Appropriate oral hygiene significantly reduces the possibility of oral infections.However,dental caries and periodontal diseases are major oral health issues causing chronic diseases due to poor oral health.Recently,h...Appropriate oral hygiene significantly reduces the possibility of oral infections.However,dental caries and periodontal diseases are major oral health issues causing chronic diseases due to poor oral health.Recently,herbal compounds have gained interest in maintaining oral health.Extracts of burdock root(Arctium),noni fruit(Morinda citrifolia),and neem leaf(Azadirachta indica)are now used as intracanal medicaments in endodontics and periodontics.Plectranthus amboinicus species and other plants produces essential oil likeβ-caryophyllene,p-cymene,andγ-terpinene can exhibit antibacterial activity;highlighting phytoconstituents plays a vital role in oral health.The COVID-19 pandemic highlighted the importance of hygiene and sanitization,to curb SARS-CoV-2.Oral cavity is among the gateways for virus entry into saliva.Saliva is a potential reservoir of SARS-CoV-2,and there is an increased risk of infection if there is any fissure in the mouth.This enables entry of virus into the vascular system through gingival or periodontal pocket,possibly reaching lung periphery then to lung vessels by interacting with endothelial surface receptors triggering pulmonary vasoconstriction and lung damage due to endothelial dysfunction.This review aims to draw attention to the possible route of SARS-CoV-2 infection via the oral cavity and the importance of oral hygiene against COVID-19.展开更多
Objective:To characterize the neurocognitive sequelae of cerebral malaria(CM)in an adultsample of the city of Benguela,Angola.Methods:A neuropsychological assessment was carriedout in 22 subjects with prior history of...Objective:To characterize the neurocognitive sequelae of cerebral malaria(CM)in an adultsample of the city of Benguela,Angola.Methods:A neuropsychological assessment was carriedout in 22 subjects with prior history of CM ranging from 6 to 12 months after the infection.Theobtained results were compared to a control group with no previous history of cerebral malaria.The study was conducted in Benguela Central Hospital,Angola in 2011.Results:CM groupobtained lower results on the two last trials of a verbal learning task and on an abstract reasoningtest.Conclusions:CM is associated to a slower verbal learning rate and to difficulties in theability to discriminate and perceive relations between new elements.展开更多
Psoriasis is a chronic, recurrent inflammatory cutaneous disease. Psoriasis patients alternate between periods of remission and periods of exacerbation of the disease. Usually, psoriasis severity is clinically evaluat...Psoriasis is a chronic, recurrent inflammatory cutaneous disease. Psoriasis patients alternate between periods of remission and periods of exacerbation of the disease. Usually, psoriasis severity is clinically evaluated using tools like Psoriasis Area and Severity Index that present some limitations and subjectivity. Clinicians select the therapy according to psoriasis severity, aiming that patients achieve longer remission periods and improve their quality of life. Biological markers for diagnosis and prognosis of psoriasis help to establish its severity and to monitor the therapeutic response; moreover, biomarkers of psoriasis assist clinicians in their therapeutic decision to treat psoriasis and to choose earlier and more adequate therapeutic strategies, avoiding or minimising worsening of psoriasis. With these markers, they would be able to monitor therapeutics, avoiding unnecessary therapeutic surcharge or changes to a more aggressive therapy. As any attempt to identify these biomarkers should be encouraged, in this review,we will debate published data concerning the proposal of biomarkers to evaluate severity and response to treatment of psoriasis vulgaris.展开更多
In this retrospective study we have investigated the anxiety as an impact of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Huntington disease (HD), Machado-Joseph disease (MJD)?and famili...In this retrospective study we have investigated the anxiety as an impact of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Huntington disease (HD), Machado-Joseph disease (MJD)?and familial amyloidotic polyneuropathy (FAP)?V30MTTR. The study included 686 subjects: 586 (85.4%) were the offspring at risk for FAP, 92 (13.4%) for HD and 8 (1.2%) to MJD. Of these, 352 received the carrier result and 305 the non-carrier result. As indicator of anxiety distress was taken the Self-Rating Anxiety Scale of Zung (SAS), applied in the pre-test and the three post-test moments: three weeks, 6 months and one year after notification of test results. Values decreased significantly along the four evaluation moments, regardless the studied disease or test result. For female population, SAS means cores revealed results of clinical anxiety at pre-test, only decreasing to non clinical scores a year after PST disclosure.展开更多
In this retrospective study, we have researched the psychological impact of pre-symptomatic testing (PST) for 2 autosomal dominant late-onset diseases: Huntington disease (HD and familial amyloidotic polyneuropathy (F...In this retrospective study, we have researched the psychological impact of pre-symptomatic testing (PST) for 2 autosomal dominant late-onset diseases: Huntington disease (HD and familial amyloidotic polyneuropathy (FAP) V30M TTR. The study included 53 subjects: 40 (75.5%) were the offspring at risk for FAP and 13 (24.5%) for HD. Of these, 38 (73.1%) received the carrier result and 12 (23.1%) the noncarrier result;3 of them did not want to know the result. The indicators taken for emotional distress were the subscales and global indexes of psychopathological Behavior Symptoms Inventory (BSI), applied in the pre-test and post-test, one-year after notification of results. Values decreased significantly one year after the implementation of the PST, regardless of the studied disease or test result;this seems to corroborate previous studies showing that testing does not increase pre-symptomatic levels of emotional disturbance in individuals. However, the subjects studied showed, for all subscales and global indexes of the BSI, significantly higher values than those of control groups.展开更多
