PURPOSE OF REVIEW: Men face distinctive health-related challenges as a result of biological, behavioral, and sociocultural factors. In addition, the modern healthcare system does not offer men equal opportunities and options to ensure sex-specific access and delivery to health services. Men's health concerns are, indeed, often not addressed or even forgotten. In this review, we wanted to assess the impact of biology and sociocultural effects on sex-specific life-expectancy. RECENT FINDINGS: Globally, men have a shorter life expectancy than women. With a 5.8 years gender gap in the USA and 5.4 in the EU-27 (both in 2022). Cardiovascular disease, cancer, and accidents continue to represent the primary causes of mortality for both genders with all having disproportional preponderance in men. In recent years, there has been a notable decline in age-adjusted mortality rates related to cancer, while there has been an increase in deaths from accidental and intentional self-harm. Moreover, in the United States, men are more likely than women to develop and die from nonsex-specific cancers. As a result, men's poor health affects productivity, absenteeism, and employment. SUMMARY: The status of men in healthcare is complex. It is rooted in history, culture, and institutions. To address disparities, we need a comprehensive approach that includes policy reforms, sociocultural changes, and a fair and equitable public discourse. Grassroots and top-down strategies are needed to ensure a value-based societal healthcare system acknowledging the unique health needs of men.
- MeSH
- Healthcare Disparities statistics & numerical data MeSH
- Health Status Disparities MeSH
- Health Services Accessibility statistics & numerical data MeSH
- Humans MeSH
- Life Expectancy * MeSH
- Delivery of Health Care statistics & numerical data MeSH
- Health Equity MeSH
- Sex Factors MeSH
- Men's Health * MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Geographicals
- United States MeSH
The tumor microenvironment (TME) is a complex, highly structured, and dynamic ecosystem that plays a pivotal role in the progression of both primary and metastatic tumors. Precise assessment of the dynamic spatiotemporal features of the TME is crucial for understanding cancer evolution and designing effective therapeutic strategies. Cancer is increasingly recognized as a systemic disease, influenced not only by the TME, but also by a multitude of systemic factors, including whole-body metabolism, gut microbiome, endocrine signaling, and circadian rhythm. In this review, we summarize the intrinsic, extrinsic, and systemic factors contributing to the formation of 'cold' tumors within the framework of the cancer-immunity cycle. Correspondingly, we discuss potential strategies for converting 'cold' tumors into 'hot' ones to enhance therapeutic efficacy.
- MeSH
- Circadian Rhythm MeSH
- Humans MeSH
- Tumor Microenvironment * immunology MeSH
- Neoplasms * pathology therapy MeSH
- Gastrointestinal Microbiome MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: Trichophyton mentagrophytes ITS genotype VII (TMVII) has recently been identified in France as the causative agent of dermatophyte infections transmitted during sexual activity among men who have sex with men (MSM). OBJECTIVES: Our objective was to provide new insights into the epidemiology, clinical presentation and treatment of TMVII infections based on cases diagnosed from October 2022 to September 2023 in three medical mycology laboratories in Paris. Additionally, we aimed to perform molecular characterization of TMVII strains collected in Paris, as well as in Switzerland. METHODS: We identified all isolates from skin and hair belonging to the T. mentagrophytes complex by sequencing the ITS region. For isolates corresponding to TMVII, clinical data were retrieved from medical records. For all available TMVII strains that we isolated since January 2021, we sequenced tef1α and tubb and determined the MAT locus idiomorph. RESULTS: We identified 32 cases of TMVII Infections. All cases occurred in men, 30 of whom reported having sex with men. Fifteen cases were sporadic cases including four among sex workers. The other 17 cases belonged to a single cluster involving a tantric masseur who infected 15 clients and his roommate. The median time from massage to lesion onset was 16 [2-52] days. Except for one patient, all other patients received systemic antifungal treatment with terbinafine. We observed five patients whose cultures remained positive even after 3-4 weeks of treatment and five patients experienced a relapse of the infection after discontinuing antifungal treatment. All French isolates exhibited identical tef1α and tubb sequences, as well as the same MAT idiomorph locus. They displayed variations in the tef1α sequence compared to isolates from Switzerland and the Czech Republic. CONCLUSIONS: We confirm the active circulation of TMVII among MSM in France, which is associated with challenges in diagnosis, treatment and prevention.
