Targeting leptin/CCL3-CCL4 axes in NAFLD/MAFLD: A novel role for BPF in counteracting thalamic inflammation and white matter degeneration.

Non-alcoholic fatty liver disease (NAFLD), redefined as Metabolic Associated Fatty Liver Disease (MAFLD), is characterized by an extensive multi-organ involvement. MAFLD-induced systemic inflammatory status and peripheral metabolic alteration lead to an impairment of cerebral function. Herein, we investigated a panel of leptin-related inflammatory mediators as predictive biomarkers of neuroinflammation and evaluated the possible role of Bergamot Polyphenolic Fraction (BPF) in counteracting this MAFLD-induced inflammatory cascade. Male DIAMOND mice were randomly assigned to fed chow diet and tap water or high fat diet with sugar water. Starting from week 16, mice were further divided and treated with vehicle or BPF (50 mg/kg/day), via gavage, until week 30. Magnetic resonance imaging was performed at the baseline and at week 30. Correlation and regression analyses were performed to discriminate the altered lipid metabolism in the onset of cerebral alterations. Steatohepatitis led to an increase in leptin levels, resulting in a higher expression of proinflammatory mediators. The inflammatory biomarkers involved in leptin/CCL3-CCL4 axes were correlated with the altered thalamus energetic metabolism and the white matter degeneration. BPF administration restored leptin level, improved glucose and lipid metabolism, and reduced chronic low-grade inflammatory mediators, resulting in a prevention of white matter degeneration, alterations of thalamus metabolism and brain atrophy. The highlighted positive effect of BPF, mediated by the downregulation of the inflammatory biomarkers involved in leptin/CCL3-CCL4 axes, affording novel elements to candidate BPF for the development of a therapeutic strategy aimed at counteracting MAFLD-related brain inflammation.

Large Extracellular Vesicles Derived from Natural Killer Cells Affect the Functions of Monocytes.

Communication between natural killer cells (NK cells) and monocytes/macrophages may play an important role in immunomodulation and regulation of inflammatory processes. The aim of this research was to investigate the impact of NK cell-derived large extracellular vesicles on monocyte function because this field is understudied. We studied how NK-cell derived large extracellular vesicles impact on THP-1 cells characteristics after coculturing: phenotype, functions were observed with flow cytometry. In this study, we demonstrated the ability of large extracellular vesicles produced by NK cells to integrate into the membranes of THP-1 cells and influence the viability, phenotype, and functional characteristics of the cells. The results obtained demonstrate the ability of large extracellular vesicles to act as an additional component in the immunomodulatory activity of NK cells in relation to monocytes.

Kidney Transplantation and Cellular Immunity Dynamics: Immune Cell Alterations and Association with Clinical and Laboratory Parameters.

Background/Objectives: The purpose of this study was to evaluate numerical changes in immune cells after successful kidney transplantation and associate their recovery with clinical and laboratory factors. Methods: In 112 kidney transplant recipients, we performed flow cytometry to evaluate counts of CD4+, CD8+, and regulatory T cells (Tregs), as well as natural killer (NK) cells, before kidney transplantation (T0) and three (T3), six (T6), and twelve (T12) months later. The results were associated with the recipient's age, cold ischemia time (CIT), the type of donor, dialysis method and vintage, and graft function in one year. Results: Total and CD8+ T cell counts increased gradually one year post transplantation in comparison with pre-transplantation levels, whereas the number of CD4+ T cells and Tregs increased, and the number of NK cells decreased in the first three months and remained stable thereafter. The recipient's age was negatively correlated with total, CD4+, and Treg counts at T12, whereas CIT affected only total and CD4+ T cell count. Moreover, recipients receiving kidneys from living donors presented better recovery of all T cell subsets at T12 in comparison with recipients receiving kidneys from cadaveric donors. Patients on peritoneal dialysis had increased numbers of total and CD8+ T cells, as well as NK cells. Finally, estimated glomerular filtration rate was positively correlated with Treg level and potentially CD4+ T cells one-year post transplantation. Conclusions: Successful kidney transplantation results in the recovery of most T cell subsets. Lower recipient age and better graft function contribute to increased T cell counts, whereas donor type and dialysis modality are the most important modifiable factors for optimal immune recovery.

