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1.
Mil Med ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34632516

RESUMO

INTRODUCTION: Much of the research impacting diagnosis, outcome, and treatment of traumatic brain injuries (TBIs) has favored time of consciousness criteria indicative of hemispheric blast focus alone. However, recent animal-based research has widely expanded the diagnostic knowledge base and potential treatment options. METHODS: Recent animal-based research findings of foramen magnum and occipital crest-focused blast injuries in laboratory rats were reviewed and compared to the Part I human case report. RESULTS: Comparing the human case report (Part I) to that of animal research studies found very similar neuropathological outcomes, many deep and delayed, and supports why non-cerebral-focused TBIs have gone unrecognized. The overpressure wave is funneled through skull openings of the foramen magnum, with the possibility of a rebound secondary contrecoup injury impacting the orbits, oral-nasal cavity, and ears resulting in additional occult axonal and white matter injury. CONCLUSIONS: Research analysis prompted by a human case report (Part I) has helped identify mechanisms that assist in recognizing and defining non-cerebral hemispheric-focused TBI injuries. Position of the head in relationship to the blast wave, the setting in which the blast occurs, and close diagnostic follow-up are critical to the recognition, diagnosis, and treatment of injuries that have otherwise gone unrecognized and unstudied in humans since the Vietnam War.

2.
Mil Med ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34632519

RESUMO

INTRODUCTION: The diagnosis of traumatic brain injuries is typically based on hemispheric blasts resulting in degrees of unconsciousness and associated cerebral injuries. This case report describes a Vietnam War era setting in which a traumatic blast wave struck the posterior cranium in the region of the foramen magnum, occipital crest, and other skull openings (orbit, oronasal, and ear) and the unique secondary clinical signs and symptoms experienced over time. MATERIALS AND METHODS: This case report describes secondary delayed-onset clinical signs and symptoms consistent with progressive decades-long physical and functional complications. The traumatic blast resulted in brief unconsciousness, decreased vision in left eye, confusion, right sided hemotympanum, deafness, severe tinnitus, severe nasopharynx pain and difficulty swallowing, pain in right posterior and occipital area of the head, and loss of dental amalgams. Subsequent exams revealed progressive hyperacusis, sea sickness, dysdiadochokinesis, diagnosis of 9th and 10th cranial nerve traumatic schwannomas, hyperdense changes to the frontal lobe white matter, progressive tinnitus, chronic vertigo, right-sided high-frequency hearing loss, progressive oculo-gyric crisis of Tumarkin-like seizures, left-sided chronic vitreous hemorrhage, and diminished right hemisphere performance of the brain based on neurophysiological assessment. No post-traumatic stress, depression, or other emotional or psychiatric difficulties were claimed. CONCLUSION: This case report, unique to the English language scientific literature, discusses in detail the secondary signs and symptoms of a foramen magnum and occipital crest focused-associated blast injury.

3.
Mil Med ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34632521

RESUMO

INTRODUCTION: In this report, we discuss the controversy of the diverse traumatic brain injury (TBI) categorization and taxonomy and the need to develop a new multidimensional and multidisciplinary categorization system that can be an aid in improved diagnostic and prognostic outcomes. Of interest, the heterogeneity of TBI marks the major obstacle to develop effective therapeutic interventions. Currently, the Glasgow Coma Scale has been utilized to guide in the prognosis and clinical management of TBI; it does not encompass the pathophysiological mechanisms leading to neurological deficits that can impede therapeutic interventions and consequently the failure of clinical trials. An unfortunate gap exists between advances in TBI research and existing U.S. Department of Defense (DoD) definitions, categorization, and management. Part I illustrates a unique posterior-focused TBI case report that does not fit any existing TBI definitions. Part II summarizes new animal-based TBI research that supports the case report as a legitimate TBI category. Part III critiques existing TBI criteria and their controversies. METHODS: Current DoD definitions and decision-making protocols based on concussion time alone are reviewed and compared to the myriad of additional TBI definitions that further illustrate the marked differences in definitions, especially in mild TBIs. RESULTS: The DoD definitions are not consistent with what academic research and science bring to the debate. With increasing world conflicts and wars, evaluators are not prepared to accept, evaluate, and properly manage those TBIs that are not associated with immediate levels of unconsciousness alone as the prime determinant of diagnosis and long-term severity. Despite comprehensive research, current understanding among decision-makers of progressive pathology of non-hemispheric TBIs remains limited, inconsistent, and confusing. CONCLUSIONS: This dilemma requires a multidisciplinary, science/medicine-led panel to actively reassess TBI criteria that take into consideration the latest research including non-cerebral hemispheric injuries. We recommend that DoD/Veterans Affairs establish a commission to regularly review the academic-related scientific evidence and incorporate these findings in a timely fashion into their operational definitions. This would guarantee that recognition, diagnosis, and follow-up of all TBIs are properly understood, managed, and documented.

