The gut microbiome and adult hippocampal neurogenesis: A new focal point for epilepsy?

Temporal lobe epilepsy (TLE) is a neurological disorder affecting millions of people worldwide and currently represents the most common form of focal epilepsy. Thus, the search for aetiological and pathophysiological parameters of TLE is ongoing. Preclinical work and post-mortem human studies suggest adult hippocampal neurogenesis as a potentially relevant factor in TLE pathogenesis. Although progress has been made in elucidating the molecular links between TLE and hippocampal neurogenesis, recent evidence suggests that additional peripheral mediators may be involved. The microbiota-gut-brain axis mediates bidirectional communication between the gut and the brain and could comprise a link between neurogenesis and TLE. In this review, we discuss emerging evidence highlighting a potential role for the gut microbiome in connecting TLE pathogenesis and hippocampal neurogenesis. We focus in particular on mechanisms associated with neuronal excitability, neuroinflammation and gut microbial metabolites. As the evidence does not yet support a direct link between gut microbiota-regulated hippocampal neurogenesis and TLE aetiology or pathophysiology, future studies are needed to establish whether current findings comprise circumstantial links or a potentially novel avenue for clinically relevant research.

Investigating the potential of fish oil as a nutraceutical in an animal model of early life stress.

Background: Early life stress is a key predisposing factor for depression and anxiety disorders. Selective serotonin re-uptake inhibitors (SSRI) are frequently used as the first line of pharmacology treatment for depression but have several negative qualities, i.e. a delay or absence of effectiveness and negative side-effects. Therefore, there is a growing need for new nutraceutical-based strategies to blunt the effects of adverse-life events.Objectives: This study aimed to use the maternal separation model in rats to test the efficacy of fish oil dietary supplementation, on its own and in conjunction with the SSRI anti-depressant fluoxetine, as a treatment for depressive and anxiety-like symptoms associated with early life stress.Methods: Behavioural tests (open field test, elevated plus maze test and forced swim test) and biochemical markers (corticosterone, BDNF, brain fatty acids and short chain fatty acids) were used to analyse the effects of the dietary treatments. Gut microbial communities and relating metabolites (SCFA) were analysed to investigate possible changes in the microbiota-gut-brain axis.Results: Maternally separated rats showed depressive-like behaviours in the forced swim and open field tests. These behaviours were prevented significantly by fluoxetine administration and in part by fish oil supplementation. Associated biochemical changes reported include altered brain fatty acids, significantly lower plasma corticosterone levels (AUC) and reduced brain stem serotonin turnover, compared to untreated, maternally separated (MS) rats. Untreated MS animals had significantly lower ratios of SCFA producers such as Caldicoprobacteraceae, Streptococcaceae, Rothia, Lachnospiraceae_NC2004_group, and Ruminococcus_2, along with significantly reduced levels of total SCFA compared to non-separated animals. Compared to untreated MS animals, animals fed fish oil had significantly higher Bacteroidetes and Prevotellaceae and reduced levels of butyrate, while fluoxetine treatment resulted in significantly higher levels of Neochlamydia, Lachnoclostridium, Acetitomaculum and Stenotrophomonas and, acetate and propionate.Conclusion: Despite the limitations in extrapolating from animal behavioural data and the notable differences in pharmacokinetics between rodents and humans, the results of this study provide a further advancement into the understanding of some of the complex systems within which nutraceuticals and pharmaceuticals effect the microbiota-gut-brain axis.

A New, Conservative Treatment for Perianal Fistula that May Halve the Need for Surgical Intervention: Case Series.

PURPOSE: In the last two decades, many sphincter preservation techniques have been proposed for the treatment of anal fistula. Since 2011, our surgical team has treated fistulas by sealing them with platelet-rich fibrin (PRF). This is performed actually as an outpatient process, without anaesthesia. METHODS: Patients were treated with PRF sealant, during the period June 2012-March 2017. The fibrin preparation is applied in the fistulous tract, with no need for any type of anaesthesia, and so the patient can go home immediately afterwards, without further observation. RESULTS: After an average follow-up of 26.49 months, the perianal fistula had healed completely in 52.86% of the patients (n = 37), who each received an average of 1.92 sealant operations. In another 10 cases, the sealing was initially successful, but a relapse occurred during the follow-up period. CONCLUSION: The outpatient treatment of perianal fistula with PRF is totally harmless, is very low cost and achieves very acceptable results. In our opinion, therefore, this could be considered an appropriate initial treatment for perianal fistula, with surgical treatment being reserved if this approach is unsuccessful, thereby avoiding many complications and producing significant economic savings for the health system.

