Repetitive mild closed-head injury induced synapse loss and increased local BOLD-fMRI signal homogeneity.

Repeated mild head injuries due to sports, or domestic violence and military service are increasingly linked to debilitating symptoms in the long term. Although symptoms may take decades to manifest, potentially treatable neurobiological alterations must begin shortly after injury. Better means to diagnose and treat traumatic brain injuries, requires an improved understanding of the mechanisms underlying progression and means through which they can be measured. Here, we employ a repetitive mild closed-head injury (rmTBI) and chronic variable stress (CVS) mouse model to investigate emergent structural and functional brain abnormalities. Brain imaging is achieved with [18F]SynVesT-1 positron emission tomography, with the synaptic vesicle glycoprotein 2A ligand marking synapse density and BOLD (blood-oxygen-level-dependent) functional magnetic resonance imaging (fMRI). Animals were scanned six weeks after concluding rmTBI/Stress procedures. Injured mice showed widespread decreases in synaptic density coupled with an increase in local BOLD-fMRI synchrony detected as regional homogeneity. Injury-affected regions with higher synapse density showed a greater increase in fMRI regional homogeneity. Taken together, these observations may reflect compensatory mechanisms following injury. Multimodal studies are needed to provide deeper insights into these observations.

Association of Cardiac MRI-derived Aortic Stiffness with Early Stages and Progression of Heart Failure with Preserved Ejection Fraction.

Purpose To investigate if aortic stiffening as detected with cardiac MRI is an early phenomenon in the development and progression of heart failure with preserved ejection fraction (HFpEF). Materials and Methods Both clinical and preclinical studies were performed. The clinical study was a secondary analysis of the prospective HFpEF stress trial (August 2017 through September 2019) and included 48 participants (median age, 69 years [range, 65-73 years]; 33 female, 15 male) with noncardiac dyspnea (NCD, n = 21), overt HFpEF at rest (pulmonary capillary wedge pressure [PCWP] ≥ 15 mm Hg, n = 14), and masked HFpEF at rest diagnosed during exercise stress (PCWP ≥ 25 mm Hg, n = 13) according to right heart catheterization. Additionally, all participants underwent echocardiography and cardiac MRI at rest and during exercise stress. Aortic pulse wave velocity (PWV) was calculated. The mechanistic preclinical study characterized cardiac function and structure in transgenic mice with induced arterial stiffness (Runx2-smTg mice). Statistical analyses comprised nonparametric and parametric comparisons, Spearman correlations, and logistic regression models. Results Participants with HFpEF showed increased PWV (NCD vs masked HFpEF: 7.0 m/sec [IQR: 5.0-9.5 m/sec] vs 10.0 m/sec [IQR: 8.0-13.4 m/sec], P = .005; NCD vs overt HFpEF: 7.0 m/sec [IQR: 5.0-9.5 m/sec] vs 11.0 m/sec [IQR: 7.5-12.0 m/sec], P = .01). Increased PWV correlated with higher PCWP (P = .006), left atrial and left ventricular long-axis strain (all P < .02), and N-terminal pro-brain natriuretic peptide levels (P < .001). Participants with overt HFpEF had higher levels of myocardial fibrosis, as demonstrated by increased native T1 times (1199 msec [IQR: 1169-1228 msec] vs 1234 msec [IQR: 1208-1255 msec], P = .009). Aortic stiffness was independently associated with HFpEF on multivariable analyses (odds ratio, 1.31; P = .049). Runx2-smTG mice exhibited an "HFpEF" phenotype compared with wild-type controls, with preserved left ventricular fractional shortening but an early and late diastolic mitral annulus velocity less than 1 (mean, 0.67 ± 0.39 [standard error of the mean] vs 1.45 ± 0.47; P = .004), increased myocardial collagen deposition (mean, 11% ± 1 vs 2% ± 1; P < .001), and increased brain natriuretic peptide levels (mean, 171 pg/mL ± 23 vs 101 pg/mL ± 10; P < .001). Conclusion This study provides translational evidence that increased arterial stiffness might be associated with development and progression of HFpEF and may facilitate its early detection. Keywords: MR Functional Imaging, MR Imaging, Animal Studies, Cardiac, Aorta, Heart ClinicalTrials.gov identifier NCT03260621 Supplemental material is available for this article. © RSNA, 2024.

Cannabidiol as an antipsychotic drug.

