Insight into the Effect of Methylglyoxal on the Conformation, Function, and Aggregation Propensity of α-Synuclein.

It is well-known that people suffering from hyperglycemia have a higher propensity to develop Parkinson's disease (PD). One of the most plausible mechanisms linking these two pathologies is the glycation of neuronal proteins and the pathological consequences of it. α-Synuclein, a key component in PD, can be glycated at its fifteen lysine. In fact, the end products of this process have been detected on aggregated α-synuclein isolated from in vivo. However, the consequences of glycation are not entirely clear, which are of crucial importance to understand the mechanism underlying the connection between diabetes and PD. To better clarify this, we have here examined how methylglyoxal (the most important carbonyl compound found in the cytoplasm) affects the conformation and aggregation propensity of α-synuclein, as well as its ability to cluster and fuse synaptic-like vesicles. The obtained data prove that methylglyoxal induces the Lys-Lys crosslinking through the formation of MOLD. However, this does not have a remarkable effect on the averaged conformational ensemble of α-synuclein, although it completely depletes its native propensity to form soluble oligomers and insoluble amyloid fibrils. Moreover, methylglyoxal has a disrupting effect on the ability of α-synuclein to bind, cluster and fusion synaptic-like vesicles.

Jejunal gastrointestinal stromal tumor: a diagnostic challenge.

Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors of the gastrointestinal tract and a rare cause of gastrointestinal bleeding. These tumors usually affect people over 50 years of age and they exhibit a wide range of clinical manifestations, including asymptomatic patients, nonspecific symptoms, obstruction or bleeding, which may delay diagnosis. Early diagnosis and treatment are crucial because GISTs can be aggressive and metastasize. This case highlights the importance of considering GISTs in the differential diagnosis of obscure gastrointestinal bleeding.

Rational design of a hydrolysis-resistant mycobacterial phosphoglycolipid antigen presented by CD1c to T cells.

Whereas proteolytic cleavage is crucial for peptide presentation by classical major histocompatibility complex (MHC) proteins to T cells, glycolipids presented by CD1 molecules are typically presented in an unmodified form. However, the mycobacterial lipid antigen mannosyl-ß1-phosphomycoketide (MPM) may be processed through hydrolysis in antigen presenting cells, forming mannose and phosphomycoketide (PM). To further test the hypothesis that some lipid antigens are processed, and to generate antigens that lead to defined epitopes for future tuberculosis vaccines or diagnostic tests, we aimed to create hydrolysis-resistant MPM variants that retain their antigenicity. Here, we designed and tested three different, versatile synthetic strategies to chemically stabilize MPM analogs. Crystallographic studies of CD1c complexes with these three new MPM analogs showed anchoring of the lipid tail and phosphate group that is highly comparable to nature-identical MPM, with considerable conformational flexibility for the mannose head group. MPM-3, a difluoromethylene-modified version of MPM that is resistant to hydrolysis, showed altered recognition by cells, but not by CD1c proteins, supporting the cellular antigen processing hypothesis. Furthermore, the synthetic analogs elicited T cell responses that were cross-reactive with nature-identical MPM, fulfilling important requirements for future clinical use.

Development of Non-Hydrolysable Oligosaccharide Activity-Based Inactivators for Endoglycanases: A Case Study on α-1,6 Mannanases.

There is a vast genomic resource for enzymes active on carbohydrates. Lagging far behind, however, are functional chemical tools for the rapid characterization of carbohydrate-active enzymes. Activity-based probes (ABPs) offer one chemical solution to these issues with ABPs based upon cyclophellitol epoxide and aziridine covalent and irreversible inhibitors representing a potent and widespread approach. Such inhibitors for enzymes active on polysaccharides are potentially limited by the requirement for several glycosidic bonds, themselves substrates for the enzyme targets. Here, it is shown that non-hydrolysable trisaccharide can be synthesized and applied even to enzymes with challenging subsite requirements. It was found that incorporation of carbasugar moieties, which was accomplished by cuprate-assisted regioselective trans-diaxial epoxide opening of carba-mannal synthesised for this purpose, yields inactivators that act as powerful activity-based inhibitors for α-1,6 endo-mannanases. 3-D structures at 1.35-1.47 Šresolutions confirm the design rationale and binding to the enzymatic nucleophile. Carbasugar oligosaccharide cyclophellitols offer a powerful new approach for the design of robust endoglycosidase inhibitors, while the synthesis procedures presented here should allow adaptation towards activity-based endoglycosidase probes as well as configurational isosteres targeting other endoglycosidase families.

