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In the wake of climate change, social theory has been subject to a surge of new materialist and posthuman approaches that reconfigure ontology and politics beyond the modern nature/culture binary which the Anthropocene has rendered untenable. But their (re-)turn to ontological speculation brackets the socio-epistemic situatedness and productivity of the way we think nature and its relationship to society. This paper reads Niklas Luhmann's systems theory as a posthuman perspective that can address the epistemological blind spot of materialist-ecological thought. Luhmann's ecology aligns with the former on the posthuman framing of shaping power, the productivity of an environmental outside that remains unknown, and the call for political modesty which follows. On the other hand, Luhmann's theory poses a critical challenge to materialist-ecological thought: the society/environment binary is here constitutively necessary, and its mapping onto a nature/culture binary functionally advantageous for subjects and social systems because it offers opportunities for complexity-reduction. [ABSTRACT FROM AUTHOR]

Currently, few robust data are available to provide estimates of the environmental footprint and in particular the CO2 emissions of medical devices; however, existing life cycle assessments largely indicate that reusable materials have more favorable emissions and environmental footprints compared to disposable items. Thus, the challenge for every anesthesiology department is to identify items that can be used as reusable products for ecological and other reasons. A prerequisite for the use of reusable items is hygienically correct reprocessing and packaging. Here, a distinction must be made between noncritical, semicritical and critical medical devices, depending on the type of use. In addition, a distinction must be made between categories A–C, depending on the complexity of the reprocessing. In this narrative review article common reusable items used in anesthesiology are categorized and a standardized decision algorithm for reprocessing routes is proposed. Special attention is also given to the packaging of medical devices, which can contribute to the ecological footprint to a relevant extent. This article further explains the framework under which reprocessing can take place and analyzes the current state of knowledge on the life cycle assessment of reprocessing reusable devices. This requires the special commitment of clinically active anesthesiologists to include ecological aspects in the decision to use disposable or reusable items. In the medium term, comprehensible ecological key numbers should be provided on every medical device to make the ecological costs of the articles understandable in addition to the monetary costs. [ABSTRACT FROM AUTHOR]

Brown adipose tissue (BAT) is a key thermogenic organ whose expression of uncoupling protein 1 (UCP1) and ability to maintain body temperature in response to acute cold exposure require histone deacetylase 3 (HDAC3). HDAC3 exists in tight association with nuclear receptor corepressors (NCoRs) NCoR1 and NCoR2 (also known as silencing mediator of retinoid and thyroid receptors [SMRT]), but the functions of NCoR1/2 in BAT have not been established. Here we report that as expected, genetic loss of NCoR1/2 in BAT (NCoR1/2 BAT-dKO) leads to loss of HDAC3 activity. In addition, HDAC3 is no longer bound at its physiological genomic sites in the absence of NCoR1/2, leading to a shared deregulation of BAT lipid metabolism between NCoR1/2 BAT-dKO and HDAC3 BAT-KO mice. Despite these commonalities, loss of NCoR1/2 in BAT does not phenocopy the cold sensitivity observed in HDAC3 BAT-KO, nor does loss of either corepressor alone. Instead, BAT lacking NCoR1/2 is inflamed, particularly with respect to the interleukin-17 axis that increases thermogenic capacity by enhancing innervation. Integration of BAT RNA sequencing and chromatin immunoprecipitation sequencing data revealed that NCoR1/2 directly regulate Mmp9, which integrates extracellular matrix remodeling and inflammation. These findings reveal pleiotropic functions of the NCoR/HDAC3 corepressor complex in BAT, such that HDAC3-independent suppression of BAT inflammation counterbalances stimulation of HDAC3 activity in the control of thermogenesis. [ABSTRACT FROM AUTHOR]

This paper brings the narratives of the environmental activist groups Extinction Rebellion, Just Stop Oil and Fridays for Future into conversation with Critical Anthropocene Theory and Indigenous environmentalism to interrogate pathways for and limits of environmental political action under planetary conditions marked by nonhuman shaping power. Critical Anthropocene Theory, the paper argues, can problematise the simplistic positivism and managerialism of the new 'extinction activism'. However, the conversation with Indigenous environmental practices, which flexibly manage tensions within human-nonhuman relations and centre radical social impact, reveals the political limitations of both extinction activism and critical Anthropocene thinking. The paper distinguishes the logic of fast change within existing socio-political parameters, which drives extinction activism, from Critical Anthropocene Theory's focus on ontological change as a precondition for a non-exploitative environmental politics, which deprioritises activist practice. Different from both, the paper argues that Indigenous environmental activism is marked by a yet different pragmatic approach, where both modern and non-modern political means are mobilised towards radical change. Indigenous environmentalism is marked by the dynamic co-evolution of cosmology and politics and moves flexibly between modern/nonmodern boundaries, highlighting new pathways for political action in the relational Anthropocene. [ABSTRACT FROM AUTHOR]

