Myelodysplasia cutis and VEXAS syndrome initially diagnosed as histiocytoid Sweet syndrome: A diagnostic pitfall.

Histiocytoid Sweet syndrome (H-SS) is a histopathological variant of Sweet syndrome (SS) defined by cutaneous infiltration of immature myeloid cells morphologically resembling histiocytes. The association of H-SS with underlying malignancy, particularly myelodysplastic syndromes, is well-established. Myelodysplasia cutis (MDS-cutis) has been proposed to describe cases historically diagnosed as H-SS but characterized by shared clonality of the myeloid infiltrate in skin and bone marrow. Therefore, identifying patients who might have MDS-cutis is critical for the management of the associated hematologic malignancy. VEXAS syndrome, an adult-onset autoinflammatory disease, should also be included in the histopathologic differential diagnosis of H-SS, as it shares clinical and pathologic features with MDS-cutis. Through the presentation of two cases, we aim to highlight the defining features and key clinical implications of MDS-cutis and VEXAS syndrome.

Motivations to engage in collective action: A latent profile analysis of refugee supporters.

What motivates people to participate in collective action? Some actions such as symbolic or online actions are often critiqued as performative allyship, motivated by personal gain rather than genuine concern for the cause. We aim to adjudicate this argument by examining the quality of motivations for acting, drawing on the insights of self-determination theory and the social identity approach. Using latent profile analysis, we examined whether there are different types of supporters of refugees based on their underlying motives. In Study 1, we surveyed supporters of Syrian refugees from six nations (N = 936) and measured autonomous and controlled motivation, pro-refugee identification and collective action. In Study 2 (N = 1994), we surveyed supporters of Ukrainian refugees in Romania, Hungary and the UK. We found 4-5 profiles in each sample and consistently found that supporters with high autonomous motivation take more action than disengaged or ambivalent supporters (low/neutral on all motives). However, contrary to the tenets of self-determination theory, those high in both autonomous and controlled motives were the most engaged. We conclude that the most committed supporters are those with multiple motives, but further research is needed on the role of controlled motivation.

Effective and safe implementation of robot-assisted donor nephrectomy by experienced laparoscopic surgeons.

BACKGROUND: In June 2021, the first robot-assisted donor nephrectomy (RADN) was performed at the Leiden University Medical Center (LUMC), the Netherlands. The goal of this study was to investigate whether this procedure has been implemented safely and efficiently. METHODS: RADN was retrospectively compared to laparoscopic donor nephrectomy (LDN) performed during the same time period (June 2021 until November 2022). Patients were assigned to RADN depending on the availability of the da Vinci robot and surgical team. The studied endpoints were postoperative complications, operative time, estimated blood loss, warm ischemic time (WIT), and postoperative pain experience. For analysis, the Student's t-test and Chi-squared test were used for, respectively, continuous and categorical data. RESULTS: Forty RADN were compared to 63 LDN. Total insufflation time was significantly longer in RADN compared to LDN (188 min (169-214) versus 172 min (144-194); p = 0.02). Additionally, WIT was also found to be significantly higher in the robot-assisted group (04:54 min vs. 04:07 min; p < 0.01). No statistical differences were found in postoperative outcomes (eGFR of the recipient at 3-month follow-up, RADN 54.08 mL/min ±18.79 vs. LDN 56.41 mL/min ±16.82; p = 0.52), pain experience, and complication rate. CONCLUSION: RADN was safely and efficiently implemented at the LUMC. It's results were not inferior to laparoscopic donor nephrectomy. Operative time and warm ischemic times were longer in RADN. This may relate to a learning curve effect. No clinically relevant effect on postoperative outcomes was observed.

Is doomscrolling related to celebrity worship? A cross-cultural study.

