Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. Chemokines and their receptors pl...Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. Chemokines and their receptors play a diversified and important role, either homeostatic or inflammatory and direct different immune-competent cell types to the allograft. While deeply studied in the last two decades, controversy persists as a result of chemokines’ pleiotropic actions. We report our analysis of CCR1, CCR3, CCR7, CCL5 and CX3CL1 expression or synthesis by graft-infiltrating cells in human kidney transplants (KTx). At the same time, we tested their robustness in diagnosing acute rejection. Methods: Fine-needle aspiration biopsies (Fnab) were performed either on days 7 or 14 post-transplantation among stable KTx and on the day of acute rejection (AR) diagnosis. Fnab cytopreparations were studied by the enzymatic avidin-biotin complex staining for CCR1, CCR3, CCR7 and CX3CL1. From another subgroup of cases, Fnab samples were cultured for 48 hours and the supernatants were analysed for CCL5 by ELISA. Results: The group of AR cases showed a significantly up-regulated expression of CCR1, CCR3, CCR7 and CX3CL1 and a significantly higher synthesis of CCL5. The positive predictive values were respectively 92%, 97%, 85%, 76% and 78% and negative predictive values were by the same order, 100%, 73%, 100%, 98% and 83%. Conclusions: Our study permits us to advance that CCR1 and CCR3 play a significant and non-redundant role in acute rejection, and it is the first report of CCR3 association with rejection, probably related to CCL5. The presence inside the graft of significant up-regulation for CCR7 surmises that part of antigen presentation may be performed there without being restricted to secondary lymphoid sites. Our results with CX3CL1 confirm other reports.展开更多
During the past decades, endoscopic resection techniques have gradually improved and gained more importance for the management of premalignant lesions and early cancers. These endoscopic resection techniques can be di...During the past decades, endoscopic resection techniques have gradually improved and gained more importance for the management of premalignant lesions and early cancers. These endoscopic resection techniques can be divided in 3 major groups: snare polipectomy, endoscopic mucosal resection(EMR) and endoscopic submucosal dissection(ESD). The use of submucosal injection is essential for the majority of EMR techniques and is an integral part of ESD,whereas during polipectomy it is not crucial in most cases except to prevent bleeding in large polyps and/or those with large stalks as an alternative to mechanical methods. Injection provides a lifting up effect of the lesion separating it from the muscular layer, thereby reducing thermal injury and the risk of perforation and bleeding while also facilitating en-bloc resection by improving technical feasibility. With this work, we aim to review the most common endoscopic resection techniques and the importance of submucosal injection in each one of them. For that, we present some of the most commonly used submucosal injection solutions, taking into account their advantages and disadvantages. We also discuss, based on current recommendations and our own experience, how and when to preform submucosal injection, depending on lesions features and endoscopic resection technique that′s being used, to assure complete resection and to prevent associated adverse events. Finally, we also present and discuss some new proposed submucosal injection solutions,endoscopic resection techniques and devices that may have a major impact on the future of therapeutic endoscopy.展开更多
AIM: To investigate the relationship between the -765G > C COX-2 polymorphism and the development of different gastric lesions: atrophy or intestinal metaplasia and gastric adenocarcinoma. METHODS: A cross-sectiona...AIM: To investigate the relationship between the -765G > C COX-2 polymorphism and the development of different gastric lesions: atrophy or intestinal metaplasia and gastric adenocarcinoma. METHODS: A cross-sectional study was performed involving 320 Portuguese individuals (210 without evidence of neoplastic disease, 73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal metaplasia) using a PCR-RFLP method. RESULTS: -765C allele was overrepresented in the patients with gastric adenocarcinoma (51%) when compared either with the control group (38%) or patients with atrophy or intestinal metaplasia (27%). Callele was found to be very common in our population (0.22), and a multivariate logistic regression analysis revealed nearly 3-fold increased risk for the progression to gastric adenocarcinoma in patients with atrophy or intestinal metaplasia carrying the -765C allele (OR = 2.67, 95% CI = 1.03-6.93; P = 0.04).considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.展开更多
Hypertension is a very prevalent risk factor for cardiovascular disease. The prevalence of resistant hypertension, i.e., uncontrolled hypertension with 3 or more antihypertensive agents including 1 diuretic, is betwee...Hypertension is a very prevalent risk factor for cardiovascular disease. The prevalence of resistant hypertension, i.e., uncontrolled hypertension with 3 or more antihypertensive agents including 1 diuretic, is between 5% and 30% in the hypertensive population. The causes of resistant hypertension are multifactorial and include behavioral and biological factors, such as nonadherence to pharmacological treatment. All current treatment guidelines highlight the positive role of physical exercise as a non-pharmacological tool in the treatment of hypertension. This paper draws attention to the possible role of physical exercise as an adjunct non-pharmacological tool in the management of resistant hypertension. A few studies have investigated it, employing different methodologies, and taken together they have shown promising results. In summary, the available evidence suggests that aerobic physical exercise could be a valuable addition to the optimal pharmacological treatment of patients with resistant hypertension.展开更多
