Clinical, immunological and molecular findings of 8 patients with typical and atypical severe combined immunodeficiency: identification of 7 novel mutations by whole exome sequencing.

Severe combined immunodeficiency (SCID) is one of the severe inborn errors of the immune system associated with life-threatening infections. Variations in SCID phenotypes, especially atypical SCID, may cause a significant delay in diagnosis. Therefore, SCID patients need to receive an early diagnosis. Here, we describe the clinical manifestations and genetic results of four SCID and atypical SCID patients. All patients (4 males and 4 females) in early infancy presented with SCID phenotypes within 6 months of birth. The mutations include RAG2 (p.I273T,p.G44X), IL7R (p.F361WfsTer17), ADA (c.780+1G>A), JAK3 (p.Q228Ter), LIG4 (p.G428R), and LAT (p.Y207fsTer33), as well as a previously reported missense mutation in RAG1 (p.A444V). The second report of LAT deficiency in SCID patients is presented in this study. Moreover, all variants were confirmed in patients and their parents as a heterozygous state by Sanger sequencing. The results of our study expand the clinical and molecular spectrum associated with SCID and leaky SCID phenotypes and provide valuable information for the clinical management of the patients.

Molecular findings and clinical manifestations of 18 Iranian children with Griscelli syndrome type 2: Two novel homozygote mutations in RAB27A gene in a patient.

Griscelli syndrome type 2 (GS2) is an autosomal recessive immunodeficiency characterized by hair hypopigmentation, recurrent fever, hepatosplenomegaly and pancytopenia. This study aims to find new genetic changes and clinical features in 18 children with GS2 caused by the RAB27A gene defect. In all, 18 Iranian children with GS2 who presented with silver grey hair and frequent pyogenic infection were included in this study. After recording demographic and clinical data, PCR sequencing of the RAB27A gene was performed for all exons and exon-intron boundaries. Two patients in this study were subjected to whole-exome sequencing followed by Sanger sequencing. Light microscopy study of hair showed large irregular clumps of pigment with the absence of giant granules on the blood smear. Mutation analysis of the RAB27A gene identified two novel missense mutations as homozygous in a patient, one in exon 2, c.140G>C and another in exon 4, c.328G>T. In addition, for 17 other patients, 6 reported mutations were obtained including c.514_518delCAAGC, c.150_151delAGinsC, c.400_401delAA, c.340delA, c.428T>C and c.221A>G. The mutation c.514_518delCAAGC was the most frequent and found in 10 patients; this mutation may be considered a hotspot in Iran. Early diagnosis and treatment of RAB27A deficiency can contribute to better disease outcomes. In affected families, genetic results could be urgently needed to make a timely decision about haematopoietic stem cell transplantation and prenatal diagnosis.

Multi-targeting of K-Ras domains and mutations by peptide and small molecule inhibitors.

K-Ras activating mutations are significantly associated with tumor progression and aggressive metastatic behavior in various human cancers including pancreatic cancer. So far, despite a large number of concerted efforts, targeting of mutant-type K-Ras has not been successful. In this regard, we aimed to target this oncogene by a combinational approach consisting of small peptide and small molecule inhibitors. Based on a comprehensive analysis of structural and physicochemical properties of predominantly K-Ras mutants, an anti-cancer peptide library and a small molecule library were screened to simultaneously target oncogenic mutations and functional domains of mutant-type K-Ras located in the P-loop, switch I, and switch II regions. The selected peptide and small molecule showed notable binding affinities to their corresponding binding sites, and hindered the growth of tumor cells carrying K-RasG12D and K-RasG12C mutations. Of note, the expression of K-Ras downstream genes (i.e., CTNNB1, CCND1) was diminished in the treated Kras-positive cells. In conclusion, our combinational platform signifies a new potential for blockade of oncogenic K-Ras and thereby prevention of tumor progression and metastasis. However, further validations are still required regarding the in vitro and in vivo efficacy and safety of this approach.

Clinical and immunological characteristics of 69 leukocyte adhesion deficiency-I patients.

BACKGROUND: In order to support the comprehensive classification of Leukocyte Adhesion Deficiency-I (LAD-I) severity by simultaneous screening of CD11a/CD18, this study assessed clinical, laboratory, and genetic findings along with outcomes of 69 LAD-I patients during the last 15 years. METHODS: Sixty-nine patients (40 females and 29 males) with a clinical phenotype suspected of LAD-I were referred to Immunology, Asthma, and Allergy research institute, Tehran, Iran between 2007 and 2022 for further advanced immunological screening and genetic evaluations as well as treatment, were enrolled in this study. RESULTS: The diagnosis median age of the patients was 6 months. Delayed umbilical cord separation was found in 25 patients (36.2%). The median diagnostic delay time was 4 months (min-max: 0-82 months). Forty-six patients (66.7%) were categorized as severe (CD18 and/or CD11a: below 2%); while 23 children (33.3%) were in moderate category (CD18 and/or CD11a: 2%-30%). During the follow-ups, 55.1% of children were alive with a mortality rate of 44.9%. Skin ulcers (75.4%), omphalitis (65.2%), and gingivitis (37.7%) were the most frequent complaints. Genetic analysis of the patients revealed 14 previously reported and three novel pathogenic mutations in the ITGB2 gene. The overall survival of patients with and without hematopoietic stem cell transplantation was 79.3% and 55.6%, respectively. CONCLUSION: Physicians' awareness of LAD-I considering delayed separation of umbilical cord marked neutrophilic leukocytosis, and variability in CD11 and CD18 expression levels, and genetic analysis leads to early diagnosis and defining disease severity. Moreover, the prenatal diagnosis would benefit families with a history of LAD-I.

The effects of rutin flavonoid supplement on glycemic status, lipid profile, atherogenic index of plasma, brain-derived neurotrophic factor (BDNF), some serum inflammatory, and oxidative stress factors in patients with type 2 diabetes mellitus: A double-blind, placebo-controlled trial.

This study aimed to investigate the effects of rutin flavonoid in type 2 diabetes mellitus (T2DM) patients. In this trial (double-blind, placebo-controlled), 50 T2DM patients (supplement, n = 25 and placebo, n = 25) were randomized and supplemented with 500 mg rutin or placebo per day for 3-months. At the beginning and at the end of the study, metabolic parameters including fasting blood glucose (FBG), insulin, glycosylated hemoglobin (HbA1c), homeostasis model assessment of insulin resistance (HOMO-IR), quantitative insulin sensitivity check index (QUICKI), homeostasis model assessment of ß-cell function (HOMA-ß), triglyceride (TG), total cholesterol (CHOL), high-density and low-density lipoprotein cholesterol (HDL-c and LDL-c), and atherogenic index of plasma (AIP), inflammatory and oxidative stress markers such as interleukin 6 (IL-6), total antioxidant capacity (TAC), and malondialdehyde (MDA) and brain-derived neurotrophic factor (BDNF) were assessed. The results showed a significant decrease in FBG, insulin, HbA1c, HOMO-IR, LDL-c, TG, VLDL, CHOL, LDL-c.HDL-c ratio, AIP, IL-6, and MDA and a significant increase in HDL-c, QUICKI index, BDNF, and TAC compared with the initial value (p for all <.05). In the adjusted model, the mean changes of FBG, insulin, HbA1c, HOMO-IR, LDL-c, CHOL, LDL.HDL ratio, AIP, MDA, and IL-6 were significantly lower and mean changes of QUICKI index, HDL-c, and TAC were significantly higher in the rutin group compared with the placebo group (adjusted p for all <.05). It seems that rutin may have beneficial effects on improving metabolic parameters, BDNF, and inflammatory and oxidative stress factors in T2DM patients.

Bacteriophage as a Novel Therapeutic Weapon for Killing Colistin-Resistant Multi-Drug-Resistant and Extensively Drug-Resistant Gram-Negative Bacteria.

Colistin-resistant multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) bacteria are highly lethal and many researchers have tried hard to combat these microorganisms around the world. Infections caused by these bacteria are resistant to the last resort of antibiotic therapy and have posed a major challenge in clinical and public health. Since the production of new antibiotics is very expensive and also very slow compared to the increasing rate of antibiotic resistance, researchers are suggesting the use of natural substances with high antibacterial potential. Bacteriophages are one of the most effective therapeutic measures that are known to exist for use for incurable and highly resistant infections. Phages are highly taken into consideration due to the lack of side effects, potential spread to various body organs, distinct modes of action from antibiotics, and proliferation at the site of infection. Although the effects of phages on MDR and XDR bacteria have been demonstrated in various studies, only a few have investigated the effect of phage therapy on colistin-resistant isolates. Therefore, in this review, we discuss the problems caused by colistin-resistant MDR and XDR bacteria in the clinics, explain the different mechanisms associated with colistin resistance, introduce bacteriophage therapy as a powerful remedy, and finally present new studies that have used bacteriophages against colistin-resistant isolates.

Associations between new and old anthropometric indices with type 2 diabetes mellitus and risk of metabolic complications: a cross-sectional analytical study.

BACKGROUND: Obesity can increase the risk of diabetes mellitus and complications associated with it. OBJECTIVES: The aim of this study was to estimate the associations between new and old anthropometric indices and the risk of type 2 diabetes mellitus (T2DM) and its metabolic complications. METHODS: In this cross-sectional analytical study, 110 T2DM subjects and 110 healthy controls were selected by convenience sampling. Metabolic factors were evaluated including the atherogenic index of plasma (AIP), glycemic status, lipid profile, blood pressure, kidney indices, new anthropometric indices (abdominal volume index [AVI], body shape index [ABSI], lipid accumulation product [LAP], body adiposity index [BAI], and conicity index [CI]), and old anthropometric indices (weight, body mass index [BMI], and waist and hip circumference [WC and HC]). RESULTS: Significant positive correlations were observed between AVI, LAP, and BAI and fasting blood glucose and HbA1c in the T2DM group (p < 0.001 for all associations). The odds ratio (OR) for T2DM elevated significantly with increasing BMI (OR: 1.30, 95% CI: 1.20-1.42), LAP (OR: 1.20, 95% CI: 1.13-1.27), and BAI (OR: 1.32, 95% CI: 1.21-1.43). The indices AVI (OR: 1.90, 95% CI: 1.57-2.29), LAP (OR: 1.19, 95% CI: 1.13-1.27), BAI (OR: 1.19, 95% CI: 1.12-1.26), WC (OR: 1.29, 95% CI: 1.18, 1.42), and HC (OR: 1.07, 95% CI: 1.01, 1.14) significantly increased the risk of metabolic syndrome (MetS). CONCLUSIONS: Associations were identified between obesity indices and diabetes. These indices could be used in clinical practice for evaluation and control of T2DM.

CONTEXTO: A obesidade pode aumentar o risco de diabetes melito e complicações associadas. OBJETIVOS: O objetivo deste estudo foi estimar a associação de índices antropométricos novos e antigos com o risco de diabetes melito tipo 2 (DM2) e suas complicações metabólicas. MÉTODOS: Neste estudo analítico transversal, 110 indivíduos com DM2 e 110 controles saudáveis foram selecionados por amostragem de conveniência. Foram avaliados os fatores metabólicos, incluindo índice aterogênico plasmático, estado glicêmico, perfil lipídico, pressão arterial, índices renais, índices antropométricos novos [índice de volume abdominal (AVI), índice de formato corporal (ABSI), produto de acumulação lipídica (LAP), índice de adiposidade corporal (BAI) e índice de conicidade (CI)] e índices antropométricos antigos [peso, índice de massa corporal (IMC), circunferência de cintura e quadril]. RESULTADOS: Foi observada uma correlação positiva significativa de AVI, LAP e BAI com glicemia de jejum e hemoglobina glicada no grupo DM2 (p para todos < 0,001). A odds ratio (OR) do grupo DM2 foi significativamente elevada com aumento de IMC [OR: 1,30, intervalo de confiança (IC) de 95%: 1,20-1,42], LAP (OR: 1,20, IC95%: 1,13-1,27) e BAI (OR: 1,32, IC95%: 1,21-1,43). Os índices AVI (OR: 1,90, IC95%: 1,57-2,29), LAP (OR: 1,19, IC95%: 1,13-1,27), BAI (OR: 1,19, IC95%: 1,12-1,26), WC (OR: 1,29, IC95%: 1,18-1,42) e HC (OR: 1,07, IC95%: 1,01-1,14) aumentaram significativamente o risco de síndrome metabólica. CONCLUSÕES: Foi reconhecida uma associação entre índices de obesidade e diabetes. Esses índices podem ser usados na prática clínica para avaliação e controle do DM2.

The effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status, serum melatonin and inflammatory markers in type 2 diabetes mellitus patients with chronic periodontitis: a double-blind, placebo-controlled trial.

BACKGROUND: Diabetes mellitus (DM) and periodontitis are two common chronic diseases with bidirectional relationship. Oxidative stress plays a key role in the pathogenesis of these two diseases. The aim of this study was to investigate the effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status, serum melatonin and inflammatory markers in type 2 DM patients with chronic periodontitis (CP). MATERIALS AND METHODS: In this double-blind clinical trial study, 50 type 2 DM patients with CP were randomly allocated to the intervention and control groups. The intervention and control groups received either 6 mg melatonin or placebo (2 tablets) once a day. Serum levels of melatonin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), hs-C-reactive protein (hs-CRP), clinical attachment loss (CAL), pocket depth (PD), bleeding on probing (BOP) and plaque index were evaluated in all subjects pre- and post-intervention. RESULTS: Melatonin supplementation significantly increased the mean serum levels of melatonin after intervention. The mean changes of melatonin were significantly higher in intervention group compared with control group. IL-6 and hs-CRP levels were significantly (p = 0.008 and p = 0.017, respectively) reduced in the intervention group. The mean changes of IL-6 were significantly lower in the intervention group compared with the control group (p = 0.04). In the intervention group, PD and CAL were significantly decreased after intervention (p < 0.001). There were significant differences in the mean change of PD and CAL between the intervention and control groups after intervention (p < 0.001). CONCLUSIONS: Melatonin supplementation in adjunct with non-surgical periodontal therapy might improve inflammatory and periodontal status in T2DM with CP.

Sodium Saccharin as an Effective Catalyst for Rapid One-pot Pseudo-five Component Synthesis of Dihydropyrano[2,3-g]chromenes under Microwave Irradiation.

One-pot microwave-assisted synthesis of dihydropyrano[2,3-g]chromenes catalyzed by sodium saccharin as an efficient, mild and green catalyst was studied. The method presented is a safe and eco-friendly approach for the multicomponent synthesis of dihydropyrano[2,3-g]chromene derivatives with many merits including short reaction times (in comparison with other reported results), high yields and easy work up.

Efficient synthesis of some [1,3]-oxazine derivatives in the presence of solid acid nano catalyst based on ferrierite and study on their activity against breast cancer through molecular docking calculation.

In this research, the magnetic solid acid nanocatalyst based on ferrierite has been prepared and used as catalyst for the green synthesis of some [1,3]-oxazine derivatives in water at room temperature. The synthesized compounds were obtained in high to excellent yields after short reaction times and the structure of synthesized products were investigated by spectroscopic methods such as: FT-IR, 1H NMR and 13C NMR. The prepared magnetic solid acid catalyst was characterized using XRD, FT-IR, FE-SEM, EDX, elemental mapping, TGA and VSM analysis methods. Magnetic catalyst has easy separation ability, which leads to better and easier recycling. The preparation and synthesis of [1,3]-oxazine derivatives were carried out at room temperature in the presence of M-FER/TEPA/SO3H. Easy workup, green solvent (water) and also short reaction times with high to excellent yield of products, are some of advantageous of presented method. Docking calculations on the structure of the synthesized compounds proved their medicinal properties against breast cancer cells.

