Are There Any Differences in Road Traffic Injury Outcomes between Older and Younger Adults? Setting the Grounds for Posttraumatic Senior Personal Injury Assessment Guidelines.

Injury outcomes seem to be more severe in older than younger persons. This may make personal injury assessment (PIA) particularly difficult, mainly because of seniors' previous health frailties. To set the grounds for seniors' PIA guidelines, we compared an older with a younger adult population of trauma victims and, secondarily, identified differences between the groups regarding three-dimensional and medico-legal damage parameters assessment. Using a retrospective study of victims of road traffic accidents, we compared the groups (n = 239 each), assuring similar acute injury severity (ISS standardised difference = 0.01): G1 (older adults); G2 (younger adults). Logistic regression was used to estimate the odds ratio. G1 revealed higher negative consequences when considering the three-dimensional damage assessment, with more frequent and severe outcomes, being a cause of further difficulties in daily living activities, with a loss of independence and autonomy. Nevertheless, regarding the medico-legal damage parameters, permanent functional disability did not show significant differences. This study generates evidence that reveals the need to rethink the traditional methodology of PIA in older persons, giving more relevance to the real-life contexts of each person. It is essential to: obtain complete information about previous physiologic and health states, begin the medico-legal assessment as early as possible, make regular follow-ups, and perform a multidisciplinary evaluation.

Mesial Temporal Lobe Epilepsy (MTLE) Drug-Refractoriness Is Associated With P2X7 Receptors Overexpression in the Human Hippocampus and Temporal Neocortex and May Be Predicted by Low Circulating Levels of miR-22.

Objective: ATP-gated ionotropic P2X7 receptors (P2X7R) actively participate in epilepsy and other neurological disorders. Neocortical nerve terminals of patients with Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS) express higher P2X7R amounts. Overexpression of P2X7R bolsters ATP signals during seizures resulting in glial cell activation, cytokines production, and GABAergic rundown with unrestrained glutamatergic excitation. In a mouse model of status epilepticus, increased expression of P2X7R has been associated with the down-modulation of the non-coding micro RNA, miR-22. MiR levels are stable in biological fluids and normally reflect remote tissue production making them ideal disease biomarkers. Here, we compared P2X7R and miR-22 expression in epileptic brains and in the serum of patients with MTLE-HS, respectively. Methods: Quantitative RT-PCR was used to evaluate the expression of P2X7R in the hippocampus and anterior temporal lobe of 23 patients with MTLE-HS and 10 cadaveric controls. Confocal microscopy and Western blot analysis were performed to assess P2X7R protein amounts. MiR-22 expression was evaluated in cell-free sera of 40 MTLE-HS patients and 48 healthy controls. Results: Nerve terminals of the hippocampus and neocortical temporal lobe of MTLE-HS patients overexpress (p < 0.05) an 85 kDa P2X7R protein whereas the normally occurring 67 kDa receptor protein dominates in the brain of the cadaveric controls. Contrariwise, miR-22 serum levels are diminished (p < 0.001) in MTLE-HS patients compared to age-matched control blood donors, a situation that is more evident in patients requiring multiple (>3) anti-epileptic drug (AED) regimens. Conclusion: Data show that there is an inverse relationship between miR-22 serum levels and P2X7R expression in the hippocampus and neocortex of MTLE-HS patients, which implies that measuring serum miR-22 may be a clinical surrogate of P2X7R brain expression in the MTLE-HS. Moreover, the high area under the ROC curve (0.777; 95% CI 0.629-0.925; p = 0.001) suggests that low miR-22 serum levels may be a sensitive predictor of poor response to AEDs among MTLE-HS patients. Results also anticipate that targeting the miR-22/P2X7R axis may be a good strategy to develop newer AEDs.

Post-mortem genetic investigation in sudden cardiac death victims: complete exon sequencing of forty genes using next-generation sequencing.