DCC/NTN1 complex mutations in patients with congenital hypogonadotropic hypogonadism impair GnRH neuron development.

Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disease characterized by absent puberty and infertility due to GnRH deficiency, and is often associated with anosmia [Kallmann syndrome (KS)]. The genetic etiology of CHH is heterogeneous, and more than 30 genes have been implicated in approximately 50% of patients with CHH. We hypothesized that genes encoding axon-guidance proteins containing fibronectin type-III (FN3) domains (similar to ANOS1, the first gene associated with KS), are mutated in CHH. We performed whole-exome sequencing in a cohort of 133 CHH probands to test this hypothesis, and identified rare sequence variants (RSVs) in genes encoding for the FN3-domain encoding protein deleted in colorectal cancer (DCC) and its ligand Netrin-1 (NTN1). In vitro studies of these RSVs revealed altered intracellular signaling associated with defects in cell morphology, and confirmed five heterozygous DCC mutations in 6 probands-5 of which presented as KS. Two KS probands carry heterozygous mutations in both DCC and NTN1 consistent with oligogenic inheritance. Further, we show that Netrin-1 promotes migration in immortalized GnRH neurons (GN11 cells). This study implicates DCC and NTN1 mutations in the pathophysiology of CHH consistent with the role of these two genes in the ontogeny of GnRH neurons in mice.

[PROFILES: typical portrait of the future Swiss doctors]. / PROFILES: portrait-type de nos futurs médecins !

In each professional practice, a greater or lesser part of the activity is devoted to teaching. Indeed, the transmission of the medical knowledge is an essential objective for the training of students and residents, but also an opportunity to adapt one's own practices to the current context, since fast changes are not necessarily easy to follow and assimilate. If the relationship with Medical school is rather straightforward in the university hospitals, it is not always the same for those who are more distant, but whose participation in teaching is desired, and clearly growing. In this way, it is therefore crucial that everyone is informed about recent changes to the undergraduated learning objectives (PROFILES) and the resulting needs for educational reforms for all Medical schools in Switzerland.

Dans chaque pratique professionnelle, une part plus ou moins grande de l'activité est dévolue à l'enseignement. En effet, la transmission de l'art médical représente un objectif essentiel pour la formation des étudiant·e·s et des jeunes collègues, mais aussi une opportunité pour adapter ses pratiques au contexte actuel, car les changements, rapides, ne sont pas forcément faciles à assimiler. Si, dans les hôpitaux universitaires, le contact avec les Facultés de médecine est plutôt aisé, il n'en va pas toujours de même pour ceux qui en sont plus distants, mais dont la participation à l'enseignement est souhaitée et croissante. En ce sens, il apparaît crucial que tou·te·s soient informé·e·s sur les modifications récentes des objectifs d'apprentissage prégradué (PROFILES) et sur les réformes qui en découlent pour les Facultés de médecine en Suisse.

A Coarse-Grained Molecular Dynamics Approach to the Study of the Intrinsically Disordered Protein α-Synuclein.

Intrinsically disordered proteins (IDPs) are not well described by a single 3D conformation but by an ensemble of them, which makes their structural characterization especially challenging, both experimentally and computationally. Most all-atom force fields are designed for folded proteins and give too compact IDP conformations. α-Synuclein is a well-known IDP because of its relation to Parkinson's disease (PD). To understand its role in this disease at the molecular level, an efficient methodology is needed for the generation of conformational ensembles that are consistent with its known properties (in particular, with its dimensions) and that is readily extensible to post-translationally modified forms of the protein, commonly found in PD patients. Herein, we have contributed to this goal by performing explicit-solvent, microsecond-long Replica Exchange with Solute Scaling (REST2) simulations of α-synuclein with the coarse-grained force field SIRAH, finding that a 30% increase in the default strength of protein-water interactions yields a much better reproduction of its radius of gyration. Other known properties of α-synuclein, such as chemical shifts, secondary structure content, and long-range contacts, are also reproduced. Furthermore, we have simulated a glycated form of α-synuclein to suggest the extensibility of the method to its post-translationally modified forms. The computationally efficient REST2 methodology in combination with coarse-grained representations will facilitate the simulations of this relevant IDP and its modified forms, enabling a better understanding of their roles in disease and potentially leading to efficient therapies.