This article examines Gilles Deleuze's and Giorgio Agamben's thoughts on the immanent creativity emergent from formal, impersonal life as a pathway for resistance to biopolitics. In Coldness and Cruelty, Deleuze explores masochism as the inversion of the sadistic, biopolitical use of the body which can bring forth genuinely new expressions. Agamben dismisses masochistic creativity because it leaves the dialectical ontology of biopower intact to conceptualize his form-of-life as a space of indiscernibility between ontological essence and legal-political actualization. For Agamben, the form-of-life escapes biopolitical capture because it is absolutely detached from its relations. This article argues that the radicalness of this detachment calls into question the political capacity offered by the form-of-life to actively change the relations of biopower. Against this background, Deleuze's masochistic eroticization of power offers an alternative conceptualization of relationality as external to its terms and productive of expressions which are both thoroughly immanent and genuinely creative. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy (NACT) is a standard approach of the multidisciplinary treatment of breast cancer. Depending on the biological subtype a pathological complete response in the breast (bpCR) can be achieved in up to 60% of the patients. However, only limited accuracy can be reached when using imaging for prediction of bpCR prior to surgery. Due to this diagnostic uncertainty, surgery after NACT is considered to be obligatory for all patients in order to either completely remove residual disease or to diagnose a bpCR histologically. The purpose of this trial is to evaluate the accuracy of a vacuum-assisted biopsy (VAB) to diagnose a bpCR after NACT prior to surgery.Methods: This study is a multicenter, confirmative, one-armed, intra-individually-controlled, open, diagnostic trial. The study will take place at 21 trial sites in Germany. Six hundred female patients with breast cancer after completed NACT showing at least a partial response to NACT treatment will be enrolled. A vacuum-assisted biopsy (VAB) guided either by ultrasound or mammography will be performed followed by histopathological evaluation of the VAB specimen before standard, guideline-adherent breast surgery. The study is designed to prove that the false negative rate of the VAB is below 10%.Discussion: As a bpCR is becoming a more frequent result after NACT, the question arises whether breast surgery is therapeutically necessary in such cases. To study this subject further, it will be crucial to develop a reliable test to diagnose a bpCR without surgery. During the study we anticipate possible problems in patient recruitment as the VAB intervention does not provide participating patients with any personal benefit. Hence, a proficient informed consent discussion with the patient and a detailed explanation of the study aim will be crucial for patient recruitment. Another critical issue is the histopathological VAB evaluation of a non-tumorous specimen as this may have been taken either from the former tumor region (bpCR) or outside of the (former) tumor region (non-representative VAB, sampling error).Trial Registration: The trial has been registered at clinicaltrials.gov with the identifier NCT02948764 on October 28, 2016 and at the German Clinical Trials Register ( DRKS00011761 ) on February 20, 2017. The date of enrolment of the first participant to the trial was on March 8, 2017. [ABSTRACT FROM AUTHOR]

Deficiencies in the sterile processing of medical instruments contribute to poor outcomes for patients, such as surgical site infections, longer hospital stays, and deaths. In low resources settings, such as some rural and semi-rural areas and secondary and tertiary cities of developing countries, deficiencies in sterile processing are accentuated due to the lack of access to sterilization equipment, improperly maintained and malfunctioning equipment, lack of power to operate equipment, poor protocols, and inadequate quality control over inventory. Inspired by our sterile processing fieldwork at a district hospital in Sierra Leone in 2013, we built an autonomous, shipping-container-based sterile processing unit to address these deficiencies. The sterile processing unit, dubbed “the sterile box,” is a full suite capable of handling instruments from the moment they leave the operating room to the point they are sterile and ready to be reused for the next surgery. The sterile processing unit is self-sufficient in power and water and features an intake for contaminated instruments, decontamination, sterilization via non-electric steam sterilizers, and secure inventory storage. To validate efficacy, we ran tests of decontamination and sterilization performance. Results of 61 trials validate convincingly that our sterile processing unit achieves satisfactory outcomes for decontamination and sterilization and as such holds promise to support healthcare facilities in low resources settings. [ABSTRACT FROM AUTHOR]