Hepatocarcinoma(HCC) is a highly prevalent cancer worldwide and its inflammatory background was established long ago.Recent studies have shown that innate immunity is closely related to the HCC carcinogenesis.An effec...Hepatocarcinoma(HCC) is a highly prevalent cancer worldwide and its inflammatory background was established long ago.Recent studies have shown that innate immunity is closely related to the HCC carcinogenesis.An effective innate immunity response relies on the tolllike receptors(TLR) found in several different liver cells which,through different ligands and many signaling pathways can elicit,not only a pro-inflammatory but also an oncogenic or anti-oncogenic response.Our aim was to study the role of TLRs in the liver oncogenesis and as a consequence their value as potential therapeutic targets.We performed a systematic review of PubMed searching for original articles studying the relationship between HCC and TLRs until March 2015.TLR2 appears to be a fundamental stress-sensor as its absence reveals an augmented tendency to accumulate DNAdamages and to cell survival.However,pathways are still not fully understood as TLR2 up-regulation was also associated to enhanced tumorigenesis.TLR3 has a wellknown protective role influencing crucial processes like angiogenesis,cell growth or proliferation.TLR4 works as an interesting epithelial-mesenchymal transition's inducer and a promoter of cell survival probably inducing HCC carcinogenesis even though an anti-cancer role has already been observed.TLR9's influence on carcinogenesis is also controversial and despite a potential anticancer capacity,a pro-tumorigenic role is more likely.Genetic polymorphisms in some TLRs have been found and its influence on the risk of HCC has been reported.As therapeutic targets,TLRs are already in use and have a great potential.In conclusion,TLRs have been shown to be an interesting influence on the HCCs microenvironment,with TLR3 clearly determining an antitumour influence.TLR4 and TLR9 are considered to have a positive relationship with tumour development even though,in each of them anti-tumorigenic signals have been described.TLR2 presents a more ambiguous role,possibly depending on the stage of the inflammationHCC axis.展开更多
AIM: To investigate the association between epidermal growth factor (EGF) +61A/G polymorphism and susceptibility to gastric cancer, through a cross-sectional study. METHODS: Polymerase chain reaction resctriction frag...AIM: To investigate the association between epidermal growth factor (EGF) +61A/G polymorphism and susceptibility to gastric cancer, through a cross-sectional study. METHODS: Polymerase chain reaction resctriction fragment lenght polymorphism analyses were used to genotype EGF +61 in 207 patients with gastric lesions (162 patients with gastric adenocarcinomas, 45 with atrophy or intestinal metaplasia) and 984 controls. All subjects were Caucasian. RESULTS: Genotype distribution was 23.5% for GG and 76.5% for GA/AA in the control group, 18.4% for GG and 68.6% for GA/AA in the entire group with gastric lesions and 17.9% for GG and 82.1% for GA/AA in the group with gastric adenocarcinoma. No statistically significant associations were found between EGF +61 variants and risk for developing gastric cancer [odds ratios (OR) = 1.41, 95% confidence intervals (CI): 0.90-2.21, P = 0.116]. However, the stratification of individuals by gender revealed that males carrying A alleles (EGF +61A/G or AA) had an increased risk for developing gastric cancer as compared to GG homozygous males (OR = 1.55, 95% CI: 1.05-2.28, P = 0.021). CONCLUSION: In summary, we found that males who were A carriers for EGF +61 had an increased risk for developing gastric cancer. This result may be explained by the suggestion that women secrete less gastric acid than men.展开更多
AIM: To identify demographic and clinical factors asso-ciated with disabling Crohn's disease (CD). METHODS: A systematic review and meta-analysisof observational studies, focusing on the factors that can predict t...AIM: To identify demographic and clinical factors asso-ciated with disabling Crohn's disease (CD). METHODS: A systematic review and meta-analysisof observational studies, focusing on the factors that can predict the prognosis of different outcomes of CD was undertaken. PubMed, ISI Web of Knowledge and Scopus were searched to identify studies investigat-ing the above mentioned factors in adult patients with CD. Studies were eligible for inclusion if they describe prognostic factors in CD, with inclusion and exclusion criteria defined as follows. Studies with adult patients and CD, written in English and studying association between clinical factors and at least one prognosis out-come were included. Meta-analysis of effects was un-dertaken for the disabling disease outcome, using odds ratio (OR) to assess the effect of the different factors in the outcome. The statistical method used was Mantel-Haenszel for fixed effects. The 16-item quality assess-ment tool (QATSDD) was used to assess the quality of the studies (range: 0-42). RESULTS: Of the 913 papers initially selected, sixty studies were reviewed and three were included in the systematic review and meta-analysis. The global QA-TSDD scores of papers were 18, 21 and 22. Of a total of 1961 patients enrolled, 1332 (78%) were classified with disabling disease five years after diagnosis. In two studies, age at diagnosis was a factor associated with disabling disease five years after diagnosis. Individu-als under 40 years old had a higher risk of developing disabling disease. In two studies, patients who were treated with corticosteroids on the first flare developed disabling disease five years after diagnosis. Further, perianal disease was found to be relevant in all of the studies at two and five years after diagnosis. Finally, one study showed localization as a factor associated with disabling disease five years after diagnosis, with L3 being a higher risk factor. This meta-analysis showed a significantly higher risk of developing disabling dis-ease at five years after initial diagnosis among patients younger than 40 years of age (OR=2.47, 95%CI: 1.74-3.51), with initial steroid treatment for first flare (OR=2.42, 95%CI: 1.87-3.11) and with perianal dis-ease (OR = 2.00, 95%CI: 1.41-2.85).CONCLUSION: Age at diagnosis, perianal disease, ini-tial use of steroids and localization seem to be indepen-dent prognostic factors of disabling disease.展开更多
The prevalence of pediatric obesity continues to increase worldwide,bringing with it various metabolic,functional,social,and psychological complications.1 Both the prevention and treatment of childhood obesity must be...The prevalence of pediatric obesity continues to increase worldwide,bringing with it various metabolic,functional,social,and psychological complications.1 Both the prevention and treatment of childhood obesity must be based on multidisciplinary approaches combining nutrition,physical activity(PA),and psychological support.2 As an essential element of these multicomponent strategies,regular physical activity has been acknowledged as having beneficial effects on children's and adolescents,body composition,physical fitness,and metabolic profile,as well as on their health-related quality of life,social and psychological health,and academic achievement.3,4 Given that only a relatively small proportion of children and adolescents meet the public health recommendations for PA,5 and given that weight loss exercise-based interventions suffer from a high attrition rate,there is a clear need for appropriate PAs.展开更多
