Combined Effects of Multiple Per- and Polyfluoroalkyl Substances Exposure on Allostatic Load Using Bayesian Kernel Machine Regression.

This study aims to investigate the combined effects of per- and polyfluoroalkyl substances (PFAS) on allostatic load, an index of chronic stress that is linked to several chronic diseases, including cardiovascular disease and cancer. Using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2014, this study examines the relationship between six PFAS variables (PFDE, PFNA, PFOS, PFUA, PFOA, and PFHS) and allostatic load using Bayesian Kernel Machine Regression (BKMR) analysis. The study also investigates the impact of individual and combined PFAS exposure on allostatic load using various exposure-response relationships, such as univariate, bivariate, or multivariate models. The analysis reveals that the combined exposure to PFDE, PFNA, and PFUA had the most significant positive trend with allostatic load when it was modeled as a binary variable, while PFDE, PFOS, and PFNA had the most significant positive trend with allostatic load when modeled as a continuous variable. These findings provide valuable insight into the consequences of cumulative exposure to multiple PFAS on allostatic load, which can help public health practitioners identify the dangers associated with potential combined exposure to select PFAS of interest. In summary, this study highlights the critical role of PFAS exposure in chronic stress-related diseases and emphasizes the need for effective strategies to minimize exposure to these chemicals to reduce the risk of chronic diseases. It underscores the importance of considering the combined effects of PFAS when assessing their impact on human health and offers valuable information for policymakers and regulators to develop strategies to protect public health.

The Association of Combined Per- and Polyfluoroalkyl Substances and Metals with Allostatic Load Using Bayesian Kernel Machine Regression.

Background/Objective: This study aimed to investigate the effect of exposure to per- and polyfluoroalkyl substances (PFAS), a class of organic compounds utilized in commercial and industrial applications, on allostatic load (AL), a measure of chronic stress. PFAS, such as perfluorodecanoic acid (PFDE), perfluorononanoic acid (PFNA), perfluorooctane sulfonic acid (PFOS), perfluoroundecanoic acid (PFUA), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHS), and metals, such as mercury (Hg), barium (Ba), cadmium (Cd), cobalt (Co), cesium (Cs), molybdenum (Mo), lead (Pb), antimony (Sb), thallium (TI), tungsten (W), and uranium (U) were investigated. This research was performed to explore the effects of combined exposure to PFAS and metals on AL, which may be a disease mediator. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2014 were used to conduct this study on persons aged 20 years and older. A cumulative index of 10 biomarkers from the cardiovascular, inflammatory, and metabolic systems was used to calculate AL out of 10. If the overall index was ≥ 3, an individual was considered to be chronically stressed (in a state of AL). In order to assess the dose-response connections between mixtures and outcomes and to limit the effects of multicollinearity and other potential interaction effects between exposures, Bayesian kernel machine regression (BKMR) was used. Results: The most significant positive trend between mixed PFAS and metal exposure and AL was revealed by combined exposure to cesium, molybdenum, PFHS, PFNA, and mercury (posterior inclusion probabilities, PIP = 1, 1, 0.854, 0.824, and 0.807, respectively). Conclusions: Combined exposure to metals and PFAS increases the likelihood of being in a state of AL.

The Association of Per- and Polyfluoroalkyl Substances Serum Levels and Allostatic Load by Country of Birth and the Length of Time in the United States.

