Angiosperm flowers reached their highest morphological diversity early in their evolutionary history.

Flowers are the complex and highly diverse reproductive structures of angiosperms. Because of their role in sexual reproduction, the evolution of flowers is tightly linked to angiosperm speciation and diversification. Accordingly, the quantification of floral morphological diversity (disparity) among angiosperm subgroups and through time may give important insights into the evolutionary history of angiosperms as a whole. Based on a comprehensive dataset focusing on 30 characters describing floral structure across angiosperms, we used 1201 extant and 121 fossil flowers to measure floral disparity and explore patterns of floral evolution through time and across lineages. We found that angiosperms reached their highest floral disparity in the Early Cretaceous. However, decreasing disparity toward the present likely has not precluded the innovation of other complex traits at other morphological levels, which likely played a key role in the outstanding angiosperm species richness. Angiosperms occupy specific regions of the theoretical morphospace, indicating that only a portion of the possible floral trait combinations is observed in nature. The ANA grade, the magnoliids, and the early-eudicot grade occupy large areas of the morphospace (higher disparity), whereas nested groups occupy narrower regions (lower disparity).

Integrating Fossil Flowers into the Angiosperm Phylogeny Using Molecular and Morphological Evidence.

Fossils are essential to infer past evolutionary processes. The assignment of fossils to extant clades has traditionally relied on morphological similarity and on apomorphies shared with extant taxa. The use of explicit phylogenetic analyses to establish fossil affinities has so far remained limited. In this study, we built a comprehensive framework to investigate the phylogenetic placement of 24 exceptionally preserved fossil flowers. For this, we assembled a new species-level data set of 30 floral traits for 1201 extant species that were sampled to capture the stem and crown nodes of all angiosperm families. We explored multiple analytical approaches to integrate the fossils into the phylogeny, including different phylogenetic estimation methods, topological-constrained analyses, and combining molecular and morphological data of extant and fossil species. Our results were widely consistent across approaches and showed minor differences in the support of fossils at different phylogenetic positions. The placement of some fossils agrees with previously suggested relationships, but for others, a new placement is inferred. We also identified fossils that are well supported within particular extant families, whereas others showed high phylogenetic uncertainty. Finally, we present recommendations for future analyses combining molecular and morphological evidence, regarding the selection of fossils and appropriate methodologies, and provide some perspectives on how to integrate fossils into the investigation of divergence times and the temporal evolution of morphological traits. [Angiosperms; fossil flowers; phylogenetic uncertainty; RoguePlots.].

Health and development from preconception to 20 years of age and human capital.

Optimal health and development from preconception to adulthood are crucial for human flourishing and the formation of human capital. The Nurturing Care Framework, as adapted to age 20 years, conceptualises the major influences during periods of development from preconception, through pregnancy, childhood, and adolescence that affect human capital. In addition to mortality in children younger than 5 years, stillbirths and deaths in 5-19-year-olds are important to consider. The global rate of mortality in individuals younger than 20 years has declined substantially since 2000, yet in 2019 an estimated 8·6 million deaths occurred between 28 weeks of gestation and 20 years of age, with more than half of deaths, including stillbirths, occurring before 28 days of age. The 1000 days from conception to 2 years of age are especially influential for human capital. The prevalence of low birthweight is high in sub-Saharan Africa and even higher in south Asia. Growth faltering, especially from birth to 2 years, occurs in most world regions, whereas overweight increases in many regions from the preprimary school period through adolescence. Analyses of cohort data show that growth trajectories in early years of life are strong determinants of nutritional outcomes in adulthood. The accrual of knowledge and skills is affected by health, nutrition, and home resources in early childhood and by educational opportunities in older children and adolescents. Linear growth in the first 2 years of life better predicts intelligence quotients in adults than increases in height in older children and adolescents. Learning-adjusted years of schooling range from about 4 years in sub-Saharan Africa to about 11 years in high-income countries. Human capital depends on children and adolescents surviving, thriving, and learning until adulthood.

Quantitative Image Analysis of Fibrillar Collagens Reveals Novel Diagnostic and Prognostic Biomarkers and Histotype-Dependent Aberrant Mechanobiology in Lung Cancer.