4.
Front Immunol ; 12: 746168, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646273

RESUMO

Glioblastoma (GBM) is the most common and devastating malignant brain tumor in adults. The mortality rate is very high despite different treatments. New therapeutic targets are therefore highly needed. Cell-surface proteins represent attractive targets due to their accessibility, their involvement in essential signaling pathways, and their dysregulated expression in cancer. Moreover, they are potential targets for CAR-based immunotherapy or mRNA vaccine strategies. In this context, we investigated the GBM-associated surfaceome by comparing it to astrocytes cell line surfaceome to identify new specific targets for GBM. For this purpose, biotinylation of cell surface proteins has been carried out in GBM and astrocytes cell lines. Biotinylated proteins were purified on streptavidin beads and analyzed by shotgun proteomics. Cell surface proteins were identified with Cell Surface Proteins Atlas (CSPA) and Gene Ontology enrichment. Among all the surface proteins identified in the different cell lines we have confirmed the expression of 66 of these in patient's glioblastoma using spatial proteomic guided by MALDI-mass spectrometry. Moreover, 87 surface proteins overexpressed or exclusive in GBM cell lines have been identified. Among these, we found 11 specific potential targets for GBM including 5 mutated proteins such as RELL1, CYBA, EGFR, and MHC I proteins. Matching with drugs and clinical trials databases revealed that 7 proteins were druggable and under evaluation, 3 proteins have no known drug interaction yet and none of them are the mutated form of the identified proteins. Taken together, we discovered potential targets for immune therapy strategies in GBM.

5.
Jpn J Radiol ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515926

RESUMO

INTRODUCTION: The power Doppler is a useful tool in the evaluation of pediatric acute scrotal pain. Nonetheless, it may have some inherent limitations in scrotal vascularization analysis, potentially causing unnecessary surgery. The microvascular imaging ultrasound (MicroV) is an innovative Doppler technique able to improve the detection of very low flow. This retrospective study aims to compare both power Doppler and MicroV in the evaluation of a pediatric population with early-stage scrotal pain onset, first in testis vascularization analysis, and second in their diagnostic performances. MATERIALS AND METHODS: 69 patients met the following inclusion criteria, age < 18-year-old, a clinical diagnosis of acute scrotal disease, pain onset ≤ 6 h, ultrasound examination (including B-mode, power Doppler, and MicroV), 3-months follow-up. For both power Doppler and MicroV, through a defined vascularization scale, it was evaluated the agreement in vascularization detection, and the sensitivity and specificity in US diagnostic abilities. RESULTS: Retrospective diagnoses were of 8 testicular torsion, 15 orchi-epididymitis, and 46 children with other scrotal conditions. Power Doppler provided inconclusive US evaluation in 37.68% of the cases, while MicroV only in the 1.45% (p < 0.0001). Testicular torsion and orchi-epididymitis were identified, respectively, with MicroV in 100% (sensitivity, specificity, PPV, NPV, and accuracy of 100%) and 80% of patients (80% sensitivity, 100% specificity and PPV, 94.73% NPV, 95.65% accuracy); with power Doppler the identification was, respectively, of 87.5% (87.5% sensitivity, 100% specificity and PPV, 98.38% NPV and accuracy) and of 73.3% (73.33% sensitivity, 98.14% specificity, 91.66% PPV, 92.98% NPV, 92.75% accuracy). CONCLUSIONS: Our findings indicate that MicroV is a reliable technique in vascularization detection of pediatric testes, being able also to detect vascularization in healthy testicles with no-flow at power Doppler examination. Moreover, MicroV could be a valuable ally in the US diagnostic of children with early-stage scrotal pain onset.

