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Reviews on Environmental Health Mar 2021Mercury and methyl mercury are poisonous to human body. In the recent times, exposure to mercury has been anthropogenic in nature. Within the past several decades, many...
Mercury and methyl mercury are poisonous to human body. In the recent times, exposure to mercury has been anthropogenic in nature. Within the past several decades, many incidences of mercury poisoning have been documented in several countries including Pakistan. Mercury has been ingested where it has been used to preserve crops, through the point and non-point source discharge into the surface water, and consequently entering the food chain. We conducted this scoping review of mercury and its health effects in Pakistan in order to raise the flag to a silent ongoing Minamata disease in the country. We conducted a systematic search of the available literature in Google Scholar, PubMed, and grey literature of unpublished theses and reports of various universities across the country. We found that in the northern Pakistan, suspended sediments were the major pathway of the riverine mercury transport. Sediments of Hunza and Gilgit River were found high in mercury concentrations. Gold mining leads to an increase in mercury concentration in soil and river waters flowing in this region. High concentrations up to 108 ng/L were found in Shimsal River. It is suspected that that high level of mercury transport may be leading to accumulation of mercury in major water bodies and lakes downstream. Occupational exposure to mercury and other heavy metals is common in an unregulated private sector of the country. Goldsmiths burn the amalgamated gold without personal protective measures. Direct exposure to the fumes of mercury leads to respiratory, dermatological, systemic and neurological ailments specific to mercury poisoning. We found good evidence of bioaccumulation of mercury in fish and fish products in Pakistan. The untreated waste water discharge is responsible to not only afflicted the fish but also the birds which feed on this fish. Further, the same untreated waste water from factories and agriculture runoffs affect vegetables grown in it. Studies looking at the biomarkers for mercury in humans have shown increased and even toxic levels of mercury among the most vulnerable populations of the country. Other sources of mercury exposure included mercury in traditional medicines and cigarette products. Though no evidence was found for its presence in drinking water, its existence in the food chain and occupational exposure pose great threat to the humans as well as animals.
Topics: Environmental Exposure; Environmental Monitoring; Mercury; Mercury Poisoning, Nervous System; Pakistan; Vulnerable Populations
PubMed: 32822319
DOI: 10.1515/reveh-2019-0099 -
Journal of Neurology Sep 2021Neurofilament proteins have been extensively studied in relapsing-remitting multiple sclerosis, where they are promising biomarkers of disease activity and treatment... (Review)
Review
BACKGROUND
Neurofilament proteins have been extensively studied in relapsing-remitting multiple sclerosis, where they are promising biomarkers of disease activity and treatment response. Their role in progressive multiple sclerosis, where there is a particularly urgent need for improved biomarkers, is less clear. The objectives of this systematic review are to summarise the literature on neurofilament light and heavy in progressive multiple sclerosis, addressing key questions.
METHODS
A systematic search of PubMed, Embase, Web of Science and Scopus identified 355 potential sources. 76 relevant sources were qualitatively reviewed using QUADAS-2 criteria, and 17 were identified as at low risk of bias. We summarise the findings from all relevant sources, and separately from the 17 high-quality studies.
RESULTS
Differences in neurofilament light between relapsing-remitting and progressive multiple sclerosis appear to be explained by differences in covariates. Neurofilament light is consistently associated with current inflammatory activity and future brain atrophy in progressive multiple sclerosis, and is consistently shown to be a marker of treatment response with immunosuppressive disease-modifying therapies. Associations with current or future disability are inconsistent, and there is no evidence of NFL being a responsive marker of purportedly neuroprotective treatments. Evidence on neurofilament heavy is more limited and inconsistent.
CONCLUSIONS
Neurofilament light has shown consistent utility as a biomarker of neuroinflammation, future brain atrophy and immunosuppressive treatment response at a group level. Neither neurofilament light or heavy has shown a consistent treatment response to neuroprotective disease-modifying therapies, which will require further data from successful randomised controlled trials.
Topics: Biomarkers; Humans; Intermediate Filaments; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Neurofilament Proteins
PubMed: 32447549
DOI: 10.1007/s00415-020-09917-x -
Amyloid : the International Journal of... 2019
Topics: Aged; Amyloidosis; Heart Failure; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Light Chains; Male; Nephrotic Syndrome
PubMed: 31343287
DOI: 10.1080/13506129.2019.1582022 -
Annals of Internal Medicine Aug 2019The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear.
PURPOSE
To examine evidence about the effects of nutritional supplements and dietary interventions on mortality and cardiovascular outcomes in adults.
DATA SOURCES
PubMed, CINAHL, and the Cochrane Library from inception until March 2019; ClinicalTrials.gov (10 March 2019); journal Web sites; and reference lists.
