Family planning decision-making in relation to psychiatric disorders in women: a qualitative focus group study.

BACKGROUND: Recent studies revealed an elevated likelihood of unintended pregnancies among women with psychiatric disorders compared to their counterparts without such vulnerability. Despite the importance of understanding family planning decision-making in this group, qualitative inquiries are lacking. This study explored family planning decisions among women with psychiatric disorders. METHODS: Utilizing a qualitative approach, three focus group discussions were conducted with purposive sampling: women with a history of unintended pregnancies (N = 3), women without children (N = 5), and women with a history of intended pregnancies (N = 9), all of whom had self-reported psychiatric disorders. Using thematic framework analysis, we investigated the themes "Shadow of the past," reflecting past experiences, and "Shadow of the future," reflecting future imaginaries, building upon the existing "Narrative Framework." RESULTS: The Narrative Framework formed the foundation for understanding family planning among women with psychiatric disorders. The retrospective dimension of focus group discussions provided opportunities for reflective narratives on sensitive topics, revealing emotions of regret, grief and relief. Childhood trauma, adverse events, and inadequate parenting enriched the "Shadow of the past". The "Shadow of the present" was identified as a novel theme, addressing awareness of psychiatric disorders and emotions toward psychiatric stability. Social influences, stigma, and concerns about transmitting psychiatric disorders shaped future imaginaries in the shadow of the future. CONCLUSIONS: This study enlightens how family planning decision-making in women with psychiatric disorders might be complex, as marked by the enduring impact of past experiences and societal influences in this sample. These nuanced insights underscore the necessity for tailored support for women with psychiatric disorders.

Recent studies show that women with psychiatric disorders are more likely to experience unintended pregnancies. However, the underlying reasons are not fully understood. Understanding those reasons is important to provide better healthcare. Our study explored how women with psychiatric disorders make decisions about family planning.We had conversations with different groups of women­women with unintended pregnancies, women without children, and women with intended pregnancies­through focus group discussions. We partnered with the Dutch mental health organization MIND to capture diverse opinions. Key themes and categories in the discussions were identified and organized.We found four main themes: "Shadow of the past" showed how past events, trauma, and lack of knowledge about parenting affect family planning. "Shadow of the present" revealed different feelings about family planning, the importance of the awareness of psychiatric disorders, and uncertainty about decisions. "Shadow of the future" included thoughts about becoming a mother, the impact of social influences, and concerns about passing on psychiatric disorders. "Reflections on the decision" showed how psychiatric disorders, experiences with motherhood, and feelings of regret, grief and relief had an influence on family planning decisions.In conclusion, our study highlighted the complexity of family planning decisions for women with psychiatric disorders. Past experiences and societal influences, like stigma, play a big role. These insights show the need for personalized family planning support for women with psychiatric disorders.

MYB expression by immunohistochemistry is highly specific and sensitive for detection of solid variant of adenoid cystic carcinoma of the breast among all triple-negative breast cancers.

BACKGROUND: Adenoid cystic carcinoma is a rare subtype of triple-negative breast carcinoma. These low-grade tumours, which are treated by simple mastectomy and have an excellent prognosis compared to other triple-negative breast carcinomas. Solid-variant adenoid cystic carcinomas have basaloid features and are difficult to distinguish morphologically from other triple-negative breast cancers. Breast adenoid cystic carcinoma exhibits MYB protein overexpression, which can be detected by immunohistochemistry (IHC). AIM: We compared the IHC expression of MYB in solid-variant adenoid cystic carcinoma with that in other triple-negative breast cancers. METHODS: We conducted IHC staining of 210 samples of triple-negative breast cancers, including solid-variant adenoid cystic carcinoma (n = 17), metaplastic breast carcinoma (n = 44), basaloid triple-negative breast cancer (n = 21), and other triple-negative invasive ductal carcinoma (n = 128). We classified nuclear staining of MYB as diffuse/strong (3+), focal moderate (2+), focal weak (1+), or none (0). RESULTS: All 17 solid/basaloid adenoid cystic carcinoma cases exhibited 3+ MYB expression. Of the 21 solid/basaloid triple-negative breast cancers, one (5%) had 2+ expression, seven (33%) 1+ expression, and 13 (62%) 0 expression. Of the 44 metaplastic carcinoma cases, 39 cases (89%) had no (0) staining, and the other five cases had focal weak (1+) or moderate (2+) staining. Among the 128 triple-negative invasive ductal carcinoma cases, 92 cases (72%) had no (0) staining, 36 cases (28%) exhibited focal weak (1+) or moderate (2+) staining. CONCLUSIONS: Our study revealed diffuse/strong MYB staining (3+) only in solid/basaloid adenoid cystic carcinomas. Thus, we recommend routine MYB IHC staining in triple-negative breast carcinoma with solid/basaloid morphology to improve diagnostic accuracy.

