Leukopenia and leukocytosis as strong predictors of COVID-19 severity: A cross-sectional study of the hematologic abnormalities and COVID-19 severity in hospitalized patients.

Background and Aims: Predicting severe disease is important in provocative decision-making for the management of patients with the coronavirus disease 2019 (COVID-19); However, there are still some controversies about the COVID-19's severity predicting factors. This study aimed to investigate the relationships between clinical and laboratory findings regarding COVID-19's severity in patients admitted to a tertiary hospital in Mashhad, Iran. Methods: A cross-sectional study was conducted on patients with documented COVID-19 infection based on the reverse transcription-polymerase chain reaction test. Clinical symptoms, vital signs, and medical history of the patients were recorded from their medical records. Laboratory findings and computed tomography (CT) study findings were documented. Disease severity was defined based on CT scan findings. Results: A total of 564 patients (58.8 ± 16.8 years old) were evaluated. The frequency of severe disease was 70.4%. There was a significant difference in heart rate (p = 0.0001), fever (p = 0.002), dyspnea (p = 0.0001), chest pain (p = 0.0001), diarrhea (p = 0.021), arthralgia (p = 0.0001), and chills (p = 0.044) as well as lymphopenia (p = 0.014), white blood cell count (p = 0.001), neutrophil count (p < 0.0001), lymphocyte count (p < 0.0001), and prothrombin time (p = 0.001) between disease severity groups. Predictors of severe COVID-19 were pulse rate (crude odds ratio [cOR] = 1.014, 95% confidence interval [CI] for cOR: 1.001, 1.027) and leukopenia (cOR = 3.910, 95% CI for cOR: 1.294, 11.809). Predictors for critical COVID-19 were pulse rate (cOR = 1.075, 95% CI for cOR: 1.046, 1.104), fever (cOR = 2.516, 95%CI for cOR: 1.020, 6.203), dyspnea (cOR = 4.190, 95% CI for cOR: 1.227, 14.306), and leukocytosis (cOR = 3.866, 95% CI for cOR: 1.815, 8.236). Conclusions: Leukopenia and leukocytosis have the strongest correlation with the COVID-19 severity. These findings could be a valuable guild for clinicians in COVID-19 patient management in the inpatient setting.

Immune response to COVID-19 vaccines among people living with human T-cell lymphotropic virus type 1 infection: a retrospective cohort study from Iran.

The effectiveness of COVID-19 vaccination is still unclear in individuals with underlying diseases such as HTLV-1 infection. This retrospective cohort study aimed to evaluate the humoral response of COVID-19 vaccines among people living with HTLV-1 (PLHTLV) in northeastern Iran. From December 2021 to October 2022, eighty-six HTLV-1+ subjects (50 males and 36 females; 47.7 ± 11.2 years) and 90 HTLV-1 seronegative individuals (age- and sex-matched convenient samples) were enrolled. The humoral immune response was evaluated by measuring different COVID-19 Abs in serum samples at least 28 days after receiving 2nd or 3rd doses of COVID-19 vaccines. Throughout all three rounds of immunization, Sinopharm was the most commonly used COVID-19 vaccine across all three immunization rounds. Compared to the HTLV-1- group, a significantly lower frequency of all four Abs activity was observed among PLHTLV:anti-nucleocapsid (66.3% vs 86.7%, p = 0·001), anti-spike (91.9% vs 98.9%, p = 0·027), RBD (90.7% vs 97.8%, p = 0·043), and neutralizing Abs (75.6% vs 95.5%, p < 0·001). Also, the frequency of all Abs in 28 patients with HAM/TSP was higher than that of 58 asymptomatic carriers, although this difference was statistically significant only in the case of anti-spike Abs (p = 0.002). Notably, PLHTLV-vaccinated against COVID-19 demonstrated significantly lower antibody activities, indicating a reduced humoral immune response to COVID-19 vaccines.

Unraveling The Effects of DICER1 Overexpression on Immune-Related Genes Expression in Mesenchymal Stromal/Stem Cells: Insights for Therapeutic Applications.

