Global impact and contributing factors in varicose vein disease development.

Varicose veins are convoluted, expanded, and stretched subcutaneous veins of the lower leg and are the most frequently reported medical condition. This condition has a higher prevalence in Western and developed countries. Inadequacy of the valves results in reflux of blood in the veins of the lower leg. The present study aims to describe the epidemiology and contributing factors (risk factors and pathological factors) in the development of varicose veins disease. PubMed/Medline, Science Direct, Google Scholar, SciFinder, Scopus, and Web of Science databases were explored to include potential research and review articles. Finally, 65 articles were considered appropriate to include in the study. Pain, swelling, heaviness, and tingling of the lower limbs are the most common sign and symptoms caused by varicose veins while in some individuals it is asymptomatic. The Prevalence of varicose veins varies geographically. Currently, it is reported that globally about 2%-73% of the population is affected by varicose veins while the prevalence rate in Pakistan is 16%-20%. Different risk factors associated with the advancement of varicose veins are age, gender, occupation, pregnancy, family history, smoking, BMI and obesity, exercise, genetic factor, and current lifestyle. In varicose veins, some contributory elements may also play an important role in the disease development, incorporating constant venous wall aggravation, hereditary variation, and persistent venous hypertension. This condition has now turned into a curable issue that was previously viewed broadly as less important for treatment, determining the individual's satisfaction. Moreover, the mechanisms behind the risk factors involve diet, physical work, and hormonal contribution. These are more likely to be explored.

Integrative analysis reveals methylenetetrahydrofolate dehydrogenase 1-like as an independent shared diagnostic and prognostic biomarker in five different human cancers.

BACKGROUND: Defects in methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) expression have earlier been examined in only a few human cancers. OBJECTIVES: Multi-omics profiling of MTHFD1L as a shared biomarker in distinct subtypes of human cancers. METHODS: In the current study, for the multi-omics analysis of MTHFD1L in 24 major subtypes of human cancers, a comprehensive in silico approach was adopted to mine different open access online databases including UALCAN, Kaplan-Meier (KM) plotter, LOGpc, GEPIA, Human Protein Atlas (HPA), Gene Expression across Normal and Tumor tissue (GENT2), MEXPRESS, cBioportal, STRING, DAVID, TIMER, and Comparative Toxicogenomics Database (CTD). RESULTS: We noticed that the expression of MTHFD1L was significantly higher in all the analyzed 24 subtypes of human cancers as compared with the normal controls. Moreover, MTHDF1L overexpression was also found to be significantly associated with the reduced overall survival (OS) duration of Bladder urothelial cancer (BLCA), Head and neck cancer (HNSC), Kidney renal papillary cell carcinoma (KIRP), Lung adenocarcinoma (LUAD), and Uterine corpus endometrial carcinoma (UCEC). This implies that MTHFD1L plays a significant role in the development and progression of these cancers. We further noticed that MTHFD1L was also overexpressed in BLCA, HNSC, KIRP, LUAD, and UCEC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of MTHFD1L-associated genes in five diverse pathways. We also explored few interesting correlations between MTHFD1L expression and its promoter methylation, genetic alterations, CNVs, and between CD8+ T immune cells level. CONCLUSION: In conclusion, our results elucidated that MTHFD1L can serve as a shared diagnostic and prognostic biomarker in BLCA, HNSC, KIRP, LUAD, and UCEC patients of different clinicopathological features.

Multi-Omics Analysis Identified TMED2 as a Shared Potential Biomarker in Six Subtypes of Human Cancer.

