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1.
J Pharmacopuncture ; 26(1): 94-98, 2023 Mar 31.
Article En | MEDLINE | ID: mdl-37007287

A forty-three-year-old male patient was diagnosed with an acute abscess in the dorsum of the right hand. On the 5th day of conventional pharmacological therapy the patient was still suffering, and was referred to the Outpatient department (OPD) to evacuate and drain the abscess and treat the edema around the area with Hijama (wet cupping therapy, WCT). The hand abscess was successfully cured within a week using an integrative approach of wet cupping therapy together with conventional drug therapy.

2.
Eur Arch Otorhinolaryngol ; 278(3): 833-838, 2021 Mar.
Article En | MEDLINE | ID: mdl-32601920

PURPOSE: Second branchial cleft (BC) sinus/fistula anomalies usually present in children. Their definitive management requires complete tract surgical excision, which necessities accurate extension assessment. Our aim is to propose and describe a novel intraoperative endoscopic technique that can help in evaluating the exact BC anomaly tract extension and overcome disadvantages of currently used methods including imaging and intraoperative methylene blue tract injection. METHODS: The innovative intraoperative endoscopic technique involves performing BC sinus/fistula tract intraluminal endoscopy utilizing miniature 1.3 or 1.6 mm all-in-one semi-rigid endoscopes as well as other accessory equipment currently available and used for sialendoscopy for delineation of exact tract extension followed by a complete standard surgical excision tailored to and assisted by the endoscopic procedure. RESULTS: This novel endoscopic technique was used successfully in five children (age range 8-16 years) presenting with unilateral or bilateral congenital second BC discharging fistula/sinus tracts in the neck. Intraoperative endoscopic assessment took 10-15 min and confirmed the exact tract extension and nature in all patients without complications. Five fistulas and two sinuses were identified and completely surgically resected. No recurrence has been observed after a median follow-up of 29 (range 13-45) months. CONCLUSION: Intraoperative second BC fistula/sinus tract endoscopy could help in accurately assessing anomaly extension, thereby assisting in complete surgical excision. This innovative novel endoscopic technique could avoid disadvantages of currently used methods, especially regarding radiation exposure required for imaging children in whom this anomaly usually presents.


Craniofacial Abnormalities , Fistula , Pharyngeal Diseases , Adolescent , Branchial Region/diagnostic imaging , Branchial Region/surgery , Child , Endoscopy , Fistula/diagnosis , Fistula/surgery , Humans
3.
Inorg Chem ; 59(4): 2594-2603, 2020 Feb 17.
Article En | MEDLINE | ID: mdl-32011880

Glyoxalase I (GlxI) is a member of the glyoxalase system, which is important in cell detoxification and converts hemithioacetals of methylglyoxal (a cytotoxic byproduct of sugar metabolism that may react with DNA or proteins and introduce nucleic acid strand breaks, elevated mutation frequencies, and structural or functional changes of the proteins) and glutathione into d-lactate. GlxI accepts both the S and R enantiomers of hemithioacetal, but converts them to only the S-d enantiomer of lactoylglutathione. Interestingly, the enzyme shows this unusual specificity with a rather symmetric active site (a Zn ion coordinated to two glutamate residues; Glu-99 and Glu-172), making the investigation of its reaction mechanism challenging. Herein, we have performed a series of combined quantum mechanics and molecular mechanics calculations to study the reaction mechanism of GlxI. The substrate can bind to the enzyme in two different modes, depending on the direction of its alcoholic proton (H2; toward Glu-99 or Glu-172). Our results show that the S substrate can react only if H2 is directed toward Glu-99 and the R substrate only if H2 is directed toward Glu-172. In both cases, the reactions lead to the experimentally observed S-d enantiomer of the product. In addition, the results do not show any low-energy paths to the wrong enantiomer of the product from neither the S nor the R substrate. Previous studies have presented several opposing mechanisms for the conversion of R and S enantiomers of the substrate to the correct enantiomer of the product. Our results confirm one of them for the S substrate, but propose a new one for the R substrate.