Excessive uptake of purine and glucose can lead to hyperglycemia and hyperuricemia,mediated by specific intestinal transport proteins.Currently,there is a deficiency in targeted regulation of these proteins.In this st...Excessive uptake of purine and glucose can lead to hyperglycemia and hyperuricemia,mediated by specific intestinal transport proteins.Currently,there is a deficiency in targeted regulation of these proteins.In this study,we introduce an oral approach for targeted modulation using electrospun core–shell short-fibers that settle on the intestinal mucosa.These fibers,designed for the controlled in situ release of phlorizin—a multi-transporter inhibitor—are crafted through a refined electrospinning-homogenizing process using polylactic acid and gelatin.Phlorizin is conjugated via a phenyl borate ester bond.Furthermore,a calcium alginate shell ensures intestinal disintegration triggered by pH changes.These fibers adhere to the mucosa due to their unique structure,and phlorizin is released in situ post-ingestion through glucose-sensitive cleavage of the phenyl borate ester bond,enabling dual-target inhibition of intestinal transporter proteins.Both in vitro and in vivo studies confirm that the short-fibers possess intestine-settling and glucose-responsive properties,facilitating precise control over transport proteins.Using models of hyperuricemia and diabetes in mice,treatment with short-fibers results in reduc-tions of 49.6%in blood uric acid and 17.8%in glucose levels,respectively.Additionally,16S rRNA sequencing indicates an improved intestinal flora composition.In conclusion,we have developed an innovative oral strategy for the prevention of hyperglycemia and hyperuricemia.展开更多
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 ...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.展开更多
The crime possibly perpetrated by a doctor named Vicente Urbino de Freitas in 1890 is one of the most famous cases of poisoning,and it had echoes in the Portuguese and foreign press for several decades.This prestigiou...The crime possibly perpetrated by a doctor named Vicente Urbino de Freitas in 1890 is one of the most famous cases of poisoning,and it had echoes in the Portuguese and foreign press for several decades.This prestigious doctor was convicted of the fatal poisoning of his nephew.He also attempted the homicide of two nieces and their mother-in-law,who only escaped because they obstinately refused to comply with the"therapeutics"prescribed by the family doctor.The motive of the crime should have been Vicente Urbino de Freitas'ambition to receive the family inheritance of his wife,the daughter of the well-known mer-chant Jose Antonio Sampaio of Flores Street in Porto.Vicente Urbino de Freitas was con-victed but doubt about his guilt persists for more than a century.This second work aimed to collect and analyse all the relevant and contradictory testimonial evidence of the prosecu-tion and defence witnesses.This case represents an odd historical record obtained through more than 12years of research on the first major significant Portuguese forensic case.Rare and unprecedented testimonial evidence and photographs were obtained from different countries and then repaired,since these also provide an important historical record of the medical photography.展开更多
Clinical and forensic toxicology are critically involved in the acquisition of basic skills to correctly suspect intoxication,collect biological and non-biological materials for toxicological analysis,comprehend the c...Clinical and forensic toxicology are critically involved in the acquisition of basic skills to correctly suspect intoxication,collect biological and non-biological materials for toxicological analysis,comprehend the complexities inherent to laboratory activity,and understand the fundamentals of toxicokinetics and toxicodynamics that underlie the interpretation of results.This works presents a pedagogical innovation proposal for the teaching of clinical and forensic toxicology based on a compilation of more than 3000 cases where the image was fulcra for suspicion.The experience in this article follows the model practiced in bachelors,masters,and PhD degrees,as well as in other continuing training courses,where we are teaching toxicology for more than 15 years.All these levels of education are considered fundamental to the sound development of this science.This approach aims also to offer strength to the intervention of the true toxicologist in all the toxicological phases,besides the classic analytical chemistry.Indeed,it is impossible to provide effective clinical and forensic toxicological interpretations without a proper and broad education,and not thinking exclusively in terms of laboratory techniques.In the future,it will be interesting to evaluate knowledge retention and to propose a database of videos of signs related to intoxications.展开更多