A highly specific aptamer for the SARS-CoV-2 spike protein from the authentic strain.

DNA aptamers are oligonucleotides that specifically bind to target molecules, similar to how antibodies bind to antigens. We identified an aptamer named MEZ that is highly specific to the receptor-binding domain, RBD, of the SARS-CoV-2 spike protein from the Wuhan-Hu-1 strain. The SELEX procedure was utilized to enrich the initial 31-mer oligonucleotide library with the target aptamer. The aptamer identification was performed using the novel protocol based on nanopore sequencing developed in this study. The MEZ aptamer was chemically synthesized and tested for binding with the SARS-CoV-2 RBD of the spike protein from different strains. The Kd is 6.5 nM for the complex with the RBD from the Wuhan-Hu-1 strain, which is comparable with known aptamers; the advantage is that the MEZ aptamer is smaller than known analogs. The proposed aptamer is highly selective for the RBD protein from the Wuhan-Hu-1 strain and does not form complexes with the RBD from Beta, Delta and Omicron strains. Experimental and theoretical studies together revealed the molecular mechanism of aptamer binding. The aptamer occupies the same binding site as ACE2 when bound to the RBD. The 3'-end of the MEZ aptamer is important for complex formation and is responsible for the discrimination of the RBD protein from a specific strain. The 5'-end is responsible for the formation of a loop in the 3D structure of the aptamer, which is important for proper binding.

Impact of Age of Heart Transplant Program on Patient Survival and Post-Transplant Outcomes.

BACKGROUND: The relationship between age of a heart transplant (HT) program and outcomes has not been explored. METHODS: We performed a retrospective cohort analysis of the United Network for Organ Sharing database of all adult HTs between 2009 and 2019. For each patient, we created a variable that corresponded to program age: new (<5), developing (≥5 but <10) and established (≥10) years. RESULTS: Of 20 997 HTs, 822 were at new, 908 at developing, and 19 267 at established programs. Patients at new programs were significantly more likely to have history of cigarette smoking, ischemic cardiomyopathy, and prior sternotomy. These programs were less likely to accept organs from older donors and those with a history of hypertension or cigarette use. As compared to patients at new programs, transplant patients at established programs had less frequent rates of treated rejection during the index hospitalization (HR 0.43 [95% CI, 0.36-0.53] p < 0.001) and at 1 year (HR 0.58 [95% CI, 0.49-0.70], p < 0.001), less frequently required pacemaker implantations (HR 0.50 [95% CI, 0.36-0.69], p < 0.001), and less frequently required dialysis (HR 0.66 [95% CI, 0.53-0.82], p < 0.001). However, there were no significant differences in short- or long-term survival between the groups (log-rank p = 0.24). CONCLUSION: Patient and donor selection differed between new, developing, and established HT programs but had equivalent survival. New programs had increased likelihood of treated rejection, pacemaker implantation, and need for dialysis. Standardized post-transplant practices may help to minimize this variation and ensure optimal outcomes for all patients.

Optical Thin Films in Space Environment: Investigation of Proton Irradiation Damage.

The present work reports a systematic study of the potential degradation of metals and dielectric thin films in different space environments. The mono- and bilayers selected are made of materials commonly used for the realization of optical components, such as reflective mirrors or building blocks of interferential filters. More than 400 samples were fabricated and irradiated with protons at different energies on ground-based facilities. The fluences were selected as a result of simulations of the doses delivered within a long-term space mission considering different orbits (Sun close, Jovian, and Geostationary orbits). In order to stress the samples at different depths and layer interfaces, experiments were carried out with a range of proton energies within 1 and 10 MeV values. An estimate of a safe maximum fluence has been provided for each type of sample at each energy. The damage mechanism, when present, has been investigated with different optical and structural techniques.

