Enzymatic micro/nanomotors in biomedicine: from single motors to swarms.

Micro/nanomotors (MNMs) have evolved from single self-propelled entities to versatile systems capable of performing one or multiple biomedical tasks. When single MNMs self-assemble into coordinated swarms, either under external control or triggered by chemical reactions, they offer advantages that individual MNMs cannot achieve. These benefits include intelligent multitasking and adaptability to changes in the surrounding environment. Here, we provide our perspective on the evolution of MNMs, beginning with the development of enzymatic MNMs since the first theoretical model was proposed in 2005. These enzymatic MNMs hold immense promise in biomedicine due to their advantages in biocompatibility and fuel availability. Subsequently, we introduce the design and application of single motors in biomedicine, followed by the control of MNM swarms and their biomedical applications. In the end, we propose viable solutions for advancing the development of MNM swarms and anticipate valuable insights into the creation of more intelligent and controllable MNM swarms for biomedical applications.

Prevalence, distribution, and clinical associations of suspected postictal changes on brain magnetic resonance imaging in epileptic dogs.

OBJECTIVE: To determine the prevalence of presumed postictal changes (PC) on brain MRI in epileptic dogs, describe their distribution, and recognize possible correlations with different epilepsy features. ANIMALS: 540 client-owned dogs with epilepsy and a complete medical record that underwent brain MRI at 4 veterinary referral hospitals between 2016 and 2019. PROCEDURES: Data were collected regarding signalment, seizure type, seizure severity, time between last seizure and MRI, and etiological classification of epilepsy. Postictal changes were considered when solitary or multiple intraparenchymal hyperintense lesions were observed on T2-weighted and fluid-attenuated inversion recovery images and were hypointense or isointense on T1-weighted sequences, which were not confined to a vascular territory and showed no to mild mass effect and no to mild contrast enhancement. RESULTS: Sixty-seven dogs (12.4%) showed MRI features consistent with PC. The most common brain sites affected were the piriform lobe, hippocampus, temporal neocortex, and cingulate gyrus. Dogs having suffered cluster seizures or status epilepticus were associated with a higher probability of occurrence of PC, compared to dogs with self-limiting seizures (OR 2.39; 95% confidence interval, 1.33 to 4.30). Suspected PC were detected both in dogs with idiopathic epilepsy and in those with structural epilepsy. Dogs with unknown-origin epilepsy were more likely to have presumed PC than were dogs with structural (OR 0.15; 95% confidence interval, 0.06 to 0.33) or idiopathic epilepsy (OR 0.42; 95% confidence interval, 0.20 to 0.87). Time between last seizure and MRI was significantly shorter in dogs with PC. CLINICAL RELEVANCE: MRI lesions consistent with PC were common in epileptic dogs, and the brain distribution of these lesions varied. Occurrence of cluster seizures or status epilepticus, diagnosis of unknown origin epilepsy, and lower time from last seizure to MRI are predictors of suspected PC.

Survival analysis of bevacizumab plus taxane treatment in luminal metastatic breast cancer.

BACKGROUND: The treatment of luminal metastatic breast cancer is based on endocrine therapy and chemotherapy treatment is limited to the progression of this treatment. MATERIALS & METHODS: We analyzed the efficacy of treatment with bevacizumab plus paclitaxel in 43 patients with hormone receptor-positive and HER2-negative metastatic breast cancer. DISCUSSION: Paclitaxel plus bevacizumab combination is a useful treatment in metastatic luminal breast cancer with an impressive overall survival of 31 months, similar to combination to endocrine therapy and targeted therapy in first line. In patients with hormone resistance, endocrine therapy saw worse results thus the taxol plus bevacizumab combination could be a better option. This combination does not influence the results of subsequent treatments; therefore, it could provide a good option for patients.

Selection of neoadjuvant treatment based on the 21-GENE test results in luminal breast cancer.