Combined immune checkpoint inhibitor therapy with nivolumab and ipilimumab causing acute-onset type 1 diabetes mellitus following a single administration: two case reports.

BACKGROUND: The use of immune checkpoint inhibitor (ICI) therapy is becoming a standard of care for several cancers. Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) or its ligand (PD-L1) cause a broad spectrum of autoimmune adverse events. ICI-induced type 1 diabetes mellitus (T1DM) is extremely rare (< 1%) but potentially life-threatening. It appears to be more common with PD-1 blockade (or combination immunotherapy) than with anti-CTLA-4 therapy, often during the first three to six months of therapy. CASES PRESENTATION: We report an acute onset T1DM with severe inaugural diabetic ketoacidosis (DKA) and remarkably elevated Glutamic Acid Decarboxylase antibody (GADA) titres following a single administration of combined ICI therapy with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) in two adult patients with advanced metastatic melanoma. In these cases, the time to diabetes onset was remarkably short (two and five weeks), and one presented with fulminous T1DM in a previous long-standing type 2 diabetes mellitus. CONCLUSIONS: Oncological patients treated with combination therapy of anti-PD-1 and anti-CTLA-4 can develop a particular pattern of T1DM, with very rapid onset within a few weeks after starting ICI therapy, even in the presence of an existing type 2 diabetes. ICI-induced T1DM is a medical emergency in presence of severe inaugural DKA and requires a collaboration between specialists and primary care physicians, as well as patient education, for early diagnosis and supportive care.

Evaluating CHARGE syndrome in congenital hypogonadotropic hypogonadism patients harboring CHD7 variants.

PURPOSE: Congenital hypogonadotropic hypogonadism (CHH), a rare genetic disease caused by gonadotropin-releasing hormone deficiency, can also be part of complex syndromes (e.g., CHARGE syndrome). CHD7 mutations were reported in 60% of patients with CHARGE syndrome, and in 6% of CHH patients. However, the definition of CHD7 mutations was variable, and the associated CHARGE signs in CHH were not systematically examined. METHODS: Rare sequencing variants (RSVs) in CHD7 were identified through exome sequencing in 116 CHH probands, and were interpreted according to American College of Medical Genetics and Genomics guidelines. Detailed phenotyping was performed in CHH probands who were positive for CHD7 RSVs, and genotype-phenotype correlations were evaluated. RESULTS: Of the CHH probands, 16% (18/116) were found to harbor heterozygous CHD7 RSVs, and detailed phenotyping was performed in 17 of them. Of CHH patients with pathogenic or likely pathogenic CHD7 variants, 80% (4/5) were found to exhibit multiple CHARGE features, and 3 of these patients were reclassified as having CHARGE syndrome. In contrast, only 8% (1/12) of CHH patients with nonpathogenic CHD7 variants exhibited multiple CHARGE features (P = 0.01). CONCLUSION: Pathogenic or likely pathogenic CHD7 variants rarely cause isolated CHH. Therefore a detailed clinical investigation is indicated to clarify the diagnosis (CHH versus CHARGE) and to optimize clinical management.

Papillary thyroid carcinoma with nodular fasciitis-like stroma and ß-catenin mutations should be renamed papillary thyroid carcinoma with desmoid-type fibromatosis.