Objectives: The aim of this study was to examine the association of per- and polyfluoroalkyl (PFAS) concentrations and allostatic load (AL) by the county of birth and the length of time in the United States of America (U.S.), in a representative sample of U.S. adults. Methods: Data from the 2007−2014 National Health and Nutrition Examination Survey (NHANES) were used in this cross-sectional study on the U.S. adults aged 20 and older. The analysis was stratified by the length of time in the U.S. and by the county of birth. In all, the sample contained those who were US-born (n = 10,264), Mexico-born (n = 4018), other Spanish speaking country-born (n = 2989), and other not−Hispanic speaking country-born (n = 3911). Poisson models were used to assess the differences in AL and PFAS levels depending on country of birth and length of time in the U.S. Results: Estimates indicated that those born in Other non−Spanish speaking counties had the highest PFAS levels among the country of birth category in the database. Regarding length of time in the U.S., those born in Mexico had low PFAS levels when their length of time in the U.S. was short. The Mexico-born category presented the most at-risk high serum PFAS levels, with AL levels increasing by length of time in the U.S. (p-value < 0.001). Conclusion: This study found that PFAS concentrations increased by the length of time residing in the U.S. Those born in other non−Hispanic counties had the highest PFAS levels among all the categories. In general, AL and PFAS levels are mostly associated with the length of time in the U.S., with foreign-born individuals having increased levels of both the longer they stay.

Interaction of Per- and Polyfluoroalkyl Substances and Allostatic Load among Adults in Various Occupations.

Objective: This study sought to assess the associations between occupation, serum concentrations of selected of Per- and Polyfluoroalkyl Substances (PFAS), and chronic physiological stress, as operationalized by Allostatic Load (AL), among adults aged ≥20 years. Methods: To explore the interactions of occupation with PFAS levels and AL, data from the National Health and Nutrition Examination Survey (NHANES) 2007−2014 were used. We performed Poisson regression modeling to evaluate AL's relationships with PFAS concentrations and occupations on weighted data. Results: The results demonstrated that increased AL was positively associated with different occupation groups such as a) Public Administration and b) Arts, Entertainment, and Recreation (p-values 0.018 and 0.002, respectively), and with certain PFAS concentrations (Perfluorooctanoic acid, PFOA, p-value = 0.002). Finally, AL had a strong association with the interaction of some PFAS such as Perfluorobutane sulfonic acid (PFBS) and occupation (AL: PFBS: occupation, p-value < 0.0001), with different association measures existing across varying occupations. Conclusions: Occupation and PFOA seem to be associated with AL. This suggests the need of implementing further strategies to limit the exposure to stressors and PFAS in the work environment to promote longevity among the workforce in the U.S. Finally, policymakers must do more to clearly define standards and regulations in the work environment related to PFAS exposure.

The Association between Multiple Per- and Polyfluoroalkyl Substances' Serum Levels and Allostatic Load.

Background/Objective: This study aimed to explore the association between allostatic load (AL), an index of chronic stress, with nine per- and polyfluoroalkyl substances (PFASs), a group of organic compounds used in commercial and industrial applications. The PFASs explored were perfluorohexane sulfonic acid (PFHS), perfluorodecanoic acid (PFDE), perfluorobutane sulfonic acid (PFBS), perfluoroheptanoic acid (PFHP), perflurododecanoic acid (PFDO), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS). This study was performed to better understand the association between PFASs and AL, which may be a mediator of several diseases. Methods: This study was performed on adults aged 20 and older, using the National Health and Nutrition Examination Survey (NHANES) 2007−2014 data. AL was calculated as a cumulative index of ten biomarkers from the cardiovascular, inflammatory, and metabolic system, which was dichotomized into high risk (assigned a value of 1) or low risk (assigned a value 0) depending on if the index value was ≥3 (chronic physiological stress) or <3 (less stressed). In this study, PFASs and covariates such as age, gender, ethnicity, alcohol consumption, smoking, and physical activity were explored using descriptive statistics and logistic regression modeling. Results: The results indicated that in adults, AL was more elevated in men as compared to women, in those aged ≥60 years, and varied by ethnicity. For instance, non-Hispanic Blacks had higher AL levels (mean of 3.92) compared to other ethnicities. A significant number of the participants tested for PFBS, PFHP, PFDO were below the LOD and thus these PFASs were excluded from the analysis. Our analysis demonstrated multicollinearities between variables such as PFNA, PFOS, and PFOA with variance inflation factor (VIF) values of 6.197, 6.212, and 5.139, respectively. Thus, PFASs were analyzed individually and adjusted for age, gender, ethnicity, physical activity, smoking, and alcohol consumption. The results indicated a statistically significant positive association between AL and most of the PFASs, except PFUA which was not statistically significant with a p value of 0.531. Conclusions: The findings of this study suggest that exposure to PFDE, PFNA, PFOS, PFOA, and PFHS are associated with AL when adjusted for age, gender, ethnicity, alcohol consumption, smoking, and physical activity. Future studies looking to model the effects of these factors together must consider their relationship with each other and choose different analytical approaches.