Fibrillar collagens are the most abundant extracellular matrix components in non-small cell lung cancer (NSCLC). However, the potential of collagen fiber descriptors as a source of clinically relevant biomarkers in NSCLC is largely unknown. Similarly, our understanding of the aberrant collagen organization and associated tumor-promoting effects is very scarce. To address these limitations, we identified a digital pathology approach that can be easily implemented in pathology units based on CT-FIRE software (version 2; https://loci.wisc.edu/software/ctfire) analysis of Picrosirius red (PSR) stains of fibrillar collagens imaged with polarized light (PL). CT-FIRE settings were pre-optimized to assess a panel of collagen fiber descriptors in PSR-PL images of tissue microarrays from surgical NSCLC patients (106 adenocarcinomas [ADC] and 89 squamous cell carcinomas [SCC]). Using this approach, we identified straightness as the single high-accuracy diagnostic collagen fiber descriptor (average area under the curve = 0.92) and fiber density as the single descriptor consistently associated with a poor prognosis in both ADC and SCC independently of the gold standard based on the TNM staging (hazard ratio, 2.69; 95% CI, 1.55-4.66; P < .001). Moreover, we found that collagen fibers were markedly straighter, longer, and more aligned in tumor samples compared to paired samples from uninvolved pulmonary tissue, particularly in ADC, which is indicative of increased tumor stiffening. Consistently, we observed an increase in a panel of stiffness-associated processes in the high collagen fiber density patient group selectively in ADC, including venous/lymphatic invasion, fibroblast activation (α-smooth muscle actin), and immune evasion (programmed death-ligand 1). Similarly, a transcriptional correlation analysis supported the potential involvement of the major YAP/TAZ pathway in ADC. Our results provide a proof-of-principle to use CT-FIRE analysis of PSR-PL images to assess new collagen fiber-based diagnostic and prognostic biomarkers in pathology units, which may improve the clinical management of patients with surgical NSCLC. Our findings also unveil an aberrant stiff microenvironment in lung ADC that may foster immune evasion and dissemination, encouraging future work to identify therapeutic opportunities.

Inclusion of optic neuritis in dissemination in space improves the performance of McDonald 2017 criteria in Hispanic people with suspected multiple sclerosis.

BACKGROUND: Hispanic people compared to White people with multiple sclerosis (MS) are two times more likely to present with optic neuritis (ON). ON in dissemination in space (DIS) after a single attack is not part of the current McDonald 2017 criteria. OBJECTIVE: To evaluate if adding ON in DIS (ON-modified criteria) improves the performance of the McDonald 2017 criteria in the diagnosis of MS after a single attack of ON. METHODS: Retrospective study of 102 patients of Hispanic background. Cases were reviewed between 2017 and 2021. Clinical ON was reported for 35 cases. ON in DIS was verified for 28 patients via MRI, optical coherence tomography, and/or visual evoked potential. We investigated the performance of the McDonald 2017 criteria and ON-modified criteria and calculated sensitivity, specificity, positive and negative predictive values, and accuracy. RESULTS: The ON-modified criteria significantly improved the performance of the McDonald 2017 criteria (p = 0.003) and identified an additional nine patients. Both sensitivity and accuracy increased from 64% to 74% and 62% to 71%, respectively, while specificity remained unchanged (40% (95% confidence interval (CI): 0.10, 0.70)). CONCLUSION: This study provides evidence that the inclusion of ON in DIS improved the overall performance of the McDonald 2017 criteria among Hispanic people.

Differentiating high-grade glioma progression from treatment-related changes with dynamic [18F]FDOPA PET: a multicentric study.

