Exploring the impact of epidemiological and clinical factors on the progression of canine leishmaniosis by statistical and whole genome analyses: from breed predisposition to comorbidities.

Canine leishmaniosis (CanL), caused by Leishmania infantum, is a complex disease of growing importance in Europe. Clinical manifestations result from the down-modulation of the host immune response through multiple host-parasite interactions. Although several factors might influence CanL progression, this is the first known study evaluating risk factors for its different clinical stages in a large referral hospital population (n = 35.669) from an endemic area, over a 20 year period. Genome-wide scans for selection signatures were also conducted to explore the genomic component of clinical susceptibility to L. infantum infection. The prevalence of CanL was 3.2% (16.7% stage I; 43.6% stage II; 32.1% stage III; 7.6% stage IV). Dog breed (crossbreed), bodyweight (<10 kg), living conditions (indoors), regular deworming treatment, and being vaccinated against Leishmania significantly decreased the transmission risk and the risk for developing severe clinical forms. Conversely, the detection of comorbidities was associated with advanced clinical forms, particularly chronic kidney disease, neoplasia, cryptorchidism, infectious tracheobronchitis and urate urolithiasis, although those did not impact the clinical outcome. Significant associations between an increased risk of severe clinical stages and findings in the anamnesis (renal or skin-related manifestations) and physical examination (ocular findings) were also detected, highlighting their diagnostic value in referred cases of CanL. Sixteen breeds were found to be significantly more susceptible to developing severe stages of leishmaniosis (e.g. Great Dane, Rottweiler, English Springer Spaniel, Boxer, American Staffordshire Terrier, Golden Retriever), while 20 breeds displayed a clinical resistantance phenotype and, thus, are more likely to mount an efficient immune response against L. infantum (e.g. Pointer, Samoyed, Spanish Mastiff, Spanish Greyhound, English Setter, Siberian Husky). Genomic analyses of these breeds retrieved 12 regions under selection, 63 candidate genes and pinpointed multiple biological pathways such as the IRE1 branch of the unfolded protein response, which could play a critical role in clinical susceptibility to L. infantum infection.

A nonlinear meccano for Alzheimer's emergence by amyloid ß-mediated glutamatergic hyperactivity.

The pathophysiological process of Alzheimer's disease (AD) is believed to begin many years before the formal diagnosis of AD dementia. This protracted preclinical phase offers a crucial window for potential therapeutic interventions, yet its comprehensive characterization remains elusive. Accumulating evidence suggests that amyloid-ß (Aß) may mediate neuronal hyperactivity in circuit dysfunction in the early stages of AD. At the same time, neural activity can also facilitate Aß accumulation through intricate feed-forward interactions, complicating elucidating the conditions governing Aß-dependent hyperactivity and its diagnostic utility. In this study, we use biophysical modeling to shed light on such conditions. Our analysis reveals that the inherently nonlinear nature of the underlying molecular interactions can give rise to the emergence of various modes of hyperactivity. This diversity in the mechanisms of hyperactivity may ultimately account for a spectrum of AD manifestations.

The C250T Mutation of TERTp Might Grant a Better Prognosis to Glioblastoma by Exerting Less Biological Effect on Telomeres and Chromosomes Than the C228T Mutation.

The aim of this study was to determine how TERTp mutations impact glioblastoma prognosis. MATERIALS AND METHODS: TERTp mutations were assessed in a retrospective cohort of 258 uniformly treated glioblastoma patients. RNA-sequencing and whole exome sequencing results were available in a subset of patients. RESULTS: Overall, there were no differences in outcomes between patients with mutated TERTp-wt or TERTp. However, we found significant differences according to the type of TERTp mutation. Progression-free survival (mPFS) was 9.1 months for those with the C250T mutation and 7 months for those with either the C228T mutation or TERTp-wt (p = 0.016). Overall survival (mOS) was 21.9 and 15 months, respectively (p = 0.026). This differential effect was more pronounced in patients with MGMTp methylation (mPFS: p = 0.008; mOS: p = 0.021). Multivariate analysis identified the C250T mutation as an independent prognostic factor for longer mOS (HR 0.69; p = 0.044). We found no differences according to TERTp mutation status in molecular alterations common in glioblastoma, nor in copy number variants in genes related to alternative lengthening of telomeres. Nevertheless, in the gene enrichment analysis adjusted for MGMTp methylation status, some Reactome gene sets were differentially enriched, suggesting that the C250T mutation may exert a lesser effect on telomeres or chromosomes. CONCLUSIONS: In our series, patients exhibiting the C250T mutation had a more favorable prognosis compared to those with either TERPp-wt or TERTp C228T mutations. Additionally, our findings suggest a reduced involvement of the C250T mutation in the underlying biological mechanisms related to telomeres.

