Post-Mortem Immunohistochemical Evidence of β2-Adrenergic Receptor Expression in the Adrenal Gland

The evidence from post-mortem biochemical studies conducted on cortisol and catecholamines suggest that analysis of the adrenal gland could provide useful information about its role in human pathophysiology and the stress response. Authors designed an immunohistochemical study on the expression of the adrenal β2-adrenergic receptor (β2-AR), a receptor with high-affinity for catecholamines, with the aim to show which zones it is expressed in and how its expression differs in relation to the cause of death. The immunohistochemical study was performed on adrenal glands obtained from 48 forensic autopsies of subjects that died as a result of different pathogenic mechanisms using a mouse monoclonal β2-AR antibody. The results show that immunoreactivity for β2-AR was observed in all adrenal zones. Furthermore, immunoreactivity for β2-AR has shown variation in the localization and intensity of different patterns in relation to the original cause of death. To the best of our knowledge, this is the first study that demonstrates β2-AR expression in the human cortex and provides suggestions on the possible involvement of β2-AR in human cortex hormonal stimulation. In conclusion, the authors provide a possible explanation for the observed differences in expression in relation to the cause of death

Varicella-zoster virus induces apoptosis in cell culture

peer reviewedaudience: researcherApoptosis is an active mechanism of cell death which can be initiated in response to various stimuli including virus infections. In this work, we demonstrate that lytic infection by varicella-zoster virus (VZV), a human herpesvirus, is characterized by nuclear fragmentation of DNA into oligonucleosomal fragments and by chromatin condensation. In vitro, VZV-induced cell death is actually mediated by apoptosis. The mechanisms developed by cells to protect themselves against apoptosis could be one of the parameters allowing the establishment of virus latency. In the case of VZV, which can remain latent in sensory ganglia, we have not yet identified a cellular or viral protein which could play this protective role, since the observed apoptosis mechanism seems to be independent from Bcl-2, the most frequently described inhibitor of apoptosis

Caspase 9 and caspase 3 immunohistochemical pattern in skeletal and cardiac muscles at different times after death: An experimental study on pmi estimation

(1) Background: The estimation of the post mortem interval (PMI) is a challenge for forensic pathologists because data emerging from methods commonly applied are not always conclusive, since several conditions exist that may affect the reliability of these parameters. Thus, new approaches have been proposed to overcome such a limit. In recent years, several studies have been performed on proteins analyzing their expression/degradation patterns in relation to the progressing of the post mortem interval. (2) Methods: The immunoreactivity patterns of two apoptosis mediators— Caspase 9 and Caspase 3—have been tested in order to evaluate their potential role as markers of the post mortem interval. The immunohistochemical analysis was performed on samples of skeletal and cardiac muscles obtained from rats at 0, 4, 8, 12, 24 and 72 h after death. (3) Results: The observed immunoreactivity patterns of both Caspase 9 and Caspase 3 showed a significant correlation with increasing post mortem interval either in skeletal or cardiac muscles, while the comparison of the immunoreactivity patterns of the two apoptotic mediators within each tissue appeared consistent with a preliminary activation of the “initiator” Caspase 9, which, in turn, subsequently activates the “executioner” Caspase 3. (4) Conclusion: The different expressions and decrease immunohistochemically observed on both caspases with progressing PMI support the usefulness of the combined analysis for post mortem interval estimation

BioLPG for Clean Cooking in Sub-Saharan Africa: Present and Future Feasibility of Technologies, Feedstocks, Enabling Conditions and Financing

Energy supply for clean cooking is a priority for Sub-Saharan Africa (SSA). Liquefied petroleum gas (LPG, i.e., propane or butane or a mixture of both) is an economically efficient, cooking energy solution used by over 2.5 billion people worldwide and scaled up in numerous low- and middle-income countries (LMICs). Investigation of the technical, policy, economic and physical requirements of producing LPG from renewable feedstocks (bioLPG) finds feasibility at scale in Africa. Biogas and syngas from the circular economic repurposing of municipal solid waste and agricultural waste can be used in two groundbreaking new chemical processes (Cool LPG or Integrated Hydropyrolysis and Hydroconversion (IH2)) to selectively produce bioLPG. Evidence about the nature and scale potential of bioLPG presented in this study justifies further investment in the development of bioLPG as a fuel that can make a major contribution toward enabling an SSA green economy and universal energy access. Techno-economic assessments of five potential projects from Ghana, Kenya and Rwanda illustrate what might be possible. BioLPG technology is in the early days of development, so normal technology piloting and de-risking need to be undertaken. However, fully developed bioLPG production could greatly reduce the public and private sector investment required to significantly increase SSA clean cooking capacity

Scaling up gas and electric cooking in low- and middle-income countries: climate threat or mitigation strategy with co-benefits?

