Office Of Health Assessment And Translation Research Articles

Impacts of obesity and obesogenic behaviours on climate change: a systematic review protocol

Background Unbalanced diet and sedentary habits, defined as obesogenic behaviours, are continuously rising in our society, posing serious threats to public health. Indeed, this lifestyle exacerbates pathological conditions, including obesity, metabolic syndrome, cardiovascular risk and cancer. Climate change, increasing temperatures and extreme weather exacerbate obesogenic behaviours. Climate and environment strongly influence lifestyles and can in some way promote obesogenic behaviour. However, little is known about the effects of obesogenic behaviours/obesity on climate change. To address this relation, we planned a systematic review with eventual meta-analysis. Methods Terms related to obesogenic behaviours and climate change will be used to develop the search algorithm which will be applied to four databases: PubMed, Scopus, Web of Science and EBSCO. Title and abstracts will be screened, and two reviewers will review article full-text. The risk of bias of the eligible publications will be assessed using the Office of Health Assessment and Translation (OHAT) tool. Results will be summarized narratively and if possible, meta-analysis will be performed. Discussion Obesogenic behaviours are recognized threats to public health. Instead, the effects that these habits could have on climate change are less recognized and, yet to date, no systematic review has addressed this relation. In this study we will consider the data currently available to deepen our knowledge about the role of human behaviours on greenhouse gases and climate change, and possibly identify strengths on which we can act. The identification of new strategies and guidelines could have a beneficial impact, on a short term, on public health and, on a long term, would mitigate climate changes, that in turn would reduce the incidence of obesity. Registration In accordance with PRISMA guidelines, our systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 29 October 2023 (registration number CRD42023473107).

A systematic review and BMD modeling approach to develop an AOP for humidifier disinfectant-induced pulmonary fibrosis and cell death

Dosimetry modeling and point of departure (POD) estimation using in vitro data are essential for mechanism-based hazard identification and risk assessment. This study aimed to develop a putative adverse outcome pathway (AOP) for humidifier disinfectant (HD) substances used in South Korea through a systematic review and benchmark dose (BMD) modeling. We collected in vitro toxicological studies on HD substances, including polyhexamethylene guanidine hydrochloride (PHMG-HCl), PHMG phosphate (PHMG-p), a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), CMIT, and MIT from scientific databases. A total of 193 sets of dose-response data were extracted from 34 articles reporting in vitro experimental results of HD toxicity. The risk of bias (RoB) in each study was assessed following the office of health assessment and translation (OHAT) guideline. The BMD of each HD substance at different toxicity endpoints was estimated using the US Environmental Protection Agency (EPA) BMD software (BMDS). Interspecies- or interorgan differences or most critical effects in the toxicity of the HD substances were analyzed using a 95% lower confidence limit of the BMD (BMDL). We found a critical molecular event and cells susceptible to each HD substance and constructed an AOP of PHMG-p- or CMIT/MIT-induced damage. Notably, PHMG-p induced ATP depletion at the lowest in vitro concentration, endoplasmic reticulum (ER) stress, epithelial-to-mesenchymal transition (EMT), inflammation, leading to fibrosis. CMIT/MIT enhanced mitochondrial reactive oxygen species (ROS) production, oxidative stress, mitochondrial dysfunction, resulting in cell death. Our approach will increase the current understanding of the effects of HD substances on human health and contribute to evidence-based risk assessment of these compounds.

The effects of radiofrequency exposure on adverse female reproductive outcomes: A systematic review of human observational studies with dose–response meta-analysis