Neoadjuvant chemotherapy (NAC) is an optimal option in early breast cancer, but in ER-positive/HER2-negative (luminal) is still controversial, although a survival benefit has recently been observed when a histological response by Symmans' method type 0 or I is achieved. The 21-gene Oncotype DX Breast Recurrence Score® assay (Oncotype DX®) is a validated test to assess the survival benefit of adjuvant chemotherapy in these patients but its role in the neoadjuvant setting is less established. We analyzed the results of the Oncotype DX® test in a cohort of 122 consecutive patients selected to receive NAC based on classical clinicopathological parameters and the correlation between the Oncotype DX® results and the pathological response assessed by Symmans' method. Median age was 56.5 (range 31-84) years. Initial tumor size was T1 (<20 mm) in 46 patients (37.7%), 57 (46.7%) had a T2 tumor (20-50 mm), and 19 (15.6%) had a tumor size more than 50 mm. 59 (48.4%) had axillary node involvement. The median expression estrogen and progesteron receptors by immunohistochemistry was 280 and 120 respectively and median Ki67 index was 28%. The Recurrence Score (RS) results were <11 in 21 patients (17.2%) patients, RS 11 to 25 in 58 (47.5%), and RS > 25 in 43 (35.2%). Considering the Oncotype DX test results, neoadjuvant chemotherapy was administered to 60 patients (49%), 11 (9%) received adjuvant chemotherapy and 51 (42%) no chemotherapy. Testing with the assay has therefore led to 42% fewer chemotherapy treatments. Among 60 patients receiving NAC, pathologic response was achieved for 5 patients (8.3%) with RCB-0 and 15 RCB-1 (25%). We did not find any pathological response RCB-0 and RCB-I in the 20 patients who received NAC and had a Recurrence Score result <21 for the premenopausal group, or a RS result <25 for the postmenopausal group. For patients with highest Recurrence Score results (RS > 21 or 25 according to menopausal status) it was 12% (5/40) RCB-0 and 40% (16/40) RCB-I. CONCLUSIONS: The Oncotype DX test could be a useful tool to select patients candidates for neoadjuvant chemotherapy in luminal breast cancer. Neoadjuvant chemotherapy could be avoided in 42% of patients. We found a correlation between Recurrence Score results and pathological response with 14% of RCB-0 and a total of 47% of significant pathological response type RCB-0 and RCB-I in patients with highest Recurrence Score results. Interestingly, patients with a Recurrence Score result inferior to 32 did not get any histological response type 0 and only 5% RCB-I.

1.5 Tesla Magnetic Resonance Imaging Features of Canine Intracranial Intra-axial Hematomas.

The differentiation of solitary intra-axial hematomas from hemorrhagic neoplasms based on their magnetic resonance imaging (MRI) features is challenging. The treatment and prognosis for these two disease entities are vastly different and distinction between them is often based on MRI findings alone. The aim of this study was to describe the 1.5 tesla MRI features of canine intra-axial hematomas and correlate these findings with the evolution of hemorrhages described in human brains. Retrospective evaluation of patient details, clinical signs, and MRI findings of dogs with intra-axial hematomas that were histopathologically confirmed or determined via repeat MRI study and/or resolution of neurological signs. Ten dogs met the inclusion criteria. All 10 hematoma lesions were determined to be 2-7 days in age. On MRI, all 10 hemorrhagic lesions were comprised of two distinct regions; a relatively thin T1-weighted (T1W), T2-weighted (T2W) and gradient echo (GRE) hypointense (9/10) peripheral border region and a large central region that was heterogenous but predominantly T1W, T2W and GRE hyperintense (8/10). The peripheral border region was complete in its integrity in all 10 cases on T2W and GRE sequences. Contrast enhancement was present in (6/10) hematoma lesions and was always peripheral in nature with no evidence of central enhancement associated with any of the lesions. An intra-axial hematoma should be suspected in solitary hemorrhagic space occupying lesions that have a complete hypointense peripheral rim, elicit a peripheral contrast enhancement pattern, and display the expected temporal pattern of hematoma evolution.

Presumptive Cycad Toxicosis in a Dog. Clinical and Magnetic Resonance Imaging Findings: A Case Report.

Cases of cycad toxicosis have been described in dogs that have presented with gastrointestinal, hematologic, hepatic, neurological, and carcinogenic signs. This case report describes brain magnetic resonance imaging (MRI) lesions in a dog with gastrointestinal and neurological signs secondary to cycad toxicosis. A 5-year-old neutered female Jack Russell terrier presented with a 2-days history of gastroenteric signs, progressive generalized tremors, and altered mentation after possible ingestion of Cycad revoluta. Neurologic examinations revealed disorientation, a wide-based stance, severe spasticity of the four limbs, intention tremors, severe cerebellar ataxia, decreased postural reactions in all four limbs, and intermittent decreased menace response in both eyes-all of which are consistent with a multifocal intracranial disorder involving the forebrain and cerebellum. A brain MRI showed diffuse/ill-defined, intra-axial bilateral and symmetrical changes, predominantly affecting the white matter of the cerebral hemispheres, thalamus, hippocampus, and cerebellum. A presumptive diagnosis of toxic-metabolic encephalopathy was made. Medical management of the clinical signs was performed, and the dog was discharged 7 days after presentation with no neurological abnormalities. Two and 8 weeks later, complete blood count (CBC), chemistry, electrolytes, and 8 weeks later brain MRI were performed, revealing no abnormalities. To the best of the authors' knowledge, this is the first case report describing lesions detected by brain MRI secondary to cycad toxicosis as well as a complete resolution of brain lesions on a follow-up MRI 8 weeks later.

