Prevalence of Trichomonas Infection in Relation to Human Papillomavirus (HPV) in Pap Smear Samples of Female Patients Referred to Shahid Sadoughi Hospital, Yazd (Iran).

Objectives Human papillomavirus (HPV) and Trichomonas vaginalis (TV) infections have been proposed as risk factors for cervical cancer. This study has been conducted with the aim of investigating the prevalence of TV and its relationship with HPV in women who underwent Pap smear testing as part of cancer screenings. Materials and methods The sampling of liquid-based cervical tissue was conducted among 500 women referred to the women's clinic of Shahid Sadoughi Hospital in Yazd, Iran. The studied samples were examined for Pap smear tests and microscopic identification of TV, as well as HPV-DNA detection and the determination of high-risk and low-risk HPV types by the polymerase chain reaction (PCR) method. The results were analyzed using the IBM SPSS Statistics for Windows, Version 24 (Released 2016; IBM Corp., Armonk, New York) software. Results The individuals included in the study were 16-72 years old. The prevalence rate of TV infection in this population was found to be 29.2%, and the frequency rate of HPV was reported to be approximately 19.4%, with high-risk HPV, including HPV-56, having the highest frequency. The Pap smear test results were reported as abnormal in 20.2%, and a significant correlation was observed between HPV infection and an abnormal Pap smear test (P < 0.05). In addition, a notable correlation was detected between TV infection and high-risk and low-risk HPV (P < 0.05). Conclusion According to the significant relationship found between the two pathogens, TV and HPV, in the abnormal Pap smear test results, TV infection can be considered a risk factor for HPV infection, as well as uterine lesions and cancer.

The implications of exosomes in psoriasis: disease: emerging as new diagnostic markers and therapeutic targets.

As the largest human organ, the skin is continuously exposed to various external and internal triggers that affect body homeostasis. Psoriasis is a persistent inflammatory skin condition that has a major bearing on patients' physiological functioning as well as their mental well-being. It is an autoimmune disorder and has been the focus of extensive research efforts in recent years. Cells secrete exosomes into the environment surrounding them, which comprises a lipid bilayer. The movement of cellular components like microRNAs, mRNAs, DNA, lipids, metabolites, and cell-surface proteins is mediated by exosomes. Exosomes are crucial for inducing communication between cells. There has been extensive study of exosomes, both preclinical and clinical, looking at their potential role in autoimmune diseases. Besides the role that they play in the body's basic processes, exosomes are also considered an increasingly essential part as diagnostic and therapeutic agents. In the following article, we conduct a literature review of current studies related to molecular and structural aspects of exosomes. We emphasis on the function of exosomes in pathogenesis, as well as the possibility of their usage in medicinal applications and as biomarkers.

Macrophage-Based Therapeutic Strategies in Hematologic Malignancies.

Macrophages are types of immune cells, with ambivalent functions in tumor growth, which depend on the specific environment in which they reside. Tumor-associated macrophages (TAMs) are a diverse population of immunosuppressive myeloid cells that play significant roles in several malignancies. TAM infiltration in malignancies has been linked to a poor prognosis and limited response to treatments, including those using checkpoint inhibitors. Understanding the precise mechanisms through which macrophages contribute to tumor growth is an active area of research as targeting these cells may offer potential therapeutic approaches for cancer treatment. Numerous investigations have focused on anti-TAM-based methods that try to eliminate, rewire, or target the functional mediators released by these cells. Considering the importance of these strategies in the reversion of tumor resistance to conventional therapies and immune modulatory vaccination could be an appealing approach for the immunosuppressive targeting of myeloid cells in the tumor microenvironment (TME). The combination of reprogramming and TAM depletion is a special feature of this approach compared to other clinical strategies. Thus, the present review aims to comprehensively overview the pleiotropic activities of TAMs and their involvement in various stages of cancer development as a potent drug target, with a focus on hematologic tumors.

An increase in the expression of circulating miR30d-5p and miR126-3p is associated with intermediate hyperglycaemia in Iranian population.