OBJECTIVES: Diagnostic accuracy of amino-acid PET for distinguishing progression from treatment-related changes (TRC) is currently based on single-center non-homogeneous glioma populations. Our study assesses the diagnostic value of static and dynamic [18F]FDOPA PET acquisitions to differentiate between high-grade glioma (HGG) recurrence and TRC in a large cohort sourced from two independent nuclear medicine centers. METHODS: We retrospectively identified 106 patients with suspected glioma recurrences (WHO GIII, n = 38; GIV, n = 68; IDH-mutant, n = 35, IDH-wildtype, n = 71). Patients underwent dynamic [18F]FDOPA PET/CT (n = 83) or PET/MRI (n = 23), and static tumor-to-background ratios (TBRs), metabolic tumor volumes and dynamic parameters (time to peak and slope) were determined. The final diagnosis was either defined by histopathology or a clinical-radiological follow-up at 6 months. Optimal [18F]FDOPA PET parameter cut-offs were obtained by receiver operating characteristic analysis. Predictive factors and clinical parameters were assessed using univariate and multivariate Cox regression survival analyses. RESULTS: Surgery or the clinical-radiological 6-month follow-up identified 71 progressions and 35 treatment-related changes. TBRmean, with a threshold of 1.8, best-differentiated glioma recurrence/progression from post-treatment changes in the whole population (sensitivity 82%, specificity 71%, p < 0.0001) whereas curve slope was only significantly different in IDH-mutant HGGs (n = 25). In survival analyses, MTV was a clinical independent predictor of progression-free and overall survival on the multivariate analysis (p ≤ 0.01). A curve slope > -0.12/h was an independent predictor for longer PFS in IDH-mutant HGGs CONCLUSION: Our multicentric study confirms the high accuracy of [18F]FDOPA PET to differentiate recurrent malignant gliomas from TRC and emphasizes the diagnostic and prognostic value of dynamic acquisitions for IDH-mutant HGGs. KEY POINTS: • The diagnostic accuracy of dynamic amino-acid PET, for distinguishing progression from treatment-related changes, is currently based on single-center non-homogeneous glioma populations. • This multicentric study confirms the high accuracy of static [18F]FDOPA PET images for differentiating progression from treatment-related changes in a homogeneous population of high-grade gliomas and highlights the diagnostic and prognostic value of dynamic acquisitions for IDH-mutant high-grade gliomas. • Dynamic acquisitions should be performed in IDH-mutant glioma patients to provide valuable information for the differential diagnosis of recurrence and treatment-related changes.

Cutaneous vascular structure and perfusion in patients with chronic plaque psoriasis.

BACKGROUND: Vascular dysfunction is a significant contributor to the pathophysiology of psoriasis. Some individuals have variation within the gene for vascular endothelial growth factor-A (VEGF-A), which confers an increased risk of developing psoriasis and having a severe disease phenotype, and may determine responsiveness to treatment. AIM: To determine whether patients with psoriasis have alterations in cutaneous microvascular anatomy and physiology due to expression of VEGF and whether laser Doppler imaging has utility in the assessment of this. METHODS: Twelve adult volunteers with Type 1 chronic plaque psoriasis underwent laser Doppler imaging of plaque and uninvolved skin. Skin biopsies were taken from the areas imaged for immunohistochemistry, including blood and lymphatic vessel markers, and VEGF-A isotype analysis (VEGF-A121, VEGF-A165 and VEGF-D). Venous blood was collected for DNA extraction, VEGF-A genotyping and peripheral blood mononuclear cell culture. RESULTS: Mean blood vessel area (P < 0·01), number of blood vessels (P < 0·001), number of lymphatic vessels (P < 0·001) and blood flow (P < 0·001) was significantly increased in psoriasis plaques, as was expression of VEGF-A121 (P < 0·01), VEGF-A165 (P < 0·04) and VEGF-D (P < 0·01). Blood flow within psoriasis plaques was independent of their increased vascularity (P < 0·01) and may be associated with baseline productivity of VEGF. The number of blood vessels within uninvolved skin in patients with psoriasis was associated with the VEGF-A (rs833061) genotype (P = 0·01), in a relationship suggesting an allele dosing effect. CONCLUSION: Noninvasive imaging of blood flow may help determine the cutaneous vascular signature for individual patients. This may be a useful prognostic indicator of psoriasis susceptibility and severity, and thus support selection of treatments.

Neutrophil Extracellular Traps and Cancer: Trapping Our Attention with Their Involvement in Ovarian Cancer.

