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BACKGROUND: Considering the challenges of the referral system in the family physician program and the impact of COVID-19 pandemic on the performance of the relevant ministry's programs, it is necessary to assess the performance of the referral system. This study was conducted with the aim of investigating the performance of the family physician referral system before and during COVID-19 in Golestan province. METHODS: The present repeated cross-sectional study was conducted on secondary data Recorded of 786,603 cases referred and cared by family physicians (including information on physicians' and midwives' visits, percentage of prescriptions and other information) in Golestan province from 2017 to 2022 in a census and retrospective manner. Data were collected using the reference ratio checklist and analyzed with SPSS 23 software at a significance level of less than 0.05. RESULTS: Referral to 10 types of medical specialties and 10 indicators of family physicians referral before and during COVID-19 were investigated. The highest and lowest percentages of referrals by family physicians were belonged to the surgical (17.6%) and infectious (2%) specialists before COVID-19, and internal medicine (15.07%) and urology (3%) specialists during COVID-19, respectively. Referral due to physician's diagnosis increased by 19.3% compared to before Covid-19, target group increased by 0.86%, care decreased by 2.69% and reverse referral decreased by 36.1%. The amount of population covered by rural insurance, the amount of visits to midwives, the percentage of electronic appointments in the post-Covid-19 years have changed significantly compared to before.it (P-Value < 0.05). CONCLUSION: The present study showed that the COVID-19 pandemic had a significant impact on family physician referral indicators, such as the process of referral to specialists, drug prescriptions, insurance coverage, one-time service population, and patient care, which can be used to eliminate the weaknesses and Strengthening the strengths of the programs being implemented in the face of possible pandemics is very useful and effective and can be used in the country. Finally, the results obtained from this research provide evidence to discuss the importance of the family physicians care and referral system in the face of special conditions for quality control in health policies.
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COVID-19 , Encaminhamento e Consulta , Humanos , COVID-19/epidemiologia , Encaminhamento e Consulta/estatística & dados numéricos , Encaminhamento e Consulta/tendências , Estudos Transversais , Irã (Geográfico)/epidemiologia , Médicos de Família/estatística & dados numéricos , Estudos Retrospectivos , Pandemias , Masculino , Feminino , Medicina de Família e Comunidade/estatística & dados numéricos , SARS-CoV-2RESUMO
Background: Breast cancer is one of the most important causes of cancer deaths in women. The present study was conducted to determine the relationship between demographic factors and known risk factors with breast cancer in women aged 30-69. Method: This case-control study was conducted with two matched and unmatched control groups. Three hundred fifty women aged 30-69 with breast cancer, 350 age-matched women without cancer, and 350 not age-matched women were included in the study. Controls were selected from the records of women whose breast cancer screening results were normal. Study subjects were evaluated regarding the risk factors for breast cancer. The data collection tool was a checklist including the risk factors investigated in the integrated health system. The collected data were analyzed utilizing SPSS22 software at a significance level of less than 0.05. Results: The average age in the case group was 46.63±11.77 years and 49.61±8.39 in the unmatched control group. The average age of marriage in the case group was 21.54±4.31, and the average age of women at first pregnancy in the case group was 24.06±3.39 years. In the case group, 163 people (46.57%) lived in the city, 221 people (63.14%) were over 40 years old, and 337 people (96.28%) were married. In multivariate analysis, the variable 'age of marriage' 0.821 (0.691-0.976) and 'age of first pregnancy' 1.213 (1.020-1.443) showed a significant relationship with breast cancer which were observed as predictors of breast cancer in comparison to the unmatched control group (P-value <0.05). Conclusion: The age of the first pregnancy and the type of delivery were observed as predictors of breast cancer. Therefore, by performing breast cancer screening in women who are exposed to these risk factors, early diagnosis of the disease and increasing the speed of their treatment can be significantly helped.
