Recent updates on phthalate exposure and human health: a special focus on liver toxicity and stem cell regeneration

Abstract

Phthalates have been blended in various compositions as plasticizers worldwide for a variety of purposes. Consequently, humans are exposed to a wide spectrum of phthalates that needs to be researched and understood correctly. The goal of this review is to focus on phthalate's internal exposure pathways and possible role of human digestion on liver toxicity. In addition, special focus was made on stem cell therapy in reverting liver toxicity. The known entry of higher molecular weight phthalates is through ingestion while inhalation and dermal pathways are for lower molecular weight phthalates. In human body, certain phthalates are digested through phase 1 (hydrolysis, oxidation) and phase 2 (conjugation) metabolic processes. The phthalates that are made bioavailable through digestion enter the blood stream and reach the liver for further detoxification, and these are excreted via urine and/or feces. Bis(2-ethylhexyl) phthalate (DEHP) is a compound well studied involving human metabolism. Liver plays a pivotal role in humans for detoxification of pollutants. Thus, continuous exposure to phthalates in humans may lead to inhibition of liver detoxifying enzymes and may result in liver dysfunction. The potential of stem cell therapy addressed herewith will revert liver dysfunction and lead to restoration of liver function properly.

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Impact of cadmium on forage kale ( Brassica oleracea var. viridis cv “Prover”) after 3-,10- and 56-day exposure to a Cd-spiked field soil

Abstract

Cadmium (Cd) is a highly toxic element for living organisms and is widespread in metal-contaminated soils. As organisms which can grow up on these polluted areas, plants have some protection mechanisms against Cd issues. Among the plant kingdom, the Brassicaceae family includes species which are known to be able to tolerate and accumulate Cd in their tissues. In this study, Brassica oleracea var. viridis cv "Prover" was exposed to a range of artificially Cd-contaminated soils (from 2.5 up to 20 mg kg⁻¹) during 3, 10, and 56 days and the effects on life traits, photosynthesis activity, antioxidant enzymatic activities were studied. Metal accumulation was quantified, as well as DNA damage, by means of the comet assay and immunodetection of 8-OHdG levels. Globally, B. oleracea was relatively tolerant to those Cd exposures. However, comet assay and detection of 8-OHdG revealed some DNA damage but which are not significant. According to metal accumulation analysis, B. oleracea var. viridis cv Prover could be a good candidate for alternative growing in contaminated areas.

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Carbon dioxide emissions, economic growth, energy use, and urbanization in Saudi Arabia: evidence from the ARDL approach and impulse saturation break tests

Abstract

This study investigates the existence of long-run relationship between CO₂ emissions, economic growth, energy use, and urbanization in Saudi Arabia over the period 1971–2014. The autoregressive distributed lag (ARDL) approach with structural breaks, where structural breaks are identified with the recently impulse saturation break tests, is applied to conduct the analysis. The bounds test result supports the existence of long-run relationship among the variables. The existence of environmental Kuznets curve (EKC) hypothesis has also been tested. The results reveal the non-validity of the EKC hypothesis for Saudi Arabia as the relationship between GDP and pollution is positive in both the short and the long run. Moreover, energy use increases pollution both in short and long run in the country. On the contrary, the results show a negative and significant impact of urbanization on carbon emissions in Saudi Arabia, which means that urban development is not an obstacle to the improvement of environmental quality. Consequently, policy-makers in Saudi Arabia should consider the efficiency enhancement, frugality in energy consumption, and especially increase the share of renewable energies in the total energy mix.

