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Abstract Background Huntington's disease (HD) is marked by irreversible loss of neuronal function for which currently no availability for disease‐modifying treatment exists. Advances in the understanding of disease progression can aid biomarker development, which in turn can accelerate therapeutic discovery. Methods We characterised the progression of altered dynamics of whole‐brain network states in the zQ175DN mouse model of HD using a dynamic functional connectivity (FC) approach to resting‐state fMRI and identified quasi‐periodic patterns (QPPs) of brain activity constituting the most prominent resting‐state networks. Results The occurrence of the normative QPPs, as observed in healthy controls, was reduced in the HD model as the phenotype progressed. This uncovered progressive cessation of synchronous brain activity with phenotypic progression, which is not observed with the conventional static FC approaches. To better understand the potential underlying cause of the observed changes in these brain states, we further assessed how mutant huntingtin (mHTT) protein deposition affects astrocytes and pericytes – one of the most important effectors of neurovascular coupling, along phenotypic progression. Increased cell‐type dependent mHTT deposition was observed at the age of onset of motor anomalies, in the caudate putamen, somatosensory and motor cortex, regions that are prominently involved in HD pathology as seen in humans. Conclusion Our findings provide meaningful insights into the development and progression of altered functional brain dynamics in this HD model and open new avenues in assessing the dynamics of whole brain states, through QPPs, in clinical HD research. Highlights Hyperactivity in the LCN‐linked regions within short QPPs observed before motor impairment onset. DMLN QPP presents a progressive decrease in DMLN activity and occurrence along HD‐like phenotype development. Breakdown of the LCN DMLN state flux at motor onset leads to a subsequent absence of the LCN DMLN QPP at an advanced HD‐like stage.

Abstract The expansion of wildlife ranching has been broadly linked to conservation benefits, job creation, and economic contributions. However, a more nuanced understanding of the socioeconomic contributions of wildlife ranching accounting for the enterprise diversity in the sector remains a major limitation to assessing its potential to contribute to sustainable development. We assessed several important socioeconomic contributions of diverse wildlife‐based business models, defined by their main revenue‐generating activities, within the South African wildlife ranching industry, and the financial viability of these models. Owners and managers of privately‐owned wildlife ranches and conventional agricultural farms (for comparative purposes) were interviewed in the Eastern Cape (112 ranches; 24 farms) and Limpopo provinces (152 ranches; 4 farms). We used a hierarchical clustering analysis to delineate six wildlife ranching business models. These included three more specialized models: ecotourism, trophy hunting, and wildlife breeding, and three more mixed models: mixed hunting (i.e., both meat and trophy hunting), mixed wildlife‐agriculture, and trophy hunting‐game meat. In general, ecotourism‐focused ranches employed more people in total and per hectare (median = 23 jobs; 0.008/ha), and a higher proportion of women and skilled employees (41% and 45% of employees, respectively) than the other ranching models (median = 7–21 jobs; 0.002–0.005/ha) and conventional agriculture (median = 12 jobs; 0.004/ha). Trophy hunting‐focused ranches employed the second highest number of people per hectare (0.006) although on average, a third of these jobs were seasonal. Trophy hunting ranches tended to be more profitable (median profit margin = 33%) than ecotourism (−10%), wildlife breeding (0%) and mixed‐hunting (12%) ranches, though ecotourism ranches showed very high variability (interquartile range = −32% to 14%). These findings advance our understanding of the distinct socioeconomic contributions of diverse wildlife ranches, which benefits policy discourse and implementation surrounding the industry, promoting improved industry sustainability and inclusive growth.