Experiences and mediating factors in nurses' responses to electronic device alarms: A phenomenological study.

AIM: This study aims to explore the experiences and mediating factors of nurses' responses to electronic device alarms in critical care units (CCUs). BACKGROUND: Alarm fatigue occasionally has adverse consequences for patient safety. METHODS: This qualitative study was designed and analysed following Giorgi's descriptive phenomenological approach. Seventeen nurses were theoretically sampled, reaching information saturation. Semistructured interviews were used to collect the data. RESULTS: Three central themes explained nurses' experiences: general perceptions about alarms (basic equipment of the CCU), strategies to reduce false alarms (training in the configuration of monitors, customization of the alarms to fit he patient's condition. teamwork and taking advantage of the development of technology) and key elements of the response to alarms (information about patient's condition, nurses' clinical experience, type of CCU, 'cry-wolf' phenomenon and nurse/patient ratio). CONCLUSIONS: To reduce false alarms, nurses need further postgraduate training, training on monitors and customizing alarms to fit the patient's health status. The complex process of deciding to respond to an alarm includes environmental, professional variables and patient status. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should ensure that nurses have sufficient experience and training in the CCU, improve the nurse/patient ratio, promote teamwork and ensure that the devices are the latest generation.

3D-Printed Surgical Steel Curettes for the Treatment of Perianal Fistula.

Need. The diversity of approaches proposed for the treatment of complex perianal fistulas reflects the fact that no method has yet been shown to be fully satisfactory. We believe the successful treatment of this condition is directly proportional to the amount of fibrous tissue that can be removed. Technical solution. We use a kit of small curettes, of different thicknesses and sizes, incorporating spicules that enable the physician to remove fibrous tissue from the fistula tract. The small size and varying thicknesses of the curettes enable them to mould to the curves of the fistula tract and to remove tissue by deroofing from the shallowest to the deepest layers, thus excising the entire fibrous tract. Our hospital has recently incorporated into clinical practice a new model of 3D-printed surgical steel curette, flanked by 2 lateral rings through which the suture is threaded. The central part of the curette contains radially graduated discs, the tips of which perform the debriding action, removing the fibrous tissue from the tract. Proof of concept. By using these curettes in conjunction with our standard technique (plugging the tract with platelet-rich fibrin), we have improved the success rate from 67% to 88%. Next steps. We have contacted several companies with a view to marketing this product. Conclusion. The results obtained are significantly better than those offered by the techniques in current use for the treatment of complex fistulas, without prejudice to outcomes such as anal continence and morbidity and mortality.

Quality of life in elderly people after a hip fracture: a prospective study.