AIM:To evaluate the use of web-based technologies to assess the learning curve and reassess reproducibility of a simplified version of a classification for gastric magnification chromoendoscopy (MC). METHODS: As part ...AIM:To evaluate the use of web-based technologies to assess the learning curve and reassess reproducibility of a simplified version of a classification for gastric magnification chromoendoscopy (MC). METHODS: As part of a multicenter trial, a hybrid approach was taken using a CD-ROM, with 20 films of MC lasting 5 s each and an "autorun" file triggering a local HTML frameset referenced to a remote questionnaire through an Internet connection. Three endoscopists were asked to prospectively and independently classify 10 of these films randomly selected with at least 3 d apart. The answers were centrally stored and returned to participants together with adequate feedback with the right answer. RESULTS: For classification in 3 groups, both intra- [Cohen's kappa (κ) = 0.79-1.00 to 0.89-1.00] and inter-observer agreement increased from 1st (moderate) to 6th observation (κ = 0.94). Also, agreement with reference increased in the last observations (0.90, 1.00 and 1.00, for observers A, B and C, respectively). Validity of 100% was obtained by all observers at their 4th observation. When a 4th (sub)group was considered, inter-observer agreement was almost perfect (κ=0.92) at 6th observation. The relation with reference clearly improved into κ (0.93-1.00) and sensitivity (75%-100%) at their 6th observations. CONCLUSION: This MC classification seems to be easily explainable and learnable as shown by excellent intra-and inter-observer agreement, and improved agreement with reference. A web system such as the one used in this study may be useful for endoscopic or other image based diagnostic procedures with respect to definition, education and dissemination.展开更多
Background: We studied the expression of important costimulatory molecules of lymphocyte activation and the presence of CD16<sup><span style="font-family:Verdana;vertical-align:super;">+</span...Background: We studied the expression of important costimulatory molecules of lymphocyte activation and the presence of CD16<sup><span style="font-family:Verdana;vertical-align:super;">+</span></sup><span style="font-family:Verdana;"> cells on aspiration biopsies of kidney transplants, measured three soluble factors and whe</span><span style="font-family:Verdana;">n indicated tested their robustness in diagnosing acute rejection.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Methods</span><span style="font-family:Verdana;">: Fine-needle aspiration biopsies were performed either on days seven or 14</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">30 post-transplantation among stable kidney transplants and on the day of acute rejection diagnosis, while a sample of peripheral blood was collected simultaneously. The cyto</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">preparations were studied by the enzymatic </span><span style="font-family:Verdana;">avidin biotin complex staining. The immunocytochemistry was directed to CD16, CD28, CD152, ICOS, CD40, CD154, CD26 and CD27. We performed the analysis in the peripheral blood by ELISA for soluble(s) CD16, CD26, and CD154.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Results: The group of acute rejection cases showed a significant up-regulated expression of CD16, CD26, ICOS and CD40 as compared to the group of stable cases. Both sCD16 and sCD154 were significantly higher in the blood samples of the group with acute rejection. Thymoglobulin down-regulated CD154 and sCD16. CD16, CD26 and ICOS exhibited very high sensitivity and specificity for acute rejection diagnosis.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Conclusions: The presence of CD16</span><sup><span style="font-family:Verdana;vertical-align:super;">+</span></sup><span style="font-family:Verdana;"> cells inside the graft emerged as a distinct player in acute rejection, confirming other previous reports whereas we first document that in human kidney transplants, ICOS and CD26 are significantly up-regulated and both reached positive predictive values for acute rejection ≥ 80%. The other costimulatory molecules, with the exception of CD40, though widely known, did not show robust association with immune events.</span>展开更多
<p style="text-align:justify;"> <span>Following organ transplantation</span><span>,</span><span> the outcome of the encounter between an APC and a T lymphocyte is str...<p style="text-align:justify;"> <span>Following organ transplantation</span><span>,</span><span> the outcome of the encounter between an APC and a T lymphocyte is strongly dependent on the presence of costimulatory and co-inhibitory molecules, the former associated with allograft rejection and the latter with allograft acceptance. We evaluated the expression of PD-L2, GITR, ILT-2/3/5, and ILT-4 on graft-infiltrating cells procured by Fnab from human KTx under different immunosuppressive regimens. Methods: Fnab biopsies were performed on days 7 or 14</span><span> </span><span>-</span><span> </span><span>30 in stable KTx and on the day of acute rejection diagnosis. Cytopreparations were studied by the enzymatic avidin biotin complex staining. Results: Acute rejection group </span><span>showed a significant down-regulated expression of PD-L2, GITR, and ILT-2/3/5 </span><span>as compared to stable group, while for ILT-4 we did not find significant difference. Anti-IL2</span><i><span>α</span></i><span>R and rapamicyn treatment trend to down-regulate ILT-4 expression, although meaningless. A significant</span><span>ly</span><span> positive correlation was observed between PD-L2 and GITR expression in Fnab. The PPV for acute rejection diagnosis for both PD-L2 and GITR w</span><span>as</span><span> clearly above 0.8. Conclusions: Our findings point to an early entrance of cells expressing PD-L2, GITR and ILT-2/3/5 inside human KTx who are going to remain rejection-free. Both PD-L2 and GITR shared a high ability to rule-in and rule-out acute rejection.</span> </p>展开更多