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Summary of expression of SPARC protein in cutaneous vascular neoplasms and mimickers

Publication date: Available online 15 March 2018
Source:Annals of Diagnostic Pathology
Author(s): Shakuntala H. Mauzo, Denái R. Milton, Victor G. Prieto, Carlos A. Torres-Cabala, Wei-Lien Wang, Nitin Chakravarti, Priyadharsini Nagarajan, Michael T. Tetzlaff, Jonathan L. Curry, Doina Ivan, Robert E. Brown, Phyu P. Aung
BackgroundSerum protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein, which regulates cell proliferation and facilitates intracellular transport of albumin bound particles including chemotherapeutic agents such as Nab-paclitaxel/ABI-007. Therefore the presence of SPARC may achieve higher intra-tumoral drug concentration with lower dosage and thus reduce systemic side-effects. Several trials of ABI-007, in melanoma, show promising clinical activity.DesignFifty-four cases of dermal based neoplasms were retrieved including 24 angiosarcomas (AS), 10 hemangiomas, 9 nodular melanomas, 4 Kaposi sarcomas (KS), 3 leiomyosarcomas (LMS), 3 atypical fibroxanthomas (AFX) and 1 spindle cell squamous cell carcinoma (SSCC). SPARC immunohistochemistry (IHC) was performed with a mouse monoclonal antibody.ResultsSPARC expression was detected in a majority of AS (17/24), melanomas (8/9), AFX (3/3), LMS (3/3) and KS (4/4) with some expression in hemangiomas (3/10), while being negative in SSCC (0/1); and was significantly associated with tumor group (p = 0.017). Although a significant difference in overall survival was observed between SPARC expression groups (positive vs. negative) for all patients, there was no significant difference noted among angiosarcoma patients.ConclusionWe have confirmed the presence of SPARC expression in melanoma, KS, LMS and AS and also detected it for the first time in AFX. Since paclitaxel has shown some effectiveness in AS, melanoma and KS, ABI-007 could also be beneficial in these patients.



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Pathology resident perspectives about early autopsy experiences

Publication date: Available online 14 March 2018
Source:Annals of Diagnostic Pathology
Author(s): Richard A. Prayson
The performance of autopsies remains an integral part of residency training in Anatomic Pathology. A number of medical schools no longer require an autopsy experience; therefore, a subset of pathology residents has never seen an autopsy performed prior to commencement of residency training. Although much as been written regarding student's perspectives on their medical school anatomy experiences, practically nothing has been written about resident perspectives on the autopsy experience. Surveys were sent to all Pathology resident trainees (n = 27) in a training program exploring resident perspectives on their early autopsy experiences. Of the 13 residents who completed the survey, ten indicated a discomfort level of 3 or 4 (Likert scale of 1–5 with 1 = no discomfort and 5 = very uncomfortable) associated with their first autopsy; the most commonly cited reasons included discomfort with odors/body fluids (n = 6), fear of making a mistake (n = 5), and uncertainty about what to do (n = 4). Six residents felt it would be worthwhile to engage in a discussion around the first autopsy experience to help process it. In summary, a subset of residents experience discomfort around their first autopsy experience. Sensitivity to and acknowledgement of this discomfort and an opportunity to vet feelings and concerns should be considered as part of Pathology residency education.



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Different effects of immune stimulation on chronic unpredictable mild stress-induced anxiety- and depression-like behaviors depending on timing of stimulation

Publication date: May 2018
Source:International Immunopharmacology, Volume 58
Author(s): Jiangyan Xia, Zhen Lu, Shanwu Feng, Jianjun Yang, Muhuo Ji
Stressful life events are thought to be triggering factors of numerous neuropsychiatric disorders, including anxiety and depression. However, the interactions between chronic unpredictable mild stress (CUMS) and immune stimulation have not been thoroughly investigated. In the present study, we evaluated the effects of lipopolysaccharide (LPS) challenge at different time points on CUMS-induced anxiety- and depression-like behaviors. At 1 day before, 18 or 35 days following the initial of CUMS, mice were intraperitoneally given a single LPS (0.1 mg/kg). Neurobehavioral and biochemical studies were performed at the indicated time points. LPS challenge had different effects on CUMS-induced anxiety- and depression-like behaviors depending on the timing of stimulation. When given 1 day before CUMS, LPS restored brain-derived neurotrophic factor level and reversed anxiety- and depression-like behaviors. When given at 18 days after the initial of CUMS, LPS seemed to promote the immune response and even induce a slight exacerbation of neurobehavioral performance, although the difference did not reach statistical significance. Intriguingly, when given at the end of CUMS, LPS reversed some of the anxiety- and depression-like behavior. Taken together, our study highlights the complex interaction between stress and immune challenge, suggesting therapies that modulate immune responses should be tailored to the immune status of the individual.



