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Background: Consecutive droughts and quantitative and qualitative reduction of surface and underground water resources have caused an increase in greenhouse and hydroponic cultivation for most garden crops, including strawberries, in Iran. On the other hand, most of the inputs of greenhouse crops in Iran are imported. To possibility of replacing vermicompost with peat moss under hydroponic cultivation, an experiment was done in a split plot based on randomized complete blocks design in three replications in Isfahan (Iran) Agricultural and Natural Resources Research Center in 2019. The main treatment was substrate at four levels included different levels of vermicompost (30 and 50%) and peat moss (30 and 50%) in combination with perlite and sub-treatment were Selva and Camarosa cultivars., Results: The results showed that Camarosa cultivar and Selva cultivar in (perlite/ peat moss 50:50) and Selva cultivar in (perlite / vermicompost 70:30) had maximum yield. Leaf number and chlorophyll index were maximum in Camarosa cultivar in peat moss substrates. Strawberry cultivars had the highest root fresh weight, the content of vitamin C and total soluble solids (TSS) in substrates containing vermicompost. Camarosa cultivar in (perlite / peat moss50:50) and Selva cultivar in (perlite /vermicompost 50:50) had maximum root dry weight. Also, the highest number of inflorescences was related to substrates containing peat moss and (perlite /vermicompost 70:30). Maximum amount of fresh and dry weight of shoots were observed in (perlite/ peat moss70:30). Selva cultivar had more inflorescences (16.5%) than Camarosa cultivar and Camarosa cultivar produced more fresh and dry weight of shoots (16.5%, 23.01%) than Selva cultivar., Conclusion: Expriment results highlighted the importance of considering both main and sub-treatments in agricultural research, as they interacted to influence various growth and yield parameters. 50% vermicompost treatment combined with perlite had a positive impact on plant growth and in quality index such as vitamin C content and TSS was highest. while the choice of cultivar affected different aspects of plant development. Selva cultivar was known to be more tolerant to salinity caused by vermicompost. Vermicompost is local and more economical, also salt resistant cultivars are recommended in a controlled (30%) amount of vermicompost., (© 2024. The Author(s).)

Background: Although, preliminary reports of Severe Acute Respiratory Syndrome (SARS)-CoV-2 infection suggest that the infection causes a less severe illness in children, there is now growing evidence of other rare or even serious complications of disease., Case Presentation: During the recent COVID-19 pandemic in Kerman, Iran, two children (an 8 year-old boy and a 6 year-old girl) were referred to outpatient Clinic of Pediatric Rheumatology with complaints of limping. Both children had experienced fever and mild respiratory tract infection. At the beginning of the second week of infection, they developed joint effusion. They both tested positive for coronavirus infection and were therefore diagnosed with post Coronavirus reactive arthritis. Both children were treated successfully with rest and Non-Steroidal Anti-Inflammatory Drugs (NSAID). They did not have any medical problems in the two months fallow up., Conclusions: These two cases suggest that COVID-19 may be rheumatogenic. Highlighting the need for awareness of physicians, especially pediatricians, regarding the pathogenesis margins of this virus, as late presentations are of great importance.

Background: Stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS) is an autosomal recessive disorder caused by defects in the ADP-Ribosylhydrolase Like 2 (ADPRHL2; OMIM: 618170) gene. This gene encodes the ADP-ribosylhydrolase enzyme (ARH3) that eliminates the addition of poly-ADP ribose (PAR) in the cellular stress onto proteins in the ADP-ribosylation process in which adding one or more ADP-ribose moieties onto the target proteins in the post-translational modification have occurred. In this study, we report a new case of CONDSIAS in the Iranian population. A literature review of CONDSIAS is also included., Case Presentation: A four-year-old female patient, born to a consanguineous Iranian family, was referred with various clinical symptoms including impaired speech, variable ataxia, infrequent seizures, and gradual onset of truncal hypotonia. Over time, she developed complete motor and speech regression, bilateral sensorineural hearing loss, infrequent seizures, abdominal distension and gastrointestinal (GI) intolerance, and loss of consciousness. To better molecularly diagnose, trio-whole-exome sequencing (WES) was performed on the proband and her parents. Sanger sequencing was also applied to investigate co-segregation analysis. Using in silico predictive tools, the possible impacts of the variant on the structure and function of ADPRHL2 protein were predicted. All basic metabolic tests were normal, while serial coronal magnetic resonance imaging (MRI) showed progressive cerebral and cerebellar atrophy in addition to cerebral white matter signal changes as a novel neuroimaging finding. GI intolerance was another novelty of clinical scenarios in the patient. An auditory brainstem response test showed a severe bilateral sensorineural hearing loss. An electroencephalogram also confirmed focal seizures. From the molecular perspective, a novel homozygous frameshift variant in the ADPRHL2 gene (NM_017825.2; c.636_639del, p.(Leu212fs)) was identified by WES., Conclusions: CONDSIAS is an ultra-rare neurodegenerative disorder. In the present study, we introduced extra-neurological and neuroimaging findings of this disorder in a female child caused by a novel frameshift variation in the ADPRHL2 gene.

Background: Earthquakes are one of the most destructive natural disasters in which many people are injured, disabled, or died. Iran has only 1 % of the world's population, but the percentage of its earthquake-related deaths is absolutely higher. Therefore, this study aimed to determine the level of earthquake preparedness of households and its predictors using the Health Belief Model (HBM)., Methods: This observational descriptive and analytical study was conducted on 933 households in Hamadan province, located in the west of Iran, in 2019. Multi-stage cluster random sampling was used for selecting the participants. The inclusion criteria were being at least 18 years old and being able to answer the questions. A questionnaire was used for data collection including earthquake preparedness, awareness of earthquake response, predictors of earthquake preparedness based on the HBM, and demographic information. Analysis of variance, independent t-test, and a linear regression model was used., Results: The mean age of participants was 38.24 ± 12.85 years. The average score of earthquake preparedness was low (approximately 30%). There was a significant relationship between earthquake preparedness and gender (P < 0.001), homeownership (P < 0.001), marriage status (P < 0.001), education (P < 0.001), and previous earthquake experience (P < 0.001). Regarding the HBM constructs, perceived benefits (P < 0.001), cues to action (P < 0.001), and self-efficacy (P < 0.001) were significant predictors of earthquake preparedness., Conclusions: Earthquake preparedness was insufficient. Besides, perceived benefits, cues to action, and self-efficacy were predictors of earthquake preparedness. These predictors can be taken into account, for designing and implementing related future interventions.

Background: The current diagnostic cornerstone for septic arthritis contains gram stains, bacterial culture, and cell count with a differential of aspirated synovial fluid. Recently, a synovial leukocyte esterase (LE) test has been used for diagnosing septic arthritis. Since this test measures the esterase activity of leukocytes, there is always a dilemma for using this test in patients with inflammatory arthritis., Methods: We collected the synovial fluid specimens as part of the general diagnostic protocol for patients suspected of Juvenile Idiopathic Arthritis (JIA) or Septic Arthritis (SA). Each group included 34 patients. We compared the result of the synovial LE test with the result of the culture of each patient., Results: The mean ages of patients were 64.14 ± 31.27 and 50.88 ± 23.19 months in the JIA group and septic arthritis group, respectively. The LE test results were positive in 30 specimens, trace in 3 and negative in one in the first-time test and were positive in 31 specimens and trace in 3 in the second-time test, while it was negative in all patients with JIA. Hence, the sensitivity of the synovial LE test was 80.8%, the specificity, PPV, and NPV were 78.6, 70.0, 86.8% respectively based on a positive culture., Conclusion: The leukocyte esterase strip test can be used as a rapid, bedside method for diagnosing or excluding bacterial infections in different body fluids. The synovial LE test can be used as an accurate test to rapidly rule in or out an acute articular bacterial infection, even in patients with concurrent inflammatory arthritis.

