Are mast cells implicated in asphyxia?

In a previous immunohistochemical (IHC) study, we documented the reaction of lung tissue vessels to hypoxia through the immunodetection of HIF1-α protein, a key regulator of cellular response to hypoxic conditions. Findings showing that asphyxia deaths are associated with an increase in the number of mast cell (MC)-derived tryptase enzymes in the blood suggests that HIF1-α production may be correlated with MC activation in hypoxic conditions. This hypothesis prompted us to investigate the possible role of pulmonary MC in acute asphyxia deaths. Lung of 47 medico-legal autopsy cases (35 asphyxia/hypoxia deaths, 11 controls, and 1 anaphylactic death) were processed by IHC analysis using anti-CD117 (c-Kit) antibody to investigate peri-airway and perivascular MC together with their counts and features. Results showed a significant increase in peri-vascular c-kit+ MC in some asphyxia deaths, such as hanging, strangulation, and aspiration deaths. A strong activation of MC in peri-airway and peri-vascular areas was also observed in lung samples from the anaphylaxis case, which was used as a positive control. Our study points to the potential role of MC in hypoxia and suggests that an evaluation of MC in the lungs may be a useful parameter when forensic pathologists are required to make a differential diagnosis between acute asphyxia deaths and other kinds of death

Traumatic brain injury: A forensic approach: A literature review

Traumatic brain injury (TBI) is the principal cause of invalidity and death in the population under 45 years of age worldwide. This mini-review aims to systematize the forensic approach in neuropathological studies, highlighting the proper elements to be noted during external, radiological, autoptical, and histological examinations with particular attention paid to immunohistochemistry and molecular biology. In the light of the results of this mini-review, an accurate forensic approach can be considered mandatory in the examination of suspected TBI with medico-legal importance, in order to gather all the possible evidence to corroborate the diagnosis of a lesion that may have caused, or contributed to, death. From this point of view, only the use of an evidence-based protocol can reach a suitable diagnosis, especially in those cases in which there are other neuropathological conditions (ischemia, neurodegeneration, neuro-inflammation, dementia) that may have played a role in death. This is even more relevant when corpses, in an advanced state of decomposition, are studied, where the radiological, macroscopic and histological analyses fail to give meaningful answers. In these cases, immune-histochemical and molecular biology diagnostics are of fundamental importance and a forensic neuropathologist has to know them. Particularly, MiRNAs are promising biomarkers for TBI both for brain damage identification and for medico-legal aspects, even if further investigations are required to validate the first experimental studies. In the same way, the genetic substrate should be examined during any forensic examination, considering its importance in the outcome of TBI

Mistrial or Misdiagnosis: The Importance of Autopsy and Histopathological Examination in Cases of Sudden Infant Bronchiolitis-Related Death

Pediatrics, among all the branches of medicine, is a sector not particularly affected by a high number of claims. Nevertheless, the economic value of the compensation is significantly high, for example, in cases of children who suffered multiple disabilities following perinatal lesions with a long life expectancy. In Italy, most of the claims for compensation concern surgical pathologies and infections. Among these latter, the dominant role is taken by respiratory tract infections. In this context, the purpose of this manuscript is to present a case series of infant deaths in different emergency-related facilities (ambulances, emergency rooms) denounced by relatives. Following these complaints, the autopsy was performed, and subsequent histological examinations revealed the presence of typical and pathognomonic histological findings of acute viral bronchiolitis, whose morphological appearance is poorly reported in the literature. The analysis of these cases made it possible to highlight the following conclusions: the main problems in diagnosing sudden death causes, especially in childhood, are the rapidity of death and the scarce correlation between the preexistent diseases and of the cause of death itself. For all these reasons, the autopsy, either clinical or medicolegal, is mandatory in cases of sudden unexpected infant death to manage claim requests because only the histological examinations performed on samples collected during the autopsy can reveal the real cause of death

Nandrolone decanoate interferes with testosterone biosynthesis altering blood-testis barrier components