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The S Sign: A New Radiographic Tool to Aid in the Diagnosis of Slipped Capital Femoral Epiphysis

Publication date: Available online 15 March 2018
Source:The Journal of Emergency Medicine
Author(s): Eric J. Rebich, Stephanie S. Lee, John A. Schlechter
BackgroundChildren with slipped capital femoral epiphysis (SCFE) are often seen by an array of medical professionals prior to diagnosis. Patients with mild slips, slips with knee pain, or bilateral slips can occasionally present a diagnostic challenge that increases the risk of a delay in diagnosis and associated complications.ObjectivesThis study introduces a new radiographic parameter, which we refer to as the S-sign, and analyzes its diagnostic utility on a frog-leg lateral radiograph.MethodsTwenty observers reviewed the radiographs from 35 patients with SCFE using Klein's line on anteroposterior pelvis radiographs and the S-sign on frog-leg lateral radiographs to diagnose an SCFE. Analysis included diagnostic outcomes and intraobserver and interobserver reliability.ResultsThe S-sign was more accurate at identifying an SCFE compared with Klein's line (92.4% vs. 79.2%, respectively). Sensitivity and specificity was greater for the S-sign compared with Klein's line (89.0% and 95.2% vs. 68.3% and 89.0%, respectively). A combination of the S-sign and Klein's line yielded a sensitivity of 96.5% and a specificity of 85.0%. The combination of tests was more diagnostic for an SCFE, compared with using the Klein's line, which was statistically significant (p < 0.001).ConclusionsWith increased awareness of the S-sign and a usage of the combined test, clinicians can more reliably and accurately diagnose an SCFE. Clinicians are more likely to diagnose an SCFE using the combined test, compared with solely relying on Klein's line, which we found to be statistically significant.



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The biting performance of Homo sapiens and Homo heidelbergensis

Publication date: May 2018
Source:Journal of Human Evolution, Volume 118
Author(s): Ricardo Miguel Godinho, Laura C. Fitton, Viviana Toro-Ibacache, Chris B. Stringer, Rodrigo S. Lacruz, Timothy G. Bromage, Paul O'Higgins
Modern humans have smaller faces relative to Middle and Late Pleistocene members of the genus Homo. While facial reduction and differences in shape have been shown to increase biting efficiency in Homo sapiens relative to these hominins, facial size reduction has also been said to decrease our ability to resist masticatory loads. This study compares crania of Homo heidelbergensis and H. sapiens with respect to mechanical advantages of masticatory muscles, force production efficiency, strains experienced by the cranium and modes of deformation during simulated biting. Analyses utilize X-ray computed tomography (CT) scan-based 3D models of a recent modern human and two H. heidelbergensis. While having muscles of similar cross-sectional area to H. heidelbergensis, our results confirm that the modern human masticatory system is more efficient at converting muscle forces into bite forces. Thus, it can produce higher bite forces than Broken Hill for equal muscle input forces. This difference is the result of alterations in relative in and out-lever arm lengths associated with well-known differences in midfacial prognathism. Apparently at odds with this increased efficiency is the finding that the modern human cranium deforms more, resulting in greater strain magnitudes than Broken Hill when biting at the equivalent tooth. Hence, the facial reduction that characterizes modern humans may not have evolved as a result of selection for force production efficiency. These findings provide further evidence for a degree of uncoupling between form and function in the masticatory system of modern humans. This may reflect the impact of food preparation technologies. These data also support previous suggestions that differences in bite force production efficiency can be considered a spandrel, primarily driven by the midfacial reduction in H. sapiens that occurred for other reasons. Midfacial reduction plausibly resulted in a number of other significant changes in morphology, such as the development of a chin, which has itself been the subject of debate as to whether or not it represents a mechanical adaptation or a spandrel.