6.
J Mol Neurosci ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34542809

RESUMO

The use of methamphetamine (METH) is a growing worldwide epidemic that bears grave societal implications. METH is known to exert its neurotoxic effects on the dopaminergic and serotonergic systems of the brain. In addition to this classical studied mechanism of damage, findings from our laboratory and others have shown that acute METH treatment and mechanical injury, i.e. traumatic brain injury (TBI), share common cell injury mechanism(s). Since neuro-inflammation is a signature event in TBI, we hypothesize that certain cytokine levels might also be altered in rat brain exposed to an acute METH insult. In this study, using a cytokine antibody array chip, we evaluated the serum levels of 19 cytokines in rats 24 h after exposure to a 40 mg/kg acute regimen of METH. Data were compared to rats subjected to experimental TBI using the controlled cortical impact (CCI) injury model and saline controls. Sandwich ELISA method was used to further validate some of the findings obtained from the antibody cytokine array. We confirmed that three major inflammatory-linked cytokines (IL-1ß, IL-6, and IL-10) were elevated in the METH and TBI groups compared to the saline group. Such finding suggests the involvement of an inflammatory process in these brain insults, indicating that METH use is, in fact, a stressor to the immune system where systemic involvement of an altered cytokine profile may play a major role in mediating chemical brain injury after METH use.

7.
Clin Immunol ; 230: 108815, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34339843

RESUMO

Traumatic Brain Injury (TBI) is the most prevalent of all head injuries. Microglia play an essential role in homeostasis and diseases of the central nervous system. We hypothesize that microglia may play a beneficial or detrimental role in TBI depending on their state of activation and duration. In this study, we evaluated whether TBI results in a spatiotemporal change in microglia phenotype and whether it affects sensory-motor or learning and memory functions in male C57BL/6 mice. We used a panel of neurological and behavioral tests and a multi-color flow cytometry-based data analysis followed by unsupervised clustering to evaluate isolated microglia from injured brain tissue. We characterized several microglial phenotypes and their association with cognitive deficits. TBI results in a spatiotemporal increase in activated microglia that correlated negatively with spatial learning and memory at 35 days post-injury. These observations could define therapeutic windows and accelerate translational research to improve patient outcomes.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Disfunção Cognitiva/etiologia , Microglia/fisiologia , Animais , Encéfalo/patologia , Encéfalo/fisiopatologia , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/psicologia , Disfunção Cognitiva/patologia , Disfunção Cognitiva/psicologia , Modelos Animais de Doenças , Citometria de Fluxo , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Microglia/classificação , Microglia/patologia , Modelos Neurológicos , Modelos Psicológicos , Dinâmica não Linear , Aprendizagem Espacial/fisiologia , Memória Espacial/fisiologia , Análise Espaço-Temporal , Pesquisa Médica Translacional
8.
Genes (Basel) ; 12(7)2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34356057

RESUMO

The virus responsible for the COVID-19 global health crisis, SARS-CoV-2, has been shown to utilize the ACE2 protein as an entry point to its target cells. The virus has been shown to rely on the actions of TMPRSS2 (a serine protease), as well as FURIN (a peptidase), for the critical priming of its spike protein. It has been postulated that variations in the sequence and expression of SARS-CoV-2's receptor (ACE2) and the two priming proteases (TMPRSS2 and FURIN) may be critical in contributing to SARS-CoV-2 infectivity. This study aims to examine the different expression levels of FURIN in various tissues and age ranges in light of ACE2 and TMPRSS2 expression levels using the LungMAP database. Furthermore, we retrieved expression quantitative trait loci (eQTLs) of the three genes and their annotation. We analyzed the frequency of the retrieved variants in data from various populations and compared it to the Egyptian population. We highlight FURIN's potential interplay with the immune response to SARS-CoV-2 and showcase a myriad of variants of the three genes that are differentially expressed across populations. Our findings provide insights into potential genetic factors that impact SARS-CoV-2 infectivity in different populations and shed light on the varying expression patterns of FURIN.