Sudden cardiac death (SCD) in young people is predominantly caused by genetic causes as cardiomyopathies. Hypertrophic cardiomyopathy is the most common genetic cardiovascular disease and is responsible for the major proportion of SCD in the young. The purpose of this study was to identify the genetic variants present in young SCD victims with HCM characteristics. From the Portuguese records of autopsies performed at the National Institute of Legal Medicine and Forensic Sciences, North Delegation, 16 young (16-50 years) SCD victims whose death was suspected to be a manifestation of HCM were selected. Using next-generation sequencing, the coding regions of 40 genes associated with HCM, candidates, or strongly related to HCM-phenocopies were investigated. The victims included in this study were all males, with a mean age of 33.4 ± 11.7 years, left ventricle mean thickness of 21.5 ± 6.28 mm, and the majority of deaths occurred during sleep (36%). A pathogenic or likely pathogenic variant was identified in six out of 16 (37.5%) victims, in the most common HCM genes (MYBPC3 and MYH7). Our results indicate that molecular autopsy of SCD victims contributes to a more precise identification of a cause of death, and this can be used in the prevention of SCD cases through family screening of first relatives who may carry the same pathogenic variant.

Epilepsy progression is associated with cumulative DNA methylation changes in inflammatory genes.

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most common focal epilepsy in adults. It is characterized by alarming rates of pharmacoresistance. Epileptogenesis is associated with the occurrence of epigenetic alterations, and the few epigenetic studies carried out in MTLE-HS have mainly focused on the hippocampus. In this study, we obtained the DNA methylation profiles from both the hippocampus and anterior temporal neocortex of MTLE-HS patients subjected to resective epilepsy surgery and autopsied non-epileptic controls. We assessed the progressive nature of DNA methylation changes in relation to epilepsy duration. We identified significantly altered hippocampal DNA methylation patterns encompassing multiple pathways known to be involved in epileptogenesis. DNA methylation changes were even more striking in the neocortex, wherein pathogenic pathways and genes were common to both tissues. Most importantly, DNA methylation changes at many genomic sites varied significantly with epilepsy duration. Such progressive changes were associated with inflammation-related genes in the hippocampus. Our results suggest that the neocortex, relatively spared of extensive histopathological damage, may also be involved in epilepsy development. These results also open the possibility that the observed neocortical impairment could represent a preliminary stage of epileptogenesis before the establishment of chronic lesions or a consequence of prolonged seizure exposure. Our two-tissue multi-level characterization of the MTLE-HS DNA methylome suggests the occurrence of a self-propagating inflammatory wave of epigenetic dysregulation.

Reference values for trace element levels in the human brain: A systematic review of the literature.

Some trace elements (TE) are eminently toxic for humans (e.g., Al, Pb, Hg, Cd) and its presence in the central nervous system has been linked to the etiology of neurodegenerative diseases (ND). More recently, the focus has shifted to the potential role of the imbalances on essential TE levels (e.g., Fe, Cu, Zn, Se) within the brain tissue, and they have also been identified as potentially responsible for the cognitive decline associated with normal ageing and the development of some ND, although their definite role remains unclear. Accurately, well-defined reference values for TE levels in human body fluids and tissues are indispensable to identify possible disturbances in individual cases. Moreover, since the brain is a highly heterogeneous organ, with anatomically and physiologically very different areas, a detailed mapping of TE distribution across the brain tissue of normal individuals, with an in-depth analysis of TE levels in the different brain regions, is a mandatory prior work so that the results obtained from patients suffering from ND and other brain diseases can be interpreted. This review aims to compile and summarize the available data regarding TE levels in the different human brain regions of "normal" (non-diseased) individuals in order to contribute to the establishment of robust reference values. Fifty-four studies, published since 1960, were considered. The results showed a great variability between different studies. The potential sources of this variability are discussed. The need for increased harmonization of experimental strategies is highlighted in order to improve the comparability of the data obtained.

Iodine levels in different regions of the human brain.

