Magnetoelastic Coupling Evidence by Anisotropic Crossed Thermal Expansion in Magnetocaloric RSrCoFeO6 (R = Sm, Eu) Double Perovskites.

Double perovskite oxides, characterized by their tunable magnetic properties and robust interconnection between the lattice and magnetic degrees of freedom, present an enticing foundation for advanced magnetic refrigeration materials. Herein, we delve into the influence of rare-earth elements on RSrCoFeO6 (R = Sm, Eu) disordered double perovskites by examining their structural, electronic, magnetic, and magnetocaloric properties. Temperature-dependent synchrotron X-ray diffraction analysis confirmed the stability of the orthorhombic phase (Pnma) across a wide temperature range. X-ray photoemission spectroscopy revealed that both Sm and Eu are in the 3+ state, whereas multiple states for Co2+/3+ and Fe3+/4+ are identified. The magnetic investigation and magnetocaloric effect (MCE) analysis brought to light the presence of a long-range antiferromagnetic (AFM) order with a second-order phase transition (SOPT) in both samples. The maximum magnetic entropy change ΔSMmax was approximately 0.9 J/kg K for both samples at applied field 0-7 T, manifesting prominently above Neel temperatures TN ≈ 93 K (Sm) and 84 K (Eu). Nevertheless, different relative cooling powers (RCP) of 112.6 J/kg (Sm) and 95.5 J/kg (Eu) were observed. A detailed analysis of the temperature-dependent lattice parameters shed light on a distinct magnetocaloric effect across the magnetic transition temperature, unveiling an anisotropic thermal expansion [αV = 1.41 × 10-5 K-1 (Sm) and αV = 1.54 × 10-5 K-1 (Eu)] wherein the thermal expansion axial ratio αbSm/αbEu = 0.61 became lower with increasing temperature, which suggests that the Eu sample experiences a greater thermal expansion in the b-axis direction. At the atomic bonding level, the evidence for magnetoelastic coupling around the magnetic transition temperatures TN was found through the anomalies along the average Co/Fe-O bond distance, formal valence, octahedral distortion, as well as an anisotropic lattice expansion.

Quantitative sensory testing defines the trajectory of sensory neuropathy after severe COVID-19.

AIMS: To assess sensory neuropathy development after severe COVID-19. METHODS: Patients with severe COVID-19 underwent assessment of neuropathic symptoms, tendon reflexes, and quantitative sensory testing to evaluate vibration (VPT), cold (CPT), warm (WPT) and heat perception thresholds (HPT) within 1-3 weeks of admission and after 1-year. RESULTS: 32 participants with severe COVID-19 aged 68.6 ± 12.4 (18.8 % diabetes) were assessed. At baseline, numbness and neuropathic pain were present in 56.3 % and 43.8 % of participants, respectively. On the feet, VPT, WPT, and HPT were abnormal in 81.3 %, CPT was abnormal in 50.0 % and HPT on the face was abnormal in 12.5 % of patients. At 1-year follow-up, the prevalence of abnormal VPT (81.3 % vs 50.0 %, P < 0.01), WPT (81.3 % vs 43.8 %, P < 0.01), and HPT (81.3 % vs 50.0 %, P < 0.01) decreased, with no change in CPT (P = 0.21) on the feet or HPT on the face (P = 1.0). Only participants without diabetes recovered from an abnormal VPT, CPT, and WPT. Patients with long-COVID (37.5 %) had comparable baseline VPT, WPT and CPT with those without long-COVID (P = 0.07-0.69). CONCLUSIONS: Severe COVID-19 is associated with abnormal vibration and thermal thresholds which are sustained for up to 1 year in patients with diabetes. Abnormal sensory thresholds have no association with long-COVID development.

Hippocampal subfield abnormalities and biomarkers of pathologic brain changes: from SARS-CoV-2 acute infection to post-COVID syndrome.