Assuntos
Alelos , Enzima de Conversão de Angiotensina 2 , COVID-19 , Bases de Dados de Ácidos Nucleicos , Furina , Regulação Enzimológica da Expressão Gênica , Frequência do Gene , Predisposição Genética para Doença , SARS-CoV-2/metabolismo , Serina Endopeptidases , Enzima de Conversão de Angiotensina 2/biossíntese , Enzima de Conversão de Angiotensina 2/genética , COVID-19/enzimologia , COVID-19/genética , Biologia Computacional , Feminino , Furina/biossíntese , Furina/genética , Humanos , Masculino , SARS-CoV-2/genética , Serina Endopeptidases/biossíntese , Serina Endopeptidases/genética
9.
Neuropeptides ; 90: 102185, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34419803

RESUMO

It has been shown that systemic and local administration of ultra-low dose morphine induced a hyperalgesic response via mu-opioid receptors. However, its exact mechanism(s) has not fully been clarified. It is documented that mu-opioid receptors functionally couple to T-type voltage dependent Ca+2 channels. Here, we investigated the role of T-type calcium channels, amiloride and mibefradil, on the induction of low-dose morphine hyperalgesia in male Wistar rats. The data showed that morphine (0.01 µg i.t. and 1 µg/kg i.p.) could elicit hyperalgesia as assessed by the tail-flick test. Administration of amiloride (5 and 10 µg i.t.) and mibefradil (2.5 and 5 µg i.t.) completely blocked low-dose morphine-induced hyperalgesia in spinal dorsal horn. Amiloride at doses of 1 and 5 mg/kg (i.p.) and mibefradil (9 mg/kg ip) 10 min before morphine (1 µg/kg i.p.) inhibited morphine-induced hyperalgesia. Our results indicate a role for T-type calcium channels in low dose morphine-induced hyperalgesia in rats.

10.
Mass Spectrom Rev ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34323300

RESUMO

Traumatic brain injury (TBI) represents one of the major public health concerns worldwide due to the increase in TBI incidence as a result of injuries from daily life accidents such as sports and motor vehicle transportation as well as military-related practices. This type of central nervous system trauma is known to predispose patients to several neurological disorders such as Parkinson's disease, Alzheimer's disease, chronic trauamatic encephalopathy, and age-related Dementia. Recently, several proteomic and lipidomic platforms have been applied on different TBI studies to investigate TBI-related mechanisms that have broadened our understanding of its distinct neuropathological complications. In this study, we provide an updated comprehensive overview of the current knowledge and novel perspectives of the spatially resolved microproteomics and microlipidomics approaches guided by mass spectrometry imaging used in TBI studies and its applications in the neurotrauma field. In this regard, we will discuss the use of the spatially resolved microproteomics and assess the different microproteomic sampling methods such as laser capture microdissection, parafilm assisted microdissection, and liquid microjunction extraction as accurate and precise techniques in the field of neuroproteomics. Additionally, we will highlight lipid profiling applications and their prospective potentials in characterizing molecular processes involved in the field of TBI. Specifically, we will discuss the phospholipid metabolism acting as a precursor for proinflammatory molecules such as eicosanoids. Finally, we will survey the current state of spatial neuroproteomics and microproteomics applications and present the various studies highlighting their findings in these fields.

11.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208666

RESUMO

Post-traumatic epilepsy (PTE) and neurocognitive deficits are devastating sequelae of head injuries that are common in adolescents. Investigating desperately needed treatments is hindered by the difficulties in inducing PTE in rodents and the lack of established immature rat models of pediatric PTE. Hemorrhage is a significant risk factor for PTE, but compared to humans, rats are less prone to bleeding because of their rapid blood coagulation system. In this study, we promoted bleeding in the controlled cortical impact (CCI) closed-head injury model with a 20 min pre-impact 600 IU/kg intraperitoneal heparin injection in postnatal day 35 (P35) periadolescent rats, given the preponderance of such injuries in this age group. Temporo-parietal CCI was performed post-heparin (HTBI group) or post-saline (TBI group). Controls were subjected to sham procedures following heparin or saline administration. Continuous long-term EEG monitoring was performed for 3 months post-CCI. Sensorimotor testing, the Morris water maze, and a modified active avoidance test were conducted between P80 and P100. Glial fibrillary acidic protein (GFAP) levels and neuronal damage were also assessed. Compared to TBI rats, HTBI rats had persistently higher EEG spiking and increased hippocampal GFAP levels (p < 0.05). No sensorimotor deficits were detected in any group. Compared to controls, both HTBI and TBI groups had a long-term hippocampal neuronal loss (p < 0.05), as well as contextual and visuospatial learning deficits (p < 0.05). The hippocampal astrogliosis and EEG spiking detected in all rats subjected to our hemorrhage-promoting procedure suggest the emergence of hyperexcitable networks and pave the way to a periadolescent PTE rat model.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/fisiopatologia , Suscetibilidade a Doenças , Hemorragia/etiologia , Fatores Etários , Animais , Biomarcadores , Biópsia , Lesões Encefálicas Traumáticas/diagnóstico , Modelos Animais de Doenças , Eletroencefalografia , Proteína Glial Fibrilar Ácida/metabolismo , Hemorragia/diagnóstico , Imuno-Histoquímica , Aprendizagem em Labirinto , Neurônios/metabolismo , Ratos
12.
J Proteomics ; 246: 104310, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34198014

