Neonatal kaempferol exposure attenuates impact of cerebral palsy model on neuromotor development, cell proliferation, microglia activation, and antioxidant enzyme expression in the hippocampus of rats.

OBJECTIVES: This study aims to assess the effect of neonatal treatment with kaempferol on neuromotor development, proliferation of neural precursor cells, the microglia profile, and antioxidant enzyme gene expression in the hippocampus. METHODS: A rat model of cerebral palsy was established using perinatal anoxia and sensorimotor restriction of hindlimbs during infancy. Kaempferol (1 mg/ kg) was intraperitoneally administered during the neonatal period. RESULTS: Neonatal treatment with kaempferol reduces the impact of the cerebral palsy model on reflex ontogeny and on the maturation of physical features. Impairment of locomotor activity development and motor coordination was found to be attenuated by kaempferol treatment during the neonatal period in rats exposed to cerebral palsy. Neonatal treatment of kaempferol in cerebral palsy rats prevents a substantial reduction in the number of neural precursor cells in the dentate gyrus of the hippocampus, an activated microglia profile, and increased proliferation of microglia in the sub-granular zone and in the granular cell layer. Neonatal treatment with kaempferol increases gene expression of superoxide dismutase and catalase in the hippocampus of rats submitted to the cerebral palsy model. DISCUSSION: Kaempferol attenuates the impact of cerebral palsy on neuromotor behavior development, preventing altered hippocampal microglia activation and mitigating impaired cell proliferation in a neurogenic niche in these rats. Neonatal treatment with kaempferol also increases antioxidant defense gene expression in the hippocampus of rats submitted to the cerebral palsy model.

Dietary flavonoid kaempferol reduces obesity-associated hypothalamic microglia activation and promotes body weight loss in mice with obesity.

BACKGROUND: Obesity results from an unbalance in the ingested and burned calories. Energy balance (EB) is critically regulated by the hypothalamic arcuate nucleus (ARC) by promoting appetite or anorectic actions. Hypothalamic inflammation, driven by high activation of the microglia, has been reported as a key mechanism involved in the development of diet-induced obesity. Kaempferol (KF), a flavonoid-type polyphenol present in a large number of fruits and vegetables, was shown to regulate both energy metabolism and inflammation. OBJECTIVES: In this work, we studied the effects of both the central and peripheral treatment with KF on hypothalamic inflammation and EB regulation in mice with obesity. METHODS: Obese adult mice were chronically (40 days) treated with KF (0.5 mg/kg/day, intraperitoneally). During the treatment, body weight, food intake (FI), feed efficiency (FE), glucose tolerance, and insulin sensitivity were determined. Analysis of microglia activation in the ARC of the hypothalamus at the end of the treatment was also performed. Body weight, FI, and FE changes were also evaluated in response to 5µg KF, centrally administrated. RESULTS: Chronic administration of KF decreased ∼43% of the density, and ∼30% of the ratio, of activated microglia in the arcuate nucleus. These changes were accompanied by body weight loss, decreased FE, reduced fasting blood glucose, and a tendency to improve insulin sensitivity. Finally, acute central administration of KF reproduced the effects on EB triggered by peripheral administration. CONCLUSION: These findings suggest that KF might fight obesity by regulating central processes related to EB regulation and hypothalamic inflammation.

A Robust Ensemble of Convolutional Neural Networks for the Detection of Monkeypox Disease from Skin Images.

Monkeypox is a smallpox-like disease that was declared a global health emergency in July 2022. Because of this resemblance, it is not easy to distinguish a monkeypox rash from other similar diseases; however, due to the novelty of this disease, there are no widely used databases for this purpose with which to develop image-based classification algorithms. Therefore, three significant contributions are proposed in this work: first, the development of a publicly available dataset of monkeypox images; second, the development of a classification system based on convolutional neural networks in order to automatically distinguish monkeypox marks from those produced by other diseases; and, finally, the use of explainable AI tools for ensemble networks. For point 1, free images of monkeypox cases and other diseases have been searched in government databases and processed until we are left with only a section of the skin of the patients in each case. For point 2, various pre-trained models were used as classifiers and, in the second instance, combinations of these were used to form ensembles. And, for point 3, this is the first documented time that an explainable AI technique (like GradCAM) is applied to the results of ensemble networks. Among all the tests, the accuracy reaches 93% in the case of single pre-trained networks, and up to 98% using an ensemble of three networks (ResNet50, EfficientNetB0, and MobileNetV2). Comparing these results with previous work, a substantial improvement in classification accuracy is observed.