Widespread human exposure to ledanteviruses in Uganda: A population study.

Le Dantec virus (LDV), assigned to the species Ledantevirus ledantec, genus Ledantevirus, family Rhabdoviridae has been associated with human disease but has gone undetected since the 1970s. We describe the detection of LDV in a human case of undifferentiated fever in Uganda by metagenomic sequencing and demonstrate a serological response using ELISA and pseudotype neutralisation. By screening 997 individuals sampled in 2016, we show frequent exposure to ledanteviruses with 76% of individuals seropositive in Western Uganda, but lower seroprevalence in other areas. Serological cross-reactivity as measured by pseudotype-based neutralisation was confined to ledanteviruses, indicating population seropositivity may represent either exposure to LDV or related ledanteviruses. We also describe the discovery of a closely related ledantevirus in blood from the synanthropic rodent Mastomys erythroleucus. Ledantevirus infection is common in Uganda but is geographically heterogenous. Further surveys of patients presenting with acute fever are required to determine the contribution of these emerging viruses to febrile illness in Uganda.

Setting the European standards for training in Physical and Rehabilitation Medicine.

The mission of the European Board of Physical and Rehabilitation Medicine (PRM) is to the ensure a consistent and high-level education for PRM physicians across Europe. An important action to accomplish this mission is the publication and continuous update of the European Training Requirements (ETRs) for the specialty of PRM. The first version of the ETRs for PRM was issued in 2017. The aim was to present the up-to-date training standards for trainees, trainers, and training institutions. The revision of the first ETRs, aiming to reflect the current standards in medical education and clinical advances in the field or PRM, started in 2022 and was completed in 2023. It was based on the Rehabilitation Competency Framework and the "Guide for using a contextualised competency framework to develop rehabilitation programmes and their curricula" published by the WHO in 2021. An important addition in the new version of the ETRs is the integration of Entrustable Professional Activities. In all endeavours of the creation of the ETRs, setting the highest standards of training in PRM was pursued.

Deepvirusclassifier: a deep learning tool for classifying SARS-CoV-2 based on viral subtypes within the coronaviridae family.

PURPOSE: In this study, we present DeepVirusClassifier, a tool capable of accurately classifying Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral sequences among other subtypes of the coronaviridae family. This classification is achieved through a deep neural network model that relies on convolutional neural networks (CNNs). Since viruses within the same family share similar genetic and structural characteristics, the classification process becomes more challenging, necessitating more robust models. With the rapid evolution of viral genomes and the increasing need for timely classification, we aimed to provide a robust and efficient tool that could increase the accuracy of viral identification and classification processes. Contribute to advancing research in viral genomics and assist in surveilling emerging viral strains. METHODS: Based on a one-dimensional deep CNN, the proposed tool is capable of training and testing on the Coronaviridae family, including SARS-CoV-2. Our model's performance was assessed using various metrics, including F1-score and AUROC. Additionally, artificial mutation tests were conducted to evaluate the model's generalization ability across sequence variations. We also used the BLAST algorithm and conducted comprehensive processing time analyses for comparison. RESULTS: DeepVirusClassifier demonstrated exceptional performance across several evaluation metrics in the training and testing phases. Indicating its robust learning capacity. Notably, during testing on more than 10,000 viral sequences, the model exhibited a more than 99% sensitivity for sequences with fewer than 2000 mutations. The tool achieves superior accuracy and significantly reduced processing times compared to the Basic Local Alignment Search Tool algorithm. Furthermore, the results appear more reliable than the work discussed in the text, indicating that the tool has great potential to revolutionize viral genomic research. CONCLUSION: DeepVirusClassifier is a powerful tool for accurately classifying viral sequences, specifically focusing on SARS-CoV-2 and other subtypes within the Coronaviridae family. The superiority of our model becomes evident through rigorous evaluation and comparison with existing methods. Introducing artificial mutations into the sequences demonstrates the tool's ability to identify variations and significantly contributes to viral classification and genomic research. As viral surveillance becomes increasingly critical, our model holds promise in aiding rapid and accurate identification of emerging viral strains.

Aortic dimensions in women with previous pre-eclampsia.