INTRODUCTION: Cancer is one of the most common malignancies and the leading cause of death worldwide. As a member of the transmembrane emp24 domain (Tmed)/p24 family of proteins, TMED2 expression variations have been documented earlier in only a few subtypes of human cancers, and the multi-omics profiling of TMED2 as a shared biomarker in different other subtypes of human cancers remains to be uncovered. METHODS: In the current study, TMED2 multi-omics analysis in 24 major subtypes of human cancer was performed using different authentic online databases and bioinformatics analysis including UALCAN, Kaplan-Meier (KM) plotter, Human Protein Atlas (HPA), GENT2, MEXPRESS, cBioportal, STRING, DAVID, TIMER, and CTD. RESULTS: In general, the TMED2 expression in 24 major subtypes of human cancers was higher relative to normal controls and was also strongly associated with the lower overall survival (OS) and relapse-free survival (RFS) duration of CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients. This implies that TMED2 plays a significant role in the development and progression of these cancers. Furthermore, the TMED2 overexpression was also correlated with different clinicopathological features of CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients. TMED2-associated genes network was involved in 3 diverse pathways, and finally, few stronger correlations were also explored between TMED2 expression and its promoter methylation level, genetic alterations, and CD8+ T immune cells level. CONCLUSION: In conclusion, via this in silico study, we have elucidated that TMED2 can serve as a shared diagnostic and prognostic biomarker in CESC, ESCA, HNSC, KIRC, LIHC, and LUAD patients of different clinicopathological features but, further in vitro and in vivo research should be carried out to confirm these findings.

CTHRC1 expression is a novel shared diagnostic and prognostic biomarker of survival in six different human cancer subtypes.

According to the previous reports, the collagen triple helix repeat containing 1 (CTHRC1) causes tumorigenesis by modulating the tumor microenvironment, however, the evidence is limited to a few human cancer subtypes. In the current study, we analyzed and validated the CTHRC1 expression variations in 24 different human cancer tissues paired with normal tissues using publically available databases. We observed that CTHRC1 was overexpressed in all the 24 major subtypes of human cancers and its overexpression was significantly associated with the reduced overall survival (OS) duration of head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), Lung adenocarcinoma (LUAD), stomach adenocarcinoma (STAD), and Uterine corpus endometrial carcinoma (UCEC). This implies that CTHRC1 plays a significant role in the development and progression of these cancers. We further noticed that CTHRC1 was also overexpressed in HNSC, KIRC, LIHC, LUAD, STAD, and UCEC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of CTHRC1 associated genes in seven diverse pathways. We also explored few interesting correlations between CTHRC1 expression and promoter methylation, genetic alterations, CNVs, CD8+ T immune cells infiltration, and tumor purity. In conclusion, CTHRC1 can serve as a shared diagnostic and prognostic biomarker in HNSC, KIRC, LIHC, LUAD, STAD, and UCEC patients of different clinicopathological features.

An overview on radiometric assessment and excess lifetime cancer risk of soil in Pakistan by using High Purity Germanium (HPGe) detector.

OBJECTIVES: The aim of this study is to compare the natural radioactivity and excess life time cancer risk (ELCR) factor of soil in different regions of Pakistan during last decade. Soil contains various elements and compounds including naturally occurring radioactive elements (238U, 232Th, 40K and 137Cs). Human being, animals and plants are in health risk by contaminations of natural radioactivity in soil and environmental radiometric pollution. Transferring of large amount of the natural radioactive elements in human body by nutrients may cause carcinogenic effects in human body. Pakistani soil has six types as Indus Basin Soil, Bongar Soil, Khaddar Soil, Indus delta soil, Mountainous soil and Sandy Desert Soil. In some northern region of Pakistan, naturally occurring radioactive rocks like uranuium-238 and iridium concentrations present in Gharwandi, Aram, Kingri S, Vitakri Fort Munro, Dera Bugti, Kohlu and Sibbi districts. METHODS: In this reviewed data, gamma rays spectroscopy used to determine the concentrations of 238U, 232Th and 40K with the help of High Purity Germanium (HPGe) detectors. Only the data of HPGe detector collected because of comparisons of different regions of Pakistan. RESULTS AND CONCLUSIONS: Mostly, different gamma rays energy peaks of relevant daughter radionuclides of radioactive element were used such as the energy peak lines of daughter radionuclides 214Pb (295.21 and 352 KeV) and 214Bi (609 and 1,120 KeV) used for calculating the 226Ra concentration in soil. In the recent study, it is concluded that average values of concentrations of natural radioactivity in soil in central and north regions of Pakistan are higher than permissible limit but found permissible range in south region of Pakistan. Mean values of ELCR factor were found higher, equal and lower in central, north and south regions than permissible limit, respectively. Generally, no serious health hazard due to natural radioactivity in soil were found.

An overview on the concentration of radioactive elements and physiochemical analysis of soil and water in Iraq.