Background and aim: Removing the chest tube in cardiac patients after surgery is one of the worst experiences of hospitalization in the intensive care units. Various pharmacological and non-pharmacological methods are available to control pain in these patients. This study aimed to investigate the combined effect of reflexology massage and respiratory relaxation on pain following chest tube removal in cardiac surgery patients of Shahid Beheshti Hospital in Shiraz, Iran, in 2023. Methods: This was a double-blind randomized clinical trial performed on 140 patients who underwent heart surgery and had a chest tube in Shiraz, Iran. The samples were randomly divided into four groups: 1- control group, 2- respiratory relaxation group, 3- foot reflex massage group, and 4- a combination of respiratory relaxation and reflexology massage. To collect data, two demographic questionnaires, and a visual analog scale were used. Results: The participants of the four groups were not meaningfully different in terms of age, BMI, duration of surgical operation, gender, job, education, place of residency, number of chest tubes, history of operation (P = 0.99, 0.31, 0.06, 0.81, 0.97, 0.96, 0.17, 0.10, 0.89 respectively). The mean scores of pain intensity during chest tube removal, and 15 min after chest tube removal were not statistically different among the four groups of study (P = 0.15, 0.54 respectively); However, just after chest tube removal, the mean scores of pain intensity differed meaningfully among four groups (P = 0.008). Conclusion: The results showed that reflexology massage and respiratory relaxation both reduce pain immediately after chest tube removal in heart surgery patients. Also, the combination of these two techniques was more effective in reducing patients' average pain. [ABSTRACT FROM AUTHOR]

Background: Unintentional medication discrepancies during care transitions pose a significant risk for medication errors, particularly in critically ill older patients. This study aimed to investigate the prevalence of such discrepancies during care transitions and their impact on post-discharge emergency department (ED) visits in this patient population. Methods: This retrospective cross-sectional study included patients aged 65 and older who were on chronic medications and admitted to the intensive care units of emergency departments (ED-ICUs) between 2019 and 2020. We evaluated unintentional medication discrepancies, including omissions or changes in medication type, dose, frequency, formulation, or administration route without clear clinical justification during care transition. The association between these discrepancies and post-discharge ED visits was analyzed using a multivariable Cox-proportional hazard model. Results: Of the 339 patients analyzed, 68% encountered unintentional medication discrepancies at some point during care transitions, with prevalence of 35% at admission, 20% during transfer, and 49% at discharge. After adjusting for confounding factors, patients with unintentional medication discrepancies had a twofold higher risk of ED visits within 30 days of discharge (HR = 2.13, 95% CI = 1.06–4.30). Conclusion: This study demonstrated a substantial prevalence of unintentional medication discrepancies among critically ill older adults during care transitions, significantly increasing the risk of ED visits within a month of discharge. The findings highlight the crucial need for systematic identification and management of medication discrepancies throughout the care transition process to enhance patient safety. [ABSTRACT FROM AUTHOR]

Background: Thyroid cancer is ranked as the most common malignancy within the endocrine system and the seventh most prevalent cancer in women globally. Thyroid malignancies require evaluating biomarkers capable of distinguishing between them for accurate diagnosis. We examined both mRNA and protein levels of TSPAN1 in plasma and tissue samples from individuals with thyroid nodules to aid this endeavour. Methods: In this case-control study, TSPAN1 was assessed at both protein and mRNA levels in 90 subjects, including papillary thyroid cancer (PTC; N = 60), benign (N = 30), and healthy subjects (N = 26) using enzyme-linked immunosorbent assay (ELISA) and SYBR-Green Real-Time PCR, respectively. Results: TSPAN1 plasma levels were decreased in PTC and benign compared to healthy subjects (P = 0.002). TSPAN1 mRNA levels were also decremented in the tumoral compared to the paired normal tissues (P = 0.012); this drop was also observed in PTC patients compared to benign patients (P = 0.001). Further, TSPAN1 had an appropriate diagnostic value for detecting PTC patients from healthy plasma samples with a sensitivity of 76.7% and specificity of 65.4% at the cutoff value < 2.7 (ng/ml). Conclusion: TSPAN1 levels are significantly reduced in patients with benign and PTC, demonstrating its potential value as a diagnostic biomarker. Additionally, the significant reduction in TSPAN1 mRNA expression within PTC tumor tissues may suggest its involvement in tumor progression and development. Further studies, including larger-scale validation studies and mechanistic investigations, are imperative to clarify the molecular mechanisms behind TSPAN1 and, ultimately, its clinical utility for treating thyroid disorders. [ABSTRACT FROM AUTHOR]

Background: The efficacy of mRNA-based vaccines and therapies relies on lipid nanoparticles (LNPs) as carriers to deliver mRNA into cells. The chemical structure of ionizable lipids (ILs) within LNPs is crucial in determining their delivery efficiency. Results: In this study, we synthesized 623 alkyne-bearing ionizable lipids using the A3 coupling reaction and assessed their effectiveness in mRNA delivery. ILs with specific structural features—18-carbon alkyl chains, a cis-double bond, and ethanolamine head groups—demonstrated superior mRNA delivery capabilities. Variations in saturation, double bond placement, and chain length correlated with decreased efficacy. Alkynes positioned adjacent to nitrogen atoms in ILs reduced the acid dissociation constant (pKa) of LNPs, thereby hindering mRNA delivery efficiency. Conversion of alkynes to alkanes significantly enhanced mRNA delivery of ILs both in vitro and in vivo. Moreover, combining optimized ILs with cKK-E12 yields synergistic LNPs that showed markedly augmented mRNA expression levels in vivo. Conclusions: Overall, our study provides insights into the structure–function relationships of ILs, providing a foundation for the rational design of ILs to enhance the efficacy of LNPs in mRNA delivery. [ABSTRACT FROM AUTHOR]

Background: Despite progress, under-five mortality remains high, especially in Sub-Saharan Africa and South Asia, where around 13,400 children die daily. Environmental pollutants, including PM2.5 from outdoor air and household air pollution, significantly contribute to these preventable deaths. Methods: This cross-country study combined satellite data with 113 surveys from the IPUMS-DHS dataset (1998–2019) to examine under-five child mortality in 41 developing countries. The integration of Global Annual Particulate Matter with a diameter of 2.5 micrometres or less (PM2.5) Grids from Socioeconomic Data and Applications Center (SEDAC) and geospatial data from the DHS Program enabled a focused analysis of the association between indoor and outdoor air pollution, particularly PM2.5, and child mortality rates using both logistic and multilevel logistic regression models, as well as estimating Population Attributable Fractions (PAF) to quantify the mortality burden attributable to these pollutants. Results: Outdoor air pollution, measured by a one standard deviation increase in PM2.5, significantly increased the risk of child mortality (Odds Ratio [OR]: 1.14; 95% Confidence Interval [CI]: 1.10–1.18; p < 0.001). Moderate and high household air pollution exposure also heightened this risk, with increases of 37% (OR: 1.37; 95% CI: 1.24–1.53; p < 0.001) and 40% (OR: 1.40; 95% CI: 1.26–1.56; p < 0.001), respectively, compared to no exposure. Multilevel models (Models 5a and 10a) produced similar estimates to standard logistic regression, indicating robust associations. Additionally, Population Attributable Fraction analysis revealed that approximately 11.9% of under-five mortality could be prevented by reducing ambient PM2.5 exposure and 12.0% by mitigating household air pollution. The interaction between indoor and outdoor pollution revealed complex dynamics, with moderate and high household exposure associated with a reduction in mortality risk when combined with PM2.5. Geographical disparities were observed, with stronger correlations between outdoor air pollution and child mortality in Africa compared to Asia, and more pronounced impacts in low-income countries. However, household air pollution had stronger association with child mortality in Africa and lower- and middle-income countries. Conclusions: Our findings could serve as a guide for policy development aimed at reducing under-five mortality, ultimately contributing to the attainment of the Sustainable Development Goal (SDGs). [ABSTRACT FROM AUTHOR]

Thyroid cancer (TC) represents one of the most prevalent endocrine malignancies, with a rising incidence worldwide. Epigenetic alterations, which modify gene expression without altering the underlying DNA sequence, have garnered significant attention in recent years. Increasing evidence underscores the pivotal role of epigenetic modifications, including DNA methylation, RNA methylation, and histone methylation, in the pathogenesis of TC. This review provides a comprehensive overview of these reversible and environmentally influenced epigenetic modifications, highlighting their molecular mechanisms and functional roles in TC. Additionally, the clinical implications, challenges associated with studying these epigenetic modifications, and potential future research directions are explored. [ABSTRACT FROM AUTHOR]