Strict versus Liberal Use of Sentinel Node Biopsy in Breast Cancer Surgery: Any Clinical Outcome Differences? A 20-Year Clinical Experience.

Introduction: As applied to early breast cancer (BC) patients, sentinel node biopsy (SNB) has undergone major changes over the years, especially concerning the widening of indication criteria or skipping systematic axillary lymph node dissection (ALND) after a positive SN. We aimed to ascertain whether a strict versus a more liberal use of SNB resulted in different clinical outcomes in our clinical experience. Methods: We studied consecutive BC patients undergoing SNB between January 1, 2000, and March 31, 2020. There were 1,587 patients and 1,634 SNB procedures. Cases were divided into two study groups: the "strict" SNB group (unifocal tumors up to 35 mm in which ALND was always performed for a positive SN, amounting to 1,183 SNBs), and the "liberal" SNB group (extended tumor size up to selected T3 cases, as well as multifocal or bilateral disease, and patients with previous contralateral BC, not always followed by ALND after a positive SN, amounting to 451 SNBs). Patients were closely followed up to the end of the study. Results: Clinico-pathological variables were strikingly different between study groups, with the liberal group showing a higher risk profile. Cox regression analysis for disease recurrence did not show significant differences in axillary, lymph node, or locoregional recurrence rates or distant relapse. There were no differences in survival between groups. Conclusion: It seems reasonable to adopt the liberal SNB approach, as the goal of surgical management in early BC patients must be attaining optimal locoregional disease control, no matter the differences in distant metastatic spread rates across different BC risk profiles.

Fibromyalgia pain management effectiveness from the patient perspective: a qualitative evidence synthesis.

PURPOSE: This qualitative evidence synthesis aimed to identify and integrate findings where adults with fibromyalgia discussed how they managed their pain, and their perceptions of prescribed treatments from healthcare professionals. MATERIALS AND METHODS: A comprehensive search strategy was implemented in PubMed, Scopus, ISI Web of Science, and Cinahl Plus databases. The GRADE-CERQual framework was used to evaluate the findings confidence. The findings were analyzed using an inductive thematic analysis approach. RESULTS: A total of 35 studies (N = 728) were included. The confidence in the findings ranged from high to low confidence. Patients with fibromyalgia often do not benefit from seeking medical attention due to provider stigma, and have varying views on medication effectiveness commonly reporting feeling like "walking chemists." They find mixed effects from exercise, and consider psychological support essential, although the benefits of cognitive-behavioral therapy were controversial. Combining cognitive-behavioral therapy with physical exercise appears more effective, while natural and complementary therapies have short-term benefits and high costs. CONCLUSIONS: Pain management is a source for frustration and an unmet need for patients with fibromyalgia. The current findings provide crucial insight for providers and researchers; and support the need for fibromyalgia phenotyping and precision medicine approaches to pain management.Implications for RehabilitationChronic widespread pain is the defining feature of fibromyalgia, yet pain reduction is often an unmet need for these individuals.The lack of effective treatments resulting in long-term relief proves frustrating for patients and healthcare providers.Rehabilitation professional should consider the unique insight into this complex, heterogeneous condition that this qualitative synthesis provides to better understand their patient's perspective on pain management.Given the differing perspectives on pain treatment approaches individuals with fibromyalgia report, providers should discuss with each patient their current strategies and take a patient-centered, individualized approach to form an effective treatment plan.

Characterization of a cohort of metastatic lung cancer patients harboring KRAS mutations treated with immunotherapy: differences according to KRAS G12C vs. non-G12C.