BackgroundTo inform radiofrequency electromagnetic field (RF-EMF) exposure guidelines the World Health Organization (WHO) is bringing together evidence on RF-EMF in relation to health outcomes prioritised for evaluation by experts in this field. Given this, a network of topic experts and methodologists have conducted a series of systematic reviews collecting, assessing, and synthesising data of relevance to these guidelines. Here we present a systematic review of the effect of RF-EMF exposure on adverse pregnancy outcomes in human observational studies which follows the WHO handbook for guideline development and the COSTER conduct guidelines. MethodsWe conducted a broad, sensitive search for potentially relevant records within the following bibliographic databases: MEDLINE; Embase; and the EMF Portal. Grey literature searches were also conducted through relevant databases (including OpenGrey), organisational websites and via consultation of RF-EMF experts. We included quantitative human observational studies on the effect of RF-EMF exposure in adults’ preconception or pregnant women on pre-term birth, small for gestational age (SGA; associated with intrauterine growth restriction), miscarriage, stillbirth, low birth weight (LBW) and congenital anomalies. In blinded duplicate, titles and abstracts then full texts were screened against eligibility criteria. A third reviewer gave input when consensus was not reached. Citation chaining of included studies was completed. Two reviewers’ data extracted and assessed included studies for risk of bias using the Office of Health Assessment and Translation (OHAT) tool. Random effects meta-analyses of the highest versus the lowest exposures and dose–response meta-analysis were conducted as appropriate and plausible. Two reviewers assessed the certainty in each body of evidence using the OHAT GRADE tool. ResultsWe identified 18 studies in this review; eight were general public studies (with the general public as the population of interest) and 10 were occupational studies (with the population of interest specific workers/workforces).General public studies.From pairwise meta-analyses of general public studies, the evidence is very uncertain about the effects of RF-EMF from mobile phone exposure on preterm birth risk (relative risk (RR) 1.14, 95% confidence interval (CI): 0.97–1.34, 95% prediction interval (PI): 0.83–1.57; 4 studies), LBW (RR 1.14, 95% CI: 0.96–1.36, 95% PI: 0.84–1.57; 4 studies) or SGA (RR 1.13, 95% CI: 1.02–1.24, 95% PI: 0.99–1.28; 2 studies) due to very low-certainty evidence. It was not feasible to meta-analyse studies reporting on the effect of RF-EMF from mobile phone exposure on congenital anomalies or miscarriage risk. The reported effects from the studies assessing these outcomes varied and the studies were at some risk of bias. No studies of the general public assessed the impact of RF-EMF exposure on stillbirth.Occupational studies.In occupational studies, based on dose–response meta-analyses, the evidence is very uncertain about the effects of RF-EMF amongst female physiotherapists using shortwave diathermy on miscarriage due to very low-certainty evidence (OR 1.02 95% CI 0.94–1.1; 2 studies). Amongst offspring of female physiotherapists using shortwave diathermy, the evidence is very uncertain about the effects of RF-EMF on the risk of congenital malformations due to very low-certainty evidence (OR 1.4, 95% CI 0.85 to 2.32; 2 studies). From pairwise meta-analyses, the evidence is very uncertain about the effects of RF-EMF on the risk of miscarriage (RR 1.06, 95% CI 0.96 to 1.18; very low-certainty evidence), pre-term births (RR 1.19, 95% CI 0.32 to 4.37; 3 studies; very low-certainty evidence), and low birth weight (RR 2.90, 95% CI: 0.69 to 12.23; 3 studies; very low-certainty evidence). Results for stillbirth and SGA could not be pooled in meta-analyses. The results from the studies reporting these outcomes were inconsistent and the studies were at some risk of bias. DiscussionMost of the evidence identified in this review was from general public studies assessing localised RF-EMF exposure from mobile phone use on female reproductive outcomes. In occupational settings, each study was of heterogenous whole-body RF-EMF exposure from radar, short or microwave diathermy, surveillance and welding equipment and its effect on female reproductive outcomes. Overall, the body of evidence is very uncertain about the effect of RF-EMF exposure on female reproductive outcomes.Further prospective studies conducted with greater rigour (particularly improved accuracy of exposure measurement and using appropriate statistical methods) are required to identify any potential effects of RF-EMF exposure on female reproductive outcomes of interest.

The effects of radiofrequency exposure on male fertility: A systematic review of human observational studies with dose–response meta-analysis

BackgroundThe World Health Organization (WHO) is bringing together evidence on radiofrequency electromagnetic field (RF-EMF) exposure in relation to health outcomes, previously identified as priorities for research and evaluation by experts in the field, to inform exposure guidelines. A suite of systematic reviews have been undertaken by a network of topic experts and methodologists to collect, assess and synthesise data relevant to these guidelines. Following the WHO handbook for guideline development and the COSTER conduct guidelines, we systematically reviewed the evidence on the potential effects of RF-EMF exposure on male fertility in human observational studies. MethodsWe conducted a broad and sensitive search for potentially relevant records within the following bibliographic databases: MEDLINE; Embase; Web of Science and EMF Portal. We also conducted searches of grey literature through relevant databases including OpenGrey, and organisational websites and consulted RF-EMF experts. We hand searched reference lists of included study records and for citations of these studies. We included quantitative human observational studies on the effect of RF-EMF exposure in adult male participants on infertility: sperm concentration; sperm morphology; sperm total motility; sperm progressive motility; total sperm count; and time to pregnancy. Titles and abstracts followed by full texts were screened in blinded duplicate against pre-set eligibility criteria with consensus input from a third reviewer as required. Data extraction from included studies was completed by two reviewers, as was risk of bias assessment using the Office of Health Assessment and Translation (OHAT) tool. We conducted a dose–response meta-analysis as possible and appropriate. Certainty of the evidence was assessed by two reviewers using the OHAT GRADE tool with input from a third reviewer as required. ResultsWe identified nine studies in this review; seven were general public studies (with the general public as the population of interest) and two were occupational studies (with specific workers/workforces as the population of interest).General public studies.Duration of phone use: The evidence is very uncertain surrounding the effects of RF-EMF on sperm concentration (10/6 mL) (MD (mean difference) per hour of daily phone use 1.6 106/mL, 95 % CI −1.7 to 4.9; 3 studies), sperm morphology (MD 0.15 percentage points of deviation of normal forms per hour, 95 % CI −0.21 to 0.51; 3 studies), sperm progressive motility (MD −0.46 percentage points per hour, 95 % CI −1.04 to 0.13; 2 studies) and total sperm count (MD per hour −0.44 106/ejaculate, 95 % CI −2.59 to 1.7; 2 studies) due to very low-certainty evidence. Four additional studies reported on the effect of mobile phone use on sperm motility but were unsuitable for pooling; only one of these studies identified a statistically significant effect. All four studies were at risk of exposure characterisation and selection bias; two of confounding, selective reporting and attrition bias; three of outcome assessment bias and one used an inappropriate statistical method.Position of phone: There may be no or little effect of carrying a mobile phone in the front pocket on sperm concentration, total count, morphology, progressive motility or on time to pregnancy.Of three studies reporting on the effect of mobile phone location on sperm total motility and, or, total motile count, one showed a statistically significant effect. All three studies were at risk of exposure characterisation and selection bias; two of confounding, selective reporting and attrition bias; three of outcome assessment bias and one used inappropriate statistical method.RF-EMF Source: One study indicates there may be little or no effect of computer or other electric device use on sperm concentration, total motility or total count. This study is at probably high risk of exposure characterisation bias and outcome assessment bias.Occupational studies.With only two studies of occupational exposure to RF-EMF and heterogeneity in the population and exposure source (technicians exposed to microwaves or seamen exposed to radar equipment), it was not plausible to statistically pool findings. One study was at probably or definitely high risk of bias across all domains, the other across domains for exposure characterisation bias, outcome assessment bias and confounding. DiscussionThe majority of evidence identified was assessing localised RF-EMF exposure from mobile phone use on male fertility with few studies assessing the impact of phone position. Overall, the evidence identified is very uncertain about the effect of RF-EMF exposure from mobile phones on sperm outcomes. One study assessed the impact of other RF-EMF sources on male fertility amongst the general public and two studies assessed the impact of RF-EMF exposure in occupational cohorts from different sources (radar or microwave) on male fertility.Further prospective studies conducted with greater rigour (in particular, improved accuracy of exposure measurement and appropriate statistical method use) would build the existing evidence base and are required to have greater certainty in any potential effects of RF-EMF on male reproductive outcomes. Prospero Registration: CRD42021265401 (SR3A)

