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Fluoride exposure and cognitive neurodevelopment: Systematic review and dose-response meta-analysis.Environmental Research Mar 2023Many uncertainties still surround the possible harmful effect of fluoride exposure on cognitive neurodevelopment in children. The aim of this systematic review and... (Meta-Analysis)
Meta-Analysis Review
Many uncertainties still surround the possible harmful effect of fluoride exposure on cognitive neurodevelopment in children. The aim of this systematic review and meta-analysis was to characterize this relation through a dose-response approach, by comparing the intelligence quotient (IQ) scores in the highest versus the lowest fluoride exposure category with a random-effects model, within a one-stage dose-response meta-analysis based on a cubic spline random-effects model. Out of 1996 potentially relevant literature records, 33 studies were eligible for this review, 30 of which were also suitable for meta-analysis. The summary mean difference of IQ score, comparing highest versus lowest fluoride categories and considering all types of exposure, was -4.68 (95% confidence interval-CI -6.45; -2.92), with a value of -5.60 (95% CI -7.76; -3.44) for drinking water fluoride and -3.84 (95% CI -7.93; 0.24) for urinary fluoride. Dose-response analysis showed a substantially linear IQ decrease for increasing water fluoride above 1 mg/L, with -3.05 (95% CI -4.06; -2.04) IQ points per 1 mg/L up to 2 mg/L, becoming steeper above such level. A weaker and substantially linear decrease of -2.15 (95% CI -4.48; 0.18) IQ points with increasing urinary fluoride emerged above 0.28 mg/L (approximately reflecting a water fluoride content of 0.7 mg/L). The inverse association between fluoride exposure and IQ was particularly strong in the studies at high risk of bias, while no adverse effect emerged in the only study judged at low risk of bias. Overall, most studies suggested an adverse effect of fluoride exposure on children's IQ, starting at low levels of exposure. However, a major role of residual confounding could not be ruled out, thus indicating the need of additional prospective studies at low risk of bias to conclusively assess the relation between fluoride exposure and cognitive neurodevelopment.
Topics: Child; Humans; Fluorides; Intelligence; Prospective Studies; Drinking Water; Cognition
PubMed: 36639015
DOI: 10.1016/j.envres.2023.115239 -
International Journal of Environmental... Oct 2021The load in resistance training is considered to be a critical variable for neuromuscular adaptations. Therefore, it is important to assess the effects of applying... (Review)
Review
Effects of Resistance Training Performed with Different Loads in Untrained and Trained Male Adult Individuals on Maximal Strength and Muscle Hypertrophy: A Systematic Review.
The load in resistance training is considered to be a critical variable for neuromuscular adaptations. Therefore, it is important to assess the effects of applying different loads on the development of maximal strength and muscular hypertrophy. The aim of this study was to systematically review the literature and compare the effects of resistance training that was performed with low loads versus moderate and high loads in untrained and trained healthy adult males on the development of maximal strength and muscle hypertrophy during randomized experimental designs. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (2021) were followed with the eligibility criteria defined according to participants, interventions, comparators, outcomes, and study design (PICOS): (P) healthy males between 18 and 40 years old, (I) interventions performed with low loads, (C) interventions performed with moderate or high loads, (O) development of maximal strength and muscle hypertrophy, and (S) randomized experimental studies with between- or within-subject parallel designs. The literature search strategy was performed in three electronic databases (Embase, PubMed, and Web of Science) on 22 August 2021. Twenty-three studies with a total of 563 participants (80.6% untrained and 19.4% trained) were selected. The studies included both relative and absolute loads. All studies were classified as being moderate-to-high methodological quality, although only two studies had a score higher than six points. The main findings indicated that the load magnitude that was used during resistance training influenced the dynamic strength and isometric strength gains. In general, comparisons between the groups (i.e., low, moderate, and high loads) showed higher gains in 1RM and maximal voluntary isometric contraction when moderate and high loads were used. In contrast, regarding muscle hypertrophy, most studies showed that when resistance training was performed to muscle failure, the load used had less influence on muscle hypertrophy. The current literature shows that gains in maximal strength are more pronounced with high and moderate loads compared to low loads in healthy adult male populations. However, for muscle hypertrophy, studies indicate that a wide spectrum of loads (i.e., 30 to 90% 1RM) may be used for healthy adult male populations.
