Nutraceutical Supplementation Based on Colostrum as Osteoporosis Treatment: A Pilot Study

Introduction: Naturally based treatments for osteoporosis are currently limited. The purpose of this investigation was to ascertain whether bovine colostrum supplementation can improve bone health in humans. Methods: In total 63 individuals volunteered in a 4-month supplementation project. They were stratified into three groups: 1) healthy post-menopausal women (n = 24); 2) individuals with osteopenia (n = 25); 3) people with osteoporosis (n = 14). Participants of each group were randomly assigned into two experimental sub-groups: a) the bovine colostrum (BC) supplementation (200 mL/day;5 days/week); b) the placebo sub-group. Before and after the 4-month supplementation, blood samples were obtained and bone mineral density (BMD) was measured. Dual-Energy X-ray Absorptiometry (DXA) was performed on three different anatomical sites: lumbar spine (LS), left femur neck (FN), and left forearm (Arm). Bone health markers (bone alkaline phosphatase (BAP), osteocalcin, C-terminal telopeptide (CTX-I), deoxypyridinoline (DPD)) as well as immunological markers (interleukin 6 (IL6) and immunoglobulin E (IgE)), were assessed in blood serum with enzyme immunoassays, at baseline and 4-months after BC supplementation. Results: No significant changes were found in bone densitometry factors (p > 0.05), for all studied blood parameters and their calculated effect sizes. Conclusions: It is concluded that, as studied herein, BC does not seem to affect human bone health. This pilot study though warrant the need for further research into the efficacy of BC in patients with osteoporosis.

Metabolism and metabolomics of ketamine:a toxicological approach

Ketamine is a phencyclidine derivative and a non-competitive antagonist of N-methyl-D-aspartate(NMDA)receptor for which glutamate is the full agonist.It produces a functional dissociation between the thalamocortical and limbic systems,a state that has been termed as dissociative anaesthesia.Considerable variability in the pharmacokinetics and pharmacodynamics between individuals that can affect dose-response and toxicological profile has been reported.This review aims to discuss pharmacokinetics of ketamine,namely focusing on all major and minor,active and inactive metabolites.Both ketamine optical isomers undergo hepatic biotransformation through the cytochrome P450,specially involving the isoenzymes 3A4 and 2B6.It is first N-demethylated to active metabolite norketamine.Different minor pathways have been described,namely hydroxylation of the cyclohexanone ring of ketamine and norketamine,and further conjugation with glucuronic acid to increase renal excretion.More recently,metabolomics data evidenced the alteration of several biological pathways after ketamine administration such as glycolysis,tricarboxylic acid cycle,amino acids metabolism and mitochondrial b-oxidation of fatty acids.It is expected that knowing the metabolism and metabolomics of ketamine may provide further insights aiming to better characterize ketamine from a clinical and forensic perspective.

Intranasal delivery of nanostructured lipid carriers,solid lipid nanoparticles and nanoemulsions:A current overview of in vivo studies

The management of the central nervous system(CNS)disorders is challenging,due to the need of drugs to cross the blood-brain barrier(BBB)and reach the brain.Among the various strategies that have been studied to circumvent this challenge,the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results.In addition,the encapsulation of the drugs in lipid-based nanocarriers,such as solid lipid nanoparticles(SLNs),nanostructured lipid carriers(NLCs)or nanoemulsions(NEs),can improve nose-to-brain transport by increasing the bioavailability and site-specifc delivery.This review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers(SLNs,NLCs and NEs)for nose-to-brain delivery.Based on the literature available from the past two years,we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal administration.The results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried out.Although the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear,it appears that the intranasal route together with the use of NLCs,SLNs or NEs is advantageous for targeting drugs to the brain.These systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs,so they are expected to be approved by regulatory authorities in the coming years.

Predatory journals and meetings in forensic sciences:what every expert needs to know about this“parasitic”publishing model

The emergence of the internet has transformed all areas of society.This includes the universe of scientific publications,with several publishers now exclusively focusing on the electronic format and open access model while expanding to a megajournal scope.in this context,the pandemic of predatory open access journals(POAJs)and meetings are of grave concern to the academic and research community.This new shift within academia produces a variety of new victims;namely,the authors themselves.in turn,scientific knowledge is often discredited,with the public placing less trust in science.Now more than ever,performing research with integrity and selecting a journal in which to publish requires close attention and expertise.The“predatory movement”has developed increasingly sophisticated techniques for misleading people into believing what seem to be credible professional layouts and legitimate invitations.initiatives such as the Jeffrey Beall’s list,the Cabell’s Scholarly Analytics and Think.Check.Submit offer some guidance to uncover the“parasitic”intervention of predatory journals and meetings,but specific education in this field is sorely needed.This work aims to review the main characteristics of predatory journals and meetings and to analyze this topic in the context of forensic and legal medicine research.