BACKGROUND: Iodine is a key component of the thyroid hormones thyroxine (T4) and triiodothyronine (T3), which are crucial for proper growth and development of the human body. In particular, a great body of literature has been published on the link between thyroid hormones and brain development and functioning. However, there is a lack of knowledge on the iodine levels in the human brain. The aim of this work was to determine the brain iodine levels and to contribute to the establishment of "reference" levels for iodine in the different anatomical and functional regions of normal (i.e., subjects without neurological or psychiatric diseases) human brain. METHODS: The iodine levels were determined in 14 brain regions of 52 dead subjects without evidence of neurological or psychiatric disease (n = 728 samples). Iodine was extracted from brain samples using a standard procedure and determined by inductively coupled plasma - mass spectrometry (ICP-MS). RESULTS: Four subjects presented abnormally high brain iodine levels (26.0 ±â€¯14.2 µg/g) and were excluded from the overall data analysis. The average brain iodine levels for the remaining 48 subjects was 0.14 ±â€¯0.13 µg/g dry weight. Iodine showed very heterogeneous distribution across the different brain regions, with the frontal cortex, caudate nucleus and putamen showing the highest levels. Interestingly, these brain regions are closely related to cognitive function. Iodine levels also showed a tendency to increase with age. The high levels observed in four subjects seemed to be related to previous exposure to iodine-based contrast agents widely used in radiology and computed tomography exams. CONCLUSIONS: This paper provides important data on iodine levels at different brain regions in "normal" people, which can be used to interpret eventual imbalances in subjects with mental disorders and neurodegenerative diseases.

Evidências científicas clínicas entre o novo coronavírus e a hipertensão arterial: uma revisão integrativa / Evidencia científica clínica entre el nuevo Coronavirus y la hipertensión arterial: una revisión integradora / Clinic scientific evidence between the new coronavirus and arterial hypertension: an integrative review

Objetivo: descrever as evidências clínicas do Novo Coronavírus em pacientes com Hipertensão Arterial. Método: revisão integrativa da literatura, com levantamentos de artigos em bibliotecas virtuais. Os critérios de inclusão foram: responder à pergunta norteadora, estarem disponíveis na íntegra, serem estudos primários e terem sido publicados no último ano (2019-2020). Resultados: evidenciou-se que pacientes hipertensos infectados pelo novo coronavírus apresentaram níveis baixos de linfócitos, possuíram números maiores de receptores para Enzima Angiotensina II e que o uso dos anti-hipertensivos não interfere na evolução da infecção. Conclusão: a relação entre as duas patologias é devida ao grande número de receptores para Enzima Angiotensina II, baixo número de linfócitos e que os estudos recomendaram não ser necessário a interrupção do tratamento anti-hipertensivo em pacientes com o Coronavírus. A discussão é pertinente para o desenvolvimento de melhores métodos de tratamento e assistência aos pacientes.(AU)

Objective: to describe the clinicalevidence of the new Coronavirus inpatients with hypertension. Method: integrative literature review, with surveys of articles in virtual libraries. The inclusion criteria were:answer the guiding question, be available in full, be primary studies and have been published in the last year (2019-2020). Results:it was evidenced that hypertensive patients infected by the new coronavirus had low levels of lymphocytes, had higher numbers of receptors for Enzyme Angiotensin II and that the use of antihypertensive drugs does not interfere in the evolution of the infection. Conclusion:the relationbetween the two pathologies is due to the large number of receptors for Enzyme Angiotensin II, low number of lymphocytes and that studies have recommended that it is not necessary to interrupt antihypertensive treatment in patients with Coronavirus. Thisdiscussionis pertinent to the development of better methods of treatment and assistanceto patients.(AU)

Objetivo: describir la evidencia clínicadel nuevo Coronavirus enpacientes con hipertensión.Método:revisión integradora de literatura, con levantamientos de artículos en bibliotecas virtuales. Los criterios de inclusión fueron:responder a la pregunta orientadora, estar disponible en su totalidad, ser estudios primarios y haber sido publicados en el último año (2019-2020). Resultados:se evidenció que pacientes hipertensos infectados por el nuevo coronavirus presentaban niveles bajos de linfocitos, mayor número de receptores para la Enzima Angiotensina II y que el uso de antihipertensivos no interfiere en la evolución de la infección. Conclusión:la relación entre las dos patologías se debe a la gran cantidad de receptores para la Enzima Angiotensina II, bajo número de linfocitos y que los estudios han recomendado que noes necesario interrumpir el tratamiento antihipertensivo en pacientes conCoronavirus. La discusión es pertinente para el desarrollo de mejores métodos de tratamiento y asistencia a los pacientes.(AU)

Brain expression of inflammatory mediators in Mesial Temporal Lobe Epilepsy patients.