Topics: Adolescent; Adult; Humans; Hypertrophy; Male; Men; Muscle Strength; Muscle, Skeletal; Resistance Training; Young Adult
PubMed: 34769755
DOI: 10.3390/ijerph182111237 -
Archives of Gynecology and Obstetrics Jan 2023Endometriosis is a common chronic gynecological disease defined as the presence of endometrial glands and stroma tissue outside the uterus. Gestrinone is an effective... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Endometriosis is a common chronic gynecological disease defined as the presence of endometrial glands and stroma tissue outside the uterus. Gestrinone is an effective antiestrogen that induces endometrial atrophy and/or amenorrhea. The purpose of this systematic review is to provide an evaluation of safety and effectiveness of gestrinone for the treatment of endometriosis.
METHODS
We performed a search in six electronic databases: PubMed, MEDLINE (ovid), Embase, Cochrane CENTRAL (clinical trials), Web of Science and Scopus. Our selected primary outcomes were the changes in dysmenorrhea, pain relief including pelvic pain and dyspareunia. The secondary outcomes embrace hormones parameters, pregnancy rate and adverse events.
RESULTS
Of 3269 references screened, 16 studies were included involving 1286 women. All studies compared gestrinone with other drugs treatments (placebo, Danazol, Mifepristone tablets, Leuprolide acetate, Quyu Jiedu Recipe) during 6 months. When compared with other drugs treatments, gestrinone relieved dysmenorrhea, pelvic pain, and morphologic response in the ovary. There was an increase on the pregnancy rate. Regarding the side effects observed, gestrinone showed the same adverse events and increased the risk of acne and seborrhea when compared to other treatments. Even if there was any difference in efficacy between gestrinone, danazol, leuprolide acetate, or Quyu Jiedu Recipe Chinese Medicine, it remains unclear due to insufficient data.
CONCLUSION
Based limited evidence available suggests that gestrinone appeared to be safe and may have some efficacy advantages over danazol, as well as other therapeutic interventions for treating endometriosis. However, this conclusion should be interpreted with caution, due the quality of the evidence provided is generally very low or unclear.
TRIAL REGISTRATION
CRD42021284148.
Topics: Pregnancy; Female; Humans; Endometriosis; Gestrinone; Danazol; Leuprolide; Dysmenorrhea; Pelvic Pain
PubMed: 36434439
DOI: 10.1007/s00404-022-06846-0 -
Apoptosis : An International Journal on... Aug 2022Programmed cell death is considered a key player in a variety of cellular processes that helps to regulate tissue growth, embryogenesis, cell turnover, immune response,... (Review)
Review
Programmed cell death is considered a key player in a variety of cellular processes that helps to regulate tissue growth, embryogenesis, cell turnover, immune response, and other biological processes. Among different types of cell death, apoptosis has been studied widely, especially in the field of cancer research to understand and analyse cellular mechanisms, and signaling pathways that control cell cycle arrest. Hallmarks of different types of cell death have been identified by following the patterns and events through microscopy. Identified biomarkers have also supported drug development to induce cell death in cancerous cells. There are various serological and microscopic techniques with advantages and limitations, that are available and are being utilized to detect and study the mechanism of cell death. The complexity of the mechanism and difficulties in distinguishing among different types of programmed cell death make it challenging to carry out the interventions and delay its progression. In this review, mechanisms of different forms of programmed cell death along with their conventional and unconventional methods of detection of have been critically reviewed systematically and categorized on the basis of morphological hallmarks and biomarkers to understand the principle, mechanism, application, advantages and disadvantages of each method. Furthermore, a very comprehensive comparative analysis has been drawn to highlight the most efficient and effective methods of detection of programmed cell death, helping researchers to make a reliable and prudent selection among the available methods of cell death assay. Conclusively, how programmed cell death detection methods can be improved and can provide information about distinctive stages of cell death detection have been discussed.