Scientific integrity is a learned skill.When researchers and students learn integrity in laboratories or in the classroom,they are empowered to use similar principles in other aspects of their lives.This commentary re...Scientific integrity is a learned skill.When researchers and students learn integrity in laboratories or in the classroom,they are empowered to use similar principles in other aspects of their lives.This commentary reviews the concepts related to scientific integrity at a time when science faces important challenges related to the increase number of articles produced regarding research on coronavirus disease 2019(COVID-19).Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has ignited another parallel viral pandemic,with science ranging from robust studies to dishonest studies being conducted,posted,and shared at an unprecedented rate.A balance is needed between the benefits of the rapid access to new scientific data and the threat of causing panic or erroneous clinical decisions based on mistakes or misconduct.The truth is that the“scientific research has changed the world”but now,and more than ever,“it needs to change itself”.A pandemic with a“paperdemic”will be even more complicated to manage if it progresses in an uncontrolled manner and is not properly scrutinized.展开更多
Loss or gain of chromosomes,a condition known as aneuploidy,is a common feature of tumor cells and has therefore been proposed as the driving force for tumorigenesis.Such chromosomal instability can arise during mitos...Loss or gain of chromosomes,a condition known as aneuploidy,is a common feature of tumor cells and has therefore been proposed as the driving force for tumorigenesis.Such chromosomal instability can arise during mitosis as a result of mis-segregation of the duplicated sister chromatids to the two daughter cells.In normal cells,missegregation is usually prevented by the spindle assembly checkpoint(SAC),a sophisticated surveillance mechanism that inhibits mitotic exit until all chromosomes have successfully achieved bipolar attachment to spindle microtubules.Complete abrogation of SAC activity is lethal to normal as well as to tumor cells,as a consequence of massive chromosome mis-segregation.Importantly,many human aneuploid tumor cells exhibit a weakened SAC activity that allows them to tolerate gains or losses of a small number of chromosomes;and interfering with this SAC residual activity may constitute a suitable strategy to kill cancer cells.This review focuses on the potential link between SAC and tumorigenesis,and the therapeutic strategy to target the SAC for cancer treatment.展开更多
This article aims to review general procedures for sampling of routinely collected as well as on alternative samples that may provide additional information regarding intoxication.These approaches may be applied whene...This article aims to review general procedures for sampling of routinely collected as well as on alternative samples that may provide additional information regarding intoxication.These approaches may be applied whenever sample collection for clinical and forensic toxicology is required and should be considered as general guidelines that must be adapted to each specific case.It is expected that this article will help toxicologists and other forensic experts to accomplish their mission,since the toxicological result is first influenced by the quality and quantity of the sample available for analysis.These guidelines were approved by the European Council of Legal Medicine.展开更多
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 a...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.展开更多
The"Crime of Flores Street"is one of the most famous cases of poisoning to divide public opinion in Portugal in the late 19th century, and it also demonstrated the weaknesses of the Portuguese medicolegal sy...The"Crime of Flores Street"is one of the most famous cases of poisoning to divide public opinion in Portugal in the late 19th century, and it also demonstrated the weaknesses of the Portuguese medicolegal system and attested to the importance of toxicological analysis. Vicente Urbino de Freitas was a prominent doctor, graduating from the Faculty of Medicine of the University of Coimbra in 1875. He later became Professor of Physiology at the Porto Medical-Surgical School and author of a number of books on leprosy. In 1877, he married Maria das Dores Basto Sampaio Freitas, and this was followed by the death of a number of her close relatives in suspicious circumstances, notably her brother José António Sampaio Junior and nephew Mário Guilherme Augusto de Sampaio. This review aims to retell the story of Portugal's first significant medicolegal case as well as the accompanying judicial drama that gave birth to Forensic Toxicology in Portugal and prompted the medicolegal organization that exists today. This research was carried out over a 10-year period and repre-sents undeniable historical value given the rarity of the facts compiled. At the heart of this forensic case was the use of toxicological analyses in court for which the Chemist Antònio Joaquim Ferreira da Silva played a key role. This toxicological report revealed high concen-trations of morphine, delphinine and narceine in viscera and in Mario's urine. The Mario's cause of death was attributed to poisoning by opium alkaloids. Despite the strong judicial evidence, doubts still remains as to whether Vicente Urbino de Freitas was a"monster"or a victim of circumstances and a hapless martyr.展开更多
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 ...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.展开更多