Wearable Health Devices for Diagnosis Support: Evolution and Future Tendencies.

The use of wearable devices has increased substantially in recent years. This, together with the rise of telemedicine, has led to the use of these types of devices in the healthcare field. In this work, we carried out a detailed study on the use of these devices (regarding the general trends); we analyzed the research works and devices marketed in the last 10 years. This analysis extracted relevant information on the general trend of use, as well as more specific aspects, such as the use of sensors, communication technologies, and diseases. A comparison was made between the commercial and research aspects linked to wearables in the healthcare field, and upcoming trends were analyzed.

AnkFall-Falls, Falling Risks and Daily-Life Activities Dataset with an Ankle-Placed Accelerometer and Training Using Recurrent Neural Networks.

Falls are one of the leading causes of permanent injury and/or disability among the elderly. When these people live alone, it is convenient that a caregiver or family member visits them periodically. However, these visits do not prevent falls when the elderly person is alone. Furthermore, in exceptional circumstances, such as a pandemic, we must avoid unnecessary mobility. This is why remote monitoring systems are currently on the rise, and several commercial solutions can be found. However, current solutions use devices attached to the waist or wrist, causing discomfort in the people who wear them. The users also tend to forget to wear the devices carried in these positions. Therefore, in order to prevent these problems, the main objective of this work is designing and recollecting a new dataset about falls, falling risks and activities of daily living using an ankle-placed device obtaining a good balance between the different activity types. This dataset will be a useful tool for researchers who want to integrate the fall detector in the footwear. Thus, in this work we design the fall-detection device, study the suitable activities to be collected, collect the dataset from 21 users performing the studied activities and evaluate the quality of the collected dataset. As an additional and secondary study, we implement a simple Deep Learning classifier based on this data to prove the system's feasibility.

Early Life Stress Activates Glial Cells in the Hippocampus but Attenuates Cytokine Secretion in Response to an Immune Challenge in Rat Pups.

OBJECTIVE: Early life stress (ELS) increases the vulnerability to developing psychopathological disorders in adulthood that are accompanied by brain inflammatory processes. However, it is not known how a combined double hit (stress and immune) at an early age affects the response of the neuroimmune system. Here we investigated the effect of periodic maternal separation (MS) followed by administration of lipopolysaccharide (LPS) on glial cells in the CA3 region and hilus of the hippocampus and on cytokine release on postnatal day (PN) 15. METHODS: Male rat pups were subjected to MS (3 h/day, PN1-14). MS and control pups received a single LPS injection (1 mg/kg of body weight) on PN14. They were subjected to an open field test 1 h later. The pups were sacrificed 90 min after LPS injection (PN14) or on PN15 for cytokine or immunohistological analyses, respectively. RESULTS: LPS reduced the locomotion and induced high corticosterone levels in treated pups. MS or LPS reduced microglial density and activated microglial cells in the hippocampal CA3 and hilus regions. Microglial activation was highest in MS-LPS pups. The astrocyte density was mildly reduced by MS or LPS in the CA3 region and hilus, but the reduction was maximal in MS-LPS pups. LPS increased the secretion of plasmatic interleukin (IL)-1ß, tumor necrosis factor-α, and IL-6, and of hippocampal IL-1ß protein, but these were attenuated in MS-LPS pups. CONCLUSION: Although MS and LPS activate neuroimmune cells, stress attenuates the hippocampal and peripheral cytokine response to LPS through an as-yet unidentified adaptive mechanism. These results provide information regarding the neurobiology of stress and inflammation.

Endovascular Mechanical Thrombectomy for Ischemic Stroke Treatment in the Setting of Aortic Dissection: Case Report.