<strong>Background:</strong> Ischemia-reperfusion injury of organ transplantation activates several mediators which may link the innate to the adaptive immune response. Down the cascade of TLRs, we selecte...<strong>Background:</strong> Ischemia-reperfusion injury of organ transplantation activates several mediators which may link the innate to the adaptive immune response. Down the cascade of TLRs, we selected to study the expression of Interferon Regulatory Factors (IRF)-3 and -7 inside human Kidney Transplanted (KTx) organs and the synthesis of IFN<i>α</i>, the main growth factor induced by them, in KTx aspiration biopsy cultures. Simultaneously, we tested their robustness in diagnosing Acute Rejection (AR). <strong>Methods:</strong> Fine-needle aspiration biopsies (F-nab) were performed either on day 7 or 14 post-KTx among stable patients or on the day of AR diagnosis. On Fnab cytopreparations, we studied IRF3 and IRF7 by the enzymatic avidin-biotin complex staining, and in a different group of cases we quantified IFN<i>α</i> by ELISA in 48 hours Fnab culture supernatants. <strong>Results:</strong> AR group showed a significantly up-regulated expression for IRF3 and IRF7, reaching Positive Predictive Values (PPV) of 0.824 and 0.8, respectively, as well as Negative Predictive Values (NPV) above 0.9 for both;IFN<i>α</i> presented a PPV = 1.0 and a NPV = 0.9. A variation in the results was noticed according to different immunosuppressive therapies. <strong>Conclusions:</strong> Our findings suggest that IRF3 and IRF7, and IFN<i>α</i> which they promote, may be very important players in the early days post-KTx, linking the innate with an adaptive response and triggering acute rejection. These differences were very clear-cut, lending consistency to our speculation. It would be important to scrutinize for other potential effects derived from these IRFs up-regulation which could be of clinical relevance.展开更多
Among the various types of disability that can affect humans, spinal cord injury (SCI) is undoubtedly one of the most devastating. This type of injury is a disruptive incident in the individual’s life, entails signif...Among the various types of disability that can affect humans, spinal cord injury (SCI) is undoubtedly one of the most devastating. This type of injury is a disruptive incident in the individual’s life, entails significant changes and requires a biopsychosocial adaptation. The following research aims to contribute to the study about the quality of life in individuals with SCI. The sample was composed of 36 individuals with SCI, inpatients of the Portuguese Central Region Center of Rehabilitation Medicine-Rovisco Pais, aged between 20 and 82 years old (M = 53.56, SD = 18.27). Participants completed a sociodemographic and clinical information questionnaire and measures of functioning independence and quality of life. The results indicate that individuals with SCI present a good perception of quality of life, which is promising of psychological adaptation. The results highlight the need for health professionals and family/caregivers to acquire knowledge which facilitates the process of adaptation to the clinical condition consequently contributing to the health and well-being of individuals with SCI.展开更多
Severe sepsis (SS) is one of the principal causes of admission in intensive care units (ICU), with an associated high morbidity and mortality. This study intends to characterize epidemiology of community-acquired SS (...Severe sepsis (SS) is one of the principal causes of admission in intensive care units (ICU), with an associated high morbidity and mortality. This study intends to characterize epidemiology of community-acquired SS (CASS) with special emphasis in the prevalence of multidrug resistant organisms and independent prognostic factors associated with ICU mortality. Methods: A prospective cohort study was conducted over 3.5 years, including all consecutive adult patients with CASS admitted to a mixed ICU, in a 600-bed university-affiliated hospital. Results: 1221 patients were admitted into the ICU, 25% with CASS. The mean age was 59 years and the mean SAPS (simplified acute physiological score) was II 48. Most had septic shock (67%). Respiratory (57%), intra-abdominal (22%) and urinary tract (8%) infections were the main sources of infection. The overall isolation rate was 56%. The most common identified microorganisms were Streptococcus pneumoniae (27%), Escherichia coli (22%), Staphylococcus aureus methicillin sensitive (8%) and Haemophilus influenzae (7%). The median ICU and hospital length of stay were 8 and 16 days, respectively. The ICU mortality rate was 33. Independent risk factors associated with higher mortality were older age, higher SAPS II, septic shock and chronic hepatic disease. Female gender was independently associated with lower mortality. The type of microorganism was not significantly associated with prognosis. Conclusion: CASS was highly prevalent among ICU admissions. Independent risk factors associated with ICU mortality included older age and previous comorbidities, but mainly severity of acute illness reinforcing the need for early recognition and treatment. Multidrug resistant organisms were implicated in considerable proportion of community-acquired sepsis.展开更多
Toll-like receptors (TLR) are essential for Helicobacter pylori (Hp) recognition and subsequent innate and adaptive immunity responses. TLR2 appears to be the receptor responsible for most of the immunologic reaction ...Toll-like receptors (TLR) are essential for Helicobacter pylori (Hp) recognition and subsequent innate and adaptive immunity responses. TLR2 appears to be the receptor responsible for most of the immunologic reaction against Hp infection. However, TLR4, TLR9 and eventually TLR5 may also have a synergic effect with TLR2 against Hp. It has been shown that gastric Hp infection increases TLR expression in the gastric mucosa. Moreover, recent studies have shown that human gastric carcinogenesis is associated not only with increased expression of TLR but also with decreased expression of their inhibitors such as Toll-Interacting Protein (TOLLIP) and peroxisome proliferator-activated receptor (PPAR)-g. Indeed, gastric dysplasia and adenocarcinoma are associated with high expression levels of TLR and low levels of TOLLIP and PPAR-g, suggesting increased activation of these receptors throughout human gastric carcinogenesis. In this article we discuss how these novels findings could be used not only for the diagnosis and prognosis of gastric lesions associated with Hp infection but also for their treatment. Specifically, we discuss the potential use of TLR agonists in addition to antibiotics to improve eradication rates of Hp and of TLR antagonists to slow the progression of gastric preneoplastic lesions. We also discuss the potential value of TLR signalling blockers and quantification of tumoral TLR expression, respectively, in the treatment and prognosis of gastric cancer. In conclusion, TLRs can be an important link between Hp and the sequence of gastric carcinogenesis and they can be used as biomarkers of gastric carcinogenesis. In this article, future lines of investigation related with these novel scientific findings are proposed and discussed.展开更多