Glutathione/analogs & derivatives , Lactoylglutathione Lyase/chemistry , Pyruvaldehyde/analogs & derivatives , Density Functional Theory , Humans , Models, Chemical , Protons , Stereoisomerism
4.
J Pediatr Hematol Oncol ; 42(2): 126-130, 2020 03.
Article En | MEDLINE | ID: mdl-31233466

PURPOSE: Infantile hepatic hemangioendothelioma (IHHE) is the most common hepatic vascular tumor in children. We report on the treatment outcome of our large single-center experience of patients with IHHE over a 9-year period. MATERIALS AND METHODS: A retrospective analysis of all IHHE patients treated at the Children Cancer Hospital Egypt from April 2008 through April 2017. RESULTS: In total, 28 patients (18 females, 10 males) were diagnosed with IHHE with a median age at diagnosis of 3 months. The lesions were multifocal (n=12), focal (n=10), and diffuse (n=6). Six (21.4%) patients initially had low T3 and T4. Eleven patients did not receive any treatment, whereas 1 patient underwent resectional surgery. Sixteen patients received drug treatment, 9 of whom responded well to first-line propranolol/prednisolone, whereas 7 patients needed salvage treatment. Twenty-five patients are alive, whereas 3 patients have died. CONCLUSIONS: Overall, patients with IHHE do well, a significant percentage of whom do not require drug therapy, particularly for those with small focal lesions. In patients with multifocal/diffuse disease, there is a high incidence of low T3 and T4 and while some of these patients did well without additional therapy, those with rapidly progressive lesions during treatment may do poorly.


Hemangioendothelioma/mortality , Liver Neoplasms/mortality , Prednisolone/therapeutic use , Propranolol/therapeutic use , Surgical Procedures, Operative/mortality , Antineoplastic Agents, Hormonal/therapeutic use , Combined Modality Therapy , Female , Follow-Up Studies , Hemangioendothelioma/pathology , Hemangioendothelioma/therapy , Humans , Infant , Infant, Newborn , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Male , Retrospective Studies , Survival Rate , Treatment Outcome , Vasodilator Agents/therapeutic use
5.
Int J Womens Health ; 11: 41-47, 2019.
Article En | MEDLINE | ID: mdl-30666167

OBJECTIVE: We aimed to evaluate the effect of different timing of initiation of low-molecular-weight heparin (LMWH) administration on the pregnancy outcomes in women with antiphospholipid syndrome (APS). MATERIALS AND METHODS: A randomized controlled study was conducted on women with obstetrical APS. All participants were randomly divided at documentation of positive pregnancy test into two groups; early initiation group in which LMWH therapy was started once positive pregnancy test was established (in the fifth week of gestation), and later initiation group in which LMWH therapy was started after sonographic confirmation of fetal cardiac pulsation (in the seventh week of gestation). In both groups, LMWH (enoxaparin) was given at a dose of 40 mg/day subcutaneously and the therapy continued until end of pregnancy. The primary outcome measure was ongoing pregnancy rate and the secondary outcome measures were fetal loss, live birth rate, preterm labor before 34 weeks of gestation, intrauterine growth restriction (IUGR), and congenital fetal malformations. RESULTS: Ninety-four women (48 in the early initiation group and 46 in the later initiation group) were subjected to final analysis. The ongoing pregnancy rate was significantly higher in the early initiation group than in the later initiation group (81.2% vs 60.9%; P=0.040). However, both groups were similar in the incidences of fetal loss, preterm labor before 34 weeks of gestation, and IUGR, and live birth rate. No recorded congenital fetal malformations in both groups. CONCLUSION: Early administration of LMWH for pregnant women with obstetrical APS reduces early pregnancy loss, but does not affect the incidence of late obstetrical complications.