Introduction: Acute ischemic stroke can occur in the setting of aortic dissection. Information concerning the utility of endovascular mechanical thrombectomy as an intervention for patients with aortic dissection who are experiencing an acute stroke due to large vessel occlusion is limited to a few case reports. Case series of patients presenting with this clinical situation are needed to further investigate the potential utility of this procedure when patients with acute ischemic stroke and aortic dissection are encountered. Case Presentation: We report a patient with a chronic Stanford type A aortic dissection with dissection extension into the left common carotid artery and left internal carotid artery who had a good clinical outcome following mechanical thrombectomy for a symptomatic middle cerebral artery occlusion. We also review other cases in which endovascular mechanical thrombectomy was conducted in patients with aortic dissection and acute ischemic stroke and discuss the potential risks and benefits of carotid artery stenting in this clinical situation. Conclusion: The rate of successful arterial recanalization in patients with aortic dissection, large vessel occlusion, and acute ischemic stroke treated with mechanical thrombectomy is high. The intervention has been associated with good neurological outcomes and a low rate of procedure-related complications. Additional case series are needed to help discern if our observations are present in a broader array of patients in order to identify which patients are most likely to benefit from mechanical thrombectomy.

Lance Adams Syndrome in the Setting of COVID-19 Pneumonia.

Lance-Adams syndrome (LAS) is a rare clinical presentation of hypoxic-ischemic brain injury typically occurring in the setting of cardiac arrest. It is rare for it to be associated with respiratory failure. The advent of the COVID-19 pandemic heralded a new cause of respiratory failure, and not much is known about the occurrence of Lance-Adams syndrome in the context of COVID-19 pneumonia. A 23-year-old male was brought to the emergency department (ED) after being found unconscious at home. He had prominent generalized myoclonus in the context of COVID-19 pneumonia and a possible clonazepam overdose. Magnetic resonance imaging (MRI) of the brain with and without contrast revealed findings suggestive of hypoxic-ischemic brain injury. A diagnosis of LAS was made based on electroencephalography (EEG). As LAS typically carries a relatively favorable prognosis, aggressive treatment was pursued. This resulted in a fairly good outcome, although he had to be maintained on several antiseizure medications. Our case is a rare occurrence of Lance-Adams syndrome in the setting of respiratory failure and COVID-19 pneumonia in the absence of cardiac arrest. It is critical to distinguish myoclonic status epilepticus (MSE) from Lance-Adams syndrome due to the difference in prognosis. Our case can provide future direction for studies in a larger cohort of patients to see if LAS is frequently associated with respiratory failure secondary to COVID-19 pneumonia in the absence of cardiac arrest. It is important to consider Lance-Adams syndrome as one of the emerging neurological complications of COVID-19 pneumonia.

A lightweight xAI approach to cervical cancer classification.

Cervical cancer is caused in the vast majority of cases by the human papilloma virus (HPV) through sexual contact and requires a specific molecular-based analysis to be detected. As an HPV vaccine is available, the incidence of cervical cancer is up to ten times higher in areas without adequate healthcare resources. In recent years, liquid cytology has been used to overcome these shortcomings and perform mass screening. In addition, classifiers based on convolutional neural networks can be developed to help pathologists diagnose the disease. However, these systems always require the final verification of a pathologist to make a final diagnosis. For this reason, explainable AI techniques are required to highlight the most significant data to the healthcare professional, as it can be used to determine the confidence in the results and the areas of the image used for classification (allowing the professional to point out the areas he/she thinks are most important and cross-check them against those detected by the system in order to create incremental learning systems). In this work, a 4-phase optimization process is used to obtain a custom deep-learning classifier for distinguishing between 4 severity classes of cervical cancer with liquid-cytology images. The final classifier obtains an accuracy over 97% for 4 classes and 100% for 2 classes with execution times under 1 s (including the final report generation). Compared to previous works, the proposed classifier obtains better accuracy results with a lower computational cost.

Cold-shock RNA-binding protein CspR is also exposed to the surface of Enterococcus faecalis.