This review analyzes the state and recent progress in the field of information support for pollen allergy sufferers.For decades,information available for the patients and allergologists consisted of pollen counts,whic...This review analyzes the state and recent progress in the field of information support for pollen allergy sufferers.For decades,information available for the patients and allergologists consisted of pollen counts,which are vital but insufficient.New technology paves the way to substantial increase in amount and diversity of the data.This paper reviews old and newly suggested methods to predict pollen and air pollutant concentrations in the air and proposes an allergy risk concept,which combines the pollen and pollution information and transforms it into a qualitative risk index.This new index is available in an app(Mobile Airways Sentinel NetworK-air)that was developed in the frame of the European Union grant Impact of Air POLLution on sleep,Asthma and Rhinitis(a project of European Institute of Innovation and Technology-Health).On-going transformation of the pollen allergy information support is based on new technological solutions for pollen and air quality monitoring and predictions.The new information-technology and artificial-intelligence-based solutions help to convert this information into easy-to-use services for both medical practitioners and allergy sufferers.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
文摘Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short- and long- term outcomes in renal graft recipients. Chemokines and their receptors play a diversified and important role, either homeostatic or inflammatory and direct different immune-competent cell types to the allograft. While deeply studied in the last two decades, controversy persists as a result of chemokines’ pleiotropic actions. We report our analysis of CCR1, CCR3, CCR7, CCL5 and CX3CL1 expression or synthesis by graft-infiltrating cells in human kidney transplants (KTx). At the same time, we tested their robustness in diagnosing acute rejection. Methods: Fine-needle aspiration biopsies (Fnab) were performed either on days 7 or 14 post-transplantation among stable KTx and on the day of acute rejection (AR) diagnosis. Fnab cytopreparations were studied by the enzymatic avidin-biotin complex staining for CCR1, CCR3, CCR7 and CX3CL1. From another subgroup of cases, Fnab samples were cultured for 48 hours and the supernatants were analysed for CCL5 by ELISA. Results: The group of AR cases showed a significantly up-regulated expression of CCR1, CCR3, CCR7 and CX3CL1 and a significantly higher synthesis of CCL5. The positive predictive values were respectively 92%, 97%, 85%, 76% and 78% and negative predictive values were by the same order, 100%, 73%, 100%, 98% and 83%. Conclusions: Our study permits us to advance that CCR1 and CCR3 play a significant and non-redundant role in acute rejection, and it is the first report of CCR3 association with rejection, probably related to CCL5. The presence inside the graft of significant up-regulation for CCR7 surmises that part of antigen presentation may be performed there without being restricted to secondary lymphoid sites. Our results with CX3CL1 confirm other reports.
文摘During the past decades, endoscopic resection techniques have gradually improved and gained more importance for the management of premalignant lesions and early cancers. These endoscopic resection techniques can be divided in 3 major groups: snare polipectomy, endoscopic mucosal resection(EMR) and endoscopic submucosal dissection(ESD). The use of submucosal injection is essential for the majority of EMR techniques and is an integral part of ESD,whereas during polipectomy it is not crucial in most cases except to prevent bleeding in large polyps and/or those with large stalks as an alternative to mechanical methods. Injection provides a lifting up effect of the lesion separating it from the muscular layer, thereby reducing thermal injury and the risk of perforation and bleeding while also facilitating en-bloc resection by improving technical feasibility. With this work, we aim to review the most common endoscopic resection techniques and the importance of submucosal injection in each one of them. For that, we present some of the most commonly used submucosal injection solutions, taking into account their advantages and disadvantages. We also discuss, based on current recommendations and our own experience, how and when to preform submucosal injection, depending on lesions features and endoscopic resection technique that′s being used, to assure complete resection and to prevent associated adverse events. Finally, we also present and discuss some new proposed submucosal injection solutions,endoscopic resection techniques and devices that may have a major impact on the future of therapeutic endoscopy.
基金Supported by the Portuguese League Against Cancer (Liga Portuguesa Contra o Cancro-Núcleo Regional do Norte) and AstraZeneca Foundation
文摘AIM: To investigate the relationship between the -765G > C COX-2 polymorphism and the development of different gastric lesions: atrophy or intestinal metaplasia and gastric adenocarcinoma. METHODS: A cross-sectional study was performed involving 320 Portuguese individuals (210 without evidence of neoplastic disease, 73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal metaplasia) using a PCR-RFLP method. RESULTS: -765C allele was overrepresented in the patients with gastric adenocarcinoma (51%) when compared either with the control group (38%) or patients with atrophy or intestinal metaplasia (27%). Callele was found to be very common in our population (0.22), and a multivariate logistic regression analysis revealed nearly 3-fold increased risk for the progression to gastric adenocarcinoma in patients with atrophy or intestinal metaplasia carrying the -765C allele (OR = 2.67, 95% CI = 1.03-6.93; P = 0.04).considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.
文摘Hypertension is a very prevalent risk factor for cardiovascular disease. The prevalence of resistant hypertension, i.e., uncontrolled hypertension with 3 or more antihypertensive agents including 1 diuretic, is between 5% and 30% in the hypertensive population. The causes of resistant hypertension are multifactorial and include behavioral and biological factors, such as nonadherence to pharmacological treatment. All current treatment guidelines highlight the positive role of physical exercise as a non-pharmacological tool in the treatment of hypertension. This paper draws attention to the possible role of physical exercise as an adjunct non-pharmacological tool in the management of resistant hypertension. A few studies have investigated it, employing different methodologies, and taken together they have shown promising results. In summary, the available evidence suggests that aerobic physical exercise could be a valuable addition to the optimal pharmacological treatment of patients with resistant hypertension.