Building upon evidence supporting the co-occurrence of behavioural addictions, this study delved into the relationship between social media doomscrolling and celebrity worship among university student social media users in Iran and the United States. Objectives were threefold: (a) provide psychometric support for the Social Media Doomscrolling Scale (SMDS), (b) examine psychological correlates of doomscrolling and celebrity worship, and (c) explore the relationship between doomscrolling and celebrity worship. The SMDS demonstrated good psychometric properties in the US sample, like the original study of the SMDS conducted in an Iranian sample. Doomscrolling showed a positive association with future anxiety and a negative association with psychological well-being in both US and Iranian samples. Celebrity worship was positively linked with future anxiety in the Iranian and US samples. A positive correlation emerged between doomscrolling and celebrity worship in both the US and Iranian samples. This cross-cultural study offers preliminary evidence for the co-occurrence of two emerging media-related behavioural addictions.

Long-read RNA sequencing identifies region- and sex-specific C57BL/6J mouse brain mRNA isoform expression and usage.

Alternative splicing (AS) contributes to the biological heterogeneity between species, sexes, tissues, and cell types. Many diseases are either caused by alterations in AS or by alterations to AS. Therefore, measuring AS accurately and efficiently is critical for assessing molecular phenotypes, including those associated with disease. Long-read sequencing enables more accurate quantification of differentially spliced isoform expression than short-read sequencing approaches, and third-generation platforms facilitate high-throughput experiments. To assess differences in AS across the cerebellum, cortex, hippocampus, and striatum by sex, we generated and analyzed Oxford Nanopore Technologies (ONT) long-read RNA sequencing (lrRNA-Seq) C57BL/6J mouse brain cDNA libraries. From > 85 million reads that passed quality control metrics, we calculated differential gene expression (DGE), differential transcript expression (DTE), and differential transcript usage (DTU) across brain regions and by sex. We found significant DGE, DTE, and DTU across brain regions and that the cerebellum had the most differences compared to the other three regions. Additionally, we found region-specific differential splicing between sexes, with the most sex differences in DTU in the cortex and no DTU in the hippocampus. We also report on two distinct patterns of sex DTU we observed, sex-divergent and sex-specific, that could potentially help explain sex differences in the prevalence and prognosis of various neurological and psychiatric disorders in future studies. Finally, we built a Shiny web application for researchers to explore the data further. Our study provides a resource for the community; it underscores the importance of AS in biological heterogeneity and the utility of long-read sequencing to better understand AS in the brain.

Prenatal Exposure to the 1944-45 Dutch Famine and Risk for Dementia up to Age 75: An Analysis of Primary Care Data.

BACKGROUND: A poor prenatal environment adversely affects brain development. Studies investigating long-term consequences of prenatal exposure to the 1944-45 Dutch famine have shown that those exposed to famine in early gestation had poorer selective attention, smaller brain volumes, poorer brain perfusion, older appearing brains, and increased reporting of cognitive problems, all indicative of increased dementia risk. OBJECTIVE: In the current population-based study, we investigated whether dementia incidence up to age 75 was higher among individuals who had been prenatally exposed to famine. METHODS: We included men (n=6,714) and women (n=7,051) from the Nivel Primary Care Database who had been born in seven cities affected by the Dutch famine. We used Cox regression to compare dementia incidence among individuals exposed to famine during late (1,231), mid (1,083), or early gestation (601) with those unexposed (born before or conceived after the famine). RESULTS: We did not observe differences in dementia incidence for those exposed to famine in mid or early gestation compared to those unexposed. Men and women exposed to famine in late gestation had significantly lower dementia rates compared to unexposed individuals (HR 0.52 [95%CI 0.30-0.89]). Sex-specific analyses showed a lower dementia rate in women exposed to famine in late gestation (HR 0.39 [95%CI 0.17-0.86]) but not in men (HR 0.68 [95%CI 0.33-1.41]). CONCLUSION: Although prenatal exposure to the Dutch famine has previously been associated with measures of accelerated brain aging, the present population-based study did not show increased dementia incidence up to age 75 in those exposed to famine during gestation.

Digital dermatopathology implementation: Experience at a multisite academic institution.

