-
Toxins Nov 2020Snakebite envenoming (SBE) is a public health issue in developing countries. The estimated annual global incidence of snakebites is about 5.4 million snakebites per...
Snakebite envenoming (SBE) is a public health issue in developing countries. The estimated annual global incidence of snakebites is about 5.4 million snakebites per year, resulting from 1.8 to 2.7 million cases of SBE and from 81,000 to 138,000 deaths with 400,000 survivors suffering permanent physical and psychological disabilities. There are more than 3000 species of snakes around the world: 600 are venomous and over 200 are considered to be medically important because of their clinical effects. The severity of SBE depends on several factors among which bite localization, snake's size, condition of glands and teeth, bite angle and bite duration, the microflora of the snake's mouth and victim's skin, age of the victim, weight, health status, and victim's activity after a bite. Snake venoms are mixtures of protein families, and each of these families contains many different toxins or toxin isoforms. Based on their effects, snake venoms can be classified as hemotoxic, neurotoxic, or cytotoxic and they can all act together involving multiple tissues and organs. When the bite is fatal, the mechanism of death is primarily related to the paralysis of respiratory muscles, which causes asphyxia and hypoxic-ischemic encephalopathy, but also anaphylactic shock, hemorrhagic shock, cardiomyopathy, acute tubular necrosis (ATN). The purpose of this literature review is to evaluate epidemiological and post-mortem examination findings in fatal SBEs in order to better understand the pathophysiological mechanisms, thus helping pathologists in defining the correct diagnosis.
Topics: Adolescent; Adult; Aged; Animals; Autopsy; Cause of Death; Child; Child, Preschool; Female; Forensic Pathology; Humans; Male; Middle Aged; Reproducibility of Results; Snake Bites; Snake Venoms; Snakes; Young Adult
PubMed: 33153179
DOI: 10.3390/toxins12110699 -
Andrologia Aug 2020Recent studies have found that metastatic castrated-resistant prostate cancer (mCRPC) with positive androgen receptor splice variant 7 (AR-V7) may have poor prognosis... (Meta-Analysis)
Meta-Analysis
Recent studies have found that metastatic castrated-resistant prostate cancer (mCRPC) with positive androgen receptor splice variant 7 (AR-V7) may have poor prognosis during endocrine or chemotherapy treatment, but the specific mechanism was still unclear. We had finished literature search in March 2019 from PubMed, Web of Science database, and Embase. The final results were presented in this research. The pooled results showed that AR-V7 status predicted pooled PSA-PFS (HR = 4.31, 95% CI: 2.57-7.24, p < .001), rPFS (HR = 2.39, 95% CI: 1.28-4.48, p = .006) and OS (HR = 4.27, 95% CI: 3.22-5.66, p < .001) in mCRPC patients after endocrine or chemotherapy treatment. Subgroup analysis of different treatments revealed that mCRPC patients treated with chemotherapy had significant association between positive AR-V7 and OS (HR = 2.82, 95% CI: 1.72-4.62, p < .001), and also during endocrine therapy (HR = 4.78, 95% CI: 3.33-6.86, p < .001). Our study demonstrated that AR-V7-positive mCRPC patients may have worse prognosis. AR-V7 may be an independent prognostic factor for endocrine therapy or chemotherapy in patients with mCRPC.
Topics: Humans; Male; Neoplastic Cells, Circulating; Prognosis; Prostatic Neoplasms, Castration-Resistant; Protein Isoforms; Receptors, Androgen
PubMed: 32401357
DOI: 10.1111/and.13642 -
Nutrition and Cancer 2022The term vitamin E describes tocopherols and tocotrienols, whose chemical variations result in different biological activities including antioxidants. Neuroprotective...