Neutrophils, the most abundant circulating leukocytes, play a well-known role in defense against pathogens through phagocytosis and degranulation. However, a new mechanism involving the release of neutrophil extracellular traps (NETs) composed of DNA, histones, calprotectin, myeloperoxidase, and elastase, among others, has been described. The so-called NETosis process can occur through three different mechanisms: suicidal, vital, and mitochondrial NETosis. Apart from their role in immune defense, neutrophils and NETs have been involved in physiopathological conditions, highlighting immunothrombosis and cancer. Notably, neutrophils can either promote or inhibit tumor growth in the tumor microenvironment depending on cytokine signaling and epigenetic modifications. Several neutrophils' pro-tumor strategies involving NETs have been documented, including pre-metastatic niche formation, increased survival, inhibition of the immune response, and resistance to oncologic therapies. In this review, we focus on ovarian cancer (OC), which remains the second most incidental but the most lethal gynecologic malignancy, partly due to the presence of metastasis, often omental, at diagnosis and the resistance to treatment. We deepen the state-of-the-art on the participation of NETs in OC metastasis establishment and progression and their involvement in resistance to chemo-, immuno-, and radiotherapies. Finally, we review the current literature on NETs in OC as diagnostic and/or prognostic markers, and their contribution to disease progression at early and advanced stages. The panoramic view provided in this article might pave the way for enhanced diagnostic and therapeutic strategies to improve the prognosis of cancer patients and, specifically, OC patients.

Evaluation of Immune Infiltrates in Ovarian Endometriosis and Endometriosis-Associated Ovarian Cancer: Relationship with Histological and Clinical Features.

BACKGROUND: the association between ovarian endometriosis (OE) and endometriosis-associated ovarian cancer (EAOC) is extensively documented, and misfunction of the immune system might be involved. The primary objective of this study was to identify and compare the spatial distribution of tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) in OE and EAOC. Secondary objectives included the analysis of the relationship between immunosuppressive populations and T-cell exhaustion markers in both groups. METHODS: TILs (CD3, CD4, and CD8) and macrophages (CD163) were assessed by immunochemistry. Exhaustion markers (PD-1, TIM3, CD39, and FOXP3) and their relationship with tumour-associated macrophages (CD163) were assessed by immunofluorescence on paraffin-embedded samples from n = 43 OE and n = 54 EAOC patients. RESULTS: we observed a predominantly intraepithelial CD3+ distribution in OE but both an intraepithelial and stromal pattern in EAOC (p < 0.001). TILs were more abundant in OE (p < 0.001), but higher TILs significantly correlated with a longer overall survival and disease-free survival in EAOC (p < 0.05). CD39 and FOXP3 significantly correlated with each other and CD163 (p < 0.05) at the epithelial level in moderate/intense CD4 EAOC, whereas in moderate/intense CD8+, PD-1+ and TIM3+ significantly correlated (p = 0.009). Finally, T-cell exhaustion markers FOXP3-CD39 were decreased and PD-1-TIM3 were significantly increased in EAOC (p < 0.05). CONCLUSIONS: the dysregulation of TILs, TAMs, and T-cell exhaustion might play a role in the malignization of OE to EAOC.

Changes in cannabis use in Spanish consumers during the COVID-19 lockdown according to gender, age, living situation and addiction level. / Cambios en el consumo de cannabis en consumidores españoles durante el confinamiento por la COVID-19 según sexo, edad, situación de convivencia y nivel de adicción.

The objective was to analyze the changes in cannabis use during lockdown considering sex, age, living situation and level of addiction. This descriptive and non-probabilistic study used a convenience sample of 208 participants with ages between 18-57 years (64.3% men; mean age = 31.39 years), that reported consuming cannabis. The frequency of distinct typologies of cannabis use was analyzed and the level of addiction with the Cannabis Abuse Screening Test (CAST). An online survey was used to collect the variables under study. A total of 25% consumers increased their spliff (marijuana mixed with tobacco) consumption, 11.9% increased their joint (marijuana cigarette) consumption and 11.8% increased their hashish spliff consumption. Men had higher levels of cannabis addiction, however, during lockdown they reduced their marijuana spliff consumption while both men and women increased their joint consumption. Marijuana spliff consumption showed a greater increase in the 25-29 age group, in those living with people other than relatives or a partner, alone, or with a partner and was reduced mainly in those living with parents or other relatives. The living alone 18-24 years old group, and the living with parents 35-44 years old group showed higher levels of cannabis addiction (CAST). The rate of dependent consumers who increased their marijuana spliff consumption (49%) doubled compared to consumers with no addiction and moderate addiction. Regarding joints, consumption was 1.5 times higher than for moderate addiction consumers and three times higher than those with no addiction. The risk of cannabis addiction increased in certain groups during lockdown.