Abstract To allow sea urchin aquaculture to achieve its intended scale, efficient and precise methods for measuring large numbers of urchins in commercial‐scale operations are needed. Current protocols for measuring urchin test (shell) dimensions and mass are time‐consuming and prone to high measurement error, thus inconvenient in research and impractical in a commercial context. This study investigates and compares various measurement methods with a newly developed computer vision approach developed in this study, to establish a single protocol using precise, efficient and accessible methodology for measuring live urchins. We show that urchin wet mass can vary up to 8.73% depending on time out of water; this is significantly reduced to an average of 0.1% change by allowing urchins to drip‐dry for at least 90 s prior to weighing. We found the conventional vernier calliper method used to measure urchin dimensions to be both time‐consuming and imprecise (mean coefficient of variation (CV) of 2.41% for Tripneustes gratilla). Conversely, the computer vision programme we developed measures with higher precision (mean CV of 1.55% for T. gratilla) and is considerably faster. The software uses a series of hue saturation value filters, edge detection algorithms and distortions to measure the diameter of the test (excluding spines) of multiple urchins at once. The software is open‐source, and the protocol does not require specialised equipment (can be performed with a mobile phone camera). When the computer vision application is combined with the simple procedures described in this paper, to reduce measurement inaccuracies, urchin wet mass and diameter can be more efficiently and precisely determined. For a larger scale context, this software could easily be incorporated into various tools, such as a grading machine, to completely automate various farm processes. As such, this study has potential to assist urchin data collection in both research and commercial contexts.

Abstract Widespread species experience a variety of climates across their distribution, which can structure their thermal tolerance, and ultimately, responses to climate change. For ectotherms, activity is highly dependent on temperature, its variability and availability of favourable microclimates. Thermal exposure and tolerance may be structured by the availability and heterogeneity of microclimates for species living along temperature and/or precipitation gradients – but patterns and mechanisms underlying such gradients are poorly understood. We measured critical thermal limits (CTmax and CTmin) for five populations of two sympatric lizard species, a nocturnal gecko (Chondrodactylus bibronii) and a diurnal skink (Trachylepis variegata) and recorded hourly thermal variation for a year in three types of microclimate relevant to the activity of lizards (crevice, full sun and partial shade) for six sites across a precipitation gradient. Using a combination of physiological and modelling approaches, we derived warming tolerance for the present and the end of the century. In the present climate, we found an overall wider thermal tolerance for the nocturnal species relative to the diurnal species, and no variation in CTmax but variable CTmin along the precipitation gradient for both species. However, warming tolerances varied significantly over the course of the day, across months and microhabitats. The diurnal skink was most restricted in its daily activity in the three driest sites with up to six daily hours of restricted activity in the open (i.e. outside refugia) during the summer months, while the impacts for the nocturnal gecko were less severe, due to its higher CTmax and night activity. With climate change, lizards will experience more months where activity is restricted and increased exposure to high temperatures even within the more sheltered microhabitats. Together our results highlight the importance of considering the relevant spatiotemporal scale and habitat for understanding the thermal exposure of diurnal and nocturnal species.

Abstract Lactobacillus rhamnosus GG (LGG), the well‐characterized human‐derived probiotic strain, possesses excellent properties in the maintenance of intestinal homeostasis, immunoregulation and defense against gastrointestinal pathogens in mammals. Here, we demonstrate that the SpaC pilin of LGG causes intestinal epithelium injury by inducing cell pyroptosis and gut microbial dysbiosis in zebrafish. Dietary SpaC activates Caspase‐3−GSDMEa pathways in the intestinal epithelium, promotes intestinal pyroptosis and increases lipopolysaccharide (LPS)‐producing gut microbes in zebrafish. The increased LPS subsequently activates Gaspy2−GSDMEb pyroptosis pathway. Further analysis reveals the Caspase‐3−GSDMEa pyroptosis is initiated by the species‐specific recognition of SpaC by TLR4ba, which accounts for the species‐specificity of the SpaC‐inducing intestinal pyroptosis in zebrafish. The observed pyroptosis‐driven gut injury and microbial dysbiosis by LGG in zebrafish suggest that host‐specific beneficial/harmful mechanisms are critical safety issues when applying probiotics derived from other host species and need more attention.

Abstract Aims The aim of this study is to evaluate the nurses' experiences with the Nursing Crisis Meetings and to identify nurses' needs regarding the future governance structure. Design Qualitative study. Methods Two focus groups were conducted in February 2022 with participants of the Nursing Crisis Meetings (N = 15). We used thematic analysis to describe themes. Results We identified five themes: opportunity to speak up, call for nursing leadership, call for control over practice and autonomy, development of a governance infrastructure and development of the professional nurse role. Conclusion Nurses experienced the Nursing Crisis Meetings to be a positive and empowering infrastructure, which facilitates the unique opportunity to speak up and share experiences and concerns. This new infrastructure is a promising strategy to engage nurses during a pandemic and to build on a professional governance structure. Impact This paper highlights the need for nurses to speak up and be engaged during the COVID‐19 pandemic and gives a practical example of how to put this infrastructure into practice.