BACKGROUND: Technology has revolutionized not only direct patient care but also diagnostic care processes. This study evaluates the transition from glass-slide microscopy to digital pathology (DP) at a multisite academic institution, using mixed methods to understand user perceptions of digitization and key productivity metrics of practice change. METHODS: Participants included dermatopathologists, pathology reporting specialists, and clinicians. Electronic surveys and individual or group interviews included questions related to technology comfort, trust in DP, and rationale for DP adoption. Case volumes and turnaround times were abstracted from the electronic health record from Qtr 4 2020 to Qtr 1 2023 (inclusive). Data were analyzed descriptively, while interviews were analyzed using methods of content analysis. RESULTS: Thirty-four staff completed surveys and 22 participated in an interview. Case volumes and diagnostic turnaround time did not differ across the institution during or after implementation timelines (p = 0.084; p = 0.133, respectively). 82.5% (28/34) of staff agreed that DP improved the sign-out experience, with accessibility, ergonomics, and annotation features described as key factors. Clinicians reported positive perspectives of DP impact on patient safety and interdisciplinary collaboration. CONCLUSIONS: Our study demonstrates that DP has a high acceptance rate, does not adversely impact productivity, and may improve patient safety and care collaboration.

Ethanolamine metabolism through two genetically distinct loci enables Klebsiella pneumoniae to bypass nutritional competition in the gut.

Successful microbial colonization of the gastrointestinal (GI) tract hinges on an organism's ability to overcome the intense competition for nutrients in the gut between the host and the resident gut microbiome. Enteric pathogens can exploit ethanolamine (EA) in the gut to bypass nutrient competition. However, Klebsiella pneumoniae (K. pneumoniae) is an asymptomatic gut colonizer and, unlike well-studied enteric pathogens, harbors two genetically distinct ethanolamine utilization (eut) loci. Our investigation uncovered unique roles for each eut locus depending on EA utilization as a carbon or nitrogen source. Murine gut colonization studies demonstrated the necessity of both eut loci in the presence of intact gut microbiota for robust GI colonization by K. pneumoniae. Additionally, while some Escherichia coli gut isolates could metabolize EA, other commensals were incapable, suggesting that EA metabolism likely provides K. pneumoniae a selective advantage in gut colonization. Molecular and bioinformatic analyses unveiled the conservation of two eut loci among K. pneumoniae and a subset of the related taxa in the K. pneumoniae species complex, with the NtrC-RpoN regulatory cascade playing a pivotal role in regulation. These findings identify EA metabolism as a critical driver of K. pneumoniae niche establishment in the gut and propose microbial metabolism as a potential therapeutic avenue to combat K. pneumoniae infections.

Stretch-shortening cycles protect against the age-related loss of power generation in rat single muscle fibres.

Aging is associated with impaired strength and power during isometric and shortening contractions, however, during lengthening (i.e., eccentric) contractions, strength is maintained. During daily movements, muscles undergo stretch-shortening cycles (SSCs). It is unclear whether the age-related maintenance of eccentric strength offsets age-related impairments in power generation during SSCs owing to the utilization of elastic energy or other cross-bridge based mechanisms. Here we investigated how aging influences SSC performance at the single muscle fibre level and whether performing active lengthening prior to shortening protects against age-related impairments in power generation. Single muscle fibres from the psoas major of young (∼8 months; n = 31 fibres) and old (∼32 months; n = 41 fibres) male F344BN rats were dissected and chemically permeabilized. Fibres were mounted between a force transducer and length controller and maximally activated (pCa 4.5). For SSCs, fibres were lengthened from average sarcomere lengths of 2.5 to 3.0 µm and immediately shortened back to 2.5 µm at both fast and slow (0.15 and 0.60 Lo/s) lengthening and shortening speeds. The magnitude of the SSC effect was calculated by comparing work and power during shortening to an active shortening contraction not preceded by active lengthening. Absolute isometric force was ∼37 % lower in old compared to young rat single muscle fibres, however, when normalized to cross-sectional area (CSA), there was no longer a significant difference in isometric force between age groups, meanwhile there was an ∼50 % reduction in absolute power in old as compared with young. We demonstrated that SSCs significantly increased power production (75-110 %) in both young and old fibres when shortening occurred at a fast speed and provided protection against power-loss with aging. Therefore, in older adults during everyday movements, power is likely 'protected' in part due to the stretch-shortening cycle as compared with isolated shortening contractions.