Aging is the major risk factor for neurodegenerative diseases such as Alzheimer's disease, but little is known about the processes that lead to age-related decline of brain structures and function. Here we use RNA-seq in combination with high resolution histological analyses to show that aging leads to a significant deterioration of neurovascular structures including basement membrane reduction, pericyte loss, and astrocyte dysfunction. Neurovascular decline was sufficient to cause vascular leakage and correlated strongly with an increase in neuroinflammation including up-regulation of complement component C1QA in microglia/monocytes. Importantly, long-term aerobic exercise from midlife to old age prevented this age-related neurovascular decline, reduced C1QA+ microglia/monocytes, and increased synaptic plasticity and overall behavioral capabilities of aged mice. Concomitant with age-related neurovascular decline and complement activation, astrocytic Apoe dramatically decreased in aged mice, a decrease that was prevented by exercise. Given the role of APOE in maintaining the neurovascular unit and as an anti-inflammatory molecule, this suggests a possible link between astrocytic Apoe, age-related neurovascular dysfunction and microglia/monocyte activation. To test this, Apoe-deficient mice were exercised from midlife to old age and in contrast to wild-type (Apoe-sufficient) mice, exercise had little to no effect on age-related neurovascular decline or microglia/monocyte activation in the absence of APOE. Collectively, our data shows that neurovascular structures decline with age, a process that we propose to be intimately linked to complement activation in microglia/monocytes. Exercise prevents these changes, but not in the absence of APOE, opening up new avenues for understanding the complex interactions between neurovascular and neuroinflammatory responses in aging and neurodegenerative diseases such as Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Keywords: Aggregation; aspirin; major adverse cardiovascular and cerebrovascular events; platelet inhibition; rivaroxaban; thromboxane EN Aggregation aspirin major adverse cardiovascular and cerebrovascular events platelet inhibition rivaroxaban thromboxane 1126 1128 3 12/02/21 20211101 NES 211101 In the COMPASS trial, low-dose ("vascular dose") rivaroxaban (2.5 mg twice daily) was investigated in chronic coronary syndrome (CCS) patients. TX B2 ELISA [Cayman Chemicals (Lot No. 501020)] was used to measure TX B2 levels in supernatant from washed platelets after FXa (52 µg/ml) induced platelet aggregation. [Extracted from the article]

Ambient temperature influences the molecular clock and lipid metabolism, but the impact of chronic cold exposure on circadian lipid metabolism in thermogenic brown adipose tissue (BAT) has not been studied. Here we show that during chronic cold exposure (1 wk at 4 °C), genes controlling de novo lipogenesis (DNL) including Srebp1, the master transcriptional regulator of DNL, acquired high-amplitude circadian rhythms in thermogenic BAT. These conditions activated mechanistic target of rapamycin 1 (mTORC1), an inducer of Srebp1 expression, and engaged circadian transcriptional repressors REV-ERBα and β as rhythmic regulators of Srebp1 in BAT. SREBP was required in BAT for the thermogenic response to norepinephrine, and depletion of SREBP prevented maintenance of body temperature both during circadian cycles as well as during fasting of chronically cold mice. By contrast, deletion of REV-ERBα and β in BAT allowed mice to maintain their body temperature in chronic cold. Thus, the environmental challenge of prolonged noncircadian exposure to cold temperature induces circadian induction of SREBP1 that drives fuel synthesis in BAT and is necessary to maintain circadian body temperature during chronic cold exposure. The requirement for BAT fatty acid synthesis has broad implications for adaptation to cold. [ABSTRACT FROM AUTHOR]

The mpox outbreak of 2022–2023 involved rapid global spread in men who have sex with men. We infected 18 rhesus macaques with mpox by the intravenous, intradermal, and intrarectal routes and observed robust antibody and T cell responses following all three routes of infection. Numerous skin lesions and high plasma viral loads were observed following intravenous and intradermal infection. Skin lesions peaked on day 10 and resolved by day 28 following infection. On day 28, we re-challenged all convalescent and 3 naive animals with mpox. All convalescent animals were protected against re-challenge. Transcriptomic studies showed upregulation of innate and inflammatory responses and downregulation of collagen formation and extracellular matrix organization following challenge, as well as rapid activation of T cell and plasma cell responses following re-challenge. These data suggest key mechanistic insights into mpox pathogenesis and immunity. This macaque model should prove useful for evaluating mpox vaccines and therapeutics. [Display omitted] • Mpox infection by three routes induces robust natural immunity • Natural immunity protects against mpox re-challenge • Adaptive immune responses appear critical for protection Modeling mpox infection in rhesus macaques demonstrates the protective efficacy of natural immunity induced by three routes of viral exposure against re-challenge. [ABSTRACT FROM AUTHOR]