Approximately 20% of lung adenocarcinomas harbor activating mutations at KRAS, an oncogene with the ability to alter the tumor immune microenvironment. In this retrospective study, we examined 103 patients with KRAS-mutant lung adenocarcinoma who were treated with immunotherapy-based regimens and we evaluated the clinical outcomes according to PD-L1 expression and the type of KRAS mutation. Among all patients included, 47% carried KRAS G12C mutation whereas 53% harbored KRAS non-G12C mutations. PD-L1 status was available for 77% of cases, with higher expression among KRAS G12C tumors (p = 0.01). Better overall survival and progression-free survival were observed in high PD-L1 expression tumors, regardless of KRAS mutation type. The heterogeneous nature of KRAS-mutant tumors and the presence of other co-mutations may contribute to different outcomes to immunotherapy-based strategies.

Aquatic therapy improves self-reported sleep quality in fibromyalgia patients: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the effectiveness of aquatic therapy on pain, sleep quality, psychological symptoms, quality of life, and health status in people diagnosed with fibromyalgia. METHODS: We searched PubMed, CINAHL, The Cochrane Library, PEDro and Scopus databases. Articles were eligible if they were randomised controlled trials (RCTs) analysing the effects of aquatic therapy in adult people diagnosed with fibromyalgia, and published by October of 2022 in English or Spanish. The Cochrane Risk of Bias tool was employed to conduct the methodological quality assessment of the encompassed studies, and the overall quality of evidence for each comparison was determined using the GRADE approach. RESULTS: Of 375 articles found, 22 met the inclusion criteria. Forest plot analysis of Pittsburgh sleep quality index at short- and mid-term follow-up showed a trend in favour of aquatic therapy, although not statistically significant, with weighted mean difference (WMD) = -1.71 (95% CI: -4.17 to -0.75, p = 0.17). Heterogeneity was substantial (χ2 = 8.74, df = 5 (p < 0.000001; I2 = 95%). Relating the pain outcome by fibromyalgia impact questionnaire (FIQ) short term showed a trend in favour of the aquatic therapy group with WMD = -5.04 (95% CI: - 9.26 to - 0.82, p =  = 0.02) with heterogeneity χ2 = 11.07, df = 4 (p = 0.03; I2 = 64%). Great heterogeneity was found between trials in medium term. CONCLUSION: This systematic review and meta-analysis demonstrated the effectiveness of aquatic therapy as an adjunct treatment to usual care in people suffering from fibromyalgia. Aquatic therapeutic exercise improves the symptomats of sleep quality, pain, and quality of life of adults with fibromyalgia. Further research on long-term outcomes may contribute to the currently available evidence.

Effectiveness of an exercise intervention based on preactivation of the abdominal transverse muscle in patients with chronic nonspecific low back pain in primary care: a randomized control trial.

BACKGROUND: Low back pain is one of the most common disabling pathologies in humanity worldwide. Physical exercises have been used in recent decades to reduce the pain, improve the functionality of the lumbar spine and avoid relapses. The purpose of the study is to analyze the effect of a program based on re-education exercises involving preactivation of the abdominal transverse muscle compared to conventional treatment in adults with chronic nonspecific low back pain. METHODS: A two-arm, single-blind randomized control trial with 35 primary care patients with chronic nonspecific low back pain. Both groups received a 4-week intervention. Data were collected at baseline and at the end of the intervention. Sixteen patients participated in the intervention group, and 19 patients in the control group. RESULTS: For the experimental group, the outcomes of disability and activation of the abdominal transverse muscle decreased significantly (MD -2.9; CI 95% -5.6 to -0.35; η2 = 0.14; p = 0.028) and (MD 2.3; CI 95% 0.91 to 3.67; η2 = 0.25; p = 0.002) respectively, with a large effect size, compared to the control group. There were no differences between the groups in pain intensity, thickness, and resistance of the transverse abdominal muscle. CONCLUSION: A 4-week specific program based on re-education exercises of the preactivation of the abdominal transverse muscle is more effective than conventional treatment for reducing disability and increasing the activation of the abdominal transverse muscle measured by VAS scale and PBU. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03097497. Date of registration: 31/03/2017.