文摘Hepatocarcinoma(HCC) is a highly prevalent cancer worldwide and its inflammatory background was established long ago.Recent studies have shown that innate immunity is closely related to the HCC carcinogenesis.An effective innate immunity response relies on the tolllike receptors(TLR) found in several different liver cells which,through different ligands and many signaling pathways can elicit,not only a pro-inflammatory but also an oncogenic or anti-oncogenic response.Our aim was to study the role of TLRs in the liver oncogenesis and as a consequence their value as potential therapeutic targets.We performed a systematic review of PubMed searching for original articles studying the relationship between HCC and TLRs until March 2015.TLR2 appears to be a fundamental stress-sensor as its absence reveals an augmented tendency to accumulate DNAdamages and to cell survival.However,pathways are still not fully understood as TLR2 up-regulation was also associated to enhanced tumorigenesis.TLR3 has a wellknown protective role influencing crucial processes like angiogenesis,cell growth or proliferation.TLR4 works as an interesting epithelial-mesenchymal transition's inducer and a promoter of cell survival probably inducing HCC carcinogenesis even though an anti-cancer role has already been observed.TLR9's influence on carcinogenesis is also controversial and despite a potential anticancer capacity,a pro-tumorigenic role is more likely.Genetic polymorphisms in some TLRs have been found and its influence on the risk of HCC has been reported.As therapeutic targets,TLRs are already in use and have a great potential.In conclusion,TLRs have been shown to be an interesting influence on the HCCs microenvironment,with TLR3 clearly determining an antitumour influence.TLR4 and TLR9 are considered to have a positive relationship with tumour development even though,in each of them anti-tumorigenic signals have been described.TLR2 presents a more ambiguous role,possibly depending on the stage of the inflammationHCC axis.
基金Supported by The Portuguese League Against Cancer (Liga Portuguesa Contra o Cancro-Núcleo Regional do Norte) and AstraZeneca Foundation
文摘AIM: To investigate the association between epidermal growth factor (EGF) +61A/G polymorphism and susceptibility to gastric cancer, through a cross-sectional study. METHODS: Polymerase chain reaction resctriction fragment lenght polymorphism analyses were used to genotype EGF +61 in 207 patients with gastric lesions (162 patients with gastric adenocarcinomas, 45 with atrophy or intestinal metaplasia) and 984 controls. All subjects were Caucasian. RESULTS: Genotype distribution was 23.5% for GG and 76.5% for GA/AA in the control group, 18.4% for GG and 68.6% for GA/AA in the entire group with gastric lesions and 17.9% for GG and 82.1% for GA/AA in the group with gastric adenocarcinoma. No statistically significant associations were found between EGF +61 variants and risk for developing gastric cancer [odds ratios (OR) = 1.41, 95% confidence intervals (CI): 0.90-2.21, P = 0.116]. However, the stratification of individuals by gender revealed that males carrying A alleles (EGF +61A/G or AA) had an increased risk for developing gastric cancer as compared to GG homozygous males (OR = 1.55, 95% CI: 1.05-2.28, P = 0.021). CONCLUSION: In summary, we found that males who were A carriers for EGF +61 had an increased risk for developing gastric cancer. This result may be explained by the suggestion that women secrete less gastric acid than men.
基金Supported by Centre for Research in Health Informatics Systems and Technologies(CINTESIS)
文摘AIM: To identify demographic and clinical factors asso-ciated with disabling Crohn's disease (CD). METHODS: A systematic review and meta-analysisof observational studies, focusing on the factors that can predict the prognosis of different outcomes of CD was undertaken. PubMed, ISI Web of Knowledge and Scopus were searched to identify studies investigat-ing the above mentioned factors in adult patients with CD. Studies were eligible for inclusion if they describe prognostic factors in CD, with inclusion and exclusion criteria defined as follows. Studies with adult patients and CD, written in English and studying association between clinical factors and at least one prognosis out-come were included. Meta-analysis of effects was un-dertaken for the disabling disease outcome, using odds ratio (OR) to assess the effect of the different factors in the outcome. The statistical method used was Mantel-Haenszel for fixed effects. The 16-item quality assess-ment tool (QATSDD) was used to assess the quality of the studies (range: 0-42). RESULTS: Of the 913 papers initially selected, sixty studies were reviewed and three were included in the systematic review and meta-analysis. The global QA-TSDD scores of papers were 18, 21 and 22. Of a total of 1961 patients enrolled, 1332 (78%) were classified with disabling disease five years after diagnosis. In two studies, age at diagnosis was a factor associated with disabling disease five years after diagnosis. Individu-als under 40 years old had a higher risk of developing disabling disease. In two studies, patients who were treated with corticosteroids on the first flare developed disabling disease five years after diagnosis. Further, perianal disease was found to be relevant in all of the studies at two and five years after diagnosis. Finally, one study showed localization as a factor associated with disabling disease five years after diagnosis, with L3 being a higher risk factor. This meta-analysis showed a significantly higher risk of developing disabling dis-ease at five years after initial diagnosis among patients younger than 40 years of age (OR=2.47, 95%CI: 1.74-3.51), with initial steroid treatment for first flare (OR=2.42, 95%CI: 1.87-3.11) and with perianal dis-ease (OR = 2.00, 95%CI: 1.41-2.85).CONCLUSION: Age at diagnosis, perianal disease, ini-tial use of steroids and localization seem to be indepen-dent prognostic factors of disabling disease.
文摘The prevalence of pediatric obesity continues to increase worldwide,bringing with it various metabolic,functional,social,and psychological complications.1 Both the prevention and treatment of childhood obesity must be based on multidisciplinary approaches combining nutrition,physical activity(PA),and psychological support.2 As an essential element of these multicomponent strategies,regular physical activity has been acknowledged as having beneficial effects on children's and adolescents,body composition,physical fitness,and metabolic profile,as well as on their health-related quality of life,social and psychological health,and academic achievement.3,4 Given that only a relatively small proportion of children and adolescents meet the public health recommendations for PA,5 and given that weight loss exercise-based interventions suffer from a high attrition rate,there is a clear need for appropriate PAs.