BACKGROUND: Cognitive deficits are among the main disabling symptoms in COVID-19 patients and post-COVID syndrome (PCS). Within brain regions, the hippocampus, a key region for cognition, has shown vulnerability to SARS-CoV-2 infection. Therefore, in vivo detailed evaluation of hippocampal changes in PCS patients, validated on post-mortem samples of COVID-19 patients at the acute phase, would shed light into the relationship between COVID-19 and cognition. METHODS: Hippocampal subfields volume, microstructure, and perfusion were evaluated in 84 PCS patients and compared to 33 controls. Associations with blood biomarkers, including glial fibrillary acidic protein (GFAP), myelin oligodendrocyte glycoprotein (MOG), eotaxin-1 (CCL11) and neurofilament light chain (NfL) were evaluated. Besides, biomarker immunodetection in seven hippocampal necropsies of patients at the acute phase were contrasted against eight controls. FINDINGS: In vivo analyses revealed that hippocampal grey matter atrophy is accompanied by altered microstructural integrity, hypoperfusion, and functional connectivity changes in PCS patients. Hippocampal structural and functional alterations were related to cognitive dysfunction, particularly attention and memory. GFAP, MOG, CCL11 and NfL biomarkers revealed alterations in PCS, and showed associations with hippocampal volume changes, in selective hippocampal subfields. Moreover, post mortem histology showed the presence of increased GFAP and CCL11 and reduced MOG concentrations in the hippocampus in post-mortem samples at the acute phase. INTERPRETATION: The current results evidenced that PCS patients with cognitive sequalae present brain alterations related to cognitive dysfunction, accompanied by a cascade of pathological alterations in blood biomarkers, indicating axonal damage, astrocyte alterations, neuronal injury, and myelin changes that are already present from the acute phase. FUNDING: Nominative Grant FIBHCSC 2020 COVID-19. Department of Health, Community of Madrid. Instituto de Salud Carlos III through the project INT20/00079, co-funded by European Regional Development Fund "A way to make Europe" (JAMG). Instituto de Salud Carlos III (ISCIII) through Sara Borrell postdoctoral fellowship Grant No. CD22/00043) and co-funded by the European Union (MDC). Instituto de Salud Carlos III through a predoctoral contract (FI20/000145) (co-funded by European Regional Development Fund "A way to make Europe") (MVS). Fundación para el Conocimiento Madri+d through the project G63-HEALTHSTARPLUS-HSP4 (JAMG, SOM).

Usefulness of the H-Reflex for Intraoperative Monitoring of Thoracoabdominal Aneurysms.

PURPOSE: Intraoperative neurophysiologic monitoring in thoracoabdominal aneurysms (TAAA) is essential to avoid intraoperative spinal cord injury). Motor and somatosensory evoked potentials may be considered intraoperative tools for detecting spinal cord injury. H-reflex is a well-known neurophysiologic technique to evaluate L5-S1 root. Current evidence supports the observation that H-reflex changes may occur with spinal cord damage as high as the cervical level. This study aimed to evaluate the usefulness of the H-reflex in these surgeries. METHODS: The use of intraoperative H-reflex in TAAA monitoring was evaluated in 12 patients undergoing open or endovascular repair of TAAA for a period of four years (2016-2020) using somatosensory evoked potentials (SSEPs) and transcranial motor evoked potentials (TcMEPs) and bilateral H-reflex. RESULTS: Six neurophysiologic alarms were recorded in five of the 12 patients. Summarizing the neurophysiologic changes of our series, we considered a peripheral change when we detected a unilateral loss of SSEPs, TcMEPs, and H-reflex. Instead, we assumed a central change when we detected a unilateral or bilateral loss of TcMEPs and H-reflex with normal SSEPs, which we considered a sign of spinal cord ischemia. Interestingly H-reflex always changed significantly in combination with TcMEPs in the same fashion. CONCLUSIONS: According to our series, H-reflex can detect intraoperative changes with the same sensitivity as TcMEPs in TAAA surgeries. With the support of other techniques, it can be useful to localize the origin of the lesion (peripheral or central spinal cord), to help in surgical decision-making to avoid postoperative neurologic damage. Based on our results, we recommend the systematic use of H-reflex in TAAA surgeries.