Pre- and Post-Neoadjuvant Clinicopathological Parameters Can Help in the Prognosis and the Prediction of Response in HER2+ and Triple Negative Breast Cancer.

Neoadjuvant treatment (NAT) is one of the most widely used options for HER2+ and triple negative (TN) early breast cancer (BC). Since around half of the patients treated with NAT do not achieve a pathologically complete response (pCR), biomarkers to predict resistance are urgently needed. The correlation of clinicopathological factors with pCR was studied in 150 patients (HER2 = 81; TN = 69) and pre- and post-NAT differences in tumour biomarkers were compared. Low estrogen receptor (ER) expression, high tumour-infiltrating lymphocytes (TILs) and low cT-stage were associated with pCR in HER2+ tumours (p = 0.022; p = 0.032 and p = 0.005, respectively). Furthermore, ER expression was also associated with residual cancer burden (RCB; p = 0.046) in the HER2+ subtype. Similarly, pre-NAT, low progesterone receptor expression (PR; 1-10%) was associated with higher RCB (p < 0.001) in TN tumours. Only clinical and pathological T-stage (cpT-stage) had prognostic capacity in HER2+ tumours, whereas pre-NAT cpT-stage and post-NAT TILs had this capacity for the prognosis of TN tumours. We conclude that ER and PR expression may help predict response to NAT in HER2 and TN BC and should be taken into account in residual tumours. Also, changes observed in the phenotype after NAT suggest the need to reevaluate biomarkers in surviving residual tumour cells.

Pathophysiology and mechanisms of hearing impairment related to neonatal infection diseases.

The inner ear, the organ of equilibrium and hearing, has an extraordinarily complex and intricate arrangement. It contains highly specialized structures meticulously tailored to permit auditory processing. However, hearing also relies on both peripheral and central pathways responsible for the neuronal transmission of auditory information from the cochlea to the corresponding cortical regions. Understanding the anatomy and physiology of all components forming the auditory system is key to better comprehending the pathophysiology of each disease that causes hearing impairment. In this narrative review, the authors focus on the pathophysiology as well as on cellular and molecular mechanisms that lead to hearing loss in different neonatal infectious diseases. To accomplish this objective, the morphology and function of the main structures responsible for auditory processing and the immune response leading to hearing loss were explored. Altogether, this information permits the proper understanding of each infectious disease discussed.

Physiotherapists' experiences on assisting physiotherapy users during the COVID-19 pandemic with lockdown measures in Spain.

BACKGROUND: Physiotherapists had faced a new healthcare scenario characterised by the restrictions caused by the COVID-19 pandemic. PURPOSE: To explore the impact of the COVID-19 pandemic on the physiotherapy profession from the perspective of physiotherapists working in the public and private sectors. METHODS: Qualitative study based on semi-structured personal interviews with 16 physiotherapists working in public, private, or public-private partnership sectors in Spain. The data were collected between March and June 2020. Inductive qualitative content analysis was performed. RESULTS: The participants (13 women, 3 men; aged 24-44 years) had professional experience in diverse healthcare settings (primary, hospital, home, consultations, insurance companies, associations). Five categories were identified: (1) the impact of lockdown on the health of physiotherapy users; (2) managing the demand for physiotherapy services during lockdown; (3) introducing protocols and protective measures in physiotherapy consultations; (4) changes in therapeutic approaches; and (5) future expectations in the physiotherapy care model. Physiotherapists perceived that lockdown caused a decline in the functionality of people with chronic conditions, together with a reduction in the physiotherapy services. Difficulties in prioritising users considered urgent became evident, and the inclusion of prophylactic measures affected treatment duration differently depending on the care setting and the pandemic prompted the use of telerehabilitation. DISCUSSION: The pandemic affected the functional status of chronic physiotherapy users and made treatment time, quality of care and triage protocols visible. In physiotherapy, technological barriers need to be solved, such as digital literacy, families without resources, situations of dependency and cultural barriers.

Presence of Small-Conductance Calcium-Activated Potassium (SK) Channels in the Central and Peripheral Nervous Systems and Their Role in Health and Disease.