基金Sociedade Portuguesa de Endoscopia Digestiva (Research Grant 2002)the European Society for Gastrointestinal Endoscopy
文摘AIM:To evaluate the use of web-based technologies to assess the learning curve and reassess reproducibility of a simplified version of a classification for gastric magnification chromoendoscopy (MC). METHODS: As part of a multicenter trial, a hybrid approach was taken using a CD-ROM, with 20 films of MC lasting 5 s each and an "autorun" file triggering a local HTML frameset referenced to a remote questionnaire through an Internet connection. Three endoscopists were asked to prospectively and independently classify 10 of these films randomly selected with at least 3 d apart. The answers were centrally stored and returned to participants together with adequate feedback with the right answer. RESULTS: For classification in 3 groups, both intra- [Cohen's kappa (κ) = 0.79-1.00 to 0.89-1.00] and inter-observer agreement increased from 1st (moderate) to 6th observation (κ = 0.94). Also, agreement with reference increased in the last observations (0.90, 1.00 and 1.00, for observers A, B and C, respectively). Validity of 100% was obtained by all observers at their 4th observation. When a 4th (sub)group was considered, inter-observer agreement was almost perfect (κ=0.92) at 6th observation. The relation with reference clearly improved into κ (0.93-1.00) and sensitivity (75%-100%) at their 6th observations. CONCLUSION: This MC classification seems to be easily explainable and learnable as shown by excellent intra-and inter-observer agreement, and improved agreement with reference. A web system such as the one used in this study may be useful for endoscopic or other image based diagnostic procedures with respect to definition, education and dissemination.
文摘Background: We studied the expression of important costimulatory molecules of lymphocyte activation and the presence of CD16<sup><span style="font-family:Verdana;vertical-align:super;">+</span></sup><span style="font-family:Verdana;"> cells on aspiration biopsies of kidney transplants, measured three soluble factors and whe</span><span style="font-family:Verdana;">n indicated tested their robustness in diagnosing acute rejection.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Methods</span><span style="font-family:Verdana;">: Fine-needle aspiration biopsies were performed either on days seven or 14</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">30 post-transplantation among stable kidney transplants and on the day of acute rejection diagnosis, while a sample of peripheral blood was collected simultaneously. The cyto</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">preparations were studied by the enzymatic </span><span style="font-family:Verdana;">avidin biotin complex staining. The immunocytochemistry was directed to CD16, CD28, CD152, ICOS, CD40, CD154, CD26 and CD27. We performed the analysis in the peripheral blood by ELISA for soluble(s) CD16, CD26, and CD154.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Results: The group of acute rejection cases showed a significant up-regulated expression of CD16, CD26, ICOS and CD40 as compared to the group of stable cases. Both sCD16 and sCD154 were significantly higher in the blood samples of the group with acute rejection. Thymoglobulin down-regulated CD154 and sCD16. CD16, CD26 and ICOS exhibited very high sensitivity and specificity for acute rejection diagnosis.</span><span style="font-family:Verdana;"> </span><span style="font-family:Verdana;">Conclusions: The presence of CD16</span><sup><span style="font-family:Verdana;vertical-align:super;">+</span></sup><span style="font-family:Verdana;"> cells inside the graft emerged as a distinct player in acute rejection, confirming other previous reports whereas we first document that in human kidney transplants, ICOS and CD26 are significantly up-regulated and both reached positive predictive values for acute rejection ≥ 80%. The other costimulatory molecules, with the exception of CD40, though widely known, did not show robust association with immune events.</span>
文摘<p style="text-align:justify;"> <span>Following organ transplantation</span><span>,</span><span> the outcome of the encounter between an APC and a T lymphocyte is strongly dependent on the presence of costimulatory and co-inhibitory molecules, the former associated with allograft rejection and the latter with allograft acceptance. We evaluated the expression of PD-L2, GITR, ILT-2/3/5, and ILT-4 on graft-infiltrating cells procured by Fnab from human KTx under different immunosuppressive regimens. Methods: Fnab biopsies were performed on days 7 or 14</span><span> </span><span>-</span><span> </span><span>30 in stable KTx and on the day of acute rejection diagnosis. Cytopreparations were studied by the enzymatic avidin biotin complex staining. Results: Acute rejection group </span><span>showed a significant down-regulated expression of PD-L2, GITR, and ILT-2/3/5 </span><span>as compared to stable group, while for ILT-4 we did not find significant difference. Anti-IL2</span><i><span>α</span></i><span>R and rapamicyn treatment trend to down-regulate ILT-4 expression, although meaningless. A significant</span><span>ly</span><span> positive correlation was observed between PD-L2 and GITR expression in Fnab. The PPV for acute rejection diagnosis for both PD-L2 and GITR w</span><span>as</span><span> clearly above 0.8. Conclusions: Our findings point to an early entrance of cells expressing PD-L2, GITR and ILT-2/3/5 inside human KTx who are going to remain rejection-free. Both PD-L2 and GITR shared a high ability to rule-in and rule-out acute rejection.</span> </p>
文摘<strong>Background:</strong> Ischemia-reperfusion injury of organ transplantation activates several mediators which may link the innate to the adaptive immune response. Down the cascade of TLRs, we selected to study the expression of Interferon Regulatory Factors (IRF)-3 and -7 inside human Kidney Transplanted (KTx) organs and the synthesis of IFN<i>α</i>, the main growth factor induced by them, in KTx aspiration biopsy cultures. Simultaneously, we tested their robustness in diagnosing Acute Rejection (AR). <strong>Methods:</strong> Fine-needle aspiration biopsies (F-nab) were performed either on day 7 or 14 post-KTx among stable patients or on the day of AR diagnosis. On Fnab cytopreparations, we studied IRF3 and IRF7 by the enzymatic avidin-biotin complex staining, and in a different group of cases we quantified IFN<i>α</i> by ELISA in 48 hours Fnab culture supernatants. <strong>Results:</strong> AR group showed a significantly up-regulated expression for IRF3 and IRF7, reaching Positive Predictive Values (PPV) of 0.824 and 0.8, respectively, as well as Negative Predictive Values (NPV) above 0.9 for both;IFN<i>α</i> presented a PPV = 1.0 and a NPV = 0.9. A variation in the results was noticed according to different immunosuppressive therapies. <strong>Conclusions:</strong> Our findings suggest that IRF3 and IRF7, and IFN<i>α</i> which they promote, may be very important players in the early days post-KTx, linking the innate with an adaptive response and triggering acute rejection. These differences were very clear-cut, lending consistency to our speculation. It would be important to scrutinize for other potential effects derived from these IRFs up-regulation which could be of clinical relevance.