Transcranial direct current stimulation for post-COVID fatigue: a randomized, double-blind, controlled pilot study.

Fatigue is one of the most frequent and disabling symptoms of the post-COVID syndrome. In this study, we aimed to assess the effects of transcranial direct current stimulation on fatigue severity in a group of patients with post-COVID syndrome and chronic fatigue. We conducted a double-blind, parallel-group, sham-controlled study to evaluate the short-term effects of anodal transcranial direct current stimulation (2 mA, 20 min/day) on the left dorsolateral prefrontal cortex. The modified fatigue impact scale score was used as the primary endpoint. Secondary endpoints included cognition (Stroop test), depressive symptoms (Beck depression inventory) and quality of life (EuroQol-5D). Patients received eight sessions of transcranial direct current stimulation and were evaluated at baseline, immediately after the last session, and one month later. Forty-seven patients were enrolled (23 in the active treatment group and 24 in the sham treatment group); the mean age was 45.66 ± 9.49 years, and 37 (78.72%) were women. The mean progression time since the acute infection was 20.68 ± 6.34 months. Active transcranial direct current stimulation was associated with a statistically significant improvement in physical fatigue at the end of treatment and 1 month as compared with sham stimulation. No significant effect was detected for cognitive fatigue. In terms of secondary outcomes, active transcranial direct current stimulation was associated with an improvement in depressive symptoms at the end of treatment. The treatment had no effects on the quality of life. All the adverse events reported were mild and transient, with no differences between the active stimulation and sham stimulation groups. In conclusion, our results suggest that transcranial direct current stimulation on the dorsolateral prefrontal cortex may improve physical fatigue. Further studies are needed to confirm these findings and optimize stimulation protocols.

Phytochemicals Determination, and Antioxidant, Antimicrobial, Anti-Inflammatory and Anticancer Activities of Blackberry Fruits.

A comprehensive characterization of the phytochemicals present in a blackberry fruit extract by HPLC-TOF-MS has been carried out. The main compounds in the extract were ursane-type terpenoids which, along with phenolic compounds, may be responsible for the bioactivity of the extract. In vitro antioxidant capacity was assessed through Folin-Ciocalteu (31.05 ± 4.9 mg GAE/g d.w.), FRAP (637.8 ± 3.2 µmol Fe2+/g d.w.), DPPH (IC50 97.1 ± 2.4 µg d.w./mL) and TEAC (576.6 ± 8.3 µmol TE/g d.w.) assays. Furthermore, the extract exerted remarkable effects on in vitro cellular antioxidant activity in HUVEC cells at a concentration of 5 mg/mL. Antimicrobial activity of the extract was also tested. Most sensible microorganisms were Gram-positive bacteria, such as E. faecalis, B. cereus and Gram-negative E. coli (MBC of 12.5 mg/mL). IC50 values against colon tumoral cells HT-29 (4.9 ± 0.2 mg/mL), T-84 (5.9 ± 0.3 mg/mL) and SW-837 (5.9 ± 0.2 mg/mL) were also obtained. Furthermore, blackberry extract demonstrated anti-inflammatory activity inhibiting the secretion of pro-inflammatory IL-8 cytokines in two cellular models (HT-29 and T-84) in a concentration-dependent manner. These results support that blackberry fruits are an interesting source of bioactive compounds that may be useful in the prevention and treatment of different diseases, mainly related to oxidative stress.

Establishment of a Sonotrode Extraction Method and Evaluation of the Antioxidant, Antimicrobial and Anticancer Potential of an Optimized Vaccinium myrtillus L. Leaves Extract as Functional Ingredient.