Does pyrethroid exposure lower human semen quality? a systematic review and meta-analysis.

Background: Pyrethroids are natural organic compounds extracted from flowers of pyrethrums and commonly used as domestic and commercial insecticides. Although it is effective in insect and parasitic control, its associated toxicity, including spermotoxicity, remains a challenge globally. Currently, the available reports on the effect of pyrethroids on semen quality are conflicting, hence an evaluation of its detrimental effect is pertinent. This study conducts a detailed systematic review and meta-analysis of the effects of pyrethroids on sperm quality. Materials and methods: The present study was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Using a pre-defined strategic protocol, an internet search was done using combined text words. The criteria for eligibility were selected based on Population, Exposure, Comparator, Outcome, and Study Designs (PECO) framework, and relevant data were collected. Appraisal was done using The Office of Health Assessment and Translation (OHAT) tool for the evaluation of the Risk of Bias and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group guidelines for the certainty of evidence. A quantitative meta-analysis was conducted with the Review Manager (RevMan). Results: Only 12 out of the 4, 050 studies screened were eligible for inclusion in this study. The eligible studies were from China (4), Japan (3), Poland (3), and United States (2). All the eligible studies were cross-sectional. A total of 2, 050 male subjects were included in the meta-analysis. Pyrethroid exposure significantly reduced sperm motility. Region-stratified subgroup analyses revealed that pyrethroid significantly reduced sperm motility among men in Poland and United States, and decreased sperm count among men in Japan. Pyrethroid exposure also reduced sperm concentration among men in Poland but increased sperm concentration among men in the United States. Conclusion: Although the study revealed inconsistent evidence on the detrimental effect of pyrethroids on semen quality, the findings showed that pyrethroids have deleterious potentials on sperm motility, count, and concentration. Studies focusing on the assessment of semen quality in pyrethroid-exposed men, especially at specific varying levels of exposure, and employing prospective cohort studies or controlled cross-sectional designs are recommended.

Effect of TiO2 Abutment Coatings on Peri-Implant Soft Tissue Behavior: A Systematic Review of In Vivo Studies.

Establishing a proper soft tissue adhesion around the implant abutment is essential to prevent microbial invasion, inhibit epithelial downgrowth, and obtain an optimal healing process. This systematic review aims to evaluate the real potential of TiO2 coating on the behavior of peri-implant soft tissue health and maintenance. A specific aim was to evaluate clinically and histologically the effect of TiO2 abutment coating on epithelial and connective tissue attachment. Electronic database searches were conducted from 1990 to 2023 in MEDLINE/PubMed and the Web of Science databases. In total, 15 out of 485 publications were included. Eight studies involved humans, and seven were animal studies. Exposure time ranges from 2 days to 5 years. The peri-implant soft tissue evaluations included clinical assessment (plaque index (PI), peri-implant probing pocket depth (PPD), and bleeding on probing (BoP)), histological as well as histomorphometric analysis. The Office of Health Assessment and Translation (OHAT) Risk of Bias Rating Tool for Human and Animal Studies was used to evaluate the overall quality of the studies included in the review. The results showed some variation but remained within acceptable limits. Within the limitations of this systematic review, the present findings suggest that TiO2 coatings seem to influence soft tissue healing. TiO2-coated abutments with a roughness value between 0.2 and 0.5 μm enhance soft tissue health. Sol-gel-derived TiO2 coatings induced better soft tissue attachment than noncoated machined abutment surfaces. The anodized titanium abutments demonstrate comparable clinical and histological outcomes to conventional machined abutments. However, there was variation among the included studies concerning TiO2 coating characteristics and the measured outcomes used to evaluate the soft tissue response, and therefore, quantitative analysis was not feasible. Long-term in vivo studies with standardized soft tissue analysis and coating surface parameters are necessary before a definitive conclusion can be drawn. OSF Registration No.: 10.17605/OSF.IO/E5RQV.