The term vitamin E describes tocopherols and tocotrienols, whose chemical variations result in different biological activities including antioxidants. Neuroprotective effects of alpha-tocopherol against different toxins are assumed, therefore, it is discussed as a possible protective factor for adverse effects in cancer treatment. In July 2020, a systematic search was conducted searching five databases (Embase, Cochrane, PsychInfo, Cinahl, Medline) to find studies concerning the impact of α-tocopherol application and its potential harm on cancer patients. From 7546 search results, 22 publications referring to 20 studies with 1941 patients were included. Included patients were diagnosed with various cancer types and stages. Outcome variables were overall survival of cancer, symptom management of mucositis and chemotherapy-induced peripheral neuropathy (CIPN). The studies had different methodological qualities (mainly acceptable) and reported heterogeneous results: some reported significant improvement of mucositis and CIPN while others did not find changes concerning these endpoints. Due to heterogeneous results and methodical limitations of the included studies, a clear statement regarding the effectiveness of α-tocopherol as complementary treatment for cancer patients is not possible. Despite findings regarding reduction of oral side effects, usage of α-tocopherol during therapy must be discouraged because of potential negative influence on survival rates.
Topics: Antioxidants; Humans; Mucositis; Neoplasms; Protein Isoforms; Tocotrienols; Vitamin E; alpha-Tocopherol
PubMed: 34918607
DOI: 10.1080/01635581.2021.2014905 -
Cytokine Jan 2021COVID-19, as a newly-emerged viral infection has now spread all over the world after originating in Wuhan, China. Pneumonia is the hallmark of the disease, with dyspnea...
BACKGROUND
COVID-19, as a newly-emerged viral infection has now spread all over the world after originating in Wuhan, China. Pneumonia is the hallmark of the disease, with dyspnea in half of the patients and acute respiratory distress syndrome (ARDS) in up to one -third of the cases. Pulmonary edema, neutrophilic infiltration, and inflammatory cytokine release are the pathologic signs of this disease. The anti-inflammatory effect of the photobiomodulation (PBM) has been confirmed in many previous studies. Therefore, this review study was conducted to evaluate the direct effect of PBM on the acute lung inflammation or ARDS and also accelerating the regeneration of the damaged tissues. The indirect effects of PBM on modulation of the immune system, increasing the blood flow and oxygenation in other tissues were also considered.
METHODOLOGY
The databases of PubMed, Cochrane library, and Google Scholar were searched to find the relevant studies. Keywords included the PBM and related terms, lung inflammation, and COVID-19 -related signs. Studies were categorized with respect to the target tissue, laser parameters, and their results.
RESULTS
Seventeen related papers were included in this review. All of them were in animal models. They showed that the PBM could significantly decrease the pulmonary edema, neutrophil influx, and generation of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), intracellular adhesion molecule (ICAM), reactive oxygen species (ROS), isoform of nitric oxide synthase (iNOS), and macrophage inflammatory protein 2 (MIP-2)).
CONCLUSION
Our findings revealed that the PBM could be helpful in reducing the lung inflammation and promoting the regeneration of the damaged tissue. PBM can increase the oxygenation indirectly in order to rehabilitate the affected organs. Thus, the infra-red lasers or light-emitting diodes (LEDs) are recommended in this regard.
Topics: COVID-19; Cytokines; Humans; Low-Level Light Therapy; Lung; Macrophages; Neutrophils; Pneumonia; PubMed; Pulmonary Edema; Reactive Oxygen Species; Respiratory Distress Syndrome
PubMed: 33128927
DOI: 10.1016/j.cyto.2020.155312 -
Pediatric Neurology Apr 2024To systematically evaluate the diagnostic accuracy of the creatine kinase isoenzyme-MM (CK-MM) test in newborn screening for Duchenne muscular dystrophy (DMD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To systematically evaluate the diagnostic accuracy of the creatine kinase isoenzyme-MM (CK-MM) test in newborn screening for Duchenne muscular dystrophy (DMD).
METHODS
A comprehensive literature search was conducted up to October 31, 2022, in PubMed, Embase, Cochrane Library, Web of Science, and Scopus Database. To evaluate the diagnostic value, the sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and Q∗ index were pooled. Threshold effect followed by subgroup analysis and meta-regression were performed to explore the source of heterogeneity. Sensitivity analysis was used to verify the robustness of the findings.
RESULTS
A total seven studies with 248,853 newborns was included in our meta-analysis. The pooled SEN and SPE were 1.00 (95% confidence interval [CI]: 0.89∼1.00) and 1.00 (95% CI: 1.00 to 1.00), respectively; the PLR and NLR were 1004.59 (95% CI: 251.37∼4014.91) and 0.13 (95% CI: 0.05∼0.34), respectively; the DOR was 877.96 (95% CI: 983.24∼78,366.32); the AUC and Q index were 0.8683 and 0.9326, respectively. Sensitivity analysis showed that two studies had an impact on the pooled results and mainly contributed to the heterogeneity.