Cannabidiol (CBD) is a major phytocannabinoid in the Cannabis sativa plant. In contrast to Δ9-tetrahydrocannabinol (THC), CBD does not produce the typical psychotomimetic effects of the plant. In addition, CBD has attracted increased interest due to its potential therapeutic effects in various psychiatric disorders, including schizophrenia. Several studies have proposed that CBD has pharmacological properties similar to atypical antipsychotics. Despite accumulating evidence supporting the antipsychotic potential of CBD, the mechanisms of action in which this phytocannabinoid produces antipsychotic effects are still not fully elucidated. Here, we focused on the antipsychotic properties of CBD indicated by a series of preclinical and clinical studies and the evidence currently available about its possible mechanisms. Findings from preclinical studies suggest that CBD effects may depend on the animal model (pharmacological, neurodevelopmental, or genetic models for schizophrenia), dose, treatment schedule (acute vs. repeated) and route of administration (intraperitoneal vs local injection into specific brain regions). Clinical studies suggest a potential role for CBD in the treatment of psychotic disorders. However, future studies with more robust sample sizes are needed to confirm these positive findings. Overall, although more studies are needed, current evidence indicates that CBD may be a promising therapeutic option for the treatment of schizophrenia.

Update on cannabis in human sexuality.

RATIONALE: Sexuality is a central aspect of being human that encompasses many facets. Cannabis, a widely used psychoactive substance, has been associated with various effects on sexuality. The relationship between cannabis and sexuality is complex and multifaceted, involving physiological, psychological, and social factors. OBJECTIVES: This review aims to provide an overview of the current literature on the effects of cannabis on several sexual functions, including sexual desire, arousal, orgasm, and sexual satisfaction. It also discusses the potential mechanisms underlying these effects, as well as the impact of dose and frequency of use. RESULTS: This review has revealed a complex relationship between cannabis dosage and its influence on sexuality. It appears that the frequency of cannabis use in humans has been associated with the frequency of sexual activities. Individuals who use cannabis more frequently tend to report higher levels of sexual activity. Moreover, there is a notable gender difference in how cannabis affects sexuality. In addition, we found lower doses of cannabis to be linked to heightened sexual desire and enjoyment, whereas higher doses may lead to a decrease in sexual desire and performance. CONCLUSIONS: Overall, the association between cannabis and sexuality is complex and warrants further research to better understand the psychological and neurological mechanisms that underlie the effect of cannabis on these sexuality functions and its implications for sexual health. To advance in this endeavor, a crucial step is establishing a precise measurement of dosage in human studies.

The Role of Antioxidants in the Treatment of Metabolic Dysfunction-Associated Fatty Liver Disease: A Systematic Review.

Non-alcoholic fatty liver disease (NAFLD) is a global public health problem that causes liver-related morbidity and mortality. It is also an independent risk factor for non-communicable diseases. In 2020, a proposal was made to refer to it as "metabolic dysfunction-associated fatty liver disease (MAFLD)", with concise diagnostic criteria. Given its widespread occurrence, its treatment is crucial. Increased levels of oxidative stress cause this disease. This review aims to evaluate various studies on antioxidant therapies for patients with MAFLD. A comprehensive search for relevant research was conducted on the PubMed, SCOPUS, and ScienceDirect databases, resulting in the identification of 87 studies that met the inclusion criteria. In total, 31.1% of human studies used natural antioxidants, 53.3% used synthetic antioxidants, and 15.5% used both natural and synthetic antioxidants. In human-based studies, natural antioxidants showed 100% efficacy in the treatment of MAFLD, while synthetic antioxidants showed effective results in only 91% of the investigations. In animal-based research, natural antioxidants were fully effective in the treatment of MAFLD, while synthetic antioxidants demonstrated effectiveness in only 87.8% of the evaluations. In conclusion, antioxidants in their natural form are more helpful for patients with MAFLD, and preserving the correct balance of pro-oxidants and antioxidants is a useful way to monitor antioxidant treatment.

Is genotoxicity a suitable biomarker for monitoring anabolic-androgenic steroids exposure in vivo? A systematic review and meta-analysis.