OBJECTIVE: The immunoregulatory properties of mesenchymal stromal/stem cells (MSCs) bring a promise for the treatment of inflammatory diseases. However, their ability to suppress the immune system is unstable. To enhance their effectiveness against immune responses, it may be necessary to manipulate MSCs. Although some dsRNA transcripts come from invading viruses, the majority of dsRNA has an endogenous origin and is known as endo-siRNA. DICER1 is a ribonuclease protein that can generate small RNAs to modulate gene expression at the post-transcriptional level. We aimed to evaluate the expression of several immune-related genes at mRNA and protein levels in MSCs overexpressing DICER1 exogenously. MATERIALS AND METHODS: In this comparative transcriptomic experimental study, the adipose-derived MSCs (Ad-MSCs) were transfected using the pCAGGS-Flag-hsDicer vector for the DICER1 overexpression. Following the RNA extraction, mRNA expression level of DICER1 and several inflammatory cytokines were examined. We performed a relative real-time polymerase chain reaction (PCR) assay and transcriptome analysis between two groups including DICER1- transfected MSCs and control MSCs. Moreover, media from the transfected MSCs were evaluated for various interferon response factors by ELISA. RESULTS: The overexpression of DICER1 is associated with a significant increase in the mRNA expression level of COX-2, DDX-58, IFIH1, MYD88, RNase L, TLR3/4, and TDO2 genes and a downregulation of the TSG-6 gene in MSCs. Moreover, the expression levels of IL-1, 6, 8, 17, 18, CCL2, INF-γ, TGF-ß, and TNF-α were higher in the DICER1-transfected MSCs group. CONCLUSION: It seems that the ectopic expression of DICER1 in Ad-MSCs is linked to alterations in the expression level of immune-related genes. It is suggested that the manipulation of immune-related pathways in MSCs via the Dicer1 overexpression could facilitate the development of MSCs with distinct immunoregulatory phenotypes.

Mutational landscape of phenylketonuria in Iran.

To date more than 1000 different variants in the PAH gene have been identified in patients with phenylketonuria (PKU). In Iran, several studies have been performed to investigate the genetics bases of the PKU in different parts of the country. In this study, we have analysed and present an update of the mutational landscape of the PAH gene as well as the population genetics and frequencies of detected variants for each cohort. Published articles on PKU mutations in Iran were identified through a comprehensive PubMed, Google Scholar, Web of Science (ISI), SCOPUS, Elsevier, Wiley Online Library and SID literature search using the terms: "phenylketonuria", "hyperphenylalaninemia", and "PKU" in combination with "Iran", "Iranian population", "mutation analysis", and "Molecular genetics". Among the literature-related to genetics of PKU, 18 studies were on the PKU mutations. According to these studies, in different populations of Iran 1497 patients were included for mutation detection that resulted in detection of 129 different mutations. Results of genetic analysis of the different cohorts of Iranian PKU patients show that the most prevalent mutation in Iran is the pathogenic splice variant c.1066-11G > A, occurring in 19.54% of alleles in the cohort. Four other common mutations were p.Arg261Gln, p.Pro281Leu, c.168 + 5G > C and p.Arg243Ter (8.18%, 6.45%, 5.88% and 3.7%, respectively). One notable feature of the studied populations is its high rate of consanguineous marriages. Considering this feature, determining the prevalent PKU mutations could be advantageous for designing screening and diagnostic panels in Iran.

Effect of citalopram and sertraline on the expression of miRNA- 124, 132, and 16 and their protein targets in patients with depression.