El objetivo fue analizar el consumo de cannabis durante el confinamiento según sexo, edad, situación de convivencia y nivel de adicción. Estudio descriptivo no probabilístico con una muestra de conveniencia de 208 participantes con edades entre 18-57 años (64,3% hombres; edad media = 31,39 años) que reportaron consumir cannabis. Se analizó la frecuencia de distintas tipologías de consumo de cannabis y el nivel de adicción con el Cannabis Abuse Screening Test (CAST). La recogida de datos se realizó mediante encuesta online. El 25% de consumidores aumentó su consumo de porros de marihuana mezclada con tabaco; el 11,9% de cigarros de marihuana; y el 11,8% de porros de hachís mezclado con tabaco. Los hombres presentaron mayor nivel de adicción al cannabis. Sin embargo, redujeron su consumo de porros durante el confinamiento. Hombres y mujeres incrementaron su consumo de cigarros de marihuana. El consumo de porros se incrementó mayormente en el grupo de 25-29 años, entre quienes convivían con personas distintas a familiares y pareja, vivían solas, o en pareja; y se redujo entre quienes vivían con progenitores o familiares. Mostraron mayor nivel de adicción al cannabis (CAST) el grupo entre 18-24 años que vive solo y el grupo entre 35-44 años que convive con sus progenitores. Los consumidores con dependencia que incrementan su consumo de porros (49%) fue dos veces superior respecto a los grupos sin adicción y con adicción moderada. El consumo de cigarros de marihuana (20,8%) fue 1,5 veces superior que para adicción moderada y más del triple que para sin adicción. El riesgo de adicción a cannabis aumentó en ciertos grupos durante el confinamiento.

Primary central nervous system lymphoma: advances in its pathogenesis, molecular markers and targeted therapies.

PURPOSE OF REVIEW: Primary central nervous system lymphoma (PCNSL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) located in the CNS with a less favorable prognosis. Recent information addressing the disease molecular heterogeneity is paving the way for tailored treatment strategies. This article reviews current work on the pathogenesis of the disease, potential biomarkers, and treatments. RECENT FINDINGS: Previous molecular classifications of PCNSL, built on DLBCL heterogeneity, did not properly address its intrinsic variability. Recent evidence has shown the existence of four different molecular PCNSL subtypes with associated multiomic characteristics, including prognostic relevance. Several studies have identified the tumor microenvironment (TME) as a driving prognostic factor in PCNSL. Therapy efforts continue mainly into targeting either the NF-κß (nuclear factor kappa-light-chain enhancer of activated B cells) pathway or modulating the TME through immunomodulatory drugs (lenalidomide) or immunotherapy (antiprogrammed cell death 1/programmed cell death 1 ligand 1). SUMMARY: Despite the increasing understanding of PCNSL pathogenesis with recent studies, future efforts are still needed to yield diagnostic biomarkers to detect either PCNSL or its molecular subtypes and hence ease routine clinical use.

Prognostic factors in primary central nervous system lymphoma.

PURPOSE OF REVIEW: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal diffuse large B cell lymphoma. Despite its apparent immunopathological homogeneity, PCNSL displays a wide variability in outcome. Identifying prognostic factors is of importance for patient stratification and clinical decision-making. The purpose of this review is to focus on the clinical, neuroradiological and biological variables correlated with the prognosis at the time of diagnosis in immunocompetent patients. RECENT FINDINGS: Age and performance status remain the most consistent clinical prognostic factors. The current literature suggests that neurocognitive dysfunction is an independent predictor of poor outcome. Cumulating data support the prognostic value of increased interleukin-10 level in the cerebrospinal fluid (CSF), in addition to its interest as a diagnostic biomarker. Advances in neuroimaging and in omics have identified several semi-quantitative radiological features (apparent diffusion restriction measures, dynamic contrast-enhanced perfusion MRI (pMRI) pattern and 18F-fluorodeoxyglucose metabolism) and molecular genetic alterations with prognostic impact in PCNSL. SUMMARY: Validation of new biologic and neuroimaging markers in prospective studies is required before integrating future prognostic scoring systems. In the era of radiomic, large clinicoradiological and molecular databases are needed to develop multimodal artificial intelligence algorithms for the prediction of accurate outcome.

Altered T-cell subset distribution in the viral reservoir in HIV-1-infected individuals with extremely low proviral DNA (LoViReTs).