Impact of organophosphate pesticides exposure on human semen parameters and testosterone: a systematic review and meta-analysis.

Organophosphate (OP) pesticides have been associated with a decline in semen quality, although there are still considerable arguments about the magnitude of the association. This study provides a systematic review and meta-analysis of the impacts of OP pesticides on semen quality and male reproductive hormones. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols. Strategic search was conducted using combined text words as search terms. The eligibility criteria were developed based on Population, Exposure, Comparator, Outcome, and Study designs (PECOS) framework. Relevant data were extracted, risk of bias was evaluated by The Office of Health Assessment and Translation (OHAT) tool, and certainty of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group guidelines. Quantitative meta-analysis was performed by using Review Manager. A total of 766 male subjects (349 exposed to OP pesticides and 417 unexposed controls) were included in the meta-analysis. There was no significant difference in the ejaculate volume, seminal fluid volume, sperm multiple anomaly index, sperm, and leukocytes levels of the OP-exposed subjects compared to the control. In addition, OP pesticides exposure did not significantly affect serum concentrations of FSH, LH, and testosterone in subjects who were exposed to OP pesticides compared to their unexposed counterparts. However, we found a significant reduction in the sperm count, sperm concentration, progressive sperm motility, total sperm motility, and normal sperm morphology of OP pesticides-exposed subjects compared to the unexposed subjects. However, after subtype and sensitivity analyses, exposure to OP pesticides did not reduce sperm count. Also, after sensitivity analysis, OP pesticides exposure did not alter progressive sperm motility. This study demonstrates that OP pesticides exposure reduced sperm count, concentration, total and progressive motility, and normal sperm morphology, possibly via a testosterone-independent mechanism.

The Role of Vitamins in Oral Potentially Malignant Disorders and Oral Cancer: A Systematic Review.

Micronutrients are vital for general and oral health, and their potential anti-cancer properties are documented. We explore beneficial vitamins for oral potentially malignant disorders (OPMDs) and oral cancer (OC), assessing the therapeutic impacts of essential vitamin supplementation. We systematically review evidence on vitamin supplementation's therapeutic effects for OPMDs and OC. Relevant studies were identified through comprehensive searches of MEDLINE, Evidence-Based Medicine, and Web of Science until 16 May 2023. All studies underwent risk of bias using criteria modified from the Office of Health Assessment and Translation (OHAT) tool. We analysed 80 papers. Vitamin K, studied in vitro, shows promising therapeutic potential. Vitamin C, investigated in vivo (animals and humans), demonstrated mixed animal results and generally positive human trial effects. Vitamin A's efficacy varied, with positive monotherapy or adjunct effects. Vitamins B and D showed therapeutic benefits. Oral cancer research was extensive, with a focus on oral lichen planus and oral leukoplakia among the 11 OPMDs. All bias levels were reported in 'selective reporting' and 'performance', except for "definitely high" in the 'selection', 'detection', and 'attrition/exclusion' domains. Evidence of vitamin interventions for OPMDs and OC ranges from mixed to promising. Standardizing the study design and outcomes would enhance future research.

Antimicrobial effect of platelet-rich fibrin: A systematic review of in vitro evidence-based studies.

This systematic review (SR) aimed to evaluate the antimicrobial potential of different types of platelet-rich fibrin (PRF) often used in regenerative treatments. An electronic search was performed in four databases and in Gray literature for articles published until January, 2023. The eligibility criteria comprised in vitro studies that evaluated the antimicrobial effect of different types of PRF. For the analysis of the risk of bias within studies, the modified OHAT (Office of Health Assessment and Translation) tool was used. For the evaluation of the results, a qualitative critical analysis was carried out in the synthesis of the results of the primary studies. Sixteen studies published between 2013 and 2021 were included in this SR. The antimicrobial effects of PRF variations (PRF, injectable PRF [I-PRF], PRF with silver nanoparticles [agNP-PRF], and horizontal PRF [H-PRF]), were analyzed against 16 types of bacteria from the oral, periodontal, and endodontic environments. All types of PRF showed significant antimicrobial action, with the antibacterial efficacy being more expressive than the fungal one. The I-PRF, H-PRF, and agNP-PRF subtypes improve antimicrobial activity. According to the OHAT analysis, no study was classified as having a high risk of bias. Evidence suggests that PRF variations have significant antimicrobial activity, with bacterial action being greater than fungal. Evolutions such as I-PRF, H-PRF, and agNP-PRF improve antimicrobial activity. Future studies analyzing the clinical effect of these platelets are fundamental. This SR was registered in INPLASY under number INPLASY202340016.