"More support, less distress?": Examining the role of social norms in alleviating practitioners' psychological distress in the context of assisted dying services.

This study explores how providing assisted dying services affects the psychological distress of practitioners. It investigates the influence of professional norms that endorse such services within their field. Study 1 included veterinarians (N = 137, 75.2% female, Mage = 43.1 years, SDage = 12.7 years), and Study 2 health practitioner students (N = 386, 71.0% female, Mage = 21.0 years, SDage = 14.4 years). In both studies, participants indicated their degree of psychological distress following exposure to scenarios depicting assisted dying services that were relevant to their respective situations. In Study 1, we found that higher willingness to perform animal euthanasia was associated with lower distress, as were supportive norms. In Study 2, a negative association between a greater willingness to perform euthanasia and lower psychological distress occurred only when the provision of such services was supported by professional norms. In conclusion, psychological distress is buffered by supportive professional norms.

Fusion-driven cutaneous and superficial mesenchymal and adnexal tumors-A clinicopathologic and molecular study of 15 cases, including a novel case of ACTB::ZMIZ2-rearranged adnexal carcinoma.

BACKGROUND: While the list of fusion-driven soft tissue neoplasms is expanding rapidly, their importance among cutaneous and superficial mesenchymal and adnexal neoplasms remains poorly understood. This challenge is especially evident in cases with ambiguous histopathology that are difficult to classify based on morphology. AIMS: Our goal was to investigate the benefits of next-generation sequencing in diagnosing complex cutaneous neoplasms. MATERIALS & METHODS: Departmental archives were searched for fusion-driven cutaneous neoplasms. Slides were retrieved and clinical information including follow-up was obtained. RESULTS: Fifteen cases occurred in eight female and seven male patients, with a median age of 26 years (range: 1-83) at diagnosis. Tumors involved the extremities (9), scalp (5), and head and neck (1). Predominant features included myoepithelial (5), nested spindled with clear cytoplasm (2), atypical adnexal/squamoid (2), small round blue cell (2), cellular spindled (3), and fibrohistiocytic morphology (1). Most frequently encountered fusions involved EWSR1 (6) fused to ERG (1), FLI1 (1), CREB1 (2), CREM (1), PBX3 (1), followed by PLAG1 (4) with LIFR (2), TRPS1 (1) and CHCHD7. Additional fusions encountered were YAP1::NUTM1, EML4::ALK, SS18::SSX1 (2), and a novel fusion: ACTB::ZMIZ2. Integration of histologic features and molecular findings led to final diagnoses of primary cutaneous Ewing sarcoma (2), soft tissue myoepithelioma (4), cutaneous syncytial myoepithelioma (1), cutaneous adnexal carcinoma (1), porocarcinoma (1), inflammatory myofibroblastic tumor (1), synovial sarcoma (2), clear cell sarcoma (2), and angiomatoid fibrous histiocytoma (1). DISCUSSION AND CONCLUSION: Our results show that fusion testing can be a helpful diagnostic tool, especially in cases with unusual or uncommon morphology in superficial sites. Furthermore, it can allow for the identification of potential therapeutic targets in some instances.

Intra-colony spatial variance of oxyregulation and hypoxic thresholds for key Acropora coral species.