Potassium (K+) channels establish and maintain the resting potential of most living cells. Their activity is predominantly regulated by the membrane voltage or the K+ gradient across the cell membrane. However, many cells also express small-conductance calcium-activated potassium (SK) channels, which have the unique ability to translate changes in the level of the intracellular second messenger, Ca2+ to changes in the membrane K+ conductance and, therefore, the resting membrane potential. This article reviews the structure, presence, distribution, and function of SK channels, their pharmacological modulation, and their role in health and disease, emphasizing nociception and pain.

Effectiveness of eHealth therapeutic education interventions in the management of fibromyalgia: protocol for a systematic review and meta-analysis.

INTRODUCTION: Non-pharmacological approaches have shown promising results in improving symptoms and quality of life of patients with fibromyalgia. However, these approaches may not be easily accessible or feasible for everyone. eHealth interventions may offer a more convenient and cost-effective approach to reach a wider range of patients with fibromyalgia and improve their outcomes. As eHealth tools become more prevalent in clinical practice, it is crucial to understand their effectiveness, limitations and how they can be integrated into standard care to optimise clinical outcomes. This systematic review aims to evaluate the effectiveness of eHealth therapeutic education interventions in managing fibromyalgia. METHODS AND ANALYSIS: Randomised controlled trials including eHealth therapeutic education interventions for individuals ≥18 years old with fibromyalgia, published in English or Spanish, will be retrieved by searching the databases PubMed, CINAHL Plus, EMBASE, Scopus, ISI Web of Science, PsycINFO and the Cochrane Central Register of Controlled Trials. Covidence software will be used for the selection of studies and data extraction. The risk of bias and the certainty of evidence will be assessed using the Cochrane Risk of Bias Assessment tool. We plan to perform a meta-analysis contingent on the number of studies retrieved and the interstudy heterogeneity, which will be explored with I2 statistics. ETHICS AND DISSEMINATION: This protocol and the subsequent systematic review will not collect individual-level data and do not require approval by an ethical committee. We intend to disseminate the study results via peer-reviewed scientific journals and relevant (inter)national conferences. PROSPERO REGISTRATION NUMBER: CRD42022343373.

Natural monoterpenes-laden electrospun fibrous scaffolds for endodontic infection eradication.

This investigation aimed to synthesize poly(D,L-lactide) (PLA)-based fibrous scaffolds containing natural essential oils (i.e., linalool and citral) and determine their antimicrobial properties and cytocompatibility as a clinically viable cell-friendly disinfection strategy for regenerative endodontics. PLA-based fibrous scaffolds were fabricated via electrospinning with different concentrations of linalool and citral. The micromorphology and average diameter of the fibers was investigated through scanning electron microscopy (SEM). The chemical composition of the scaffolds was inferred by Fourier-transform infrared spectroscopy (FTIR). Antimicrobial efficacy against Enterococcus faecalis and Actinomyces naeslundii was also evaluated by agar diffusion and colony-forming units (CFU) assays. The scaffolds' cytocompatibility was determined using dental pulp stem cells (DPSCs). Statistical analyses were performed and the significance level was set at α = 5%. Linalool and citral's incorporation in the PLA fibrous scaffolds was confirmed in the FTIR spectra. SEM images indicate no morphological changes upon inclusion of the essential oils, except the reduced diameter of 40% linalool-laden fibers (p < 0.05). Importantly, significant antimicrobial properties were reported for citral-containing scaffolds for CFU/mL counts (p < 0.05), while only 20% and 40% linalool-laden scaffolds reduced CFU/mL (p < 0.05). Meanwhile, the inhibition halos were verified in a concentration-dependent manner for all monoterpenes-laden scaffolds. Citral- and linalool-laden PLA-based fibrous scaffolds showed acceptable cytocompatibility. The incorporation of natural monoterpenes did not alter the scaffolds' fibrous morphology, promoted antimicrobial action against endodontic pathogens, and preserved DPSCs viability. Linalool- and citral-laden electrospun scaffolds hold promise as naturally derived antimicrobial therapeutics for applications in regenerative endodontics.

Comparison between two viscosupplementation protocols for temporomandibular joint osteoarthritis.