The aim of this study was to investigate whether nandrolone decanoate (ND) use affects testosterone production and testicular morphology in a model of trained and sedentary mice. A group of mice underwent endurance training while another set led a sedentary lifestyle and were freely mobile within cages. All experimental groups were treated with either ND or peanut oil at different doses for 6 weeks. Testosterone serum levels were measured via liquid chromatography-mass spectrometry. Western blot analysis and quantitative real-time PCR were utilized to determine gene and protein expression levels of the primary enzymes implicated in testosterone biosynthesis and gene expression levels of the blood-testis barrier (BTB) components. Immunohistochemistry and immunofluorescence were conducted for testicular morphological evaluation. The study demonstrated that moderate to high doses of ND induced a diminished serum testosterone level and altered the expression level of the key steroidogenic enzymes involved in testosterone biosynthesis. At the morphological level, ND induced degradation of the BTB by targeting the tight junction protein-1 (TJP1). ND stimulation deregulated metalloproteinase-9, metalloproteinase-2 (MMP-2) and the tissue inhibitor of MMP-2. Moreover, ND administration resulted in a mislocalization of mucin-1. In conclusion, ND abuse induces a decline in testosterone production that is unable to regulate the internalization and redistribution of TJP1 and may induce the deregulation of other BTB constituents via the inhibition of MMP-2. ND may well be considered as both a potential inducer of male infertility and a potential risk factor to a low endogenous bioavailable testosterone

Primary motor cortex excitability in karate athletes: A transcranial magnetic stimulation study

Purpose: The mechanisms involved in the coordination of muscle activity are not completely known: to investigate adaptive changes in human motor cortex Transcranial magnetic stimulation (TMS) was often used. The sport models are frequently used to study how the training may affect the corticospinal system excitability: Karate represents a valuable sport model for this kind of investigations for its high levels of coordination required to athletes. This study was aimed at examining possible changes in the resting motor threshold (rMT) and in the corticospinal response in karate athletes, and at determining whether athletes are characterized by a specific value of rMT. Methods: We recruited 25 right-handed young karate athletes and 25 matched non-athletes. TMS was applied to primary motor cortex (M1). Motor evoked potential (MEP) were recorded by two electrodes placed above the first dorsal interosseous (FDI) muscle. We considered MEP latencies and amplitudes at rMT, 110% of rMT, and 120% of rMT. Results: The two groups were similar for age (p > 0.05), height (p > 0.05) and body mass (p > 0.05). The TMS had a 70-mm figure-of-eight coil and a maximum output of 2.2 T, placed over the left motor cortex. During the stimulation, a mechanical arm kept the coil tangential to the scalp, with the handle at 45° respect to the midline. The SofTaxic navigator system (E.M.S. Italy, www.emsmedical.net) was used in order to correctly identifying and repeating the stimulation for every subject. Compared to non-athletes, athletes showed a lower resting motor threshold (p < 0.001). Furthermore, athletes had a lower MEP latency (p < 0.001) and a higher MEP amplitude (p < 0.001) compared to non-athletes. Moreover, a ROC curve for rMT was found significant (area: 0.907; sensitivity 84%, specificity 76%). Conclusions: As the main finding, the present study showed significant differences in cortical excitability between athletes and non-athletes. The training can improve cortical excitability inducing athletes' modifications, as demonstrated in rMT and MEP values. These finding support the hypothesis that the sport practice determines specific brain organizations in relationship with the sport challenges

Diabetes-Related Autoantibodies in Children With Acute Lymphoblastic Leukemia

[No abstract available

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Parallel Driving and Modulatory Pathways Link the Prefrontal Cortex and Thalamus

Pathways linking the thalamus and cortex mediate our daily shifts from states of attention to quiet rest, or sleep, yet little is known about their architecture in high-order neural systems associated with cognition, emotion and action. We provide novel evidence for neurochemical and synaptic specificity of two complementary circuits linking one such system, the prefrontal cortex with the ventral anterior thalamic nucleus in primates. One circuit originated from the neurochemical group of parvalbumin-positive thalamic neurons and projected focally through large terminals to the middle cortical layers, resembling ‘drivers’ in sensory pathways. Parvalbumin thalamic neurons, in turn, were innervated by small ‘modulatory’ type cortical terminals, forming asymmetric (presumed excitatory) synapses at thalamic sites enriched with the specialized metabotropic glutamate receptors. A second circuit had a complementary organization: it originated from the neurochemical group of calbindin-positive thalamic neurons and terminated through small ‘modulatory’ terminals over long distances in the superficial prefrontal layers. Calbindin thalamic neurons, in turn, were innervated by prefrontal axons through small and large terminals that formed asymmetric synapses preferentially at sites with ionotropic glutamate receptors, consistent with a driving pathway. The largely parallel thalamo-cortical pathways terminated among distinct and laminar-specific neurochemical classes of inhibitory neurons that differ markedly in inhibitory control. The balance of activation of these parallel circuits that link a high-order association cortex with the thalamus may allow shifts to different states of consciousness, in processes that are disrupted in psychiatric diseases