CONCLUSIONS
CK-MM test demonstrated high accuracy in newborn screening for DMD and may be a valuable alternative in the early diagnosis of the disease followed by confirmatory genetic testing.
Topics: Humans; Infant, Newborn; Muscular Dystrophy, Duchenne; Neonatal Screening; Isoenzymes; Sensitivity and Specificity; Creatine Kinase
PubMed: 38350306
DOI: 10.1016/j.pediatrneurol.2024.01.010 -
Autoimmunity Reviews Jul 2019Alternative splicing is an important form of RNA processing that affects nearly all human genes. The differential expression of specific transcript and protein isoforms...
OBJECTIVE
Alternative splicing is an important form of RNA processing that affects nearly all human genes. The differential expression of specific transcript and protein isoforms holds the potential of novel biomarkers for complex diseases. In this systematic review, we compiled the existing literature on aberrant alternative splicing events in multiple sclerosis (MS).
METHODS
A systematic literature search in the PubMed database was carried out and supplemented by screening the reference lists of the identified articles. We selected only MS-related original research studies which compared the levels of different isoforms of human protein-coding genes. A narrative synthesis of the research findings was conducted. Additionally, we performed a case-control analysis using high-density transcriptome microarray data to reevaluate the genes that were examined in the reviewed studies.
RESULTS
A total of 160 records were screened. Of those, 36 studies from the last two decades were included. Most commonly, peripheral blood samples were analyzed (32 studies), and PCR-based techniques were usually employed (27 studies) for measuring the expression of selected genes. Two studies used an exploratory genome-wide approach. Overall, 27 alternatively spliced genes were investigated. Nine of these genes appeared in at least two studies (CD40, CFLAR, FOXP3, IFNAR2, IL7R, MOG, PTPRC, SP140 and TNFRSF1A). The microarray data analysis confirmed differential alternative pre-mRNA splicing for 19 genes.
CONCLUSIONS
An altered RNA processing of genes mediating immune signaling pathways has been repeatedly implicated in MS. The analysis of individual exon-level expression patterns is stimulated by the advancement of transcriptome profiling technologies. In particular, the examination of genes encoded in MS-associated genetic regions may provide important insights into the pathogenesis of the disease and help to identify new biomarkers.
Topics: Alternative Splicing; Gene Expression; Humans; Multiple Sclerosis
PubMed: 31059848
DOI: 10.1016/j.autrev.2019.05.010 -
Acta Obstetricia Et Gynecologica... Sep 2019Progestogens are widely used for the conservative treatment of endometrial hyperplasia and early endometrial cancer. Nevertheless, they do not achieve the regression in...
INTRODUCTION
Progestogens are widely used for the conservative treatment of endometrial hyperplasia and early endometrial cancer. Nevertheless, they do not achieve the regression in all cases. Although several immunohistochemical markers have been assessed to predict the response to treatment, their usefulness is still unclear. We aimed to analyze the usefulness of each immunohistochemical marker studied in predicting the response to progestogens in endometrial hyperplasia and early endometrial cancer.
MATERIAL AND METHODS
Electronic databases were searched for relevant articles from January 2000 to June 2018. All studies assessing the association of immunohistochemical markers with the outcome of the progestogen-based therapy in endometrial hyperplasia and early endometrial cancer were included. The expression of immunohistochemical markers in pretreatment phase and changes of expression during the follow-up were evaluated in relation to response to therapy and relapse.
RESULTS
Twenty-seven studies with 1360 women were included in the systematic review; 43 immunohistochemical markers were assessed. The most studied predictive markers in the pretreatment phase were progesterone and estrogen receptors, although with conflicting results; their isoforms, and in particular progesterone receptor B, appeared more promising. Further studies are needed to confirm the usefulness of mismatch repair proteins, Dusp6, GRP78 and PTEN combined with other molecules such as phospho-AKT or phospho-mTOR. In the follow-up phase, Nrf2 and survivin showed the stronger evidence; a role may also be played by Bcl2 and Ki67. Further studies are necessary for Fas, NCoR, AKR1C1, HE4, PAX2 and SPAG9.