BACKGROUND: Hip fracture is an important social and medical problem due to its increasing prevalence, the consequences for health and the economic impact on the health care system, but there is no doubt that it also has repercussions on health-related quality of life (HRQoL). Hence the importance of understanding and determining the impact of the condition on everyday life from the perspective of the patient's physical, emotional and social well-being. PURPOSE: To determine the impact of hip fracture on HRQoL of people over the age of 65 1 month after surgery, related factors and the effects on functional ability and mood. METHODS: Prospective observational study conducted in the traumatology units of two university hospitals in the province of Cáceres with consecutive sampling of all patients over the age of 65 admitted for hip fracture surgery during the study period. Sociodemographic and clinical data were recorded at the time of admission and prospectively at the follow-up visit 1 month later. Clinical, social, quality of life (EQ-5D-), basic functional and instrumental capacity (Barthel Index (BI) and Lawton & Brody Scale), and geriatric depression (Yesavage) variables were collected. RESULTS: The study included 224 patients with a median age of 84.6 years (SD ± 6.1), 76.3% were female. Charlson's comorbidity was 5.3 (SD ± 1.2). The EQ-5D index decreased from 0.62 (SD ± 0.35) to 0.16 at 1 month follow up (SD ± 0.20) p <  0.001. The mean Visual Analog Scale (VAS) score of EQ-5D decreased from 72.8 (SD ±15.8) to 48.3 (SD ± 17.2) p <  0.001. All dimensions of EQ-5D showed a significant reduction from the time of pre-fracture status to 1 month after surgery. Independent factors associated with HRQoL 1 month after surgery were pre-fracture status Barthel Index score, Lawton and Brody scale, presence of depression, and type of surgery. CONCLUSIONS: After a hip fracture, patients experience considerable deterioration in their HRQoL, especially in self-care, daily activities, and mobility. There is also a significant decline in functional capacity for both the basic and instrumental activities of daily living. One month after surgery, HRQoL is a long way from pre-fracture levels.

Naturally Derived Polyphenols Protect Against Corticosterone-Induced Changes in Primary Cortical Neurons.

BACKGROUND: Polyphenols are phytochemicals that have been associated with therapeutic effects in stress-related disorders. Indeed, studies suggest that polyphenols exert significant neuroprotection against multiple neuronal injuries, including oxidative stress and neuroinflammation, but the mechanisms are unclear. Evidence indicates that polyphenol neuroprotection may be mediated by activation of Nrf2, a transcription factor associated with antioxidant and cell survival responses. On the other hand, in stress-linked disorders, Fkbp5 is a novel molecular target for treatment because of its capacity to regulate glucocorticoid receptor sensitivity. However, it is not clear the role Fkbp5 plays in polyphenol-mediated stress modulation. In this study, the neuroprotective effects and mechanisms of the naturally derived polyphenols xanthohumol and quercetin against cytotoxicity induced by corticosterone were investigated in primary cortical cells. METHODS: Primary cortical cells containing both neurons and astrocytes were pre-incubated with different concentrations of quercetin and xanthohumol to examine the neuroprotective effects of polyphenols on cell viability, morphology, and gene expression following corticosterone insult. RESULTS: Both polyphenols tested prevented the reduction of cell viability and alterations of neuronal/astrocytic numbers due to corticosterone exposure. Basal levels of Bdnf mRNA were also decreased after corticosterone insult; however, this was reversed by both polyphenol treatments. Interestingly, the Nrf2 inhibitor blocked xanthohumol but not quercetin-mediated neuroprotection. In contrast, we found that Fkbp5 expression is exclusively modulated by quercetin. CONCLUSIONS: These results suggest that naturally derived polyphenols protect cortical cells against corticosterone-induced cytotoxicity and enhance cell survival via modulation of the Nrf2 pathway and expression of Fkbp5.

Inferring Static Hand Poses from a Low-Cost Non-Intrusive sEMG Sensor.

Every year, a significant number of people lose a body part in an accident, through sickness or in high-risk manual jobs. Several studies and research works have tried to reduce the constraints and risks in their lives through the use of technology. This work proposes a learning-based approach that performs gesture recognition using a surface electromyography-based device, the Myo Armband released by Thalmic Labs, which is a commercial device and has eight non-intrusive low-cost sensors. With 35 able-bodied subjects, and using the Myo Armband device, which is able to record data at about 200 MHz, we collected a dataset that includes six dissimilar hand gestures. We used a gated recurrent unit network to train a system that, as input, takes raw signals extracted from the surface electromyography sensors. The proposed approach obtained a 99.90% training accuracy and 99.75% validation accuracy. We also evaluated the proposed system on a test set (new subjects) obtaining an accuracy of 77.85%. In addition, we showed the test prediction results for each gesture separately and analyzed which gestures for the Myo armband with our suggested network can be difficult to distinguish accurately. Moreover, we studied for first time the gated recurrent unit network capability in gesture recognition approaches. Finally, we integrated our method in a system that is able to classify live hand gestures.