Radiotherapy is the standard of care for breast cancer. However, surviving radioresistant cells can repopulate following treatment and provoke relapse. Better understanding of the molecular mechanisms of radiation resistance may help to improve treatment of radioresistant tumours. To emulate radiation therapy at the cellular level, we exposed MCF7 breast cancer cells to daily radiation doses of 2 Gy up to an accumulated dose of 20 Gy. Fractionally irradiated cells (FIR20) displayed increased clonogenic survival and population doubling time as compared with age‐matched sham‐irradiated cells and untreated parental MCF7 cells. RNA‐sequencing revealed a core signature of 229 mRNAs and 7 circular RNAs of which the expression was significantly altered in FIR20 cells. Dysregulation of several top genes was mirrored at the protein level. The FIR20 cell transcriptome overlapped significantly with canonical radiation response signatures and demonstrated a remarkable commonality with radiation and endocrine therapy resistance expression profiles, suggesting crosstalk between both acquired resistance pathways, as indicated by reduced sensitivity to tamoxifen cytotoxicity of FIR20 cells. Using predictive analyses and functional enrichment, we identified a gene‐regulatory network that promotes stemness and inflammatory signalling in FIR20 cells. We propose that these phenotypic traits render breast cancer cells more radioresistant but may at the same time serve as potential targets for combination therapies.

Background Coronary flow reserve (CFR) and microvascular resistance reserve (MRR) are physiological parameters to assess coronary microvascular dysfunction. CFR and MRR can be assessed using bolus or continuous thermodilution, and the correlation between these methods has not been clarified. Furthermore, their association with angina and quality of life is unknown. Methods and Results In total, 246 consecutive patients with angina and nonobstructive coronary arteries from the multicenter Netherlands Registry of Invasive Coronary Vasomotor Function Testing (NL‐CFT) were investigated. The 36‐item Short Form Health Survey Quality of Life and Seattle Angina questionnaires were completed by 153 patients before the invasive measurements. CFR and MRR were measured consecutively with bolus and continuous thermodilution. Mean continuous thermodilution‐derived coronary flow reserve (CFRabs) was significantly lower than mean bolus thermodilution‐derived coronary flow reserve (CFRbolus) (2.6±1.0 versus 3.5±1.8; P

Abstract Benzophenones are widely supplemented in personal care products, but little is known about its neurodevelopmental toxicity. The previous epidemiological study discovered a negative correlation between maternal exposure to a benzophenone metabolite 4‐hydroxybenzophenone (4HBP) and child's neurodevelopment, yet the causal relationship and detailed mechanism remain to be defined. Here, it is reported that prenatal, but not postnatal, exposure to environmentally relevant level of 4HBP impairs hippocampus development and causes cognitive dysfunction in offspring mice. Transcriptomic analyses reveal that 4HBP induces the endoplasmic reticulum stress‐induced apoptotic signaling and inflammatory response in hippocampal neural stem cells. Mechanistically, 4HBP exposure activates protein kinase R‐like ER kinase (PERK) signaling, which induces CHOP, inhibits IκB translation, and transactivates p65, thereby promoting inflammation and apoptosis on multiple levels. Importantly, genetic or pharmacological inhibition of PERK pathway significantly attenuates 4HBP‐induced NFκB signaling and neurodevelopmental abnormalities in mice and in a human brain organoid model. The study uncovers the neurodevelopmental toxicity of BP and cautions its exposure during pregnancy.