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OBJECTIVE: To systematically review the reported cases of Creutzfeldt-Jakob disease (CJD) in Iran. METHODS: A comprehensive literature review of CJD cases in Iran was undertaken using the PubMed®, Scopus® and Google Scholar databases. In addition, the Iranian database MagIran was searched for Persian language reports. Case selection used the following criteria: (i) patients of Iranian origin; (ii) publication in peer-reviewed journals or reputable medical databases; (iii) a definitive diagnosis of CJD based on established diagnostic criteria. RESULTS: Thirteen cases from twelve reports were included in this systematic review. The majority of the cases were female (11 of 13; 84.6%). The mean ± SD age of patients at hospital admission was 59.38 ± 7.44 years. The findings of the case review suggested that the prevalence of CJD in Iran is not fully established. CJD may be misdiagnosed alongside other clinical signs. The most prevalent early indications of the disease were psychiatric and neurological in nature. A considerable delay in diagnosis was observed in some cases and there was a shortage of brain autopsy records. CONCLUSION: Efforts to improve diagnostic capabilities, promote awareness and establish monitoring systems are necessary for managing the challenges of providing an early diagnosis of CJD in Iran.
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Síndrome de Creutzfeldt-Jakob , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/epidemiologia , Síndrome de Creutzfeldt-Jakob/patologia , Humanos , Irã (Geográfico)/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Encéfalo/patologia , Encéfalo/diagnóstico por imagem , PrevalênciaRESUMO
Flavonoids, a diverse group of polyphenolic compounds found in various plant-based foods, have garnered attention for their potential in combating Hepatitis B Virus (HBV) infection. Flavonoids have demonstrated promising anti-HBV activities by interfering with multiple stages of the HBV life cycle, making them promising candidates for novel antiviral agents. Certain plant families, such as Theaceae, Asteraceae, Lamiaceae, and Gentianaceae, are of particular interest for their flavonoid-rich members with anti-HBV activities. Evidences, both in vitro and in vivo, supports the anti-HBV potential of flavonoids. These subsets of compound exert their anti-HBV effects through various mechanisms, including inhibiting viral entry, disrupting viral replication, modulating transcription factors, enhancing the immune response, and inducing autophagy. The antioxidant properties of flavonoids play a crucial role in modulating oxidative stress associated with HBV infection. Several flavonoids like epigallocatechin gallate (EGCG), proanthocyanidin (PAC), hexamethoxyflavone, wogonin, and baicalin have shown significant anti-HBV potential, holding promise as therapeutic agents. Synergistic effects between flavonoids and existing antiviral therapies offer a promising approach to enhance antiviral efficacy and reduce drug resistance. Challenges, including limited bioavailability, translation from preclinical studies to clinical practice, and understanding precise targets, need to be addressed. Future research should focus on clinical trials, combination therapies, and the development of flavonoid derivatives with improved bioavailability, and optimizing their effectiveness in managing chronic HBV infections.
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Hepatite B Crônica , Hepatite B , Humanos , Vírus da Hepatite B/fisiologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Hepatite B/tratamento farmacológico , Hepatite B Crônica/tratamento farmacológico , Flavonoides/farmacologia , Replicação ViralRESUMO
INTRODUCTION: In humans, approximately 5% of all cancers are attributable to HPV infection. Prophylactic vaccines can inhibit viral migration and persistence. However, further studies are still required to develop such treatments. To achieve this goal, we designed a therapeutic HPV DNA vaccine encoding a construct of E6/E7/L1 and used NSP4 antigen as an adjuvant to assess the efficiency of this construct in generating antigen-specific antitumor immune responses. MATERIALS AND METHODS: Sixty female C57BL/6 mice (6-8 weeks old) were purchased from the Institute Pasteur of Iran. Through a subcutaneous (s.c) injection of a suspension of 100 µl PBS containing 106 TC-1 cells/mouse in the back side, 30 of them became cancerous, while 30 of them were healthy control mice. To amplify E6/E7/L1-pcDNA3 and NSP4-pcDNA3, the competent cells of DH5α and to generate a tumor, TC-1 cell line was used. Mice were then immunized with the HPV DNA vaccine. Cell proliferation was assessed by MTT assay. Finally, cytokine responses (IL-4, IL-12, IFN- γ) were measured in the supernatant of mice spleen cells. RESULT: Mice receiving the NSP4/E6-E7-L1 vaccine had the highest stimulatory index compared to other groups, although it was not statistically significant. Interleukin 4/12 and IFN-γ production were significantly higher in E6-E7-L1 / NSP4 group and E6-E7-L1 group compared to other groups (P < 0.05). Among different groups, E6/E7/L1 + NSP4 group was able to slow down the tumor growth process, but it was not significant (p > 0.05). Among the aforementioned cytokines, IFN-γ and IL-12 are among the cytokines that stimulate the Th1 pathway and IL-4 cytokine stimulates the Th2 pathway and B lymphocytes. CONCLUSION: Our data revealed that the present vaccine can reduce tumor size, and cytokine measurement showed that it stimulates innate and acquired immune responses, thus it can be a therapeutic vaccine in the tumor-bearing mice model.
