Evolving the Anthropocene: linking multi-level selection with long-term social–ecological change

To what degree is cultural multi-level selection responsible for the rise of environmentally transformative human behaviors? And vice versa? From the clearing of vegetation using fire to the emergence of agriculture and beyond, human societies have increasingly sustained themselves through practices that enhance environmental productivity through ecosystem engineering. At the same time, human societies have increased in scale and complexity from mobile bands of hunter-gatherers to telecoupled world systems. We propose that these long-term changes are coupled through positive feedbacks among social and environmental changes, coevolved primarily through selection acting at the group level and above, and that this can be tested by combining archeological evidence with mechanistic experiments using an agent-based virtual laboratory (ABVL) approach. A more robust understanding of whether and how cultural multi-level selection couples human social change with environmental transformation may help in addressing the long-term sustainability challenges of the Anthropocene

Synthetic tethered silver nanoparticles on reduced graphene oxide for alkaline oxygen reduction catalysis

There is currently an enormous drive to move away from the use of Pt group metals in catalysis, particularly for fuel cells, because of their increasing rarity and cost. Simultaneously, there have been advances in the application of graphene supported nanoparticular catalysts. However, these Pt-free, graphene supported catalysts can be complex to produce, show poor catalytic activity and degrade quickly due to particle agglomeration or isolation. Herein, we report a one-pot synthesis of silver nanoparticles (NPs) tethered to a reduced graphene oxide (rGO) template via organic linkages. This is one of the few silver precursor formations that have been combined with graphene oxide (GO) to simultaneously establish linkage binding sites, reduce GO and yield tethered nanoparticles. These materials are shown to efficiently catalyze the oxygen reduction reaction in alkaline environments, with aminoethanol linkages to 21.55 ± 2.88 nm Ag particles exhibiting the highest catalytic activity via the four-electron pathway. This method, therefore, offers a straightforward route to produce effective catalysts from inexpensive precursors, which could be developed further for significant industrial application

Therapeutic approach in glioblastoma multiforme with primitive neuroectodermal tumor components: case report and review of the literature

Glioblastoma multiforme (GBM) is the most common and aggressive malignant glioma that is treated with first-line therapy, using surgical resection followed by local radiotherapy and concomitant/adjuvant temozolomide (TMZ) treatment. GBM is characterised by a high local recurrence rate and a low response to therapy. Primitive neuroectodermal tumour (PNET) of the brain revealed a low local recurrence rate; however, it also exhibited a high risk of cerebrospinal fluid (CSF) dissemination. PNET is treated with surgery followed by craniospinal irradiation (CSI) and platinum-based chemotherapy in order to prevent CSF dissemination. GBM with PNET-like components (GBM/PNET) is an emerging variant of GBM, characterised by a PNET-like clinical behaviour with an increased risk of CSF dissemination; it also may benefit from platinum-based chemotherapy upfront or following failure of GBM therapy. The results presented regarding the management of GBM/PNET are based on case reports or case series, so a standard therapeutic approach for GBM/PNET is not defined, constituing a challenging diagnostic and therapeutic dilemma. In this report, a case of a recurrent GBM/PNET treated with surgical resection and radiochemotherapy as Stupp protocol, and successive platinum-based chemotherapy due to the development of leptomeningeal dissemintation and an extracranial metastasis, is discussed. A review of the main papers regarding this rare GBM variant and its therapeutic approach are also reported. In conclusion, GBM/PNET should be treated with a multimodal approach including surgery, chemoradiotherapy, and/or the early introduction of CSI and platinum-based chemotherapy upfront or at recurrence

Upstaging nodal status in colorectal cancer using ex vivo fluorescence sentinel lymph node mapping: preliminary results

Background: Sentinel lymph node (SLN) mapping using near-infrared fluorescence (NIRF) imaging is a recent technique to improve nodal staging in several tumors. The presence of colorectal cancer (CRC) micro-metastases has recently been defined as N1 disease and no longer as N1mi, determining the need for adjuvant chemotherapy. In CRC, the reported rate of SLN micro-metastases detected by ultrastaging techniques is as high as 30%. The aim of this prospective study is to report the preliminary results of the sensitivity analysis of NIRF imaging for ex vivo SLN mapping and the research of micro-metastases in CRC, in patients with node-negative disease (NND). Material and methods: On the specimen of 22 CRC patients, 1 mL of ICG (5 mg/mL) was injected submucosally around the tumor to identify SLNs. NND SLNs were further investigated with ultrastaging techniques. Results: Three-hundred and sixty-three lymph nodes were retrieved (59 SLNs; mean per case: 2.7). The detection, sensitivity and false-negative rate were 100%, 100% and 0% respectively. Ultrastaging investigations showed no micro-metastases in the NND SLNs. Conclusions: The ex vivo SLN fluorescence-based detection in CRC was confirmed to be easy to perform and reliable. In this preliminary results report of an ongoing study, the SLN assay was congruent with the nodal status, as confirmed by histological investigations

Efficacy of acute administration of inhaled argon on traumatic brain injury in mice