Significance of the balance between intracellular glutathione and polyethylene glycol for successful release of small interfering RNA from gold nanoparticles

为特定的基因 silencing 的小介入 RNA (siRNAs ) 的治疗学的诺言依赖于到细胞质的功能的 siRNAs 的成功的交货。他们到一个确定的交货平台的变化形式例如金 nanoparticles，为治疗疾病并且推进我们细胞的过程的理解提供巨大的潜力。他们的成功或失败依赖于两个进房间和功能的 siRNA 的随后的细胞内部的版本的 nanoparticles 的举起。在这研究，利用金 nanoparticle 对 C-MYC 的 调停siRNA 的交货，我们试图决定我们是否能完成在一个癌症房间击倒与细胞内部的谷胱甘肽的底层排队，并且如果有的话，聚乙烯乙二醇(木钉)决定影响 ligand 密度在上击倒，考虑到决定最佳的 nanoparticle 设计完成 C-MYC 击倒。我们表明那，不管木钉密度，在有相对低的谷胱甘肽层次的房间击倒能被完成，以及为在细胞内部的环境的劈开的 siRNA 的可获得性上的木钉的位的阻碍者的可能的效果。当击倒时，金 nanoparticle 举起经由传播电子显微镜学和集体光谱学被表明被在里面房间 westerns 和 BrdU 加入分别地在蛋白质和生理的层次(在 S 阶段的房间) 决定。

Epigenomic mediation after adverse childhood experiences:a systematic review and meta-analysis

Epigenetic mechanisms are potential mediators of the physiological response to abuse by altering the genetic predisposition of the cellular response to the environment,leading to changes in the regulation of multiple organ systems.This study was established to review the epigenetic mechanisms associated with childhood abuse as well as the long-term deter-minants that these epigenetic changes may have on future illness.We retrospectively ana-lysed the effect of exposure to adverse childhood experiences(ACEs,specifically those relating to childhood maltreatment)between the ages of 0 and 16years on the human epi-genome,as well as possible clinical associations.After meeting inclusion and exclusion crite-ria,36 articles were included in this systematic review.Eight of these studies did not find a relationship between childhood maltreatment and DNA methylation.Of the remaining 28 studies,nine were genome-wide association studies,whereas the rest were candidate gene studies,mainly studying effects on neuroendocrine,serotoninergic and immunoregulatory systems.Meta-analysis of correlation coefficients from candidate gene studies estimated an association of childhood adversity and DNA methylation variation at r=0.291(P<0.0001),and meta-analysis of two epigenome-wide association studies(EWASs)identified 44 differen-tially methylated CpG sites.In conclusion,childhood maltreatment may mediate epigenetic mechanisms through DNA methylation,thereby affecting physiological responses and con-ferring a predisposition to an increased risk for psychopathology and forensic repercussions.Similar evidence for somatic illnesses is not yet available.

Efficacy assessment of peracetic acid in the removal of synthetic 17α-ethinyl estradiol contraceptive hormone in wastewater

Increasing concerns have been raised on endocrine disrupting chemicals like the sex hormone 17 a-ethinylestradiol(EE2),the more since traditional wastewater(WW) treatments appear to be ineffective for their removal.The efficacy of the relatively novel disinfectant peracetic acid(PAA) in EE2 removal was evaluated,as well as its potential effects on WW quality parameters.The treatments tested for EE2 removal were also evaluated in terms of toxicity,through the determination of biochemical responses(antioxidant enzymes,lipid peroxidation and vitellogenin induction) using zebrafish(Danio rerio) as a biological model.PAA contact times less than 20 min appeared insufficient regardless of the PAA dose tested,but a 100% EE2 removal was attained at a PAA concentration of 15 mg/L with a contact time of20 min.Total suspended solids,chemical oxygen demand and pH in PAA treatments remained well within levels set in European legislation for WW discharge.EE2 induced signific ant increased vitellogenin(VTG) levels in both female and male fish,indic ating increased estrogenic activity,especially in males suggesting an endocrine disruption effect.With the addition of PAA(15 mg/L),however,VTG levels in both sexes returned to control values.Although this PAA treatment showed increased levels of the antioxidant enzyme catalase,the lipid peroxidation levels were similar or even lower than in controls.Overall the results suggest that the use of PAA appears a promising way forward as a less toxic alternative to chlorine disinfection with high efficiency in the removal of EDC like EE2.