Steroids stand for a class of hormones (natural and synthetic) known to be helpful for a number of disorders. Despite the aforementioned beneficial effects of using these hormones, anabolic-androgenic steroids (AAS) are also widely abused in a non-therapeutic manner for muscle-building and strength-increasing properties that may lead to genotoxicity in different tissues. The present study aims to understand whether genotoxicity may be a suitable biomarker for AAS exposure in vivo in both experimental animal and human studies. All studies published in PubMed/Medline, Scopus, and Web of Science electronic databases that presented data on DNA damage caused by AAS were analyzed. A total of 15 articles were included in this study, and after thoroughly reviewing the studies, a total of 8 articles were classified as Strong, 6 were classified as Moderate, and only 1 was classified as Weak, totaling 14 studies being considered either Strong or Moderate. This classification makes it possible to consider the present findings as reliable. The meta-analysis data revealed a statistically significant difference in Wistar rat testis cells with AAS compared to control for tail length and % tail DNA (p < 0.001), so that the selected articles were considered homogeneous and the I2 of 0% indicated low heterogeneity. In summary, genotoxicity can be considered a suitable biomarker for monitoring AAS exposure as a result of DNA breakage and oxidative DNA damage.

Embodied Communication, Sensed Atmospheres, Joint Situations: Human-Horse Encounters from a Neophenomenological Perspective.

This article shows that the German philosopher Hermann Schmitz's new phenomenology can make a valuable contribution to human-animal studies. The three concepts suitable for this purpose are, first, Schmitz's concept of embodied communication, which can be applied to trans-species encounters; second, his understanding of atmospheres, which are always co-communicated in trans-species encounters; and, third, his conception of situation, which can help with analyzing the relationship of society to animals. My contribution applies these three basic elements of new phenomenology-embodied communication, atmosphere, and situation-to the analysis of the encounters between humans and horses. This paper demonstrates that embodied communication in particular is not only a worthwhile object of research but can also serve as a mode of producing scientific insight.

Fetus Exposure to Drugs and Chemicals: A Holistic Overview on the Assessment of Their Transport and Metabolism across the Human Placental Barrier.

BACKGROUND: The placenta exerts a crucial role in fetus growth and development during gestation, protecting the fetus from maternal drugs and chemical exposure. However, diverse drugs and chemicals (xenobiotics) can penetrate the maternal placental barrier, leading to deleterious, adverse effects concerning fetus health. Moreover, placental enzymes can metabolize drugs and chemicals into more toxic compounds for the fetus. Thus, evaluating the molecular mechanisms through which drugs and chemicals transfer and undergo metabolism across the placental barrier is of vital importance. In this aspect, this comprehensive literature review aims to provide a holistic approach by critically summarizing and scrutinizing the potential molecular processes and mechanisms governing drugs and chemical transfer and metabolism across the placental barrier, which may lead to fetotoxicity effects, as well as analyzing the currently available experimental methodologies used to assess xenobiotics placental transfer and metabolism. METHODS: A comprehensive and in-depth literature review was conducted in the most accurate scientific databases such as PubMed, Scopus, and Web of Science by using relevant and effective keywords related to xenobiotic placental transfer and metabolism, retrieving 8830 published articles until 5 February 2024. After applying several strict exclusion and inclusion criteria, a final number of 148 relevant published articles were included. RESULTS: During pregnancy, several drugs and chemicals can be transferred from the mother to the fetus across the placental barrier by either passive diffusion or through placental transporters, resulting in fetus exposure and potential fetotoxicity effects. Some drugs and chemicals also appear to be metabolized across the placental barrier, leading to more toxic products for both the mother and the fetus. At present, there is increasing research development of diverse experimental methodologies to determine the potential molecular processes and mechanisms of drug and chemical placental transfer and metabolism. All the currently available methodologies have specific strengths and limitations, highlighting the strong demand to utilize an efficient combination of them to obtain reliable evidence concerning drug and chemical transfer and metabolism across the placental barrier. To derive the most consistent and safe evidence, in vitro studies, ex vivo perfusion methods, and in vivo animal and human studies can be applied together with the final aim to minimize potential fetotoxicity effects. CONCLUSIONS: Research is being increasingly carried out to obtain an accurate and safe evaluation of drug and chemical transport and metabolism across the placental barrier, applying a combination of advanced techniques to avoid potential fetotoxic effects. The improvement of the currently available techniques and the development of novel experimental protocols and methodologies are of major importance to protect both the mother and the fetus from xenobiotic exposure, as well as to minimize potential fetotoxicity effects.

Effect of whitening dentifrices on dental enamel: an analysis of color, microhardness, and surface roughness in vitro.