Redemption or Manipulation? Revisiting the Art of a Serial Killer-A Dialogue.

This article revisits an ongoing dialogue between the co-authors, examining their divergent perspectives on whether the art of serial killers was used to perpetuate their psychopathic cycles after their murderous sprees were interrupted, or whether the art-particularly a piece done by one serial killer, Glen Rogers-reflects remorse and redemption. The two art therapists draw from their own clinical and professional experiences to argue their respective outlooks. After explaining what art therapy is, re-examining the concept of murderabilia, and underscoring psychopathy, this article provides an in-depth evaluation of two art pieces done by the serial killer through both of their viewpoints. Ultimately, while neither author completely changed their overall conclusions, elements from both sides of the argument were found relevant. Ultimately, this article emphasized the chaotic and messy connections between art and violence, yet through new perspectives explored on the complexities and motivations within the mayhem, mutual understandings emerged.

Immune responses to oligomeric α-synuclein in Parkinson's disease peripheral blood mononuclear cells.

Parkinson's disease displays clinical heterogeneity, presenting with motor and non-motor symptoms. Heterogeneous phenotypes, named brain-first and body-first, may reflect distinct α-synuclein pathology starting either in the central nervous system or in the periphery. The immune system plays a prominent role in the central and peripheral pathology, with misfolded α-synuclein being placed at the intersection between neurodegeneration and inflammation. Here, we characterized the inflammatory profile and immune-phenotype of peripheral blood mononuclear cells (PBMCs) from Parkinson's disease patients upon stimulation with α-synuclein monomer or oligomer, and investigated relationships of immune parameters with clinical scores of motor and non-motor symptoms. Freshly isolated PBMCs from 21 Parkinson's disease patients and 18 healthy subjects were exposed in vitro to α-synuclein species. Cytokine/chemokine release was measured in the culture supernatant by Multiplex Elisa. The immune-phenotype was studied by FACS-flow cytometry. Correlation analysis was computed between immune parameters and parkinsonian motor and non-motor scales. We found that Parkinson's disease patients exhibited a dysregulated PBMC-cytokine profile, which remained unaltered after exposure to α-synuclein species and correlated with both motor and non-motor severity, with a strong correlation observed with olfactory impairment. Exposure of PBMCs from healthy controls to α-synuclein monomer/oligomer increased the cytokine/chemokine release up to patient's values. Moreover, the PBMCs immune phenotype differed between patients and controls and revealed a prominent association of the Mos profile with olfactory impairment, and of NK profile with constipation. Results suggest that a deranged PBMC-immune profile may reflect distinct clinical subtypes and would fit with the recent classification of Parkinson's disease into peripheral-first versus brain-first phenotype.

Validation of LC-MS/MS method for opioid monitoring in Valencia City wastewater: Assessment of synthetic wastewater as potential aid.

In this study, a comprehensive and sensitive method for the simultaneous detection of 17 opioids (OPs) and their human metabolites in wastewater using high-performance liquid chromatography coupled to tandem mass spectrometry was validated. The chromatographic separations of opioids were carried out on a Kinetex® Biphenyl column (1.7 µm, 100 Å, 50 × 2.1 mm). A synthetic wastewater approach was used for recovery studies to mimic a contaminant-free matrix. Two solid-phase extraction (SPE) sorbents (hydrophilic-lipophilic balance and mixed mode with the previous phase and a weak cationic exchange) were studied to optimize sample treatment and obtain higher recoveries. The mixed mode was chosen because the recoveries of 17 target analytes at three spiked concentrations (25, 50, and 100 ng mL-1) were > 80 % for 75 % of the analytes in a simulated wastewater. The intra- and inter-day relative standard deviations (RSDs) were between ±1 % and ±20 %. The method limits of quantification ranged from 5 to 25 ng L-1, the only exceptions being heroin (275 ng L-1) and morphine-3ß-glucuronide (250 ng L-1). Suppression/enhancement is comparable between the synthetic and the influent wastewater. The analytical method was applied to the OPs analysis in twenty-one influent samples collected from the treatment plants treating the wastewater of Valencia City (Spain). Twelve OPs were detected with total daily concentrations ranging from 1 ng L-1 to 2135 ng L-1. The widespread presence of these compounds in water suggests potential widespread exposure, highlighting the need for increased environmental awareness. Furthermore, the estimated daily intake results raise concerns about opioid use as a potential future health and social issue.