Effects of Radiofrequency Electromagnetic Field (RF-EMF) exposure on pregnancy and birth outcomes: A systematic review of experimental studies on non-human mammals

Effects of Radiofrequency Electromagnetic Field (RF-EMF) exposure on pregnancy and birth outcomes: A systematic review of experimental studies on non-human mammals

Ambient temperature and mental health: a systematic review and meta-analysis

Increasing evidence indicates that ambient outdoor temperature could affect mental health, which is especially concerning in the context of climate change. We aimed to comprehensively analyse the current evidence regarding the associations between ambient temperature and mental health outcomes. We did a systematic review and meta-analysis of the evidence regarding associations between ambient outdoor temperature and changes in mental health outcomes. We searched WebOfScience, Embase, PsychINFO, and PubMed for articles published from database origin up to April 7, 2022. Eligible articles were epidemiological, observational studies in humans of all ages, which evaluated real-world responses to ambient outdoor temperature, and had mental health as a documented outcome; studies of manipulated or controlled temperature or those with only physical health outcomes were excluded. All eligible studies were synthesised qualitatively. If three or more studies reported the same or equivalent effect statistics and if they had equivalent exposure, outcome, and metrics, the studies were pooled in a random-effects meta-analysis. The risk of bias for individual studies was assessed using the Newcastle-Ottawa Scale. The quality of evidence across studies was assessed using the Office of Health Assessment and Translation (OHAT) approach. 114 studies were included in the systematic review, of which 19 were suitable for meta-analysis. Three meta-analyses were conducted for suicide outcomes: a 1°C increase in mean monthly temperature was associated with an increase in incidence of 1·5% (95% CI 0·8-2·2, p<0·001; n=1 563 109, seven effects pooled from three studies); a 1°C increase in mean daily temperature was associated with an increase in incidence of 1·7% (0·3-3·0, p=0·014; n=113 523, five effects pooled from five studies); and a 1°C increase in mean monthly temperature was associated with a risk ratio of 1·01 (95% CI 1·00-1·01, p<0·001; n=111 794, six effects pooled from three studies). Three meta-analyses were conducted for hospital attendance or admission for mental illness: heatwaves versus non-heatwave periods were associated with an increase in incidence of 9·7% (95% CI 7·6-11·9, p<0·001; n=362 086, three studies); the risk ratio at the 99th percentile of daily mean temperature compared with the 50th percentile was 1·02 (95% CI 1·01-1·03, p=0·006; n=532 296, three studies); and no significant association was found between a 10°C increase in daily mean temperature and hospital attendance. In a qualitative narrative synthesis, we found that ambient outdoor temperature (including absolute temperatures, temperature variability, and heatwaves) was positively associated with attempted and completed suicides (86 studies), hospital attendance or admission for mental illness (43 studies), and worse outcomes for community mental health and wellbeing (19 studies), but much of the evidence was of low certainty with high heterogeneity. Increased temperature and temperature variability could be associated with increased cases of suicide and suicidal behaviour, hospital attendance or admission for mental illness, and poor community health and wellbeing. Climate change is likely to increase temperature anomalies, variability, and heatwaves as well as average temperatures; as such, health system leaders and policy makers must be adequately prepared and should develop adaptation strategies. More high-quality, standardised research is required to improve our understanding of these effects. None.

Combining Photothermal Therapy with A NanohybridBased Drug Delivery Strategy for Slow-Released Doxorubicin: A Treatment for Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world. Surgical intervention remains the primary treatment option for resectable liver cancer. However, the low curative resection ratio, high metastatic ratio, and risk of recurrence make this treatment less than ideal. Additionally, the choice of liver transplantation is limited by the availability of donors. This literature review aimed to discuss the combination strategy of photothermal therapy and nanohybrid-based chemotherapy delivery, which are expected to address the challenges in HCC treatment. Methods: We conducted literature searches in Pubmed, Scopus, ProQuest, and Google Scholar using combined keywords such as “hepatocellular carcinoma”, “polyethylene glycol”, “doxorubicin”, “mesoporous silica”, “CuS”, “nanoparticle”, and “photothermal therapy”. Based on the assessment of validity and applicability aspects using modified Oxford CEBM (Center for Evidence-Based Management) and OHAT (Office of Health Assessment and Translation) checklist tools for preclinical studies, all the selected studies fulfilled the eligibility criteria. Results: Photothermal therapy promotes necrosis and apoptosis of HCC cells by ‘heating’ the cancer cells. Meanwhile, the chemotherapy agent doxorubicin, modified with mesoporous silica nanohybrids and encapsulated copper sulfate polyethylene glycol (PEG-DOX-MSN-CuS), enhances the efficiency and duration of drug circulation in the blood, reduces drug clearance, and minimizes retention by the reticuloendothelial system. By utilizing near-infrared light induction from photothermal therapy, doxorubicin can be slowly released, leading to significantly improved effectiveness. In vitro studies have demonstrated that this this combination strategy achieves over 90% HCC cell death at a chemotherapy concentration of 80 µg/mL, in conjunction with near-infrared light induction. The optimal release time for doxorubicin was recored at a concise 20 minutes. Conclusions: Given the numerous benefits associated with this combination of strategies, photothermal therapy using PEG-DOX-MSN-CuS holds significant expected to be a promising treatment for HCC.