6.
J Obstet Gynaecol India ; 68(3): 185-191, 2018 Jun.
Article En | MEDLINE | ID: mdl-29895997

OBJECTIVE: To describe the use of intrauterine inflated Foley's catheter balloon for control of postpartum hemorrhage (PPH) during cesarean section (CS) in cases of abnormally invasive placenta previa aiming to preserve the uterus. METHODS: Retrospective case-control study of the data of women who underwent elective CS on abnormally adherent placenta previa was carried out. Women in whom inflated Foley's catheter balloon was used for control of PPH during CS (n = 40) were compared with a control group of women who underwent elective CS by the same technique but without use of intrauterine catheter balloon (n = 38). RESULTS: Use of intrauterine inflated Foley's catheter balloon significantly reduced the estimated amount of blood loss (P = 0.008), amounts of crystalloids, colloids and packed red blood cells transfusion (P = 0.025, 0.017 and 0.022, respectively), and the need for bilateral internal iliac artery (IIA) ligation (P = 0.016). No significant difference was observed between both groups regarding the use of massive transfusion protocol, performing cesarean hysterectomy, relaparotomy, and admission to the intensive care unit. CONCLUSION: Application of an intrauterine inflated Foley's catheter balloon during CS in cases of morbidly adherent placenta previa helps to control PPH with preservation of the uterus and decreases the need for the invasive IIA ligation.

7.
Can J Physiol Pharmacol ; 94(8): 907-17, 2016 Aug.
Article En | MEDLINE | ID: mdl-27245695

Metabolic syndrome (MS) is a cluster of hypertension, insulin resistance, dyslipidaemia, and hyperuricemia. This study was designed to assess the effect of telmisartan and pioglitazone on high fructose induced MS. Thirty-five male albino rats were classified into 5 groups: A, normal diet; B, high-fructose diet (HFD) subdivided into B1 (HFD only), B2 (telmisartan, 5 mg/kg), B3 (pioglitazone, 10 mg/kg), and B4 (telmisartan + pioglitazone). Administration of the drugs was started after the rats had been on HFD for 4 weeks and continued for 4 weeks. Body mass (BM), blood pressure (BP), uric acid (UA), total cholesterol, triglycerides (TG), high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c), blood urea nitrogen (BUN), creatinine, and nitric oxide (NO) were measured and the levels of fasting glucose and fasting insulin were estimated. Compared with group B1, telmisartan treatment significantly decreased BP, BM, serum glucose, insulin, UA, urea, cholesterol, TGA, and LDL and significantly increased HDL, whereas pioglitazone treatment significantly decreased BP, serum glucose, insulin, UA, urea, creatinine, cholesterol, TGA, and LDL and significantly increased HDL. Co-administration of pioglitazone + telmisartan significantly decreased insulin, urea, and creatinine compared with telmisartan alone. Combined telmisartan + pioglitazone allowed better control of BP, hyperglycaemia, insulin resistance, and the amelioration of BM increase that may be associated with pioglitazone treatment.


Benzimidazoles/administration & dosage , Benzoates/administration & dosage , Fructose/toxicity , Hypoglycemic Agents/administration & dosage , Metabolic Syndrome/chemically induced , Metabolic Syndrome/drug therapy , Thiazolidinediones/administration & dosage , Animals , Blood Glucose/drug effects , Blood Glucose/metabolism , Drug Therapy, Combination , Insulin Resistance/physiology , Male , Metabolic Syndrome/metabolism , Pioglitazone , Rats , Rats, Sprague-Dawley , Telmisartan , Treatment Outcome
8.
Ann Saudi Med ; 35(1): 23-30, 2015.
Article En | MEDLINE | ID: mdl-26142934

OBJECTIVES: Preoperative chemoradiation (CRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). The outcomes of preoperative CRT in Saudi patients with LARC have not been widely studied. The study reports long-term outcomes after preoperative CRT followed by curative surgery in Saudi patients with LARC. DESIGN AND SETTINGS: A retrospective, single-institutional study performed in the tertiary care oncology center in Saudi Arabia. MATERIALS AND METHODS: A total of 154 out of 204 patients with LARC were treated with preoperative CRT and followed by surgery at the oncology center between September 2005 and November 2012. Data regarding the response rates, toxicity profile, locoregional control (LRC), distant metastasis control (DMC), overall survival (OS), and disease-free survival (DFS) rates were analyzed. RESULTS: The median age of the study population was 56.6 years (range: 26-89). Predominant clinical stages were IIA (70 patients; 45.4%) and IIIB (49 patients; 31.8%). Majority of patients (79.8%) underwent a complete total mesorectal excision (TME). Complete pathological response (ypT0N0) was seen in 26 patients (16.8%). At 5 years, locoregional recurrence (LR) was reported in 12 patients (7.8%), and distant metastases were noted in 33 patients (21.4%). The 5-year cumulative LRC, DMC, OS, and DFS rates were 91%, 71.3%, 78%, and 64.8%, respectively. Stage, nodal status, circumferential margins, ypT0N0, and adjuvant chemotherapy were found to be important prognostic factors for DFS. CONCLUSION: The results of preoperative CRT followed by surgery and adjuvant chemotherapy in Saudi population are comparable with international data.