Diversity of the Formicidae (Hymenoptera) carrion communities in Lisbon (Portugal): preliminary approach as seasonal and geographic indicators

The value of the Formicidae (Insecta,Hymenoptera) community in forensic investigations is poorly studied in Portugal.In order to better understand the structure and dynamics of this group of insects in cadavers and their putative value in forensic investigations,studies were carried out in Lisbon area during one year.Piglet carcasses were used as a model of human decomposition.The entomofauna attracted to the carcasses was collected over a period of about 2 months in each season of the year.The collection of ants was performed at regular intervals,daily in the first 23 days and then with intervals of 2,3 or 5 days until the end of the experiment.Five stages of cadaveric decomposition were recognized with the ants being present in all of them.Three hundred and nine specimens were captured: 7 in autumn,6 in winter,90 in spring and 206 in summer.These specimens belong to three subfamilies and seven different species.Four of them had never been mentioned before as being associated to cadavers in this geographical area.Spring and summer had the greater diversity of species and a larger number of individuals.Temnothorax luteus was the dominant species in spring and Tapinoma nigerrimum in summer.Corroborating the information of other similar studies carried out in the Iberian Peninsula,the sarcosaprophagous Formicidae community found in Lisbon is unique and different from other studied locations,which supports the need to perform regional studies.Our results shown that ants do not present a definite pattern of succession,but some species have the potential to be seasonal or geographic indicators.

Liquid biopsies in myeloid malignancies

Hematologic malignancies are the most common type of cancer affecting children and young adults,and encompass diseases,such as leukemia,lymphoma,and myeloma,all of which impact blood associated tissues such as the bone marrow,lymphatic system,and blood cells.Clinical diagnostics of these malignancies relies heavily on the use of bone marrow samples,which is painful,debilitating,and not free from risks for leukemia patients.Liquid biopsies are based on minimally invasive assessment of markers in the blood(and other fluids)and have the potential to improve the efficacy of diagnostic/therapeutic strategies in leukemia patients,providing a useful tool for the real time molecular profiling of patients.The most promising noninvasive biomarkers are circulating tumor cells,circulating tumor DNA,microRNAs,and exosomes.Herein,we discuss the role of assessing these circulating biomarkers for the understanding of tumor progression and metastasis,tumor progression dynamics through treatment and for follow-up.

Phylogenetic relationships and morphological reappraisal of Melanommataceae(Pleosporales)

The family Melanommataceae is widespread in temperate and subtropical regions and species invariably occur on twigs or bark of various woody plants in terrestrial,marine or freshwater habitats.In this paper,the type species of 26 genera of the family are re-described and illustrated.A multi-gene phylogeny based on maximum likelihood and Bayesian analyses of LSU,SSU,RPB2 and EF-1αsequence data of species of Melanommataceae is provided.The new genera,Muriformistrickeria,Pseudostrickeria and Thysanolaenae are introduced.Anomalemma is synonymized under Exosporiella.Acrocordiopsis,Astrosphaeriella,Beverwykella,Caryosporella,Sporidesmiella and Pseudotrichia are excluded from Melanommataceae based on molecular phylogenetic analyses.Presently,20 genera are accepted in Melanommataceae.Based on the phylogenetic data,five new species,Byssosphaeria siamensis,Herpotrichia vaginatispora,Pseudostrickeria muriformis,Pseudostrickeria ononidis and Muriformistrickeria rubi,are introduced.

Systemic humoral responses of non-muscle-invasive bladder cancer during BCG treatment: less is more

Aim:Intravesical Bacille Calmette-Guérin(BCG)is the mainstay adjuvant treatment of non-muscle-invasive bladder cancer.However,one third of the patients on BCG regimen relapse within the first year of treatment.This study aimed at identifying biomarkers to predict response to BCG treatment.Methods:Gene expression was analyzed in blood cells of 58 patients treated with BCG through six consecutive weekly instillations and then at month 3,6,9,and 12.Cytokines tumor necrosis factor(TNF)-α,interleukin(IL)-10,interferon(IFN)-γ,IL-1β,IL-2,IL-4,and IL-6;chemokines CCL2,CCL3,CCL8,CXCL9,and IP-10;and mediators of cytotoxicity CTLA4,Fas-L,Perf,GNLY,NOS2A,and HMOX-1 were analyzed before the 1st and the 6th week instillation and 24 h after to assess fast(within 24 h)and prolonged changes resulting from treatment.Results:BCG instillation led to fast-increased expression of IL-1β,TNF-α,and IL-10 genes.When compared to relapsing patients,patients with no relapses within one year showed significantly lower expression of IL-1βat 1st week and less IFN-γ,HMOX-1,and GNLY at week 6.HMOX-1 and GNLY were independent predictive biomarkers,and values above the cut-off≥110 and≥13.0‰mRNA,respectively,were considered prejudicial factors.Patients with two HMOX-1 and GNLY factors had highest(66.7%)relapsing risk.Conclusion:Assessing immunomodulators’expression in blood allows the establishment of predictive cut-off values and identification of probabilities for patients’relapses after BCG treatment.