Nearly three billion people in low- and middle-income countries (LMICs) rely on polluting fuels, resulting in millions of avoidable deaths annually. Polluting fuels also emit short-lived climate forcers (SLCFs) and greenhouse gases (GHGs). Liquefied petroleum gas (LPG) and grid-based electricity are scalable alternatives to polluting fuels but have raised climate and health concerns. Here, we compare emissions and climate impacts of a business-as-usual household cooking fuel trajectory to four large-scale transitions to gas and/or grid electricity in 77 LMICs. We account for upstream and end-use emissions from gas and electric cooking, assuming electrical grids evolve according to the 2022 World Energy Outlook’s ‘Stated Policies’ Scenario. We input the emissions into a reduced-complexity climate model to estimate radiative forcing and temperature changes associated with each scenario. We find full transitions to LPG and/or electricity decrease emissions from both well-mixed GHG and SLCFs, resulting in a roughly 5 millikelvin global temperature reduction by 2040. Transitions to LPG and/or electricity also reduce annual emissions of PM2.5 by over 6 Mt (99%) by 2040, which would substantially lower health risks from household air pollution. Full transitions to LPG or grid electricity in LMICs improve climate impacts over BAU trajectories

Ectopic internal carotid artery presenting as an oropharyngeal mass

Ectopic internal carotid artery (ICA) is a very rare variation. The major congenital abnormalities of the ICA can be classified as agenesis, aplasia and hypoplasia, and they can be unilateral or bilateral. Anomalies of the neck artery may be vascular neoplasms or ectopic position. Carotid angiograms provide absolute confirmation of an aberrant carotid artery, while EcoColorDoppler (ECD) gives also important information about the evaluation of carotid vassels. Nevertheless Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) of the neck provide spatial information about the adjacent pharyngeal anatomy and are less invasive than angiogram. Injuries to the ICA during simple pharyngeal surgical procedures can be catastrophic due to the risk of massive bleeding. We report a case of a 56 year-old male patient suffering from dysphagia associated with aberrant ICA manifesting itself as a pulsative protruding of the left lateral wall of the oropharynx

Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimal residual disease-oriented GIMEMA LAL1913

Early recognition of Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) cases could impact on the management and outcome of this subset of B-lineage ALL. In order to assess the prognostic value of the Ph-like status in a pediatric-inspired, minimal residual disease (MRD)driven trial, we screened 88 B-lineage ALL cases negative for major fusion genes (BCR-ABL1, ETV6-RUNX1, TCF3-PBX1 and KTM2Ar) enrolled in the GIMEMA LAL1913 front-line protocol for adult BCR/ABL1-negative ALL. The screening - performed using the “BCR/ABL1-like predictor” - identified 28 Ph-like cases (31.8%), characterized by CRLF2 overexpression (35.7%), JAK/STAT pathway mutations (33.3%), IKZF1 (63.6%), BTG1 (50%) and EBF1 (27.3%) deletions, and rearrangements targeting tyrosine kinases or CRLF2 (40%). The correlation with outcome highlighted that: i) the complete remission rate was significantly lower in Ph-like compared to non-Ph-like cases (74.1% vs. 91.5%, P=0.044); ii) at time point 2, decisional for transplant allocation, 52.9% of Ph-like cases versus 20% of non-Ph-like were MRD-positive (P=0.025); iii) the Ph-like profile was the only parameter associated with a higher risk of being MRD-positive at time point 2 (P=0.014); iv) at 24 months, Ph-like patients had a significantly inferior event-free and disease-free survival compared to non-Ph-like patients (33.5% vs. 66.2%, P=0.005 and 45.5% vs. 72.3%, P=0.062, respectively). This study documents that Ph-like patients have a lower complete remission rate, event-free survival and disease-free survival, as well as a greater MRD persistence also in a pediatric-oriented and MRD-driven adult ALL protocol, thus reinforcing that the early recognition of Ph-like ALL patients at diagnosis is crucial to refine risk-stratification and to optimize therapeutic strategies

Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimale residual disease-oriented GIMEMA LAL1913

Early recognition of Ph-like acute lymphoblastic leukemia cases could impact on the management and outcome of this subset of B-lineage ALL. To assess the prognostic value of the Ph-like status in a pediatric-inspired, minimal residual disease (MRD)-driven trial, we screened 88 B-lineage ALL cases negative for the major fusion genes (BCR-ABL1, ETV6-RUNX1, TCF3-PBX1 and KTM2Ar) enrolled in the GIMEMA LAL1913 front-line protocol for adult BCR/ABL1-negative ALL. The screening - performed using the “BCR/ABL1-like predictor” - identified 28 Ph-like cases (31.8%), characterized by CRLF2 overexpression (35.7%), JAK/STAT pathway mutations (33.3%), IKZF1 (63.6%), BTG1 (50%) and EBF1 (27.3%) deletions, and rearrangements targeting tyrosine kinases or CRLF2 (40%). The correlation with outcome highlighted that: i) the complete remission (CR) rate was significantly lower in Ph-like compared to non-Ph-like cases (74.1% vs 91.5%, p=0.044); ii) at time point 2 (TP2), decisional for transplant allocation, 52.9% of Ph-like cases vs 20% of non-Phlike were MRD-positive (p=0.025); iii) the Ph-like profile was the only parameter associated with a higher risk of being MRD-positive at TP2 (p=0.014); iv) at 24 months, Ph-like patients had a significantly inferior event-free and disease-free survival compared to non-Ph-like patients (33.5% vs 66.2%, p=0.005 and 45.5% vs 72.3%, p=0.062, respectively). This study documents that Ph-like patients have a lower CR rate, EFS and DFS, as well as a greater MRD persistence also in a pediatric-oriented and MRD-driven adult ALL protocol, thus reinforcing that the early recognition of Ph-like ALL patients at diagnosis is crucial to refine risk-stratification and to optimize therapeutic strategies

Compensating control participants when the intervention is of significant value: experience in Guatemala, India, Peru and Rwanda

The Household Air Pollution Intervention Network (HAPIN) trial is a randomised controlled trial in Guatemala, India, Peru and Rwanda to assess the health impact of a clean cooking intervention in households using solid biomass for cooking. The HAPIN intervention—a liquefied petroleum gas (LPG) stove and 18-month supply of LPG—has significant value in these communities, irrespective of potential health benefits. For control households, it was necessary to develop a compensation strategy that would be comparable across four settings and would address concerns about differential loss to follow-up, fairness and potential effects on household economics. Each site developed slightly different, contextually appropriate compensation packages by combining a set of uniform principles with local community input. In Guatemala, control compensation consists of coupons equivalent to the LPG stove’s value that can be redeemed for the participant’s choice of household items, which could include an LPG stove. In Peru, control households receive several small items during the trial, plus the intervention stove and 1 month of fuel at the trial’s conclusion. Rwandan participants are given small items during the trial and a choice of a solar kit, LPG stove and four fuel refills, or cash equivalent at the end. India is the only setting in which control participants receive the intervention (LPG stove and 18 months of fuel) at the trial’s end while also being compensated for their time during the trial, in accordance with local ethics committee requirements. The approaches presented here could inform compensation strategy development in future multi-country trials

Mapping the prion protein distribution in marsupials: insights from comparing opossum with mouse CNS

The cellular form of the prion protein (PrP(C)) is a sialoglycoprotein widely expressed in the central nervous system (CNS) of mammalian species during neurodevelopment and in adulthood. The location of the protein in the CNS may play a role in the susceptibility of a species to fatal prion diseases, which are also known as the transmissible spongiform encephalopathies (TSEs). To date, little is known about PrP(C) distribution in marsupial mammals, for which no naturally occurring prion diseases have been reported. To extend our understanding of varying PrP(C) expression profiles in different mammals we carried out a detailed expression analysis of PrP(C) distribution along the neurodevelopment of the metatherian South American short-tailed opossum (Monodelphis domestica). We detected lower levels of PrP(C) in white matter fiber bundles of opossum CNS compared to mouse CNS. This result is consistent with a possible role for PrP(C) in the distinct neurodevelopment and neurocircuitry found in marsupials compared to other mammalian species