Type 2 diabetes is the most prevalent metabolic disease worldwide. The disease is characterised by high blood glucose levels and recently it has been shown that changes in the plasma levels of several miRNAs (miRNA) are associated with the disease. Interestingly, alterations in circulating miRNAs occur years before the onset of the disease and demonstrate predictive power. In this study, we carried out RT-qPCR to examine the plasma levels of two type 2 diabetes specific miRNAs, miR-30d-5p and miR-126-3p in an Iranian population of non-diabetic control individuals, subjects with intermediate hyperglycaemia and type 2 diabetic individuals with hyperglycaemia. We found that the plasma levels of miR-30d and miR-126 increase by 3.1 and 11.16 times, respectively, in individuals with intermediate hyperglycaemia compared to non-diabetic controls. However, no significant changes in the expression of these two miRNAs have been observed between type 2 diabetic individuals and non-diabetic subjects. Our results confirm that alterations in the plasma levels of miR-30d-5p and miR-126-3p could be used as diagnostic markers of type 2 diabetes in the Iranian population as well.

NMR spectral analysis of strongly second-order 6-, 8-, 9- and 10- spin-systems (1 H─19 F, 19 F─19 F, and 13 C─19 F) in perfluorotoluyl- and tetrafluoro-pyridyl-aromatics using the lineshape method ANATOLIA.

A simple to use nuclear magnetic resonance analysis method has been tested on complex 1 H, 19 F, and 13 C multiplets. This open-source line-shape analysis method analysis of total lineshape (ANATOLIA)1 provides some significant advantages over traditional assign-iterate methods of NMR spectral analysis by avoiding false minima and progressing optimisation to the global minimum. The target molecules are 1-perfluorotol-4-yl-2-perfluorotol-4-yl-oxymethyl-1H-benzimidazole (molecule-I) and 1-tetrafluoropyrid-4-yl-2-tetrafluoropyrid-4-yl-thio-1H-benzimidazole (molecule-II) which were produced as part of a family of fluorinated drug scaffolds prepared for anticancer and antiparasitic screening. Spectra display significant second-order effects with 1 H Δδ = 3.68 and 4.67 Hz for the aromatic hydrogen "triplets", with 19 F 4 JAA' , 4 JBB' , 4 JXX' , and 4 JYY' coupling constants range from +4.8 to -14.0 Hz and for 13 C-isotopomers 19 F Δδ of up to 111.56 Hz. A spin-system of six coupling nuclei (Ha Hb Hc Hd FY FY' ) was analysed in 12 s, a spin-system of nine coupling fluorine nuclei (AA'BB'CCC-YY') was analysed within 2 min, and 10 coupling nuclei (XX'YY'ZZZ-BB'-Hd ) was optimised in 6 min using a laptop computer. ANATOLIA was also robust enough to be able to yield accurate spectral values from inaccurate input values. In both compounds, a fluorine-fluorine coupling constant was identified between the two fluoro-aromatic rings (FBB' and FYY' ) of +4.05 and +4.67 Hz and attributed to a through-space interaction. Ab initio structure optimisations and coupling constant calculations provided useful input data for spectral analysis. A modern 19 F nuclear magnetic resonance spectrum of perfluorotoluene (octafluorotoluene) and analysis from 1975 was used as a test data set to assess ANATOLIA.

Sensitive Monogenic Noninvasive Prenatal Diagnosis by Targeted Haplotyping.

During pregnancy, cell-free DNA (cfDNA) in maternal blood encompasses a small percentage of cell-free fetal DNA (cffDNA), an easily accessible source for determination of fetal disease status in risk families through non-invasive procedures. In case of monogenic heritable disease, background maternal cfDNA prohibits direct observation of the maternally inherited allele. Non-invasive prenatal diagnostics (NIPD) of monogenic diseases therefore relies on parental haplotyping and statistical assessment of inherited alleles from cffDNA, techniques currently unavailable for routine clinical practice. Here, we present monogenic NIPD (MG-NIPD), which requires a blood sample from both parents, for targeted locus amplification (TLA)-based phasing of heterozygous variants selectively at a gene of interest. Capture probes-based targeted sequencing of cfDNA from the pregnant mother and a tailored statistical analysis enables predicting fetal gene inheritance. MG-NIPD was validated for 18 pregnancies, focusing on CFTR, CYP21A2, and HBB. In all cases we could predict the inherited alleles with >98% confidence, even at relatively early stages (8 weeks) of pregnancy. This prediction and the accuracy of parental haplotyping was confirmed by sequencing of fetal material obtained by parallel invasive procedures. MG-NIPD is a robust method that requires standard instrumentation and can be implemented in any clinic to provide families carrying a severe monogenic disease with a prenatal diagnostic test based on a simple blood draw.