Objectives: This study aimed to evaluate the effect of SSRIs on the expression of miRNAs and their protein targets. Materials and Methods: In a 100 day open-label study of citalopram (n=25) and sertraline (n=25), levels of miRNA 16, 132, and 124 and glucocorticoid receptor (GR), Brain-derived neurotrophic factor (BDNF), and serotonin transporter (SERT) protein expression were measured by QRT-PCR and western blot in healthy control (n=20), patients with depression at the baseline, and same patients after 100 days of treatment. Results: Expression levels of GR and BDNF proteins were lower in the depressed group before treatment as compared with the healthy group (P<0.0001). The SERT level was higher among the depressed group before treatment in comparison with the healthy group (P<0.0001). The level of GR and BDNF significantly increased, and SERT expression decreased after receiving sertraline (P<0.05). When the depressed group received citalopram, only SERT and GR were altered (P<0.05). Among the microRNAs' expression investigated, mir-124 and mir-132 were higher, and mir-16 was lower among the depressed compared with the healthy group (P<0.0001). Individuals receiving citalopram only showed an increase in the expression of mir-16 while administration of sertraline led to a significant increase in the expression of mir-16 and a decrease in mir-124 and mir-132 (P<0.05). Conclusion: This elucidated the relationship between antidepressant treatment and the expression of different microRNA that control gene expression in various pathways involved in depressed patients. Receiving SSRI can affect the level of these proteins and their relevant microRNAs.

The correlation between imaging findings and breast cancer cell receptors status.

INTRODUCTION: Breast cancer is the most common malignancy among women, and subtypes are mainly defined based on hormone receptors such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). The relationship between breast cancer subtypes and imaging features in mammography and sonography has been studied but the results are controversial. The purpose of this study was to determine the relationship between the hormonal receptor status of breast tumors and the radiologic feature of the tumors on mammography and sonography. METHODS: Eighty patients with breast cancer enrolled in this cross-sectional study. ER, PR, and HER2 determined by immunohistochemistry. Every patient underwent mammography and sonography before the biopsy. We evaluated the relationship between the hormonal receptor status and radiographic features of tumors on breast sonography and mammography. RESULTS: The majority of the patients (n=75 (93.8%)) were diagnosed with invasive ductal carcinoma (IDC). The mean and standard deviation of the age was 49 ± 9 years. There was no significant relationship between the hormonal receptor status and the sonographic margin and shape (P>0.05). However, PR (P=0.002) and ER (P=0.001) status were significantly correlated with posterior features on sonography. ER-positive patients were more likely to have indistinct or speculated masses on mammography (P=0.017). Irregular or oval masses on mammography were higher in patients with ER (p=0.032). CONCLUSION: There was a significant correlation between PR and ER status and posterior features on sonography. Positive ER was associated with indistinct or speculated masses on mammography, as well as irregular or oval masses.

Adverse events following immunisation with the first dose of sputnik V among Iranian health care providers.

Purpose: Since late 2019, the novel coronavirus disease has been a global concern, and alongside preventive strategies, including social distancing and personal hygiene, vaccination is now the primary hope for controlling the pandemic. Sputnik V is an adenovirus vector vaccine used against coronavirus disease 2019 (COVID-19) among Iranian health care providers, and there is a lack of information regarding the Adverse Events Following Immunisation (AEFI) by Sputnik V among the Iranian population. The present study aimed to evaluate AEFI by Sputnik V vaccine among Iranian population. Materials and Methods: Every member of the Islamic Republic of Iran Medical Council received their first dose of the Sputnik V vaccine in Mashhad (Iran) and was referred to receive their second dose enrolled in the present study and asked to fill an English language checklist asking about development of any AEFI following immunization with the first dose of Sputnik V vaccine. Results: A total number of 1,347 with a mean±standard deviation age of 56.2±9.6 years filled the checklist. Most of the participants were male (838 [62.2%]). The present study demonstrated that immunization with the first dose of Sputnik V results in at least one AEFI in 32.8% of the Iranian medical council members. Most of the AEFI was related to musculoskeletal symptoms, including myalgia. By considering the age of 55 years as a cut-off point, individuals younger than 55 had a higher rate of AEFI (41.3% vs. 22.5%, p=0.0001). Male gender, use of analgesics, beta-blockers, and previous COVID-19 infection have a lower chance of developing AEFI (p<0.05). Conclusion: The present study demonstrated that most of the AEFI was related to musculoskeletal symptoms, including myalgia, and older individuals, male gender and those receiving analgesics and beta-blockers were less likely to develop AEFI following immunization with the first dose of Sputnik V.