Background: Despite the presence of evidence that establishes a strong correlation between oxidative stress and thyroid cancer, there exists a scarcity of research that investigates the specific role of glutathione as an important antioxidant in this particular context. The objective of this study was to assess the altered balance of oxidative stress in cases of thyroid cancer, which includes both papillary thyroid carcinoma (PTC) and micro PTC (mPTC), by examining and comparing the total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), reduced glutathione (GSH), oxidized glutathione (GSSG), and GSSG/GSH ratio with those of individuals diagnosed with multinodular goiter (MNG) as well as Healthy subjects. Materials and methods: Plasma samples were collected from 92 patients (23 mPTC, 23 PTC, 23 MNG, 23 Healthy). The levels of TAC, TOS, GSH, and GSSG were measured using a commercial assay kits, and the OSI and GSSG/GSH ratio were calculated for each sample. Statistical analyses were performed to compare the oxidative stress between the groups. Results: The plasma levels of TOS were significantly higher in the mPTC, PTC, and MNG groups compared to the Healthy individuals (p < 0.05). The OSI in the mPTC and PTC groups showed a significant increase compared to the Healthy group (p < 0.05). The levels of GSH in mPTC and PTC were markedly lower compared to the Healthy subjects (p < 0.01). Interestingly, the concentration of GSH in mPTC was found to be considerably lower than in PTC and MNG patients (p < 0.01). Conclusion: These findings indicate that GSH may be a useful biomarker for evaluating oxidative stress and antioxidant system status in patients with PTC, especially mPTC. Low levels of GSH may indicate increased levels of oxidative stress, which may contribute to the development and progression of mPTC to PTC. [ABSTRACT FROM AUTHOR]

Background: We have previously identified an unsuspected role for GJB3 showing that the deficiency of this connexin protein induces aneuploidy in human and murine cells and accelerates cell transformation as well as tumor formation in xenograft models. The molecular mechanisms by which loss of GJB3 leads to aneuploidy and cancer initiation and progression remain unsolved. Methods: GJB3 expression levels were determined by RT-qPCR and Western blot. The consequences of GJB3 knockdown on genome instability were assessed by metaphase chromosome counting, multinucleation of cells, by micronuclei formation and by the determination of spindle orientation. Interactions of GJB3 with α-tubulin and F-actin was analyzed by immunoprecipitation and immunocytochemistry. Consequences of GJB3 deficiency on microtubule and actin dynamics were measured by live cell imaging and fluorescence recovery after photobleaching experiments, respectively. Immunohistochemistry was used to determine GJB3 levels on human and murine bladder cancer tissue sections. Bladder cancer in mice was chemically induced by BBN-treatment. Results: We find that GJB3 is highly expressed in the ureter and bladder epithelium, but it is downregulated in invasive bladder cancer cell lines and during tumor progression in both human and mouse bladder cancer. Downregulation of GJB3 expression leads to aneuploidy and genomic instability in karyotypically stable urothelial cells and experimental modulation of GJB3 levels alters the migration and invasive capacity of bladder cancer cell lines. Importantly, GJB3 interacts both with α-tubulin and F-actin. The impairment of these interactions alters the dynamics of these cytoskeletal components and leads to defective spindle orientation. Conclusion: We conclude that deregulated microtubule and actin dynamics have an impact on proper chromosome separation and tumor cell invasion and migration. Consequently, these observations indicate a possible role for GJB3 in the onset and spreading of bladder cancer and demonstrate a molecular link between enhanced aneuploidy and invasive capacity cancer cells during tumor cell dissemination. [ABSTRACT FROM AUTHOR]

Background Medicine smuggling poses a serious public health threat, limiting patients’ safe and timely access to this essential resource. Thus, this study aims to identify the factors contributing to the vulnerability to medicine smuggling and propose effective strategies to combat this issue in Iran. Methods An analysis of news media was conducted using qualitative content analysis. News text items related to medicine smuggling were retrieved from various online news sources between March 21, 2017, and May 21, 2023. To select health-oriented and general online news stations, news agencies, and newspapers, the purposeful sampling method with a maximum variation strategy was used. The selected sources included Mehr News Agency, Khabar Online, Islamic Consultative Assembly News Agency (ICANA), Islamic Republic News Agency (IRNA), Iranian Students News Agency (ISNA), Hamshahri, Donya-e-Eqtesad newspapers, Webda, Sepid Online, and Iran’s Food and Drug Administration News Agency (IFDANA). All data coding was manually done using Microsoft Excel software version 2016. Results A total of 277 news articles were found to meet the established criteria for inclusion. The analysis revealed four main themes, each with several sub-themes, that shed light on the factors that drive vulnerability and the strategies to combat medicine smuggling. These themes are the economic environment, government and stewardship, information technology systems, and socio-cultural factors. The economic environment emerged as the most significant theme, encompassing medicine selection, reimbursement, and procurement, all of which affect the smuggling of pharmaceuticals in Iran. Conclusion To combat medicine smuggling, it is important to adjust policies based on the identified vulnerabilities. Effective strategies to reverse pharmaceutical smuggling include capacity building of pharmaceutical manufacturing companies, implementing regulated and enhanced supervisory and rulemaking policies, strengthening health insurance, improving e-infrastructure, and increasing public awareness through collaborative approaches involving various stakeholders within and outside the health system. [ABSTRACT FROM AUTHOR]

Objectives: The population of older adults continues to grow in Iran, with pharmaceutical costs as a leading driver of household health-related costs. The present study was conducted to estimate the out-of-pocket pharmaceutical expenditure and its socioeconomic predictors among households with the elderly in Iran. Method: This study is a secondary analysis using 2019 national household expenditure and income survey data in Iran. The sample size was 9381 households with at least one member older than 65. The double-hurdle model in STATA 16 was used to examine the association between independent variables and households' out-of-pocket pharmaceutical expenditures. Results: The mean out-of-pocket pharmaceutical expenditures for each household with elderly member was $8065 per year. There was a positive association between the (female) gender of the household head, urban residence, employment status, insurance expenditure and a higher level of education of the head of the household with the out-of-pocket pharmaceutical expenditures (P < 0.05). The income of elderly households did not affect these expenditures (P > 0.05). Conclusions: This study showed that the socioeconomic characteristics of elderly families not only influenced their decision to enter the medicine market, but also the rate of medicine purchase. It is helpful to manage and control the pharmaceutical costs among the elderly. [ABSTRACT FROM AUTHOR]

This review article presents an in-depth analysis of the current state of research on receptor tyrosine kinase regulatory non-coding RNAs (RTK-RNAs) in solid tumors. RTK-RNAs belong to a class of non-coding RNAs (nc-RNAs) responsible for regulating the expression and activity of receptor tyrosine kinases (RTKs), which play a critical role in cancer development and progression. The article explores the molecular mechanisms through which RTK-RNAs modulate RTK signaling pathways and highlights recent advancements in the field. This include the identification of potential new RTK-RNAs and development of therapeutic strategies targeting RTK-RNAs. While the review discusses promising results from a variety of studies, encompassing in vitro, in vivo, and clinical investigations, it is important to acknowledge the challenges and limitations associated with targeting RTK-RNAs for therapeutic applications. Further studies involving various cancer cell lines, animal models, and ultimately, patients are necessary to validate the efficacy of targeting RTK-RNAs. The specificity of ncRNAs in targeting cellular pathways grants them tremendous potential, but careful consideration is required to minimize off-target effects, the article additionally discusses the potential clinical applications of RTK-RNAs as biomarkers for cancer diagnosis, prognosis, and treatment. In essence, by providing a comprehensive overview of the current understanding of RTK-RNAs in solid tumors, this review emphasizes their potential as therapeutic targets for cancer while acknowledging the associated challenges and limitations. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer disease is known as the most common cancer among women. Lack of knowledge and awareness is a leading cause of breast cancer, and since nearly all women are increasingly susceptible to this disease, training screening behaviors for early detection is proven essential in order to reduce breast cancer mortality. Therefore, the present study was designed to determine the effect of educational intervention based on the Health Action Model in improving breast cancer screening behaviors in women aged 30 to 69 in Kashan, Iran. Methods: This quasi-experimental study was conducted on 162 women aged 30–69 years old among the clients of Comprehensive health service centers in Kashan, Iran and they were assigned to intervention and control groups. The research instrument included a questionnaire assessed within three phases: baseline, 3-months, and 6-months, containing Health Action Model (HAM) structures and also three screening behaviors. The intervention consisted of a model-based education package and was carried out over 2 months. To evaluate the effect of the intervention, the mean of model structures and proportion screening behaviors in the third and sixth months were compared with the baseline phase. All analyses were carried out using SPSS, version 22. Results: The intervention and control groups were homogeneous regarding the structures of the HAM and the proportion of screening behaviors in the baseline phase (p > 0.05). In the 3-month (p < 0.05) and 6-month (p < 0.05) phases, the mean scores of the HAM constructs in the intervention group were found higher compared with the control group. Moreover, the proportion of clinical breast examinations in the intervention group was statistically higher than in the control group in the 3-month (p < 0.001) and 6-month (p < 0.001) phases. In addition, the proportion of mammography performed in the 3-month (p = 0.002) and 6-month (p < 0.001) phases were reported to be higher in the intervention group compared with the control group. Conclusion: Overall, these results provide important insight into the effectiveness of the interventions based on the Health Action Model in promoting breast cancer screening behaviors and the determinants of such behaviors. [ABSTRACT FROM AUTHOR]