OBJECTIVES: This study aimed to evaluate the influence of different whitening toothpastes on color change and alteration in enamel surface roughness and microhardness compared to a conventional toothpaste. METHOD AND MATERIALS: Fifty bovine incisors were selected, cleaned, and stored before being divided into five groups: a conventional toothpaste group (C) and three whitening toothpaste groups containing different abrasive agents: silica (S), hydrogen peroxide (PH), and activated charcoal (CA). Specimens underwent simulated brushing, staining with black tea solution, and subsequent analyses of color, surface roughness, and microhardness. Statistical analysis was performed using three-way ANOVA and Tukey post-hoc tests (P < .05). RESULTS: The results showed that the color analysis revealed similar whitening potential among all toothpastes. Otherwise, showed significant differences in surface roughness (P < .001) and microhardness (P < .001) after simulated brushing. While all toothpastes caused a decrease in microhardness, the charcoal-based toothpaste showed a significant increase in surface roughness compared to the initial condition. CONCLUSION: All toothpastes demonstrated whitening capability. Surface roughness changed after brushing with activated charcoal-based whitening toothpaste, but final roughness was similar across all groups. Whitening toothpastes led to a decrease in enamel microhardness, with similar final performance across all toothpastes analyzed.

The effect of curcumin on paraoxonase 1 protein levels, gene expression, and enzyme activity: A systematic review of animal interventional studies.

BACKGROUND AND AIMS: Paraoxonase (PON) proteins have various hydrolytic activities. The PON family is able to detoxify oxidized low-density lipoprotein. Additionally, differentiation of monocytes into macrophages, as the first stage in the development of atherosclerosis, is suppressed by PON 1. The effects of polyphenols including curcumin on PON1 have been investigated in studies. In this study, our main goal is to investigate curcumin's effect on PON1 protein levels, gene expression, and enzyme activity in animal interventional studies. METHODS: The literature was searched through the online databases including PubMed, SCOPUS, Embase, and Google Scholar until May 2022. RESULTS: Curcumin administration can increase the PON1 enzyme activity. Also, it probably has a positive role in increasing the PON1 gene expression. However, concerning the PON1 protein values, results are contradictory. CONCLUSIONS: The findings of this study suggested positive role of curcumin in increasing PON1 enzyme activities, gene expression, and protein levels. DATA AVAILABILITY: Data are available from the corresponding author (Kheirouris@tbzmed.ac.ir).

The Potential Effects of the Ketogenic Diet in the Prevention and Co-Treatment of Stress, Anxiety, Depression, Schizophrenia, and Bipolar Disorder: From the Basic Research to the Clinical Practice.

BACKGROUND: The ketogenic diet (KD) has been highly developed in the past for the treatment of epileptic pathological states in children and adults. Recently, the current re-emergence in its popularity mainly focuses on the therapy of cardiometabolic diseases. The KD can also have anti-inflammatory and neuroprotective activities which may be applied to the prevention and/or co-treatment of a diverse range of psychiatric disorders. PURPOSE: This is a comprehensive literature review that intends to critically collect and scrutinize the pre-existing research basis and clinical data of the potential advantageous impacts of a KD on stress, anxiety, depression, schizophrenia and bipolar disorder. METHODS: This literature review was performed to thoroughly represent the existing research in this topic, as well as to find gaps in the international scientific community. In this aspect, we carefully investigated the ultimate scientific web databases, e.g., PubMed, Scopus, and Web of Science, to derive the currently available animal and clinical human surveys by using efficient and representative keywords. RESULTS: Just in recent years, an increasing amount of animal and clinical human surveys have focused on investigating the possible impacts of the KD in the prevention and co-treatment of depression, anxiety, stress, schizophrenia, and bipolar disorder. Pre-existing basic research with animal studies has consistently demonstrated promising results of the KD, showing a propensity to ameliorate symptoms of depression, anxiety, stress, schizophrenia, and bipolar disorder. However, the translation of these findings to clinical settings presents a more complex issue. The majority of the currently available clinical surveys seem to be moderate, usually not controlled, and have mainly assessed the short-term effects of a KD. In addition, some clinical surveys appear to be characterized by enormous dropout rates and significant absence of compliance measurement, as well as an elevated amount of heterogeneity in their methodological design. CONCLUSIONS: Although the currently available evidence seems promising, it is highly recommended to accomplish larger, long-term, randomized, double-blind, controlled clinical trials with a prospective design, in order to derive conclusive results as to whether KD could act as a potential preventative factor or even a co-treatment agent against stress, anxiety, depression, schizophrenia, and bipolar disorder. Basic research with animal studies is also recommended to examine the molecular mechanisms of KD against the above psychiatric diseases.