In the last decade, radiation physics brought about a revolution in health science by improving scientific equipment and useful methodologies for measurement. Human beings are affected by ionizing radiations that radiate from radioactive elements. The quantity of radioactive elements is different inside and outside the earth's surface. Soil and water are exigencies of human lives which are contaminated by radioactive elements. These radioactive elements enter into the human body through drinking, eating and breathing. On reaching hazardous limits in the human body, these radioactive elements cause stomach cancer, lung cancer and leukemia. Measurement of radioactive elements in soil and water is helpful in monitoring the health issues caused by exposure to these elements. In Iraq, numerous studies about natural radioactivity, radon concentration and physiochemical parameters have been conducted by different researchers, of which most of the studies were conducted in Barsa, Nasirya, Najaf, Karbala, Baghdad, Balad, Kirkuk, Erbil, Mosul and Dohuk cities. This article aims to review and compile the studies conducted in these cities of Iraq from 2011 to 2019. In most articles, high-purity germanium (HPGe), RAD7 and CR-39 detectors are used for radioactivity and radon measurement. These cities are located in the low-high folded and Mesopotamian zones. From this study, it can be concluded that radon concentration in soil and water was greater in the Mesopotamian and lower in the low-high folded zones. Higher concentrations of natural radioactivity in water and soil were found in the low-high folded zone in Iraq. However, most of the conducted studies show that concentrations of radon and natural radioactivity are above the permissible limits recommended by the International Commission on Radiological Protection (ICRP) and World Health Organization (WHO). The values of physiochemical parameters were found to be greater in the Mesopotamian zone, but overall they are not above the permissible limits.

Dosimetric, Radiobiological and Secondary Cancer Risk Evaluation in Head-and-Neck Three-dimensional Conformal Radiation Therapy, Intensity-Modulated Radiation Therapy, and Volumetric Modulated Arc Therapy: A Phantom Study.

This analysis estimated secondary cancer risks after volumetric modulated arc therapy (VMAT) and compared those risks to the risks associated with other modalities of head-and-neck (H&N) radiotherapy. Images of H&N anthropomorphic phantom were acquired with a computed tomography scanner and exported via digital imaging and communications in medicine (DICOM) standards to a treatment planning system. Treatment plans were performed using a VMAT dual-arc technique, a nine-field intensity-modulated radiation therapy (IMRT) technique, and a four-field three-dimensional conformal therapy (3DCRT) technique. The prescription dose was 66.0 Gy for all three techniques, but to accommodate the range of dosimeter responses, we delivered a single dose of 6.60 Gy to the isocenter. The lifetime risk for secondary cancers was estimated according to National Council on Radiation Protection and Measurements (NCRP) Report 116. VMAT delivered the lowest maximum doses to esophagus (23 Gy), and normal brain (40 Gy). In comparison, maximum doses for 3DCRT were 74% and 40%, higher than those for VMAT for the esophagus, and normal brain, respectively. The normal tissue complication probability and equivalent uniform dose for the brain (2.1%, 0.9%, 0.8% and 3.8 Gy, 2.6 Gy, 2.3 Gy) and esophagus (4.2%, 0.7%, 0.4% and 3.7 Gy, 2.2 Gy, 1.8 Gy) were calculated for the 3DCRT, IMRT and VMAT respectively. Fractional esophagus OAR volumes receiving more than 20 Gy were 3.6% for VMAT, 23.6% for IMRT, and 100% for 3DCRT. The calculations for mean doses, NTCP, EUD and OAR volumes suggest that the risk of secondary cancer induction after VMAT is lower than after IMRT and 3DCRT.

High-dose chemotherapy and peripheral hematopoietic stem cell transplantation in relapsed/refractory Hodgkin's lymphoma.