Topics: Apoptosis; Biomarkers; Cell Death; Signal Transduction
PubMed: 35713779
DOI: 10.1007/s10495-022-01735-y -
Current Environmental Health Reports Dec 2023We performed a systematic review and meta-analysis on the relation between fluoride exposure and skeletal fluorosis (SF) using a novel statistical methodology for... (Meta-Analysis)
Meta-Analysis Review
PURPOSE OF REVIEW
We performed a systematic review and meta-analysis on the relation between fluoride exposure and skeletal fluorosis (SF) using a novel statistical methodology for dose-response modeling.
RECENT FINDINGS
Skeletal fluorosis, a major health issue that is endemic in some regions, affects millions of people worldwide. However, data regarding the dose-response relation between fluoride exposure and SF are limited and outdated. We included twenty-three studies in the meta-analysis. When comparing the highest versus the lowest fluoride category, the summary risk ratio (RR) for SF prevalence was 2.05 (95% CI 1.60; 2.64), with a value of 2.73 (95% CI 1.92; 3.90) for drinking water and 1.40 (95% CI 0.90; 2.17) for urinary fluoride. The RR by the risk of bias (RoB) was 2.37 (95% CI 1.56; 3.58) and 1.78 (95% CI 1.34; 2.36) for moderate and high RoB studies, respectively. The dose-response curve based on a one-stage cubic spline regression model showed an almost linear positive relation between exposure and SF occurrence starting from relatively low concentrations up to 5 mg/L and 2.5 mg/L, respectively, for water and urinary fluoride, with no substantial increase above this threshold. The RR for developing moderate-severe forms increases at 5.00 mg/L and 2.5 mg/L of water and urinary fluoride, respectively. Better-quality studies are needed to confirm these results, but greater attention should be given to water fluoride levels to prevent SF, in addition to the other potential adverse effects of fluoride exposure.
Topics: Humans; Fluorides; Fluorosis, Dental; Drinking Water; Prevalence
PubMed: 37861949
DOI: 10.1007/s40572-023-00412-9 -
Child's Nervous System : ChNS :... Feb 2022Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas. Despite the difficulties regarding the complex nuclear infrastructure... (Meta-Analysis)
Meta-Analysis Review
PURPOSES
Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas. Despite the difficulties regarding the complex nuclear infrastructure and consequent small number of brachytherapy studies, recent discoveries relating tumour characteristics to sensitivity to brachytherapy have stimulated this extensive systematic review and meta-analysis of the recent results aiming to summarise its efficacy and complications.
METHODS
The systematic review was structured using PRISMA statements. The MEDLINE database was systematically reviewed from March 2010 to February 2021 to identify qualified trials dealing with radioisotope brachytherapy in cystic craniopharyngiomas in the paediatric population, emphasising tumour control rates and complications.
RESULTS
A total of 228 individuals were analysed, of which 66 were children. The minimum average follow-up was 5 years. Considering the paediatric trials, partial and complete responses were achieved in 89% of patients with exclusively cystic lesions, compared to 58% in non-exclusively cystic lesions. The former observed progression in 3% of patients, while in the latter, 35% was reported. Visual and endocrine improvement reached 64% and 20%, respectively, in the first group, in contrast to 48% and 7% in the second group, respectively. There were similar results considering the non-exclusive paediatric series, but with less expressive numbers.
CONCLUSION
These results reinforce the positive impact of radioisotope brachytherapy in the treatment of predominant monocystic or multicystic craniopharyngiomas, especially in the paediatric population, grounded by impressive tumour control rates, lower morbidities and single application in the majority of the cases. In the future, specific morphological tumour characteristics might be considered for a more assertive patient selection.