Potential of Chlorogenic Acid in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Animal Studies and Clinical Trials-A Narrative Review.

Chlorogenic acid (CGA) is a natural polyphenol found in coffee, tea, vegetables, and fruits. It exhibits strong antioxidant activity and possesses several other biological properties, including anti-inflammatory effects, antimicrobial activity, and insulin-sensitizing properties. Moreover, it may improve lipid and glucose metabolism. This review summarizes the available information on the therapeutic effect of CGA in metabolic dysfunction-associated steatotic liver disease (MASLD). As the literature search engine, the browsers in the PubMed, Scopus, Web of Science databases, and ClinicalTrials.gov register were used. Animal trials and clinical studies suggest that CGA has promising therapeutic potential in treating MASLD and hepatic steatosis. Its mechanisms of action include antioxidant, anti-inflammatory, and anti-apoptotic effects via the activation of the Nrf2 signaling pathway and the inhibition of the TLR4/NF-κB signaling cascade. Furthermore, the alleviation of liver disease by CGA also involves other important molecules such as AMPK and important physiological processes such as the intestinal barrier and gut microbiota. Nevertheless, the specific target cell and key molecule to which CGA is directed remain unidentified and require further study.

The complex role of the chemokine CX3CL1/Fractalkine in major depressive disorder: A narrative review of preclinical and clinical studies.

Evidence suggests that neuroinflammation exhibits a dual role in the pathogenesis of major depressive disorder (MDD), both potentiating the onset of depressive symptoms and developing as a consequence of them. Our narrative review focuses on the role of the chemokine fractalkine (FKN) (also known as CX3CL1), which has gained increasing interest for its ability to induce changes to microglial phenotypes through interaction with its corresponding receptor (CX3CR1) that may impact neurophysiological processes relevant to MDD. Despite this, there is a lack of a clear understanding of the role of FKN in MDD. Overall, our review of the literature shows the involvement of FKN in MDD, both in preclinical models of depression, and in clinical studies of depressed patients. Preclinical studies (N = 8) seem to point towards two alternative hypotheses for FKN's role in MDD: a) FKN may drive pro-inflammatory changes to microglia that contribute towards MDD pathogenesis; or b) FKN may inhibit pro-inflammatory changes to microglia, thereby exerting a protective effect against MDD pathogenesis. Evidence for a) primarily derives from preclinical chronic stress models of depression in mice, whereas for b) from preclinical inflammation models of depression. Whereas, in humans, clinical studies (N = 4) consistently showed a positive association between FKN and presence of MDD, however it is not clear whether FKN is driving or moderating MDD pathogenesis. Future studies should aim for larger and more controlled clinical cohorts, in order to advance our understanding of FKN role both in the context of stress and/or inflammation.

Extracellular vesicles in the diagnosis and treatment of cardiovascular disease. What's behind? What do we need to implement them into clinical practice?

Extracellular vesicles (EVs) represent a heterogeneous group of particles secreted by cells to transfer information from the cell of origin to recipient cells by carrying various bioactive molecules. Numerous PubMed records on EVs reveal a burgeoning interest in EV-research, with a notable subset focusing on the potential diagnostic and therapeutic applications of EVs for diverse diseases, including cardiovascular disease (CVD), currently a globally leading cause of mortality. However, this great diagnostic and clinical potential has not yet been translated into clinical practice. No EV-based biomarkers and EV-therapeutic products have been approved, and EV-based therapy for CVD has not yet been shown to be effective. Therefore, this paper aims to scrutinize available data and identify what is needed to translate the underlying potential of EVs into specific EV-biomarkers and EV-therapeutic tools applicable in clinical practice.

MSC-Based Cell Therapy in Neurological Diseases: A Concise Review of the Literature in Pre-Clinical and Clinical Research.

Mesenchymal stem cells (MSCs) are multipotent stromal cells with the ability to self-renew and multi-directional differentiation potential. Exogenously administered MSCs can migrate to damaged tissue sites and participate in the repair of damaged tissues. A large number of pre-clinical studies and clinical trials have demonstrated that MSCs have the potential to treat the abnormalities of congenital nervous system and neurodegenerative diseases. Therefore, MSCs hold great promise in the treatment of neurological diseases. Here, we summarize and highlight current progress in the understanding of the underlying mechanisms and strategies of MSC application in neurological diseases.