Inflammation, Lifestyle Factors, and the Microbiome-Gut-Brain Axis: Relevance to Depression and Antidepressant Action.

Depression is considered a major public health concern, where existing pharmacological treatments are not equally effective across all patients. The pathogenesis of depression involves the interaction of complex biological components, such as the immune system and the microbiota-gut-brain axis. Adjunctive lifestyle-oriented approaches for depression, including physical exercise and special diets are promising therapeutic options when combined with traditional antidepressants. However, the mechanisms of action of these strategies are incompletely understood. Accumulating evidence suggests that physical exercise and specific dietary regimens can modulate both the immune system and gut microbiota composition. Here, we review the current information about the strategies to alleviate depression and their crosstalk with both inflammatory mechanisms and the gut microbiome. We further discuss the role of the microbiota-gut-brain axis as a possible mediator for the adjunctive therapies for depression through inflammatory mechanisms. Finally, we review existing and future adjunctive strategies to manipulate the gut microbiota with potential use for depression, including physical exercise, dietary interventions, prebiotics/probiotics, and fecal microbiota transplantation.

A kinematic, imaging and electromyography dataset for human muscular manipulability index prediction.

Human Muscular Manipulability is a metric that measures the comfort of an specific pose and it can be used for a variety of applications related to healthcare. For this reason, we introduce KIMHu: a Kinematic, Imaging and electroMyography dataset for Human muscular manipulability index prediction. The dataset is comprised of images, depth maps, skeleton tracking data, electromyography recordings and 3 different Human Muscular Manipulability indexes of 20 participants performing different physical exercises with their arm. The methodology followed to acquire and process the data is also presented for future replication. A specific analysis framework for Human Muscular Manipulability is proposed in order to provide benchmarking tools based on this dataset.

Artificial Intelligence-based System for Detecting Attention Levels in Students.

The attention level of students in a classroom can be improved through the use of Artificial Intelligence (AI) techniques. By automatically identifying the attention level, teachers can employ strategies to regain students' focus. This can be achieved through various sources of information. One source is to analyze the emotions reflected on students' faces. AI can detect emotions, such as neutral, disgust, surprise, sadness, fear, happiness, and anger. Additionally, the direction of the students' gaze can also potentially indicate their level of attention. Another source is to observe the students' body posture. By using cameras and deep learning techniques, posture can be analyzed to determine the level of attention. For example, students who are slouching or resting their heads on their desks may have a lower level of attention. Smartwatches distributed to the students can provide biometric and other data, including heart rate and inertial measurements, which can also be used as indicators of attention. By combining these sources of information, an AI system can be trained to identify the level of attention in the classroom. However, integrating the different types of data poses a challenge that requires creating a labeled dataset. Expert input and existing studies are consulted for accurate labeling. In this paper, we propose the integration of such measurements and the creation of a dataset and a potential attention classifier. To provide feedback to the teacher, we explore various methods, such as smartwatches or direct computers. Once the teacher becomes aware of attention issues, they can adjust their teaching approach to re-engage and motivate the students. In summary, AI techniques can automatically identify the students' attention level by analyzing their emotions, gaze direction, body posture, and biometric data. This information can assist teachers in optimizing the teaching-learning process.

UrOAC: Urban objects in any-light conditions.

In the past years, several works on urban object detection from the point of view of a person have been made. These works are intended to provide an enhanced understanding of the environment for blind and visually challenged people. The mentioned approaches mostly rely in deep learning and machine learning methods. Nonetheless, these approaches only work with direct and bright light, namely, they will only perform correctly on daylight conditions. This is because deep learning algorithms require large amounts of data and the currently available datasets do not address this matter. In this work, we propose UrOAC, a dataset of urban objects captured in a range of different lightning conditions, from bright daylight to low and poor night-time lighting conditions. In the latter, the objects are only lit by low ambient light, street lamps and headlights of passing-by vehicles. The dataset depicts the following objects: pedestrian crosswalks, green traffic lights and red traffic lights. The annotations include the category and the bounding-box of each object. This dataset could be used for improve the performance at night-time and under low-light conditions of any vision-based method that involves urban objects. For instance, guidance and object detection devices for the visually challenged or self-driving and intelligent vehicles.