Background: Coronary artery diseases (CADs) are the most important non‑communicable diseases (NCDs), which cause the highest number of deaths around the world. Hypertension (HTN), dyslipidemia (DL), diabetes mellitus (DM), obesity (OB), low physical activity (LPA), smoking, opium consumption (OC) and anxiety are the most important CAD risk factors, which are more dangerously present in combination in some patients. Methods: A total of 5835 people aged 15 to 75 years were enrolled in the phase 1 (2012) and followed up to the phase 2 (2017) of the population-based Kerman coronary artery diseases risk factors study (KERCADRS). The prevalence and pattern of different combinations of CAD risk factors (double to quintuple) and their 5-year incidence rates were assessed. Results: The prevalence of single CAD risk factors (RFs) in phase 2 was 50.2% (DL), 47.1% (LPA), 28.1% (abdominal obesity), 21.2% (OB), 16.5% (HTN), 9.2% (smoking), 9.1% (OC), and 8.4% (DM). The most frequent combination of risk factors was LPA plus DL (23.9%), metabolic syndrome (19.6%), and DL plus OB (17.8%). The 5-year incidence rates of multiple comorbidities (in persons per 100 person-years) was DL plus LPA (2.80%), HTN plus DL (1.53%), and abdominal obesity (AOB) plus DL (1.47%). The most participants (84.4%) suffered from at least one RF, while 54.9% had at least two and 29.9% had at least three RFs. Conclusion: The results showed that a large portion of the study population suffers from multiple CAD RFs. The findings underscore the importance of identifying multiple CAD risk factors to reduce the overall burden of these NCDs. [ABSTRACT FROM AUTHOR]

Background: A heavy financial burden is imposed on patients suffering from chronic diseases due to medicine out-of-pocket payments. Objectives: This study focuses on assessing the affordability of medications used for chronic respiratory diseases (CRDs) such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) in Iran, specifically on the category R medicines listed in the 2017 Iran drug list (IDL) that are used for the treatment of these diseases, based on the anatomical therapeutic chemical (ATC) drug code. Methods: The affordability of medicines in mono and combination therapy approaches was assessed in CRDs using the World Health Organization/Health Action International (WHO/HAI) methodology. Accordingly, if out-of-pocket payment for 30-days of pharmacotherapy exceeds one day for the lowest-paid unskilled government worker (LPGW), it's considered non-affordable. Results: Based on the monotherapy approach, our finding demonstrates that all generic medicines of category R were affordable. However, branded drugs such as Symbicort®, Pulmicort Respules®, Flusalmex®, Seretide®, Fluticort Plus®, Seroflo®, and Salmeflo® cost between 1.2 and 2.5 days' wage of LPGW and considered unaffordable despite 70% insurance coverage. Moreover, based on the affordability ratio in the combination therapy approach, all medicines used in asthma, COPD, and CF patients with mild respiratory problems are affordable except omalizumab (inj), which is non-affordable due to its high price and no insurance coverage. Conclusion: Results showed that the existing insurance coverage does not protect households from hardship, so more considerations are needed such as different insurance schedules and patient support programs. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the potential interaction between dietary intake and genetics on incident colorectal cancer (CRC) and whether adherence to healthy dietary habits could attenuate CRC risk in individuals at high genetic risk. Methods: We analyzed prospective cohort data of 374,004 participants who were free of any cancers at enrollment in UK Biobank. Dietary scores were created based on three dietary recommendations of the World Cancer Research Fund (WCRF) and the overall effects of 11 foods on CRC risks using the inverse-variance (IV) method. Genetic risk was assessed using a polygenic risk score (PRS) capturing overall CRC risk. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs (confidence intervals) of associations. Interactions between dietary factors and the PRS were examined using a likelihood ratio test to compare models with and without the interaction term. Results: During a median follow-up of 12.4 years, 4,686 CRC cases were newly diagnosed. Both low adherence to the WCRF recommendations (HR = 1.12, 95% CI = 1.05–1.19) and high IV-weighted dietary scores (HR = 1.27, 95% CI = 1.18–1.37) were associated with CRC risks. The PRS of 98 genetic variants was associated with an increased CRC risk (HRT3vsT1 = 2.12, 95% CI = 1.97–2.29). Participants with both unfavorable dietary habits and a high PRS had a more than twofold increased risk of developing CRC; however, the interaction was not significant. Adherence to an overall healthy diet might attenuate CRC risks in those with high genetic risks (HR = 1.21, 95% CI = 1.08–1.35 for high vs. low IV-weighted dietary scores), while adherence to WCRF dietary recommendations showed marginal effects only (HR = 1.09, 95% CI = 1.00–1.19 for low vs. high WCRF dietary scores). Conclusion: Dietary habits and the PRS were independently associated with CRC risks. Adherence to healthy dietary habits may exert beneficial effects on CRC risk reduction in individuals at high genetic risk. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is one of the main causes of death from cancer around the world, imposing a significant economic burden on the families and healthcare system. The present study aimed at determining the economic burden of breast cancer in the patients referred to the medical centers in Fars province in southern Iran in 2021. Methods: This cross-sectional study is a partial economic evaluation and a cost-of-illness study with a bottom-up and prevalence-based approach, conducted in Fars province in southern Iran in 2021 from the societal perspective. A total of 230 patients were randomly included in the study, and a researcher-made data collection form was used to collect the required data. The data on direct medical costs were collected using the information on patients' medical and financial records. On the other hand, the data on direct non-medical and indirect costs were obtained using self-reports by the patients or their companions. The Excel 2016 software was used to analyze the collected data. Results: The results showed that the annual cost of each breast cancer patient in the studied sample was 11,979.09 USD in 2021. Direct medical costs accounted for the largest share of costs (70.69%, among which the cost of radiotherapy was the highest one. The economic burden of the disease in the country was estimated at 193,090,952 USD. Conclusions: In general, due to the high prevalence of breast cancer and the chronicity of this disease, its medical costs can impose a heavy economic burden on society, the health system, the insurance system, and patients. Thus, in order to reduce the costs, the following suggestions can be offered: the use of advanced radiotherapy techniques, increasing the insurance coverage of required services, establishing low-cost accommodation centers near medical centers for the patients and their companions, providing specialized medical services for the patients in towns, using the Internet and virtual space to follow up the treatment of the patients, and carrying out free screening programs and tests for faster diagnosis of the infected patients and susceptible or exposed people. [ABSTRACT FROM AUTHOR]