PURPOSE: High-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) is used to treat patients with relapsed Hodgkin's lymphoma. In this retrospective study we report our experience with patients who underwent HDCT and ASCT. METHODS: All patients ≥15 years old with relapsed/refractory Hodgkin's lymphoma who underwent HDCT and ASCT between June 2001 and December 2013 were included. RESULTS: Fifty-four patients were identified. Median age at transplant was 22 years (range 15-49 years); 26 were men and 28 were women. Forty-eight patients (89%) underwent HDCT and ASCT after achieving a radiological response to salvage chemotherapy. The rate of radiological complete response to salvage chemotherapy was 13% and reached 50% within 3 months of ASCT in assessable patients. After a median follow-up of 25 months, 31 patients (57%) were still alive with no evidence of relapse or progression. Median event-free survival (EFS) was 24 months (95% CI 8.7-39.3) and 3-year EFS was 56%. Median overall survival (OS) was not reached and 3-year OS was 82.5%. Bulky mediastinal disease at relapse, hemoglobin level, and number of salvage regimens did not significantly impact EFS in univariate and multivariate analyses. After transplantation there was a trend towards longer EFS (30 vs. 24 months; p = 0.36) in patients with a longer time from the end of first-line treatment until relapse (≥12 vs. <12 months). The 100-day transplant-related mortality was 5.5%. CONCLUSIONS: HDCT and ASCT for relapsed/refractory Hodgkin's lymphoma is safe. Our findings are consistent with published phase III results. Longer follow-up is warranted.

Evaluations of secondary cancer risk in spine radiotherapy using 3DCRT, IMRT, and VMAT: A phantom study.

This study evaluated the secondary cancer risk from volumetric-modulated arc therapy (VMAT) for spine radiotherapy compared with intensity-modulated radiotherapy (IMRT) and 3-dimensional conformal radiotherapy (3DCRT). Computed tomography images of an Radiological Physics Center spine anthropomorphic phantom were exported to a treatment planning system (Pinnacle(3), version 9.4). Radiation treatment plans for spine were prepared using VMAT (dual-arc), 7-field IMRT (beam angles: 110°, 130°, 150°, 180°, 210°, 230°, and 250°), and 4-field 3DCRT technique. The mean and maximum doses, dose-volume histograms, and volumes receiving more than 2 and 4Gy to organs at risk (OARs) were calculated and compared. The lifetime risk for secondary cancers was estimated according to the National Cancer Registry Programme Report 116. VMAT delivered the lowest maximum dose to the esophagus (4.03Gy), bone (8.11Gy), heart (2.11Gy), spinal cord (6.45Gy), and whole lung (5.66Gy) as compared with other techniques (IMRT and 3DCRT). The volumes of OAR (esophagus) receiving more than 4Gy were 0% for VMAT, 27.06% for IMRT, and up to 32.35% for 3DCRT. The estimated risk for secondary cancer in the respective OAR is considerably lower in VMAT compared with other techniques. The results of maximum doses and volumes of OARs suggest that the risk of secondary cancer induction for the spine in VMAT is lower than IMRT and 3DCRT, whereas VMAT has the best target coverage compared with the other techniques.

Medicinal plants combating against cancer--a green anticancer approach.

Cancer is the most deadly disease that causes the serious health problems, physical disabilities, mortalities, and morbidities around the world. It is the second leading cause of death all over the world. Although great advancement have been made in the treatment of cancer progression, still significant deficiencies and room for improvement remain. Chemotherapy produced a number of undesired and toxic side effects. Natural therapies, such as the use of plant-derived products in the treatment of cancer, may reduce adverse and toxic side effects. However, many plants exist that have shown very promising anticancer activities in vitro and in vivo but their active anticancer principle have yet to be evaluated. Combined efforts of botanist, pharmacologist and chemists are required to find new lead anticancer constituent to fight disease. This review will help researchers in the finding of new bioactive molecules as it will focus on various plants evaluated for anticancer properties in vitro and in vivo.

Prevalence, risk factors and disease knowledge of breast cancer in Pakistan.

Breast cancer is the most common cancer in females all over the world with approximately one million new cases each year as well as one of second leading causes of death among females. In Pakistan, the most frequently diagnosed cancer among females is also breast cancer, accounting for nearly one in nine female patients. Its incidence in Pakistan is 2.5 times higher than that in neighboring countries like Iran and India. The risk factors associated with breast cancer are age, family history, early menarche, intake of combined estrogen and progestin menopausal hormones, alcohol consumption, physical inactivity, low socioeconomic status and lack of awareness regarding the disease. This mini-review article aims to provide awareness about breast cancer as well as an updated knowledge about the prevalence, risk factors and disease knowledge of breast cancer in Pakistan.