BACKGROUND: HIV cure strategies aim to eliminate viral reservoirs that persist despite successful antiretroviral therapy (ART). We have previously described that 9% of HIV-infected individuals who receive ART harbor low levels of provirus (LoViReTs). METHODS: We selected 22 LoViReTs matched with 22 controls ART suppressed for more than 3 years with fewer than 100 and more than 100 HIV-DNA copies/106  CD4+ T cells, respectively. We measured HIV reservoirs in blood and host genetic factors. Fourteen LoViReTs underwent leukapheresis to analyze replication-competent virus, and HIV-DNA in CD4+ T-cell subpopulations. Additionally, we measured HIV-DNA in rectum and/or lymph node biopsies from nine of them. RESULTS: We found that LoViReTs harbored not only lower levels of total HIV-DNA, but also significantly lower intact HIV-DNA, cell-associated HIV-RNA, and ultrasensitive viral load than controls. The proportion of intact versus total proviruses was similar in both groups. We found no differences in the percentage of host factors. In peripheral blood, 71% of LoViReTs had undetectable replication-competent virus. Minimum levels of total HIV-DNA were found in rectal and lymph node biopsies compared with HIV-infected individuals receiving ART. The main contributors to the reservoir were short-lived transitional memory and effector memory T cells (47% and 29%, respectively), indicating an altered distribution of the HIV reservoir in the peripheral T-cell subpopulations of LoViReTs. CONCLUSION: In conclusion, LoViReTs are characterized by low levels of viral reservoir in peripheral blood and secondary lymphoid tissues, which might be explained by an altered distribution of the proviral HIV-DNA towards more short-lived memory T cells. LoViReTs can be considered exceptional candidates for future interventions aimed at curing HIV.

Circadian rhythms in psoriasis and the potential of chronotherapy in psoriasis management.

The physiology and pathology of the skin are influenced by daily oscillations driven by a master clock located in the brain, and peripheral clocks in individual cells. The pathogenesis of psoriasis is circadian-rhythmic, with flares of disease and symptoms such as itch typically being worse in the evening/night-time. Patients with psoriasis have changes in circadian oscillations of blood pressure and heart rate, supporting wider circadian disruption. In addition, shift work, a circadian misalignment challenge, is associated with psoriasis. These features may be due to underlying circadian control of key effector elements known to be relevant in psoriasis such as cell cycle, proliferation, apoptosis and inflammation. Indeed, peripheral clock pathology may lead to hyperproliferation of keratinocytes in the basal layers, insufficient apoptosis of differentiating keratinocytes in psoriatic epidermis, dysregulation of skin-resident and migratory immune cells and modulation of angiogenesis through circadian oscillation of vascular endothelial growth factor A (VEGF-A) in epidermal keratinocytes. Chronotherapeutic effects of topical steroids and topical vitamin D analogues have been reported, suggesting that knowledge of circadian phase may improve the efficacy, and therapeutic index of treatments for psoriasis. In this viewpoint essay, we review the current literature on circadian disruption in psoriasis. We explore the hypothesis that psoriasis is circadian-driven. We also suggest that investigation of the circadian components specific to psoriasis and that the in vitro investigation of circadian regulation of psoriasis will contribute to the development of a novel chronotherapeutic treatment strategy for personalised psoriasis management. We also propose that circadian oscillations of VEGF-A offer an opportunity to enhance the efficacy and tolerability of a novel anti-VEGF-A therapeutic approach, through the timed delivery of anti-VEGF-A drugs.

Antivascular endothelial growth factor-A therapy: a novel personalized treatment approach for psoriasis.

Chronic plaque psoriasis is an inflammatory skin disease in which genetic predisposition along with environmental factors lead to the development of the disease, which affects 2% of the UK's population and is associated with extracutaneous morbidities and a reduced quality of life. A complex crosstalk between innate and adaptive immunity, the epithelia and the vasculature maintain the inflammatory milieu in psoriasis. Despite the development of promising treatment strategies, mostly targeting the immune system, treatments fail to fulfil every patient's goals. Vascular endothelial growth factor-A (VEGF-A) mediates angiogenesis and is upregulated in the plaques and plasma of patients with psoriasis. Transgenic expression of VEGF-A in experimental models led to the development of skin lesions that share many psoriasis features. Targeting VEGF-A in in vivo models of psoriasis-like inflammation resulted in disease clearance. Anti-angiogenesis treatments are widely used for cancer and eye disease and there are clinical reports of patients treated with VEGF-A inhibitors who have experienced Psoriasis Area and Severity Index improvement. Existing psoriasis treatments downregulate VEGF-A and angiogenesis as part of their therapeutic effect. Pharmacogenetics studies suggest the existence of different genetic signatures within patients with psoriasis that correspond with different treatment responsiveness and disease severity. There is a subset of patients with psoriasis with an increased predisposition to produce high levels of VEGF-A, who may be most likely to benefit from anti-VEGF-A therapy, offering an opportunity to personalize treatment in psoriasis. Anti-VEGF-A therapies may offer an alternative to existing anticytokine strategies or be complementary to standard treatments for the management of psoriasis.