Various histological variants of papillary thyroid carcinoma have been reported, some with clinical implications, some with peculiar, sometimes misleading morphologies. One of these rare and poorly characterized variants is papillary thyroid carcinoma with nodular fasciitis-like stroma, of which fewer than 30 cases have been documented, mostly as isolated reports. It is a dual tumor comprising a malignant epithelial proliferation that harbors typical features of conventional papillary thyroid carcinoma, admixed with a prominent mesenchymal proliferation resembling nodular fasciitis or fibromatosis. Thus, the terms papillary thyroid carcinoma with nodular fasciitis-like stroma and papillary thyroid carcinoma with fibromatosis-like stroma are used interchangeably; however, the former term suggests a self-limited and regressing disease, whereas the latter one suggests a recurrent and potentially aggressive one. Better genetic and ultrastructural characterization could lead to more appropriate terminology and management. We performed detailed clinicopathological and molecular analyses of two cases of PTC with prominent mesenchymal proliferation that developed in the thyroid gland of two male patients aged 34 and 48. In both cases, the epithelial component harbored a heterozygous somatic activating BRAF mutation (p.V600E). Also, in both cases, the mesenchymal component showed typical aberrant nuclear and cytoplasmic immunoreactivity for ß-catenin and harbored a heterozygous somatic activating mutation in the corresponding CTNNB1 gene (p.S45P). This mutation has never been reported in thyroid stroma; in other tissues, it is typical of desmoid-type fibromatosis rather than nodular fasciitis-like stroma. We therefore propose that in cases of papillary thyroid carcinoma with a prominent mesenchymal component, mutations in CTNNB1 should be sought; when they are present, the term 'papillary thyroid carcinoma with desmoid-type fibromatosis' should be used. As the mesenchymal component of these tumors is not expected to concentrate radioactive iodine, special considerations apply to clinical evaluation and follow-up, which should be brought to the attention of the treating specialist.

Surgical treatment of acromegaly according to the 2010 remission criteria: systematic review and meta-analysis.

BACKGROUND: In 2010, the Acromegaly Consensus Group revised the criteria for cure of acromegaly and thus rates of surgical remission need to be revised in light of these new thresholds. Two subgroups consisted of patients with discordant GH and IGF-1 levels and patients in remission according to the 2000 criteria, but not to the 2010 criteria, have been reported after adenomectomy and for these subgroups the precise incidence and management has not been established. The objective of the study was to update rates of surgical remission and complications and to evaluate the incidence, management, and long-term outcome of the two previously described subgroups of patients. METHODS: Systematic review and meta-analysis of surgical series that defined remission according to the 2010 biochemical criteria. RESULTS: We included 13 studies (1105 patients). The pooled rate of overall surgical remission was 54.8 % (95 % CI 44.4-65.2 %), and 72.2 % with previous criteria. Remission was achieved in 77.9 % (95 % CI 68.1-87.6 %) of microadenomas; 52.7 % (95 % CI 41-64.4 %) of macroadenomas; 29 % (95 % CI 20.1-37.8 %) of invasive and 68.8 % (95 % CI 60-77.6 %) of non-invasive adenomas. Complication rates were 1.2 % (95 % CI 0.6-1.9 %) for CSF leak, 1.3 % (95 % CI 0.6-2.1 %) for permanent diabetes insipidus, 8.7 % (95 % CI 4.8-12.5 %) for new anterior pituitary dysfunction and 0.6 % (95 % CI 0.1-1.1 %) for severe intraoperative hemorrhage. We identified an intermediate group of patients, defined as: (1) Remission according to one, but not the other biochemical criteria (GH or IGF-1) or 2010 criteria (14.3 % and 47.1 % cases), (2) Remission according to 2000, but not 2010 criteria (13.2-58.8 % cases). Two studies reported a remission rate of 56.5 % and 100 %, in the two subgroups respectively, in a long-term outcome without adjuvant therapy. CONCLUSIONS: Overall remission with transsphenoidal surgery is achieved in ∼55 % of patients. For the intermediate group of patients, future prospective studies with long-term follow-up are required to determine the long-term biochemical remission rates and clinical implications.

Mechanistic insights into protonation state as a critical factor in hFPPS enzyme inhibition.

Zoledronate and risedronate are the most powerful available nitrogen-containing bisphosphonates used in the treatment of bone-resorption disorders. Knowledge about inhibition mechanisms of these molecules is based on available crystallographic structures of human farnesyl pyrophosphate synthase (hFPPS). However, there is a lack of information explaining the inhibition potency of these two molecules compared to the natural substrate, dimethylallyl pyrophosphate. We carried out a molecular dynamics study that shown: (1) that NBPs potency is related to higher electrostatic interactions with the metallic cluster of the active site than to the natural substrate, and (2) the protonation of the R2 side chain is a critical factor to stabilize the NBPs into a closely irreversible ternary complex with the hFPPS.

Mechanistic insights in glycation-induced protein aggregation.