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Neoplasias , Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Vacinas de DNA , Humanos , Feminino , Animais , Camundongos , Vacinas de DNA/genética , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , Linfócitos T Citotóxicos , Interleucina-4 , Infecções por Papillomavirus/prevenção & controle , Camundongos Endogâmicos C57BL , Vacinas contra Papillomavirus/genética , Adjuvantes Imunológicos , DNA , Citocinas , Interleucina-12RESUMO
Failure to neutralize HBsAg and subsequent escape from the host immune system may be caused by HBsAg mutations, particularly in the "a" determinant, which alters the antigenicity of the protein. The purpose of this study was to examine the frequency of S gene mutations in three generations of HBV cases in northeastern Iran. In this study, 90 patients with chronic HBV were assigned to three groups according to the inclusion criteria. The plasma were utilized to extract viral DNA, and the PCR was applied. Direct sequencing and alignment were performed on the S gene, using reference sequence. The results indicated that all HBV genomes were categorized as the genotype D/ayw2. Among 79 point mutations detected, 36.8% were silent, and 56.2% were missense. In the S region, mutations were observed in 88.9% of CHB subjects studied. In the three-generation group, 21.5% of mutations were in the "a" determinant, and 2.6%, 19.5%, and 87.0% of these mutations were observed in antigenic epitopes of CTLs, CD4+, and B cells, respectively. In addition, 56.7% of mutations occurred at Major Hydrophilic Region. S143L and G145R mutations which the most prevalent in the three-generation (36.7%, 20%), and two-generation (42.5%, 20%) groups, related to the failure of HBsAg detection, vaccine, and immunotherapy escape. The findings showed that most of the mutations were concentrated in the B cell epitope. Most CHB cases from the three-generation, especially grandmothers, had HBV S gene mutations and subsequent amino acid mutations, suggesting that these mutations may be critical for pathogenesis and vaccine evasion.
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Hepatite B Crônica , Hepatite B , Humanos , Vírus da Hepatite B/genética , Antígenos de Superfície da Hepatite B/genética , Mutação , Vacinas contra Hepatite B , Genótipo , DNA Viral/genética , DNA Viral/químicaRESUMO
The presence of polymorphisms in the human leukocyte antigen (HLA)-DQB1 gene, along with its expression, has been demonstrated to be correlated with spontaneous clearance and susceptibility to HBV infection. The present study aimed to evaluate the possible role of genetic polymorphisms in HLA-DQB1 in three generations of patients with chronic hepatitis B (CHB). Based on the inclusion criteria, 90 CHB patients, 18 individuals recovered from HBV infection, and 40 healthy subjects were chosen. The DNA contents of the whole blood samples were extracted in order to perform HLA-DQB1 typing by the PCR technique. Besides whole blood samples, sera were applied to measure liver function tests (LFTs), as well as the titers of anti-HDV and anti-HCV. Also, in all CHB patients were measured liver stiffness (LSM) by Fibro Scan. The results of HLA-DQB1 polymorphisms (rs2856718 and rs7453920) demonstrated that the majority of polymorphisms in CHB patients were HLA-DQB1*03, HLA-DQB1*05, HLA-DQB1*04:01 and HLA-DQB1*03:01 that associated with HBV persistence and chronicity. Among the patients who showed these polymorphisms, the mean±SD, LSM was 4±1.57 KPa and most of them, F grade was reported as F2, which was a sign of disease progression towards chronicity. HLA polymorphisms imputation revealed that HLA-DQB1*06:04 (3.4%, P-Value= 0.2) was detected only in healthy subjects as protective polymorphism, while the allele HLA-DQB1*03:03 was reported in both healthy subjects (P-Value= 0.06) and recovered patients (P-Value= 0.1) as suppressor of CHB formation. The allele HLA-DQB1*05:02 was found in both healthy subjects (3.4%) and CHB patients (4.5%) which was associated with risk to liver cirrhosis (P-Value= 0, OR: 0.002 0.95CI: 0.000-0.15). HLA polymorphism analysis indicated that 17.39% of patients who were seropositive for anti-HCV carried the HLA-DQB1*03:01. HBV resistance or infection risk could be assessed by DBQ1 typing. The existence of polymorphisms in HLA gene could influence the clearance (HLA-DQB1*03:03) or susceptibility and persistence of infection (HLA-DQB1*03, HLA-DQB1*05, HLA-DQB1*04:01 and HLA-DQB1*03:01). These results have the potential to improve personalized therapy and prognosis for HBV infection.