Vaccinium myrtillus L. (bilberry) leaves are an important by-product of berry production that may be used as a source of phenolic compounds which have a positive effect on human health. Therefore, an ultrasound-assisted extraction via sonotrode has been used for the first time to recover bioactive compounds from bilberry leaves. The extraction has been optimized using a Box-Behnken design. The influence of ethanol:water ratio (v/v), time of extraction (min) and amplitude (%) were evaluated considering total phenolic content (TPC) and antioxidant capacity (DPPH and FRAP assays) as dependent variables in a response surface methodology (RSM). Optimum values for the independent factors were 30:70 ethanol/water (v/v), 5 min of extraction and 55% amplitude. The empirical values of the independent variables using the optimized conditions were 217.03 ± 4.92 mg GAE/g d.w. (TPC), 271.13 ± 5.84 mg TE/g d.w. (DPPH) and 312.21 ± 9.30 mg TE/g d.w. (FRAP). The validity of the experimental design was confirmed using ANOVA and the optimal extract was characterized using HPLC-MS. A total of 53 compounds were tentatively identified, of which 22 were found in bilberry leaves for the first time. Among them, chlorogenic acid was the most abundant molecule, representing 53% of the total phenolic compounds identified. Additionally, the antimicrobial and anticancer activities of the optimum extract were tested. Gram-positive bacteria demonstrated high sensitivity to bilberry leaves extract in vitro, with MBC values of 6.25 mg/mL for Listeria monocytogenes, Listeria innocua and Enterococcus faecalis, and 0.8 mg/mL for Staphylococcus aureus and Bacillus cereus. Furthermore, bilberry leaves extract exerted in vitro antiproliferative activity against HT-29, T-84 and SW-837 colon tumor cells with IC50 values of 213.2 ± 2.5, 1140.3 ± 5.2 and 936.5 ± 4.6 µg/mL, respectively. Thus, this rapid ultrasound-assisted extraction method has demonstrated to be an efficient technique to obtain bilberry leaves extract with in vitro antioxidant, antimicrobial and anticancer capacities that may be useful for the food industry as natural preservative or even for the production of functional foods or nutraceuticals.

Distinct GSDMB protein isoforms and protease cleavage processes differentially control pyroptotic cell death and mitochondrial damage in cancer cells.

Gasdermin (GSDM)-mediated pyroptosis is functionally involved in multiple diseases, but Gasdermin-B (GSDMB) exhibit cell death-dependent and independent activities in several pathologies including cancer. When the GSDMB pore-forming N-terminal domain is released by Granzyme-A cleavage, it provokes cancer cell death, but uncleaved GSDMB promotes multiple pro-tumoral effects (invasion, metastasis, and drug resistance). To uncover the mechanisms of GSDMB pyroptosis, here we determined the GSDMB regions essential for cell death and described for the first time a differential role of the four translated GSDMB isoforms (GSDMB1-4, that differ in the alternative usage of exons 6-7) in this process. Accordingly, we here prove that exon 6 translation is essential for GSDMB mediated pyroptosis, and therefore, GSDMB isoforms lacking this exon (GSDMB1-2) cannot provoke cancer cell death. Consistently, in breast carcinomas the expression of GSDMB2, and not exon 6-containing variants (GSDMB3-4), associates with unfavourable clinical-pathological parameters. Mechanistically, we show that GSDMB N-terminal constructs containing exon-6 provoke cell membrane lysis and a concomitant mitochondrial damage. Moreover, we have identified specific residues within exon 6 and other regions of the N-terminal domain that are important for GSDMB-triggered cell death as well as for mitochondrial impairment. Additionally, we demonstrated that GSDMB cleavage by specific proteases (Granzyme-A, Neutrophil Elastase and caspases) have different effects on pyroptosis regulation. Thus, immunocyte-derived Granzyme-A can cleave all GSDMB isoforms, but in only those containing exon 6, this processing results in pyroptosis induction. By contrast, the cleavage of GSDMB isoforms by Neutrophil Elastase or caspases produces short N-terminal fragments with no cytotoxic activity, thus suggesting that these proteases act as inhibitory mechanisms of pyroptosis. Summarizing, our results have important implications for understanding the complex roles of GSDMB isoforms in cancer or other pathologies and for the future design of GSDMB-targeted therapies.