Self Emulsifying Delivery System of Cissus quadrangularis: Evidence of Enhanced Efficacy and Promising Pharmacokinetic Profile in the Management of Osteoporosis.

Treatment therapies used to manage osteoporosis are associated with severe side effects. So worldwide herbs are widely studied to develop alternative safe & effective treatments. Cissus quadrangularis (CQ) has a significant role in bone health and fracture healing. It is documented that its extracts increase osteoblastic differentiation & mineralization. Currently, Cissus quadrangularis is available in the form of tablets in the market for oral delivery. But these conventional forms are associated with poor bioavailability. There is a need for a novel drug delivery system with improving oral bioavailability. Therefore, a Cissus quadrangularis-loaded self-emulsifying drug delivery system (CQ-SEDDS) was developed which disperses rapidly in the gastrointestinal fluids, yielding nano-emulsions containing a solubilized drug. This solubilized form of the drug can be easily absorbed through lymphatic pathways and bypass the hepatic first-pass effect. The emulsification efficiency, zeta potential, globule size, in-vitro dissolution, ex-vivo, in-vivo and bone marker studies were performed to assess the absorption and permeation potential of CQ incorporated in SEDDS. CQ-SEDDS with excipients Tween 80, Cremophor RH40, Transcutol HP & α-Tocopherol acetate had shown about 76% enhancement in the bioavailability of active constituents of CQ. This study provided the pre-clinical data of CQ-SEDDS using osteoporotic rat model studies.

Effects of electroacupuncture on postoperative cognitive dysfunction and its underlying mechanisms: a literature review of rodent studies.

With the aging of the population, the health of the elderly has become increasingly important. Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients following general anesthesia or surgery. It is characterized by cognitive decline that may persist for weeks, months, or even longer. Electroacupuncture (EA), a novel therapy that combines physical nerve stimulation with acupuncture treatment from traditional Chinese medicine, holds potential as a therapeutic intervention for preventing and treating POCD, particularly in elderly patients. Although the beneficial effects of EA on POCD have been explored in preclinical and clinical studies, the reliability of EA is limited by methodological shortcomings, and the underlying mechanisms remain largely unexplored. Therefore, we have synthesized existing evidence and proposed potential biological mechanisms underlying the effects of EA on neuroinflammation, oxidative stress, autophagy, the microbiota-gut-brain axis, and epigenetic modification. This review summarizes recent advances in EA and POCD, provides a theoretical foundation, explores potential molecular mechanisms for the prevention and treatment of POCD, and offers a basis for conducting relevant clinical trials.

Zoofolkloristics: Imagination as a Critical Component.

Nonhuman animal protagonists of folklore texts in the European space have tended to be perceived primarily as performing a symbolic and metaphoric function. But behind the symbols and the metaphors hide real flesh-and-blood nonhuman animals, and flesh-and-blood humans interacting with them, mostly from a position of power. The emerging discipline of zoofolkloristics considers nonhuman animals in their own right. Through critical analysis of folklore material, zoofolkloristics examines the role of animals and power relations within the interspecies entanglement with the aim of deconstructing the oppressive system and establishing multispecies justice. We begin this paper with a brief reflection on the 'historical animal' as an embodied being and a human construct. We then perform a critical re-reading of three animal-related folklore texts from the Slovenian tradition and, applying Hubert Zapf's concept of imaginative counter-discourse, consider the potential of imagination as a methodological tool in the transformative program of zoofolkloristics. Implications for animal ethics, liberation, and conservation are also discussed.

Morquio A Syndrome: Identification of Differential Patterns of Molecular Pathway Interactions in Bone Lesions.

Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disease (LSD) caused by deficiency of a hydrolase enzyme, N-acetylgalactosamine-6-sulfate sulfatase, and characterized clinically by mainly musculoskeletal manifestations. The mechanisms underlying bone involvement in humans are typically explored using invasive techniques such as bone biopsy, which complicates analysis in humans. We compared bone proteomes using DDA and SWATH-MS in wild-type and MPS IVA knockout mice (UNT) to obtain mechanistic information about the disease. Our findings reveal over 1000 dysregulated proteins in knockout mice, including those implicated in oxidative phosphorylation, oxidative stress (reactive oxygen species), DNA damage, and iron transport, and suggest that lactate dehydrogenase may constitute a useful prognostic and follow-up biomarker. Identifying biomarkers that reflect MPS IVA clinical course, severity, and progression have important implications for disease management.