OBJECTIVE: This clinical trial aimed to compare the efficacy of two protocols using high molecular weight hyaluronic acid (HA) intra-articular injection in patients with temporomandibular joint (TMJ) osteoarthritis and evaluate involvement of subchondral bone changes and psychosocial factors as predictors of HA treatment. METHODS: Twenty-one individuals were divided into two groups: (A) received three intra-articular HA injections, and (B) received one injection. Outcomes observed were pain intensity, functional limitation, maximum voluntary mouth opening, maximum assisted mouth opening, and treatment tolerability. Follow-ups were performed weekly for 21 days, and two months after the treatment started. RESULTS: No statistically significant intergroup differences were observed in any of the evaluated outcomes. However, Group A showed significant improvement in all outcomes, whereas Group B showed significant improvement only in pain intensity and functional limitation. CONCLUSION: This study demonstrated the effectiveness of both protocols in terms of pain intensity and functional limitation caused by osteoarthritis.

Prevalence of HPV-DNA and E6 mRNA in lung cancer of HIV-infected patients.

HIV-infected individuals could be at a greater risk for developing lung cancer than the general population due to the higher prevalence in the former of human papillomavirus (HPV) in the oral cavity and higher smoking rates. Our aim was to assess HPV prevalence and E6 viral oncogene transcription in lung cancer samples from HIV-infected individuals. This was a single-center, retrospective study of a cohort of HIV-1-infected patients diagnosed with and treated for lung cancer. Pathological lung samples archived as smears or formalin-fixed paraffin-embedded blocks were subjected to HPV genotyping, detection of human p16 protein and assessment for HPV E6 mRNA expression. Lung cancer samples from 41 patients were studied, including squamous cell carcinoma (32%), adenocarcinoma (34%), non-small cell cancer (27%), and small cell cancer (7%). HPV DNA was detected in 23 out of 41 (56%, 95% CI 41-70%) of samples and high-risk (HR)-HPV types were detected in 16 out of 41 (39%, 95% CI 26-54%), HPV-16 being the most prevalent [13/16 (81.3%, 95% CI 57.0-93%]. In samples with sufficient material left: expression of p16 was detected in 3 out of 10 (30%) of HR-HPV DNA-positive tumors and in 3 out of 7 (43%) of the negative ones; and E6 mRNA was detected in 2 out of 10 (20%) of HPV-16-positive samples (squamous lung cancers). These two patients had a background of a previous HPV-related neoplasia and smoking. HR-HPV DNA detection was prevalent in lung cancers in HIV-infected patients. However, viral oncogene expression was limited to patients with previous HPV-related cancers.

Photocrosslinkable methacrylated gelatin hydrogel as a cell-friendly injectable delivery system for chlorhexidine in regenerative endodontics.

OBJECTIVES: This work sought to formulate photocrosslinkable chlorhexidine (CHX)-laden methacrylated gelatin (CHX/GelMA) hydrogels with broad spectrum of action against endodontic pathogens as a clinically viable cell-friendly disinfection therapy prior to regenerative endodontics procedures. METHODS: CHX/GelMA hydrogel formulations were successfully synthesized using CHX concentrations between 0.12 % and 5 % w/v. Hydrogel microstructure was evaluated by scanning electron microscopy (SEM). Swelling and enzymatic degradation were assessed to determine microenvironmental effects. Compression test was performed to investigate the influence of CHX incorporation on the hydrogels' biomechanics. The antimicrobial and anti-biofilm potential of the formulated hydrogels were assessed using agar diffusion assays and a microcosms biofilm model, respectively. The cytocompatibility was evaluated by exposing stem cells from human exfoliated deciduous teeth (SHEDs) to hydrogel extracts (i.e., leachable byproducts obtained from overtime hydrogel incubation in phosphate buffer saline). The data were analyzed using One- and Two-way ANOVA and Tukey's test (α = 0.05). RESULTS: CHX/GelMA hydrogels were effectively prepared. NMR spectroscopy confirmed the incorporation of CHX into GelMA. The addition of CHX did not change the micromorphology (pore size) nor the swelling profile (p > 0.05). CHX incorporation reduced the degradation rate of the hydrogels (p < 0.001); whereas, it contributed to increased compressive modulus (p < 0.05). Regarding the antimicrobial properties, the incorporation of CHX showed a statistically significant decrease in the number of bacteria colonies at 0.12 % and 0.5 % concentration (p < 0.001) and completely inhibited the growth of biofilm at concentration levels 1 %, 2 %, and 5 %. Meanwhile, the addition of CHX, regardless of the concentration, did not lead to cell toxicity, as cell viability values were above 70 %. SIGNIFICANCE: The addition of CHX into GelMA showed significant antimicrobial action against the pathogens tested, even at low concentrations, with the potential to be used as a cell-friendly injectable drug delivery system for root canal disinfection prior to regenerative endodontics.