Carcinoma/therapy , Chemoradiotherapy, Adjuvant/mortality , Rectal Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/pathology , Chemotherapy, Adjuvant , Combined Modality Therapy/statistics & numerical data , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/epidemiology , Neoplasm Staging , Rectal Neoplasms/pathology , Rectum/surgery , Retrospective Studies , Saudi Arabia , Treatment Outcome
9.
Anticancer Agents Med Chem ; 15(4): 517-26, 2015.
Article En | MEDLINE | ID: mdl-25929576

A series of N-aryl derivatives of pyrrole and its related derivatives of fused form (namely; tetrahydroindole and dihydroindenopyrroles) were prepared in fair to good yields. The newly synthesized compounds were confirmed using IR, (1)H NMR, Mass spectral and elemental analysis. Tetrahydrobenzo[b] pyrroles Ia-d, 1,4-dihydroindeno[1,2-b]pyrroles IIa,b and pyrroles IIIa-c,e were evaluated for anticancer activity, coinciding with the antioxidant activity; using Di-Phenyl Picryl Hydrazyl (DPPH) tests. The cytotoxicity of the tested compounds (at a concentration of 100 and 200 µg /mL) was performed against HepG-2 and EACC cell lines. Compounds Ib, d and IIa showed promising antioxidant activity beside their anticancer activity. Docking studies were employed to justify the promising anticancer activity of Ib,d and IIa. Protein kinase (PKase)-PDB entry 1FCQ was chosen as target enzyme for this purpose using the MOLSOFT ICM 3.4-8C program. The docking results of the tested compounds went aligned with the respective anticancer assay results.


Antineoplastic Agents/chemistry , Antioxidants/chemistry , Nitriles/chemistry , Pyrimidines/chemistry , Pyrroles/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Antioxidants/chemical synthesis , Antioxidants/pharmacology , Biphenyl Compounds/chemistry , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Molecular Docking Simulation , Nitriles/chemical synthesis , Nitriles/pharmacology , Picrates/chemistry , Protein Kinases/chemistry , Pyrimidines/chemical synthesis , Pyrimidines/pharmacology , Pyrroles/chemical synthesis , Pyrroles/pharmacology , Structure-Activity Relationship
10.
Fetal Diagn Ther ; 38(1): 65-76, 2015.
Article En | MEDLINE | ID: mdl-25999366

OBJECTIVES: Analysis of DNA from small numbers of cells, such as fetal cells in maternal blood, is a major limiting factor for their use in clinical applications. Traditional methods of single-cells whole genome amplification (SCs-WGA) and accurate analysis have been challenging to date. Our purpose was to assess the feasibility of using a few fetal cells to determine fetal sex and major chromosomal abnormalities by quantitative fluorescent polymerase chain reaction (QF-PCR). METHODS: Cultured cells from 26 amniotic fluid samples were used for standard DNA extraction and recovery of 5 fetal cells by laser-capture microdissection. SCs-WGA was performed using the DNA from the microdissected cells. PCR amplification of short tandem repeats specific for chromosomes 13, 18, 21, X and Y was performed on extracted and amplified DNA. Allele dosage and sexing were quantitatively analyzed following separation by capillary electrophoresis. RESULTS: Microsatellite QF-PCR analysis showed high concordance in chromosomal copy number between extracted and amplified DNA when 5 or more cells were used. Results were in concordance with that of conventional cytogenetic analysis. CONCLUSION: Satisfactory genomic coverage can be obtained from SCs-WGA. Clinically, SCs-WGA coupled with QF-PCR can provide a reliable, accurate, rapid and cost-effective method for detection of major fetal chromosome abnormalities.