Neuroinflammation may be central in epileptogenesis. In this study we analysed inflammatory reaction markers in brain tissue of Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS) patients. TLR4, IL-1ß and IL-10 gene expression as well as the presence of activated HLA-DR+ microglia was evaluated in 23 patients and 10 cadaveric controls. Inflammation characterized by the presence of HLA-DR+ microglia and TLR4, IL-1ß overexpression was evident in hippocampus and anterior temporal cortex of MTLE-HS patients. Anti-inflammatory IL-10 was also overexpressed in MTLE-HS patients. Our results show that hippocampal neuroinflammation extends beyond lesional limits, as far as the anterior temporal cortex.

Metals transfer from tobacco to cigarette smoke: Evidences in smokers' lung tissue.

Tobacco use kills millions of people every year around the world. The current level of 11 metals in tobacco was determined and their transfer rate to cigarette smoke was calculated as the difference between the total metal content in cigarettes and the amount present in its ashes. The metals content was also determined in the lung tissue of smokers and non-smokers in order to evaluate the marks that smoking leaves in this tissue. Metals content in tobacco ranged from less than 1µg/g (Co, Cd, Pb, As and Tl) to several hundreds of µg/g (Al, Mn and Ba). The highest transfer rate from tobacco to cigarette smoke was found for Tl (85-92%) and Cd (81-90%), followed by Pb (46-60%) and As (33-44%). Significantly higher levels of As, Cd and Pb were found in the lung tissue of smokers compared to non-smokers, showing that smoking results in an increase of these metals in the lungs and that they contribute to the carcinogenic potential of cigarette smoke. This study presents important data on current metals content in tobacco and its transference to cigarette smoke and provides evidence of their accumulation in smokers' lung tissue.

Adenosine A2A receptor and ecto-5'-nucleotidase/CD73 are upregulated in hippocampal astrocytes of human patients with mesial temporal lobe epilepsy (MTLE).

Refractoriness to existing medications of up to 80 % of the patients with mesial temporal lobe epilepsy (MTLE) prompts for finding new antiepileptic drug targets. The adenosine A2A receptor emerges as an interesting pharmacological target since its excitatory nature partially counteracts the dominant antiepileptic role of endogenous adenosine acting via inhibitory A1 receptors. Gain of function of the excitatory A2A receptor has been implicated in a significant number of brain pathologies commonly characterized by neuronal excitotoxicity. Here, we investigated changes in the expression and cellular localization of the A2A receptor and of the adenosine-generating enzyme, ecto-5'-nucleotidase/CD73, in the hippocampus of control individuals and MTLE human patients. Western blot analysis indicates that the A2A receptor is more abundant in the hippocampus of MTLE patients compared to control individuals. Immunoreactivity against the A2A receptor predominates in astrocytes staining positively for the glial fibrillary acidic protein (GFAP). No co-localization was observed between the A2A receptor and neuronal cell markers, like synaptotagmin 1/2 (nerve terminals) and neurofilament 200 (axon fibers). Hippocampal astrogliosis observed in MTLE patients was accompanied by a proportionate increase in A2A receptor and ecto-5'-nucleotidase/CD73 immunoreactivities. Given our data, we hypothesize that selective blockade of excessive activation of astrocytic A2A receptors and/or inhibition of surplus adenosine formation by membrane-bound ecto-5'-nucleotidase/CD73 may reduce neuronal excitability, thus providing a novel therapeutic target for drug-refractory seizures in MTLE patients.