Chemotherapy is an efficient treatment in primary CNS MALT lymphoma.

BACKGROUND: Mucosae-associated lymphoid tissue (MALT) lymphomas are a rare and poorly understood form of primary central nervous system lymphoma (PCNSL). The aim of this study was to better describe these tumors, their management and their long-term prognosis. METHODS: Patients with primary CNS MALT lymphoma (PCNSML) were retrospectively selected from the database on PCNSL of the Pitié-Salpêtrière Hospital. RESULTS: Of 662 PCNSL, 11 (1.7%) PCNSML (9 females and 2 males, median age: 56 years) were selected. The median time from first symptoms to diagnosis was 13 months. Location was dural in 8 cases and parenchymal in 3 cases. The disease was multifocal/diffuse in 7 cases. In first line, all patients received chemotherapy (high-dose methotrexate (HD-MTX) based chemotherapy (n = 4) and non-HD-MTX-based chemotherapy (n = 7)), preceded by surgery in 4 cases. None received radiotherapy. According to the IPCG (International PCNSL Collaborative Group) criteria, the overall response rate was 7/11 (64%). At latest news, 5 patients had persistent contrast enhancement, stable with no treatment since a median of 57 months, raising the question of complete response despite persisting contrast enhancement. No patient developed neurotoxicity except for one patient who subsequently received radiotherapy. The median follow-up was 109 months. The median progression-free survival was 78.0 months and the 10-year overall survival rate was 90%. CONCLUSION: This is the largest series demonstrating that chemotherapy is an efficient treatment in PCNSML, with an excellent long-term outcome and the absence of neurotoxicity, and calling into question the relevance of the IPCG criteria for the evaluation of response.

Efficacy of capacitive resistive monopolar radiofrequency in the physiotherapeutic treatment of chronic pelvic pain syndrome: A randomized controlled trial.

AIM: To evaluate the efficacy of adjuvant, capacitive resistive monopolar radiofrequency (CRMRF, INDIBA) treatment at 448 kHz together with physiotherapeutic techniques compared to a sham treatment with the same techniques, for pain reduction and quality of life (QoL) improvements in patients with chronic pelvic pain syndrome (CPPS). METHODS: A triple-blind, randomized controlled trial (RCT) including patients with CPPS randomly allocated (1:1) to a CRMRF-activated group (intervention) or a CRMRF-deactivated one (control). Both groups received physiotherapeutic techniques and pain education weekly for 10 consecutive weeks. Data from a visual analogical scale and the SF-12 questionnaire were collected at trial commencement and repeated at the 5th and 10th sessions. Pain intensity was considered the main outcome. For the comparisons between variables, the χ2 and Student's t test were used. Superiority was analyzed by estimating the mean change (95% confidence interval). Analysis was performed for the per-protocol and the intention-to-treat populations. The statistical significance level was set at p < 0.05. RESULTS: Eighty-one patients were included (67.9% women) with a mean age of 43.6 years (SD 12.9). CRMRF lessened pain scores by more than 2 points and improved QoL by 5 points. There were no relevant side effects and overall adherence to the treatment was 86.4%. CONCLUSIONS: This is the first RCT that evaluates the efficacy of CRMRF (INDIBA) compared to a sham treatment, and demonstrates its superiority in decreasing pain and improving QoL. Such results may lead to greater prescribing of CRMRF when treating CPPS patients.

Hippocampal infarction: redefining transient global amnesia.