Protein glycation causes loss-of-function through a process that has been associated with several diabetic-related diseases. Additionally, glycation has been hypothesized as a promoter of protein aggregation, which could explain the observed link between hyperglycaemia and the development of several aggregating diseases. Despite its relevance in a range of diseases, the mechanism through which glycation induces aggregation remains unknown. Here we describe the molecular basis of how glycation is linked to aggregation by applying a variety of complementary techniques to study the nonenzymatic glycation of hen lysozyme with ribose (ribosylation) as the reducing carbohydrate. Ribosylation involves a chemical multistep conversion that induces chemical modifications on lysine side chains without altering the protein structure, but changing the protein charge and enlarging its hydrophobic surface. These features trigger lysozyme native-like aggregation by forming small oligomers that evolve into bigger insoluble particles. Moreover, lysozyme incubated with ribose reduces the viability of SH-SY5Y neuroblastoma cells. Our new insights contribute toward a better understanding of the link between glycation and aggregation.

Myocardial repolarization dispersion and late gadolinium enhancement in patients with hypertrophic cardiomyopathy.

BACKGROUND: Growing evidence suggests that late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) is an additive marker of disease severity, and possibly of arrhythmic risk, in hypertrophic cardiomyopathy (HCM). We investigated the possible relationship between LGE and markers of myocardial repolarization dispersion in HCM. METHODS AND RESULTS: Eighty-five HCM outpatients underwent CMR and short-period electrocardiogram analysis to calculate the temporal myocardial repolarization dispersion through the QT variance normalized for QT mean (QTVN) and the QT variability index (QTVI). The QT dispersion in the spatial domain was also obtained. Patients with LGE (62%) had higher left atrial volume, maximum wall thickness, and left ventricular mass (P<0.0001), as well as a greater prevalence of non-sustained ventricular tachycardia (P<0.0001) and hypotensive blood pressure response (P=0.044). Both QTVN and QTVI were higher in the group with LGE (P<0.0001). At multivariate analysis, using QTVI as the dependent variable, %LGE (P<0.0001), age (P<0.0001), left ventricular outflow obstruction (P=0.038), and sudden cardiac death risk factor burden (P=0.020) reached statistical significance. Otherwise, only %LGE (P=0.005) and left ventricular mass index (P=0.015) remained associated with QTVN. CONCLUSIONS: Temporal myocardial repolarization dispersion correlates with LGE extent. Whether these variables could be useful in HCM clinical management warrants confirmation by larger prospective studies.

An overview on glycation: molecular mechanisms, impact on proteins, pathogenesis, and inhibition.

The formation of a heterogeneous set of advanced glycation end products (AGEs) is the final outcome of a non-enzymatic process that occurs in vivo on long-life biomolecules. This process, known as glycation, starts with the reaction between reducing sugars, or their autoxidation products, with the amino groups of proteins, DNA, or lipids, thus gaining relevance under hyperglycemic conditions. Once AGEs are formed, they might affect the biological function of the biomacromolecule and, therefore, induce the development of pathophysiological events. In fact, the accumulation of AGEs has been pointed as a triggering factor of obesity, diabetes-related diseases, coronary artery disease, neurological disorders, or chronic renal failure, among others. Given the deleterious consequences of glycation, evolution has designed endogenous mechanisms to undo glycation or to prevent it. In addition, many exogenous molecules have also emerged as powerful glycation inhibitors. This review aims to provide an overview on what glycation is. It starts by explaining the similarities and differences between glycation and glycosylation. Then, it describes in detail the molecular mechanism underlying glycation reactions, and the bio-molecular targets with higher propensity to be glycated. Next, it discusses the precise effects of glycation on protein structure, function, and aggregation, and how computational chemistry has provided insights on these aspects. Finally, it reports the most prevalent diseases induced by glycation, and the endogenous mechanisms and the current therapeutic interventions against it.

Understanding the effect of the membrane-mimetic micelles on the interplay between α-synuclein and Cu(II)/Cu(I) cations.