Maternal pesticide exposure and risk of preterm birth: A systematic review and meta-analysis

BackgroundMaternal pesticide exposure might be associated with adverse pregnancy outcomes through triggering inflammation and oxidative stress and disrupting endocrine functions. Yet the association between prenatal pesticide exposure and risk of preterm birth remains inconclusive. ObjectivesTo conduct a systematic review and meta-analysis of human observational studies using the Office of Health Assessment and Translation (OHAT) framework to explore the association of per ten-fold increase of pesticide concentrations in maternal biological samples during pregnancy with risk of preterm birth and length of gestational age at birth. Data sourceFive English (PubMed, Embase, Cochrane Library, Web of Science and Scopus) and 3 Chinese databases (China national knowledge infrastructure (CNKI), Wanfang Data, and Chinese Biomedical Literature Database (CBM)) were searched till Jan 18th, 2023. Study eligibility criteria, participants, and interventionsTo be included, pesticide exposure should be measured in maternal biological samples during pregnancy and in log-transformed forms. The primary outcome was preterm birth and the secondary outcome was gestational age at birth. Study appraisal, synthesis methods and confidence assessmentQuality of studies was evaluated using OHAT Risk of Bias Tool. Evidence was quantitatively synthesized with Correlated and Hierarchical Effects (CHE) model. The confidence rating in the body of evidence was done using OHAT. ResultsA total of 21 studies reported by 18 papers were included, with 7 studies for preterm birth and 19 for gestational age at birth. The meta-analysis found a ten-fold increase of pesticide concentrations was potentially associated with risk of preterm birth (pooled OR = 1.28; 95%CI: 0.93, 1.78) and shortened gestational age at birth (β = −0.10; 95%CI: −0.21, 0.01). Sampling biospecimens in different trimesters was identified as a potential modifier in the association between pesticide exposure and length of gestational age (F = 2.77, P < 0.05). For studies that collected samples at any time during pregnancy, pesticide exposure was found to be associated with shortened length of gestational age (β = −0.43; 95%CI: −0.81, −0.06). The confidence rating in the body of evidence was “moderate” and “very low” for preterm birth and gestational age at birth, respectively. ConclusionOur result suggested moderate evidence of an association between pesticide exposure and higher risk of preterm birth. Yet more studies are still needed with larger sample size and careful considerations of confounders and accuracy of outcome measurements. Attention is also required on other pesticide compounds in addition to organochlorine and organophosphorus pesticides, and on windows of susceptibility.

Extracellular Vesicle-Based Drug Delivery Systems for Head and Neck Squamous Cell Carcinoma: A Systematic Review.

It is estimated that there are over 890,000 new cases of head and neck squamous cell carcinoma (HNSCC) worldwide each year, accounting for approximately 5% of all cancer cases. Current treatment options for HNSCC often cause significant side effects and functional impairments, thus there is a challenge to discover more acceptable treatment technologies. Extracellular vesicles (EVs) can be utilized for HNSCC treatment in several ways, for example, for drug delivery, immune modulation, as biomarkers for diagnostics, gene therapy, or tumor microenvironment modulation. This systematic review summarizes new knowledge regarding these options. Articles published up to 11 December 2022, were identified by searching the electronic databases PubMed/MEDLINE, Scopus, Web of Science, and Cochrane. Only full-text original research papers written in English were considered eligible for analysis. The quality of studies was assessed using the Office of Health Assessment and Translation (OHAT) Risk of Bias Rating Tool for Human and Animal Studies, modified for the needs of this review. Of 436 identified records, 18 were eligible and included. It is important to note that the use of EVs as a treatment for HNSCC is still in the early stages of research, so we summarized information on challenges such as EV isolation, purification, and standardization of EV-based therapies in HNSCC.