Dietary Milk Phospholipids Attenuate Chronic Stress-Induced Changes in Behavior and Endocrine Responses across the Lifespan.

SCOPE: Increasing scientific evidence is validating the use of dietary strategies to support and improve brain health throughout the lifespan, with tailored nutritional interventions catering for specific life stages. Dietary phospholipid supplementations in early life and adulthood are shown to alleviate some of the behavioral consequences associated with chronic stress. This study aims to explore the protective effects of a tailored phospholipid-enriched buttermilk on behavioral and endocrine responses induced by chronic psychosocial stress in adulthood, and to compare these effects according to the life stage at which the supplementation is started. METHODS AND RESULTS: A novel developed phospholipid-enriched dairy product is assessed for its effects on social, anxiety- and depressive-like behaviors, as well as the stress response and cognitive performance following chronic psychosocial stress in C57BL/6J mice, with supplementation beginning in adulthood or early life. Milk phospholipid supplementation from birth protects adult mice against chronic stress-induced changes in endocrine response to a subsequent acute stressor and reduces innate anxiety-like behavior in non-stressed animals. When starting in adulthood, the dietary intervention reverses the anxiety-like phenotype caused by chronic stress exposure. CONCLUSION: Dairy-derived phospholipids exert differential protective effects against chronic psychosocial stress depending on the targeted life stage and duration of the dietary supplementation.

Microbially-derived short-chain fatty acids impact astrocyte gene expression in a sex-specific manner.

Recent investigations in neuroscience implicate the role of microbial-derived metabolites, such as short-chain fatty acids (SCFAs) in brain health and disease. The SCFAs acetate, propionate and butyrate have pleiotropic effects within the nervous system. They are crucial for the maturation of the brain's innate immune cells, the microglia, and modulate other glial cells through the aryl-hydrocarbon receptor. Investigations in preclinical and clinical models find that SCFAs exert neuroprotective and antidepressant affects, while also modulating the stress response and satiety. However, many investigations thus far have not assessed the impact of sex on SCFA activity. Our novel investigation tested the impact of physiologically relevant doses of SCFAs on male and female primary cortical astrocytes. We find that butyrate (0-25 â€‹µM) correlates with increased Bdnf and Pgc1-α expression, implicating histone-deacetylase inhibitor pathways. Intriguingly, this effect is only seen in females. We also find that acetate (0-1500 â€‹µM) correlates with increased Ahr and Gfap expression in males only, suggesting immune modulatory pathways. In males, propionate (0-35 â€‹µM) correlates with increased Il-22 expression, further suggesting immunomodulatory actions. These findings show a novel sex-dependent impact of acetate and butyrate, but not propionate on astrocyte gene expression.

Accurate Multilevel Classification for Wildlife Images.

The most common approaches for classification rely on the inference of a specific class. However, every category could be naturally organized within a taxonomic tree, from the most general concept to the specific element, and that is how human knowledge works. This representation avoids the necessity of learning roughly the same features for a range of very similar categories, and it is easier to understand and work with and provides a classification for each abstraction level. In this paper, we carry out an exhaustive study of different methods to perform multilevel classification applied to the task of classifying wild animals and plant species. Different convolutional backbones, data setups, and ensembling techniques are explored to find the model which provides the best performance. As our experimentation remarks, in order to achieve the best performance on the datasets that are arranged in a tree-like structure, the classifier must feature an EfficientNetB5 backbone with an input size of 300 × 300 px, followed by a multilevel classifier. In addition, a Multiscale Crop data augmentation process must be carried out. Finally, the accuracy of this setup is a 62% top-1 accuracy and 88% top-5 accuracy. The architecture could benefit for an accuracy boost if it is involved in an ensemble of cascade classifiers, but the computational demand is unbearable for any real application.

Preoperative calculation of angles of vision and working area in laparoscopic surgery to treat a giant hiatal hernia.