Susceptibility weighted imaging at 1.5 Tesla magnetic resonance imaging in dogs: Comparison with T2*-weighted gradient echo sequence and its clinical indications.

Susceptibility weighted imaging (SWI) is a high resolution, fully velocity-compensated, three-dimensional gradient echo (GE) MRI technique. In humans, SWI has been reported to be more sensitive than T2*-weighted GE sequences in the identification of both intracranial hemorrhage and intra-vascular deoxyhemoglobin. However, published clinical studies comparing SWI to T2*-weighted GE sequences in dogs are currently lacking. The aim of this retrospective, observational study was to compare SWI and T2*-weighted GE sequences in a group of dogs with intracranial disease. Medical records were searched for dogs that underwent a brain MRI examination that included T2*-weighted GE and SWI sequences. The presence and appearance of non-vascular and vascular signal voids observed on T2*-weighted GE and SWI were compared. Thirty-two dogs were included with the following diagnoses: presumed and confirmed intracranial neoplasia (27), cerebrovascular accidents (3), and trauma (2). Hemorrhagic lesions were significantly more conspicuous on SWI than T2*-weighted GE sequences (P < .0001). Venous structures were well defined in all SWI sequences, and poorly defined in all dogs on T2*-weighted GE. Susceptibility weighted imaging enabled identification of vascular abnormalities in 30 of 32 (93.8%) dogs, including: neovascularization in 19 of 32 (59.4%) dogs, displacement of perilesional veins in five of 32 (15.6%) dogs, and apparent dilation of perilesional veins in 10 of 32 (31.3%) dogs. Presence of neovascularization was significantly associated with T1-weighted post-contrast enhancement (P = .0184). Hemorrhagic lesions and venous structures were more conspicuous on SWI compared to T2*-weighted GE sequences. Authors recommend adding SWI to standard brain protocols in dogs for detecting hemorrhage and identifying venous abnormalities for lesion characterization.

Clinical features and MRI characteristics of presumptive constrictive myelopathy in 27 pugs.

Constrictive myelopathy has been described in pugs with paraparesis and is characterized by fibrous connective and granulation tissue within the dura mater causing spinal cord compression and focal gliosis. An association between constrictive myelopathy and caudal articular process (CAP) dysplasia is suspected; however, some studies have reported CAP dysplasia as an incidental finding. The imaging appearance of constrictive myelopathy is currently limited to a small number of cases. The aim of this multicenter, retrospective, descriptive study was to detail the magnetic resonance imaging (MRI) characteristics and to correlate these with clinical signs of presumptive constrictive myelopathy in pugs. Medical databases from five veterinary referral hospitals were reviewed to identify pugs with pelvic limb ataxia and paresis, that had a complete record of signalment, neurological examination, and MRI of the thoracolumbar spinal cord. The exclusion criteria were pugs with other conditions, such as unequivocal subarachnoid diverticula, hemivertebrae causing vertebral canal stenosis, intervertebral disc extrusions/protrusions, and multifocal/diffuse lesions. Twenty-seven pugs met the inclusion criteria. All cases were ambulatory with paraparesis and ataxia. Nearly 60% were incontinent. Magnetic resonance imaging revealed a focal myelopathy in all cases showing one or more of the following lesions: CAP dysplasia (25/27), focal subarachnoid space irregular margination (26/27) with circumferential or dorsal contrast enhancement (10/12), and a symmetric V-shaped ventral extradural lesion (23/27). This study describes specific MRI features of pugs with presumptive constrictive myelopathy, which authors hypothesize to be a consequence of chronic micro-motion. Our results may help in diagnosing and subsequently treating this condition, which may warrant vertebral stabilization.

Use of Three-Dimensional Printing Models for Veterinary Medical Education: Impact on Learning How to Identify Canine Vertebral Fractures.