CspR has been characterized recently as a cold-shock RNA-binding protein in Enterococcus faecalis, a natural member of the gastro-intestinal tract capable of switching from a commensal relationship with the host to an important nosocomial pathogen. In addition to its involvement in the cold-shock response, CspR also plays a role in the long-term survival and virulence of E. faecalis. In the present study, we demonstrated that anti-CspR immune rabbit serum protected larvae of Galleria mellonella against a lethal challenge of the WT strain. These results suggested that CspR might have a surface location. This hypothesis was verified by Western blot that showed detection of CspR in the total as well as in the surface protein fraction. In addition, identification of surface polypeptides by proteolytic shaving of intact bacterial cells followed by liquid chromatography-MS-MS revealed that cold-shock proteins (EF1367, EF2939 and CspR) were present on the cell surface. Lastly, anti-CspR immune rabbit serum was used for immunolabelling and detected with colloidal gold-labelled goat anti-rabbit IgG in order to determine the immunolocalization of CspR on E. faecalis WT strain. Electron microscopy images confirmed that the cold-shock protein RNA-binding protein CspR was present in both cytoplasmic and surface parts of the cell. These data strongly suggest that CspR, in addition to being located intracellularly, is also present in the extracellular protein fraction of the cells and has important functions in the infection process of Galleria larvae.

A 5-year follow-up of Achilles tendon reconstruction using a full-thickness graft processed with the clearant method and retrograde fixation in the calcaneus: a case study of an amateur soccer player.

We present a case of a 41-year-old male amateur soccer player with no comorbidities, who experienced a rerupture of the Achilles tendon 5 years after his initial end-to-end plasty. To address this, we opted for a full-thickness reconstruction using a graft under the Clearant Process of the Achilles tendon. As an innovative approach, we proposed an alternative fixation technique, employing a Bio Composite Arthrex 9 mm x 35 mm interference screw, placed at the apex of the calcaneus body. For a period of 5 years, the patient underwent regular imaging follow-ups with Magnetic Resonance Imaging (MRI) and clinical assessments using the Foot and Ankle Ability Measure Activity Subscale Score and Foot and Ankle Ability Measure Sports Subscale Score. This case highlights the importance of exploring novel fixation methods for Achilles tendon reconstruction, particularly in cases of rerupture. The use of the Bio Composite Arthrex screw, in conjunction with the Clearant Process graft, demonstrated promising results both in imaging and functional outcomes, but more case studies with positive results are needed to evaluate the effectiveness of this reconstruction.

Trigeminal neuralgia secondary to vascular compression and neurocysticercosis: illustrative case.

BACKGROUND: Trigeminal neuralgia (TN) is a frequent neurosurgical problem negatively influencing the quality of life of patients. The standard surgical treatment is microvascular decompression for primary cases and decompression of the mass effect, mainly tumors, for secondary cases. Neurocysticercosis (NCC) in the cerebellopontine angle is a rare etiology of TN. The authors report a case in which NCC cysts around the trigeminal nerve coexisted with a vascular loop, which compressed the exit of the trigeminal nerve from the pons. OBSERVATIONS: A 78-year-old woman presented with a 3-year history of persistent severe pain in the left side of her face, refractory to medical treatment. On gadolinium-enhanced magnetic resonance imaging, cystic lesions were observed around the left trigeminal nerve and a vascular loop was also present and in contact with the nerve. A retrosigmoid approach for cyst excision plus microvascular decompression of the trigeminal nerve was successfully performed. There were no complications. The patient was discharged without facial pain. LESSONS: Albeit rare, TN secondary to NCC cysts should be considered in the differential diagnosis in NCC-endemic regions. In this case, the cause of the neuralgia was probably both problems, because when both were treated, the patient improved.

A novel class of selective acetylcholinesterase inhibitors: synthesis and evaluation of (E)-2-(benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles.

(E)-2-(benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles are described as a new class of selective inhibitors of acetylcholinesterase (AChE). The most potent compound in the series exhibited good AChE inhibitory activity (IC50 = 64 µM). Compound 7f was found to be more selective than galanthamine in inhibiting AChE and it showed a moderate selectivity index. Kinetic studies on AChE indicated that a competitive type of inhibition pattern exist for these acrylonitrile derivates. Molecular docking models of the ligand-AChE complexes suggest that compound 7 g is located on the periphery of the AChE active site.