Combination therapy via nanoparticulate systems has already been proposed as a synergistic approach for cancer treatment. Herein, undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles （UnTH...Combination therapy via nanoparticulate systems has already been proposed as a synergistic approach for cancer treatment. Herein, undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles （UnTHCPSi NPs） loaded with sorafenib and surface-biofunctionalized with anti-CD326 antibody （Ab） were developed for cancer chemo-immunotherapy in MCF-7 and MDA-MB-231 breast cancer cells. The cytocompatibility study showed no significant toxicity for the bare and antibody-conjugated UnTHCPSi （Un-Ab） NPs at concentrations lower than 200 μg·mL^-1. Compared to the bare UnTHCPSi, Un-Ab NPs loaded with sorafenib reduced the premature drug release in plasma, increasing the probability of proper drug targeting. In addition, high cellular interaction and subsequent internalization of the Un-Ab NPs into the cells expressing CD326 antigen demonstrated the possibility of improving antigen-mediated endocytosis via CD326 targeting. While an in vitro antitumor study revealed a higher inhibitory effect of the sorafenib-loaded Un-Ab NPs compared to the drug-loaded UnTHCPSi NPs in the CD326 positive MCF-7 cells, there was no difference in the anti-proliferation impact of both the abovementioned NPs in the CD326 negative MDA-MB-231 cells, suggesting CD326 as an appropriate receptor for Ab-mediated drug delivery. It was also shown that the anti-CD326 Ab can act as an immunotherapeutic agent by inducing antibody dependent cellular cytotoxicity and enhancing the interaction of effector immune and cancer cells for subsequent phagocytosis and cytokine secretion. Hence, the developed nanovectors can be applied for simultaneous tumor-selective drug targeting and immunotherapy.展开更多
Victim identification through dental features is one of the main objectives of forensic dentistry.In circumstances where information regarding antemortem dental records is missing,reconstruction of a biological profil...Victim identification through dental features is one of the main objectives of forensic dentistry.In circumstances where information regarding antemortem dental records is missing,reconstruction of a biological profile can be useful as a first step toward personal identification.This reconstructive method provides valuable information,namely regarding the individual’s ancestry,through the detection and degree of expression of dental morphological traits,which may help to restrict the number of candidates for identification.Technological advances allowed the development of alternative methods for dental evaluation,that complement or substitute those already in use in clinical practice.Among these,intraoral three‑dimensional(3D)images are increasingly used in dentistry,as they have a high level of accuracy and are easy to obtain and store.However,a fundamental question regarding forensic dentistry is whether they allow recognition and analysis of dental morphological traits in detail,namely those related to ancestry.In this study,we evaluated 20 teeth morphological features using intraoral 3D imaging from 77 individuals from Northern Portugal.Our results showed that it was possible to identify and classify a large part of the main morphological traits used in the estimation of ancestry.As these 3D images present sufficient morphological detail to be classified,we believe that future applications of this technique can be expected in forensic dentistry.展开更多
The objective of this study was to compare the outcomes of nonfatal road traffic accidents by the victims’age group and sex.We used the Portuguese medico-legal rules for personal injury assessment,in the scope of the...The objective of this study was to compare the outcomes of nonfatal road traffic accidents by the victims’age group and sex.We used the Portuguese medico-legal rules for personal injury assessment,in the scope of the Civil Law in that country,which includes a three-dimensional methodology.This was a retrospective study including 667 victims of road traffic accidents aged 3–94 years old.Their final medico-legal reports all used the Portuguese methodology for personal injury assessment.Outcomes were analysed by the victims’age group(children,working-age adults,and older people)and sex.Road traffic accidents were generally serious(ISS mean 9.5),with higher severity in children and older people.The most frequent body sequelae were musculoskeletal(64.8%),which were associated with functional and situational outcomes.Temporary damage resulted in an average length of impairment of daily life of 199.6 days,171.7 days to return to work,and an average degree of quantum doloris(noneconomic damage related to physical and psychological harm)of 3.7/7.The average permanent damage was 7.3/100 points for Permanent Functional Deficit,0.43/3 for Permanent Professional Repercussion,2/7 for Permanent Aesthetic Damage,3.9/7 for Permanent Repercussion on Sexual Activity and 3.2/7 for Permanent Repercussion on Sport and Leisure Activities.Overall,19%of people became permanently dependent(10.6%needed third-party assistance).The medico-legal methodology used,considering victims’real-life situation,allows a comprehensive assessment.There were several significant differences among the three age groups but none between sexes.These differences and the impact of the more severe cases justify further detailed medico-legal studies in these specific situations on children,older people,and severely injured victims.展开更多
Trans-resveratrol(RSV)is recognised as a bioactive ingredient in the development of functional foods.Its stability,solubility,and bioavailability constraints can be overcome by delivery systems,not yet tested in foods...Trans-resveratrol(RSV)is recognised as a bioactive ingredient in the development of functional foods.Its stability,solubility,and bioavailability constraints can be overcome by delivery systems,not yet tested in foods.This study aims at evaluating the impact of two delivery systems on the stability,antioxidant activity,bioaccessibility and bioavailability of RSV integrated into a bread matrix:an inclusion complex of RSV andγ-cyclodextrin(γCD⋅RSV)and RSV loaded zein nanoparticles(nZ-RSV).Wheat bread was supplemented with 0.5%of pure RSV(RSV-bread)and equivalent amounts ofγ-CD⋅RSV and nZ-RSV.The amount of RSV recovered from the hydroethanolic extracts ofγ-CD⋅RSV-and nZ-RSV-bread was 70.3%and 62.8%of the initial amount,respectively,lower than RSV-bread extract,89.0%,indicating lower degradability during bread preparation.Both vehicles helped to retain RSV antioxidant activity but did not increase RSV bioaccessibility(c.a.40%for free RSV andγCD⋅RSV,and 29%for nZ-RSV).In vitro tests on intestinal cell monolayers showed that,after 4 h of contact,only 5.0%of the initially available amount of RSV was able to permeate the intestinal barrier in all samples.Thus,bread itself is a vehicle for RSV integration into our daily diet,without the need for an additional delivery system.展开更多