Identification of Mutations Causing Aberrant Termination and Deficient Splice Donor Site on the HBA1 Gene.

α-Thalassemia (α-thal) is a common genetic disorder in Iran and many parts of the world. Genetic defects on the α-globin gene cluster can result in α-thal that may develop a clinical phenotype varying from almost asymptomatic to a lethal hemolytic anemia. In the present study, four Iranian individuals with hypochromic microcytic anemia, who revealed none of the known mutations responsible for α-thal, were subjected for further investigations. The thalassemic phenotype of these patients resulted from abnormal RNA splicing sites owing to a missense at the splice donor site, a truncated protein or hemoglobin (Hb) variants as a result of two different substitutions on the α1-globin gene. The clinical presentation of mild anemia in these individuals showed the contribution of these novel mutations in α-thal in spite of the dominantly expressed α2-globin gene. This study describes hematological manifestations of subjects carrying some novel mutations comparable to the reported phenotype of α(+)-thal trait.

Homozygosity for the AATAAA > AATA- - Polyadenylation Site Mutation on the α2-Globin Gene Causing Transfusion-Dependent Hb H Disease in an Iranian Patient: A Case Report.

We describe a case of Hb H disease associated with homozygosity for a two nucleotide deletion in the polyadenylation signal of the α2-globin gene (HBA2: c.*93_*94delAA). The patient, a 27-year-old son of a consanguineous couple, needs regular blood transfusions every 6 months.

A 21 Nucleotide Duplication on the α1- and α2-Globin Genes Involves a Variety of Hypochromic Microcytic Anemias, From Mild to Hb H Disease.

α-Thalassemia (α-thal) is a common genetic disorder in Iran and many parts of the world. Genetic defects in the α-globin gene cluster can result in α-thal that may develop into a clinical phenotype varying from almost asymptomatic to a lethal hemolytic anemia. Loss of one functional α gene, indicated as heterozygous α(+)-thal, shows minor hematological abnormalities. Homozygosity for α(+)- or heterozygosity for α(0)-thal have more severe hematological abnormalities due to a markedly reduced α chain output. At the molecular level, the absence of three α-globin genes resulting from the compound heterozygous state for α(0)- and α(+)-thal, lead to Hb H disease. Here we present a 21 nucleotide (nt) duplication consisting of six amino acids and 3 bp of intronic sequence at the exon-intron boundary, in both the α-globin genes, detected by direct DNA sequencing. This duplication was identified in three patients originating from two different Iranian ethnic groups and one Arab during more than 12 years. The clinical presentation of these individuals varies widely from a mild asymptomatic anemia (heterozygote in α1-globin gene) to a severely anemic state, diagnosed as an Hb H individual requiring blood transfusion (duplication on the α2-globin gene in combination with the - -(MED) double α-globin gene deletion). The third individual, who was homozygous for this nt duplication on the α1-globin gene, showed severe hypochromic microcytic anemia and splenomegaly. In the last decade, numerous α-globin mutations have demonstrated the necessity of prenatal diagnosis (PND) for α-thal, and this study has contributed another mutation as important enough that needs to be considered.

Venous plasma serotonin is not a proper biomarker for pulmonary arterial hypertension.