STUDY SELECTION
English-language, randomized controlled trials (RCTs) and meta-analyses of RCTs that assessed the effects of nutritional supplements or dietary interventions on all-cause mortality or cardiovascular outcomes, such as death, myocardial infarction, stroke, and coronary heart disease.
DATA EXTRACTION
Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence.
DATA SYNTHESIS
Nine systematic reviews and 4 new RCTs were selected that encompassed a total of 277 trials, 24 interventions, and 992 129 participants. A total of 105 meta-analyses were generated. There was moderate-certainty evidence that reduced salt intake decreased the risk for all-cause mortality in normotensive participants (risk ratio [RR], 0.90 [95% CI, 0.85 to 0.95]) and cardiovascular mortality in hypertensive participants (RR, 0.67 [CI, 0.46 to 0.99]). Low-certainty evidence showed that omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) was associated with reduced risk for myocardial infarction (RR, 0.92 [CI, 0.85 to 0.99]) and coronary heart disease (RR, 0.93 [CI, 0.89 to 0.98]). Folic acid was associated with lower risk for stroke (RR, 0.80 [CI, 0.67 to 0.96]; low certainty), whereas calcium plus vitamin D increased the risk for stroke (RR, 1.17 [CI, 1.05 to 1.30]; moderate certainty). Other nutritional supplements, such as vitamin B6, vitamin A, multivitamins, antioxidants, and iron and dietary interventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low- to moderate-certainty evidence).
LIMITATIONS
Suboptimal quality and certainty of evidence.
CONCLUSION
Reduced salt intake, omega-3 LC-PUFA use, and folate supplementation could reduce risk for some cardiovascular outcomes in adults. Combined calcium plus vitamin D might increase risk for stroke.
PRIMARY FUNDING SOURCE
None.
Topics: Cardiovascular Diseases; Cause of Death; Coronary Disease; Diet, Healthy; Dietary Supplements; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic; Stroke; United States
PubMed: 31284304
DOI: 10.7326/M19-0341 -
Human Reproduction Update Jul 2019Approximately 50% of pregnancy losses are caused by chromosomal abnormalities, such as aneuploidy. The remainder has an apparent euploid karyotype, but it is plausible...
BACKGROUND
Approximately 50% of pregnancy losses are caused by chromosomal abnormalities, such as aneuploidy. The remainder has an apparent euploid karyotype, but it is plausible that there are cases of pregnancy loss with other genetic aberrations that are not currently routinely detected. Studies investigating the use of exome sequencing and chromosomal microarrays in structurally abnormal pregnancies and developmental disorders have demonstrated their clinical application and/or potential utility in these groups of patients. Similarly, there have been several studies that have sought to identify genes that are potentially causative of, or associated with, spontaneous pregnancy loss, but the evidence has not yet been synthesized.
OBJECTIVE AND RATIONALE
The objective was to identify studies that have recorded monogenic genetic contributions to pregnancy loss in euploid pregnancies, establish evidence for genetic causes of pregnancy loss, identify the limitations of current evidence, and make recommendations for future studies. This evidence is important in considering additional research into Mendelian causes of pregnancy loss and appropriate genetic investigations for couples experiencing recurrent pregnancy loss.
SEARCH METHODS
A systematic review was conducted in MEDLINE (1946 to May 2018) and Embase (1974 to May 2018). The search terms 'spontaneous abortion', 'miscarriage', 'pregnancy loss', or 'lethal' were used to identify pregnancy loss terms. These were combined with search terms to identify the genetic contribution including 'exome', 'human genome', 'sequencing analysis', 'sequencing', 'copy number variation', 'single-nucleotide polymorphism', 'microarray analysis', and 'comparative genomic hybridization'. Studies were limited to pregnancy loss up to 20 weeks in humans and excluded if the genetic content included genes that are not lethal in utero, PGD studies, infertility studies, expression studies, aneuploidy with no recurrence risk, methodologies where there is no clinical relevance, and complex genetic studies. The quality of the studies was assessed using a modified version of the Newcastle-Ottawa scale.
OUTCOMES
A total of 50 studies were identified and categorized into three themes: whole-exome sequencing studies; copy number variation studies; and other studies related to pregnancy loss including recurrent molar pregnancies, epigenetics, and mitochondrial DNA aberrations. Putatively causative variants were found in a range of genes, including CHRNA1 (cholinergic receptor, nicotinic, alpha polypeptide 1), DYNC2H1 (dynein, cytoplasmic 2, heavy chain 1), and RYR1 (ryanodine receptor 1), which were identified in multiple studies. Copy number variants were also identified to have a causal or associated link with recurrent miscarriage.