Aneuploidy , Chromosome Disorders/diagnosis , Prenatal Diagnosis/methods , Chromosomes, Human, Pair 13 , Chromosomes, Human, Pair 18 , Chromosomes, Human, Pair 21 , Chromosomes, Human, X , Chromosomes, Human, Y , Female , Humans , Pregnancy , Real-Time Polymerase Chain Reaction
11.
Prenat Diagn ; 34(9): 878-85, 2014 Sep.
Article En | MEDLINE | ID: mdl-24752776

OBJECTIVE: Physical separation by density gradient centrifugation (DGC) is usually used as an initial step of multistep enrichment protocols for purification of fetal cells (FCs) from maternal blood. Many protocols were designed but no single approach was efficient enough to provide noninvasive prenatal diagnosis. Procedures and methods were difficult to compare because of the nonuniformity of protocols among different groups. Recovery of FCs is jeopardized by their loss during the process of enrichment. Any loss of FCs must be minimized because of the multiplicative effect of each step of the enrichment process. The main objective of this study was to evaluate FC loss caused by DGC. METHODS: Fetal cells were quantified in peripheral blood samples obtained from both euploid and aneuploid pregnancies before and after enrichment by buoyant DGC using Histopaque 1.119 g/mL. RESULTS: Density gradient centrifugation results in major loss of 60% to 80% of rare FCs, which may further complicate subsequent enrichment procedures. Eliminating aggressive manipulations can significantly minimize FC loss. CONCLUSION: Data obtained raise questions about the appropriateness of the DGC step for the enrichment of rare FCs and argues for the use of the alternative nonaggressive version of the procedure presented here or prioritizing other methods of enrichments.


Centrifugation, Density Gradient , Down Syndrome/diagnosis , Maternal Serum Screening Tests/methods , Case-Control Studies , Female , Humans , In Situ Hybridization, Fluorescence , Linear Models , Male , Multivariate Analysis , Pregnancy
12.
Prenat Diagn ; 34(6): 538-46, 2014 Jun.
Article En | MEDLINE | ID: mdl-24578229

OBJECTIVE: Detection of rare fetal cells (FCs) in the maternal circulation could be used for non-invasive prenatal diagnosis. Considering that FCs in maternal blood are present in extremely low frequency, manual scanning is cumbersome, time-consuming, and unsuitable for clinical applications. As an alternative, we optimized a custom-made classifier for automatic detection of FCs. METHODS: Using MetaSystems' automated platform, we developed a robust detection algorithm and validated its efficiency on retrieval of rare XY cells in a pure population of XX cells. Slides were scanned for presence of predefined XY cells after fluorescence in situ hybridization (FISH) and primed in situ labeling (PRINS). Retrieval of FCs was also performed on samples from maternal blood. RESULTS: The efficiency of detection of rare XY cells was 88% using FISH (117/133) in comparison with 78% (53/68) with PRINS. FC frequencies per 1 mL of maternal blood ranged from 3 to 6 FCs in normal pregnancies versus 13 to 21 FCs in Down syndrome pregnancies. CONCLUSION: Automatic scanning was more efficient and consistent than manual scanning for detection of rare FCs and required considerably less operator time. Automatic scanning using FISH is more sensitive than that using PRINS. The study validates automatic scanning retrieval of FCs from maternal blood.


Blood Cells/cytology , Fetus/cytology , Image Processing, Computer-Assisted/methods , Prenatal Diagnosis/methods , Primed In Situ Labeling , Blood Cells/pathology , Electronic Data Processing/methods , Female , Hematologic Tests/methods , Humans , In Situ Hybridization, Fluorescence , Karyotyping/methods , Pregnancy , Sensitivity and Specificity
13.
J Biomed Biotechnol ; 2012: 610856, 2012.
Article En | MEDLINE | ID: mdl-22505816

Fluorescence in situ hybridization (FISH) and manual scanning is a widely used strategy for retrieving rare cellular events such as fetal cells in maternal blood. In order to determine the efficiency of these techniques in detection of rare cells, slides of XX cells with predefined numbers (1-10) of XY cells were prepared. Following FISH hybridization, the slides were scanned blindly for the presence of XY cells by different observers. The average detection efficiency was 84% (125/148). Evaluation of probe hybridization in the missed events showed that 9% (2/23) were not hybridized, 17% (4/23) were poorly hybridized, while the hybridization was adequate for the remaining 74% (17/23). In conclusion, manual scanning is a relatively efficient method to recover rare cellular events, but about 16% of the events are missed; therefore, the number of fetal cells per unit volume of maternal blood has probably been underestimated when using manual scanning.