- MeSH
- Antifungal Agents * therapeutic use MeSH
- Arthrodermataceae MeSH
- Adult MeSH
- Genotype * MeSH
- Homosexuality, Male MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Terbinafine therapeutic use MeSH
- Tinea * microbiology epidemiology drug therapy MeSH
- Trichophyton * genetics isolation & purification MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- France MeSH
BACKGROUND: Although neuromelanin-sensitive magnetic resonance imaging (NM-MRI) has been used to evaluate early neurodegeneration in Parkinson's disease, studies concentrating on the locus coeruleus (LC) in pre-dementia stages of dementia with Lewy bodies (DLB) are lacking. OBJECTIVES: The aims were to evaluate NM-MRI signal changes in the LC in patients with mild cognitive impairment with Lewy bodies (MCI-LB) compared to healthy controls (HC) and to identify the cognitive correlates of the changes. We also aimed to test the hypothesis of a caudal-rostral α-synuclein pathology spread using NM-MRI of the different LC subparts. METHODS: A total of 38 MCI-LB patients and 59 HCs underwent clinical and cognitive testing and NM-MRI of the LC. We calculated the contrast ratio of NM-MRI signal (LC-CR) in the whole LC as well as in its caudal, middle, and rostral MRI slices, and we compared the LC-CR values between the MCI-LB and HC groups. Linear regression analyses were performed to assess the relationship between the LC-CR and cognitive outcomes. RESULTS: The MCI-LB group exhibited a significant reduction in the right LC-CR compared to HCs (P = 0.021). The right LC-CR decrease was associated with impaired visuospatial memory in the MCI-LB group. Only the caudal part of the LC exhibited significant LC-CR decreases in MCI-LB patients compared to HCs on both sides (P < 0.0001). CONCLUSIONS: This is the first study that focuses on LC-CRs in MCI-LB patients and analyzes the LC subparts, offering new insights into the LC integrity alterations in the initial stages of DLB and their clinical correlates. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
- MeSH
- alpha-Synuclein metabolism MeSH
- Lewy Body Disease * diagnostic imaging pathology MeSH
- Cognitive Dysfunction * diagnostic imaging pathology physiopathology etiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Locus Coeruleus * diagnostic imaging pathology MeSH
- Magnetic Resonance Imaging * MeSH
- Neuropsychological Tests MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Renal cell carcinoma (RCC) is a disease typified by anomalies in cell metabolism. The function of mitochondria, including subunits of mitochondrial respiratory complex II (CII), in particular SDHB, are often affected. Here we investigated the state and function of CII in RCC patients. METHODS: We evaluated tumour tissue as well as the adjacent healthy kidney tissue of 78 patients with RCC of different histotypes, focusing on their mitochondrial function. As clear cell RCC (ccRCC) is by far the most frequent histotype of RCC, we focused on these patients, which were grouped based on the pathological WHO/ISUP grading system to low- and high-grade patients, indicative of prognosis. We also evaluated mitochondrial function in organoids derived from tumour tissue of 7 patients. RESULTS: ccRCC tumours were characterized by mutated von Hippel-Lindau gene and high expression of carbonic anhydrase IX. We found low levels of mitochondrial DNA, protein and function, together with CII function in ccRCC tumour tissue, but not in other RCC types and non-tumour tissues. Mitochondrial content increased in high-grade tumours, while the function of CII remained low. Tumour organoids from ccRCC patients recapitulated molecular characteristics of RCC tissue. CONCLUSIONS: Our findings suggest that the state of CII, epitomized by its assembly and SDHB levels, deteriorates with the progressive severity of ccRCC. These observations hold the potential for stratification of patients with worse prognosis and may guide the exploration of targeted therapeutic interventions.