Objectives: Immunoglobulin A deficiency (IgAD) is a common disease with an unknown genetic defect, characterized by the decreased or absent IgA with other isotypes normal, normal subclasses, and specific antibodies. Patients with this disorder represent a spectrum of clinical manifestations including infections, autoimmune disorders, malignancy, and allergic diseases. The current study aimed to evaluate their prevalence and categorized them. Methods: We searched PubMed, Web of Science, and Scopus databases to find eligible studies from the earliest available date to January 2022 with standard keywords. Pooled estimates of clinical manifestations prevalence and the corresponding 95% confidence intervals were calculated using random-effects models. Results: The most prevalent clinical manifestations belonged to infection (64.8%) followed by allergic diseases (26.16%) and autoimmunity (22.0%), respectively. In selective IgA deficiency patients as the largest group of IgAD in current study, celiac disease (6.57%), Inflammatory bowel disease (4.01%), and rheumatoid arthritis (3.80%) were the most prevalent autoimmunity. Meanwhile, the most frequent infection was respiratory tract infection, fungal infection, and gastrointestinal infection at 50.74%, 18.48%, and 15.79%, respectively. In addition, the pooled prevalence of asthma, allergic rhinitis, and allergic conjunctivitis were 19.06%, 15.46%, and 11.68%, respectively which were reported as the most widespread allergic diseases. Conclusions: Our results showed that apart from undiagnosed IgAD patients, IgAD patients represent a wide range of clinical manifestations. Infection, allergy, and autoimmunity are the most common clinical manifestations. The concurrent presence of IgA and IgG subtypes deficiency could be associated with increased susceptibility to infection. Considering the probability of developing new clinical complications during follow-up, periodic assessments of IgAD patients should be inspected. [ABSTRACT FROM AUTHOR]

Background: Primary antibody deficiencies (PAD) are characterized by a heterogeneous clinical presentation and low prevalence, contributing to a median diagnostic delay of 3–10 years. This increases the risk of morbidity and mortality from undiagnosed PAD, which may be prevented with adequate therapy. To reduce the diagnostic delay of PAD, we developed a screening algorithm using primary care electronic health record (EHR) data to identify patients at risk of PAD. This screening algorithm can be used as an aid to notify general practitioners when further laboratory evaluation of immunoglobulins should be considered, thereby facilitating a timely diagnosis of PAD. Methods: Candidate components for the algorithm were based on a broad range of presenting signs and symptoms of PAD that are available in primary care EHRs. The decision on inclusion and weight of the components in the algorithm was based on the prevalence of these components among PAD patients and control groups, as well as clinical rationale. Results: We analyzed the primary care EHRs of 30 PAD patients, 26 primary care immunodeficiency patients and 58,223 control patients. The median diagnostic delay of PAD patients was 9.5 years. Several candidate components showed a clear difference in prevalence between PAD patients and controls, most notably the mean number of antibiotic prescriptions in the 4 years prior to diagnosis (5.14 vs. 0.48). The final algorithm included antibiotic prescriptions, diagnostic codes for respiratory tract and other infections, gastro-intestinal complaints, auto-immune symptoms, malignancies and lymphoproliferative symptoms, as well as laboratory values and visits to the general practitioner. Conclusions: In this study, we developed a screening algorithm based on a broad range of presenting signs and symptoms of PAD, which is suitable to implement in primary care. It has the potential to considerably reduce diagnostic delay in PAD, and will be validated in a prospective study. Trial registration The consecutive prospective study is registered at clinicaltrials.gov under NCT05310604 [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that diagnostic salivary tests measuring inflammatory biomarkers are being developed to assess inflammatory status for early detection, prevention, and progression of periodontal disease. Therefore, the aim of the present study was to investigate and identify the salivary biomarker that can predict the inflammatory status of periodontal disease. Methods: A total of 36 patients (28 women and 8 men) with an average age of 57 years were investigated. Unstimulated saliva was collected from the recruited subjects and analyzed using SillHa, a saliva-testing device that measures bacteria count, saliva buffer capacity, acidity, leukocyte esterase, protein, and ammonia. Periodontal parameters were then obtained by clinical examination and initial periodontal therapy was performed. Data obtained with SillHa were compared with clinical periodontal parameters at baseline, re-examination (three months from baseline), and final examination (six months from re-examination). Results: Leukocyte esterase activity in saliva measured by SillHa; BOP and PCR measured by clinical examination showed a significant difference between baseline and final examination and between re-examination and final examination. Patients in the lower median group (group 1) had a significant difference in leukocyte esterase activity between baseline and final examination and re-examination and final examination. In addition, patients in Group 1 had significantly lower BOP between baseline and final examination. While patients in the higher median group (group 2) showed a modest decrease in leukocyte esterase activity, which was significant only between baseline and final examination, no significant changes were observed concerning BOP. Furthermore, the associated systemic disease was observed in 30% and 81.2% of group 1 and 2 patients, respectively. Conclusion: The results suggest that leukocyte esterase activity in saliva measured by SillHa could serve as a reliable diagnostic marker for monitoring inflammatory status in periodontal disease. [ABSTRACT FROM AUTHOR]

Background: Anaplastic thyroid carcinoma (ATC) is the most aggressive subtype of thyroid cancer. In this study, we used a three-dimensional in vitro system to evaluate the effect of a dual MEK/Aurora kinase inhibitor, BI-847325 anticancer drug, on several cellular and molecular processes involved in cancer progression. Methods: Human ATC cell lines, C643 and SW1736, were grown in alginate hydrogel and treated with IC50 values of BI-847325. The effect of BI-847325 on inhibition of kinases function of MEK1/2 and Aurora kinase B (AURKB) was evaluated via Western blot analysis of phospho-ERK1/2 and phospho-Histone H3 levels. Sodium/iodide symporter (NIS) and thyroglobulin (Tg), as two thyroid-specific differentiation markers, were measured by qRT-PCR as well as flow cytometry and immunoradiometric assay. Apoptosis was assessed by Annexin V/PI flow cytometry and BIM, NFκB1, and NFκB2 expressions. Cell cycle distribution and proliferation were determined via P16, AURKA, and AURKB expressions as well as PI and CFSE flow cytometry assays. Multidrug resistance was evaluated by examining the expression of MDR1 and MRP1. Angiogenesis and invasion were investigated by VEGF expression and F-actin labeling with Alexa Fluor 549 Phalloidin. Results: Western blot results showed that BI-847325 inhibits MEK1/2 and AURKB functions by decreasing phospho-ERK1/2 and phospho-Histone H3 levels. BI-847325 induced thyroid differentiation markers and apoptosis in ATC cell lines. Inversely, BI-847325 intervention decreased multidrug resistance, cell cycle progression, proliferation, angiogenesis, and invasion at the molecular and/or cellular levels. Conclusion: The results of the present study suggest that BI-857,325 might be an effective multi-targeted anticancer drug for ATC treatment. [ABSTRACT FROM AUTHOR]

Background: Medication reconciliation (MedRec) is a widely accepted tool for the identification and resolution of unintended medication discrepancies (UMD).Objective: This study aimed at assessing the magnitude and associated factors of UMD identified through medication reconciliation upon patient admission to the internal medicine wards.Methods: Prospective cross-sectional study was conducted at the internal medicine wards of Felege Hiwot and Tibebe Ghion comprehensive specialized hospitals in Bahir Dar city, Northwest Ethiopia, from May 01 to July 30, 2021. Data were collected by using a data abstraction format prepared based on standard MedRec tools and previous studies on medication discrepancy. Pharmacists-led MedRec was made by following the WHO High5s "retroactive medication reconciliation model". SPSS® (IBM Corporation) version 25.0 was used to analyze the data with descriptive and inferential statistics. A binary logistic regression analysis was used to identify factors associated with UMD. A statistical significance was declared at a p-value < 0.05.Results: Among 635 adult patients, 248 (39.1%) of them had at least one UMD. The most frequent types of UMDs were omission (41.75%) and wrong dose (21.9%). The majority (75.3%) of pharmacists' interventions were accepted. Polypharmacy at admission (p-value < 0.001), age ≥ 65 (p-value = 0.001), a unit increase on the number of comorbidities (p-value = 0.008) and information sources used for MedRec (p-value < 0.001), and medium (p-value = 0.019) and low adherence (p-value < 0.001) were significantly associated with UMD.Conclusion: The magnitude of UMD upon patient admission to the internal medicine wards was considerably high. Omission and the wrong dose of medication were common. Older age, polypharmacy, low and medium adherence, and an increase in the number of comorbidities and information sources used for MedRec are significantly associated with UMDs. Pharmacists' interventions were mostly acceptable. Thus, the implementation of pharmacists-led MedRec in the two hospitals is indispensable for patient safety. [ABSTRACT FROM AUTHOR]