文摘Appropriate oral hygiene significantly reduces the possibility of oral infections.However,dental caries and periodontal diseases are major oral health issues causing chronic diseases due to poor oral health.Recently,herbal compounds have gained interest in maintaining oral health.Extracts of burdock root(Arctium),noni fruit(Morinda citrifolia),and neem leaf(Azadirachta indica)are now used as intracanal medicaments in endodontics and periodontics.Plectranthus amboinicus species and other plants produces essential oil likeβ-caryophyllene,p-cymene,andγ-terpinene can exhibit antibacterial activity;highlighting phytoconstituents plays a vital role in oral health.The COVID-19 pandemic highlighted the importance of hygiene and sanitization,to curb SARS-CoV-2.Oral cavity is among the gateways for virus entry into saliva.Saliva is a potential reservoir of SARS-CoV-2,and there is an increased risk of infection if there is any fissure in the mouth.This enables entry of virus into the vascular system through gingival or periodontal pocket,possibly reaching lung periphery then to lung vessels by interacting with endothelial surface receptors triggering pulmonary vasoconstriction and lung damage due to endothelial dysfunction.This review aims to draw attention to the possible route of SARS-CoV-2 infection via the oral cavity and the importance of oral hygiene against COVID-19.
基金Supported by the Cooperativa de Ensino Superior Politécnico e Universitário(Grant No.03-UNIPSA-CICS-2011)
文摘Objective:To characterize the neurocognitive sequelae of cerebral malaria(CM)in an adultsample of the city of Benguela,Angola.Methods:A neuropsychological assessment was carriedout in 22 subjects with prior history of CM ranging from 6 to 12 months after the infection.Theobtained results were compared to a control group with no previous history of cerebral malaria.The study was conducted in Benguela Central Hospital,Angola in 2011.Results:CM groupobtained lower results on the two last trials of a verbal learning task and on an abstract reasoningtest.Conclusions:CM is associated to a slower verbal learning rate and to difficulties in theability to discriminate and perceive relations between new elements.
文摘Psoriasis is a chronic, recurrent inflammatory cutaneous disease. Psoriasis patients alternate between periods of remission and periods of exacerbation of the disease. Usually, psoriasis severity is clinically evaluated using tools like Psoriasis Area and Severity Index that present some limitations and subjectivity. Clinicians select the therapy according to psoriasis severity, aiming that patients achieve longer remission periods and improve their quality of life. Biological markers for diagnosis and prognosis of psoriasis help to establish its severity and to monitor the therapeutic response; moreover, biomarkers of psoriasis assist clinicians in their therapeutic decision to treat psoriasis and to choose earlier and more adequate therapeutic strategies, avoiding or minimising worsening of psoriasis. With these markers, they would be able to monitor therapeutics, avoiding unnecessary therapeutic surcharge or changes to a more aggressive therapy. As any attempt to identify these biomarkers should be encouraged, in this review,we will debate published data concerning the proposal of biomarkers to evaluate severity and response to treatment of psoriasis vulgaris.
文摘In this retrospective study we have investigated the anxiety as an impact of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Huntington disease (HD), Machado-Joseph disease (MJD)?and familial amyloidotic polyneuropathy (FAP)?V30MTTR. The study included 686 subjects: 586 (85.4%) were the offspring at risk for FAP, 92 (13.4%) for HD and 8 (1.2%) to MJD. Of these, 352 received the carrier result and 305 the non-carrier result. As indicator of anxiety distress was taken the Self-Rating Anxiety Scale of Zung (SAS), applied in the pre-test and the three post-test moments: three weeks, 6 months and one year after notification of test results. Values decreased significantly along the four evaluation moments, regardless the studied disease or test result. For female population, SAS means cores revealed results of clinical anxiety at pre-test, only decreasing to non clinical scores a year after PST disclosure.
文摘In this retrospective study, we have researched the psychological impact of pre-symptomatic testing (PST) for 2 autosomal dominant late-onset diseases: Huntington disease (HD and familial amyloidotic polyneuropathy (FAP) V30M TTR. The study included 53 subjects: 40 (75.5%) were the offspring at risk for FAP and 13 (24.5%) for HD. Of these, 38 (73.1%) received the carrier result and 12 (23.1%) the noncarrier result;3 of them did not want to know the result. The indicators taken for emotional distress were the subscales and global indexes of psychopathological Behavior Symptoms Inventory (BSI), applied in the pre-test and post-test, one-year after notification of results. Values decreased significantly one year after the implementation of the PST, regardless of the studied disease or test result;this seems to corroborate previous studies showing that testing does not increase pre-symptomatic levels of emotional disturbance in individuals. However, the subjects studied showed, for all subscales and global indexes of the BSI, significantly higher values than those of control groups.