The Plausible Use of Mango (Mangifera indica) Peel Isoquercitrin as Adjuvant Therapy for Colorectal Cancer: Translating Research from Bench to Bedside

A deadly and debilitating disease, colorectal cancer (CRC), is rapidly becoming a significant threat to public health. However, current therapeutic approaches are still hampered by various side effects. Due to its benefits and remarkable apoptotic impact on cancer cells, plant-derived flavonoids now garner interest as candidates for cancer therapy. Isoquercitrin, a flavonoid commonly found in fruit plants, especially mangoes, is notable due to its ability to inhibit cancer development through various mechanisms. This review aims to highlight the use of isoquercitrin extracted from mango peels in inhibiting CRC carcinogenesis. A literature search was done on Pubmed, Proquest, and Google Scholar using inclusion and exclusion criteria, and a narrative review was synthesised using the evidence gathered. Validity assessment was done through the the Office of Health Assessment and Translation (OHAT) and Oxford Center for Evidence-Based Medicine (CEBM) critical assessment tools. Evidence suggested that isoquercitrin is promising as adjuvant therapy in CRC. It may inhibit overaccumulation of cytoplasmic β-catenin and its translocation into the nucleus, thus downregulating the expression of target proto-oncogenes leading to carcinogenesis of colon crypts. Isoquercitrin concentration in mango peel is abundant, 557.7 mg/kg in dried mango peel and 31.0 mg/kg in pure extracts. A pharmacology study approved that a daily intake of 5.4 mg/kgBW of isoquercitrin has an effective anticancer effect. This substance has good oral bioavailability and is well-tolerated but inhibits the metabolising enzymes CYP1A1 and CYP1B1. In conclusion, isoquercitrin is a potential adjuvant in inhibiting CRC growth with minimum costs and side effects.

Long-term exposure to traffic-related air pollution and non-accidental mortality: A systematic review and meta-analysis

BackgroundThe health effects of traffic-related air pollution (TRAP) continue to be of important public health interest across the globe. Following its 2010 review, the Health Effects Institute appointed a new expert Panel to systematically evaluate the epidemiological evidence regarding the associations between long-term exposure to TRAP and selected health outcomes. This paper describes the main findings of the systematic review on non-accidental mortality. MethodsThe Panel used a systematic approach to conduct the review. An extensive search was conducted of literature published between 1980 and 2019. A new exposure framework was developed to determine whether a study was sufficiently specific to TRAP, which included studies beyond the near-roadway environment. We performed random-effects meta-analysis when at least three estimates were available of an association between a specific exposure and outcome. We evaluated confidence in the evidence using a modified Office of Health Assessment and Translation (OHAT) approach, supplemented with a broader narrative synthesis. ResultsThirty-six cohort studies were included. Virtually all studies adjusted for a large number of individual and area-level covariates—including smoking, body mass index, and individual and area-level socioeconomic status—and were judged at a low or moderate risk for bias. Most studies were conducted in North America and Europe, and a few were based in Asia and Australia. The meta-analytic summary estimates for nitrogen dioxide, elemental carbon and fine particulate matter—pollutants with more than 10 studies—were 1.04 (95% CI 1.01, 1.06), 1.02 (1.00, 1.04) and 1.03 (1.01, 1.05) per 10, 1 and 5 µg/m3, respectively. Effect estimates are interpreted as the relative risk of mortality when the exposure differs with the selected increment. The confidence in the evidence for these pollutants was judged as high, because of upgrades for monotonic exposure–response and consistency across populations. The consistent findings across geographical regions, exposure assessment methods and confounder adjustment resulted in a high confidence rating using a narrative approach as well. ConclusionsThe overall confidence in the evidence for a positive association between long-term exposure to TRAP and non-accidental mortality was high.

Association between exposure to light at night (LAN) and sleep problems: A systematic review and meta-analysis of observational studies.

Accumulating evidence have investigated the effects of nighttime light exposure on sleep problems. Nevertheless, the evidence of the relationship between light at night (LAN) and sleep problems remains scarce and inconsistent. Conducted a systematic review and meta-analysis based on observational studies to examine the association between LAN exposure and sleep problems among human subjects. We systematically searched three databases (PubMed, Web of Science, and Embase) to identify potentially eligible studies through May 25, 2022. The risk of bias and the quality of the generated evidence were assessed by two authors using the National Toxicology Program's Office of Health Assessment and Translation (OHAT) risk of bias rating tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guideline. Random-effects model was applied to synthesize the risk estimates across eligible studies. The heterogeneity of included studies was quantified by the statistics of I2. A total of 7 cross-sectional studies comprising 577,932 participants were included. Individuals with higher levels of LAN exposure were associated with a 22 % (Summary Odds Ratio, SOR: 1.22, 95 %CI: 1.13-1.33) increased prevalence of sleep problems. The pooled effect size of indoor LAN exposure (SOR: 1.74, 95%CI: 1.27-2.37) associated with sleep problems was significantly higher than outdoor LAN exposure (SOR: 1.19, 95%CI: 1.11-1.29; P = 0.022). Additionally, dose-response analysis demonstrated that LAN intensity threshold exceeding 5.8 nW/cm2/sr (SOR: 1.04, 95%CI: 1.01-1.07) had a significant effect on sleep problems and the prevalence of sleep problems was increasing with increase in LAN intensity. Overall, our findings support the detrimental effects of LAN exposure on sleep. Maintaining bedroom darkness at night may be a feasible measure to reduce the prevalence of sleep problems. Future longitudinal studies with more advanced LAN assessment methods are required to move the field forward.

The cutaneous effects of blue light from electronic devices: a systematic review with health hazard identification.