CONCLUSIONS
Several immunohistochemical markers might be helpful in predicting the response to conservative treatment of endometrial hyperplasia and early endometrial cancer on pretreatment and follow-up specimens. Further studies are needed to confirm their usefulness and possibly integrate them in a predictive immunohistochemical panel.
Topics: Biomarkers, Tumor; Conservative Treatment; Endometrial Hyperplasia; Endometrial Neoplasms; Endoplasmic Reticulum Chaperone BiP; Female; Humans; Immunohistochemistry; Predictive Value of Tests; Progestins
PubMed: 30793281
DOI: 10.1111/aogs.13587 -
Technology in Cancer Research &... 2021The purpose of this meta-analysis was to study the prognostic effects of androgen receptor splicing variant 7 (AR-V7) on metastatic castration-resistant prostate cancer... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this meta-analysis was to study the prognostic effects of androgen receptor splicing variant 7 (AR-V7) on metastatic castration-resistant prostate cancer (mCRPC) under different treatment options (chemotherapy, hormone therapy).
METHODS
We conducted a systematic search of PubMed, EMBASE and Cochrane databases for clinical studies up to June 4, 2021, and used prostate-specific antigen (PSA) progression free-survival (PSA-PFS), radiologic PFS (r-PFS), overall survival (OS) and PSA response rate (PSA RR) as the main endpoints. Subgroup analyses were conducted based on the source of the specimens. STATA v.15 software was used for data analysis.
RESULTS
Twenty-one studies were included in this meta-analysis, with a total of 1578 samples. In the abiraterone (AA)/enzalutamide (E) treatment group, AR-V7 positive patients had worse PSA-PFS (hazard ratio [HR] = 3.40; 95% confidence interval [95%CI] 2.56-4.51; < 0.05) and worse r-PFS (HR = 2.69; 95%CI 1.70-4.24; < 0.05) and OS (HR = 3.02; 95%CI 1.73-5.30; < 0.05). Multivariate Cox regression results showed that AR-V7 positive status was an independent risk factor for OS in the AA/E treatment group. In the taxane treatment group, AR-V7-positive and negative patients had similar PSA-PFS (HR = 0.87; 95%CI 0.46-1.63; = 0.657), r-PFS (HR = 1.01; 95%CI 0.53-1.96; = 0.965) and OS (HR = 1.50; 95%CI 0.89-2.52; = 0.127). For AR-V7-positive patients, the difference in OS between taxane and AA/E treatment was not statistically significant (HR = 1.03; 95%CI 0.52-2.06; = 0.930). However, multivariate Cox regression results suggested that for AR-V7-positive patients, taxane therapy was a protective factor for OS (HR = 0.35; 95%CI 0.20-0.60; < 0.05).
CONCLUSION
The expression of AR-V7 indicates a poor prognosis and is an independent risk factor for OS in AA/E-treated mCRPC patients. However, AR-V7 positive status does not play the same role in taxane-treated patients. In addition, compared to AA/E, taxane treatment is a protective factor for OS in AR-V7-positive patients. AR-V7 may thus be an effective biomarker for treatment prognosis in patients with mCRPC.
Topics: Alternative Splicing; Biomarkers, Tumor; Humans; Male; Prognosis; Proportional Hazards Models; Prostatic Neoplasms, Castration-Resistant; RNA Isoforms; Receptors, Androgen
PubMed: 34313171
DOI: 10.1177/15330338211035260 -
Alzheimer's Research & Therapy Jan 2018The MAPT c.1216C > T (p.Arg406Trp; R406W) mutation is a known cause of frontotemporal dementia with Parkinsonism linked to chromosome 17 tau with Alzheimer's...
BACKGROUND
The MAPT c.1216C > T (p.Arg406Trp; R406W) mutation is a known cause of frontotemporal dementia with Parkinsonism linked to chromosome 17 tau with Alzheimer's disease-like clinical features.