Transventricular endoscopic approach to the anterior interhemispheric fissure for neurocysticercosis: illustrative cases.

BACKGROUND: Neurocysticercosis (NCC) is a global public health problem. It is a complex disease to manage and a cause of great morbidity and mortality in affected patients. Conventional surgical approaches have been used for many years, but currently, minimally invasive approaches are being used with good results. The authors present a case of NCC in the anterior interhemispheric fissure that was treated with a transventricular endoscopic approach. OBSERVATIONS: A 32-year-old male patient was admitted for persistent moderate headache and dizziness. Gadolinium-enhanced magnetic resonance imaging (MRI) showed multiple parenchymal, ventricular, and subarachnoid cystic lesions, especially in the anterior interhemispheric space. A transventricular endoscopic approach was selected and applied. There were no complications during surgery. Pathological analysis confirmed the diagnosis of NCC. Control MRI demonstrated the absence of cysts in the anterior interhemispheric space. LESSONS: Minimally invasive approaches are an excellent alternative for patients with NCC, especially if a patient requires more than one surgery.

Non-small cell lung cancer diagnosis aid with histopathological images using Explainable Deep Learning techniques.

BACKGROUND: Lung cancer has the highest mortality rate in the world, twice as high as the second highest. On the other hand, pathologists are overworked and this is detrimental to the time spent on each patient, diagnostic turnaround time, and their success rate. OBJECTIVE: In this work, we design, implement, and evaluate a diagnostic aid system for non-small cell lung cancer detection, using Deep Learning techniques. METHODS: The classifier developed is based on Artificial Intelligence techniques, obtaining an automatic classification result between healthy, adenocarcinoma and squamous cell carcinoma, given an histopathological image from lung tissue. Moreover, a report module based on Explainable Deep Learning techniques is included and gives the pathologist information about the image's areas used to classify the sample and the confidence of belonging to each class. RESULTS: The results show a system accuracy between 97.11 and 99.69%, depending on the number of classes classified, and a value of the area under ROC curve between 99.77 and 99.94%. CONCLUSIONS: The classification results obtain a substantial improvement according to previous works. Thanks to the given report, the time spent by the pathologist and the diagnostic turnaround time can be reduced.

Long-term activation of hippocampal glial cells and altered emotional behavior in male and female adult rats after different neonatal stressors.

Early life stress increases the risk of developing psychiatric diseases in adulthood. Severe neonatal infections can also contribute to the development of affective illnesses. Stress and infections both trigger the immediate activation of the neuroimmune system. We compared the long-term effects of neonatal single or combined stress-immune challenges on emotional behavior and glial cell responses in the hippocampus. Male and female Sprague Dawley rats were randomly allocated across four conditions: (1) control + vehicle; (2) maternal separation (MS, 3 h/day on postnatal days [PN] 1-14) + vehicle; (3) control + lipopolysaccharide (LPS, 0.5. mg/kg, PN14); (4) MS + LPS. The rats' behaviors were analyzed from PN120 in males and from PN150 in diestrous females. LPS, but not MS, increased anxiety-like behavior in male rats; however, in females, it increased with both challenges. Depressive-like behavior increased after MS-but not LPS-in males and females. Combined stressors increased depressive-like behavior in both sexes. All stressors promoted microglial activation in CA3 and hilus in males and females. MS and LPS increased the astrocytic density within the male hilus, but LPS only increased it in CA3. MS prevented the rise in astrocytic density with LPS. In females, MS reduced the astrocytic population of the hilus and CA3 areas. Taken together, the behavioral and glial cell responses to early life challenges are sex-dependent and cell-type specific. This suggests a sexual dimorphism in the nature of the adverse event faced. These results have implications for understanding the emergence of psychiatric illnesses.

Stereotactic surgery for neurocysticercosis of the 4th ventricle: illustrative cases.