Implementation of Educational-Interactive-Psychiatric Management Software for Patients with Bipolar Disorder.

Background: Bipolar disorder is considered a psychiatric disease without any effective screening questionnaire to monitor and manage Iranian patients. This study aims to implement a researcher-made questionnaire in the form of educational interactive software for better management of patients with bipolar disorder and prevent further complications. Methods: The present cross-sectional study evaluated the efficacy of psychoeducational-interactive-therapeutic software for patients with bipolar disorder, which is a network-based software providing a researcher-made questionnaire in a planned manner. This software can predict the occurrence of future bipolar episodes for each patient by using artificial intelligence algorithms after the occurrence of two mood episodes as the training phase. The patients with bipolar disorder were asked to use the software for a year and their mood episodes were compared before and after using the software. We evaluate the reliability of the questionnaires in the software with internal consistency using alpha Cronbach test and test-retest analysis. Face validity and content validity were also evaluated. Results: The content validity index of the instrument was 93%, and the Cronbach's alpha coefficient of the whole questionnaire was 0.955. Also, the ICC coefficient for this questionnaire is above 0.70, and the correlation coefficient of the answers in all constructs of the questionnaire is more than 0.8. Thirty male patients with bipolar disorder who experienced four episodes of mood swings per year experienced an average of 2 mood episodes per year following the use of this software. Conclusion: Our Psychoeducational-interactive-therapeutic software is the first Persian language software based on artificial intelligence to monitor clinical symptoms in patients with bipolar disorder, which uses a standard questionnaire to predict the incidence of episodes of depression and mania in these patients.

Experiencing Pain or Orgasm with Color Synesthesia: A Rare Case in a Young Previously Healthy Male.

Objective: Synesthesia is a unique experience with an unclear mechanism. The clinical condition usually presents when a sensation stimulates other senses. While more than 150 types of synesthesia have been reported; however, some types are considered uncommon, and co-occurrence of these rare types of synesthesia are rare. In the present report, we described a case of synesthesia with experience of pain and orgasm in color. Method : A 31-year old healthy male presented with visual equity changes during orgasm. In addition, he described a color-pain sensation every time he experienced severe chest pain during his childhood. None of these sensations negatively affected his daily or sexual life. Based on the patient's history, a possible diagnosis of synesthesia was made and further clinical evaluations were performed. Results: The patient did not have any color vision abnormalities or problems in solving Hooper visual organization test, bells test, Rey complex figure test, card sorting test, and Trail making tests. The Brief Male Sexual Inventory did not reveal any sexual dysfunction. Therefore, regarding the patient's experiences without any visual disturbance and absence of any underlying diseases, the diagnosis of synesthesia was made. Conclusion: The present report demonstrates coexistence of a rare form of synesthesia as orgasm to color with specific pain to color synesthesia. In contrast to previous reports, our case demonstrated color orgasm as a type of synesthesia that might not negatively affect sex life in men.

Human T-lymphotropic virus type 1 and novel coronavirus disease 2019; More complex than just a simple coinfection.

The recent coronavirus disease 2019 (COVID-19) significantly affected many people worldwide, especially those with underlying diseases. While some people with underlying illnesses, including cardiovascular diseases, are more vulnerable to develop severe COVID-19, other populations, including people who have autoimmune diseases, may develop severe diseases similar to the general population. The severity and outcome of COVID-19 are reviewed in individuals with underlying viral diseases, including acquired immune deficiency syndrome and hepatitis, however, some infectious diseases, including human T-lymphotropic virus type 1 (HTLV-1) diseases, is under-reported in the literature. HTLV-1 is a sexually transmitted disease that is endemic in some parts of the world. Infected patients may develop clinical symptoms of HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP) and adult T cell leukemia (ATL) or may remain asymptomatic during their life. To the best of our knowledge, no clinical studies evaluate the severity and outcomes of SARS-CoV-2 infection in HTLV-1 infected patients. We aimed to review the pathogenesis of both of these viral infections and discuss their similarities in provoking immune responses. Although HTLV-1 infected patients may have had variable degrees of inflammation and immune system dysregulation, the available data is limited to conclude that HTLV-1 infected patients may be more vulnerable to developing severe COVID-19 in contrast to the general population.