Background: Monocarboxylate transporter 1 (MCT1) deficiency has recently been described as a rare cause of recurrent ketosis, the result of impaired ketone utilization in extrahepatic tissues. To date, only six patients with this condition have been identified, and clinical and biochemical details remain incomplete.Results: The present work reports a patient suffering from severe, recurrent episodes of metabolic acidosis and psychomotor delay, showing a pathogenic loss-of-function variation c.747_750del in homozygosity in SLC16A1 (which codes for MCT1). Persistent ketotic and lactic acidosis was accompanied by an abnormal excretion of organic acids related to redox balance disturbances. Together with an altered bioenergetic profile detected in patient-derived fibroblasts, this suggests possible mitochondrial dysfunction. Brain MRI revealed extensive, diffuse bilateral, symmetric signal alterations for the subcortical white matter and basal ganglia, together with corpus callosum agenesia.Conclusions: These findings suggest that the clinical spectrum of MCT1 deficiency not only involves recurrent atacks of ketoacidosis, but may also cause lactic acidosis and neuromotor delay with a distinctive neuroimaging pattern including agenesis of corpus callosum and other brain signal alterations. [ABSTRACT FROM AUTHOR]

Background: Oguchi disease is a rare type of congenital stationary night blindness associated with an abnormal fundus appearance. It is inherited in an autosomal recessive manner where two types exist according to the gene affected; type 1 associated with S-antigen (SAG) gene mutations and type 2 associated with rhodopsin kinase (GRK1) gene mutations.Purpose: The aim of this work was to describe the clinical and genetic findings of the first two reported families of Oguchi disease in Egypt and African region.Methods: Four members of two consanguineous Egyptian families with history of night blindness since childhood underwent complete ophthalmological examination, standard automated static perimetry, fundus color photography, fundus autofluorescence (FAF), fundus fluorescein angiography (FFA) in light-adapted state and spectral-domain optical coherence tomography (SD-OCT) of both the macula and the optic nerve head as well as central corneal thickness with repeated fundus photography following prolonged dark adaptation. Mutation screening of 7 coding exons of GRK1 gene and 15 coding exons of SAG gene as well as some flanking regions were performed using Sanger sequencing technique. The variants were tested for pathogenicity using different in silico functional analysis tools.Results: The clinical examination and investigations confirmed Oguchi disease phenotype. One patient showed p.R193* (c.577C > T) which is a previously reported SAG gene mutation in a homozygous form. The other three patients from a different family showed (c.649-1 G > C), a novel canonical splice site SAG gene mutation in a homozygous form.Conclusion: The identification of the novel canonical splice site SAG gene variant in three members of the same family with clinically confirmed Oguchi disease reinforces its pathogenicity. A fourth patient from another family carried a previously reported mutation in the same gene. SAG gene variants may be the underlying genetic cause for Oguchi disease in Egypt. Our findings have expanded the spectrum of Oguchi disease-associated mutations in SAG gene and may serve as a basis for genetic diagnosis for Oguchi disease. [ABSTRACT FROM AUTHOR]

Background: Vitamin D (Vit D) deficiency/insufficiency is an important risk factor for several chronic conditions. We aimed to evaluate the knowledge and behavior of female adolescents with respect to the association between sunlight exposure, sunscreen use, and Vit D status.Methods: This cross-sectional survey was performed in northeastern Iran, among 940 female adolescents in January 2015. Each subject completed a questionnaire containing items about demographic characteristics, knowledge about Vit D and their use of sunscreen. Serum Vit D levels were measured using an electrochemiluminescence method and dietary intake of Vit D was assessed using a Food Frequency Questionnaire. Statistical analyses were conducted using SPSS software. A P value < 0.05 was considered statistically significant.Results: Few of the participants were aware of the biological functions of Vit D (8.8%), the causes of Vit D deficiency (16.7%), and the sources of Vit D (9.3%). Less than half of the participants used sunscreen during the day. The serum levels of Vit D in subjects who used sunscreen were significantly lower than those who did not (p = 0.004). However, there was no significant association between their knowledge about Vit D and serum Vit D, or dietary intake of Vit D.Conclusion: There appears to be a lack of coherence between lifestyle, behavior and knowledge that may affect the Vit D status of adolescent girls in northeastern Iran. This information provides a basis for developing public health planning (workshops or training at the college level) for the prevention of Vit D deficiency especially in adolescent girls. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence indicates that vitamin D deficiency has been increased globally over the last two decades. However, the majority of these studies are concerned with cities and there is scant information regarding the prevalence of vitamin D in rural areas. The main aim of this study was to investigate the prevalence of vitamin D deficiency and its associated risk factors among the rural population in Bushehr province which shares the longest border with the Persian Gulf. Methods: The rural inhabitants of more than 25 years old from three mountainous, plain, and seashore areas of Bushehr province were selected through a stratified multi-cluster random sampling method. After obtaining the participants' demographic and anthropometric data and their past medical history, serum 25-hydroxyvitamin D [25(OH)D] was measured using ELISA. Results: A total of 1806 (means ±SD, 46± 14years old) rural subjects (35 % males and 65 % females) participated in this study. The prevalence of vitamin D deficiency, insufficiency, and sufficiency were 28 %, 50 %, and 22 %, respectively. The deficiency of vitamin D in women was higher than in men (OR=1.27, 95 % CI: 1.05 to 1.54, P=0.04). There was a positive significant correlation between age and serum vitamin D levels. Men with vitamin D deficiency had higher BMI (P=0.008); this association was not observed among women (P=0.7). There was no significant difference between the food item's consumption frequencies, and vitamin D status (P>0.05). The mountainous, and plain areas had the highest and lowest vitamin D levels, respectively. Conclusions: Although, Bushehr province is located in a sunny part of Iran, the prevalence of vitamin D deficiency was high among its rural population. The shift of their lifestyle patterns and rapid industrialization in these rural areas may be responsible. Therefore, the enrichment of dietary sources with vitamin D and the use of vitamin D supplements are recommended to tackle the high prevalence of vitamin D deficiency in the rural population of the northern part of the Persian Gulf. [ABSTRACT FROM AUTHOR]

Background: Severe combined immunodeficiency (SCID) is a group of relatively rare primary immunodeficiency disorders (PIDs), characterized by disturbed development of T cells and B cells, caused by several genetic mutations that bring on different clinical presentations. SCID may be inherited as an autosomal recessive or an X-linked genetic trait. Case presentation: A 6-year-old male presented with a history of food allergy, productive coughs, and recurrent purulent rhinitis, poor weight gain and hypothyroidism. The total count of CD4+ T lymphocytes, along with their naïve and central memory subpopulations, as well as central memory CD8+ T cells were decreased in flow cytometry. A nucleotide substitution in exon one of interleukin 2 receptor gamma chain (IL-2RG) gene (c.115 G>A, p.D39N, ChrX: 70,331,275) was reported, based on which the diagnosis of X-liked SCID was confirmed. Antiviral and antibiotic prophylaxis, along with monthly IVIG (intravenous immunoglobulin) was started and the patient was subsequently referred for hematopoietic stem cell transplantation. Conclusion: PIDs should be considered as the differential diagnosis in any patient with unexplained and bizarre symptoms associated with recurrent infections, allergic and autoimmune manifestations. Clinicians should also bear X-SCID in mind in case of approach to any patient with poor weight gain, unusual allergic or endocrine manifestations, even in the case of a normal or increased level of serum immunoglobulins or T and B cells numbers. [ABSTRACT FROM AUTHOR]

