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The kidney sessions of the 2017 Banff Conference focused on 2 areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i‐IFTA) and its relationship to T cell–mediated rejection (TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody‐mediated rejection (ABMR). In confirmation of previous studies, it was independently demonstrated by 2 groups that i‐IFTA is associated with reduced graft survival. Furthermore, these groups presented that i‐IFTA, particularly when involving >25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with underimmunosuppression. The classification was thus revised to include moderate i‐IFTA plus moderate or severe tubulitis as diagnostic of chronic active TCMR. Other studies demonstrated that certain molecular classifiers improve diagnosis of ABMR beyond what is possible with histology, C4d, and detection of donor‐specific antibodies (DSAs) and that both C4d and validated molecular assays can serve as potential alternatives and/or complements to DSAs in the diagnosis of ABMR. The Banff ABMR criteria are thus updated to include these alternatives. Finally, the present report paves the way for the Banff scheme to be part of an integrative approach for defining surrogate endpoints in next‐generation clinical trials. The Banff consortium presents revisions to the diagnostic criteria for T cell– and antibody‐mediated kidney transplant rejection, including specific criteria for chronic active T cell–mediated rejection, plus prospects for integrative endpoints in clinical trials. See related articles on pages 321, 364, and 377.

What are the psychological consequences of the increasingly politicized nature of the COVID-19 pandemic in the United States relative to similar Western countries? In a two-wave study completed early (March) and later (December) in the pandemic, we found that polarization was greater in the United States ( N = 1,339) than in Canada ( N = 644) and the United Kingdom. ( N = 1,283). Political conservatism in the United States was strongly associated with engaging in weaker mitigation behaviors, lower COVID-19 risk perceptions, greater misperceptions, and stronger vaccination hesitancy. Although there was some evidence that cognitive sophistication was associated with increased polarization in the United States in December (but not March), cognitive sophistication was nonetheless consistently negatively correlated with misperceptions and vaccination hesitancy across time, countries, and party lines. Furthermore, COVID-19 skepticism in the United States was strongly correlated with distrust in liberal-leaning mainstream news outlets and trust in conservative-leaning news outlets, suggesting that polarization may be driven by differences in information environments.

Author(s): Lochmuller, Hanns; Behin, Anthony; Tournev, Ivailo; Tarnopolsky, Mark; Horvath, Rita; Pogoryelova, Oksana; Shah, Jinay; Koutsoukos, Tony; Skrinar, Alison; Kakkis, Emil; Bedrosian, Camille L; Mozaffar, Tahseen | Abstract: BackgroundGNE myopathy is a rare, autosomal recessive, muscle disease caused by mutations in GNE and is characterized by rimmed vacuoles on muscle biopsy and progressive distal to proximal muscle weakness.ObjectiveInvestigate the clinical presentation and progression of GNE myopathy.MethodsThe GNE Myopathy Disease Monitoring Program was an international, prospective, observational study in subjects with GNE myopathy. Muscle strength was assessed with hand-held dynamometry (HHD), with upper extremity (UE) and lower extremity (LE) composite scores reflecting upper and lower extremity muscle groups, respectively. The GNE myopathy-Functional Activity Scale (GNEM-FAS) was used to further assess impairment in mobility, upper extremity function, and self-care.ResultsEighty-seven of 101 enrolled subjects completed the trial until study closure by the sponsor; 60 completed 36 months. Mean (SD) HHD UE composite score decreased from 34.3 kg (32.0) at baseline to 29.4 kg (32.6) kg at month 36 (LS mean change [95%CI]: -3.8 kg [-5.9, -1.7]; P = 0.0005). Mean (SD) HHD LE composite score decreased from 32.0 kg (34.1) at baseline to 25.5 kg (31.2) at month 36 (LS mean change [95%CI]: -4.9 [-7.7, -2.2]; P = 0.0005). GNEM-FAS scores were more severe at baseline in subjects who walked l200 meters versus ≥200 meters in 6 minutes; in both groups, GNEM-FAS total, mobility, UE, and self-care scores decreased from baseline through month 36.ConclusionsThese findings demonstrate progressive decline in muscle strength in GNE myopathy and provide insight into the appropriate tools to detect clinically meaningful changes in future GNE myopathy interventional trials.