OBJECTIVES: Serotonin (5-HT) most likely plays an important role in the pathogenesis of pulmonary arterial hypertension (PAH). We aimed to test if venous plasma 5-HT is a potential biomarker of PAH. We also measured venous blood ß-thromboglobulin (ß-TG) in all participants to ensure that any increase in serotonin levels measured is due to platelet release. DESIGN: Blood samples from patients (n = 9) with pulmonary arterial hypertension (Group 1 of the World Health Organization classification of pulmonary hypertension) as well as healthy volunteers (n = 9) were analyzed. We used enzyme-linked immunosorbent assay (ELISA) to measure venous platelet-poor plasma 5-HT and ß-TG in patients with pulmonary arterial hypertension (PAH) and in age-matched normal controls. RESULTS: Venous platelet-free plasma 5-HT and ß-TG were almost similar in patients with PAH and healthy controls with only a slight trend toward increased 5-HT levels in patients with PAH. No correlation was found between venous platelet-poor plasma 5-HT and disease severity. There was no association between venous plasma 5-HT and the mean pulmonary artery pressure. CONCLUSIONS: Our data suggest that 5-HT is not significantly elevated in venous platelet-free plasma in patients with PAH and may accordingly not be a useful biomarker in this condition.

Serotonin in blood: assessment of its origin by concomitant determination of ß-thromboglobulin (platelets) and chromogranin A (enterochromaffin cells).

BACKGROUND: Serotonin is produced in enterochromaffin (EC) cells, taken up and stored in platelets and released during platelet activation. Measurement of platelet-poor plasma serotonin is difficult, mainly due to platelet activation during blood sampling. We aimed to establish a method to assess the influence of platelet release upon platelet-poor plasma serotonin measurement by concomitant determination of serotonin, ß-thromboglobulin (ß-TG) and chromogranin A (CgA). METHODS: Blood samples from patients with thrombocytosis, thrombocytopenia and small intestinal neuroendocrine (EC-cell) tumors (SI-NETs) as well as healthy volunteers were analyzed. We also measured serotonin in venous and arterial samples from patients undergoing coronary angiography to evaluate peripheral serotonin metabolism. RESULTS: Serotonin and CgA were significantly higher in patients with SI-NETs compared to all other groups implying EC cell origin of serotonin in patients with SI-NETs. We found that the serotonin concentration was similar in patients with thrombocytosis and thrombocytopenia, whereas plasma ß-TG was higher and lower respectively. A high EDTA concentration in the sampling tubes gave significantly lower serotonin concentrations. Serotonin concentrations did not differ between arterial and venous blood. CONCLUSIONS: Our methodology to measure platelet-poor plasma serotonin was appropriate. Blood platelet numbers did not affect the level of serotonin in contrast to ß-TG.

Diagnostic accuracy of endoscopic ultrasonography in patients with inconclusive magnetic resonance imaging diagnosis of biliopancreatic abnormalities.

AIM: To determine the sensitivity and specificity of endoscopic ultrasonography (EUS) in patients with inconclusive magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP) in pancreatobiliary abnormalities. METHODS: During 10 months, patients with pancreatobiliary diseases referred to endoscopic retrograde cholangiopancreatography (ERCP) because of inconclusive MRI/MRCP diagnosis were scheduled to undergo endoscopic ultrasonography. Patients were divided into four major groups: patients with (i) resectable periampullary neoplasms who were referred to a surgeon, (ii) unresectable periampullary cancer who underwent ERCP for biliary stenting, (iii) bile duct stone who were referred to ERCP for stone extraction, and (iv) normal pancreatobiliary tract. Reference standards for comparison were ERCP, surgery, a biopsy confirming malignancy, or the clinical course during follow up (at least 12 months) in cases without evidences of malignancy. RESULTS: One hundred and seven patients (51 men; mean [SD] age 60.0 [15.5]) were included in the study. Final diagnoses were common bile duct (CBD) stone (n = 24), periampullary neoplasms (n = 46), others (n = 23) and no pathologic findings (n = 14). EUS determined the staging for clinical decision-making in 47 patients with neoplasms which showed that tumors in 34 patients (79.1%) were unresectable (advanced stage). After EUS, 47 patients (43.9%) did not require ERCP. The accuracy of EUS for the diagnosis of CBD stone and periampullary neoplasms were 96.3% and 99.1%, respectively. CONCLUSIONS: EUS is a useful modality in cases of inconclusive MRI/MRCP indicating pancreatobiliary disorders.