Background This study aimed to explore the ability of a minimal invasive biopsy to diagnose a pathological complete response (pCR = ypT0) in the breast. Methods Ultrasound-guided, vacuum-assisted, minimal invasive biopsy (VAB) was performed in 50 patients after neoadjuvant chemotherapy and before breast surgery. Negative predictive values (NPV) and false negative rates (FNR) to predict a pCR in surgical specimen were the main outcome measures. To assess the possible sampling error, the representativeness of the sample was evaluated by the biopsy performing physician (subjectively based on the visibility in ultrasound), by radiography of the biopsy specimen, and by the pathologist (based on histopathology). Results The cohort (n = 50) consisted of 15 (30%) triple negative breast cancers, 13 (26%) human epidermal growth factor receptor 2 (HER2) positive and 22 (44%) hormone receptor positive/HER2 negative cancers. ypT0 was diagnosed in 23 (46%) cases. In the overall cohort (n = 50), VAB yielded an NPV of 76.7% and an FNR of 25.9%. Given a representative VAB sample, according to the histopathological evaluation (n = 38), the NPV was 94.4% (95% CI 87.1–100.0) and the FNR 4.8% (95% CI 0.0–11.6). Non-representative VABs were mainly due to bad visibility of the target lesion in ultrasound. Conclusion A VAB can accurately diagnose a pCR, given a histopathologically representative sample. [ABSTRACT FROM AUTHOR]

Aging-related impairments in hippocampus-dependent cognition have been attributed to maladaptive changes in the functional properties of pyramidal neurons within the hippocampal subregions. Much evidence has come from work on CA1 pyramidal neurons, with CA3 pyramidal neurons receiving comparatively less attention despite its age-related hyperactivation being postulated to interfere with spatial processing in the hippocampal circuit. Here, we use whole-cell current-clamp to demonstrate that aged rat (29 -32 months) CA3 pyramidal neurons fire significantly more action potentials (APs) during theta-burst frequency stimulation and that this is associated with faster AP repolarization (i.e., narrower AP half-widths and enlarged fast afterhyperpolarization). Using a combination of patch-clamp physiology, pharmacology, Western blot analyses, immunohistochemistry, and array tomography, we demonstrate that these faster AP kinetics are mediated by enhanced function and expression of Kv4.2/Kv4.3 A-type K+ channels, particularly within the perisomatic compartment, of CA3 pyramidal neurons. Thus, our study indicates that inhibition of these A-type K+ channels can restore the intrinsic excitability properties of aged CA3 pyramidal neurons to a young-like state. [ABSTRACT FROM AUTHOR]

Lipid-lowering therapy is one major cornerstone of medical treatment of cardiovascular disease in order to modulate atherosclerosis. Statins, ezetimibe and novel PCSK9-inhibitors are already recommended in current guidelines and were shown to improve lipid profiles and have positive effects on the rate of ischemic events and cardiovascular mortality. Recent studies suggest that the concept of "The lower the better" might be valid at least regarding low density lipoproteins. In addition, lowering lipoprotein (a) still displays a major challenge in lipid therapy. Furthermore, also lowering triglycerides seems to improve cardiovascular outcome. Regarding triglycerides, icosapent ethyl, a polyunsaturated fatty acid recently attracted attention showing cardiovascular risk reduction due to triglyceride lowering. Therefore, new therapeutic strategies and drug classes are eagerly awaited. Targeting LDL, bempedoic acid and the siRNA inclisiran provide promising results. Moreover, regarding TG a monoclonal antibody called evinacumab and an antisense-oligonucleotide against ANGPTL3 showed effective TG-lowering. At least, using antisense-oligonucleotides against ApoC-III and Lp(a) resulted in promising outcomes. In this review, current and future options for lipid management are presented depending on different drug classes. [ABSTRACT FROM AUTHOR]