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Hepatite B Crônica , Hepatite B , Humanos , Hepatite B Crônica/genética , Predisposição Genética para Doença , Polimorfismo Genético , Alelos , Cirrose Hepática/genética , Vírus da Hepatite B/genética , Hepatite B/genéticaRESUMO
Neuroblastoma (NB) is a common cancer in childhood responsible for 15 % of fatalities by pediatric cancers. Epigenetic factors play an important role in the pathogenesis of NB. Recently, it has been demonstrated that circular RNAs (circRNAs, ciRNAs), a newly identified class of non-coding RNAs, are also dysregulated in NB. CircRNAs mediate their functions by regulating gene expression mainly through microRNA (miRNA) sponging. The dysregulation (abnormal upregulation or downregulation) of circRNAs is involved in tumorigenesis of a variety of tumors including NB. It seems that the expression of some circRNAs is correlated with NB prognosis and clinical features. CircRNAs might be favorable as a diagnostic/prognostic biomarker and therapeutic target. However, due to the lack of studies, it is difficult to make a conclusion regarding the clinical benefits of circRNAs. In this review, we discussed the circRNAs that experimentally have been proved to be dysregulated in NB tissues and cancer cells.
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COVID-19 is a rapidly spreading disease, which has caught the world by surprise. Millions of people suffer from illness, and the mortality rates are dramatically high. Currently, there is no specific and immediate treatment for this disease. Remedies are limited to supportive regiments and few antiviral and anti-inflammatory drugs. The lack of a definite cure for COVID-19 is the reason behind its high mortality and global prevalence. COVID-19 can lead to a critical illness with severe respiratory distress and cytokine release. Increased oxidative stress and excessive production of inflammatory cytokines are vital components of severe COVID-19. Micronutrients, metalloids, and vitamins such as iron, manganese, selenium, Zinc, Copper, vitamin A, B family, and C are among the essential and trace elements that play a pivotal role in human nutrition and health. They participate in metabolic processes that lead to energy production. In addition, they support immune functions and act as antioxidants. Therefore, maintaining an optimal level of micronutrients intake, particularly those with antioxidant activities, is essential to fight against oxidative stress, modulate inflammation, and boost the immune system. Therefore, these factors could play a crucial role in COVID-19 prevention and treatment. In this review, we aimed to summarize antiviral properties of different vitamins and minerals. Moreover, we will investigate the correlation between them and their effects in COVID-19 patients.
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Tratamento Farmacológico da COVID-19 , Selênio , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antivirais , Suplementos Nutricionais , Humanos , Micronutrientes/farmacologia , Micronutrientes/uso terapêutico , Minerais/uso terapêutico , Selênio/uso terapêutico , Vitamina A , Vitaminas/farmacologia , Vitaminas/uso terapêuticoRESUMO
Background: The aim of this study was to evaluate reinfection and fungal infections among 785 patients with COVID-19 disease admitted to Baqiyatallah Hospital in Northeastern Iran after the onset of the COVID-19 epidemic. Materials & Methods: In this descriptive-analytic study (20 February-21 July 2020), reinfection and fungal infections among 785 patients were investigated using epidemiological questionnaire, clinical trials, Real-time PCR and CT scan (chest computed tomography) from the hospital HIS (hospital's information system) and collected samples. Results: Reinfection and one oral candidiasis were diagnosed in one 68-year-old man and one 47-year-old man 63 and 42 days after the initial infection, respectively. Conclusion: The research results showed that exposure to COVID-19 may not establish long-term protective immunity to all patients.