METHODS
We compiled clinical data from a new Swedish kindred with R406W mutation. Seven family members were followed longitudinally for up to 22 years. Radiological examinations were performed in six family members and neuropathological examinations in three. We systematically reviewed the literature and compiled clinical, radiological, and neuropathological data on 63 previously described R406W heterozygotes and 3 homozygotes.
RESULTS
For all cases combined, the median age of onset was 56 years and the median disease duration was 13 years. Memory impairment was the most frequent symptom, behavioral disturbance and language impairment were less common, and Parkinsonism was rare. Disease progression was most often slow. The most frequent clinical diagnosis was Alzheimer's disease. R406W homozygotes had an earlier age at onset and a higher frequency of behavioral symptoms and Parkinsonism than heterozygotes. In the new Swedish kindred, a consistent imaging finding was ventromedial temporal lobe atrophy, which was evident also in early disease stages as a widening of the collateral sulcus with ensuing atrophy of the parahippocampal gyrus. Unlike previously published R406W carriers, all three autopsied patients from the novel family showed neuropathological similarities with progressive supranuclear palsy, with predominant four-repeat (exon 10+) tau isoform (4R) tauopathy and neurofibrillary tangles accentuated in the basal-medial temporal lobe. Amyloid-β pathology was absent.
CONCLUSIONS
Dominance of 4R over three-repeat (exon 10-) tau isoforms contrasts with earlier reports of R406W patients and was not sufficiently explained by the presence of H1/H2 haplotypes in two of the autopsied patients. R406W patients often show a long course of disease with marked memory deficits. Both our neuropathological results and our imaging findings revealed that the ventromedial temporal lobes were extensively affected in the disease. We suggest that this area may represent the point of origin of tau deposition in this disease with relatively isolated tauopathy.
Topics: Age of Onset; Aged; Brain; Dementia; Disease Progression; Family; Female; Humans; Longitudinal Studies; Male; Middle Aged; Mutation; tau Proteins
PubMed: 29370822
DOI: 10.1186/s13195-017-0330-2 -
Clinical Pharmacology and Therapeutics Aug 2020Relatively few studies exist in the literature that discuss the effects of diet on drug metabolism and how this can affect interindividual differences in systemic drug... (Meta-Analysis)
Meta-Analysis
Relatively few studies exist in the literature that discuss the effects of diet on drug metabolism and how this can affect interindividual differences in systemic drug exposure. Several studies have investigated the effects of cruciferous vegetables (Cruciferae) or their constituents on drug-metabolizing activity, as these vegetables form an important part of many peoples' diets. In general, the ingestion of cruciferous vegetables is associated with induction of cytochrome P450 (CYP) 1A2 activity in vivo; however, there is contention between reports, and the clinical significance of potential diet-drug interactions remains unclear. This study reports a systematic review, critical appraisal, and meta-analysis of the published literature in this area, and discusses the clinical significance of Cruciferae-enriched diets in the context of diet-drug interactions. Twenty-three dietary intervention trials with drug metabolism end points were identified across Embase, Medline, and the Cochrane Controlled Register of Trials (CENTRAL). Cruciferous vegetables represented in the literature included broccoli, Brussels sprout, cabbage, cauliflower, radish, and watercress. A range of phase I and II drug-metabolizing enzymes and phenotyping metrics were represented in the literature. The meta-analyses performed demonstrated a significant effect on CYP1A2 and glutathione S-transferase-alpha (GST-α), with consumption of Cruciferae increasing the activities of these enzymes by 20-40% and 15-35%, respectively. The results herein suggest that patients undergoing pharmacotherapy with CYP1A2 or GST-α substrates could have altered drug exposure profiles if they regularly eat large or variable amounts of cruciferous vegetables. Recommendations regarding the design of future randomized, controlled trials to test hypotheses in this area are included.
Topics: Brassicaceae; Clinical Trials as Topic; Cytochrome P-450 CYP1A2; Diet; Food-Drug Interactions; Glutathione Transferase; Humans; Isoenzymes; Metabolic Detoxication, Phase I; Metabolic Detoxication, Phase II; Nutritive Value; Pharmaceutical Preparations; Risk Assessment; Risk Factors; Substrate Specificity; Vegetables
PubMed: 32086800
DOI: 10.1002/cpt.1811