Vertebral fractures and luxations are common causes of neurological emergencies in small-animal patients. The objective of this study was to evaluate the impact of three-dimensional printing (3Dp) models on how veterinary students understand and learn to identify canine spinal fractures and to compare 3Dp models to computed tomography (CT) images and three-dimensional CT (3D-CT) reconstructions. Three spinal fracture models were generated by 3Dp. Sixty first-year veterinary students were randomized into three teaching module groups (CT, 3D-CT, or 3Dp) and asked to answer a multiple-choice questionnaire with 12 questions that covered normal spinal anatomy and the identification of vertebral fractures. We used four additional questions to evaluate the overall learning experience and knowledge acquisition. Results showed that students in the 3Dp group performed significantly better than those in the CT (p < .001) and the 3D-CT (p < .001) groups. Students in the 3Dp and 3D-CT groups answered all questions more quickly than the CT group (3Dp versus CT, p < .001; 3D-CTversus CT, p < .001), with no significant differences between the 3Dp and 3D-CT groups (p = .051). Only the degree of knowledge acquisition that the students considered they had acquired during the session showed significant differences between groups (p = .01). In conclusion, across first-year veterinary students, 3Dp models facilitated learning about normal canine vertebral anatomy and markedly improved the identification of canine spinal fractures. Three-dimensional printing models are an easy and inexpensive teaching method that could be incorporated into veterinary neuroanatomy classes to improve learning in undergraduate students.

Machine learning in critical care: state-of-the-art and a sepsis case study.

BACKGROUND: Like other scientific fields, such as cosmology, high-energy physics, or even the life sciences, medicine and healthcare face the challenge of an extremely quick transformation into data-driven sciences. This challenge entails the daunting task of extracting usable knowledge from these data using algorithmic methods. In the medical context this may for instance realized through the design of medical decision support systems for diagnosis, prognosis and patient management. The intensive care unit (ICU), and by extension the whole area of critical care, is becoming one of the most data-driven clinical environments. RESULTS: The increasing availability of complex and heterogeneous data at the point of patient attention in critical care environments makes the development of fresh approaches to data analysis almost compulsory. Computational Intelligence (CI) and Machine Learning (ML) methods can provide such approaches and have already shown their usefulness in addressing problems in this context. The current study has a dual goal: it is first a review of the state-of-the-art on the use and application of such methods in the field of critical care. Such review is presented from the viewpoint of the different subfields of critical care, but also from the viewpoint of the different available ML and CI techniques. The second goal is presenting a collection of results that illustrate the breath of possibilities opened by ML and CI methods using a single problem, the investigation of septic shock at the ICU. CONCLUSION: We have presented a structured state-of-the-art that illustrates the broad-ranging ways in which ML and CI methods can make a difference in problems affecting the manifold areas of critical care. The potential of ML and CI has been illustrated in detail through an example concerning the sepsis pathology. The new definitions of sepsis and the relevance of using the systemic inflammatory response syndrome (SIRS) in its diagnosis have been considered. Conditional independence models have been used to address this problem, showing that SIRS depends on both organ dysfunction measured through the Sequential Organ Failure (SOFA) score and the ICU outcome, thus concluding that SIRS should still be considered in the study of the pathophysiology of Sepsis. Current assessment of the risk of dead at the ICU lacks specificity. ML and CI techniques are shown to improve the assessment using both indicators already in place and other clinical variables that are routinely measured. Kernel methods in particular are shown to provide the best performance balance while being amenable to representation through graphical models, which increases their interpretability and, with it, their likelihood to be accepted in medical practice.

Traumatic L7 articular processes fracture and spondylolisthesis following dorsal lumbosacral laminectomy in a cat.

CASE SUMMARY: A 12-year-old neutered male domestic shorthair cat was presented to our referral hospital with a chronic history of tenesmus and lumbosacral pain. A diagnosis of degenerative lumbosacral stenosis (DLSS) was made and a standard dorsal L7-S1 laminectomy was performed uneventfully, with complete recovery within 1 month. The cat was brought back 4 months later for investigation of lumbosacral pain after having suffered a minor traumatic event. Neurological examination identified a low tail carriage, weakness, exercise intolerance, left pelvic limb lameness and diminished withdrawal reflexes in both pelvic limbs with severe sacrocaudal pain. A traumatic facet fracture of the L7 articular processes and subsequent spondylolisthesis was diagnosed. A second surgery was performed to stabilise the region. The cat was normal on neurological examination 1 month later and no further clinical signs were noted. RELEVANCE AND NOVEL INFORMATION: This is the first description of a fracture and spondylolisthesis as a possible postoperative complication after L7-S1 dorsal laminectomy in a cat. The case highlights the importance of postoperative changes in the supportive structures of the lumbosacral spine in cats after surgical treatment of DLSS.