Dual-controlled broadband terahertz absorber based on graphene and Dirac semimetal.

We proposed a dual-controlled broadband terahertz (THz) absorber based on graphene and Dirac semimetal. Calculated results show that the absorptance over 90% is achieved in the frequency range of 4.79-8.99 THz for both transverse electric (TE) and transverse magnetic (TM) polarizations. Benefiting from the advantage of the dielectric constant of these materials varying with chemical doping or gate voltage, the simulation results exhibit that the absorbance bandwidth can be controlled independently or jointly by varying the Fermi energy of the graphene or Dirac semimetal patterns instead of redesigning the absorbers. Impedance matching theory was introduced to analyze the absorption spectra changing with EF. The bandwidth and absorptivity of the proposed absorber are almost independent of changing the incident angle θ up to 35° and 40° for TE and TM modes, respectively. It works well even at a larger incident angle. Because of the symmetry of the structure, this designed absorber is polarization insensitive and almost the same absorptivity for both polarizations. Furthermore, the physical mechanisms were further disclosed by the electric field distributions. The proposed broadband and dual-controlled absorber may have potential applications in various fields of high-performance terahertz devices.

Complete Ectopia Cordis: A Case Report and Literature Review.

Ectopia cordis is a congenital heart exposure defined as complete or partial protrusion of heart through ventral defect in the thoracoabdominal wall alone or with other viscera in cases of pentalogy of Cantrell. This condition was first described by Haller et al. in 1706; since then many advances have been made. Diagnosis of ectopia cordis is done prenatally in well-equipped health facility by antenatal ultrasound scan so that early diagnosis and management plan can be initiated. The index case was delivered to uneducated rural family and admitted at 3 days of life and survived for seven days, even though most literatures state that majority died within four days even with surgery. So, in view of this, we presented this case report to deliberately draw the attention of paediatrician/obstetrician to the fact that even though this condition is rare, proactive search and diagnosis should be made and early treatment should be instituted, so that such a child may be salvaged.

HbAHP-25, an In-Silico Designed Peptide, Inhibits HIV-1 Entry by Blocking gp120 Binding to CD4 Receptor.

Human Immunodeficiency Virus (HIV-1) poses a serious threat to the developing world and sexual transmission continues to be the major source of new infections. Therefore, the development of molecules, which prevent new HIV-1 infections, is highly warranted. In the present study, a panel of human hemoglobin (Hb)-α subunit derived peptides and their analogues, with an ability to bind gp120, were designed in-silico and their anti-HIV-1 activity was evaluated. Of these peptides, HbAHP-25, an analogue of Hb-α derived peptide, demonstrated significant anti-HIV-1 activity. HbAHP-25 was found to be active against CCR5-tropic HIV-1 strains (ADA5 and BaL) and CXCR4-tropic HIV-1 strains (IIIB and NL4-3). Surface plasmon resonance (SPR) and ELISA revealed direct interaction between HbAHP-25 and HIV-1 envelope protein, gp120. The peptide prevented binding of CD4 to gp120 and blocked subsequent steps leading to entry and/or fusion or both. Anti-HIV activity of HbAHP-25 appeared to be specific as it failed to inhibit the entry of HIV-1 pseudotyped virus (HIV-1 VSV). Further, HbAHP-25 was found to be non-cytotoxic to TZM-bl cells, VK2/E6E7 cells, CEM-GFP cells and PBMCs, even at higher concentrations. Moreover, HbAHP-25 retained its anti-HIV activity in presence of seminal plasma and vaginal fluid. In brief, the study identified HbAHP-25, a novel anti-HIV peptide, which directly interacts with gp120 and thus has a potential to inhibit early stages of HIV-1 infection.