Updates on the Epidemiology of the Human T-Cell Leukemia Virus Type 1 Infection in the Countries of the Eastern Mediterranean Regional Office of the World Health Organization with Special Emphasis on the Situation in Iran.

BACKGROUND: The epidemiology and prevalence of the Human T-cell leukemia virus type-1 (HTLV-1) infection represent a recommended priority by global health agencies. An in-depth revision to update the status of this infection in countries including those of the Eastern Mediterranean Regional Office (EMRO) of the World Health Organization is hence required. METHODS: Ninety-seven studies evaluating the HTLV-1 infection in low- and high-risk populations in EMRO countries were retrieved from the international electronic databases and were used to assess the epidemiological status of the infection in these countries. RESULTS: Most epidemiologic reports were published from Iran, with more than 50% of Iranian prisoners and around 4% of healthy individuals reported to have the infection. In Egypt, a considerable prevalence of the virus spans around 1.11% of blood donors. Foci of HTLV-1 infection are also present in some countries and require a careful epidemiological evaluation. In the other EMRO countries, a lower prevalence that does not exceed 1% was reported. CONCLUSION: The epidemiology and prevalence of HTLV-1 in the EMRO countries require a tight revision and update. Published studies reveal a scarce distribution of the virus in the African countries of EMRO, while a lower prevalence is denoted in the Asian countries of EMRO, except in Iran, where the prevalence is high.

A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders.

The human body is full of an extensive number of commensal microbes, consisting of bacteria, viruses, and fungi, collectively termed the human microbiome. The initial acquisition of microbiota occurs from both the external and maternal environments, and the vast majority of them colonize the gastrointestinal tract (GIT). These microbial communities play a central role in the maturation and development of the immune system, the central nervous system, and the GIT system and are also responsible for essential metabolic pathways. Various factors, including host genetic predisposition, environmental factors, lifestyle, diet, antibiotic or nonantibiotic drug use, etc., affect the composition of the gut microbiota. Recent publications have highlighted that an imbalance in the gut microflora, known as dysbiosis, is associated with the onset and progression of neurological disorders. Moreover, characterization of the microbiome-host cross talk pathways provides insight into novel therapeutic strategies. Novel preclinical and clinical research on interventions related to the gut microbiome for treating neurological conditions, including autism spectrum disorders, Parkinson's disease, schizophrenia, multiple sclerosis, Alzheimer's disease, epilepsy, and stroke, hold significant promise. This review aims to present a comprehensive overview of the potential involvement of the human gut microbiome in the pathogenesis of neurological disorders, with a particular emphasis on the potential of microbe-based therapies and/or diagnostic microbial biomarkers. This review also discusses the potential health benefits of the administration of probiotics, prebiotics, postbiotics, and synbiotics and fecal microbiota transplantation in neurological disorders.

Role of miRNA gene variants in the susceptibility and pharmacogenetics of colorectal cancer.

Colorectal cancer (CRC) is one of the most significant challenges in the field of cancer pathology. miRNAs are among the genetic factors associated with the disease. Although many studies have reviewed the expression patterns of various miRNAs in CRC, few studies have focused on different variants of miRNA. In the present review, miRNA variants have been categorized into three subgroups, including miRNA variants that predict susceptibility to CRC, miRNA variants that predict the clinical parameters of CRC and finally, miRNA variants that predict the pharmacological aspects of CRC. Moreover, a comprehensive review of potentially functional miRNA-associated SNPs as well as their importance as candidate cancer biomarkers are discussed.

PLA2G6 gene mutation and infantile neuroaxonal degeneration; report of three cases from Iran.