Multimodal neuroimaging in post-COVID syndrome and correlation with cognition.

Brain changes have been reported in the first weeks after SARS-CoV-2 infection. However, limited literature exists about brain alterations in post-COVID syndrome, a condition increasingly associated with cognitive impairment. The present study aimed to evaluate brain functional and structural alterations in patients with post-COVID syndrome, and assess whether these brain alterations were related to cognitive dysfunction. Eighty-six patients with post-COVID syndrome and 36 healthy controls were recruited and underwent neuroimaging acquisition and a comprehensive neuropsychological assessment. Cognitive and neuroimaging examinations were performed 11 months after the first symptoms of SARS-CoV-2. Whole-brain functional connectivity analysis was performed. Voxel-based morphometry was performed to evaluate grey matter volume, and diffusion tensor imaging was carried out to analyse white-matter alterations. Correlations between cognition and brain changes were conducted and Bonferroni corrected. Post-COVID syndrome patients presented with functional connectivity changes, characterized by hypoconnectivity between left and right parahippocampal areas, and between bilateral orbitofrontal and cerebellar areas compared to controls. These alterations were accompanied by reduced grey matter volume in cortical, limbic and cerebellar areas, and alterations in white matter axial and mean diffusivity. Grey matter volume loss showed significant associations with cognitive dysfunction. These cognitive and brain alterations were more pronounced in hospitalized patients compared to non-hospitalized patients. No associations with vaccination status were found. The present study shows persistent structural and functional brain abnormalities 11 months after the acute infection. These changes are associated with cognitive dysfunction and contribute to a better understanding of the pathophysiology of the post-COVID syndrome.

The Predictive Value of the Residency AOBFP In-Service Exam, Produced and Administered by ACOFP.

BACKGROUND AND OBJECTIVES: Board certification is acknowledged as the mainstay for ensuring quality physician-delivered health care within medical specialties. The American College of Osteopathic Family Physicians (ACOFP) administers the American Osteopathic Board of Family Physicians' (AOBFP) In-Service Examination (ISE) to provide residents and program directors with a formative examination to assess competency and preparation for successful completion of the AOBFP certifying examination (CE). Unique assessment processes are integral to monitoring development of the osteopathic family physician throughout training and into practice, and to verify their competency for the safety and protection of the public. This study sought to investigate whether performance on the AOBFP ISE predicted performance on the AOBFP CE, and thereby successfully equipped residents to safely enter medical practice. METHODS: In 2020, data from 1,893 PGY-1 through PGY-3 residents (2016-2018), whose ISE scores could be matched with scores on the AOBFP initial board CE, were analyzed for this study. RESULTS: Correlations among ISE administrations across 3 years of postgraduate medical education were in the mid-to-high .6 range; the ISE scores correlated with CE scores in the mid .4 to high .5 range. Less reliable measures of positive predictive value were 0.99, and sensitivity was 0.91. CONCLUSIONS: Results suggest that ISE administrations during residency training are effective in developing remediation strategies for subsequent successful CE performance. The inclusion of osteopathic principles in the AOBFP CE necessitates inclusion of osteopathic content in resident training exams like ISE.

Gasdermin B over-expression modulates HER2-targeted therapy resistance by inducing protective autophagy through Rab7 activation.