The role of aquaporins in hearing function and dysfunction.

The inner ear is composed by tiny and complex structures that, together with peripheral and central auditory pathways, are responsible for hearing processing. However, not only the anatomy of the cochlea, its compartments and related structures are complex. The mechanisms involved in the regulation of homeostasis in the inner ear fluid, which determines the ionic gradient necessary for hearing and balancing sensory excitability, is an intricate phenomenon that involves several molecules. Among them, Aquaporins (AQP) play a significant role in this process. AQP are part of a family of small, integral membrane proteins that regulate different processes, including bidirectional water and ionic flow in the inner ear. Changes in the expression of these proteins are essential to auditory physiology and several pathophysiological processes in the inner ear. This review focuses on the role of AQP in health and disease of the auditory system.

Recombinant Integrin ß1 Signal Peptide Blocks Gliosis Induced by Aß Oligomers.

Glial cells participate actively in the early cognitive decline in Alzheimer's disease (AD) pathology. In fact, recent studies have found molecular and functional abnormalities in astrocytes and microglia in both animal models and brains of patients suffering from this pathology. In this regard, reactive gliosis intimately associated with amyloid plaques has become a pathological hallmark of AD. A recent study from our laboratory reports that astrocyte reactivity is caused by a direct interaction between amyloid beta (Aß) oligomers and integrin ß1. Here, we have generated four recombinant peptides including the extracellular domain of integrin ß1, and evaluated their capacity both to bind in vitro to Aß oligomers and to prevent in vivo Aß oligomer-induced gliosis and endoplasmic reticulum stress. We have identified the minimal region of integrin ß1 that binds to Aß oligomers. This region is called signal peptide and corresponds to the first 20 amino acids of the integrin ß1 N-terminal domain. This recombinant integrin ß1 signal peptide prevented Aß oligomer-induced ROS generation in primary astrocyte cultures. Furthermore, we carried out intrahippocampal injection in adult mice of recombinant integrin ß1 signal peptide combined with or without Aß oligomers and we evaluated by immunohistochemistry both astrogliosis and microgliosis as well as endoplasmic reticulum stress. The results show that recombinant integrin ß1 signal peptide precluded both astrogliosis and microgliosis and endoplasmic reticulum stress mediated by Aß oligomers in vivo. We have developed a molecular tool that blocks the activation of the molecular cascade that mediates gliosis via Aß oligomer/integrin ß1 signaling.

Use of a gamified website to increase pain neurophysiology knowledge and improve satisfaction and motivation among students studying for a degree in physiotherapy: a quasi-experimental study.

BACKGROUND: The scientific evidence highlights the difficulties that healthcare professionals experience when managing patients with chronic pain. One of the causes of this difficulty could be related to the acquired training and the lack of knowledge about the neurophysiology of pain. In the present study, we assessed the effectiveness of a gamified web platform in acquiring knowledge about pain neurophysiology and determining the satisfaction and motivation of students of the Degree in Physiotherapy at the University of Lleida. METHODS: A quasi-experimental study was carried out with a sample of 60 students who had access to a gamified web platform that included notes, videos, and clinical cases prepared by the teaching staff and was based on a previous study that included patients and healthcare professionals. RESULTS: The results show that after the intervention, there was a statistically significant increase in knowledge about the neurophysiology of pain, and the effect size was in the desired area of ​​effect. Likewise, many students considered that their motivation had increased as a result of the methodology used in the present study. CONCLUSIONS: The results support the use of this methodology to promote knowledge about the neurophysiology of pain while improving students' motivation.