α-Synuclein (αS) is a presynaptic protein whose aggregates are considered as a hallmark of Parkinson's disease (PD). Although its physiological function is still under debate, it is widely accepted that its functions are always mediated by its interaction with membranes. The association of αS with phospholipid membranes occurs concomitant to its folding from its monomeric, unfolded state towards an antiparallel amphipathic α-helix. Besides this, copper ions can also bind αS and modify its aggregation propensity. The effect of Cu(II) and Cu(I) on the lipid-αS affinity and on the structure of the membrane-bound αS have not yet been studied. This knowledge is relevant to understand the molecular pathogenesis of PD. Therefore, we have here studied the affinities between Cu(II) and Cu(I) and the micelle-bound αS, as well as the effect of these cations on the structure of micelle-bound αS. Cu(II) or Cu(I) did not affect the α-helical structure of the micelle-bound αS. However, while Cu(I) binds at the same sites of αS in the presence or in the absence of micelles, the micelle-bound αS displays different Cu(II) binding sites than unbound αS. In any case, sodium docecyl sulphate -micelles reduce the stability of the αS complexes with both Cu(II) and Cu(I). Finally, we have observed that the micelle-bound αS is still able to prevent the Cu(II)-catalysed oxidation of neuronal metabolites (e.g. ascorbic acid) and the formation of reactive oxygen species, thus this binding does not impair its biological function as part of the antioxidant machinery.

Stereotypes and Prejudices in Nursing Prison Activities: A Reflection.

BACKGROUND: In the prison environment, the nursing profession has particularly complex peculiarities and aspects, so much so that prison nurses require advanced specialist skills and specific education. Can nurses' stereotypes and prejudices in prison settings affect nursing care? What are nurses' perceptions of the prison environment and people in detention? This study aims, on one hand, to outline the figure of the nurse in the prison environment and current regulations and, on the other hand, to explore whether and how stereotypes and prejudices may affect the way care is provided. METHODS: Starting with an analysis of the literature, the authors administered a questionnaire to a group of nurses who shared data and reflections. RESULTS: This study sheds a new light on nursing in the prison environment, exploring how nurses' stereotypes and prejudices may affect the care of patients. CONCLUSIONS: It would be desirable to develop research in this field to enable a more conscious approach to a world that is still considered distant and dangerous, and to overcome the misperceptions and prejudices that may negatively affect the way of caring.

Effects of age and heart failure on human cardiac stem cell function.

Currently, it is unknown whether defects in stem cell growth and differentiation contribute to myocardial aging and chronic heart failure (CHF), and whether a compartment of functional human cardiac stem cells (hCSCs) persists in the decompensated heart. To determine whether aging and CHF are critical determinants of the loss in growth reserve of the heart, the properties of hCSCs were evaluated in 18 control and 23 explanted hearts. Age and CHF showed a progressive decrease in functionally competent hCSCs. Chronological age was a major predictor of five biomarkers of hCSC senescence: telomeric shortening, attenuated telomerase activity, telomere dysfunction-induced foci, and p21(Cip1) and p16(INK4a) expression. CHF had similar consequences for hCSCs, suggesting that defects in the balance between cardiomyocyte mass and the pool of nonsenescent hCSCs may condition the evolution of the decompensated myopathy. A correlation was found previously between telomere length in circulating bone marrow cells and cardiovascular diseases, but that analysis was restricted to average telomere length in a cell population, neglecting the fact that telomere attrition does not occur uniformly in all cells. The present study provides the first demonstration that dysfunctional telomeres in hCSCs are biomarkers of aging and heart failure. The biomarkers of cellular senescence identified here can be used to define the birth date of hCSCs and to sort young cells with potential therapeutic efficacy.

Female Homicide in Italy in 2021: Different Criminological and Psychopathological Perspectives on the Phenomenon.

The intentional homicide of female victims, which is most commonly perpetrated by intimate partners or family members, has been recognized in recent years as a matter of grave public concern that needs to be addressed from the cultural and judicial perspectives. To allow an in-depth criminological and psychopathological evaluation of female homicide in Italy in 2021 to be conducted, the authors performed a newspaper report analysis of the phenomenon. All female homicides that occurred in Italy in 2021 (n = 119) were included in the study. The analysis confirmed the low rate of female homicides in Italy when compared with other countries and also showed the phenomenon to be more complex than usually described. The highest rate of homicides was observed in elderly females when compared with other age groups, implying different criminological considerations and suggesting that gender-based violence may only explain some of the identified cases. The high incidence of suicide or attempted suicide among offenders, together with the high incidence of reported mental disorders in that population, suggests that a psychopathological perspective on the phenomenon of female homicide could help with the development and implementation of preventive strategies that focus on managing mental health at a territorial level and intervening in difficult domestic situations.