BACKGROUND: Neurocysticercosis, caused by the larval stage of Taenia solium, affects the cerebral ventricles in 20-30% of cases and may lead to hydrocephalus and other neurological morbidity. Conventional treatment for cysts in the 4th ventricle includes open surgery (suboccipital approach) and neuroendoscopy, with the latter being the option of choice. Stereotactic surgery, minimally invasive, offers a good alternative for this type of deep lesion. OBSERVATIONS: The authors report the cases of two women, 30 and 45 years old, who presented with headache, dizziness, and ataxia and were diagnosed with 4th ventricle cysticercosis. Magnetic resonance imaging (MRI) revealed dilated 4th ventricles (approximately 2.5 cm in both cases, with cystic images inside the ventricular cavity). Both patients were treated with stereotactic surgery via a suboccipital transcerebellar approach. Cyst material was extracted, and the diagnosis was confirmed by pathological examination. The surgeries had no complications and resulted in clinical improvement. Control MRI scans showed reduction of the volume of the ventricle without residual cysts. LESSONS: Minimally invasive stereotactic surgery provided a safe alternative for 4th ventricle neurocysticercosis cysts, with more benefits than risks in comparison with conventional techniques.

IoT garment for remote elderly care network.

The elderly is a continuous growth sector thanks to the life expectancy increase in Western society. This sector is especially at risk from the appearance of respiratory diseases and, therefore, is the most affected sector in the COVID-19 epidemic. Many of these elderly require continuous care in residences or by specialized caregivers, but these personal contacts put this sector at risk. In this work, an IoT system for elderly remote monitoring is studied, designed, developed and tested. This system is composed by a smart garment that records information from various physiological sensors in order to detect falls, sudden changes in body temperature, heart problems and heat stroke; This information is sent to a cloud server through a gateway located in the patient's residence, allowing to real-time monitor remotely patient's activity using a customized App, as well as receiving alerts in dangerous situations. This system has been tested with professional caregivers, obtaining usability and functionality surveys; and, in addition, a detailed power-consumption study has been carried out. The results, compared with other similar systems, demonstrate that the proposed one is useful, usable, works in real time and has a decent power consumption that allows the patient to carry it during all day without charging the battery.

Endoscopic endonasal surgery for massive subarachnoid neurocysticercosis: illustrative case.

BACKGROUND: Subarachnoid neurocysticercosis (NCC) is associated with high morbidity and mortality rates. Conventional transcranial approaches and transventricular endoscopy have been previously reported for extraparenchymal NCC and ventricular NCC, respectively. By October 2019, endonasal endoscopic approaches had not been used for the treatment of NCC. OBSERVATIONS: A 54-year-old-woman with NCC was admitted with acute neurological deterioration due to severe intracranial hypertension caused by massive subarachnoid NCC cysts, as evidenced on magnetic resonance imaging (MRI) with great brainstem compression. The case was discussed, and an endoscopic endonasal resection of the NCC cysts was scheduled. The diagnosis was confirmed by pathological anatomy. There were no complications in the surgery, with marked neurological improvement. Control MRIs demonstrated a significant reduction of NCC cysts. LESSONS: Minimally invasive approaches are an excellent alternative for skull-base tumoral and infectious pathology. Prior knowledge of the pathophysiology and the authors' experience in the management of patients with NCC allowed them to propose this approach, with optimal results.

Enantioseparation of pharmaceutical compounds by multiplexed capillary electrophoresis using highly sulphated alpha-, beta- and gamma-cyclodextrins.

A multiplexed capillary electrophoresis (CE) system equipped with 96 channels was evaluated for high-throughput screening of enantiomers of solutes of pharmaceutical interest. Using highly (DS approximately 12) sulphated alpha-, beta- and gamma-cyclodextrins under acidic conditions (pH 2.5) only 48 channels could be used because of the high conductivity of the chiral selectors. Method transfer from a single channel to a 48 channel CE system is described. Under optimised conditions, the analysis time on the multiplexed 48 channel CE system is ca. five to eight times the analysis time on the single channel CE system. The figures of merit for the multiplexed system are presented as well as performance evaluation including throughput and productivity gain. Intra-day precision (n=6) ranged from 2.0 to 16.5% and from 2.2 to 15.5% for migration time and resolution, respectively. These values increased with ca. 10% for intermediate precision.