基金supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(81930051 and 22105127)+1 种基金the Shanghai Municipal Health Commission(2022XD055 and 202140128)the Shanghai Jiao Tong University School of Medicine PhD Cultivation Fund for Science and Innovation(24KCPYYB005).
文摘Excessive uptake of purine and glucose can lead to hyperglycemia and hyperuricemia,mediated by specific intestinal transport proteins.Currently,there is a deficiency in targeted regulation of these proteins.In this study,we introduce an oral approach for targeted modulation using electrospun core–shell short-fibers that settle on the intestinal mucosa.These fibers,designed for the controlled in situ release of phlorizin—a multi-transporter inhibitor—are crafted through a refined electrospinning-homogenizing process using polylactic acid and gelatin.Phlorizin is conjugated via a phenyl borate ester bond.Furthermore,a calcium alginate shell ensures intestinal disintegration triggered by pH changes.These fibers adhere to the mucosa due to their unique structure,and phlorizin is released in situ post-ingestion through glucose-sensitive cleavage of the phenyl borate ester bond,enabling dual-target inhibition of intestinal transporter proteins.Both in vitro and in vivo studies confirm that the short-fibers possess intestine-settling and glucose-responsive properties,facilitating precise control over transport proteins.Using models of hyperuricemia and diabetes in mice,treatment with short-fibers results in reduc-tions of 49.6%in blood uric acid and 17.8%in glucose levels,respectively.Additionally,16S rRNA sequencing indicates an improved intestinal flora composition.In conclusion,we have developed an innovative oral strategy for the prevention of hyperglycemia and hyperuricemia.
文摘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.
文摘The crime possibly perpetrated by a doctor named Vicente Urbino de Freitas in 1890 is one of the most famous cases of poisoning,and it had echoes in the Portuguese and foreign press for several decades.This prestigious doctor was convicted of the fatal poisoning of his nephew.He also attempted the homicide of two nieces and their mother-in-law,who only escaped because they obstinately refused to comply with the"therapeutics"prescribed by the family doctor.The motive of the crime should have been Vicente Urbino de Freitas'ambition to receive the family inheritance of his wife,the daughter of the well-known mer-chant Jose Antonio Sampaio of Flores Street in Porto.Vicente Urbino de Freitas was con-victed but doubt about his guilt persists for more than a century.This second work aimed to collect and analyse all the relevant and contradictory testimonial evidence of the prosecu-tion and defence witnesses.This case represents an odd historical record obtained through more than 12years of research on the first major significant Portuguese forensic case.Rare and unprecedented testimonial evidence and photographs were obtained from different countries and then repaired,since these also provide an important historical record of the medical photography.
文摘Clinical and forensic toxicology are critically involved in the acquisition of basic skills to correctly suspect intoxication,collect biological and non-biological materials for toxicological analysis,comprehend the complexities inherent to laboratory activity,and understand the fundamentals of toxicokinetics and toxicodynamics that underlie the interpretation of results.This works presents a pedagogical innovation proposal for the teaching of clinical and forensic toxicology based on a compilation of more than 3000 cases where the image was fulcra for suspicion.The experience in this article follows the model practiced in bachelors,masters,and PhD degrees,as well as in other continuing training courses,where we are teaching toxicology for more than 15 years.All these levels of education are considered fundamental to the sound development of this science.This approach aims also to offer strength to the intervention of the true toxicologist in all the toxicological phases,besides the classic analytical chemistry.Indeed,it is impossible to provide effective clinical and forensic toxicological interpretations without a proper and broad education,and not thinking exclusively in terms of laboratory techniques.In the future,it will be interesting to evaluate knowledge retention and to propose a database of videos of signs related to intoxications.
基金supported by grants from CESPU[grant numbers TramTap-CESPU-2016,Chronic-TramTap_CESPU_2017 and TraTapMDMA-CESPU-2018]。
文摘Scientific integrity is a learned skill.When researchers and students learn integrity in laboratories or in the classroom,they are empowered to use similar principles in other aspects of their lives.This commentary reviews the concepts related to scientific integrity at a time when science faces important challenges related to the increase number of articles produced regarding research on coronavirus disease 2019(COVID-19).Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has ignited another parallel viral pandemic,with science ranging from robust studies to dishonest studies being conducted,posted,and shared at an unprecedented rate.A balance is needed between the benefits of the rapid access to new scientific data and the threat of causing panic or erroneous clinical decisions based on mistakes or misconduct.The truth is that the“scientific research has changed the world”but now,and more than ever,“it needs to change itself”.A pandemic with a“paperdemic”will be even more complicated to manage if it progresses in an uncontrolled manner and is not properly scrutinized.