The relevant role of long non-coding RNAs (lncRNAs) in cancer is currently a matter of increasing interest. Medullary thyroid cancer (MTC) is a rare neuroendocrine tumor (2-5% of all thyroid cancer) derived from the parafollicular C-cells which secrete calcitonin. About 75% of all medullary thyroid cancers are believed to be sporadic medullary thyroid cancer (sMTC), whereas the remaining 25% correspond to inherited cancer syndromes known as Multiple Endocrine Neoplasia type 2 (MEN2). MEN2 syndrome, with autosomal dominant inheritance is caused by germline gain of function mutations in RET proto-oncogene. To date no lncRNA has been associated to MEN2 syndrome and only two articles have been published relating long non-coding RNA (lncRNA) to MTC: the first one linked MALAT1 with sMTC and, in the other, our group determined some new lncRNAs in a small group of sMTC cases in fresh tissue (RMST, FTX, IPW, PRNCR1, ADAMTS9-AS2 and RMRP). The aim of the current study is to validate such novel lncRNAs previously described by our group by using a larger cohort of patients, in order to discern their potential role in the disease. Here we have tested three up-regulated (RMST, FTX, IPW) and one down-regulated (RMRP) lncRNAs in our samples (formalin fixed paraffin embedded tissues from twenty-one MEN2 and ten sMTC patients) by RT-qPCR analysis. The preliminary results reinforce the potential role of RMST, FTX, IPW and RMRP in the pathogenesis of MTC. [ABSTRACT FROM AUTHOR]

Background: Low back pain (LBP) is the most frequent complaint in clinical practice. Electroacupuncture treatment may be effective; however, the supporting evidence is still limited, especially in older adults.Objective: The current study is a randomized controlled trial that aims to evaluate the clinical efficacy of electroacupuncture in older adults with LBP.Methods: A five-arm randomized controlled trial with patients and evaluators blinded to the group allocation. A total of 125 participants with non-specific LBP will be randomly assigned into one of five groups: three electroacupuncture groups (low, high, and alternating frequency); one control group; and one placebo group. The electroacupuncture will be applied twice a week (30 min per session) for five weeks. The primary clinical outcome measure will be pain intensity. The secondary outcomes include: quality of pain; physical functioning; perceived overall effect; emotional functionality; patient satisfaction; and psychosocial factors. Patients will be evaluated before the first session, immediately after the last, and followed up after six and 12 months to check the medium- and long-term effects.Discussion: Although electroacupuncture is increasingly used to treat LBP, there is no guidance regarding the parameters used, which leads to inconsistent results. Thus, the effect of electroacupuncture (EA) on LBP remains controversial and requires more studies, especially in the older adult population.Conclusion: This is the first randomized controlled trial to evaluate the efficacy of different frequencies of electroacupuncture for treating chronic LBP in older adults. This study will provide evidence on the effectiveness of electroacupuncture as an alternative treatment method for LBP and will entail wider debate about an appropriate acupuncture intervention in this population.Trial Registration: Clinicaltrials.gov, NCT03802045. Registered on 14 January 2019. [ABSTRACT FROM AUTHOR]

Background: Species belonging to the genus Lernaea are cosmopolitan parasites that can infect many different freshwater fish hosts. Due to a high degree of morphological intraspecific variability and high levels of interspecific similarities, their classification is extremely difficult and controversial. Although the suitability of the shape of cephalic horns has been questioned decades ago by some experimental infection studies, this character still plays the central role in the identification of Lernaea spp. Methods: We used the nominal species Lernaea cyprinacea and Lernaea cruciata to test the hypothesis that the shape of the anchor can exhibit host-induced morphological variability, and that the two taxa may be synonymous. Results: We examined 517 wild or farmed specimens of five host fish species (four cyprinids and a mosquitofish), and found that all 16 parasite specimens collected from mosquitofish could be morphologically identified as L. cruciata, whereas the remaining 25 parasite specimens were all identified as L. cyprinacea. We experimentally infected goldfish and mosquitofish specimens with offspring (copepodids) of a single L. cyprinacea specimen: the adult parasites from goldfish were morphologically identified as L. cyprinacea, and those from mosquitofish as L. cruciata. We then used molecular data to corroborate that all these specimens are conspecific. Conclusions: Our results suggest that L. cyprinacea and L. cruciata may be synonyms, misidentified as different species as a result of host-induced morphological variation. Given the current shortage of molecular data for the genus Lernaea, in order to resolve the taxonomy of this genus (determine the exact number of species), future studies should aim to sequence as much molecular data as possible, and conduct further experimental infections. [ABSTRACT FROM AUTHOR]

B lymphocyte-induced maturation protein-1 (Blimp-1) serves as a master regulator of the development and function of antibody-producing B cells. Given that its function in T lymphocytes has been identified within the past decade, we review recent findings with emphasis on its role in coordinated control of gene expression during the development, differentiation, and function of T cells. Expression of Blimp-1 is mainly confined to activated T cells and is essential for the production of interleukin (IL)-10 by a subset of forkhead box (Fox)p3+ regulatory T cells with an effector phenotype. Blimp-1 is also required to induce cell elimination in the thymus and critically modulates peripheral T cell activation and proliferation. In addition, Blimp-1 promotes T helper (Th) 2 lineage commitment and limits Th1, Th17 and follicular helper T cell differentiation. Furthermore, Blimp-1 coordinates with other transcription factors to regulate expression of IL-2, IL-21 and IL-10 in effector T lymphocytes. In CD8+ T cells, Blimp-1 expression is distinct in heterogeneous populations at the stages of clonal expansion, differentiation, contraction and memory formation when they encounter antigens. Moreover, Blimp-1 plays a fundamental role in coordinating cytokine receptor signaling networks and transcriptional programs to regulate diverse aspects of the formation and function of effector and memory CD8+ T cells and their exhaustion. Blimp-1 also functions as a gatekeeper of T cell activation and suppression to prevent or dampen autoimmune disease, antiviral responses and antitumor immunity. In this review, we discuss the emerging roles of Blimp-1 in the complex regulation of gene networks that regulate the destiny and effector function of T cells and provide a Blimp-1-dominated transcriptional framework for T lymphocyte homeostasis. [ABSTRACT FROM AUTHOR]

Background: Suppressor of cytokine signaling 1 (SOCS1) is considered a tumor suppressor due to frequent epigenetic and micro-RNA-mediated repression of its gene expression in diverse cancers. In prostate cancer (PCa), elevated expression of miR-30d that targets SOCS1 mRNA is associated with increased risk of disease recurrence. SOCS1 can mediate its tumor suppressor functions by diverse mechanisms such as inhibiting the JAK-STAT signaling pathway, promoting the tumor suppressor functions of p53, attenuating MET receptor tyrosine kinase signaling and blocking the oncogenic potential of the cell cycle inhibitor p21CIP1 (p21). Here, we studied the expression of SOCS1 and the downstream targets of its putative tumor suppressor functions (p53, MET and p21) in human PCa specimens to evaluate their significance as markers of disease prognosis.Methods: Tissue microarrays were constructed of 78 archived prostatectomy specimens that were grouped according to the recommendations of the International Society of Urological Pathology (ISUP) based on the Gleason patterns. SOCS1, p53, MET and p21 protein expression were evaluated by immunohistochemical staining alongside the common prostate cancer-related markers Ki67, prostein and androgen receptor. Statistical correlations between the staining intensities of these markers and ISUP grade groups, local invasion or lymph node metastasis were evaluated.Results: SOCS1 showed diffuse staining in the prostatic epithelium. SOCS1 staining intensity correlated inversely with the ISUP grade groups (ρ = -0.4687, p <0.0001) and Ki67 (ρ = -0.2444, p = 0.031), and positively with prostein (ρ = 0.3511, p = 0.0016). Changes in SOCS1 levels did not significantly associate with those of p53, MET or p21. However, p21 positively correlated with androgen receptor expression (ρ = -0.1388, p = 0.0003). A subset of patients with regional lymph node metastasis, although small in number, showed reduced SOCS1 expression and increased expression of MET and p21.Conclusions: Our findings suggest that evaluating SOCS1 and p21 protein expression in prostatectomy specimens may have a prognostic value in identifying the aggressive disease. Hence, prospective studies with larger numbers of metastatic PCa specimens incorporating clinical correlates such as disease-free and overall survival are warranted. [ABSTRACT FROM AUTHOR]