Modeling the evolution of Schizosaccharomyces pombe populations with multiple killer meiotic drivers.

Meiotic drivers are selfish genetic loci that can be transmitted to more than half of the viable gametes produced by a heterozygote. This biased transmission gives meiotic drivers an evolutionary advantage that can allow them to spread over generations until all members of a population carry the driver. This evolutionary power can also be exploited to modify natural populations using synthetic drivers known as "gene drives." Recently, it has become clear that natural drivers can spread within genomes to birth multicopy gene families. To understand intragenomic spread of drivers, we model the evolution of 2 or more distinct meiotic drivers in a population. We employ the wtf killer meiotic drivers from Schizosaccharomyces pombe, which are multicopy in all sequenced isolates, as models. We find that a duplicate wtf driver identical to the parent gene can spread in a population unless, or until, the original driver is fixed. When the duplicate driver diverges to be distinct from the parent gene, we find that both drivers spread to fixation under most conditions, but both drivers can be lost under some conditions. Finally, we show that stronger drivers make weaker drivers go extinct in most, but not all, polymorphic populations with absolutely linked drivers. These results reveal the strong potential for natural meiotic drive loci to duplicate and diverge within genomes. Our findings also highlight duplication potential as a factor to consider in the design of synthetic gene drives.

Macrophages and Natural Killers Degrade α-Synuclein Aggregates.

Amyloid oligomers and fibrils are protein aggregates that exert a high cell toxicity. Efficient degradation of these protein aggregates can minimize the spread and progression of neurodegeneration. In this study, we investigate the properties of natural killer (NK) cells and macrophages in the degradation of α-synuclein (α-Syn) aggregates grown in a lipid-free environment and in the presence of phosphatidylserine and cholesterol (PS/Cho), which are lipids that are directly associated with the onset and progression of Parkinson's disease. We found that both types of α-Syn aggregates were endocytosed by neurons, which caused strong damage to cell endosomes. Our results also indicated that PS/Cho vesicles drastically increased the toxicity of α-Syn fibrils formed in their presence compared to the toxicity of α-Syn aggregates grown in a lipid-free environment. Both NK cells and macrophages were able to degrade α-Syn and α-Syn/Cho monomers, oligomers, and fibrils. Quantitative analysis of protein degradation showed that macrophages demonstrated substantially more efficient internalization and degradation of amyloid aggregates in comparison to NK cells. We also found that amyloid aggregates induced the proliferation of macrophages and NK cells and significantly changed the expression of their cytokines and chemokines.

Suspected serial killers and unsuspected statistical blunders.

A whole branch of theoretical statistics devotes itself to the analysis of clusters, the aim being to distinguish an apparent cluster arising randomly from one that is more likely to have been produced as a result of some systematic influence. There are many examples in medicine and some that involve both medicine and the legal field; criminal law in particular. Observed clusters or a series of cases in a given setting can set off alarm bells, the recent conviction of Lucy Letby in England being an example. It was an observed cluster, a series of deaths among neonates, that prompted the investigation of Letby. There have been other similar cases in the past and there will be similar cases in the future. Our purpose is not to reconsider any particular trial but, rather, to work with similar, indeed more extreme numbers of cases as a way to underline the statistical mistakes that can be made when attempting to make sense of the data. These notions are illustrated via a made-up case of 10 incidents where the anticipated count was only 2. The most common statistical analysis would associate a probability of less than 0.00005 with this outcome: A very rare event. However, a more careful analysis that avoids common pitfalls results in a probability close to 0.5, indicating that, given the circumstances, we were as likely to see 10 or more as we were to see less than 10.