基金H.B.was supported by grant#04-GBMC-CICS-09,from CESPU–Cooperativa de Ensino Superior Politécnico e Universitário.
文摘Loss or gain of chromosomes,a condition known as aneuploidy,is a common feature of tumor cells and has therefore been proposed as the driving force for tumorigenesis.Such chromosomal instability can arise during mitosis as a result of mis-segregation of the duplicated sister chromatids to the two daughter cells.In normal cells,missegregation is usually prevented by the spindle assembly checkpoint(SAC),a sophisticated surveillance mechanism that inhibits mitotic exit until all chromosomes have successfully achieved bipolar attachment to spindle microtubules.Complete abrogation of SAC activity is lethal to normal as well as to tumor cells,as a consequence of massive chromosome mis-segregation.Importantly,many human aneuploid tumor cells exhibit a weakened SAC activity that allows them to tolerate gains or losses of a small number of chromosomes;and interfering with this SAC residual activity may constitute a suitable strategy to kill cancer cells.This review focuses on the potential link between SAC and tumorigenesis,and the therapeutic strategy to target the SAC for cancer treatment.
基金Ricardo Dinis-Oliveira acknowledges Fundacao para a Ciencia e a Tecnologia(FCT)for his Investigator Grant(IF/01147/2013).
文摘This article aims to review general procedures for sampling of routinely collected as well as on alternative samples that may provide additional information regarding intoxication.These approaches may be applied whenever sample collection for clinical and forensic toxicology is required and should be considered as general guidelines that must be adapted to each specific case.It is expected that this article will help toxicologists and other forensic experts to accomplish their mission,since the toxicological result is first influenced by the quality and quantity of the sample available for analysis.These guidelines were approved by the European Council of Legal Medicine.
基金Ricardo Dinis-Oliveira acknowledges FEDER under Pro-gram PT2020[project number 007265–UID/QUI/50006/2013]the support from project NORTE-01-0145-FEDER-000024+1 种基金sustained by Norte Portugal Regional Oper-ational Program(NORTE 2020)under the PORTUGAL 2020 Partnership Agreement(DESignBIOtecHealth-New Technologies for three Health Challenges of Modern Socie-ties:Diabetes,Drug Abuse and Kidney Diseases),through the European Regional Development Fund(ERDF).
文摘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.
基金Ricardo Dinis-Oliveira acknowledges Fundacao para a Ciencia e a Tecnologia(FCT)for his Investigator Grant[grant number IF/01147/2013]This work was supported by FEDER under Program PT2020[grant number 007265-UID/QUI/50006/2013].
文摘The"Crime of Flores Street"is one of the most famous cases of poisoning to divide public opinion in Portugal in the late 19th century, and it also demonstrated the weaknesses of the Portuguese medicolegal system and attested to the importance of toxicological analysis. Vicente Urbino de Freitas was a prominent doctor, graduating from the Faculty of Medicine of the University of Coimbra in 1875. He later became Professor of Physiology at the Porto Medical-Surgical School and author of a number of books on leprosy. In 1877, he married Maria das Dores Basto Sampaio Freitas, and this was followed by the death of a number of her close relatives in suspicious circumstances, notably her brother José António Sampaio Junior and nephew Mário Guilherme Augusto de Sampaio. This review aims to retell the story of Portugal's first significant medicolegal case as well as the accompanying judicial drama that gave birth to Forensic Toxicology in Portugal and prompted the medicolegal organization that exists today. This research was carried out over a 10-year period and repre-sents undeniable historical value given the rarity of the facts compiled. At the heart of this forensic case was the use of toxicological analyses in court for which the Chemist Antònio Joaquim Ferreira da Silva played a key role. This toxicological report revealed high concen-trations of morphine, delphinine and narceine in viscera and in Mario's urine. The Mario's cause of death was attributed to poisoning by opium alkaloids. Despite the strong judicial evidence, doubts still remains as to whether Vicente Urbino de Freitas was a"monster"or a victim of circumstances and a hapless martyr.
文摘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.
文摘Combination therapy via nanoparticulate systems has already been proposed as a synergistic approach for cancer treatment. Herein, undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles （UnTHCPSi NPs） loaded with sorafenib and surface-biofunctionalized with anti-CD326 antibody （Ab） were developed for cancer chemo-immunotherapy in MCF-7 and MDA-MB-231 breast cancer cells. The cytocompatibility study showed no significant toxicity for the bare and antibody-conjugated UnTHCPSi （Un-Ab） NPs at concentrations lower than 200 μg·mL^-1. Compared to the bare UnTHCPSi, Un-Ab NPs loaded with sorafenib reduced the premature drug release in plasma, increasing the probability of proper drug targeting. In addition, high cellular interaction and subsequent internalization of the Un-Ab NPs into the cells expressing CD326 antigen demonstrated the possibility of improving antigen-mediated endocytosis via CD326 targeting. While an in vitro antitumor study revealed a higher inhibitory effect of the sorafenib-loaded Un-Ab NPs compared to the drug-loaded UnTHCPSi NPs in the CD326 positive MCF-7 cells, there was no difference in the anti-proliferation impact of both the abovementioned NPs in the CD326 negative MDA-MB-231 cells, suggesting CD326 as an appropriate receptor for Ab-mediated drug delivery. It was also shown that the anti-CD326 Ab can act as an immunotherapeutic agent by inducing antibody dependent cellular cytotoxicity and enhancing the interaction of effector immune and cancer cells for subsequent phagocytosis and cytokine secretion. Hence, the developed nanovectors can be applied for simultaneous tumor-selective drug targeting and immunotherapy.