Background/Purpose. We aimed to investigate the influence of the sampling site on the variability of ACT measurement. Activated clotting time (ACT) has been used for decades in cardiac surgery and interventional cardiology to assess unfractionated heparin activity. However, standardized protocols for the use of ACT measurement in the catheterization laboratory are lacking. Methods/Materials. After elective cardiac catheterization, ACT measurements were collected in simultaneously obtained blood samples from three different sample sites: the arterial catheter, arterial sheath, and peripheral intravenous line. Measurements were performed using the i-Stat® device (Abbott, Princeton, NJ, USA). The study was conducted with approval of the local medical ethical committee. Results. In 100 patients (mean age 67.1, 65% male), no significant differences were observed in ACT values obtained from the guiding catheter and arterial sheath (mean difference (MD) −18.3 s; standard deviation (SD) 96 s; P=0.067). Contrarily, ACT values obtained from the intravenous line were significantly lower as compared to values obtained from the guiding catheter (MD 25.7 s; SD 75.5; P=0.003) and arterial sheath (MD 39 s; SD 102.8; P

Abstract Private land conservation areas (PLCAs) have become critical for achieving global conservation goals, but we lack understanding of how and when these areas respond to global pressures and opportunities. In southern Africa, where many PLCAs rely on trophy hunting as an income‐generating strategy, a potential ban on trophy hunting locally or abroad holds unknown consequences for the future conservation of these lands. In this study, we investigate the consequences of a potential trophy hunting ban in PLCAs in two biodiversity hotspots in South Africa's Eastern and Western Cape provinces. We used semistructured interviews with PLCA managers and owners to elicit perceived impacts of an internationally imposed trophy hunting ban on conservation activities in PLCAs, and to probe alternative viable land uses. The majority of interviewees believed that both the economic viability of their PLCA and biodiversity would be lost following a hunting ban. Owners would primarily consider transitioning to ecotourism or livestock farming, but these options were constrained by the social‐ecological context of their PLCA (e.g., competition with other PLCAs, ecological viability of farming). Our results suggest that a trophy hunting ban may have many unintended consequences for biodiversity conservation, national economies, and the livelihoods of PLCA owners and employees. Along with similar social‐ecological studies in other areas and contexts, our work can inform policy decisions around global trophy hunting regulation.

Abstract Views that protected area (PA) expansion relies predominantly on land purchased by government are increasingly being challenged. The inclusion of privately owned PAs (PPAs) in national conservation strategies is now commonplace, but little is known about their long‐term persistence and how it compares to that of state‐owned PAs. We undertook the first long‐term assessment of the dynamics of a national system of terrestrial PPAs, assessing its growth, as well as its resilience to downgrading, downsizing, and degazettement (PADDD). Between 1926 and 2018, 6.2% of all private nature reserves established in South Africa were degazetted, compared to 2.2% of state‐owned nature reserves. Privately owned PA growth exceeded that of state‐owned PAs. Trends in PA establishment differed between privately owned and state‐owned PAs, reflecting different legislative, political, and economic events. Our findings highlight the value of enabling legislative environments to facilitate PPA establishment, and demonstrate the potential of PPAs as a long‐term conservation strategy.

Abstract Metal–organic frameworks (MOFs) are emerging materials for luminescent and photochemical applications. Armed with femto to millisecond spectroscopies, and fluorescence microscopy, the photobehaviors of two Ce‐based MOFs are unravelled: Ce‐NU‐1000 and Ce‐CAU‐24‐TBAPy. It is observed that both MOFs show ligand‐to‐cluster charge transfer reactions in ≈100 and ≈70 fs for Ce‐NU‐1000 and Ce‐CAU‐24‐TBAPy, respectively. The formed charge separated states, resulting in electron and hole generation, recombine in different times for each MOF, being longer in Ce‐CAU‐24‐TBAPy: 1.59 and 13.43 µs than in Ce‐NU‐1000: 0.64 and 4.91 µs. The linkers in both MOFs also undergo a very fast intramolecular charge transfer reaction in ≈160 fs. Furthermore, the Ce‐NU‐1000 MOF reveals excimer formation in 50 ps, and lifetime of ≈14 ns. The lack of this interlinkers event in Ce‐CAU‐24‐TBAPy arises from topological restriction and demonstrates the structural differences between the two frameworks. Single‐crystal fluorescence microscopy of Ce‐CAU‐24‐TBAPy shows the presence of a random distribution of defects along the whole crystal, and their impact on the observed photobehavior. These findings reflect the effect of linkers topology and metal clusters orientations on the outcome of electronic excitation of reticular structure, key to their applicability in different fields of science and technology, such as photocatalysis and photonics.