BACKGROUND: Giant hiatal hernias still pose a major challenge to digestive surgeons, and their repair is sometimes a highly complex task. This is usually performed by laparoscopy, while the role of the thoracoscopic approach has yet to be clearly defined. AIM: To preoperatively detect patients with a giant hiatal hernia in whom it would not be safe to perform laparoscopic surgery and who, therefore, would be candidates for a thoracoscopic approach. METHODS: In the present study, using imaging test we preoperatively simulate the field of vision of the camera and the working area (instrumental access) that can be obtained in each patient when the laparoscopic approach is used. RESULTS: From data obtained, we can calculate the access angles that will be obtained in a preoperative computerised axial tomography coronal section, according to the location of the trocar. We also provide the formula for performing the angle calculations If the trocars are placed in loss common situations, thus enabling us to determine the visibility and manoeuvrability for any position of the trocars. CONCLUSION: The working area determines the cases in which we can operate safely and those in which certain areas of the hernia cannot be accessed, which is when the thoracoscopic approach would be safer.

Novel suturing technique, based on physical principles, achieves a breaking point double that obtained by conventional techniques.

BACKGROUND: Sutures have been used to repair wounds since ancient times. However, the basic suture technique has not significantly changed. In Phase I of our project, we proposed a "double diabolo" suture design, using a theoretical physical study to show that this suture receives 50% less tension than conventional sutures, and so a correspondingly greater force must be applied to break it. AIM: To determine whether these theoretical levels of resistance were met by the new type of suture. METHODS: An observational study was performed to compare three types of sutures, using a device that exerted force on the suture until the breaking point was reached. The tension produced by this traction was measured. The following variables were considered: Tearing stress on entry/exit points, edge separation stress, and suture break stress. The study sample consisted of 30 sutures with simple interrupted stitches (Group 1), 30 with continuous stitches (Group 2), and 30 with the "double diabolo" design (Group 3). RESULTS: The mean degree of force required to reach the breaking point for each of these variables (tearing, separation, and final breaking) was highest in Group 3 (14.56, 18.28, and 21.39 kg), followed by Group 1 (7.36, 10.38, and 12.81 kg) and Group 2 (5.77, 7.7, and 8.71 kg). These differences were statistically significant (P < 0.001) in all cases. CONCLUSION: The experimental results show that with the "double diabolo" suture, compared with conventional sutures, greater force must be applied to reach the breaking point (almost twice as much as in the simple interrupted suture and more than double that required for the continuous suture). If these results are confirmed in Phase III (the clinical phase) of our study, we believe the double diabolo technique should be adopted as the standard approach, especially when the suture must withstand significant tension (e.g., laparotomy closure, thoracotomy closure, diaphragm suture, or hernial orifice closure).

Review of incomplete macroscopic resections (R2) in rectal cancer: Treatment, prognosis and future perspectives.

Colorectal cancer is one of the most prevalent tumours, but with improved treatment and early detection, its prognosis has greatly improved in recent years. However, when the tumour is locally advanced at diagnosis or if there is local recurrence, it is more difficult to perform a complete tumour resection, and there may be a residual macroscopic tumour. In this paper, we review the literature on residual macroscopic tumour resections, concerning both locally advanced primary tumours and recurrences, evaluating the main problems encountered, the treatments applied, the prognosis and future perspectives in this field.

Microbiota from young mice counteracts selective age-associated behavioral deficits.

The gut microbiota is increasingly recognized as an important regulator of host immunity and brain health. The aging process yields dramatic alterations in the microbiota, which is linked to poorer health and frailty in elderly populations. However, there is limited evidence for a mechanistic role of the gut microbiota in brain health and neuroimmunity during aging processes. Therefore, we conducted fecal microbiota transplantation from either young (3-4 months) or old (19-20 months) donor mice into aged recipient mice (19-20 months). Transplant of a microbiota from young donors reversed aging-associated differences in peripheral and brain immunity, as well as the hippocampal metabolome and transcriptome of aging recipient mice. Finally, the young donor-derived microbiota attenuated selective age-associated impairments in cognitive behavior when transplanted into an aged host. Our results reveal that the microbiome may be a suitable therapeutic target to promote healthy aging.