Investigating the effect of levothyroxine replacement on cholesterol levels in hypothyroid patients.

Introduction: Effects of levothyroxine therapy on the lipid profile of hypothyroid patients lead to decrease in the risk of cardiovascular diseases and mortality. Objective: Overt or subclinical hypothyroid dysfunction has negative effects on lipid metabolism and leads to hypercholesterolemia that in turn increases the risk of cardiovascular diseases and mortality. In this matter, several interventional studies investigated the effects of levothyroxine therapy on the lipid profile of hypothyroid patients, and conflicting results have been obtained. The current research aims to investigate the effect of levothyroxine replacement on cholesterol levels in hypothyroid patients. Methods: The present prospective study examined 112 patients (mean age of 43.80 ± 14.36 years) with overt hypothyroidism. To do so, 72.3% of patients were females. Levothyroxine replacement therapy was prescribed for patients, and they were examined monthly to evaluate the effects of therapy on their lipid profiles. After reaching normal thyroid stimulating hormone (TSH), the patients' laboratory parameters, including TSH, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, were surveyed. Results: After Levothyroxine therapy, there was a significant reduction in mean TSH (62.03 vs. 2.33 ± 1.95; P < 0.0001), triglycerides (145.57 ± 88.65 vs. 121.91 ± 59.52, P = 0.002), cholesterol (203.90 ± 53.73 vs. 166.65 ± 40.07, P < 0.0001), and serum LDL (123.61 ± 45.03 vs. 95.99 ± 24.20, P < 0.0001), but the mean value of serum HDL did not show any significant change (54.18 ± 16.60 vs. 51.59 ± 18.38, P = 0.274). Conclusions: Levothyroxine therapy has beneficial effects on lipid profile in patients with overt hypothyroidism because it decreases serum triglyceride, total cholesterol, and LDL. However, levothyroxine therapy does not significantly change HDL levels.

Therapeutic effect of ferrous sulfate in diabetic patients with iron deficiency anaemia: a randomised controlled trial.

Iron deficiency anaemia (IDA) and diabetes mellitus (DM) are most prevalent disease, that diabetic patients are more prone to IDA. Therefore, the main aim of this study was to investigate the relationship between patients with diabetes and IDA in relation to taking iron pills daily and every other day to reduce the effects related to it. Ninety-one participants were enroled and randomly divided into two groups, with a final analysis cohort of 72 patients. The primary focus was on changes in serum Hb and Ferritin levels. The screening phase lasted 24 weeks, leading to 72 eligible participants meeting the criteria for entry into the study. Additionally, the study examined alternations in Hb and Hb A1C levels after treating patients with iron deficiency. The Hb and ferritin level contrasts between groups were not significant (P = 0.096 and P = 0.500, respectively). The relationship between Hb A1C and Hb levels before and after treatment was positive and significant (r 2 = 0.187). The results of the present study show that although the effectiveness of using oral iron supplements did not have a significant difference in terms of increasing haemoglobin and ferritin, the use of oral iron once every other day was more effective than the use of oral iron every day, and also in this study Like other studies, this result concluded that there is a negative correlation between Hb A1C and Hb, and to check the status of Hb A1C in diabetics, the level of Hb should be considered first.

Comparison of metabolic risk factors, lipid indices, healthy eating index, and physical activity among premenopausal, menopausal, and postmenopausal women.