WIDER IMPLICATIONS
Identification of genes that are causative of or predisposing to pregnancy loss will be of significant individual patient impact with respect to counselling and treatment. In addition, knowledge of specific genes that contribute to pregnancy loss could also be of importance in designing a diagnostic sequencing panel for patients with recurrent pregnancy loss and also in understanding the biological pathways that can cause pregnancy loss.
Topics: Abortion, Habitual; Abortion, Spontaneous; DNA Copy Number Variations; Female; Genetic Predisposition to Disease; Genomic Instability; Humans; Karyotyping; Ploidies; Pregnancy; Risk Factors
PubMed: 31150545
DOI: 10.1093/humupd/dmz015 -
Frontiers in Neuroscience 2019Dementia has become a major global public health challenge with a heavy economic burden. It is urgently necessary to understand dementia pathogenesis and to identify...
Dementia has become a major global public health challenge with a heavy economic burden. It is urgently necessary to understand dementia pathogenesis and to identify biomarkers predicting risk of dementia in the preclinical stage for prevention, monitoring, and treatment. Metabolomics provides a novel approach for the identification of biomarkers of dementia. This systematic review aimed to examine and summarize recent retrospective cohort human studies assessing circulating metabolite markers, detected using high-throughput metabolomics, in the context of disease progression to dementia, including incident mild cognitive impairment, all-cause dementia, and cognitive decline. We systematically searched the PubMed, Embase, and Cochrane databases for retrospective cohort human studies assessing associations between blood (plasma or serum) metabolomics profile and cognitive decline and risk of dementia from inception through October 15, 2018. We identified 16 studies reporting circulating metabolites and risk of dementia, and six regarding cognitive performance change. Concentrations of several blood metabolites, including lipids (higher phosphatidylcholines, sphingomyelins, and lysophophatidylcholine, and lower docosahexaenoic acid and high-density lipoprotein subfractions), amino acids (lower branched-chain amino acids, creatinine, and taurine, and higher glutamate, glutamine, and anthranilic acid), and steroids were associated with cognitive decline and the incidence or progression of dementia. Circulating metabolites appear to be associated with the risk of dementia. Metabolomics could be a promising tool in dementia biomarker discovery. However, standardization and consensus guidelines for study design and analytical techniques require future development.
PubMed: 31031585
DOI: 10.3389/fnins.2019.00343 -
Pflugers Archiv : European Journal of... May 2019Human-induced pluripotent stem cells (hiPSC) can be differentiated to cardiomyocytes at high efficiency and are increasingly used to study cardiac disease in a human...
Human-induced pluripotent stem cells (hiPSC) can be differentiated to cardiomyocytes at high efficiency and are increasingly used to study cardiac disease in a human context. This review evaluated 38 studies on hypertrophic (HCM) and dilated cardiomyopathy (DCM) of different genetic causes asking to which extent published data allow the definition of an in vitro HCM/DCM hiPSC-CM phenotype. The data are put in context with the prevailing hypotheses on HCM/DCM dysfunction and pathophysiology. Relatively consistent findings in HCM not reported in DCM were larger cell size (156 ± 85%, n = 15), more nuclear localization of nuclear factor of activated T cells (NFAT; 175 ± 65%, n = 3), and higher β-myosin heavy chain gene expression levels (500 ± 547%, n = 8) than respective controls. Conversely, DCM lines showed consistently less force development than controls (47 ± 23%, n = 9), while HCM forces scattered without clear trend. Both HCM and DCM lines often showed sarcomere disorganization, higher NPPA/NPPB expression levels, and arrhythmic beating behaviour. The data have to be taken with the caveat that reporting frequencies of the various parameters (e.g. cell size, NFAT expression) differ widely between HCM and DCM lines, in which data scatter is large and that only 9/38 studies used isogenic controls. Taken together, the current data provide interesting suggestions for disease-specific phenotypes in HCM/DCM hiPSC-CM but indicate that the field is still in its early days. Systematic, quantitative comparisons and robust, high content assays are warranted to advance the field.
Topics: Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Cell Differentiation; Humans; Induced Pluripotent Stem Cells; Mutation; Myocardial Contraction; Myocytes, Cardiac; Phenotype
PubMed: 30324321
DOI: 10.1007/s00424-018-2214-0 -
PloS One 2016To allow early diagnosis and monitoring of disease progression, there is a need for biomarkers in amyotrophic lateral sclerosis (ALS). Neurofilaments (NF) are emerging... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To allow early diagnosis and monitoring of disease progression, there is a need for biomarkers in amyotrophic lateral sclerosis (ALS). Neurofilaments (NF) are emerging protein biomarkers in other neurological diseases, and are of possible use in ALS.