- MeSH
- Antigens, Neoplasm MeSH
- Adult MeSH
- Carbonic Anhydrase IX metabolism genetics MeSH
- Carcinoma, Renal Cell * pathology metabolism genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- DNA, Mitochondrial genetics metabolism MeSH
- Mitochondria * metabolism pathology genetics MeSH
- Mutation MeSH
- Von Hippel-Lindau Tumor Suppressor Protein genetics metabolism MeSH
- Kidney Neoplasms * pathology metabolism genetics MeSH
- Electron Transport Complex II * metabolism genetics MeSH
- Aged MeSH
- Succinate Dehydrogenase genetics metabolism MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Developing bioinspired materials to convert sunlight into electricity efficiently is paramount for sustainable energy production. Fluorescent proteins are promising candidates as photoactive materials due to their high fluorescence quantum yield and absorption extinction coefficients in aqueous media. However, developing artificial bioinspired photosynthetic systems requires a detailed understanding of molecular interactions and energy transfer mechanisms in the required operating conditions. Here, the supramolecular self-assembly and photophysical properties of fluorescent proteins complexed with organic dyes are investigated in aqueous media. Supercharged mGreenLantern protein, mutated to have a charge of +22, is complexed together with anionic zinc phthalocyanines having 4 or 16 carboxylate groups. The structural characterization reveals a strong electrostatic interaction between the moieties, accompanied by partial conformational distortion of the protein structure, yet without compromising the mGreenLantern chromophore integrity as suggested by the lack of emission features related to the neutral form of the chromophore. The self-assembled biohybrid shows a total quenching of protein fluorescence, in favor of an energy transfer process from the protein to the phthalocyanine, as demonstrated by fluorescence lifetime and ultrafast transient absorption measurements. These results provide insight into the rich photophysics of fluorescent protein-dye complexes, anticipating their applicability as water-based photoactive materials.
- MeSH
- Anions chemistry MeSH
- Fluorescent Dyes chemistry MeSH
- Spectrometry, Fluorescence MeSH
- Indoles * chemistry metabolism MeSH
- Isoindoles MeSH
- Luminescent Proteins * chemistry metabolism MeSH
- Organometallic Compounds * chemistry metabolism MeSH
- Energy Transfer MeSH
- Zinc Compounds MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. It has been suggested that neurodevelopmental factors contribute to the etiology of BD, but a specific neurodevelopmental phenotype (NDP) of the disorder has not been identified. Our objective was to define and characterize an NDP in BD and validate its associations with clinical outcomes, polygenic risk scores, and treatment responses. METHODS: We analyzed the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort of 4468 patients with BD, a validation cohort of 101 patients with BD, and 2 independent replication datasets of 274 and 89 patients with BD. Using factor analyses, we identified a set of criteria for defining NDP. Next, we developed a scoring system for NDP load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and gender with bootstrap replications. RESULTS: Our study established an NDP in BD consisting of 9 clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention-deficit/hyperactivity disorder, early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, and specific learning disorders. Patients with higher NDP load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between NDP load and polygenic risk score for attention-deficit/hyperactivity disorder, suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and attention-deficit/hyperactivity disorder. CONCLUSIONS: The proposed NDP constitutes a promising clinical tool for patient stratification in BD.
- MeSH
- Bipolar Disorder * genetics MeSH
- Adult MeSH
- Phenotype * MeSH
- Attention Deficit Disorder with Hyperactivity genetics MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Multifactorial Inheritance genetics MeSH
- Neurodevelopmental Disorders genetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The formation of memories is a complex, multi-scale phenomenon, especially when it involves integration of information from various brain systems. We have investigated the differences between a novel and consolidated association of spatial cues and amphetamine administration, using an in situ hybridisation method to track the short-term dynamics during the recall testing. We have found that remote recall group involves smaller, but more consolidated groups of neurons, which is consistent with their specialisation. By employing machine learning analysis, we have shown this pattern is especially pronounced in the VTA; furthermore, we also uncovered significant activity patterns in retrosplenial and prefrontal cortices, as well as in the DG and CA3 subfields of the hippocampus. The behavioural propensity towards the associated localisation appears to be driven by the nucleus accumbens, however, further modulated by a trio of the amygdala, VTA and hippocampus, as the trained association is confronted with test experience. Moreover, chemogenetic analysis revealed central amygdala as critical for linking appetitive emotional states with spatial contexts. These results show that memory mechanisms must be modelled considering individual differences in motivation, as well as covering dynamics of the process.