BACKGROUND: Gasdermin B (GSDMB) over-expression promotes poor prognosis and aggressive behavior in HER2 breast cancer by increasing resistance to therapy. Decoding the molecular mechanism of GSDMB-mediated drug resistance is crucial to identify novel effective targeted treatments for HER2/GSDMB aggressive tumors. METHODS: Different in vitro approaches (immunoblot, qRT-PCR, flow cytometry, proteomic analysis, immunoprecipitation, and confocal/electron microscopy) were performed in HER2 breast and gastroesophageal carcinoma cell models. Results were then validated using in vivo preclinical animal models and analyzing human breast and gastric cancer samples. RESULTS: GSDMB up-regulation renders HER2 cancer cells more resistant to anti-HER2 agents by promoting protective autophagy. Accordingly, the combination of lapatinib with the autophagy inhibitor chloroquine increases the therapeutic response of GSDMB-positive cancers in vitro and in zebrafish and mice tumor xenograft in vivo models. Mechanistically, GSDMB N-terminal domain interacts with the key components of the autophagy machinery LC3B and Rab7, facilitating the Rab7 activation during pro-survival autophagy in response to anti-HER2 therapies. Finally, we validated these results in clinical samples where GSDMB/Rab7/LC3B co-expression associates significantly with relapse in HER2 breast and gastric cancers. CONCLUSION: Our findings uncover for the first time a functional link between GSDMB over-expression and protective autophagy in response to HER2-targeted therapies. GSDMB behaves like an autophagy adaptor and plays a pivotal role in modulating autophagosome maturation through Rab7 activation. Finally, our results provide a new and accessible therapeutic approach for HER2/GSDMB + cancers with adverse clinical outcome.

Effects of deep brain stimulation on the kinematics of gait and balance in patients with idiopathic Parkinson's disease.

BACKGROUND: Advanced stages of idiopathic Parkinson's disease are often characterised by gait alterations and postural instability. Despite improvements in patients' motor symptoms after deep brain stimulation of the subthalamic nucleus, its effects on gait and balance remain a matter of debate. This study investigated the effects of deep brain stimulation on balance and kinematic parameters of gait. METHODS: The gait of 26 patients with advanced idiopathic Parkinson's disease was analysed before and after (between 3 and 6 months) after bilateral deep brain stimulation of the subthalamic nucleus. Computerised analysis was used to study cadence, number of cycles with the correct support sequence, number of cycles, duration of the cycle stages, and knee and ankle goniometry. Balance, postural instability, and mobility were assessed using the Tinetti and Timed Up and Go test. FINDINGS: After stimulation, the following changes were significant (p < 0.01): number of cycles with the correct support sequence, number of total cycles, and foot contact. Patients improved significantly (p < 0.01) in the Tinetti and Timed Up and Go tests, the risk factors for falls changed from high (median 17) to low (median 25), and they improved from minor dependence (statistical median 14) to normality (statistical median 8.70). INTERPRETATION: Deep brain stimulation to inhibit hyperactivity of the subthalamic nucleus was associated with an improvement in the space-time variables of gait and balance in patients with Parkinson's disease for up to 3-6 months. These results highlight the major role of the subthalamic nucleus in motor control mechanisms during locomotion and balance.

The relationship between retinal layers and brain areas in asymptomatic first-degree relatives of sporadic forms of Alzheimer's disease: an exploratory analysis.