Dinoflagellates are microbial eukaryotes that have exceptionally large nuclear genomes; however, their organelle genomes are small and fragmented and contain fewer genes than those of other eukaryotes. The genus Amoebophrya (Syndiniales) comprises endoparasites with high genetic diversity that can infect other dinoflagellates, such as those forming harmful algal blooms (e.g., Alexandrium). We sequenced the genome (~100 Mb) of Amoebophrya ceratii to investigate the early evolution of genomic characters in dinoflagellates. The A. ceratii genome encodes almost all essential biosynthetic pathways for self-sustaining cellular metabolism, suggesting a limited dependency on its host. Although dinoflagellates are thought to have descended from a photosynthetic ancestor, A. ceratii appears to have completely lost its plastid and nearly all genes of plastid origin. Functional mitochondria persist in all life stages of A. ceratii, but we found no evidence for the presence of a mitochondrial genome. Instead, all mitochondrial proteins appear to be lost or encoded in the A. ceratii nucleus. The parasitic marine dinoflagellate Amoebophrya is the first known eukaryote with aerobic mitochondria without a genome.

Supramolecular polymeric networks are capable of producing gels that exhibit stimulus responsive, self-healing properties and are useful in a variety of applications. In this work, a pillar[5]arene derivative bearing a single azide functionality was prepared and coupled via strain-promoted azide–alkyne cycloaddition chemistry to a conjugated polyimine consisting of dibenzocyclooctyne units in its backbone. The resulting polypillar[5]arene structure was found to form inclusion complexes with cyanoalkanes and produced organogels when mixed with cyanoalkyl-functionalized polymers. The resulting gels could be hydrolyzed by exposure to acid and could subsequently be regenerated by dehydration. In addition, these organogels exhibited self-healing behavior if severed and reconnected.

Sleep serves crucial learning and memory functions in both nervous and immune systems. Microglia are brain immune cells that actively maintain health through their crucial physiological roles exerted across the lifespan, including phagocytosis of cellular debris and orchestration of neuroinflammation. The past decade has witnessed an explosive growth of microglial research. Considering the recent developments in the field of microglia and sleep, we examine their possible impact on various pathological conditions associated with a gain, disruption, or loss of sleep in this focused mini-review. While there are extensive studies of microglial implication in a variety of neuropsychiatric and neurodegenerative diseases, less is known regarding their roles in sleep disorders. It is timely to stimulate new research in this emergent and rapidly growing field of investigation. Peer reviewed

Background: Arterial hypertension and its organ sequelae show characteristics of T cell–mediated inflammatory diseases. Experimental anti-inflammatory therapies have been shown to ameliorate hypertensive end-organ damage. Recently, the CANTOS study (Canakinumab Antiinflammatory Thrombosis Outcome Study) targeting interleukin-1β demonstrated that anti-inflammatory therapy reduces cardiovascular risk. The gut microbiome plays a pivotal role in immune homeostasis and cardiovascular health. Short-chain fatty acids (SCFAs) are produced from dietary fiber by gut bacteria and affect host immune homeostasis. Here, we investigated effects of the SCFA propionate in 2 different mouse models of hypertensive cardiovascular damage. Methods: To investigate the effect of SCFAs on hypertensive cardiac damage and atherosclerosis, wild-type NMRI or apolipoprotein E knockout–deficient mice received propionate (200 mmol/L) or control in the drinking water. To induce hypertension, wild-type NMRI mice were infused with angiotensin II (1.44 mg·kg–1·d–1 subcutaneous) for 14 days. To accelerate the development of atherosclerosis, apolipoprotein E knockout mice were infused with angiotensin II (0.72 mg·kg–1·d–1 subcutaneous) for 28 days. Cardiac damage and atherosclerosis were assessed using histology, echocardiography, in vivo electrophysiology, immunofluorescence, and flow cytometry. Blood pressure was measured by radiotelemetry. Regulatory T cell depletion using PC61 antibody was used to examine the mode of action of propionate. Results: Propionate significantly attenuated cardiac hypertrophy, fibrosis, vascular dysfunction, and hypertension in both models. Susceptibility to cardiac ventricular arrhythmias was significantly reduced in propionate-treated angiotensin II–infused wild-type NMRI mice. Aortic atherosclerotic lesion area was significantly decreased in propionate-treated apolipoprotein E knockout–deficient mice. Systemic inflammation was mitigated by propionate treatment, quantified as a reduction in splenic effector memory T cell frequencies and splenic T helper 17 cells in both models, and a decrease in local cardiac immune cell infiltration in wild-type NMRI mice. Cardioprotective effects of propionate were abrogated in regulatory T cell–depleted angiotensin II–infused mice, suggesting the effect is regulatory T cell–dependent. Conclusions: Our data emphasize an immune-modulatory role of SCFAs and their importance for cardiovascular health. The data suggest that lifestyle modifications leading to augmented SCFA production could be a beneficial nonpharmacological preventive strategy for patients with hypertensive cardiovascular disease. Supplemental Digital Content is available in the text.

