This is a systematical report on the potential health risk of heavy metals from the leather industries in Pakistan based on multiple biological matrices of the exposed workers and indoor dust ...samples. The adverse impacts of heavy metals on the oxidative enzyme and their risks to workers' health were also explored. Our results indicated that the level of Cr in indoor industrial dust was more than twice, compared to the background household dust. Blood, urine and hair samples of exposed workers showed significantly high concentrations of heavy metals, compared to those in the control group. Superoxide dismutase (SOD) level in the blood samples expressed significant positive correlation with Cr and Ni. Total hazard quotients (HQs)/hazard index (HI) were >1, and Cr (VI) exhibited higher cancer risks than that of Cd in the exposed workers. In addition, the PCA-MLR analysis confirmed that the industrial sections; cutting, shivering/crusting, and stitching were the principal contributors of heavy metals in the biological entities of the workers. Taken together, our results highlighted the occupationally exposed groups would likely to experience the potential health risks due to excessive exposure to the heavy metals from the leather industries.
Cancer Associated Macrophage-Like cells (CAMLs) are polynucleated circulating stromal cells found in the bloodstream of numerous solid-tumor malignancies. Variations within CAML size have been ...associated with poorer progression free survival (PFS) and overall survival (OS) in a variety of cancers; however, no study has evaluated their clinical significance in esophageal cancer (EC).
To examine this significance, we ran a 2 year prospective pilot study consisting of newly diagnosed stage I-III EC patients (n = 32) receiving chemoradiotherapy (CRT). CAML sizes were sequentially monitored prior to CRT (BL), ~ 2 weeks into treatment (T1), and at the first available sample after the completion of CRT (T2).
We found CAMLs in 88% (n = 28/32) of all patient samples throughout the trial, with a sensitivity of 76% (n = 22/29) in pre-treatment screening samples. Improved 2 year PFS and OS was found in patients with CAMLs < 50 μm by the completion of CRT over patients with CAMLs ≥ 50 μm; PFS (HR = 12.0, 95% CI = 2.7-54.1, p = 0.004) and OS (HR = 9.0, 95%CI = 1.9-43.5, p = 0.019).
Tracking CAML sizes throughout CRT as a minimally invasive biomarker may serve as a prognostic tool in mapping EC progression, and further studies are warranted to determine if presence of these cells prior to treatment suggest diagnostic value for at-risk populations.
Tumor necrosis factor α (TNF-α) has been demonstrated to be a therapeutic target for autoimmune diseases. However, this biological therapy exhibits some inevitable disadvantages, such as risk of ...infection. Thus, small-molecule alternatives by targeting TNF-α production signaling pathway are still in demand. Herein, we describe the design, synthesis, and structure–activity relationships of 3-aryindanone compounds regarding their modulation of TNF-α production. Among them, ( R )-STU104 exhibited the most potent inhibitory activity on TNF-α production, which suppressed the TAK1/MKK3/p38/MnK1/MK2/elF4E signal pathways through binding with MKK3 and disrupting the TAK1 phosphorylating MKK3. As a result, ( R )-STU104 demonstrated remarkable dose–effect relationships on both acute and chronic mouse UC models. In addition to its good pharmacokinetic (PK) and safety profile, ( R )-STU104 showed better anti-UC efficacy in vivo at 10 mg/kg/d than mesalazine at the dose of 50 mg/kg/d. These results suggested that TAK1–MKK3 interaction inhibitors could be potentially utilized for the treatment of UC.
An outcome of considerable concern among breast cancer survivors is the development of second primary breast cancer. However, evidence regarding how potentially modifiable lifestyle factors modulate ...second breast cancer risk is limited. We evaluated the relationships between obesity, alcohol consumption, and smoking on risk of second primary invasive contralateral breast cancer among breast cancer survivors.
Utilizing a population-based nested case-control study design, we enrolled 365 patients diagnosed with an estrogen receptor-positive (ER+) first primary invasive breast cancer and a second primary contralateral invasive breast cancer, and 726 matched controls diagnosed with only an ER+ first primary invasive breast cancer. Obesity, alcohol use, and smoking data were ascertained from medical record reviews and participant interviews. Using conditional logistic regression we evaluated associations between these three exposures and second primary contralateral breast cancer risk.
Obesity, consumption of >or= 7 alcoholic beverages per week, and current smoking were all positively related to risk of contralateral breast cancer (odds ratio OR, 1.4; 95% CI, 1.0 to 2.1; OR, 1.9; 95% CI, 1.1 to 3.2; and OR, 2.2; 95% CI, 1.2 to 4.0, respectively). Compared with women who consumed fewer than seven alcoholic beverages per week and were never or former smokers, women who consumed >or= 7 drinks per week and were current smokers had a 7.2-fold (95% CI, 1.9 to 26.5) elevated risk of contralateral breast cancer.
Our population-based study adds to the limited available literature and suggests that obesity, smoking, and alcohol consumption influence contralateral breast cancer risk, affording breast cancer survivors three means of potentially reducing this risk.
Purpose
Controversy exists regarding the potential relationship between antidepressant use and risk of breast cancer. No previous studies have evaluated the relationship between antidepressant use ...after diagnosis of ductal carcinoma in situ (DCIS) and risk of a subsequent breast cancer restricted to women with a history of DCIS.
Methods
We conducted a population-based, nested case–control study in western Washington State. Cases included 337 women diagnosed with DCIS and a subsequent breast cancer and they were compared to 592 individually matched controls (on age, year of DCIS diagnosis, primary treatment, histology, grade, and disease-free survival time) who were diagnosed with DCIS but not a subsequent breast cancer. Information on antidepressant use after DCIS diagnosis was obtained from comprehensive medical records reviews. Antidepressant use was defined as greater or equal to 3 months of duration.
Results
Antidepressant use after initial DCIS was associated with a 1.4-fold increased risk of a subsequent breast cancer event (adjusted OR 1.41, 95% CI 1.02, 1.95). Similar risks were observed when assessing individual antidepressant classes, however, there was no sufficient power across specific classes of antidepressants.
Conclusions
Antidepressant use after DCIS diagnosis was associated with an increased risk of subsequent breast cancer in women. Further studies are needed to confirm the associations observed.
People with HIV (PWHIV) are at increased risk for osteoporosis and fractures, because of the effects of HIV and inflammation and antiretroviral therapy (ART) initiation as well as traditional risk ...factors. This review from recent literature focuses on sex differences in rates of bone disease, risk of fractures, and effects of ART.
Women with HIV in resource-constrained settings experience bone loss because of the additive effect of initiating TDF-containing ART during pregnancy, lactation, and menopause. Children and adolescents experience lower bone accrual during the pubertal growth years. There has been less focus on bone health in recent trials of ART containing tenofovir alafenamide and/or integrase inhibitors. Very few clinical trials or studies compare sex-specific changes in inflammation, immune activation, response to ART and bone turnover or change in BMD resulting in significant knowledge gaps.
More data is needed to determine changes in prevalence of osteopenia, osteoporosis, and fractures in the era of immediate initiation of ART at high CD4 cell counts and the use of more bone-friendly ART. The long-term effects of ART and low bone mass on fractures in the ageing population of PWHIV is yet to be realized.
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