Topics: Brachytherapy; Child; Craniopharyngioma; Humans; Pituitary Neoplasms
PubMed: 34618201
DOI: 10.1007/s00381-021-05378-3 -
Journal of Functional Biomaterials May 2023Exosomes have been proven to play a positive role in tendon and tendon-bone healing. Here, we systematically review the literature to evaluate the efficacy of exosomes... (Review)
Review
Exosomes have been proven to play a positive role in tendon and tendon-bone healing. Here, we systematically review the literature to evaluate the efficacy of exosomes in tendon and tendon-bone healing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic and comprehensive review of the literature was performed on 21 January 2023. The electronic databases searched included Medline (through PubMed), Web of Science, Embase, Scopus, Cochrane Library and Ovid. In the end, a total of 1794 articles were systematically reviewed. Furthermore, a "snowball" search was also carried out. Finally, forty-six studies were included for analysis, with the total sample size being 1481 rats, 416 mice, 330 rabbits, 48 dogs, and 12 sheep. In these studies, exosomes promoted tendon and tendon-bone healing and displayed improved histological, biomechanical and morphological outcomes. Some studies also suggested the mechanism of exosomes in promoting tendon and tendon-bone healing, mainly through the following aspects: (1) suppressing inflammatory response and regulating macrophage polarization; (2) regulating gene expression, reshaping cell microenvironment and reconstructing extracellular matrix; (3) promoting angiogenesis. The risk of bias in the included studies was low on the whole. This systematic review provides evidence of the positive effect of exosomes on tendon and tendon-bone healing in preclinical studies. The unclear-to-low risk of bias highlights the significance of standardization of outcome reporting. It should be noted that the most suitable source, isolation methods, concentration and administration frequency of exosomes are still unknown. Additionally, few studies have used large animals as subjects. Further studies may be required on comparing the safety and efficacy of different treatment parameters in large animal models, which would be conducive to the design of clinical trials.
PubMed: 37367263
DOI: 10.3390/jfb14060299 -
Strahlentherapie Und Onkologie : Organ... Dec 2023Tumor-associated macrophages (TAMs) are the most represented cells of the immune system in the tumor microenvironment (TME). Besides its effects on cancer cells,... (Review)
Review
OBJECTIVE
Tumor-associated macrophages (TAMs) are the most represented cells of the immune system in the tumor microenvironment (TME). Besides its effects on cancer cells, radiation therapy (RT) can alter TME composition. With this systematic review, we provide a better understanding on how RT can regulate macrophage characterization, namely the M1 antitumor and the M2 protumor polarization, with the aim of describing new effective RT models and exploration of the possibility of integrating radiation with other available therapies.
METHODS
A systematic search in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was carried out in PubMed, Google Scholar, and Scopus. Articles from January 2000 to April 2020 which focus on the role of M1 and M2 macrophages in the response to RT were identified.
RESULTS
Of the 304 selected articles, 29 qualitative summary papers were included in our analysis (16 focusing on administration of RT and concomitant systemic molecules, and 13 reporting on RT alone). Based on dose intensity, irradiation was classified into low (low-dose irradiation, LDI; corresponding to less than 1 Gy), moderate (moderate-dose irradiation, MDI; between 1 and 10 Gy), and high (high-dose irradiation, HDI; greater than 10 Gy). While HDI seems to be responsible for induced angiogenesis and accelerated tumor growth through early M2-polarized TAM infiltration, MDI stimulates phagocytosis and local LDI may represent a valid treatment option for possible combination with cancer immunotherapeutic agents.
CONCLUSION
TAMs seem to have an ambivalent role on the efficacy of cancer treatment. Radiation therapy, which exerts its main antitumor activity via cell killing, can in turn interfere with TAM characterization through different modalities. The plasticity of TAMs makes them an attractive target for anticancer therapies and more research should be conducted to explore this potential therapeutic strategy.
Topics: Humans; Tumor-Associated Macrophages; Neoplasms; Macrophages; Tumor Microenvironment
PubMed: 37347290
DOI: 10.1007/s00066-023-02097-3 -
Frontiers in Systems Neuroscience 2022Although neural plasticity is now widely studied, there was a time when the idea of adult plasticity was antithetical to the mainstream. The essential stumbling block...