Contribution to the determination of the place of death by drowning - A study of diatoms' biodiversity in Douro river estuary.

The role of the investigation of diatoms' presence in organs and body fluids of an individual found dead in a liquid medium and the relevant contribution to the forensic diagnosis of drowning remain controversial. Furthermore, the absence of an exact and well-defined method for diatoms' analysis makes its study a challenging task. Considering this medico-legal problem and the absence of forensic studies on this subject in Portugal, this work aimed to determine the drowning place of dead individuals based on the analysis of diatom species found in different tissues (lung, liver, kidney, bone marrow) and stomach content. Diatom species found in biological samples were compared with those present in the liquid medium where the corpses were found. A total of 37 cases of death by drowning in Oporto metropolitan area were studied. A seasonal database of the diatom species found in Douro river estuary was built based on water samples collected at nine selected places. Diatoms' extractions were performed by a chemical method using 37% (w/w) hydrochloridric acid for the biological samples and 96% (w/w) sulfuric acid for water samples. Diatoms were found in 63% of total cases but only in lung and gastric content samples. The absence of diatoms in other organs is probably related with a quick death, which may have stopped blood circulation almost immediately, preventing diatom contamination of the other organs. A strong relationship between the diatom species found in the biological samples and those found in water samples of the respective drowning place was observed. Due to the high anthropogenic influence on the Douro estuary no significant differences were observed between the five sampling places, making it extremely difficult to determine the exact estuary location of the drowning. The importance of the creation of a diatom database of the potential drowning places (e.g., rivers, seas, lakes) becomes clear in this study. It also shows that, in cases of drowning, the collection of a water sample from the drowning place is crucial. This is the only way to allow a rigorous comparison of the diatom species in water and biological samples.

A FT-NIR spectroscopy methodology to estimate firing distance based on the direct analysis of the bullet impact surface.

A new methodology to estimate firing distance based on the direct analysis of organic components of gunshot residues (GSRs) on the bullet impact surface using Fourier transform near-infrared (FT-NIR) spectroscopy is proposed. Mathematical models relating firing distance with spectral information were developed using data obtained from a series of shots performed with a Glock model 17C (114 mm barrel length and 9 × 19 mm cartridges) at different distances, from 20 to 90 cm, against a white 40 × 40 cm square cloth (70% polyester/30% cotton) target. The study was repeated with two different types of ammunition. Spectra were obtained around the bullet entrance hole at 4 perpendicular directions and at 5 radial distances in diffuse reflectance mode with the assistance of a fiber optic probe. Principal component analysis showed that FT-NIRS displayed sensitivity in the recognition of the differences between the GSRs from the two different types of ammunition. Partial least squares regression models allowed the estimation of firing distance for both types of ammunition. Prediction errors lower than 11 cm were obtained for shots up to 90 cm.

Alkali metals levels in the human brain tissue: Anatomical region differences and age-related changes.

The link between trace elements imbalances (both "toxic" and "essential") in the human brain and neurodegenerative disease has been subject of extensive research. More recently, some studies have highlighted the potential role of the homeostasis deregulation of alkali metals in specific brain regions as key factor in the pathogenesis of neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease. Using flame atomic emission spectrometry and inductively coupled plasma-mass spectrometry after microwave-assisted acid digestion of the samples, alkali metals (Na, K, Li, Rb and Cs) were determined in 14 different areas of the human brain (frontal cortex, superior and middle temporal gyri, caudate nucleus, putamen, globus pallidus, cingulated gyrus, hippocampus, inferior parietal lobule, visual cortex of the occipital lobe, midbrain, pons, medulla and cerebellum) of adult individuals (n=42; 71±12, range: 50-101 years old) with no known history and evidence of neurodegenerative, neurological or psychiatric disorder. Potassium was found as the most abundant alkali metal, followed by Na, Rb, Cs and Li. Lithium, K and Cs distribution showed to be quite heterogeneous. On the contrary, Rb and Na appeared quite homogeneously distributed within the human brain tissue. The lowest levels of Na, K, Rb and Li were found in the brainstem (midbrain, medulla and pons) and cerebellum, while the lowest levels of Cs were found in the frontal cortex. The highest levels of K (mean±sd; range 15.5±2.5; 8.9-21.8mg/g) Rb (17.2±6.1; 3.9-32.4µg/g and Cs (83.4±48.6; 17.3-220.5ng/g) were found in putamen. The highest levels of Na and Li were found in the frontal cortex (11.6±2.4; 6.6-17.1mg/g) and caudate nucleus (7.6±4.6 2.2-21.3ng/g), respectively. Although K, Cs and Li levels appear to remain largely unchanged with age, some age-related changes were observed for Na and Rb levels in particular brain regions (namely in the hippocampus).