RESUMO

Metabolome and proteome profiling of biofluids, e.g., urine, plasma, has generated vast and ever-increasing amounts of knowledge over the last few decades. Paradoxically, omics analyses of sweat, one of the most readily available human biofluids, have lagged behind. This review capitalizes on the current knowledge and state of the art analytical advances of sweat metabolomics and proteomics. Moreover, current applications of sweat omics such as the discovery of disease biomarkers and monitoring athletic performance are also presented in this review. Another area of emerging knowledge that has been highlighted herein lies in the role of skin host-microbiome interactions in shaping the sweat metabolite-protein profiles. Discussion of future research directions describes the need to have a better grasp of sweat chemicals and to better understand how they function as aided by advances in omics tools. Overall, the role of sweat as an information-rich biofluid that could complement the exploration of the skin metabolome/proteome is emphasized.


Assuntos
Metaboloma , Proteoma , Humanos , Metabolômica , Proteoma/metabolismo , Proteômica , Suor/metabolismo
13.
J Integr Neurosci ; 20(2): 463-469, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34258948

RESUMO

Meningiomas are amongst the most commonly encountered intracranial tumors. The majority of these tumors arise intracranially, and the remaining incidents occur along the spinal cord. Meningiomas tend to grow gradually, with many tumors arising in inaccessible locations. Such sporadic behavior poses a therapeutic challenge to clinicians, causing incomplete tumor resections that often lead to recurrence. Therefore, ongoing research seeks to find alternative systematic treatments for meningiomas, with gene-based therapeutics of high interest. Subsequently, genetic studies characterized frequent somatic mutations in NF2, TRAF7, KLF4, AKT1, SMO, and PIK3CA. These genes are communally exhibited in 80% of sporadic meningiomas. In addition, other genes such as the DUSP family, the NR4 family, CMKOR, and FOSL2, have been identified as key players in spinal meningiomas. In this perspective, we aim to investigate current genetic-based studies, with the ongoing research mainly focused on the above NF2, TRAF7, KLF4, AKT1, SMO, and PIK3CA genes and their involved pathways. In addition, this perspective can serve as a potential cornerstone for future genetic analyses of meningioma cases.

14.
Front Public Health ; 9: 657996, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150702

RESUMO

A massive chemical detonation occurred on August 4, 2020 in the Port of Beirut, Lebanon. An uncontrolled fire in an adjacent warehouse ignited ~2,750 tons of Ammonium Nitrate (AN), producing one of the most devastating blasts in recent history. The blast supersonic pressure and heat wave claimed the lives of 220 people and injured more than 6,500 instantaneously, with severe damage to the nearby dense residential and commercial areas. This review represents one of the in-depth reports to provide a detailed analysis of the Beirut blast and its health and environmental implications. It further reviews prior AN incidents and suggests actionable recommendations and strategies to optimize chemical safety measures, improve emergency preparedness, and mitigate the delayed clinical effects of blast and toxic gas exposures. These recommended actionable steps offer a starting point for government officials and policymakers to build frameworks, adopt regulations, and implement chemical safety protocols to ensure safe storage of hazardous materials as well as reorganizing healthcare system disaster preparedness to improve emergency preparedness in response to similar large-scale disasters and promote population safety. Future clinical efforts should involve detailed assessment of physical injuries sustained by blast victims, with systemic mitigation and possible treatment of late blast effects involving individuals, communities and the region at large.