BACKGROUND: Two main genetic risks for sporadic Alzheimer's disease (AD) are a family history and ɛ4 allele of apolipoprotein E. The brain and retina are part of the central nervous system and share pathophysiological mechanisms in AD. METHODS: We performed a cross-sectional study with 30 participants without a family history of sporadic AD (FH-) and noncarriers of ApoE ɛ4 (ApoE ɛ4-) as a control group and 34 participants with a family history of sporadic AD (FH+) and carriers of at least one ɛ4 allele (ApoE ɛ4+). We analyzed the correlations between macular volumes of retinal layers and thickness of the peripapillary retinal nerve fiber layer (pRNFL) measured by optical coherence tomography (OCT) with the brain area parameters measured by magnetic resonance imaging (MRI) in participants at high genetic risk of developing AD (FH+ ApoE ɛ4+). RESULTS: We observed a significant volume reduction in the FH+ ApoE ɛ4+ group compared with the control group in some macular areas of (i) macular RNFL (mRNFL), (ii) inner plexiform layer (IPL), (iii) inner nuclear layer (INL), and (iv) outer plexiform layer (OPL). Furthermore, in the FH+ ApoE ɛ4+ group, the retinal sectors that showed statistically significant volume decrease correlated with brain areas that are affected in the early stages of AD. In the same group, the peripapillary retinal nerve fiber layer (pRNFL) did not show statistically significant changes in thickness compared with the control group. However, correlations of these sectors with the brain areas involved in this disease were also found. CONCLUSIONS: In cognitively healthy participants at high genetic risk of developing sporadic forms of AD, there are significant correlations between retinal changes and brain areas closely related to AD such as the entorhinal cortex, the lingual gyrus, and the hippocampus.

Metástasis ósea como presentación del linfoma de Hodgkin. Reporte de un caso / Bone Metastasis as a Presentation of Hodgkin's Lymphoma. A Case Report

RESUMEN La afectación ósea en un paciente con linfoma de Hodgkin generalmente se presenta después de diagnosticado, pero de manera inusual puede hacerlo desde el comienzo de la sintomatología. Se presenta el caso de una mujer joven que comenzó con manifestaciones óseas. En un inicio se consideraron otros diagnósticos que fueron revalorados por el avance y persistencia de la sintomatología hasta llegar a la confirmación diagnóstica de linfoma de Hodgkin, variedad esclerosis nodular. Después de evidenciarse en resonancia magnética nuclear imágenes de lesiones óseas mixtas se logró su diagnóstico definitivo en una biopsia de ganglio linfático que mostró las características células de Reed-Sternberg. Dada la poca frecuencia de estos casos se considera necesaria su publicación para alertar sobre la inclusión de este pensamiento diagnóstico en pacientes que presentan dolores óseos como inicio de un cáncer aún no diagnosticado.

ABSTRACT Bone involvement in a patient with Hodgkin's lymphoma usually occurs after diagnosis, but unusually it can occur from the onset of symptoms. The case of a young woman who began with bone manifestations is presented. Initially, other diagnoses were considered, which were reassessed due to the progression and persistence of symptoms until diagnostic confirmation of Hodgkin's lymphoma of the nodular sclerosis variety. After evidence of mixed bone lesions in magnetic resonance imaging, a definitive diagnosis was achieved in a lymph node biopsy that showed the characteristic Reed-Sternberg cells. Due to the infrequency of these cases, its publication is considered necessary to alert about the inclusion of this diagnostic thought in patients who present bone pain as the beginning of a cancer not yet diagnosed.

Persistent olfactory dysfunction after COVID-19 is associated with reduced perfusion in the frontal lobe.

BACKGROUND: Olfactory dysfunction is common during SARS-CoV-2 infection. The pathophysiology of the persistence of this symptom and the potential relationship with central nervous system involvement is unknown. AIM OF THE STUDY: To evaluate the neural correlates of persistent olfactory dysfunction in a series of patients with post-COVID syndrome. METHODS: Eighty-two patients with post-COVID syndrome were assessed with the Brief Smell Identification Test and a multimodal MRI study including 3D-T1, T2-FLAIR, diffusion-tensor imaging, and arterial spin labeling. Olfactory and neuroimaging examinations were performed 11.18 ± 3.78 months after the acute infection. Voxel-based brain mapping analyses were conducted to correlate the olfactory test with brain volumes, white matter microstructure, and brain perfusion. RESULTS: Olfactory dysfunction was associated with lower tissue perfusion in the orbital and medial frontal regions in the arterial spin labeling sequence. Conversely, no statistically significant findings were detected in brain volumes and diffusion-tensor imaging. Mild changes in paranasal sinuses and nasal cavities were detected in 9.75% of cases, with no association with olfactory deficits. CONCLUSIONS: We provide new insights regarding the pathophysiology of persistent olfactory dysfunction after COVID-19, involving the main brain regions associated with the olfactory system.