The biologic effects of visible light, particularly blue light, on the skin at doses and irradiances representative of sunlight have been established. Recent research studies investigated the effects of blue light (BL) from electronic screen devices; however, it is unclear if the evidence can be generalized to real life. The aim of this systematic review was to evaluate available evidence regarding clinical effects of BL emitted from electronic devices on human skin using the framework established by the Office of Health Assessment and Translation (OHAT). A systematic literature search was conducted by two librarians in Ovid MEDLINE, Embase.com, and Web of Science for relevant articles published from 1946 to March 2022. In vitro and in vivo studies that investigated the effects of BL from electronic devices on skin were included. From the 87 articles gathered from database searches and 1 article identified from citation search, only 9 met the inclusion criteria (6 in vitro and 3 in vivo studies). Human and animal literature with the highest level of evidence ratings were considered with mechanistic data to form one of five human hazard identifications for each outcome category using the OHAT protocol: (1) known, (2) presumed, (3) suspected, (4) not classifiable, or (5) not identified to be a hazard to humans. Literature-based evidence integration did not identify exposure to BL from electronic devices as a hazard to skin pigmentation, redness, yellowness, or melasma exacerbation. Exposure to BL from electronic devices was not classified as a skin photoaging hazard. Low confidence in representative exposure characterization drove high OHAT risk-of-bias ratings for the majority of included studies. While these conclusions hold true for the limited existing data, a larger number of future studies with high-confidence evidence are needed to verify and strengthen hazard identification conclusions.

Data quality evaluation criteria for systematic review of epidemiology studies under the Toxic Substances Control Act (TSCA): refinement through practical application in risk evaluation

BACKGROUND AND AIM: The 2016 Frank R. Lautenberg Chemical Safety for the 21st Century Act and the 2017 Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act (TSCA) require the U.S. Environmental Protection Agency (EPA) to conduct risk evaluations using the best available science and weight of the scientific evidence. Therefore, EPA has developed systematic review methods including data quality evaluation criteria to evaluate scientific studies in specific disciplines including epidemiology. EPA has aimed to refine these criteria for practical application in risk evaluation of high-priority chemicals under TSCA. METHODS: EPA considered the pros and cons of multiple existing systematic review frameworks and guidance documents and drew upon these methodologies to develop data quality evaluation domains, metrics, and criteria for the systematic review of epidemiology studies under TSCA. EPA refined these domains, metrics, and criteria through practical application to add specificity to increase consistency among evaluators and to harmonize with the evaluation of animal toxicology studies under TSCA. RESULTS: EPA adopted aspects of methods including the National Toxicology Program (NTP) Office of Health Assessment and Translation (OHAT) and EPA’s Integrated Risk Information System (IRIS) methods, but also aimed to be consistent with other disciplines and to address TSCA scientific standards. CONCLUSIONS: EPA has further refined data quality evaluation criteria for systematic review of epidemiology studies under TSCA in response to comments from peer reviewers, the public, the National Academies, and the TSCA Science Advisory Committee on Chemicals (SACC). Systematic review of epidemiology studies is a critical component of protecting human health under TSCA. DISCLAIMER: The views expressed in this presentation are solely those of the authors and do not represent the policies of EPA. Mention of trade names or commercial products should not be interpreted as an endorsement by EPA. KEY WORDS: Systematic Review, Data Quality Evaluation

Evidence synthesis of Observational Studies in Environmental Health: Lessons Learned from a Systematic Review on Traffic-Related Air Pollution

Background: There is a long tradition in environmental health of using frameworks for evidence synthesis. Recently, frameworks were developed for evidence synthesis in clinical medicine, including Grading of Recommendations Assessment, Development and Evaluation (GRADE). The US Office of Health Assessment and Translation (OHAT) elaborated a GRADE type protocol for evidence synthesis in environmental health to assess the &amp;#x22;quality in a body of evidence”. Methods: We describe lessons learned in synthesizing evidence from observational studies of environmental health effects, drawing on our experience of applying the OHAT approach in a large systematic review on traffic-related air pollution and health outcomes. Results: We outlined key elements of and suggested improvements to the GRADE/OHAT approach. To maximize what can be learned from observational studies in environmental health, a &amp;#x22;narrative” approach is needed to complement the mechanistic up-and-downgrading of certain factors in the evaluation of the quality of a body of evidence. This &amp;#x22;narrative” approach links more directly to current and widely accepted evidence synthesis frameworks, such as from the US EPA and IARC. We argue that observational studies can offer high confidence evidence in environmental health, where randomized controlled trials are generally not feasible. All relevant studies should be included in evidence synthesis, beyond the subset of the available evidence often included in meta-analyses. Sources of heterogeneity can both strengthen and weaken the confidence in the evidence. Consistency of associations across study designs, populations, and exposure assessment methods provides additional confidence in the results. Publication bias should be explored beyond statistical methods and is not necessarily expected in large and collaborative studies. We call for identifying and quantifying possible key biases, their most likely direction, and their potential impacts on the results. Conclusions: GRADE-type frameworks require substantial modification to align better with features of environmental health questions and the studies that address them.