Oxygen (O2) availability is essential for healthy coral reef functioning, yet how continued loss of dissolved O2 via ocean deoxygenation impacts performance of reef building corals remains unclear. Here, we examine how intra-colony spatial geometry of important Great Barrier Reef (GBR) coral species Acropora may influence variation in hypoxic thresholds for upregulation, to better understand capacity to tolerate future reductions in O2 availability. We first evaluate the application of more streamlined models used to parameterise Hypoxia Response Curve data, models that have been used historically to identify variable oxyregulatory capacity. Using closed-system respirometry to analyse O2 drawdown rate, we show that a two-parameter model returns similar outputs as previous 12th-order models for descriptive statistics such as the average oxyregulation capacity (Tpos) and the ambient O2 level at which the coral exerts maximum regulation effort (Pcmax), for diverse Acropora species. Following an experiment to evaluate whether stress induced by coral fragmentation for respirometry affected O2 drawdown rate, we subsequently identify differences in hypoxic response for the interior and exterior colony locations for the species Acropora abrotanoides, Acropora cf. microphthalma and Acropora elseyi. Average regulation capacity across species was greater (0.78-1.03 ± SE 0.08) at the colony interior compared with exterior (0.60-0.85 ± SE 0.08). Moreover, Pcmax occurred at relatively low pO2 of <30% (±1.24; SE) air saturation for all species, across the colony. When compared against ambient O2 availability, these factors corresponded to differences in mean intra-colony oxyregulation, suggesting that lower variation in dissolved O2 corresponds with higher capacity for oxyregulation. Collectively, our data show that intra-colony spatial variation affects coral oxyregulation hypoxic thresholds, potentially driving differences in Acropora oxyregulatory capacity.

Local and Systemic Effects of Bioactive Food Ingredients: Is There a Role for Functional Foods to Prime the Gut for Resilience?

Scientific advancements in understanding the impact of bioactive components in foods on the gut microbiota and wider physiology create opportunities for designing targeted functional foods. The selection of bioactive ingredients with potential local or systemic effects holds promise for influencing overall well-being. An abundance of studies demonstrate that gut microbiota show compositional changes that correlate age and disease. However, navigating this field, especially for non-experts, remains challenging, given the abundance of bioactive ingredients with varying levels of scientific substantiation. This narrative review addresses the current knowledge on the potential impact of the gut microbiota on host health, emphasizing gut microbiota resilience. It explores evidence related to the extensive gut health benefits of popular dietary components and bioactive ingredients, such as phytochemicals, fermented greens, fibres, prebiotics, probiotics, and postbiotics. Importantly, this review distinguishes between the potential local and systemic effects of both popular and emerging ingredients. Additionally, it highlights how dietary hormesis promotes gut microbiota resilience, fostering better adaptation to stress-a hallmark of health. By integrating examples of bioactives, this review provides insights to guide the design of evidence-based functional foods aimed at priming the gut for resilience.

Viral infections in pregnancy and impact on offspring neurodevelopment: mechanisms and lessons learned.

Pregnant individuals with viral illness may experience significant morbidity and have higher rates of pregnancy and neonatal complications. With the growing number of viral infections and new viral pandemics, it is important to examine the effects of infection during pregnancy on both the gestational parent and the offspring. Febrile illness and inflammation during pregnancy are correlated with risk for autism, attention deficit/hyperactivity disorder, and developmental delay in the offspring in human and animal models. Historical viral epidemics had limited follow-up of the offspring of affected pregnancies. Infants exposed to seasonal influenza and the 2009 H1N1 influenza virus experienced increased risks of congenital malformations and neuropsychiatric conditions. Zika virus exposure in utero can lead to a spectrum of abnormalities, ranging from severe microcephaly to neurodevelopmental delays which may appear later in childhood and in the absence of Zika-related birth defects. Vertical infection with severe acute respiratory syndrome coronavirus-2 has occurred rarely, but there appears to be a risk for developmental delays in the infants with antenatal exposure. Determining how illness from infection during pregnancy and specific viral pathogens can affect pregnancy and neurodevelopmental outcomes of offspring can better prepare the community to care for these children as they grow. IMPACT: Viral infections have impacted pregnant people and their offspring throughout history. Antenatal exposure to maternal fever and inflammation may increase risk of developmental and neurobehavioral disorders in infants and children. The recent SARS-CoV-2 pandemic stresses the importance of longitudinal studies to follow pregnancies and offspring neurodevelopment.