Hemoglobin expression in nonerythroid cells: novel or ubiquitous?

Hemoglobin (Hb) is a major protein involved in transport of oxygen (O2). Red blood cells (RBCs) contain maximum amount of Hb and because of their unique structure and plasticity they transport O2 to various tissues of the body at an optimal concentration. Recently, it has been reported that, apart from RBCs, Hb is also expressed by nonerythroid cells such as epithelial cells of different origin. The cells expressing Hb are from the tissues where maintenance of O2 homeostasis is of paramount importance. Hb expression has been observed in the epithelial cells from human tissues including lungs, neurons, retina, and endometrium. Our group has recently demonstrated that Hb is expressed by the cervicovaginal epithelial cells. We further showed that, apart from maintaining O2 homeostasis, Hb and the peptides derived from it play an indispensable role in the protection of vaginal epithelium by exhibiting antimicrobial activity. In this review, we discuss the significance of Hb expression in vaginal epithelial cells and its role in the recognition of pathogens thereby reducing the risk and/or severity of inflammation and/or infections and the possible mechanism by which Hb exhibits antimicrobial and antioxidative functions.

MicroRNA let-7f: a novel regulator of innate immune response in human endocervical cells.

PROBLEM: Endocervical epithelial cells express pattern recognition receptors (PRRs) that aid in innate immune responses. Mechanisms regulating signaling of PRRs are poorly understood. METHODS OF STUDY: Endocervical cells (End1/E6E7) were treated with ligands of TLR9 and RIG-I once or after pre-stimulation with same ligand. Cytokine responses were determined by ELISA. Differential gene expression was analyzed by microarray. Differentially expressed genes were validated by qPCR /Western blot. Role of let-7f was studied by inhibition and over-expression studies using commercial inhibitors and let-7f encoding plasmids, respectively. RESULTS: Single stimulation of cells with TLR9 ligand, but not RIG-I ligand, induced tolerance to subsequent challenge to the same ligand. Stimulation with TLR9 decreased let-7f and increased its target Blimp-1. Conversely, RIG-I stimulation increased let-7f and decreased Blimp-1 expression. Inhibition and over-expression revealed let-7f is involved in induction of immune tolerance. CONCLUSION: We identify let-7f as a novel regulator of PRR signaling in endocervical cells.

Frequency of helicobacter pylori in distal oesophageal mucosa of patients with dyspepsia.

BACKGROUND: Helicobacter pylori (H. pylori) is one of the common causes of dyspepsia. The present study was conducted to find the frequency of H. pylori in the distal oesophageal mucosa of patients with dyspepsia. METHODS: This descriptive cross sectional study was conducted in Services Hospital Lahore. History and physical examination was recorded and after informed consent oesophagoduodenoscopy of all the patients with the symptoms of dyspepsia was done. Findings were noted and gastric antral and distal oesophageal biopsies taken simultaneously. Both specimen were preserved in 10% formalin and sent for histopathological examination for the presence of H. pylori. RESULTS: Out of the 116 patients, 16 patients were between ages 16-30, 82 patients were between ages 31-45 years and 18 were over 45 years of age. Thus percentage of subjects between 31-45 years was maximum i.e., 70.68%. Seventy-six (65.5%) of the patientswere male and 40 (34.5%) were females.The H pylori was found in 40 (34.5%) patients in gastric antral biopsy and it was isolated in only 14 (12.1%) patients in distal esophageal biopsies. CONCLUSION: H. pylori positivity was low in the distal oesophageal mucosa of patients with dyspepsia despite its presence in gastric mucosa. A close relationship could not be established between H. pylori in the distal oesophagus and gastric antral mucosa in dyspeptic patients. Based on these findings, it seems that there is no significant evidence for an important pathogenic role for H. pylori infection in the development of pathologic dyspepsia and chronic gastroesophageal reflux disease.