-related diseases (IgG4-RD) and other autoimmune diseases.Methods:A total of 35 patients with IgG4-RD and 937 patients with autoimmune diseases who received treatment in Beijing Hospital from January 2021 to July 2022, and 200 subjects who concurrently underwent health checkups in the same hospital were included in this study. The IMMAGE 800 and BN II automatic special protein analyzers were used to detect IgG and IgG4. The receiver operating characteristic (ROC) curve of IgG4 and IgG4/IgG ratio was plotted.Results:Serum IgG4 level and IgG4/IgG ratio in the IgG4-RD group were 2.83 (2.01, 5.07) g/L and 25% (18%, 43%) respectively, which were higher than 0.35 (0.16, 0.72) g/L, 3% (1%, 6%) in the autoimmune disease group and 0.27 (0.14, 0.49) g/L, 2% (1%, 4%) in the healthy control group ( U = 795.50, 82.50, 1 744.50, 205.50, all P < 0.001). Taking IgG4 ≥ 1.35 g/L as the standard, patients with IgG4 ≥ 1.35 g/L in the three groups were screened out. There was a statistically significant difference in IgG4/IgG ratio between the IgG4-RD group and the non-IgG4-RD group ( U = 453.50, P < 0.001). The ROC curve of IgG4 and IgG4/IgG ratio showed that when IgG4 was 1.47 g/L, the sensitivity was 91.7%, the specificity was 83.5%, and the area under the ROC curve was 0.96. When IgG4/IgG was 12.5%, the sensitivity was 91.4%, the specificity was 85%, and the area under the ROC curve was 0.96. Taking IgG4 ≥ 1.47 g/L and IgG4/IgG ≥ 12.5% as the diagnostic criteria of IgG4-RD, the sensitivity was 94.3%, the specificity was 85.9%, and the area under the ROC curve was 0.96, which were higher than the sensitivity (87.2%) and diagnostic specificity (82.6%) provided by IgG4 alone. Conclusion:Because non-IgG4-RD diseases can also have the phenomenon of increased IgG4, when IgG4 ≥ 1.47 g/L is taken as the diagnostic criteria, its diagnostic sensitivity and specificity are the highest. Combined detection of IgG4 and IgG4/IgG ratio can increase the diagnostic efficacy of IgG4-RD.