BACKGROUND AND AIMS: Transient global amnesia (TGA) is a clinical syndrome characterized by sudden anterograde amnesia not accompanied by other neurological symptoms. There is no consensus on the underlying pathophysiological mechanism. However, diffusion-weighted imaging (DWI) of the magnetic resonance imaging (MRI) has demonstrated hippocampal lesions in as many as 50% of cases. This paper describes a series of patients with TGA and hippocampal lesions. METHODS: This study assessed vascular risk factors in patients older than age 18 admitted to the Hospital Universitario San Ignacio, Bogota, Colombia, from May 2017 to June 2020 with a diagnosis of TGA and evidence of hippocampal ischemic lesion on 3 Tesla brain MRI. RESULTS: The authors identified 36 patients, 72.2% female, with mean age 62 years. Cardiovascular risk factors, most frequently high blood pressure, carotid disease, and dyslipidemia, were present in 75% of these patients. Hippocampal lesions were unilateral in 80% of cases, with median size 2.5 mm, most frequently located at the hippocampal body. Approximately 14% of patients also presented acute ischemic lesions in locations other than the hippocampus. CONCLUSIONS: TGA is a clinical entity previously considered to have undetermined etiology. The present study used brain MRI to identify a group of patients with hippocampal ischemic lesions, finding associated vascular risk factors in a high proportion of them.

Epidemiology of Obesity.

Obesity is in theory defined on the basis of the excess health risk caused by adiposity exceeding the size normally found in the population, but for practical reasons, the World Health Organization (WHO) has defined obesity as a body mass index (weight (kg)/height (m)2) of 30 or above for adults. WHO considers the steep increases in prevalence of obesity in all age groups, especially since the 1970s as a global obesity epidemic. Today, approximately 650 million adult people and approximately 340 million children and adolescence (5-19 years) suffer from obesity. It is generally more prevalent among women and older age groups than among men and younger age groups. Beyond the necessity of availability of food, evidence about causes of obesity is still very limited. However, studies have shown that obesity 'runs in families', where both genetics and environmental, and especially social, factors play important roles. Obesity is associated with an increased risk of many adverse medical, mental and social consequences, including a strong relation to type 2 diabetes. Type 2 diabetes and related metabolic syndrome and diseases are major contributors to the excess morbidity and mortality associated with obesity.

'C'mon, let's talk: a pilot study of mental health literacy program for Filipino migrant domestic workers in the United Kingdom.

PURPOSE: This pilot study of a culturally adapted online mental health literacy (MHL) program called 'Tara, Usap Tayo!' (C'mon, Let's Talk) aims to assess the acceptability, appropriateness, feasibility, and potential effectiveness in improving the help-seeking behavior of Filipino migrant domestic workers in the United Kingdom (UK). METHODS: Using mixed methods, we conducted a non-randomized single-group study of the online MHL program with 21 participants. The development of this intervention was guided by the Medical Research Council Framework for developing complex interventions and utilized Heim & Kohrt's (2019) framework for cultural adaptation. Content materials from the WHO Mental Health Gap Action Program (mhGAP), WHO Problem Management Plus (PM +) and Adult Improving Access to Psychological Therapies (IAPT) were modified and translated into the Filipino language. The MHL program was delivered online in three sessions for two hours each session. Data were collected at three time points: (T1) pretest; (T2) posttest; and (3) follow-up test. Quantitative data on participants' attitudes towards help-seeking and level of mental health literacy as outcome measures of potential intervention effectiveness were collected at T1, T2 and T3, while focus group discussions (FGDs) to assess participants' feedback on the acceptability, feasibility, and appropriateness of the online MHL program were conducted immediately at T2. Data analysis was done using a thematic approach for qualitative data from the FGDs and descriptive statistics and repeated-measures ANOVA were used to assess the difference in the T1, T2, and T3 tests. Both quantitative and qualitative results were then integrated and triangulated to answer the research questions. RESULTS: The online MHL program is generally acceptable, appropriate, and feasible for use among Filipino migrant domestic workers. Preliminary findings lend support for its possible effectiveness in improving mental health literacy and help-seeking propensity. The cultural adaptation made in the content, form, and delivery methods of the intervention was acceptable and feasible for this target subcultural group. CONCLUSION: By improving their mental health literacy and help-seeking propensity, this online MHL program has the potential to provide support to the mental health and well-being of Filipino migrant domestic workers in the UK. Further feasibility study or large-scale randomized controlled trial is needed to confirm the preliminary findings of this study.