BACKGROUND: Pre-eclampsia is a pregnancy related disorder associated with hypertension and vascular inflammation, factors that are also involved in the pathological pathway of aortic dilatation and aneurysm development. It is, however, unknown if younger women with previous pre-eclampsia have increased aortic dimensions. We tested the hypothesis that previous pre-eclampsia is associated with increased aortic dimensions in younger women. METHODS: The study was a cross-sectional cohort study of women with previous pre-eclampsia, aged 40-55, from the PRECIOUS population matched by age and parity with women from the general population. Using contrast-enhanced CT, aortic diameters were measured in the aortic root, ascending aorta, descending aorta, at the level of the diaphragm, suprarenal aorta, and infrarenal aorta. RESULTS: 1355 women (684 with previous pre-eclampsia and 671 from the general population), with a mean (standard deviation) age of 46.9 (4.4) were included. The pre-eclampsia group had larger mean (standard deviation) aortic diameters (mm) in all measured segments from the ascending to the infrarenal aorta (ascending: 33.4 (4.0) vs. 31.4 (3.7), descending: 23.9 (2.1) vs. 23.3 (2.0), diaphragm: 20.8 (1.8) vs. 20.4 (1.8), suprarenal: 22.9 (1.9) vs. 22.0 (2.0), infrarenal: 19.3 (1.6) vs. 18.6 (1.7), p â€‹< â€‹0.001 for all, also after adjustment for age, height, parity, menopause, dyslipidemia, smoking and chronic hypertension. Guideline-defined ascending aortic aneurysms were found in 8 vs 2 women (p â€‹= â€‹0.12). CONCLUSIONS: Women with previous pre-eclampsia have larger aortic dimensions compared with women from the general population. Pre-eclampsia was found to be an independent risk factor associated with a larger aortic diameter.

The conversation about family planning and desire for children in mental healthcare: Patients' perspective versus Professionals' perspective in a mixed methods study.

BACKGROUND: Reproductive health and mental health are intertwined, but studies investigating family planning needs and desire for children in mental healthcare are scarce. METHODS: We studied the experiences of (former) patients, those with close relationships with the (former) patients (close ones) and mental health professionals (MHP) on discussing family planning and desire for children in mental healthcare. We combined quantitative (two nationwide surveys) and qualitative data (four focus groups) in a mixed-methods approach with sequential analytical design. RESULTS: Combined data from focus groups (n = 19 participants) and two surveys (n = 139 MHPs and n = 294 (former) patients and close ones) showed that a considerable group of MHPs (64.0%), patients (40.9%) and close ones (50.0%) found that family planning should be discussed by a psychiatrist. However, several obstacles impeded a conversation, such as fear of judgment, lack of time and knowledge and limited opportunity for in-depth exploration of life themes in therapeutic relationships. CONCLUSIONS: To increase the autonomy of patients in discussing family planning, we suggest MHPs explore the desire to discuss family planning with all patients in the reproductive phase of life, prior to discussing contraceptive care. MHPs should receive education about psychiatric vulnerability in relation to family planning and desire for children, and patients and close ones should be empowered to initiate a conversation themselves.

Autologous CD19- targeting CAR T cells in refractory juvenile dermatomyositis.

OBJECTIVES: To report safety and efficacy of CD19-targeting CAR T cells in a child with refractory juvenile dermatomyositis (JDM). PATIENTS AND METHODS: We describe the case of a 12-year-old Caucasian boy with severe, chronically active JDM, refractory to multiple immunosuppressive treatment lines, including B-cell depletion with rituximab. The patient received a single infusion of fresh, autologous, second-generation anti-CD19 CAR T-cell product (lentiviral vector) manufactured on the Prodigy device (1x106 CAR T cells/kg), after lymphodepletion with cyclophosphamide (1000 mg/m2 over 2 days) and fludarabine (90 mg/m2 over 3 days). Immunosuppressive and glucocorticoid treatment were withdrawn before leukapheresis and CAR T-cell infusion. RESULTS: Before anti-CD19 CAR T-cell therapy, the patient had persistent severe skin and muscular disease activity. CAR T cells expanded significantly (peak at day 7, 32.69 cells/µL). Complete B-cell depletion was documented on day 5 in blood and at week 2 in bone marrow. The patient presented fever as part of mild cytokine release syndrome (G1), transient anemia (G2) and neutropenia (G4). Neither infection nor neurotoxicity were observed. Laboratory tests, MRI imaging, Physician's Global Assessment of disease activity (PGA), Childhood Myositis Assessment Scale (CMAS) and Cutaneous Assessment Tool for myositis (CAT) were performed at baseline and follow-up to assess treatment response, showing remarkable progressive improvement that persists over time, even after B-cell recovery. CONCLUSIONS: This JDM patient with severe chronic disease, refractory to multiple treatments, achieved sustained B-cell depletion and ongoing immunosuppressive drug-free clinical and radiological improvement eight months after a single infusion of anti-CD19 CAR T cells.