Abstract This Technical Report describes the activities developed in the scope of the EU‐FORA Fellowship, within the work programme of risk assessment (RA) of exotic disease incursion and spread, developed at Wageningen Bioveterinary Research (WBVR). The programme focused on the work carried out in the Generic risk assessment for introduction of animal diseases (G‐RAID) project, which brings together a number of different generic RA tools from multiple European partners. The aim of the fellowship was to gain understanding of veterinary import risk assessment by using different RA tools and to learn how different algorithms can be used to calculate disease incursion risks. G‐RAID's tools cover a wide range of RA methodologies; from purely qualitative, to semi‐quantitative and fully stochastic quantitative methods, which allowed the fellow to understand a variety of algorithms used to produce the final risk estimate. The fellowship programme provided the fellow with the chance to learn in detail about how generic RAs are performed across Europe, understanding how to deal with the uncertainty and variability involved in RAs and the potential problems of data availability and reliability. The fellow made an inventory of publicly available databases on disease occurrence and international trade that could be used for import RA and assessed their quality and usefulness for the different generic RA tools. The programme also provided the fellow the opportunity to perform several import risk assessments using the RA tools of G‐RAID. She completed a RA on African swine fever using the MINTRISK model developed by WBVR. Furthermore, she assessed the risk of foot and mouth disease introduction using the Rapid Risk Assessment Tool (RRAT) model developed by WBVR and the COMPARE model developed by the Animal and Plant Health Agency (APHA). To this end, the fellow completed a short‐term visit to APHA, enabling her to have additional training in quantitative RA and to expand her professional network in this area.

Background Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage in elderly adults; however, presymptomatic diagnosis of CAA is difficult. Hereditary cerebral hemorrhage with amyloidosis–Dutch type (HCHWA‐D) is a rare autosomal‐dominant disease that leads to pathology similar to sporadic CAA. Presymptomatic HCHWA‐D mutation carriers provide a unique opportunity to study CAA‐related changes before any symptoms have occurred. In this study we investigated early CAA‐related alterations in the white matter. Methods and Results We investigated diffusion magnetic resonance imaging (dMRI) data for 15 symptomatic and 11 presymptomatic HCHWA‐D mutation carriers and 30 noncarrier control participants using 4 different approaches. We looked at (1) the relation between age and global dMRI measures for mutation carriers versus controls, (2) voxel‐wise dMRI, (3) independent component‐clustered dMRI measures, and (4) structural connectomics between presymptomatic or symptomatic carriers and controls. Fractional anisotropy decreased, and mean diffusivity and peak width of the skeletonized mean diffusivity increased significantly over age for mutation carriers compared with controls. In addition, voxel‐wise and independent component‐wise fractional anisotropy, and mean diffusivity, and structural connectomics were significantly different between HCHWA‐D patients and control participants, mainly in the periventricular frontal and occipital regions and in the occipital lobe. We found no significant differences between presymptomatic carriers and control participants. Conclusions The dMRI technique is sensitive in detecting alterations in symptomatic HCHWA‐d carriers but did not show alterations in presymptomatic carriers. This result indicates that dMRI may be less suitable for identifying early white matter changes in CAA.

Abstract. Phosphatidylinositol 3-kinase-delta (PI3Kδ) signaling is critical for proliferation, survival, homing, and tissue retention of malignant B cells. Idelalisib, a selective oral inhibitor of PI3Kδ, has shown considerable single-agent activity in patients with heavily pretreated chronic lymphocytic leukemia (CLL). This study evaluated the safety and clinical activity of idelalisib in combination with bendamustine (IB) or rituximab (IR) or both (IBR) in patients with relapsed or refractory (R/R) CLL. Idelalisib was given continuously at 100 or 150 mg twice daily in combination with rituximab (375 mg/m2 weekly × 8 doses), bendamustine (70 or 90 mg/m2, days 1 and 2 every 4 weeks × 6 cycles) or BR (rituximab, 375 mg/m2 every 4 weeks and bendamustine, 70 mg/m2, days 1 and 2 every 4 weeks × 6 cycles). The primary endpoint was safety; secondary endpoints included overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS). Fifty-two patients (median age 64 years) with a median of 3 prior therapies were enrolled. ORR was 84.6% (89.5% IR group, 77.8% IB group, and 86.7% IBR group). The overall median PFS was 25.6 months, and median DOR was 26.6 months. The most common grade ≥3 adverse events (≥10% of patients) were pneumonia (19.2%), diarrhea (13.5%), and febrile neutropenia (17.3%). Idelalisib-based combination therapy with bendamustine and/or rituximab was highly active, resulting in durable tumor control in patients with heavily pretreated R/R CLL. However, its tolerability profile suggests that these regimens should be used cautiously in this patient population. ClinicalTrials.gov ID: NCT01088048.

BackgroundIntestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine‐N‐oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge. Methods and ResultsWe performed a double‐blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan‐donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d6‐choline and d3‐carnitine (eg, labeled and unlabeled TMAO in plasma and 24‐hour urine after oral ingestion of 250 mg of both isotope‐labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. 18F‐fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan‐donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan‐donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic 18F‐fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells. ConclusionsSingle lean vegan‐donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation. Clinical Trial RegistrationURL: http://www.trialregister.nl. Unique identifier: NTR 4338.

Escherichia (E.) coli is the most common causative pathogen in peritonitis, the second most common cause of sepsis. Granzymes (gzms) are serine proteases traditionally implicated in cytotoxicity and, more recently, in the inflammatory response. We here sought to investigate the role of gzms in the host response to E. coli-induced peritonitis and sepsis in vivo. For this purpose, we used a murine model of E. coli intraperitoneal infection, resembling the clinical condition commonly associated with septic peritonitis by this bacterium, in wild-type and gzmA-deficient (gzmA−/−), gzmB−/−, and gzmAxB−/−mice. GzmA and gzmB were predominantly expressed by natural killer cells, and during abdominal sepsis, the percentage of these cells expressing gzms in peritoneal lavage fluid decreased, while the amount of expression in the gzm+ cells increased. Deficiency of gzmA and/or gzmB was associated with increased bacterial loads, especially in the case of gzmB at the primary site of infection at late stage sepsis. While gzm deficiency did not impact neutrophil recruitment into the abdominal cavity, it was accompanied by enhanced nucleosome release at the primary site of infection, earlier hepatic necrosis, and more renal dysfunction. These results suggest that gzms influence bacterial growth and the host inflammatory response during abdominal sepsis caused by E. coli.

Introduction HIV‐induced changes in cytokine responses to bacteria may influence susceptibility to bacterial infections and the consequent inflammatory response. Methods We examined the impact of HIV on whole blood responsiveness to bacterial stimulation in asymptomatic subjects and patients with bacterial bloodstream infection (BSI). Whole blood was stimulated ex vivo with two bacterial Toll‐like receptor agonists (lipopolysaccharide and lipoteichoic acid) and two pathogens (Streptococcus pneumoniae and non‐typhoidal Salmonella), which are relevant in HIV‐positive patients. Production of interferon‐γ, tumour necrosis factor‐α, interleukin‐1β and interleukin‐6 was used as a read‐out. Results In asymptomatic subjects, HIV infection was associated with reduced interferon‐γ, release after stimulation and priming of the pro‐inflammatory cytokine response to non‐typhoidal Salmonella. In patients with BSI, we found no such priming effect, nor was there evidence for more profound sepsis‐induced immunosuppression in BSI patients with HIV co‐infection. Conclusions These results suggest a complex effect of HIV on leukocyte responses to bacteria. However, in patients with sepsis, leukocyte responses were equally blunted in patients with and without HIV infection.

Blue whales in the Northern Indian Ocean are a morphologically and acoustically distinct population restricted to these waters. Off Sri Lanka a portion of the population concentrates near shore where they are exposed to a range of anthropogenic threats. We review available data to determine anthropogenic threats/stressors faced by this population and assign subjective rankings for the population-level severity of each threat/stressor based on severity, scope, and immediacy. With the cessation of direct illegal catches on this population in the late 1960s, we ranked ship strike as the most important population-level threat. Incidental catch, which includes entanglement and bycatch, is also important as it can result in death. Other less important stressors that may negatively impact this population include threats resulting from oil and gas development and pollution. However, some stressors can have a long-term cumulative impact that is difficult to assess. The most important research needed for the conservation of these whales is to obtain an estimate of the size of the population using photo-identification methods.