OBJECTIVES: Infantile neuroaxonal degeneration (INAD) is a rare subgroup of neurodegeneration with brain iron accumulation (NBIA) disorders. This progressive disorder may develop during the early years of life. Affected individuals mostly manifest developmental delay and/or psychomotor regression as well as other neurological deficits. In the present study, we discussed 3 INAD patients diagnosed before the age of 10 by using Whole-Exome Sequencing (WES). MATERIALS AND METHODS: We evaluated 3 pediatric patients with clinical phenotypes of INAD who underwent WES. Sanger sequencing was performed for co-segregation analysis of the variants in the families. An in-silico study was conducted for identification of the molecular function of the identified genetic variants in the PLA2G6 gene. RESULTS: We detected three novel genetic variants in the PLA2G6 gene including a homozygous missense (NM_003560.2; c.1949T>C; p.Phe650Ser), a splicing (NM_001349864; c.1266-1G>A) and a frameshift variant (NM_003560.4; c.1547_1548dupCG; p.Gly517ArgfsTer29). Since the variants were not previously reported in literature or population databases, we performed in-silico studies for these variants and demonstrated their potential pathogenicity. CONCLUSION: The current study reports novel genetic variants in the PLA2G6 gene in the Iranian population, emphasizing the importance of high-throughput genetic testing in rare diseases.

Association of vitamin D status with liver and kidney disease: A systematic review of clinical trials, and cross-sectional and cohort studies.

Background: Vitamin D deficiency (VDD) is a major public health problem. There are few comprehensive systematic reviews about the relationship between Vitamin D status and liver and renal disease in Iran. Methods: We systemically searched the following databases: Web of Science; PubMed; Cochrane Library; Scopus; Science Direct; Google Scholar and two Iranian databases (Scientific Information Database (SID) and IranMedex) up until November 2017 to identify all randomized control trials (RCTs), case control, cross-sectional and cohort studies investigating the association between vitamin D and any form of liver or kidney disease. Results: Vitamin D insufficiency, or deficiency (VDD), is highly prevalent in Iran, reports varying between 44.4% in Isfahan to 98% in Gorgan. There is also a high prevalence of VDD among patients with liver or kidney disease, and the administration of vitamin D supplements may have beneficial effects on lipid profile, blood glucose, liver function and fatty liver disease, and bone health. Low serum vitamin D levels are related with abnormalities in these laboratory and clinical parameters. Conclusion: VDD is prevalent in patients with chronic liver or renal disease in Iran. There appear to be several beneficial effects of vitamin D supplementation in vitamin D deficient patients with liver or kidney disease.

Molecular determinants of response to 5-fluorouracil-based chemotherapy in colorectal cancer: The undisputable role of micro-ribonucleic acids.

5-flurouracil (5-FU)-based chemotherapy is the main pharmacological therapy for advanced colorectal cancer (CRC). Despite significant progress in the treatment of CRC during the last decades, 5-FU drug resistance remains the most important cause of failure in CRC therapy. Resistance to 5-FU is a complex and multistep process. Different mechanisms including microsatellite instability, increased expression level of key enzyme thymidylate synthase and its polymorphism, increased level of 5-FU-activating enzymes and mutation of TP53 are proposed as the main determinants of resistance to 5-FU in CRC cells. Recently, micro-ribonucleic acids (miRNA) and their alterations were found to have a crucial role in 5-FU resistance. In this regard, the miRNA-mediated mechanisms of 5-FU drug resistance reside among the new fields of pharmacogenetics of CRC drug response that has not been completely discovered. Identification of the biological markers that are related to response to 5-FU-based chemotherapy is an emerging field of precision medicine. This approach will have an important role in defining those patients who are most likely to benefit from 5-FU-based chemotherapy in the future. Thereby, the identification of 5-FU drug resistance mechanisms is an essential step to predict and eventually overcome resistance. In the present comprehensive review, we will summarize the latest knowledge regarding the molecular determinants of response to 5-FU-based chemotherapy in CRC by emphasizing the role of miRNAs.

Telemedicine and Computer-Based Technologies during Coronavirus Disease 2019 Infection; A Chance to Educate and Diagnose.