INTRODUCTION: In this study, we aimed to compare metabolic risk factors, lipid indices, healthy eating index, and physical activity among premenopausal, menopausal, and postmenopausal women. METHODS: In this cross-sectional study, a total of 4,732 women participating in the Hoveyzeh Cohort Study were placed into three groups of premenopausal (n=736), menopausal (n=396), and postmenopausal (n=917) women, according to the inclusion and exclusion criteria . RESULTS: The prevalence of metabolic syndrome was 43.3%, 55.6%, and 62.8% in premenopausal, menopausal, and postmenopausal women, respectively. After menopause, the prevalence of hypertension (50.2%), dyslipidemia (61.2%), diabetes (37.7%), and abdominal obesity according to the Iranian guidelines (75.9%) was higher than before menopause. Based on the results, cardiovascular disease had the highest prevalence after menopause (23%). The weight-adjusted waist index (WWI) had the highest odds ratio (OR) among indices, with values of 2.94 and 1.93 in menopausal and postmenopausal women, respectively (P<0.001). According to the Healthy Eating Index-2015 (HEI-2015), the total consumption of fruits, vegetables, seafood, and protein was higher in premenopausal women than in postmenopausal women, and the consumption of foods containing sugar was higher in menopausal women than in premenopausal women. The results showed that the level of physical activity was the highest and the lowest in premenopausal and postmenopausal women, respectively (P<0.001). CONCLUSION: Menopause leads to an increase in the prevalence of metabolic syndrome. The Atherogenic Index of Plasma (AIP), Triglyceride Glucose (TyG) index, WWI, and physical activity index increased in postmenopausal women compared to premenopausal women. The TyG index, WWI, and HEI-2015 did not show significant differences between the groups, based on the multiple regression analysis.

Clinical significance of CD166 and HER-2 in different types of gastric cancer.

INTRODUCTION: Cluster of differentiation 166 (CD166), a cancer stem cell (CSC) marker, and human epidermal growth factor receptor 2 (HER-2) are expressed in a diversity of malignancies and is associated with tumor progression. Although studies regarding the importance of CSC markers and HER-2 in gastric cancer (GC) have rapidly developed, their clinicopathological, prognosis, and diagnosis value still remain unsatisfying in GC. Therefore, the present study aims to investigate the clinical, prognostic, and diagnostic significance of CD166 and HER-2 in different histological types of GC. MATERIALS AND METHODS: Bioinformatic analysis was applied to determine the clinical importance of CD166 and HER-2 expression based on their tissue localization in primary GC tumors and the normal adjacent samples. The expression patterns, clinical significance, prognosis, and diagnosis value of CD166 and HER-2 proteins in tissue microarrays (TMAs) of 206 GC samples, including Signet Ring Cell (SRC) and intestinal types and also 28 adjacent normal tissues were evaluated using immunohistochemistry (IHC). RESULTS: The results indicated that the expression of CD166 (membranous and cytoplasmic) and HER-2 were significantly up-regulated in tumor cells compared to adjacent normal tissues (P = 0.010, P < 0.001, and P = 0.011, respectively). A statistically significant association was detected between a high level of membranous expression of CD166 and lymphovascular invasion (P = 0.006); We also observed a statistically significant association between high cytoplasmic expression of CD166 protein and more invasion of the subserosa (P = 0.040) in the SRC type. In contrast, there was no correlation between the expression of HER-2 and clinicopathologic characteristics. Both CD166 and HER-2 showed reasonable accuracy and high specificity as diagnostic markers. CONCLUSION: Our results confirmed that increased membranous and cytoplasmic expression of CD166 showed clinical significance in the SRC type and is associated with the progression of the disease and more aggressive tumor behaviors. These findings can be used to assist in designating subgroups of patients that require different follow-up strategies, and also, they might be utilized as the prognostic or diagnostic biomarkers in these types of GC for prospective clinical application.

Amidation of multiwalled carbon nanotubes in mild and efficient conditions.

Functionalization of Multi Walled Carbon Nanotubes (MWCNTs) with amines under a two step reaction is studied. In the first step, maleic anhydride graft to the MWCNT (Mah-g-MWCNTs) surfaces via a polymerization process with benzoylproxide as initiator. Active anhydride groups on the surfaces of MWCNTs, react with amines to give a polyamido chain attached to the MWCNTs surfaces. The reaction products have high solubility and disperse stability in organic solvents. FTIR, TGA and elemental analysis (CHN) were used to characterization of the achieved products.