Background: The TALLYHO/Jng (TH) mouse is a polygenic model for obesity and type 2 diabetes first described in the literature in 2001. The origin of the TH strain is an outbred colony of the Theiler Original strain and mice derived from this source were selectively bred for male hyperglycemia establishing an inbred strain at The Jackson Laboratory. TH mice manifest many of the disease phenotypes observed in human obesity and type 2 diabetes. Results: We sequenced the whole genome of TH mice maintained at Marshall University to a depth of approximately 64.8X coverage using data from three next generation sequencing runs. Genome-wide, we found approximately 4.31 million homozygous single nucleotide polymorphisms (SNPs) and 1.10 million homozygous small insertions and deletions (indels) of which 98,899 SNPs and 163,720 indels were unique to the TH strain compared to 28 previously sequenced inbred mouse strains. In order to identify potentially clinically-relevant genes, we intersected our list of SNP and indel variants with human orthologous genes in which variants were associated in GWAS studies with obesity, diabetes, and metabolic syndrome, and with genes previously shown to confer a monogenic obesity phenotype in humans, and found several candidate variants that could be functionally tested using TH mice. Further, we filtered our list of variants to those occurring in an obesity quantitative trait locus, tabw2, identified in TH mice and found a missense polymorphism in the Cidec gene and characterized this variant's effect on protein function. Conclusions: We generated a complete catalog of variants in TH mice using the data from whole genome sequencing. Our findings will facilitate the identification of causal variants that underlie metabolic diseases in TH mice and will enable identification of candidate susceptibility genes for complex human obesity and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Blastocystis species are common enteric human parasites and carriage has been linked to Irritable Bowel Syndrome (IBS), particularly diarrhoea-predominant IBS. The spectrum of immune reactivity to Blastocystis proteins has been reported previously in symptomatic patients. We investigated differences in serum immunoglobulin profiles between patients with IBS, both positive and negative for Blastocystis carriage, and healthy controls (HC). Methods: Forty diarrhoea-predominant IBS patients (26 patients positive for Blastocystis sp., 14 negative patients) and forty HC (24 positive, 16 Blastocystis-negative) were enrolled. Age, gender, ethnicity and serum immunoglobulin A (IgA) levels were recorded and faecal specimens were analysed using smear, culture and polymerase chain reaction amplification of ribosomal DNA. Sera were tested in Western blots and the reactivities compared to known targets using monoclonal antibodies Blastofluor® (Blastocystis specific antibody), MAb1D5 (cytopathicto Blastocystis cells), anti-promatrix metalloprotease-9 (anti-MMP-9) and SDS-PAGE zymograms. Results: Levels of serum IgA were significantly lower in Blastocystis carriers (p < 0.001) but had no relationship to symptoms. Western blots demonstrated serum IgG antibodies specific for Blastocystis proteins of 17,27,37,50,60-65, 75-90, 95-105 and 150 kDa MW. Reactivity to the 27, 50 and 75-95 kDa proteins were found more frequently in the IBS group compared to the HC's (p < 0.001) and correlation was greater for Blastocystis-positive IBS patients (p < 0.001) than for negative IBS patients (p < 0.05). MAb1D5 reacted with proteins of 27 and 100 kDa, and anti-MMP-9 with 27, 50 and 75-100 kDa proteins. Bands were seen in zymograms around 100 kDa. Conclusions: Low serum IgA levels are associated with Blastocystis carriage. All IBS patients were more likely to demonstrate reactivity with Blastocystis proteins of 27 kDa (likely a cysteine protease), 50 and 75-95 kDa MW compared to HC. The presence of antibodies to these Blastocystis proteins in some Blastocystis-negative subjects suggests either prior exposure to Blastocystis organisms or antibody cross reactivities. The anti-proMMP-9 reaction at 50 and 75-100 kDa and the zymogram result suggest that metalloproteases may be important Blastocystis antigens. Trial registration: Australian and New Zealand Clinical Trials registry ACTRN: 12611000918921. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence on non-pharmacological interventions for gout. The aim of the study was to determine whether a footwear intervention can reduce foot pain and musculoskeletal disability in people with gout. Methods: Thirty-six people with gout participated in a prospective intervention study over 8 weeks. Participants selected one of 4 pairs of shoes and thereafter wore the shoes for 8 weeks. The primary outcome was foot pain using a 100 mm visual analogue scale. Secondary outcomes related to function and disability were also analysed. Results: The Cardio Zip shoe was selected by 58% of participants. Compared with baseline, overall scores for all shoes at 8-weeks demonstrated a decrease in foot pain (p = 0.03), general pain (p = 0.012), Health Assessment Questionnaire (HAQ)-II (p = 0.016) and Leeds Foot Impact Scale (LFIS) impairment subscale (p = 0.03). No significant differences were observed in other patient reported outcomes including patient global assessment, LFIS activity subscale, and Lower Limb Task Questionnaire subscales (all p > 0.10). We observed significant improvements between baseline measurements using the participants' own shoes and the Cardio Zip for foot pain (p = 0.002), general pain (p = 0.001), HAQ-II (p = 0.002) and LFIS impairment subscale (p = 0.004) after 8 weeks. The other three shoes did not improve pain or disability. Conclusions: Footwear with good cushioning, and motion control may reduce foot pain and disability in people with gout. [ABSTRACT FROM AUTHOR]

The article cites a research study that reports the clinical manifestation of hyper-IgE syndromes, rare and complex primary immunodeficiencies. They are characterized by particular susceptibility to staphylococcal and mycotic infections and by a heterogeneous genetic origin. In this study, the classical hyper-IgE syndrome and the autosomal recessive hyper-IgE syndrome have been recognized.

Background: Hepatocellular carcinoma (HCC) is the fifth most common neoplasia in the world. In the past, treatment of advanced HCC with conventional antineoplastic drugs did not result in satisfactory outcomes: recently, in this patient population the oral multikinase inhibitor sorafenib has been able to induce a statistically significant improvement of overall survival. Similarly to other anti-angiogenic drugs employed in other tumour types, also sorafenib seldom induces the dimensional tumour shrinking usually observed with conventional cytotoxic drugs: data gathered from studies carried out with sorafenib and other competitors under development do not report any complete response in HCV-induced HCC. Case presentation: An 84-year old man with a long-lasting history of chronic HCV hepatitis was referred to our Institution for an ultrasonography investigation of a focal hepatic lesion. To better characterize the liver disease and clearly define the diagnosis of the focal hepatic lesion, the patient was hospitalized in our department. Laboratory and instrumental investigations confirmed the clinical picture of HCV-related liver cirrhosis and identified a hepatic lesion of about 6 cm featuring infiltrating HCC with thrombosis of the portal trunk. Due to the advanced stage of the disease, therapy with sorafenib 400 mg bid was started. Right from one month after the treatment was started, a reduction of alpha-fetoprotein level was observed which, by the third month, turned down within the normal limits. In addition the CT scan showed 50% reduction of the neoplastic lesion along with canalization of the portal trunk. At the sixth month the normalization of the alpha-fetoprotein level at the lower limit of normality was confirmed and the MRI showed complete disappearance of the neoplasia. In addition a reduction of a metallo-proteinase serum level was obserdved. At the twelfth month a further MRI confirmed complete response had been maintained. At present the patient is in a follow-up program to evaluate the duration of the complete response. Conclusions: This case is worth mentioning since, to the best of our knowledge, it represents the first evidence of complete response to sorafenib in an elderly patient with advanced HCV-related HCC. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is one of the major risk factors for chronic hepatitis, which may progress to cirrhosis and hepatocellular carcinoma, as well as for type II mixed cryoglobulinemia (MC), which may further evolve into an overt B-cell non-Hodgkin's lymphoma (NHL). It has been previously shown that B-cell receptor (BCR) repertoire, expressed by clonal B-cells involved in type II MC as well as in HCV-associated NHL, is constrained to a limited number of variable heavy (VH)- and light (VL)- chain genes. Among these, the VK3-20 light chain idiotype has been selected as a possible target for passive as well as active immunization strategy. In the present study, we describe the results of a multiparametric analysis of the innate and early adaptive immune response after ex vivo stimulation of human immune cells with the VK3-20 protein. This objective has been pursued by implementing high-throughput technologies such as multiparameter flow cytometry and multiplex analysis of cytokines and chemokines. [ABSTRACT FROM AUTHOR]