Overweight and Obesity Is Associated with Higher Risk of Perceived Stress and Poor Sleep Quality in Young Adults.

Background and Objectives: Overweight and obesity are growing public health challenges, particularly concerning young adults. University life presents a unique set of stressors that may influence weight management alongside sleep quality. In this cross-sectional study, we aimed to investigate the association between overweight or obesity, stress, and sleep quality in a large sample of Greek university students. Materials and Methods: The study recruited 2116 active students from across various Greek universities. Participants completed questionnaires on sociodemographics, academic performance, and physical activity levels using the International Physical Activity Questionnaire (IPAQ). Stress and sleep quality were assessed using the Perceived Stress Scale (PSS) and the Pittsburgh Sleep Quality Index (PSQI), respectively. Body weight and height were directly measured to calculate Body Mass Index (BMI). Results: Our analysis of 2116 Greek university students revealed significant associations between various factors and overweight/obesity. Compared to their rural counterparts, young adults in urban areas had an 88% higher prevalence of overweight/obesity (p = 0.0056). Regular smokers were twice as likely to be overweight or obese (p = 0.0012). Notably, those with low physical activity levels displayed a more than two-fold increased risk (p = 0.0008) compared to those with moderate or high activity levels. Similarly, students with moderate or high perceived stress levels had a more than two-fold prevalence of overweight/obesity compared to those with low stress (p = 0.0005). Inadequate sleep quality was also associated with an 86% higher risk of overweight/obesity (p = 0.0007). Interestingly, good academic performance showed a 57% greater prevalence of overweight/obesity compared to very good/excellent performance (p = 0.0103). Conclusions: Our findings reveal that perceived stress and poor sleep quality are significant risk factors for overweight and obesity in this young adult population.

Morphological and Molecular Identification of Phytophthora capsici Isolates with Differential Pathogenicity in Sechium edule.

Chayote (Sechium edule) is a crop of great economic and pharmaceutical importance in Mexico. Chayote is affected by Phytophthora capsici, which causes plant wilt and fruit rot. Three isolates of P. capsici (A1-C, A2-H, and A3-O) were obtained from three producing areas in Veracruz, Mexico. Morphometric characteristics of sporangia and the colony pattern on three different media were described. They were molecularly identified by amplification of the internal transcribed spacer region (ITS) and the partial sequence of cytochrome c oxidase subunit 1 (COI), sequences that were phylogenetically analyzed. The mating type, pathogenicity in S. edule fruits, and sensitivity to metalaxyl were determined. Isolate A1-C presented the largest sporangium; all sporangia were papillated, with different morphologies and pedicel lengths. All isolates showed different colony patterns: chrysanthemum (A1-C), stellate (A2-H), and petaloid (A3-O). The topology of the phylogenetic tree was similar for the ITS region and COI gene, the sequences of the three isolates clustered with sequences of the genus Phytophthora classified in group 2b, corroborating their identity as P. capsici. The mating type of isolates A1-C and A3-O was A2 and of isolate A2-H was A1. The pathogenicity test indicated that isolate A1-C was the most virulent and with intermediate sensitivity to metalaxyl. This work suggests that P. capsici isolates from various production areas in Mexico may exhibit morphological and virulence variability.

Aedes albopictus saliva contains a richer microbial community than the midgut.