Deaths resulting from the use of firearms by police against motor vehicles: Study of cases in Porto, Portugal.

The objective of this study was to investigate the terminal ballistics of police shootings in which the bullets went through any motor vehicle structure before fatally wounding the occupants. 6 cases that occurred in Porto district between 1998 and 2013 were studied. The firearms used were 7.65 mm (n = 1) or 9 mm (n = 3) calibre semi-automatic pistols and 9 mm calibre submachine guns (n = 2); the bullets were full metal jacket type. The metal jacket of the collected projectiles was totally or partially destroyed in 3 cases. It exhibited a deformed structure in all cases. The trajectories of the bullets in the vehicles were always more or less linear, even when initial impact was at an oblique angle. The entry holes in the victims' bodies were larger or much larger in size than the calibre of the bullets. They were located, with the exception of one of the cases, in the left half of the body. The trajectories in the victims' bodies were from front to back, in one case, and from back to front in all others. Exit wounds were only found in two cases. Death occurred immediately after the victim was shot only in one case, despite a vital structure has been hit in all cases. The cases studied support the idea that the use of firearms against vehicles with the sole intention of immobilisation entails uncontrollable danger to the lives of the occupants, and especially when done by police forces not specifically trained for that purpose. Therefore, such use of firearms should be avoided.

Up-regulation of P2X7 receptor-mediated inhibition of GABA uptake by nerve terminals of the human epileptic neocortex.

OBJECTIVE: Thirty percent of patients with epilepsy are refractory to medication. The majority of these patients have mesial temporal lobe epilepsy (MTLE). This prompts for new pharmacologic targets, like ATP-mediated signaling pathways, since the extracellular levels of the nucleotide dramatically increase during in vitro epileptic seizures. In this study, we investigated whether sodium-dependent high-affinity γ-aminobutyric acid (GABA) and glutamate uptake by isolated nerve terminals of the human neocortex could be modulated by ATP acting via slow-desensitizing P2X7 receptor (P2X7R). METHODS: Modulation of [(3) H]GABA and [(14) C]glutamate uptake by ATP, through activation of P2X7R, was investigated in isolated nerve terminals of the neocortex of cadaveric controls and patients with drug-resistant epilepsy (non-MTLE or MTLE) submitted to surgery. Tissue density and distribution of P2X7R in the human neocortex was assessed by Western blot analysis and immunofluorescence confocal microscopy. RESULTS: The P2X7R agonist, 2'(3')-O-(4-benzoylbenzoyl)ATP (BzATP, 3-100 µm) decreased [(3) H]GABA and [(14) C]glutamate uptake by nerve terminals of the neocortex of controls and patients with epilepsy. The inhibitory effect of BzATP (100 µm) was prevented by the selective P2X7R antagonist, A-438079 (3 µm). Down-modulation of [(14) C]glutamate uptake by BzATP (100 µm) was roughly similar in controls and patients with epilepsy, but the P2X7R agonist inhibited more effectively [(3) H]GABA uptake in the epileptic tissue. Neocortical nerve terminals of patients with epilepsy express higher amounts of the P2X7R protein than control samples. SIGNIFICANCE: High-frequency cortical activity during epileptic seizures releases huge amounts of ATP, which by acting on low-affinity slowly desensitizing ionotropic P2X7R, leads to down-modulation of neuronal GABA and glutamate uptake. Increased P2X7R expression in neocortical nerve terminals of patients with epilepsy may, under high-frequency firing, endure GABA signaling and increase GABAergic rundown, thereby unbalancing glutamatergic neuroexcitation. This study highlights the relevance of the ATP-sensitive P2X7R as an important negative modulator of GABA and glutamate transport and prompts for novel antiepileptic therapeutic targets.