- MeSH
- Amphetamine pharmacology MeSH
- Amygdala physiology MeSH
- Hippocampus * physiology MeSH
- Memory Consolidation * physiology MeSH
- Rats MeSH
- Brain physiology MeSH
- Neurons physiology metabolism MeSH
- Nucleus Accumbens * physiology MeSH
- Reward * MeSH
- Memory physiology MeSH
- Cues MeSH
- Prefrontal Cortex physiology MeSH
- Mental Recall * physiology MeSH
- Machine Learning MeSH
- Ventral Tegmental Area * physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Class A G protein-coupled receptors (GPCRs) continue to garner interest for their essential roles in cell signalling and their importance as drug targets. Although numerous drugs in the clinic target these receptors, over 60% GPCRs remain unexploited. Moreover, the adverse effects triggered by the available unbiased GPCR modulators, limit their use and therapeutic value. In this context, the elucidation of biased signalling has opened up new pharmacological avenues holding promise for safer therapeutics. Functionally selective ligands favour receptor conformations facilitating the recruitment of specific effectors and the modulation of the associated pathways. This review surveys the current drug discovery landscape of GPCR-biased modulators with a focus on recent advances. Understanding the biological effects of this preferential coupling is at different stages depending on the Class A GPCR family. Therefore, with a focus on individual GPCR families, we present a compilation of the functionally selective modulators reported over the past few years. In doing so, we dissect their therapeutic relevance, molecular determinants and potential clinical applications. LINKED ARTICLES: This article is part of a themed issue Complexity of GPCR Modulation and Signaling (ERNST). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.14/issuetoc.
- MeSH
- Humans MeSH
- Ligands MeSH
- Drug Discovery * MeSH
- Receptors, G-Protein-Coupled * metabolism agonists MeSH
- Signal Transduction drug effects MeSH
- Drug Development MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
As one of the most significant global health emergencies, COVID-19 has placed extraordinary demands on healthcare systems worldwide. In India, its widespread transmission has been influenced by the country's diverse climatic conditions, geo-ecological complexity, and dense population. This, vector-borne diseases (VBDs)-including malaria, dengue, kala azar, Japanese encephalitis, and chikungunya-have long posed additional challenges to public health infrastructure. Intriguingly, prior exposure to these diseases may shape immune responses, potentially conferring cross-protection against multiple pathogens. A cross-sectional study aimed at assessing the role of VBDs in COVID-19 incidence and mortality revealed a multifaceted relationship. Prior dengue exposure was linked to an increased risk of SARS-CoV-2 infection and mortality, whereas kala azar, Japanese encephalitis, and chikungunya appeared to have protective influences. Notably, malaria had statistically significant protective effects against both SARS-CoV-2 infection and mortality (p < 0.04). These findings suggest that immune mechanisms-such as cross-reactive antibodies or immune regulation-may alter susceptibility to COVID-19. Given the substantial protective effect of malaria, further investigation is warranted to clarify the underlying biological processes involved. Insights from this study could guide public health strategies, optimize resource allocation, and refine intervention measures in regions where both COVID-19 and VBDs remain major concerns.
- MeSH
- COVID-19 * mortality epidemiology transmission MeSH
- Dengue epidemiology MeSH
- Chikungunya Fever epidemiology MeSH
- Incidence MeSH
- Humans MeSH
- Malaria epidemiology MeSH
- Vector Borne Diseases * epidemiology mortality MeSH
- Cross-Sectional Studies MeSH
- SARS-CoV-2 MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- India MeSH