An Unprecedented Bloom of Oceanic Dinoflagellates (Karenia spp.) Inside a Fjord within a Highly Dynamic Multifrontal Ecosystem in Chilean Patagonia.

At the end of summer 2020, a moderate (~105 cells L-1) bloom of potential fish-killing Karenia spp. was detected in samples from a 24 h study focused on Dinophysis spp. in the outer reaches of the Pitipalena-Añihue Marine Protected Area. Previous Karenia events with devastating effects on caged salmon and the wild fauna of Chilean Patagonia had been restricted to offshore waters, eventually reaching the southern coasts of Chiloé Island through the channel connecting the Chiloé Inland Sea to the Pacific Ocean. This event occurred at the onset of the COVID-19 lockdown when monitoring activities were slackened. A few salmon mortalities were related to other fish-killing species (e.g., Margalefidinium polykrikoides). As in the major Karenia event in 1999, the austral summer of 2020 was characterised by negative anomalies in rainfall and river outflow and a severe drought in March. Karenia spp. appeared to have been advected in a warm (14-15 °C) surface layer of estuarine saline water (S > 21). A lack of daily vertical migration patterns and cells dispersed through the whole water column suggested a declining population. Satellite images confirmed the decline, but gave evidence of dynamic multifrontal patterns of temperature and chl a distribution. A conceptual circulation model is proposed to explain the hypothetical retention of the Karenia bloom by a coastally generated eddy coupled with the semidiurnal tides at the mouth of Pitipalena Fjord. Thermal fronts generated by (topographically induced) upwelling around the Tic Toc Seamount are proposed as hot spots for the accumulation of swimming dinoflagellates in summer in the southern Chiloé Inland Sea. The results here provide helpful information on the environmental conditions and water column structure favouring Karenia occurrence. Thermohaline properties in the surface layer in summer can be used to develop a risk index (positive if the EFW layer is thin or absent).

An investigation into the association between cannibalism and serial killers.

The aim of the current study was to compare and contrast non-cannibalistic and cannibalistic serial killers. Using case study data, the present study assessed common patterns among the life histories of cannibalistic serial killers compared to those of a control sample of serial killers that did not commit cannibalism. These include but are not limited to childhood experiences, socio-economic status, biological abnormalities and life events. Results indicated that factors that may differentiate cannibals from non-cannibals likely result from childhood influences, rather than influences at the time of the kill. Findings may be used to identify potential warning signs or triggers for cannibalistic behaviour.

Anxiolytic, Analgesic and Anti-Inflammatory Effects of Peptides Hmg 1b-2 and Hmg 1b-4 from the Sea Anemone Heteractis magnifica.

Acid-sensing ion channels (ASICs) have been known as sensors of a local pH change within both physiological and pathological conditions. ASIC-targeting peptide toxins could be potent molecular tools for ASIC-manipulating in vitro, and for pathology treatment in animal test studies. Two sea anemone toxins, native Hmg 1b-2 and recombinant Hmg 1b-4, both related to APETx-like peptides, inhibited the transient current component of human ASIC3-Δ20 expressed in Xenopus laevis oocytes, but only Hmg 1b-2 inhibited the rat ASIC3 transient current. The Hmg 1b-4 action on rASIC3 as a potentiator was confirmed once again. Both peptides are non-toxic molecules for rodents. In open field and elevated plus maze tests, Hmg 1b-2 had more of an excitatory effect and Hmg 1b-4 had more of an anxiolytic effect on mouse behavior. The analgesic activity of peptides was similar and comparable to diclofenac activity in an acid-induced muscle pain model. In models of acute local inflammation induced by λ-carrageenan or complete Freund's adjuvant, Hmg 1b-4 had more pronounced and statistically significant anti-inflammatory effects than Hmg 1b-2. It exceeded the effect of diclofenac and, at a dose of 0.1 mg/kg, reduced the volume of the paw almost to the initial volume. Our data highlight the importance of a comprehensive study of novel ASIC-targeting ligands, and in particular, peptide toxins, and present the slightly different biological activity of the two similar toxins.

Novel Local "Off-the-Shelf" Immunotherapy for the Treatment of Myeloma Bone Disease.