Coronavirus disease 2019 (COVID-19) is now of global concern due to its rapid dissemination across the globe. The rapid spread of this viral infection, along with many of its unknown aspects, has posed new challenges to the health care systems. The main challenging effects of COVID-19 are rapid dissemination through close contact and varying clinical severity among different individuals. Furthermore, the medical staff in endemic areas are becoming exhausted and deal with a considerable level of job burnout, which can negatively affect their medical decision making. Also, due to the variable pulmonary manifestations of COVID-19, some physicians may misdiagnose patients. To overcome these issues, we proposed a web-based software to aid physicians in detecting possible COVID-19 cases through online consultation with different specialists and educate the not-well experienced physicians. Our results demonstrated that this software could improve the diagnostic rate for not-well experienced physicians.

Dietary Inflammatory Index is associated with Healthy Eating Index, Alternative Healthy Eating Index, and dietary patterns among Iranian adults.

BACKGROUND: Recent investigations have evaluated the effect of the inflammatory potential of diet in several populations by calculating the Dietary Inflammatory Index (DII) score. We aimed to evaluate the association of the DII with the Healthy Eating Index (HEI), the Alternative Healthy Eating Index (AHEI), and dietary pattern (DP) among healthy Iranian adults. METHODS: A cross-sectional study was conducted among 4365 middle-aged adults. Major DPs and DII score were identified using a validated semi-quantitative food frequency questionnaire (FFQ). Poisson regression was used to evaluate the association of DPs, HEI, and AHEI across tertiles of DII. RESULTS: After adjustment for confounding variables, a low HEI (HEI < 55) and AHEI (AHEI < 56.5) were more prevalent among the participants in the highest tertile of DII compared to the first tertile (PR: 1.13, P-value <.05; PR: 1.10, P-value <.05; respectively). Adherence to a balanced healthy dietary pattern was significantly lower in subjects with a diet that was more pro-inflammatory compared to those with anti-inflammatory diet (PR: 0.85, P-value P < .01). No significant association was found between the DII and a western DP. High levels of HDL and hip and waist circumference were observed in the highest tertile of DII, and high levels of dietary intake of protein and fiber, minerals, fasting blood glucose, and monounsaturated fat were reported in the lowest tertile of DII. CONCLUSION: The highest tertile of the DII (a pro-inflammatory diet) was associated with a lower HEI, AHEI, and lower adherence to balanced DP in a representative sample of adults in Iran.

Clinical Efficacy Evaluation of Sirolimus in Congenital Hyperinsulinism.

BACKGROUND: Congenital hyperinsulinism (CHI) is a rare and life-threatening genetic disorder. Sirolimus as a mammalian target of rapamycin inhibitor may be helpful in patients with CHI who do not respond well to other treatments including diazoxide and octreotide. However, the safety and efficacy of this therapy are still unclear. This study aimed to evaluate the potential therapeutic effects of sirolimus in CHI patients with mutations in the ABCC8 and KCNJ11 genes. METHODS: During the period of this follow-up study, every child with a confirmed diagnosis of unresponsive CHI underwent genetic evaluation. Among those who had positive genetic testing, six families agreed to participate in this study. The participants were evaluated for ABCC8, KCNJ11, or HNF4α gene mutations by polymerase chain reaction (PCR) sequencing. The participants who were unresponsive to diazoxide and octreotide therapy received 0.5 mg/m2/d of sirolimus, and the dose was gradually increased until a serum concentration of 5-15 ng/ml was achieved. Then, the participants were followed up for any possible complications. RESULTS: Among the study participants, only one neonate was completely free of hypoglycemia after one year of follow-up, whereas three others experienced a partial reduction in hypoglycemic episodes over six months. One neonate underwent pancreatectomy despite receiving sirolimus. The oldest participant with a mutation in the ABCC8 gene responded well to sirolimus therapy after surgery and remained asymptomatic for 18 months. CONCLUSION: This study suggested that sirolimus therapy needs further evaluation to determine which patients will benefit the most. The genetic basis of CHI may have possible implications for determining the patient's response.