Serum tumor markers are useful to evaluate a cancer's response to treatment, for early detection of cancer relapse, and, in some cases, to diagnose malignancy. In this paper, we present two patients with significantly elevated serum tumor markers without evidence of malignant disease. An 18-year-old patient suffering from autoimmune hepatitis had markedly increased alpha-fetoprotein (aFP) levels (2,002 μg/L; normal

Background and Purpose: There is emerging evidence for a critical role for epigenetic modifiers in the development of inflammatory bowel disease (IBD). Protein arginine methyltransferase 2 (PRMT2) is responsible for the methylation of arginine residues on histones and targets transcription factors involved in many cellular processes, including gene transcription, mRNA splicing, cell proliferation, and cell differentiation. In this study, the role and underlying mechanisms of PRMT2 in colitis were studied., Experimental Approach: A mouse dextran sulfate sodium (DSS)-induced experimental colitis model was used to study PRMT2 in colitis. Lentivirus-induced PRMT2 silencing or overexpression in vivo was applied to address the role of PRMT2 in colitis. Detailed western blot and expression analysis were done to understand epigenetic changes induced by PRMT2 in colitis., Key Results: PRMT2 is highly expressed in inflammatory bowel disease patients, in inflamed murine colon and in TNF-α stimulated murine gut epithelial cells. PRMT2 overexpression aggravates, while knockdown alleviates DSS-induced colitis, suggesting that PRMT2 is a pivotal mediator of colitis in mice. Mechanistically, PRMT2 mediates colitis by increasing repressive histone mark H3R8 asymmetric methylation (H3R8me2a) at the promoter region of the suppressor of cytokine signalling 3 promoter (SOCS3). Resultant inhibition of SOCS3 expression and inhibition of SOCS3-mediated degradation of TNF receptor associated factor 5 (TRAF5) via ubiquitination led to elevated TRAF5 expression and TRAF5-mediated downstream NF-κB/MAPK activation., Conclusion and Implications: Our study demonstrates that PRMT2 acts as a transcriptional co-activator for proinflammatory genes during colitis. Hence, targeting PRMT2 may provide a novel therapeutic approach for colitis., (© 2021 The British Pharmacological Society.)

Alginate-polylysine (PLL) capsules are commonly applied for immunoisolation of living cells for the treatment of a wide variety of diseases. Large-scale application of the technique, however, is hampered by insufficient biocompatibility of the capsules with failure of the grafts as a consequence. Most studies addressing biocompatibility issues of alginate-PLL capsules have focused on the degree of overgrowth on the capsules after graft failure and not on the reaction against the capsules in the immediate posttransplant period. Therefore, capsules were implanted in the peritoneal cavity of rats and retrieved 1, 5, and 7 days later for histological examination and X-ray photoelectron spectroscopy analysis for evaluation of chemical changes at the capsule surface. After implantation, the nitrogen signal increased from 5% on day 0, to 8.6% on day 7, illustrating protein adsorption on the capsule's surface. This increase in protein content of the membrane was accompanied by an increase in the percentage of overgrown capsules from 0.5 +/- 0.3% on day 1 to 3.3 +/- 1.6% on day 7. The cellular overgrowth was composed of monocytes/macrophages, granulocytes, fibroblasts, erythrocytes, multinucleated giant cells, and basophils. This overgrowth was not statical as generally assumed but rather dynamic as illustrated by our observation that at day 1 after implantation we mainly found monocytes/macrophages and granulocytes that on later time points were substituted by fibroblasts. As the inflammatory reaction predictably interfere with survival of encapsulated cells, efforts should be made to suppress activities or recruitment of inflammatory cells. These efforts may be temporary rather than permanent because most inflammatory cells have disappeared after 2 weeks of implantation., (Copyright 2002 Wiley Periodicals, Inc.)