BACKGROUND: Whilst there has been progress in supportive treatment for traumatic brain injury (TBI), specific neuroprotective interventions are lacking. Models of ischaemic heart and brain injury show the therapeutic potential of argon gas, but it is still not known whether inhaled argon (iAr) is protective in TBI. We tested the effects of acute administration of iAr on brain oedema, tissue micro-environmental changes, neurological functions, and structural outcome in a mouse model of TBI. METHODS: Anaesthetised adult C57BL/6J mice were subjected to severe TBI by controlled cortical impact. Ten minutes after TBI, the mice were randomised to 24 h treatments with iAr 70%/O2 30% or air (iCtr). Sensorimotor deficits were evaluated up to 6 weeks post-TBI by three independent tests. Cognitive function was evaluated by Barnes maze test at 4 weeks. MRI was done to examine brain oedema at 3 days and white matter damage at 5 weeks. Microglia/macrophages activation and functional commitment were evaluated at 1 week after TBI by immunohistochemistry. RESULTS: iAr significantly accelerated sensorimotor recovery and improved cognitive deficits 1 month after TBI, with less white matter damage in the ipsilateral fimbria and body of the corpus callosum. Early changes underpinning protection included a reduction of pericontusional vasogenic oedema and of the inflammatory response. iAr significantly reduced microglial activation with increases in ramified cells and the M2-like marker YM1. CONCLUSIONS: iAr accelerates recovery of sensorimotor function and improves cognitive and structural outcome 1 month after severe TBI in adult mice. Early effects include a reduction of brain oedema and neuroinflammation in the contused tissue

Predictive role of diffusion-weighted MRI in the assessment of response to total neoadjuvant therapy in locally advanced rectal cancer

Objective To investigate the predictive role of diffusion-weighted magnetic resonance imaging (DW-MRI) in the assessment of response to total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC). Methods In this single-center retrospective study, patients with LARC who underwent staging MRI and TNT were enrolled. MRI-based staging, tumor volume, and DWI-ADC values were analyzed. Patients were classified as complete responders (pCR) and non-complete responders (non-pCR), according to post-surgical outcome. Pre-treatment ADC values were compared to pathological outcome, post-treatment downstaging, and reduction of tumor volume. The diagnostic accuracy of DWI-ADC in differentiating between pCR and non-pCR groups was calculated with receiver operating characteristic (ROC) analysis. Results A total of 36 patients were evaluated (pCR, n = 20; non-pCR, n = 16). Pre-treatment ADC values were significantly different between the two groups (p = 0.034), while no association was found between pre-TNT tumor volume and pathological response. ADC values showed significant correlations with loco-regional downstaging after therapy (r = -0.537, p = 0.022), and with the reduction of tumor volume (r = -0.480, p = 0.044). ADC values were able to differentiate pCR from non-pCR patients with a sensitivity of 75% and specificity of 70%. Conclusions ADC values on pre-treatment MRI were strongly associated with the outcome in patients with LARC, both in terms of pathological response and in loco-regional downstaging after TNT, suggesting the use of DW-MRI as a potential predictive tool of response to therapy

cAMP-specific phosphodiesterase 8A and 8B isoforms are differentially expressed in human testis and Leydig cell tumor

Cyclic adenosine monophosphate/Protein kinase A (cAMP/PKA) signaling pathway is the master regulator of endocrine tissue function. The level, compartmentalization and amplitude of cAMP response are finely regulated by phosphodiesterases (PDEs). PDE8 is responsible of cAMP hydrolysis and its expression has been characterized in all steroidogenic cell types in rodents including adrenal and Leydig cells in rodents however scarce data are currently available in humans. Here we demonstrate that human Leydig cells express both PDE8A and PDE8B isoforms. Interestingly, we found that the expression of PDE8B but not of PDE8A is increased in transformed Leydig cells (Leydig cell tumors-LCTs) compared to non-tumoral cells. Immunofluorescence analyses further reveals that PDE8A is also highly expressed in specific spermatogenic stages. While the protein is not detected in spermatogonia it accumulates nearby the forming acrosome, in the trans-Golgi apparatus of spermatocytes and spermatids and it follows the fate of this organelle in the later stages translocating to the caudal part of the cell. Taken together our findings suggest that 1) a specific pool(s) of cAMP is/are regulated by PDE8A during spermiogenesis pointing out a possible new role of this PDE8 isoform in key events governing the differentiation and maturation of human sperm and 2) PDE8B can be involved in Leydig cell transformation

Prospective comparative trial on nerve-sparing radical prostatectomy using a robot-assisted versus laparoscopic technique: expectation versus satisfaction and impact on surgical margins

Introduction: The aim of this study was to analyze whether differences exist in a population selected for a nerve-sparing (NS) procedure between robot-assisted (RARP) and laparoscopic radical prostatectomy (LRP), and whether they can have an impact on surgical margins (SM) status. Material and methods: This is a single center prospective comparative trial on prostate cancer patients submitted to a RARP-NS or LRP-NS. A self-administered questionnaire on expectations before surgery, and level of satisfaction after surgery was used. Results: A total of 134 cases were included in our analysis. A higher percentage of capsular bulging was found in the RARP group, compared to the LRP group (p = 0.077). At biopsy, the percentage of positive cores and multifocality were higher in the RARP group (p = 0.005). Positive SM (SM+) rate was higher in the RARP, than in LRP group (p = 0.046). On univariable analysis, the risk of SM+ increased 1.95 times using RARP when compared with LRP. On multivariable analysis, the surgical approach did not maintain a significant predictive role in terms of risk for SM+. Expectations before surgery were mainly focused on oncological radicality, however in the RARP group a higher percentage of cases focused on sexual function recovery. Satisfaction after surgery was lower in the RARP than in the LRP group. Conclusions: Comparing LRP-NS with RARP-NS in a high-volume single center, the expectation/satisfaction ratio is in favor of LRP. Worse oncologic preoperative characteristics in the RARP group may influence the higher incidence of SM+. However, the surgical approach does not result as a significant and independent factor able to influence SM positivity