Efficient synthesis of 1,2-disubstituted benzimidazoles catalyzed by phosphoric acid as a homogeneous catalyst under mild conditions and investigating their anti-diabetes properties through molecular docking studies and calculations.

A green practical method for the efficient synthesis of 1-benzyl-2-phenyl-benzimidazole and its derivatives using phosphoric acid as an eco-friendly homogeneous catalyst from the condensation reaction of o-phenylenediamine (OPD) and aromatic aldehydes (bearing electron-withdrawing and electron-releasing groups) in methanol under thermal conditions is described. The advantages of this environmentally benign and safe protocol include short reaction times, very mild reaction conditions, excellent yields, not requiring specialized equipment, and simple workup procedures. This method obtained the desired products in moderate to excellent yields between 61-89% within a short period of time of about 13-30 minutes under mild reaction conditions. Finally, with the help of computational chemistry and drug design methods, the anti-diabetic properties of these compounds were studied and investigated. All the synthesized compounds bind to an agonist in the active site of the 4ll1 protein. These connections lead to the inactivation of this protein and create beneficial effects during the treatment of diabetes. In the synthesized compounds, one of the ligands establishes hydrogen bonds with glutamine 107 residues through nitrogens, and in addition, it establishes Π bonds with tyrosine 72. In this study, it was found that these compounds have the potential to become an oral anti-diabetic drug.

Risk Reassessment of Differentiated Thyroid Cancer in Ahvaz, Iran: A Cross-sectional Retrospective Study.

Background: Accurate evaluation of response to treatment in differentiated thyroid cancer (DTC) is the sine qua non of preventing over-treatment in low-risk patients and implementing appropriate interventions in high-risk individuals. Objectives: This study aimed to assess the response to therapy in DTC patients based on dynamic stratification method. Methods: In this cross-sectional study, 154 medical records of subjects with DTC (with at least 6 months after total thyroidectomy) and referred to endocrinology clinics in Ahvaz, Iran, from April 2020 to May 2021 were examined. Patients were stratified according to a dynamic risk stratification system (informed by their specific clinical, histopathological, and ultrasonography findings, and other diagnostic imagines) into four groups: Excellent response (ER), indeterminate response (IR), biochemical incomplete response (BIR), and structural incomplete response (SIR). Results: For a mean follow-up period of 28.59 months, excellent response to treatment was observed in 92 patients (59.7%), indeterminate response to treatment was found in 32 patients (20.8%), biochemical incomplete response was detected in 2 patients (1.3%), and structural incomplete response was seen in 28 patients (18.2%). In the group with low risk of recurrence, ER and IR were observed in 79.2% and 15.6% of the patients, respectively (P < 0.0001). In the group with an intermediate risk of recurrence, ER was found in 32% of the patients, while IR and SIR + BIR were seen in 34% and 34% of the patients, respectively (P < 0.0001). No cases of ER or IR were observed in the group with high risk (P = 0.001). Conclusions: In sum, response to treatment significantly varied based on dynamic risk stratification, with ER being highest in the low-risk group, less likely in moderate risk group, and undetected in the high-risk group.

Evaluation of the Effect of Barberry Root (Berberis Vulgaris) on the Prevention of Metabolic Syndrome Caused by Atypical Antipsychotic Drugs in Patients with Schizophrenia: A Three-Blind Placebo-Controlled Clinical Trial.