Blood Cells/cytology , Fetus/cytology , In Situ Hybridization, Fluorescence/methods , Models, Biological , Adult , Blood Cells/chemistry , Female , Humans , In Situ Hybridization, Fluorescence/standards , Male , Pregnancy , Prenatal Diagnosis , Regression Analysis , Reproducibility of Results , Sensitivity and Specificity
14.
Int J Prosthodont ; 24(1): 55-7, 2011.
Article En | MEDLINE | ID: mdl-21210005

The aim of this study was to quantify the frequency of positive radiographic findings in edentulous arches. Panoramic radiographs from 271 patients who were edentulous in one or both arches were evaluated for the presence of retained root fragments, impacted teeth, foreign bodies, radiolucencies, radiopacities, mental foramina at or near the crest of the residual alveolar ridge, and maxillary sinus proximity to the crest of the residual alveolar ridge. One or more of these radiographic observations were found in 51.7% of the examined films. The most frequent finding (30.6%) was close approximation of the maxillary sinus to the crest of the ridge. These results underscore the importance of panoramic examination of edentulous patients in detecting potential problems before complete denture treatment. However, prescribing such an examination in patients seeking replacement dentures requires a thorough patient history and clinical examination.


Jaw, Edentulous/diagnostic imaging , Radiography, Panoramic , Adult , Aged , Aged, 80 and over , Alveolar Process/diagnostic imaging , Dental Arch/diagnostic imaging , Female , Foreign Bodies/diagnostic imaging , Humans , Male , Mandible/diagnostic imaging , Maxilla/diagnostic imaging , Maxillary Sinus/diagnostic imaging , Middle Aged , Molar, Third/diagnostic imaging , Mouth, Edentulous/diagnostic imaging , Osteosclerosis/diagnostic imaging , Periapical Abscess/diagnostic imaging , Radicular Cyst/diagnostic imaging , Tooth Root/diagnostic imaging , Tooth, Impacted/diagnostic imaging
15.
Am Heart J ; 157(1): 118-24, 2009 Jan.
Article En | MEDLINE | ID: mdl-19081407

BACKGROUND: Occupational doses from fluoroscopy-guided interventional procedures are the highest ones registered among medical staff using x-rays. The aim of the present study was to evaluate the order of magnitude of cancer risk caused by professional radiation exposure in modern invasive cardiology practice. METHODS: From the dosimetric Tuscany Health Physics data bank of 2006, we selected dosimetric data of the 26 (7 women, 19 men; age 46 +/- 9 years) workers of the cardiovascular catheterization laboratory with effective dose >2 mSv. Effective dose (E) was expressed in milliSievert, calculated from personal dose equivalent registered by the thermoluminescent dosimeter, at waist or chest, under the apron, according to the recommendations of National Council of Radiation Protection. Lifetime attributable risk of cancer was estimated using the approach of Biological Effects of Ionizing Radiation 2006 report VII. RESULTS: Cardiac catheterization laboratory staff represented 67% of the 6 workers with yearly exposure >6 mSv. Of the 26 workers with 2006 exposure >2 mSv, 15 of them had complete records of at least 10 (up to 25) consecutive years. For these 15 subjects having a more complete lifetime dosimetric history, the median individual effective dose was 46 mSv (interquartile range = 24-64). The median risk of (fatal and nonfatal) cancer (Biological Effects of Ionizing Radiation 2006) was 1 in 192 (interquartile range = 1 in 137-1 in 370). CONCLUSIONS: Cumulative professional radiological exposure is associated with a non-negligible Lifetime attributable risk of cancer for the most exposed contemporary cardiac catheterization laboratory staff.


Cardiac Catheterization , Neoplasms, Radiation-Induced/epidemiology , Neoplasms, Radiation-Induced/etiology , Occupational Diseases/epidemiology , Occupational Diseases/etiology , Occupational Exposure/adverse effects , Female , Humans , Male , Middle Aged , Risk Factors
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