A novel approach for skin lesion symmetry classification with a deep learning model.

Skin cancer has become a public health problem due to its increasing incidence. However, the malignancy risk of the lesions can be reduced if diagnosed at an early stage. To do so, it is essential to identify particular characteristics such as the symmetry of lesions. In this work, we present a novel approach for skin lesion symmetry classification of dermoscopic images based on deep learning techniques. We use a CNN model, which classifies the symmetry of a skin lesion as either "fully asymmetric", "symmetric with respect to one axis", or "symmetric with respect to two axes". Moreover, we introduce a new dataset of labels for 615 skin lesions. During the experimentation framework, we also evaluate whether it is beneficial to rely on transfer learning from pre-trained CNNs or traditional learning-based methods. As a result, we present a new simple, robust and fast classification pipeline that outperforms methods based on traditional approaches or pre-trained networks, with a weighted-average F1-score of 64.5%.

Combined Stimulation of the Substantia Nigra and the Subthalamic Nucleus for the Treatment of Refractory Gait Disturbances in Parkinson's Disease: A Preliminary Study.

Deep brain stimulation of the subthalamic nucleus is efficient for the treatment of motor symptoms (i.e., tremors) in patients with Parkinson's disease. Gait disorders usually appear during advanced stages of idiopathic Parkinson's disease in up to 80% of patients and have an important impact on their quality of life. The effects of deep brain stimulation of the subthalamic nucleus on gait and balance are still controversial. For this reason, alternative targets have been considered, such as stimulation of the pedunculopontine nucleus and the pars reticulata of substantia nigra, involved in the integration of the functional connections for gait. Due to the proximity of the subthalamic nucleus to the substantia nigra, their combined stimulation is feasible and may lead to better outcomes, improving axial symptoms. Our objective was to prospectively compare simultaneous stimulation of both structures versus conventional subthalamic stimulation in improving gait disorders. In ten patients with advanced Parkinson's disease, deep brain stimulation leads (eight linear contacts) were implanted, and gait analysis was performed 6 months after surgery in off-stimulation and after 4 weeks of dual or single subthalamic stimulation. An improvement in gait parameters was confirmed with both stimulation conditions, with better results with combined substantia nigra and subthalamic stimulation compared with conventional subthalamic stimulation. Further studies are needed to determine if this effect remains after long-term dual-target stimulation.

A Deep Learning-Based Workflow for Dendritic Spine Segmentation.

The morphological analysis of dendritic spines is an important challenge for the neuroscientific community. Most state-of-the-art techniques rely on user-supervised algorithms to segment the spine surface, especially those designed for light microscopy images. Therefore, processing large dendritic branches is costly and time-consuming. Although deep learning (DL) models have become one of the most commonly used tools in image segmentation, they have not yet been successfully applied to this problem. In this article, we study the feasibility of using DL models to automatize spine segmentation from confocal microscopy images. Supervised learning is the most frequently used method for training DL models. This approach requires large data sets of high-quality segmented images (ground truth). As mentioned above, the segmentation of microscopy images is time-consuming and, therefore, in most cases, neuroanatomists only reconstruct relevant branches of the stack. Additionally, some parts of the dendritic shaft and spines are not segmented due to dyeing problems. In the context of this research, we tested the most successful architectures in the DL biomedical segmentation field. To build the ground truth, we used a large and high-quality data set, according to standards in the field. Nevertheless, this data set is not sufficient to train convolutional neural networks for accurate reconstructions. Therefore, we implemented an automatic preprocessing step and several training strategies to deal with the problems mentioned above. As shown by our results, our system produces a high-quality segmentation in most cases. Finally, we integrated several postprocessing user-supervised algorithms in a graphical user interface application to correct any possible artifacts.