文摘Victim identification through dental features is one of the main objectives of forensic dentistry.In circumstances where information regarding antemortem dental records is missing,reconstruction of a biological profile can be useful as a first step toward personal identification.This reconstructive method provides valuable information,namely regarding the individual’s ancestry,through the detection and degree of expression of dental morphological traits,which may help to restrict the number of candidates for identification.Technological advances allowed the development of alternative methods for dental evaluation,that complement or substitute those already in use in clinical practice.Among these,intraoral three‑dimensional(3D)images are increasingly used in dentistry,as they have a high level of accuracy and are easy to obtain and store.However,a fundamental question regarding forensic dentistry is whether they allow recognition and analysis of dental morphological traits in detail,namely those related to ancestry.In this study,we evaluated 20 teeth morphological features using intraoral 3D imaging from 77 individuals from Northern Portugal.Our results showed that it was possible to identify and classify a large part of the main morphological traits used in the estimation of ancestry.As these 3D images present sufficient morphological detail to be classified,we believe that future applications of this technique can be expected in forensic dentistry.
文摘The objective of this study was to compare the outcomes of nonfatal road traffic accidents by the victims’age group and sex.We used the Portuguese medico-legal rules for personal injury assessment,in the scope of the Civil Law in that country,which includes a three-dimensional methodology.This was a retrospective study including 667 victims of road traffic accidents aged 3–94 years old.Their final medico-legal reports all used the Portuguese methodology for personal injury assessment.Outcomes were analysed by the victims’age group(children,working-age adults,and older people)and sex.Road traffic accidents were generally serious(ISS mean 9.5),with higher severity in children and older people.The most frequent body sequelae were musculoskeletal(64.8%),which were associated with functional and situational outcomes.Temporary damage resulted in an average length of impairment of daily life of 199.6 days,171.7 days to return to work,and an average degree of quantum doloris(noneconomic damage related to physical and psychological harm)of 3.7/7.The average permanent damage was 7.3/100 points for Permanent Functional Deficit,0.43/3 for Permanent Professional Repercussion,2/7 for Permanent Aesthetic Damage,3.9/7 for Permanent Repercussion on Sexual Activity and 3.2/7 for Permanent Repercussion on Sport and Leisure Activities.Overall,19%of people became permanently dependent(10.6%needed third-party assistance).The medico-legal methodology used,considering victims’real-life situation,allows a comprehensive assessment.There were several significant differences among the three age groups but none between sexes.These differences and the impact of the more severe cases justify further detailed medico-legal studies in these specific situations on children,older people,and severely injured victims.
基金supported by the NETDIAMOND project POCI-01-0145-FEDER-016385,University of Aveiro and LAQV-REQUIMTE(UIDB/50006/2020)Andreia Silva acknowledges FCT for the Ph.D.grant SFRH/BD/142100/2018。
文摘Trans-resveratrol(RSV)is recognised as a bioactive ingredient in the development of functional foods.Its stability,solubility,and bioavailability constraints can be overcome by delivery systems,not yet tested in foods.This study aims at evaluating the impact of two delivery systems on the stability,antioxidant activity,bioaccessibility and bioavailability of RSV integrated into a bread matrix:an inclusion complex of RSV andγ-cyclodextrin(γCD⋅RSV)and RSV loaded zein nanoparticles(nZ-RSV).Wheat bread was supplemented with 0.5%of pure RSV(RSV-bread)and equivalent amounts ofγ-CD⋅RSV and nZ-RSV.The amount of RSV recovered from the hydroethanolic extracts ofγ-CD⋅RSV-and nZ-RSV-bread was 70.3%and 62.8%of the initial amount,respectively,lower than RSV-bread extract,89.0%,indicating lower degradability during bread preparation.Both vehicles helped to retain RSV antioxidant activity but did not increase RSV bioaccessibility(c.a.40%for free RSV andγCD⋅RSV,and 29%for nZ-RSV).In vitro tests on intestinal cell monolayers showed that,after 4 h of contact,only 5.0%of the initially available amount of RSV was able to permeate the intestinal barrier in all samples.Thus,bread itself is a vehicle for RSV integration into our daily diet,without the need for an additional delivery system.