Police shootings against civilians in Portugal: Contextual, forensic medical and judicial characterization.

The aim of this study was to analyse the circumstances, the forensic assessment and the legal assessment of police shootings of civilians, according to the severity of the victim's injuries. Sixty-nine cases tried in Portuguese criminal courts were analysed. Of the 32 cases that resulted in death, 16 were on the public thoroughfare and 13 were in the victim's vehicle or in third-party vehicles. The majority of the lethal cases occurred when the region of the body hit was the thorax/abdomen. The firearm most frequently used was a semi-automatic 9 mm pistol. In cases resulting in death police officers involved were convicted whilst those involved in non-lethal cases were acquitted. The results of this study can be taken into account by Portuguese authorities for the implementation of policies that will allow the restriction of firearms use by police officers to situations of imminent danger of death or serious injury and that will make it possible to avoid shooting at fleeing civilians.

Detailed characterization of incretin cell distribution along the human small intestine.

BACKGROUND: Incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), are physiologic stimulants of insulin release that have been implicated in diabetes remission after bariatric surgery. The detailed distribution of incretin cells along the human small gut, so far unknown, is of utmost importance for the understanding of the metabolic changes observed after bariatric surgery because diabetes remission rate varies according to the type of anatomic rearrangement. OBJECTIVE: To characterize the distribution of incretin producing cells along the human jejunum-ileum. SETTING: Academic public institution. METHODS: Small intestines (n = 30) from autopsies were sampled every 20 cm along their entire length and tissue microarrays were constructed. The percentage of immunohistochemistry-stained cell areas for GLP-1, GIP, and chromogranin A at each segment length was quantified using a computer-aided analysis tool. RESULTS: The percentage of stained area for GLP-1 immunoreactive cells was found to be significantly higher from 200 cm from Treitz ligament onward compared with the first 80 cm of the small intestine, whereas GIP immunoreactive cells were predominant expressed in the first 80 cm. In contrast, chromogranin A expression was constant along the entire jejunum-ileum. CONCLUSION: The uneven distribution of GLP-1-expressing cells, with a higher density from 200 cm of the jejunum-ileum, could contribute to explain the improvement of glycemic profile of diabetic patients observed after anatomic rearrangement of the intestinal tract, in particular when subjected to gastric bypass with longer biliopancreatic limbs.

Necromechanics: Death-induced changes in the mechanical properties of human tissues.

After the death phenomenon, the rigor mortis development, characterized by body stiffening, is one of the most evident changes that occur in the body. In this work, the development of rigor mortis was assessed using a skinfold caliper in human cadavers and in live people to measure the deformation in the biceps brachii muscle in response to the force applied by the device. Additionally, to simulate the measurements with the finite element method, a two-dimensional model of an arm section was used. As a result of the experimental procedure, a decrease in deformation with increasing postmortem time was observed, which corresponds to an increase in rigidity. As expected, the deformations for the live subjects were higher. The finite element method analysis showed a correlation between the c1 parameter of the neo-Hookean model in the 4- to 8-h postmortem interval. This was accomplished by adjusting the c1 material parameter in order to simulate the measured experimental displacement. Despite being a preliminary study, the obtained results show that combining the proposed experimental procedure with a numerical technique can be very useful in the study of the postmortem mechanical modifications of human tissues. Moreover, the use of data from living subjects allows us to estimate the time of death paving the way to establish this process as an alternative to the existing techniques. This solution constitutes a portable, non-invasive method of estimating the postmortem interval with direct quantitative measurements using a skinfold caliper. The tools and methods described can be used to investigate the subject and to gain epidemiologic knowledge on rigor mortis phenomenon.