International audience; Phosphorus (P) is a non-renewable resource, and its recovery and recycling are necessary for meeting future P demands and environmental conservation. Ash and hydrochar from incineration and hydrothermal liquefaction (HTL) of municipal sludge, respectively, represent promising sources for efficient P recovery. The full-scale application of wet-chemical techniques has proven their technical feasibility for P recovery from sludge-derived ash. HTL for sludge treatment has received significant attention for producing biocrude with net-positive energy recovery. P recovery from the solid by-product of sludge HTL, hydrochar, is a critical step in holistic sustainable sludge management. This review aims to guide P recovery from sludge-derived ash and hydrochar by presenting recent advances in wet-chemical extraction and precipitation. By comparing their characteristics, ash and hydrochar derived from municipal sludge exhibit similar feasibilities and challenges for P recovery. Extraction is recognized as the critical step for P recovery. The advantages and disadvantages of various P extraction approaches are provided. Acidic extraction achieves high efficiency (up to 100%) but requires removal of co-extracted heavy metals. Alkaline extraction prevents metals contamination but shows low efficiency (<70%). Sequential extraction is first identified as an important advance in this review, with promising P extraction efficiencies (70–91%) and low metal interferences. Three possible fertilizers (struvite, calcium phosphates, and vivianite) are recommended through the final precipitation, given their pros and cons of recovery. Ultimately, this review highlights the need for a wastewater biorefinery integrating wastewater treatment, HTL (energy recovery), and nutrient recovery for sustainable sludge management.

Resume Objectifs Les violences politiques peuvent pousser sur les routes de l’exil la ou les soutiens amicaux, familiaux et culturels sont moins presents et les adversites se vivent par consequent souvent seules. Ces bouleversements existentiels affectent les sexualites des personnes survivant ces violences. Pourtant, celles-ci sont rarement au cœur des parcours de soin posttraumatique. Methode Nous proposons d’etudier les enjeux clinique et politique des sexualites dans l’apres trauma pour des populations migrantes et racisees. A partir d’illustrations tirees de nos experiences cliniques, nous proposons de presenter nos approches psychotherapeutiques ecosociale et transculturelle afin de discuter les sexualites au regard de la notion de relationnalite et de la facon dont celle-ci se traduit en termes de parentalite et de conjugalite. Resultats Nous presentons une pratique psychotherapeutique narrative et relationnelle prenant en consideration les aspects psychologiques, sociaux et politiques du trauma. Nous proposons trois vignettes de personnes exilees qui se questionnent dans l’apres trauma autour de leur sexualite, identite et capacite a faire famille. Ce travail autour de la relation est un travail intersubjectif informe par le contexte en proposant des interventions culturellement sensibles. Conclusion Pour les populations ayant eu l’experience de violences sociales et politiques, le trauma se manifeste dans leurs vies dans leurs aspects sociaux et intimes. Ce qui vient faire le lien entre l’intime et le politique est la relationnalite. Celle-ci peut faire echo aux difficultes a creer des relations de confiance et peut se manifester dans les difficultes d’adaptation, mais aussi dans des enjeux familiaux, conjugaux et sexuels.