Until the last quarter of the 20th century, sex was not recognized as a variable in health research, nor was it believed to be a factor that could affect health and illness. Researchers preferred studying male models for a variety of reasons, such as simplicity, lower costs, hormone confounding effects, and fear of liability from perinatal exposure in case of pregnancy. Equitable representation is imperative for determining the safety, effectiveness, and tolerance of therapeutic agents for all consumers. Decades of female models’ underrepresentation in preclinical studies has resulted in inequality in the understanding, diagnosis, and treatment of disease between the sexes. Sex bias has been highlighted as one of the contributing factors to the poor translation and replicability of preclinical research. There have been multiple calls for action, and the inclusion of sex as a biological variable is increasingly supported. However, although there has been substantial progress in the efforts to include more female models in preclinical studies, disparities today remain. In the present review, we consider the current standard practice of the preclinical research setting, why the sex bias exists, why there is the need to include female models, and what risks may arise from continuing this exclusion from experimental design.

Background: COVID-19 is characterized by an uncontrolled inflammatory response with high pro-inflammatory cytokine production through the activation of intracellular pathways, such as mitogen-activated protein kinase (MAPK). Viruses are able to exploit the MAPK pathway to their advantage; this pathway relevance to severe COVID-19 is poorly described. The aim of this study was to quantify biomarkers involved in the MAPK pathway and to clarify its possible role in affecting some COVID-19-related clinical features. Methods: H-RAS, C-RAF, MAPK1, MAPK2, and ERK were quantified through ELISA, and genetic polymorphisms were evaluated through real-time PCR. Results: We prospectively recruited 201 individuals (158 positive and 43 negative for SARS-CoV-2): 35 were male, and their median age was 65 years. MAPK-related biomarker levels were increased in SARS-CoV-2-positive participants (n = 89) compared to negative ones (n = 29). Dyspnea was reported by 48%; this symptom was associated with PBMC C-RAF levels in positive participants (p = 0.022) and type of ventilation (p = 0.031). The highest degree of ventilation was used by 8% for invasive ventilation and 41% for continuous positive airway pressure (CPAP). Conclusions: This is the first study that showed a possible contribution of MAPK-related biomarkers in affecting COVID-19 clinical features, and this may be relevant for identifying COVID-19 positive participants at risk of serious complications.

Background: The use of herbs to treat illnesses was common in all historical eras. Our aim was to describe the phytotherapeutic substances that cancer patients use most commonly, and to determine whether their use can increase side effects. Methods: This was a retrospective and descriptive study conducted among older adults actively undergoing chemotherapy, admitted at the Oncology DH Unit (COES) of the Molinette Hospital AOU Città della Salute e della Scienza in Turin (Italy). Data collection was conducted through the distribution of self-compiled and closed-ended questionnaires during chemotherapy treatment. Results: A total of 281 patients were enrolled. Evaluating retching and sage consumption was statistically significant in multivariate analysis. The only risk factor for dysgeusia was chamomile consumption. Ginger, pomegranate, and vinegar use were retained as mucositis predictors. Conclusions: Phytotherapeutic use needs more attention in order to decrease the risks of side effects, toxicity, and ineffective treatment. The conscious administration of these substances should be promoted for safe use and to provide the reported benefits.

(1) Background: In clinical settings, data regarding sex are rarely investigated. In women, factors such as body size and composition, hormonal variations, metabolism, and access to care systems and therapy could strongly influence the pharmacological management and the outcome of the therapy. To underline this sex-related difference, we retrospectively collected data from adrenocortical carcinoma patients treated with mitotane, and then evaluated sex-related pharmacokinetics parameters. (2) Methods: A fully validated chromatographic method was used to quantify mitotane concentration in plasma collected from adult patients, also considering the active metabolite ortho,para,dichlorodiphenylethene (o,p′-DDE). Statistical analyses were used to evaluate the sex influence on drugs pharmacokinetics. (3) Results: We found that sex resulted as predictive factor of plasma mitotane and o,p′-DDE concentrations and significantly influenced the attainment of the therapeutic target of mitotane, implying that female sex could be a risk factor of treatment failure. (4) Conclusions: These results suggest that mitotane therapy should be modulated according to patient sex. Furthermore, the proposed approach could contribute to facilitating and disseminating sex-specific pharmacology.

Orotic acid (OA) is an intermediate metabolite of pyrimidine nucleotide biosynthesis and represents a minor diet constituent. The measurement of urinary orotic acid is useful in confirming the diagnosis of hereditary metabolic diseases. Moreover, it could be of interest to know how the physiological concentration of this metabolite changes in relation to different conditions of clinical normality. The purpose of this study was to determine the orotic acid concentration in the urine of healthy patients, to observe normal oroticuria and to evaluate if the expression of pyrimidine intermediate biosynthesis differs between healthy males and females. The orotic acid concentration in urine was performed via the ICH M10-validated analytical method. Unexpectedly, females showed a greater oroticuria than males in pediatric age (0–10); conversely, we did not find significant differences until 70 years of age. The LC-MS/MS method was suitable for use in the differential diagnosis of hereditary metabolic disease and metabolic monitoring of anticancer drug-induced toxicity. The analytical protocol was found to be rapid and ideal, and was used in the routine analysis of a clinical chemistry laboratory. The biochemical aspects related to the expression of pyrimidine biosynthesis should be further investigated in light of the obtained results.

Tyrosine kinase inhibitors work by blocking the tyrosine kinases responsible for the dysregulation of intracellular signalling pathways in tumour cells. This study looked at the impact of age and sex on the levels of imatinib, dasatinib, nilotinib, and ponatinib in plasma and cerebrospinal fluid samples of patients with chronic myeloid leukaemia. Imatinib and dasatinib were used to treat the majority of the enrolled patients, and most of them were paediatrics. A total of 82.4% of the patients were men; however, sex-related differences in the drugs’ pharmacokinetics were not found. Age and imatinib plasma concentration were found to be inversely correlated. The dasatinib concentrations in plasma were found to be substantially lower than those found in cerebrospinal fluid, particularly in paediatrics. Analysing the obtained data, we can state that therapeutic drug monitoring is a useful method for adjusting a patient’s treatment schedule that depends on drug concentrations in biological fluids. The use of therapeutic drug monitoring in conjunction with tyrosine kinase inhibitors for the treatment of chronic myeloid leukaemia is supported by a number of sources of evidence. As a result, as the research develops, the tyrosine kinase inhibitor therapeutic drug monitoring classification needs to be refined in terms of factors like sex and age.