文摘Among the various types of disability that can affect humans, spinal cord injury (SCI) is undoubtedly one of the most devastating. This type of injury is a disruptive incident in the individual’s life, entails significant changes and requires a biopsychosocial adaptation. The following research aims to contribute to the study about the quality of life in individuals with SCI. The sample was composed of 36 individuals with SCI, inpatients of the Portuguese Central Region Center of Rehabilitation Medicine-Rovisco Pais, aged between 20 and 82 years old (M = 53.56, SD = 18.27). Participants completed a sociodemographic and clinical information questionnaire and measures of functioning independence and quality of life. The results indicate that individuals with SCI present a good perception of quality of life, which is promising of psychological adaptation. The results highlight the need for health professionals and family/caregivers to acquire knowledge which facilitates the process of adaptation to the clinical condition consequently contributing to the health and well-being of individuals with SCI.
基金supported by an unrestricted grant from ASSUCIP-Associacao dos Amigos da Unidade de Cuidados Intensivos Polivalente,Hospital de Santo António,Porto,Portugal(Intensive Care Unit Support Association).
文摘Severe sepsis (SS) is one of the principal causes of admission in intensive care units (ICU), with an associated high morbidity and mortality. This study intends to characterize epidemiology of community-acquired SS (CASS) with special emphasis in the prevalence of multidrug resistant organisms and independent prognostic factors associated with ICU mortality. Methods: A prospective cohort study was conducted over 3.5 years, including all consecutive adult patients with CASS admitted to a mixed ICU, in a 600-bed university-affiliated hospital. Results: 1221 patients were admitted into the ICU, 25% with CASS. The mean age was 59 years and the mean SAPS (simplified acute physiological score) was II 48. Most had septic shock (67%). Respiratory (57%), intra-abdominal (22%) and urinary tract (8%) infections were the main sources of infection. The overall isolation rate was 56%. The most common identified microorganisms were Streptococcus pneumoniae (27%), Escherichia coli (22%), Staphylococcus aureus methicillin sensitive (8%) and Haemophilus influenzae (7%). The median ICU and hospital length of stay were 8 and 16 days, respectively. The ICU mortality rate was 33. Independent risk factors associated with higher mortality were older age, higher SAPS II, septic shock and chronic hepatic disease. Female gender was independently associated with lower mortality. The type of microorganism was not significantly associated with prognosis. Conclusion: CASS was highly prevalent among ICU admissions. Independent risk factors associated with ICU mortality included older age and previous comorbidities, but mainly severity of acute illness reinforcing the need for early recognition and treatment. Multidrug resistant organisms were implicated in considerable proportion of community-acquired sepsis.
文摘Toll-like receptors (TLR) are essential for Helicobacter pylori (Hp) recognition and subsequent innate and adaptive immunity responses. TLR2 appears to be the receptor responsible for most of the immunologic reaction against Hp infection. However, TLR4, TLR9 and eventually TLR5 may also have a synergic effect with TLR2 against Hp. It has been shown that gastric Hp infection increases TLR expression in the gastric mucosa. Moreover, recent studies have shown that human gastric carcinogenesis is associated not only with increased expression of TLR but also with decreased expression of their inhibitors such as Toll-Interacting Protein (TOLLIP) and peroxisome proliferator-activated receptor (PPAR)-g. Indeed, gastric dysplasia and adenocarcinoma are associated with high expression levels of TLR and low levels of TOLLIP and PPAR-g, suggesting increased activation of these receptors throughout human gastric carcinogenesis. In this article we discuss how these novels findings could be used not only for the diagnosis and prognosis of gastric lesions associated with Hp infection but also for their treatment. Specifically, we discuss the potential use of TLR agonists in addition to antibiotics to improve eradication rates of Hp and of TLR antagonists to slow the progression of gastric preneoplastic lesions. We also discuss the potential value of TLR signalling blockers and quantification of tumoral TLR expression, respectively, in the treatment and prognosis of gastric cancer. In conclusion, TLRs can be an important link between Hp and the sequence of gastric carcinogenesis and they can be used as biomarkers of gastric carcinogenesis. In this article, future lines of investigation related with these novel scientific findings are proposed and discussed.
文摘This review analyzes the state and recent progress in the field of information support for pollen allergy sufferers.For decades,information available for the patients and allergologists consisted of pollen counts,which are vital but insufficient.New technology paves the way to substantial increase in amount and diversity of the data.This paper reviews old and newly suggested methods to predict pollen and air pollutant concentrations in the air and proposes an allergy risk concept,which combines the pollen and pollution information and transforms it into a qualitative risk index.This new index is available in an app(Mobile Airways Sentinel NetworK-air)that was developed in the frame of the European Union grant Impact of Air POLLution on sleep,Asthma and Rhinitis(a project of European Institute of Innovation and Technology-Health).On-going transformation of the pollen allergy information support is based on new technological solutions for pollen and air quality monitoring and predictions.The new information-technology and artificial-intelligence-based solutions help to convert this information into easy-to-use services for both medical practitioners and allergy sufferers.
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.