BACKGROUND: Past findings demonstrate that arthropods can egest midgut microbiota into the host skin leading to dual colonization of the vertebrate host with pathogens and saliva microbiome. A knowledge gap exists on how the saliva microbiome interacts with the pathogen in the saliva. To fill this gap, we need to first define the microbial composition of mosquito saliva. METHODS: The current study aimed at analyzing and comparing the microbial profile of Aedes albopictus saliva and midgut as well as assessing the impact of Zika virus (ZIKV) infection on the midgut and saliva microbial composition. Colony-reared Ae. albopictus strains were either exposed to ZIKV infectious or noninfectious bloodmeal. At 14 ays postinfection, the 16S V3-V4 hypervariable rRNA region was amplified from midgut and saliva samples and sequenced on an Illumina MiSeq platform. The relative abundance and diversity of midgut and saliva microbial taxa were assessed. RESULTS: We observed a richer microbial community in the saliva compared with the midgut, yet some of the microbial taxa were common in the midgut and saliva. ZIKV infection did not impact the microbial diversity of midgut or saliva. Further, we identified Elizabethkingia spp. in the Ae. albopictus saliva. CONCLUSIONS: This study provides insights into the microbial community of the Ae. albopictus saliva as well as the influence of ZIKV infection on the microbial composition of its midgut and saliva. The identification of Elizabethkingia spp., an emerging pathogen of global health significance, in Ae. albopictus saliva is of medical importance. Future studies to assess the interactions between Ae. albopictus saliva microbiome and ZIKV could lead to novel strategies for developing transmission barrier tools.

Effects of a Multicomponent Preventive Intervention in Women at Risk of Sarcopenia: A Pilot Study.

Sarcopenia is defined by the presence of decreased skeletal muscle mass, strength, and functionality in older people. Multicomponent interventions represent an alternative to non-pharmacological treatment for preventing disease progression. This study aimed to evaluate the effects of a multicomponent intervention approach in women at risk of sarcopenia. METHODS: A quasi-experimental pilot study of 12 weeks was conducted, with 24 sessions of dancing and resistance exercises and 12 sessions of nutritional education. The outcomes were changes in muscle mass, grip strength, gait speed, and body composition. The project was registered on Clinical Trials: NCT06038500 (14 September 2023). RESULTS: Twelve women aged 55-75 years participated in this study; after the intervention, changes were found in the following variables: grip strength, from 18.70 (17.98-19.23) at baseline to 21.57 (20.67-23.16) kg (p = 0.002); gait speed, from 0.95 (0.81-1.18) at baseline to 1.34 (1.20-1.47) m/s (p = 0.003); and hip circumference, from 99.75 (94.75-110.37) at baseline to 97.65 (93.92-109.50) cm (p = 0.023). Other measurements that appeared without changes were appendicular skeletal muscle mass, from 21.17 (18.58-22.33) at baseline to 20.77 (18.31-22.39) kg (p = 0.875), and the appendicular skeletal muscle mass index, from 8.64 (8.08-9.35) at baseline to 8.81 (7.91-9.38) kg/m2 (p = 0.875) after the intervention. CONCLUSIONS: The three-month multicomponent intervention in women at risk of sarcopenia improved their grip strength and gait speed.

Spark-Discharge-Activated 3D-Printed Electrochemical Sensors.

3D printing technology is a tremendously powerful technology to fabricate electrochemical sensing devices. However, current conductive filaments are not aimed at electrochemical applications and therefore require intense activation protocols to unleash a suitable electrochemical performance. Current activation methods based on (electro)chemical activation (using strong alkaline solutions and organic solvents and/or electrochemical treatments) or combined approaches are time-consuming and require hazardous chemicals and dedicated operator intervention. Here, pioneering spark-discharge-activated 3D-printed electrodes were developed and characterized, and it was demonstrated that their electrochemical performance was greatly improved by the effective removal of the thermoplastic support polylactic acid (PLA) as well as the formation of sponge-like and low-dimensional carbon nanostructures. This reagent-free approach consists of a direct, fast, and automatized spark discharge between the 3D-electrode and the respective graphite pencil electrode tip using a high-voltage power supply. Activated electrodes were challenged toward the simultaneous voltammetric determination of dopamine (DP) and serotonin (5-HT) in cell culture media. Spark discharge has been demonstrated as a promising approach for conductive filament activation as it is a fast, green (0.94 GREEnness Metric Approach), and automatized procedure that can be integrated into the 3D printing pipeline.

Comparison of Small Blood Vessel Diameter with Intravascular Ultrasound and Coronary Angiography for Guidance of Percutaneous Coronary Intervention.