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COVID-19 , Candidíase , Micoses , Humanos , Masculino , RNA Viral/genética , ReinfecçãoRESUMO
Astrocyte elevated gene-1 (AEG-1) is a positive regulator of tumorigenesis in human cancer cells. Human AEG-1 gene is located in chromosome 8q22 having 12 exons/11 introns. Chromosome 8q22 is known to be a hot spot for genomic alterations in several cancerous cells involving HCC. The aim of the study was assess association between the negative regulatory region of AEG-1 promoter mutations and genetic susceptibility to hepatocellular carcinoma. The negative regulatory region of the human AEG-1 promoter was evaluated in a total of 50 Iranian hepatocellular carcinomas (HCC) patients. For investigating AEG-1 promoter polymorphisms the PCR-sequencing method was used. In this study was found two new mutation C>T (-633) and G>C (-660) in the patient group. But it was not revealed the statistically significant association between any mutations in this region of the AEG-1 promoter with HCC susceptibility. According to presented data, we can say that the negative regulatory region of the AEG-1 promoter mutations did not exihibit significant relevance with hepatocellular carcinoma. We recommend further studies on the efficacy of the AEG-1 promoter in therapeutic targeting of the HCC.
Resumo: O gene AEG-1 é um regulador positivo da tumorigênese em células cancerígenas humanas. O gene humano AEG-1 está localizado no cromossomo 8q22 com 12 exons/11 introns. O cromossomo 8q22 é conhecido por ser um hotspot para alterações genômicas em várias células cancerígenas que envolvem o CHC. O objetivo do estudo foi avaliar a associação entre a região reguladora negativa das mutações do promotor AEG-1 e a suscetibilidade genética ao carcinoma hepatocelular. A região reguladora negativa do promotor humano AEG-1 foi avaliada em um total de 50 pacientes iranianos com carcinomas hepatocelulares (CHC). Para investigar os polimorfismos do promotor AEG-1, utilizou-se o método de sequenciação por PCR. Neste estudo foram encontradas duas novas mutações C>T (-633) e G>C (-660) no grupo de pacientes. Mas não foi revelada a associação estatisticamente significante entre quaisquer mutações nessa região do promotor AEG-1 com suscetibilidade ao CHC. De acordo com os dados apresentados, podemos dizer que a região reguladora negativa das mutações do promotor AEG-1 não demonstrou relevância significativa com o carcinoma hepatocelular. Recomendamos estudos adicionais sobre a eficácia do promotor AEG-1 no direcionamento terapêutico do CHC.
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Pacientes , Astrócitos , Carcinoma Hepatocelular , Predisposição Genética para Doença , CarcinogêneseRESUMO
The prevalence of Hepatitis C virus (HCV) is approximately 3% around the world. This virus causes chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The effectiveness of interferon-α and ribavirin therapy is about 50% and is associated with significant toxicity and cost. Hence, generating new vaccines or drugs is an obligation. However, there is no vaccine available for clinical use. DNA vaccines have some advantages such as producing feasibility and generating intensive cellular and humoral immune responses. Activation and improvement of natural immune defense mechanisms is a necessity for the development of an effective HCV vaccine. This article discusses the current status of therapies for hepatitis C, the promising new therapies and the experimental strategies to develop an HCV vaccine.
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Hepatitis C virus (HCV) chronic infection is a worldwide health problem, and numerous efforts have been invested to develop novel vaccines. An efficient vaccine requires broad immune response induction against viral proteins. To achieve this goal, we constructed a DNA vaccine expressing nonstructural 3 (NS3) gene (pcDNA3.1-HCV-NS3) and assessed the immune response in C57BL/6 mice. In this study, the NS3 gene was amplified with a nested-reverse transcriptase-polymerase chain reaction (RT-PCR) method using sera of HCV-infected patients with genotype 1a. The resulting NS3 gene was subcloned into a pcDNA3.1 eukaryotic expression vector, and gene expression was detected by western blot. The resultant DNA vaccine was co-administered with interleukin-12 (IL-12) as an adjuvant to female C57BL/6 mice. After the final immunizations, lymphocyte proliferation, cytotoxicity, and cytokine levels were assessed to measure immune responses. Our data suggest that co-administration of HCV NS3 DNA vaccine with IL-12 induces production of significant levels of both IL-4 and interferon (IFN)-γ (p<0.05). Cytotoxicity and lymphocyte proliferation responses of vaccinated mice were significantly increased compared to control (p<0.05). Collectively, our results demonstrated that co-administration of HCV NS3 and IL-12 displayed strong immunogenicity in a murine model.