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Association of PON1 gene polymorphisms with polycystic ovarian syndrome risk: a meta-analysis of case–control studies

Abstract

Purpose

Evidences showed that paraoxonase 1 (PON1) gene polymorphism has an impact on women's susceptibility to polycystic ovarian syndrome (PCOS) by influencing the expression and activity of PON1. However, the effects of three PON1 polymorphisms (− 108 C>T, L55M and Q192R) on the incidence of PCOS have generated inconsistent results. Here, we conducted a meta-analysis to investigate the association between PON1 polymorphisms and PCOS risk.

Methods

All eligible trials were identified via systematic searches of multiple literature databases. Outcome data were synthesized by using crude odds ratio with 95% confidence interval. Heterogeneity was assessed with the I² test. Publication bias and subgroup analyses were also performed.

Results

A total of 2449 cases and 1977 controls from nine studies were selected for analysis. The pooled results showed a significant association between PCOS risk and PON1 − 108 C/T polymorphism in the following genetic models [allelic, 0.72 (0.56–0.92); homozygote, 0.51 (0.32–0.82); heterozygote, 0.44 (0.25–0.78); and dominant 0.47 (0.29–0.77)]. For the PON1 192 Q/R polymorphism, a significant relationship was found in the allelic model [0.62 (0.41–0.93)] and recessive model [0.61 (0.37–0.98)]. PCOS risk was also linked to PON1 L55M polymorphism in the heterozygote model [0.62 (0.39–0.98)] and dominant model [0.63 (0.41–0.96)].

Conclusions

Our study has shown that PON1 − 108 C/T polymorphism might be associated with increased risk of PCOS under the allelic, homozygote, heterozygote, and dominant models. Additionally, PON1 192 Q/R and L55M polymorphisms were significantly related only in the allelic and recessive model, and in the heterozygote and dominant model, respectively.

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Pembrolizumab in Advanced Gastric and Gastroesophageal Junction Cancer

This single cohort study evaluates the safety and efficacy of pembrolizumab in patients with previously treated advanced gastric or gastroesophageal junction cancer.

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Hepatocellular Carcinoma With Portal Venous Invasion

The growing incidence of hepatocellular carcinoma (HCC) is a major global public health challenge. The mortality rate for HCC is very high, and most available treatment options remain palliative. Early-stage HCC can be treated with curative intent with transplantation, resection, or ablation. Level 1 evidence from randomized clinical trials has demonstrated a survival advantage for transarterial chemoembolization (TACE) vs supportive care for intermediate-stage HCC and for systemic therapy with sorafenib, lenvatinib, regorafenib, and cabozantinib for advanced-stage HCC. Recently, immune checkpoint inhibitors have demonstrated impressive antitumor activity with high response rates in advanced HCC, and phase 3 trials are ongoing to assess survival benefits.

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Incorrect Spelling in Byline

In the Original Investigation titled "Baseline Surveillance in Li-Fraumeni Syndrome Using Whole-Body Magnetic Resonance Imaging: A Meta-analysis," published online August 3, 2017, and in the December 2017 print issue, the surname of Lorenzo Mannelli was spelled incorrectly as Manelli. This article has been corrected online.

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Recurrence in Resected Gastroenteropancreatic Neuroendocrine Tumors

This cohort study examines recurrence outcomes in patients with fully resected gastroenteropancreatic neuroendocrine tumors.

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Transarterial Chemoembolization Plus External Beam Radiotherapy vs Sorafenib in Hepatocellular Carcinoma

This randomized clinical trial evaluates the efficacy and safety of transarterial chemoembolization plus external beam radiotherapy compared with sorafenib in patients with hepatocellular carcinoma and macroscopic vascular invasion.