OBJECTIVE
The aim of this study is to evaluate the utility of NF levels as blood or cerebrospinal fluid (CSF) biomarker in patients with ALS.
METHODS
A systematic search of Pubmed, Embase and Scopus was performed. Methodological quality assessment was applied to refine the final search results. Meta-analysis of the data was performed.
RESULTS
Level of NF heavy chain and light chains were significantly elevated in the CSF of ALS patients compared to healthy controls/controls without parenchymal central nervous system (CNS) involvement and ALS mimic disease patients. NF light chain level in CSF was higher in ALS patients than in neurological patients with CNS involvement (SMD = 1.352, P = 0.01). NF light chain concentration in blood was higher in ALS patients than healthy controls/controls without CNS involvement (SMD = 1.448, P<0.0001). NF heavy chain levels in CSF were negatively correlated disease duration and ALSFRS-R ((r = -0.447, P<0.0001; r = -0.486, P<0.0001). NF light chain levels in CSF were negatively correlated with disease duration (r = -0.273, P = 0.011).
CONCLUSION
NF heavy and light chain levels have potential use as a marker of neural degeneration in ALS, but are not specific for the disease, and are more likely to be used as measures of disease progression.
Topics: Amyotrophic Lateral Sclerosis; Biomarkers; Disease Progression; Humans; Neurofilament Proteins
PubMed: 27732645
DOI: 10.1371/journal.pone.0164625 -
Blood Apr 2016Since the first description of the natural history of chronic lymphocytic leukemia (CLL) by David Galton in 1966, the considerable heterogeneity in the disease course... (Meta-Analysis)
Meta-Analysis Review
Since the first description of the natural history of chronic lymphocytic leukemia (CLL) by David Galton in 1966, the considerable heterogeneity in the disease course has been well recognized. The Rai and Binet staging systems described ∼40 years ago have proven to be robust prognostic tools. Over the past 2 decades, several novel biological, genetic, and molecular markers have been shown to be useful adjuncts to the Rai and Binet staging systems. In this systematic review, we examined the role of immunoglobulin heavy-chain variable region gene (IGHV) mutation status and genetic abnormalities determined by interphase fluorescence in situ hybridization (FISH) in patients with newly diagnosed CLL. The cumulative evidence presented in this systematic review is sufficient to recommend that FISH and IGHV be performed as standard clinical tests for all patients with newly diagnosed CLL in those countries with the resources to do so. In addition to clinical stage, these parameters could represent the minimal standard initial prognostic evaluation for patients with CLL. This approach will allow the application of powerful, recently developed prognostic indices (all of which are dependent on IGHV and FISH results) to all patients with newly diagnosed CLL.
Topics: Female; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Variable Region; In Situ Hybridization, Fluorescence; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Prognosis
PubMed: 26841802
DOI: 10.1182/blood-2015-10-620864 -
World Neurosurgery Nov 2015Intracranial aneurysms (IAs) remain a devastating clinical challenge, and the pathogenesis of IA formation and progression continues to be unclear. Biomarker analysis... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Intracranial aneurysms (IAs) remain a devastating clinical challenge, and the pathogenesis of IA formation and progression continues to be unclear. Biomarker analysis can help us understand IA development. The authors performed a systematic review of current literature on genetic and serum biomarkers for IAs in an attempt to identify diagnostic/prognostic factors for ruptured and unruptured aneurysms.
METHODS
All relevant studies on PubMed that reported blood/cerebrospinal fluid (CSF) biomarkers and genes that regulate biomarker levels for IAs were assessed for whether the biomarkers/genes studied correlated with IA formation and rupture.
RESULTS
Thirty-three studies were reviewed. IAs are associated with an increase in levels of immunologic markers, particularly complement C3 and C9, immunoglobulins IgG and IgM, M1/M2 macrophages, monocytes, and B and T lymphocytes; increase in blood and CSF levels of adhesion molecules; selectins found on vascular endothelium, platelets, and leukocytes; doubled ratios of elastase-to-alpha-1-antitrypsin as controls; elevated levels of neurofilament heavy chain SM135 and S-100 post rupture; and locus 19q13 with many candidate genes.
CONCLUSION
Though the pathophysiology of the disease remains unclear, the current literature supports the role of inflammatory and cell adhesion molecules, enzymes and hormones that effect cerebral vasculature, and other cerebral proteins related to brain and vascular damage in both the formation and progression to rupture of IAs. Future investigations are needed to validate results from previous studies and identify new diagnostic/prognostic biomarkers of IAs.
Topics: Aneurysm, Ruptured; Animals; Biomarkers; Humans; Intracranial Aneurysm; Prognosis
PubMed: 26117089
DOI: 10.1016/j.wneu.2015.06.034