Myeloma bone disease (MBD) is one of the major complications in multiple myeloma (MM)-the second most frequent hematologic malignancy. It is characterized by the formation of bone lesions due to the local action of proliferating MM cells, and to date, no effective therapy has been developed. In this study, we propose a novel approach for the local treatment of MBD with a combination of natural killer cells (NKs) and mesenchymal stem cells (MSCs) within a fibrin scaffold, altogether known as FINM. The unique biological properties of the NKs and MSCs, joined to the injectable biocompatible fibrin, permitted to obtain an efficient "off-the-shelf" ready-to-use composite for the local treatment of MBD. Our in vitro analyses demonstrate that NKs within FINM exert a robust anti-tumor activity against MM cell lines and primary cells, with the capacity to suppress osteoclast activity (~60%) within in vitro 3D model of MBD. Furthermore, NKs' post-thawing cytotoxic activity is significantly enhanced (~75%) in the presence of MSCs, which circumvents the decrease of NKs cytotoxicity after thawing, a well-known issue in the cryopreservation of NKs. To reduce the tumor escape, we combined FINM with other therapeutic agents (bortezomib (BZ), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)), observing a clear therapeutic synergistic effect in vitro. Finally, the therapeutic efficacy of FINM in combination with BZ and TRAIL was assessed in a mouse model of MM, achieving 16-fold smaller tumors compared to the control group without treatment. These results suggest the potential of FINM to serve as an allogeneic "off-the-shelf" approach to improve the outcomes of patients suffering from MBD.

The role of monocytes and natural killers' immunophenotypic subsets in bronchial asthma in children.

Objective: Childhood bronchial asthma (BA) is a globally significant chronic disease with major health consequences. Recently, focus on the role of the innate immune system has been highlighted. Therefore, this study explores the role of circulating monocytes and natural killer (NK) clusters in childhood asthma.Methods: This case-control study enrolled 50 children with asthma divided equally into severe and mild groups and 26 healthy children. Flow-cytometry analysis was used to identify circulating blood monocytes and natural killers' subsets. In addition, pulmonary function test (spirometry) for children with asthma was performed.Results: This study showed significant negative correlations between frequency of total circulating, classical, intermediate, and nonclassical monocytes with ratio of forced expiratory volume/forced vital capacity (FEV1/FVC) (r = -0.637, P < 0.001; r = -0.575, P < 0.001; r = -0.657, P < 0.001; r = -0.329, P = 0.004, respectively). Also, there was significant negative correlations between frequency of total NKs and CD56dim CD16+ NK with FEV1/FVC (r = -0.584, P < 0.001) and (r = -0.579, P < 0.001). Significant predictors of childhood asthma severity were frequencies of total monocytes, total NKs, intermediate monocytes, and CD56dimCD16+ NK.Conclusion: Finally, we concluded that the FEV1/FVC is linked to aberrations of monocytes' and natural killers' immunophenotypic subsets in children with asthma. The frequencies of total monocytes and NK are significant predictors of severity of childhood asthma. The frequencies of CD14high CD16+ intermediate monocytes and CD56dim CD16+ NK cells are the best independent predictors of severity in children with asthma.

O crime como ato perverso: uma análise das cartas de assassinos seriais / El crimen como un acto perverso: un análisis de cartas de asesinos en serie / Crime as a perverse act: analysis of letters from serial killers

RESUMO. Este trabalho se insere no campo teórico da psicanálise e tem por objetivo discutir, a partir do conceito de perversão, a relação entre o ato perverso e os assassinatos em série, através das comunicações que certos autores desse tipo de crime realizaram com a mídia e com as forças da lei. Para a realização desse objetivo foi feita uma análise de conteúdo, segundo Bardin (2011), em 35 cartas enviadas por sete assassinos em série diferentes para a grande mídia ou para a polícia. Como resultado, encontra-se o fato de que a estrutura desses documentos é bastante similar e apresentam descrições de seus crimes, seus estados mentais, além de ameaças à população e um deboche direcionado às autoridades e forças policiais. Por fim, nota-se que a estrutura do ato perverso, conforme pensada por Freud e Lacan, está presente nas cartas estudadas, que pertencem a épocas e lugares distintos, e cujos autores não tiveram contato direto entre si.