Objective: Metabolic syndrome is a potential side effect of atypical antipsychotics which are the current standard treatment for schizophrenia. Therefore, we aimed to examine the effect of barberry root (Berberis vulgaris) on the prevention of metabolic syndrome caused by atypical antipsychotic drugs in patients with schizophrenia. Method : Our research was a three-blind randomized clinical trial. The participants included all patients who were diagnosed with schizophrenia through the SCID-5 questionnaire and based on the DSM-5-TR criteria by two psychiatric experts. These patients were randomly divided into intervention and placebo groups. During a three-month treatment period, the intervention group received three 500 mg capsules of barberry root extract daily, whereas the placebo group received the same capsules containing 500 mg of starch powder. Metabolic syndrome variables including fasting blood glucose, serum lipids (triglyceride and cholesterol), blood pressure, weight and waist circumference were measured before and after the treatment as outcome measure. Chi-square and t-tests were used for data analysis using SPSS-22 software. Results: At the beginning of the study, there was no significant difference between the intervention group (n = 41) and the placebo group (n = 47) in terms of demographic factors, and pre-treatment assessments including weight, waist size, fasting blood HDL, fasting blood triglycerides and systolic and diastolic blood pressure and fasting blood glucose (P > 0.05). Within group analysis showed that some metabolic factors significantly increased in both groups after the treatment (P < 0.05). Indeed, in both groups, metabolic syndrome measures worsened after the three-month treatment period. The parameters of weight and waist size were significantly higher in the intervention group than the placebo group after treatment (P < 0.05). Conclusion: Barberry root extract was not able to control the Effects of antipsychotic drugs on metabolic syndrome in schizophrenia.

Antibody Production after COVID-19 Vaccination in Patients with Inborn Errors of Immunity.

Background: Few studies have evaluated COVID-19 vaccine efficacy in patients with inborn errors of immunity (IEI). Objective: To evaluate the levels of antibody (Ab) production and function after COVID-19 vaccination in IEI patients with phagocytic, complement, and Ab deficiencies and their comparison with healthy controls. Methods: Serum samples were collected from 41 patients and 32 healthy controls at least one month after the second dose of vaccination, while clinical evaluations continued until the end of the third dose. Levels of specific anti-receptor-binding domain (RBD) IgG and anti-RBD neutralizing antibodies were measured using EUROIMMUN and ChemoBind kits, respectively. Conventional SARS-CoV-2 neutralization test (cVNT) was also performed. Cutoff values of ≤20, 20-80, and ≥80 (for cVNT and Chemobined) and 0.8-4.2, 4.2-8.5, and ≥8.5 (for EUROIMMUN) were defined as negative/weak, positive/moderate, and positive/significant, respectively. Results: A considerable distinction was observed between the Ab-deficient patients and the controls for Ab concentration (EUROIMMUN, p<0.01) and neutralization (ChemoBind, p<0.001). However, there was no significant difference compared with the other patient groups. A near-zero cVNT in Ab-deficient patients was found compared to the controls (p<0.01). A significant correlation between the two kits was found using the whole data (R2=0.82, p<0.0001). Conclusion: Despite varying degrees of Ab production, all Ab deficient patients, as well as almost half of those with complement and phagocytic defects, did not effectively neutralize the virus (cVNT). In light of the decreased production and efficiency of the vaccine, a revised immunization plan may be needed in IEI.

Evaluation of Insulin Resistance (HOMA-IR) for Patients with and without Thyroid Nodules: A Patient-Based Study.

Background: The aim of this study was to assess the prevalence of insulin resistance (HOMA-IR) between patients with and without thyroid nodules. Materials and Methods: This case-control study was performed on 86 patients with normal Thyroid-stimulating hormone (TSH) level (0.5-4.5 mIU/L) with thyroid nodules, who referred to Imam Khomeini and Golestan Hospitals (Ahvaz, Iran). Furthermore, 43 nonnodule patients with normal TSH level and normal thyroid ultrasonography were recruited from the general population as control group. The insulin resistance was evaluated for them made and the HOMA-IR ≥2.5 was defined as insulin resistance. Results: The mean of HOMA-IR value was significantly higher in thyroid nodule patients compared to controls (3.02 ± 1.92 vs. 1.10 ± 1.55; P < 0.001). Insulin resistance was seen in 49 thyroid nodule patients (57.0%), and 4 patients (9.3%) in the control group (P < 0.0001). Waist circumference, body mass index, fasting blood sugar, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and insulin levels were significantly higher in the thyroid nodule group. Conclusions: Our study shows there is an association between insulin resistance and thyroid nodules. The patients with thyroid nodules have higher HOMA-IR value.