Cerebellar–Motor Cortex Connectivity: One or Two Different Networks?

Anterior-posterior (AP) and posterior-anterior (PA) pulses of transcranial magnetic stimulation over the primary motor cortex (M1) appear to activate distinct interneuron networks that contribute differently to two varieties of physiological plasticity and motor behaviors (Hamada et al., 2014). The AP network is thought to be more sensitive to online manipulation of cerebellar (CB) activity using transcranial direct current stimulation. Here we probed CB-M1 interactions using cerebellar-brain inhibition (CBI) on young healthy female and male individuals. Transcranial magnetic stimulation (TMS) over the cerebellum produced maximal CBI of PA-evoked EMG responses at an inter-stimulus interval of 5ms (PA-CBI), whereas the maximum effect on AP responses was at 7ms (AP-CBI), suggesting that CB-M1 pathways with different conduction times interact with AP and PA networks. In addition, paired associative stimulation using ulnar nerve stimulation and PA TMS pulses over M1, a protocol used in human studies to induce cortical plasticity, reduced PA-CBI but not AP-CBI, indicating that cortical networks process cerebellar inputs in distinct ways. Finally, PA-CBI and AP-CBI were differentially modulated after performing two different types of motor learning tasks that are known to process cerebellar input in different ways. The data presented here are compatible with the idea that applying different TMS currents to the cerebral cortex may reveal cerebellar inputs to both the premotor cortex and M1. Overall, these results suggest there are two independent CB-M1networks that contribute uniquely to different motor behaviors

SICI during changing brain states: Differences in methodology can lead to different conclusions

Background: Short-latency intracortical inhibition (SICI) is extensively used to probe GABAergic inhibitory mechanisms in M1. Task-related changes in SICI are presumed to reflect changes in the central excitability of GABAergic pathways. Usually, the level of SICI is evaluated using a single intensity of conditioning stimulus so that inhibition can be compared in different brain states. Objective: Here, we show that this approach may sometimes be inadequate since distinct conclusions can be drawn if a different CS intensity is used. Methods: We measured SICI using a range of CS intensities at rest and during a warned simple reaction time task. Conclusions: Our results show that SICI changes that occurred during the task could be either larger or smaller than at rest depending on the intensity of the CS. These findings indicate that careful interpretation of results are needed when a single intensity of CS is used to measure task-related physiological changes

Cerebellar-M1 Connectivity Changes Associated with Motor Learning Are Somatotopic Specific

One ofthefunctions ofthe cerebellum in motor learning isto predict and accountfor systematic changestothe body or environment. This form of adaptive learning is mediated by plastic changes occurring within the cerebellar cortex. The strength of cerebellar-to-cerebral pathways for a given muscle may reflect aspects of cerebellum-dependent motor adaptation. These connections with motor cortex (M1) can be estimated as cerebellar inhibition (CBI): a conditioning pulse of transcranial magnetic stimulation delivered to the cerebellum before a test pulse over motor cortex. Previously, we have demonstrated that changes in CBI for a given muscle representation correlate with learning a motor adaptation task with the involved limb. However, the specificity of these effects is unknown. Here, we investigated whether CBI changes in humans are somatotopy specific and how they relate to motor adaptation. We found that learning a visuomotor rotation task with the right hand changed CBI, not only for the involved first dorsal interosseous of the right hand, but also for an uninvolved right leg muscle, the tibialis anterior, likely related to inter-effector transfer of learning. In two follow-up experiments, we investigated whether the preparation of a simple hand or leg movement would produce a somatotopy-specific modulation of CBI. We found that CBI changes only for the effector involved in the movement. These results indicate that learning-related changes in cerebellar–M1 connectivity reflect a somatotopy-specific interaction. Modulation of this pathway is also present in the context of interlimb transfer of learning

Modulation of surface bio-functionality by using gold nanostructures on protein repellent surfaces