RESUMEN. Este trabajo es parte del campo teórico del psicoanálisis y tiene como objetivo identificar los comportamientos comunes que están presentes en diferentes actos perversos, más específicamente en las comunicaciones que los asesinos en serie llevan a cabo con los medios de comunicación y las fuerzas de la ley. Para lograr este objetivo, se realizó un análisis de contenido, según Bardin (2011) sobre 35 cartas enviadas por siete asesinos en serie diferentes a los principales medios de comunicación o la policía. Como resultado, existe el hecho de que la estructura de estos documentos es bastante similar y presenta descripciones de sus crímenes, sus estados mentales, además de las amenazas a la población y un libertinaje dirigido a las autoridades y las fuerzas policiales. Finalmente, se observa que la estructura del acto perverso, como lo piensan las teorías de Freud y Lacan, tiende a repetirse en los sujetos estudiados, que pertenecen a diferentes tiempos y lugares y que no tuvieron contacto directo entre sí.

ABSTRACT This work is part of the theoretical field of psychoanalysis and aims to discuss, from the concept of perversion, the relationship between the perverse act and serial murders, through the communications that certain authors of this type of crime made with the media and with the forces of the law. To achieve this objective, a content analysis was carried out, according to Bardin (2011), on thirty-five letters sent by seven different serial killers to the mainstream media or the police. As a result, there is the fact that the structure of these documents is quite similar and presents descriptions of their crimes, their mental states, in addition to threats to the population and a debauchery directed at the authorities and police forces. Finally, it is noted that the structure of the perverse act, as thought by the theories of Freud and Lacan, is present in the studied letters, which belong to different times and places, and whose authors had no direct contact with each other.

The wtf meiotic driver gene family has unexpectedly persisted for over 100 million years.

Meiotic drivers are selfish elements that bias their own transmission into more than half of the viable progeny produced by a driver+/driver- heterozygote. Meiotic drivers are thought to exist for relatively short evolutionary timespans because a driver gene or gene family is often found in a single species or in a group of very closely related species. Additionally, drivers are generally considered doomed to extinction when they spread to fixation or when suppressors arise. In this study, we examine the evolutionary history of the wtf meiotic drivers first discovered in the fission yeast Schizosaccharomyces pombe. We identify homologous genes in three other fission yeast species, S. octosporus, S. osmophilus, and S. cryophilus, which are estimated to have diverged over 100 million years ago from the S. pombe lineage. Synteny evidence supports that wtf genes were present in the common ancestor of these four species. Moreover, the ancestral genes were likely drivers as wtf genes in S. octosporus cause meiotic drive. Our findings indicate that meiotic drive systems can be maintained for long evolutionary timespans.

Is IFN expression by NK cells a hallmark of severe COVID-19?

Natural Killer cells (NK) are crucial in host defense against viruses. There are many unanswered questions about the immune system in COVID-19, especially the mechanisms that contribute to the development of mild or severe forms of the disease. Although NK cells may have an essential role in the pathogenesis of COVID-19, the mechanisms involved in this process are not yet fully elucidated. Here, we demonstrate that CD3-CD56+ NK cells frequency in the volunteers who recovered from mild COVID-19 (Mild CoV) presented a significant increase compared to the healthy control (HC) and individuals recovering from severe COVID-19 (Severe CoV) groups. Furthermore, distinct IFN profiles in recovered COVID-19 patients with mild or severe clinical forms of the disease were observed in the total NK cells (CD3-CD56+). In the first group, NK cells express increased levels of IFN-α compared to the severe CoV, while higher production of IFN-γ in severe CoV was found. Moreover, NK cells in mild CoV express more cytolytic granules depicted by granzyme B and perforin. Compared to HC, PBMCs from mild CoV presented higher Ki-67 and TIM-3 production after Pool CoV-2 and Pool Spike CoV-2 peptides stimulus. In addition, non-stimulated PBMCs in the mild CoV group had higher NK TIM-3+ frequency than severe CoV. In the mild CoV group, Pool Spike CoV-2 and Pool CoV-2 peptides stimuli elicited higher granzyme B and perforin coexpression and IFN-α production by PBMCs. However, in severe CoV, Pool Spike CoV-2 reduced the coexpression of granzyme B, perforin, and CD107a suggesting a decrease in the cytotoxic activity of NK cells. Therefore, our study shows that NK cells may have a crucial role in COVID-19 with the involvement of IFN-α and cytotoxic properties that aid in developing qualified immune responses. Furthermore, the data suggest that higher amounts of IFN-γ may be linked to the severity of this disease.

Youth Serial Killers: Psychological and Criminological Profiles.

Serial murder is a specific type of violent crime that falls into the crime category of multicide. According to the nomenclature of the Federal Bureau of Investigation's Violent Crime Classification Manual and Academic Researchers for the Classification of Violent Crimes, most serial killers are adults. However, serial murder is also committed by young people, although to a lesser extent. Young serial killers are a topic of relevance in areas such as psychology, criminology, and the justice system. Given that the study of the variables that could be the basis of such multicide criminality is not conclusive, the need for further research is evident. The homicides perpetrated by children and young people point to a social panorama that is alarming due to their young age. This issue is prevalent enough to conduct a review. The performed review concludes the importance of psychosocial factors to better understand the process by which children and young people commit crimes as serious as serial murders. The scope of the problem of serial murders perpetrated by minors is controversial because it often depends on how the number of real cases is counted. Although official statistics indicate the low prevalence of juvenile serial killers, childhood is a period in which antisocial behaviour can have its beginning. Some authors consider that it is not uncommon for the first murder of this type to occur in adolescence. It is important to consider psychopathy as an influential factor in the various forms of serial criminal conduct committed by children and young people. The research works consulted provide evidence of the special relevance of psychopathy in the generation of serious juvenile delinquency.

Late antibody-mediated rejection in a kidney transplant recipient: COVID 19 induced?

BACKGROUND: Antibody-mediated rejection (AMR) was described in kidney transplant patients after viral infections, such as the cytomegalovirus. Very few cases were recently reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, probably in the context of lowering of immunosuppressive therapy. To date, no direct immunological link was proved to explain a connection between the coronavirus disease 19 (COVID-19) infection and antibody-mediated rejection (AMR) if it exists. CASE PRESENTATION: Here we try to find this association by presenting the case of a low immunological risk patient who presented, six years post-transplant, with c4d negative antibody mediated rejection due to an anti-HLA-C17 de novo donor specific antibody (DSA) after contracting the coronavirus disease 19. The HLA-Cw17 activated the antibody-dependent cell-mediated cytotoxicity via the KIR2DS1 positive NK cells. DISCUSSION AND CONCLUSIONS: This case report may prove a direct role for COVID-19 infection in AMRs in the kidney transplant recipients, leading us to closely monitor kidney transplant recipients, especially if they have "at-risk" donor antigens.

Passage and the evolution of virulence in invertebrate pathogens: Fundamental and applied perspectives.

Understanding the ecological and genetic factors that determine the evolution of virulence has broad value for invertebrate pathology. In addition to helping us understand the fundamental biology of our study organisms this body of theory has important applications in microbial biocontrol. Experimental tests of virulence theory are often carried out in invertebrate models and yet theory rarely informs applied passage experiments that aim to increase or maintain virulence. This review summarizes recent progress in this field with a focus on work most relevant to biological control: the virulence of invertebrate pathogens that are 'obligate killers' and which require cadavers for the production of infectious propagules. We discuss recent theory and fundamental and applied experimental evolution with bacteria, fungi, baculoviruses and nematodes. While passage experiments using baculoviruses have a long history of producing isolates with increased virulence, studies with other pathogens have not been so successful. Recent passage experiments that have applied evolution of virulence frameworks based on cooperation (kin selection) have produced novel methods and promising mutants with increased killing power. Evolution of virulence theory can provide plausible explanations for the varied results of passage experiments as well as a predictive framework for improving artificial selection.