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Breast Cancer Differences by Race Due to Screening Disparities

To the Editor Black breast cancer patients have the highest breast cancer mortality rate, at least partly because black women are more likely to develop triple-negative breast cancer (TNBC). In addition, while outcomes for estrogen receptor/progesterone receptor–positive breast cancer are generally worse for blacks compared with whites, there are no significant differences in outcomes between blacks and whites for TNBC. Two potential reasons for the overall breast cancer survival gap are (1) disparities in access to care and (2) inherent biological differences. To address the latter, Huo and colleagues recently investigated genetic differences between breast cancers in white and black patients using data from The Cancer Genome Atlas (TCGA). They reported a number of biological differences between black and white breast cancers. Interestingly, most tumor genomic differences between races were explained by subtype. Taking all these past and present data into account, I am not convinced that there are inherent genetic differences between blacks and whites that explain the differences in breast cancer outcomes based on race or ancestry and the proportion of breast cancers that are TNBC. Rather, these differences can be largely explained by disparities in access to care.

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Standard vs Dose-Escalated Radiotherapy in Medium-Risk Prostate Cancer

This randomized clinical trial assesses whether dose-escalated radiation therapy vs standard dose improves survival for men with intermediate-risk prostate cancer.

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Using the Cancer Moonshot to Conquer Cancer Disparities

This Viewpoint describes how the Cancer Moonshot Initiative provides an opportunity to address cancer disparities and inequities and ways to ensure that its goals are achieved.

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A pragmatic randomised controlled trial and economic evaluation of family therapy versus treatment as usual for young people seen after second or subsequent episodes of self-harm: the Self-Harm Intervention – Family Therapy (SHIFT) trial.

Family therapy was not more effective than treatment as usual in reducing young people's repetition of self-harm leading to hospital attendance.

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Community-Based Health Literacy Interventions: Proceedings of a Workshop [Prepublication Draft].

In its landmark report, Health Literacy: A Prescription to End Confusion, the Institute of Medicine noted that there are 90 million adults in the United States with limited health literacy who cannot fully benefit from what the health and health care systems have to offer. Since the release of that report, health literacy has become a vibrant research field that has developed and disseminated a wide range of tools and practices that have helped organizations, ranging in size from large health care systems to individual health care providers and pharmacists, to engage in health literate discussions with and provide health literate materials for patients and family members. Improving the health literacy of organizations can be an important component of addressing the social determinants of health and achieving the triple aim of improving the patient experience, improving the health of populations, and reducing the cost of care. However, the focus on organizations does not address the larger issue of how to improve health literacy across the U.S. population.

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Neuroanatomical connections between kisspeptin neurones and somatostatin neurones in female and male rat hypothalamus: a possible involvement of SSTR1 in kisspeptin release

Abstract

Somatostatin (SST) a neuropeptide involved in the central modulation of several physiological functions, is co-distributed in the same hypothalamic areas as kisspeptin (KP), the most potent secretagogue of the gonadotropin-releasing hormone (GnRH) secretion known to date. As SST infused intracerebroventricularly (icv) evoked a potent inhibition of GnRH release, we explored neuroanatomical relationships between KP and SST populations in male and female rats. For that, intact males and ovariectomised oestradiol-replaced females were killed and their brains processed in order to simultaneously detect KP, SST and synapsin, a marker for synapses. We observed numerous appositions of KP on SST neurones both in female and male arcuate nucleus (ARC) and ventromedial hypothalamus. A large association between SST terminals and KP neurones at the level of the pre-optic area (POA) was also observed in female rats and in a more limited frame in males. Finally, most KP neurones from the ARC showed SST appositions in both sexes. To determine whether SST could affect KP cell activity, we assessed whether SST receptors (SSTR) were present on KP neurones in the ARC. We also looked for the presence of SSTR1 and SSTR2A in the brain of male rats. Brains were processed through a sequential double immunocytochemistry in order to detect KP and SSTR1 or KP and SSTR2A. We observed overlapping distributions of immunoreactive neurones for SSTR1 and KP and counted approximately one third of KP neurones with SSTR1. In contrast, neurones labelled for SSTR2A or KP were often juxtaposed in the ARC and the occurrence of double-labelled neurones was sporadic (<5%). These results suggest that SST action on KP neurones would pass mainly through SSTR1 at the level of the ARC.

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