Assuntos
Desastres , Nitratos , Explosões , Humanos , Líbano , Nitratos/efeitos adversos
15.
Cell Chem Biol ; 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34102146

RESUMO

Here, we present an approach to identify N-linked glycoproteins and deduce their spatial localization using a combination of matrix-assisted laser desorption ionization (MALDI) N-glycan mass spectrometry imaging (MSI) and spatially resolved glycoproteomics. We subjected glioma biopsies to on-tissue PNGaseF digestion and MALDI-MSI and found that the glycan HexNAc4-Hex5-NeuAc2 was predominantly expressed in necrotic regions of high-grade canine gliomas. To determine the underlying sialo-glycoprotein, various regions in adjacent tissue sections were subjected to microdigestion and manual glycoproteomic analysis. Results identified haptoglobin as the protein associated with HexNAc4-Hex5-NeuAc2, thus directly linking glycan imaging with intact glycopeptide identification. In total, our spatially resolved glycoproteomics technique identified over 400 N-, O-, and S- glycopeptides from over 30 proteins, demonstrating the diverse array of glycosylation present on the tissue slices and the sensitivity of our technique. Ultimately, this proof-of-principle work demonstrates that spatially resolved glycoproteomics greatly complement MALDI-MSI in understanding dysregulated glycosylation.

16.
Mass Spectrom Rev ; 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34159615

RESUMO

Glycosylation is one of the most significant and abundant posttranslational modifications in mammalian cells. It mediates a wide range of biofunctions, including cell adhesion, cell communication, immune cell trafficking, and protein stability. Also, aberrant glycosylation has been associated with various diseases such as diabetes, Alzheimer's disease, inflammation, immune deficiencies, congenital disorders, and cancers. The alterations in the distributions of glycan and glycopeptide isomers are involved in the development and progression of several human diseases. However, the microheterogeneity of glycosylation brings a great challenge to glycomic and glycoproteomic analysis, including the characterization of isomers. Over several decades, different methods and approaches have been developed to facilitate the characterization of glycan and glycopeptide isomers. Mass spectrometry (MS) has been a powerful tool utilized for glycomic and glycoproteomic isomeric analysis due to its high sensitivity and rich structural information using different fragmentation techniques. However, a comprehensive characterization of glycan and glycopeptide isomers remains a challenge when utilizing MS alone. Therefore, various separation methods, including liquid chromatography, capillary electrophoresis, and ion mobility, were developed to resolve glycan and glycopeptide isomers before MS. These separation techniques were coupled to MS for a better identification and quantitation of glycan and glycopeptide isomers. Additionally, bioinformatic tools are essential for the automated processing of glycan and glycopeptide isomeric data to facilitate isomeric studies in biological cohorts. Here in this review, we discuss commonly employed MS-based techniques, separation hyphenated MS methods, and software, facilitating the separation, identification, and quantitation of glycan and glycopeptide isomers.

17.
Curr Med Chem ; 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34102966

RESUMO

Cannabis is the most widely trafficked and abused illicit drug due to its calming psychoactive properties. It has been increasingly recognized as having potential health benefits and relatively less adverse health effects as compared to other illicit drugs; however, growing evidence clearly indicates that cannabis is associated with considerable adverse cardiovascular events. Recent studies have linked cannabis use to myocardial infarction (MI); yet, very little is known about the underlying mechanisms. A MI is a cardiovascular disease characterized by a mismatch in the oxygen supply and demand of the heart, resulting in ischemia and subsequent necrosis of the myocardium. Since cannabis is increasingly being considered a risk factor for MI, there is a growing need for better appreciating its potential health benefits and consequences. Here, we discuss the cellular mechanisms of cannabis that lead to an increased risk of MI. We provide a thorough and critical analysis of cannabinoids' actions, which include modulation of adipocyte biology, regional fat distribution, and atherosclerosis, as well as precipitation of hemodynamic stressors relevant in the setting of a MI. By critically dissecting the modulation of signaling pathways in multiple cell types, this paper highlights the mechanisms through which cannabis may trigger life-threatening cardiovascular events. This then provides a framework for future pharmacological studies which can identify targets or develop drugs that modulate cannabis' effects on the cardiovascular system as well as other organ systems. Cannabis' impact on the autonomic outflow, vascular smooth muscle cells, myocardium, cortisol levels and other hemodynamic changes are also mechanistically reviewed.