Do conspiracy beliefs fuel support for reactionary social movements? Effects of misbeliefs on actions to oppose lockdown and to "stop the steal".

Pundits have speculated that the spread of conspiracies and misinformation (termed "misbeliefs") is leading to a resurgence of right-wing, reactionary movements. However, the current empirical picture regarding the relationship between misbeliefs and collective action is mixed. We help clarify these associations by using two waves of data collected during the COVID-19 Pandemic (in Australia, N = 519, and the United States, N = 510) and democratic elections (in New Zealand N = 603, and the United States N = 609) to examine the effects of misbeliefs on support for reactionary movements (e.g., anti-lockdown protests, Study 1; anti-election protests, Study 2). Results reveal that within-person changes in misbeliefs correlate positively with support for reactionary collective action both directly (Studies 1-2) and indirectly by shaping the legitimacy of the authority (Study 1b). The relationship between misbelief and legitimacy is, however, conditioned by the stance of the authority in question: the association is positive when authorities endorse misbeliefs (Study 1a) and negative when they do not (Study 1b). Thus, the relationship between conspiracy beliefs and action hinges upon the alignment of the content of the conspiracy and the goals of the collective action.

Algal symbiont diversity in Acropora muricata from the extreme reef of Bouraké associated with resistance to coral bleaching.

Widespread coral bleaching has generally been linked to high water temperatures at larger geographic scales. However, the bleaching response can be highly variable among individual of the same species, between different species, and across localities; what causes this variability remains unresolved. Here, we tracked bleached and non-bleached colonies of Acropora muricata to see if they recovered or died following a stress event inside the semi-enclosed lagoon of Bouraké (New Caledonia), where corals are long-term acclimatized to extreme conditions of temperature, pH and dissolved oxygen, and at a nearby control reef where conditions are more benign. We describe Symbiodiniaceae community changes based on next-generation sequencing of the ITS2 marker, metabolic responses, and energetic reserve measures (12 physiological traits evaluated) during the La Niña warm and rainy summer in 2021. Widespread coral bleaching (score 1 and 2 on the coral colour health chart) was observed only in Bouraké, likely due to the combination of the high temperatures (up to 32°C) and heavy rain. All colonies (i.e., Bouraké and reference site) associated predominantly with Symbiodinaceae from the genera Cladocopium. Unbleached colonies in Bouraké had a specific ITS2-type profile (proxies for Symbiodiniaceae genotypes), while the bleached colonies in Bouraké had the same ITS2-type profile of the reef control colonies during the stress event. After four months, the few bleached colonies that survived in Bouraké (B2) acquired the same ITS2 type profiles of the unbleached colonies in Bouraké. In terms of physiological performances, all bleached corals showed metabolic depression (e.g., Pgross and Rdark). In contrast, unbleached colonies in Bouraké maintained higher metabolic rates and energetic reserves compared to control corals. Our study suggests that Acropora muricata enhanced their resistance to bleaching thanks to specific Symbiodiniaceae associations, while energetic reserves may increase their resilience after stress.

Use of Genomics to Develop Novel Therapeutics and Personalize Hypertension Therapy.

Hypertension is a prevalent public health problem, contributing to >10 million deaths annually. Though multiple therapeutics exist, many patients suffer from treatment-resistant hypertension or try several medications before achieving blood pressure control. Genomic advances offer mechanistic understanding of blood pressure variability, therapeutic targets, therapeutic response, and promise a stratified approach to treatment of primary hypertension. Cyclic guanosine monophosphate augmentation, aldosterone synthase inhibitors, and angiotensinogen blockade with silencing RNA and antisense therapies are among the promising novel approaches. Pharmacogenomic studies have also been done to explore the genetic bases underpinning interindividual variability in response to existing therapeutics. A polygenic approach using risk scores is likely to be the next frontier in stratifying responses to existing therapeutics.