Effects of radiofrequency electromagnetic field (RF-EMF) exposure on male fertility: A systematic review of experimental studies on non-human mammals and human sperm in vitro.

BACKGROUND: The World Health Organization is coordinating an international project aimed at systematically reviewing the evidence regarding the association between radiofrequency electromagnetic field (RF-EMF) exposure and adverse health effects. Reproductive health outcomes have been identified among the priority topics to be addressed. OBJECTIVES: To evaluate the effect of RF-EMF exposure on male fertility of experimental mammals and on human sperm exposed in vitro. METHODS: Three electronic databases (PubMed, Scopus and EMF Portal) were last searched on September 17, 2022. Two independent reviewers screened the studies, which were considered eligible if met the following criteria: 1) Peer-reviewed publications of sham controlled experimental studies, 2) Non-human male mammals exposed at any stage of development or human sperm exposed in vitro, 3) RF-EMF exposure within the frequency range of 100 kHz-300 GHz, including electromagnetic pulses (EMP), 4) one of the following indicators of reproductive system impairment:Two reviewers extracted study characteristics and outcome data. We assessed risk of bias (RoB) using the Office of Health Assessment and Translation (OHAT) guidelines. We categorized studies into 3 levels of overall RoB: low, some or high concern. We pooled study results in a random effects meta-analysis comparing average exposure to no-exposure and in a dose-response meta-analysis using all exposure doses. For experimental animal studies, we conducted subgroup analyses for species, Specific Absorption Rate (SAR) and temperature increase. We grouped studies on human sperm exposed in vitro by the fertility status of sample donors and SAR. We assessed the certainty of the evidence using the GRADE approach after excluding studies that were rated as "high concern" for RoB. RESULTS: One-hundred and seventeen papers on animal studies and 10 papers on human sperm exposed in vitro were included in this review. Only few studies were rated as "low concern" because most studies were at RoB for exposure and/or outcome assessment. Subgrouping the experimental animal studies by species, SAR, and temperature increase partly accounted for the heterogeneity of individual studies in about one third of the meta-analyses. In no case was it possible to conduct a subgroup analysis of the few human sperm in vitro studies because there were always 1 or more groups including less than 3 studies. Among all the considered endpoints, the meta-analyses of animal studies provided evidence of adverse effects of RF-EMF exposure in all cases but the rate of infertile males and the size of the sired litters. The assessment of certainty according to the GRADE methodology assigned a moderate certainty to the reduction of pregnancy rate and to the evidence of no-effect on litter size, a low certainty to the reduction of sperm count, and a very low certainty to all the other meta-analysis results. Studies on human sperm exposed in vitro indicated a small detrimental effect of RF-EMF exposure on vitality and no-effect on DNA/chromatin alterations. According to GRADE, a very low certainty was attributed to these results. The few studies that used EMP exposure did not show effects on the outcomes. A low to very low certainty was attributed to these results. DISCUSSION: Many of the studies examined suffered of severe limitations that led to the attribution of uncertainty to the results of the meta-analyses and did not allow to draw firm conclusions on most of the endpoints. Nevertheless, the associations between RF-EMF exposure and decrease of pregnancy rate and sperm count, to which moderate and low certainty were attributed, are not negligible, also in view of the indications that in Western countries human male fertility potential seems to be progressively declining. It was beyond the scope of our systematic review to determine the shape of the dose-response relationship or to identify a minimum effective exposure level. The subgroup and the dose-response fitting analyses did not show a consistent relationship between the exposure levels and the observed effects. Notably, most studies evaluated RF-EMF exposure levels that were higher than the levels to which human populations are typically exposed, and the limits set in international guidelines. For these reasons we cannot provide suggestions to confirm or reconsider current human exposure limits. Considering the outcomes of this systematic review and taking into account the limitations found in several of the studies, we suggest that further investigations with better characterization of exposure and dosimetry including several exposure levels and blinded outcome assessment were conducted. PROTOCOL REGISTRATION: Protocols for the systematic reviews of animal studies and of human sperm in vitro studies were published in Pacchierotti et al., 2021. The former was also registered in PROSPERO (CRD42021227729 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID = 227729) and the latter in Open Science Framework (OSF Registration DOI https://doi.org/10.17605/OSF.IO/7MUS3).