18.
Subst Abus ; 42(3): 264-265, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33955819

RESUMO

Lebanon, a small middle-income nation in western Asia, has been crippled by decades of political turmoil and armed conflict. A "quadruple crisis" hit the country over the past years, starting with the protracted humanitarian Syrian refugee crisis, followed by a severe socioeconomic collapse, the global COVID-19 pandemic, and lastly the Beirut port catastrophic blast. With the exposure to repetitive traumatic events and associated organic brain injury, the Lebanese population has become at a higher risk of addiction, among other psychiatric comorbidities. With the scarce statistics about the topic and limited addiction services in the country, collaborative local efforts and international help are urgently needed to fight the upcoming substance use epidemic. Raising awareness, providing adequate training, and securing resources for the management of both addiction and trauma are of utmost importance.


Assuntos
Transtornos Relacionados ao Uso de Substâncias/epidemiologia , COVID-19 , Desastres , Recessão Econômica , Humanos , Líbano/epidemiologia , Pandemias , Refugiados
19.
Int J Mol Sci ; 22(6)2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33804739

RESUMO

External root resorption (ERR) is a silent destructive phenomenon detrimental to dental health. ERR may have multiple etiologies such as infection, inflammation, traumatic injuries, pressure, mechanical stimulations, neoplastic conditions, systemic disorders, or idiopathic causes. Often, if undiagnosed and untreated, ERR can lead to the loss of the tooth or multiple teeth. Traditionally, clinicians have relied on radiographs and cone beam computed tomography (CBCT) images for the diagnosis of ERR; however, these techniques are not often precise or definitive and may require exposure of patients to more ionizing radiation than necessary. To overcome these shortcomings, there is an immense need to develop non-invasive approaches such as biomarker screening methods for rapid and precise diagnosis for ERR. In this review, we performed a literature survey for potential salivary or gingival crevicular fluid (GCF) proteomic biomarkers associated with ERR and analyzed the potential pathways leading to ERR. To the best of our knowledge, this is the first proteomics biomarker survey that connects ERR to body biofluids which represents a novel approach to diagnose and even monitor treatment progress for ERR.


Assuntos
Biomarcadores , Biologia Computacional/métodos , Proteômica , Reabsorção da Raiz/diagnóstico , Reabsorção da Raiz/terapia , Biologia de Sistemas/métodos , Gerenciamento Clínico , Suscetibilidade a Doenças , Líquido do Sulco Gengival/metabolismo , Humanos , Proteômica/métodos , Radiografia , Reabsorção da Raiz/etiologia , Transdução de Sinais
20.
Gynecol Obstet Invest ; 86(1-2): 13-26, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33902044

RESUMO

OBJECTIVE: Pre-eclampsia (PE) is a serious disease of pregnancy and one of the major causes of morbidity and mortality for both the mother and baby. This systematic review aims to detect the role of high-sensitivity C-reactive protein (CRP) in the detection of PE. METHODS: Thirty-four articles published between 2001 and 2019 were included in this review. The articles were extracted from OVID Medline and Embase. The study designs of these articles are randomized controlled, cohort, case-control, and cross-sectional studies evaluating CRP as a marker to predict or early diagnose PE. The quality assessment of these articles is made by the modified Quality Assessment of Diagnostic Accuracy Studies 2 tool. Meta-analysis was not done because of clinical and statistical heterogeneity. RESULTS: A positive association between CRP levels and the development of PE was confirmed in 18 studies. This positive effect was addressed in patients with normal BMI (<25 kg/m2) in 3 studies and in overweight patients in 2 studies. One study addressed this positive association in patients with a BMI ranging between 28 and 31 kg/m2. Three studies determined a cutoff level of CRP above which a significant risk of PE development should be suspected. These levels ranged between 7 and 15 mg/L. CONCLUSION: CRP is a promising cost-effective biomarker that may be used in the prediction of PE. A CRP level higher than 15 mg/L may suggest initiation of low-dose aspirin in low-risk pregnancies.


Assuntos
Proteína C-Reativa/metabolismo , Pré-Eclâmpsia/diagnóstico , Biomarcadores/sangue , Feminino , Humanos , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/prevenção & controle , Gravidez
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