Major cardiovascular events (MACEs) are a cause of major mortality worldwide. The narrowing and blockage of coronary arteries with atherosclerotic plaques are diagnosed and treated with percutaneous coronary intervention (PCI). During this procedure, coronary angiography (CAG) remains the most widely used guidance modality for the evaluation of the affected blood vessel. The measurement of the blood vessel diameter is an important factor to consider in order to decide if stent colocation is suitable for the intervention. In this regard, a small blood vessel (<2.75 mm) is majorly left without stent colocation; however, small vessel coronary artery disease (SvCAD) is a significant risk factor for the recurrence of MACEs, maybe due to the lack of a standardized treatment related to the diameter of the affected blood vessel; therefore, a more precise measurement is needed. The use of CAG for the measurement of the blood vessel diameter has some important limitations that can be improved with the use of newer techniques such as intravascular ultrasound (IVUS), although at higher costs, which might explain its underuse. To address differences in blood vessel diameter measurements and identify specific cases where IVUS might be of additional benefit for the patient, we conducted a retrospective study in patients who underwent PCI for MACEs with affection for at least one small blood vessel. We compared the measurements of the affected small blood vessels' diameter obtained by CAG and IVUS to identify cases of reclassification of the affected blood vessel; additionally, we underwent a multivariate analysis to identify risk factors associated with blood vessel reclassification. We included information from 48 patients with a mean ± SD age of 69.1 ± 11.9 years; 70.8% were men and 29.2% were women. The mean diameter with CAG and IVUS was 2.1 mm (95% CI 1.9-2.2), and 2.8 (2.8-3.0), respectively. The estimated difference was of 0.8 mm (95% CI 0.7-0.9). We found a significant positive low correlation in diameter measurements of small blood vessels obtained with CAG and IVUS (r = 0.1242 p = 0.014). In total, 37 (77%) patients had a reclassification of the affected blood vessel with IVUS. In 21 cases, the affected blood vessel changed from a small to a medium size (2.75-3.00 mm), and in 15 cases, the affected vessel changed from a small to a large size (<3.00 mm). The Bland-Altman plot was used to evaluate agreement in measurements with CAG and IVUS. The change in blood vessel classification with IVUs was important for the decision of intervention and stent collocation. The only variable associated with reclassification of blood vessels after adjustment in a multivariate analysis was T2D (type 2 diabetes) (p = 0 0.035). Our findings corroborate that blood vessels might appear smaller with CAG, especially in patients with T2D; therefore, at least in these cases, the use of IVUS is recommended over CAG.

The PP2A regulatory subunit PPP2R2A controls NAD+ biosynthesis to regulate T cell subset differentiation in systemic autoimmunity.

The protein phosphatase 2A (PP2A) regulatory subunit PPP2R2A is involved in the regulation of immune response. We report that lupus-prone mice with T cells deficient in PPP2R2A display less autoimmunity and nephritis. PPP2R2A deficiency promotes NAD+ biosynthesis through the nicotinamide riboside (NR)-directed salvage pathway in T cells. NR inhibits murine Th17 and promotes Treg cell differentiation, in vitro, by PΑRylating histone H1.2 and causing its reduced occupancy in the Foxp3 loci and increased occupancy in the Il17a loci, leading to increased Foxp3 and decreased Il17a transcription. NR treatment suppresses disease in MRL.lpr mice and restores NAD+-dependent poly [ADP-ribose] polymerase 1 (PARP1) activity in CD4 T cells from patients with systemic lupus erythematosus (SLE), while reducing interferon (IFN)-γ and interleukin (IL)-17 production. We conclude that PPP2R2A controls the level of NAD+ through the NR-directed salvage pathway and promotes systemic autoimmunity. Translationally, NR suppresses lupus nephritis in mice and limits the production of proinflammatory cytokines by SLE T cells.

The Evolution of Hemophilia Therapeutics: An Illustrated Review.

Hemophilia is a rare genetic bleeding disorder historically associated with high morbidity and mortality. Some individuals with hemophilia suffer associated chronic joint disease, chronic pain, and other physical and mental health challenges. In the last 50 years, a better understanding of the pathophysiology of the disease has resulted in extraordinary therapeutic advances leading to enhanced quality of life and increased life expectancy. We present an illustrated review of the evolution of hemophilia treatment from the development of non-factor therapies to gene therapy.