Although neural plasticity is now widely studied, there was a time when the idea of adult plasticity was antithetical to the mainstream. The essential stumbling block arose from the seminal experiments of Hubel and Wiesel who presented convincing evidence that there existed a critical period for plasticity during development after which the brain lost its ability to change in accordance to shifts in sensory input. Despite the zeitgeist that mature brain is relatively immutable to change, there were a number of examples of adult neural plasticity emerging in the scientific literature. Interestingly, some of the earliest of these studies involved visual plasticity in the adult cat. Even earlier, there were reports of what appeared to be functional reorganization in adult rat somatosensory thalamus after dorsal column lesions, a finding that was confirmed and extended with additional experimentation. To demonstrate that these findings reflected more than a response to central injury, and to gain greater control of the extent of the sensory loss, peripheral nerve injuries were used that eliminated ascending sensory information while leaving central pathways intact. Merzenich, Kaas, and colleagues used peripheral nerve transections to reveal unambiguous reorganization in primate somatosensory cortex. Moreover, these same researchers showed that this plasticity proceeded in no less than two stages, one immediate, and one more protracted. These findings were confirmed and extended to more expansive cortical deprivations, and further extended to the thalamus and brainstem. There then began a series of experiments to reveal the physiological, morphological and neurochemical mechanisms that permitted this plasticity. Ultimately, Mowery and colleagues conducted a series of experiments that carefully tracked the levels of expression of several subunits of glutamate (AMPA and NMDA) and GABA (GABAA and GABAB) receptor complexes in primate somatosensory cortex at several time points after peripheral nerve injury. These receptor subunit mapping experiments revealed that membrane expression levels came to reflect those seen in early phases of critical period development. This suggested that under conditions of prolonged sensory deprivation the adult cells were returning to critical period like plastic states, i.e., developmental recapitulation. Here we outline the heuristics that drive this phenomenon.
PubMed: 36762289
DOI: 10.3389/fnsys.2022.1086680 -
Cancer Gene Therapy Jun 2023Chimeric Antigen Receptor (CAR) T cell therapy is an effective treatment approach for patients with relapsed or refractory acute lymphoblastic leukemia (R/R B-ALL).... (Meta-Analysis)
Meta-Analysis
Long-term response to autologous anti-CD19 chimeric antigen receptor T cells in relapsed or refractory B cell acute lymphoblastic leukemia: a systematic review and meta-analysis.
Chimeric Antigen Receptor (CAR) T cell therapy is an effective treatment approach for patients with relapsed or refractory acute lymphoblastic leukemia (R/R B-ALL). However, identifying the factors that influence long-term response to this therapy is necessary to optimize patient selection and treatment allocation. We conducted a literature review and meta-analysis to investigate the use of autologous anti-CD19 CAR T cell therapy in both pediatric and adult patients with R/R B-ALL, using several databases including MEDLINE, Cochrane Central, ScienceDirect, Web of Science, Journals@Ovid, Embase, and clinicaltrial.gov. A total of 38 reports were analyzed, which enrolled 2134 patients. Time-to-event endpoints were estimated using reconstructed patient survival data. The study explored key modulators of response, including costimulatory domains, disease status, age, and lymphodepletion. The median overall survival and event-free survival were 36.2 months [95% CI 28.9, NR] and 13.3 months [95% CI 12.2, 17], respectively. The overall response rate was 76% [95% CI 71, 81]. The use of 4-1BB costimulatory domain in the CAR construct, administration of low-dose cyclophosphamide lymphodepletion, and pretreatment morphologic remission were associated with better overall survival, with hazard ratios of 0.72, 0.56, and 0.66, respectively. Morphologic remission and 4-1BB domain were associated with better event-free survival, with hazard ratios of 0.66 and 0.72, respectively. These findings suggest that CAR T cell therapy may offer long-term benefits to patients with R/R B-ALL. However, further research is needed to optimize patient selection and better understand the impact of various factors on the outcome of CAR T cell therapy.
Topics: Adult; Humans; Child; Receptors, Chimeric Antigen; Receptors, Antigen, T-Cell; Immunotherapy, Adoptive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antigens, CD19; T-Lymphocytes
PubMed: 36750666
DOI: 10.1038/s41417-023-00593-3