Long-term follow-up of common bile duct diameter after endoscopic sphincterotomy in patients with common bile duct stones.

BACKGROUND AND AIMS: To determine the time to normalization of common bile duct (CBD) diameter after endoscopic sphincterotomy and stone extraction in patients with choledocholithiasis. METHODS: Patients with CBD dilation due to choledocholithiasis were enrolled. CBD diameter was measured by transabdominal ultrasonography before, and repeated after one, three, six and twelve months after endoscopic sphincterotomy and stone extraction, until normalization of CBD diameter. RESULTS: Of 115 cases enrolled over a 36-month period, CBD diameter reversed to normal in 71 (61.7%) patients after one month. Of the remaining 44 patients, CBD diameter reversed to normal in 36 patients (including 3 in whom repeat ERCP revealed choledocholithiasis) at the end of three months. CBD diameter had not reversed to normal diameter in 8 (18.2%) patients; none of these patients had symptoms. Two of them had asymptomatic dilated CBD after 6 months with no abnormal liver function tests (LFT); the duct reversed to normal at the last follow-up (month 12). CONCLUSIONS: Asymptomatic CBD dilation may persist in a minority of patients (18% at the end of 3 months) after removal of CBD stones. A dilated CBD can be attributed to retained choledocholithiasis within the first month, if it is associated with symptoms and abnormal LFT.

Prognostic value of endoscopic ultrasound in acute pancreatitis.

BACKGROUND/AIMS: Endoscopic ultrasonography (EUS) is a useful modality to diagnose causes of pancreatitis. The role of EUS for prediction of pancreatitis severity has not been studied. The aim of this study was to identify the utility of EUS in determining the severity of acute pancreatitis (AP). METHODS: All patients diagnosed with pancreatitis consecutively underwent EUS on the 2nd day of their admission. Atlanta criteria were used as the severity index of pancreatitis. RESULTS: During the study period, 114 patients (74 females, 40 males; mean age of 53.03 ± 17.7 years) were enrolled in the study. The most common cause of AP was gallstone (78.9%). According to the Atlanta criteria, pancreatitis was mild in 72 (63.2%) and severe in 42 (36.8%) patients. In univariate analysis, the presence of peripancreatic edema, pancreas inhomogeneity, common bile duct dilation and ascites were associated with severe pancreatitis. In multivariate analysis, only the presence of peripancreatic edema in EUS correlated with the severity of AP according to the Atlanta criteria (sensitivity, specificity and accuracy: 65.8, 75.7 and 72.2%, respectively). CONCLUSION: EUS may be a new useful imaging modality for prediction of severity of AP and may have prognostic significance in the early phase of AP. and IAP.

Endoscopic ultrasonography (EUS) in the localization of insulinoma.

OBJECTIVE: Endoscopic ultrasonography has been accepted as a sensitive modality for preoperative tumor localization in pancreas. We have aimed to determine the performance characteristics of endoscopic ultrasonography in pancreatic insulinoma localization and evaluation of relationship between the tumor size and serum-c peptide level, lowest glucose level and insulin level. METHODS: Patients suspicious to insulinoma according to clinical and laboratory findings were included. Endoscopic ultrasonography was performed and if a tumor was identified, the patient was referred for surgery. RESULTS: A total of 52 patients (24 male and 28 female) with mean age of 42.4 years underwent EUS and 43 patients underwent surgery. In one patient, a tumor was identified both by transabdominal ultrasonography and abdominal CT scan. The overall sensitivity and accuracy of endoscopic ultrasonography for detection of insulinoma was 89.5% and 83.7% respectively. The sensitivity of endoscopic ultrasonography for detection of lesions in pancreatic head, body and tail was 92.6%, 78.9%, and 40.0%, respectively. There was no relationship between c-peptide, lowest blood glucose, insulin blood levels and tumor size in surgery. CONCLUSION: EUS is an accurate method for detection of insulinoma. The accuracy depends on the location of the tumor and is greatest for tumors in the pancreatic head.