The integration of gold nanoparticles (Au NPs) or nanostructures with special optical properties on solid surfaces has become a major research topic in the field of nanobiotechnology in particular for the development of new generation of multifunctional bioanalytical platforms. This has led to considerable research efforts for developing quick and direct nanofabrication methods capable of producing well-ordered 2D nanostructured arrays with tunable morphological, chemical and optical properties. In this paper, we propose a simple and fast nanofabrication method enabling the creation of Au NPs patterns on a non-adhesive and cell repellent plasma-deposited poly(ethyleneoxide) (PEO-like) coating. The immobilization of Au NPs on PEO-like coatings does not require any prior chemical modifications and is achieved by a straightforward and stable self-assembly technique. By varying the size and the concentration of the Au NPs it is possible to control the Au NPs density and spatial distribution on the PEO-like coated surface with direct effects on the bio-functionality of the surface. These nanostructured surfaces have been tested for protein bio-recognition analysis and as a cell culture platform. The developed nanostructured platform has many potential applications in the field of protein-nanoparticle and cell-nanoparticle interaction studies, nanotoxicology and bioengineering.JRC.I.4-Nanobioscience

Efficient long-range conduction in cable bacteria through nickel protein wires

Filamentous cable bacteria display long-range electron transport, generating electrical currents over centimeter distances through a highly ordered network of fibers embedded in their cell envelope. The conductivity of these periplasmic wires is exceptionally high for a biological material, but their chemical structure and underlying electron transport mechanism remain unresolved. Here, we combine high-resolution microscopy, spectroscopy, and chemical imaging on individual cable bacterium filaments to demonstrate that the periplasmic wires consist of a conductive protein core surrounded by an insulating protein shell layer. The core proteins contain a sulfur-ligated nickel cofactor, and conductivity decreases when nickel is oxidized or selectively removed. The involvement of nickel as the active metal in biological conduction is remarkable, and suggests a hitherto unknown form of electron transport that enables efficient conduction in centimeter-long protein structures

Management of colorectal cancer presenting with synchronous liver metastases

Up to a fifth of patients with colorectal cancer (CRC) present with synchronous hepatic metastases. In patients with CRC who present without intestinal obstruction or perforation and in whom comprehensive whole-body imaging confirms the absence of extrahepatic disease, evidence indicates a state of equipoise between several different management pathways, none of which has demonstrated superiority. Neoadjuvant systemic chemotherapy is advocated by current guidelines, but must be integrated with surgical management in order to remove the primary tumour and liver metastatic burden. Surgery for CRC with synchronous liver metastases can take a number of forms: the 'classic' approach, involving initial colorectal resection, interval chemotherapy and liver resection as the final step; simultaneous removal of the liver and bowel tumours with neoadjuvant or adjuvant chemotherapy; or a 'liver-first' approach (before or after systemic chemotherapy) with removal of the colorectal tumour as the final procedure. In patients with rectal primary tumours, the liver-first approach can potentially avoid rectal surgery in patients with a complete response to chemoradiotherapy. We overview the importance of precise nomenclature, the influence of clinical presentation on treatment options, and the need for accurate, up-to-date surgical terminology, staging tests and contemporary management options in CRC and synchronous hepatic metastatic disease, with an emphasis on multidisciplinary care

Motor primitives in space and time via targeted gain modulation in cortical networks

Motor cortex (M1) exhibits a rich repertoire of activities to support the generation of complex movements. Recent network models capture many qualitative aspects of M1 dynamics, but they can generate only a few distinct movements (all of the same duration). We demonstrate that simple modulation of neuronal input–output gains in recurrent neuronal network models with fixed connectivity can dramatically reorganize neuronal activity and consequently downstream muscle outputs. We show that a relatively small number of modulatory control units provide sufficient flexibility to adjust high-dimensional network activity using a simple reward-based learning rule. Furthermore, novel movements can be assembled from previously-learned primitives and we can separately change movement speed while preserving movement shape. Our results provide a new perspective on the role of modulatory systems in controlling recurrent cortical activity.Our work was supported by grants from the Wellcome Trust (TPV and JPS WT100000, 246 GH 202111/Z/16/Z) and the Engineering and Physical Sciences Research Council (JPS)

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks