Effectiveness and safety of Tachosil® as a ventricular sealant: an observational cohort study.

PURPOSE: Surgery close to or in contact with the ventricular system is challenging due to the complications. We sought to evaluate the effectiveness and safety of TachoSil® as a ventricular sealant in preventing complications after cranial surgery with an open ventricular system (OVS). METHODS: This is a single-center and prospective cohort study We included patients who underwent elective surgery for supratentorial craniotomy and periventricular pathology between December 2020 and November 2023. We registered surgical complications arising from CSF dynamics (such as percutaneous cerebrospinal fluid (CSF) leakage, hydrocephalus, pseudomeningocele), infections, and other complications (postsurgical hematoma) adverse drug reactions (ADRs), reintervention or hospital readmission up to 90 days after surgery. RESULTS: Forty interventions were performed on 39 patients, whose median age was 56 years. Eleven patients (28.2%) had antecedents of previous surgery in the same location, 5 (12.8%) had previously received radiotherapy and chemotherapy, and 11 (28.2%) were smokers. Twenty-four patients (60%) underwent surgery for high-grade glioma, 8 (20%) for low-grade gliomas, 6 (15%) for metastasis and 2 (5%) for meningioma. Throughout the study and up to 90 days after surgery, none of the patients presented an ADR. Only 2 patients (5%) presented with a surgery complications derived from ventricular opening (one patient with a percutaneous CSF leakage and one patients with external hydrocephalus). Both patients resolved with a ventriculoperitoneal shunt. CONCLUSIONS: TachoSil® is a dural sealant that can be used safely and effectively intraparenchymally in patients whose surgery involves a ventricular opening. Only 5% of treated patients presented complications arising from CSF hydrodynamics. No patients had pseudomeningocele, infections or complications related to the use of this sealant. To confirm these positive results, randomized and comparative clinical trials assessing the efficacy of TachoSil® in patients after cranial surgery with an OVS are essential. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: This study was registered in the Clinical Trials.gov (NCT05717335). Date May 1st, 2022.

Assessment of care provision integration in a community-based mental health system: balanced care model implementation in Andalusia (Spain).

BACKGROUND: Andalusia is the second largest region in Spain, and it has developed a comprehensive mental health (MH) plan that encourages the consolidation of the balanced care model. However, its geographical and socioeconomic disparity is a great challenge for a community-based MH system. Both the assessment of the implementation of the MH plan and the development of new tools to support decision-making can be considered critical. OBJECTIVES: The present study aims (i) to assess how the integration of different types of MH care may influence system performance and (ii) to check the performance evolution of the integration process geographically regarding the small MH areas of Andalusia. METHODS: The performance of the Andalusian MH system was assessed by combining Monte Carlo simulation, fuzzy inference and data envelopment analysis. The relative technical efficiency was the main performance indicator. RESULTS: A correct integration of appropriate types of MH care, according to population needs, increases the performance of the Andalusian MH system both from global and regional perspectives. The spatial representation (based on small MH areas) of the results highlights how the performance depends on specific geographical characteristics. By analyzing the identified spatial clusters, defined by different management patterns depending on user and socioeconomic characteristics, benchmark areas and areas for improvement can be studied to design evidence-informed policies and interventions. CONCLUSIONS: A global analysis of MH system performance was carried out, including both the successive integration of different types of care and its spatial evolution. Although an appropriate integration of different types of MH care has a positive effect on the Andalusian MH system, this process has different profiles depending on specific geographically based user and socioeconomic characteristics. The balanced care model can be considered the paradigm for assessing the performance of a large and populated territory such as Andalusia, which has a community-based MH system. This methodological approach (performance assessment and spatial analysis) may be used as a guide for developing future evidence-informed policies and managerial interventions.

ZEB1 Inhibits LHß Subunit Transcription When Overexpressed, but Is Dispensable for LH Synthesis in Mice.

Luteinizing hormone (LH), a heterodimeric glycoprotein produced by pituitary gonadotrope cells, regulates gonadal function. Hypothalamic gonadotropin-releasing hormone (GnRH) stimulates LH synthesis and secretion. GnRH induces LHß subunit (Lhb) expression via the transcription factor, early growth response 1 (EGR1), acting on the Lhb promoter. In contrast, overexpression of zinc finger E-box binding homeobox 1 (ZEB1) represses LH production in mice, but the underlying mechanism was not previously elucidated. Here, we observed that ZEB1 inhibited GnRH-stimulated but not basal Lhb mRNA expression in homologous murine LßT2 cells. Moreover, ZEB1 blocked GnRH and/or EGR1 induction of murine Lhb but not human LHB promoter-reporter activity in these cells. Using chimeric reporters, we mapped the species-specific ZEB1 sensitivity to sequence differences, including in Z- and E-boxes, in the proximal Lhb/LHB promoters, immediately upstream of the transcription start sites. ZEB1 bound to the murine Lhb promoter with higher affinity than to the human LHB promoter in this region. To examine ZEB1's physiological role in LH synthesis, we characterized gonadotrope-specific Zeb1 knockout mice. Loss of ZEB1 in gonadotropes did not affect LH production or secretion. Collectively, the data suggest that ZEB1, when overexpressed, can inhibit GnRH/EGR1 induction of murine Lhb transcription but does not play a necessary role in LH synthesis in mice.

New clinical approach in facial mild-moderate acne: Re-stabilization of skin microbiota balance with a topical biotechnological phytocomplex.

OBJECTIVES: Dysbiosis of the skin microbiota has been identified as a key factor in the development of acne. This study was aimed to evaluate the effect of a facial cream gel containing a biotechnological phytocomplex, niacinamide and succinic acid on the bacterial diversity of subjects with mild-moderate acne and its clinical benefits due to microbiota changes. METHODS: Open-label, clinical study in 44 subjects with mild-moderate acne treated with a facial cream gel for 8 weeks. Bacterial diversity was analyzed by 16S rRNA gene sequencing of skin samples. Clinical effects were evaluated using the IGA acne severity scale, biometric measurements, and safety. RESULTS: After 56 days of product's use, an increase in alpha and beta diversity was found (p < 0.01), with a decrease in the relative abundance of C. acnes (48.99% vs. 38.83%, p < 0.001). Regarding clinical results, a decrease in acne severity on the IGA scale (27.33%, p < 0.001), number of non-inflammatory and inflammatory lesions (respectively: 31.12%, p = 0.05; 47.27%, p < 0.001), amount of sebum (89.00%, p < 0.01) and erythema (15.35%, p < 0.01), was found. [Correction added on 19 September 2024, after first online publication: In the preceding sentence, "42.27%" has been changed to "47.27%" in this version.] Responder analysis of the IGA score showed that 61.36% of patients improved by at least one point at day 56. The product was well tolerated throughout the study. CONCLUSIONS: The use of the facial cream gel on skin was effective in rebalancing the microbiota, inhibiting biofilm formation and other virulence factors, reducing the number of mild-moderate acne lesions and sebum secretion, and consequently improving acne's severity.

Intraoperative ultrasound and magnetic resonance comparative analysis in brain tumor surgery: a valuable tool to flatten ultrasound's learning curve.

BACKGROUND: Intraoperative ultrasound (IOUS) is a profitable tool for neurosurgical procedures' assistance, especially in neuro-oncology. It is a rapid, ergonomic and reproducible technique. However, its known handicap is a steep learning curve for neurosurgeons. Here, we describe an interesting postoperative analysis that provides extra feedback after surgery, accelerating the learning process. METHOD: We conducted a descriptive retrospective unicenter study including patients operated from intra-axial brain tumors using neuronavigation (Curve, Brainlab) and IOUS (BK-5000, BK medical) guidance. All patients had preoperative Magnetic Resonance Imaging (MRI) prior to tumor resection. During surgery, 3D neuronavigated IOUS studies (n3DUS) were obtained through craniotomy N13C5 transducer's integration to the neuronavigation system. At least two n3DUS studies were obtained: prior to tumor resection and at the resection conclusion. A postoperative MRI was performed within 48 h. MRI and n3DUS studies were posteriorly fused and analyzed with Elements (Brainlab) planning software, permitting two comparative analyses: preoperative MRI compared to pre-resection n3DUS and postoperative MRI to post-resection n3DUS. Cases with incomplete MRI or n3DUS studies were withdrawn from the study. RESULTS: From April 2022 to March 2024, 73 patients were operated assisted by IOUS. From them, 39 were included in the study. Analyses comparing preoperative MRI and pre-resection n3DUS showed great concordance of tumor volume (p < 0,001) between both modalities. Analysis comparing postoperative MRI and post-resection n3DUS also showed good concordance in residual tumor volume (RTV) in cases where gross total resection (GTR) was not achieved (p < 0,001). In two cases, RTV detected on MRI that was not detected intra-operatively with IOUS could be reviewed in detail to recheck its appearance. CONCLUSIONS: Post-operative comparative analyses between IOUS and MRI is a valuable tool for novel ultrasound users, as it enhances the amount of feedback provided by cases and could accelerate the learning process, flattening this technique's learning curve.

A new topical biotechnological phytocomplex for truncal mild-moderate acne restores skin microbiota balance.

BACKGROUND: The disruption of the microbial community or dysbiosis alters the functional composition, metabolic activity, and local distribution of the microbiota leading the development of acne. The aim of this study is to evaluate the effect of a lotion containing a biotechnological phytocomplex, niacinamide, and succinic acid in the bacterial diversity of subjects with truncal mild-moderate acne and its clinical benefits due to microbiota changes. MATERIALS AND METHODS: Open, clinical study in 43 subjects with truncal mild-moderate acne treated with a lotion for 8 weeks. Bacterial diversity was analyzed by 16S rRNA gene sequencing of skin samples. Clinical effects were evaluated through IGA acne severity scale, biometric measurements, and safety. RESULTS: After 56 days of product's use, an increase in richness alpha diversity was found (p = 0.005), with a decrease in Cutibacterium acnes relative abundance (66.43% vs. 58.11%, p = 0.009). The clinical results showed a decrease in IGA score (27.59% decrease; p = 0.001), the inflammatory lesions (52.12% decrease, p = 0.006) and erythema (18.33% decrease, p = 0.007), and desquamation index (63.83% decrease, p = 0.02). The responder analysis of the IGA score showed that 60.47% of patients improved by at least one point at day 56. The product was well tolerated along the study. CONCLUSION: The use of the lotion on acneic skin was effective on rebalancing the microbiota, inhibiting biofilm formation and other virulence factors, reducing erythema and desquamation, and improving acne's severity.

Neurodegenerative Diseases: Unraveling the Heterogeneity of Astrocytes.

The astrocyte population, around 50% of human brain cells, plays a crucial role in maintaining the overall health and functionality of the central nervous system (CNS). Astrocytes are vital in orchestrating neuronal development by releasing synaptogenic molecules and eliminating excessive synapses. They also modulate neuronal excitability and contribute to CNS homeostasis, promoting neuronal survival by clearance of neurotransmitters, transporting metabolites, and secreting trophic factors. Astrocytes are highly heterogeneous and respond to CNS injuries and diseases through a process known as reactive astrogliosis, which can contribute to both inflammation and its resolution. Recent evidence has revealed remarkable alterations in astrocyte transcriptomes in response to several diseases, identifying at least two distinct phenotypes called A1 or neurotoxic and A2 or neuroprotective astrocytes. However, due to the vast heterogeneity of these cells, it is limited to classify them into only two phenotypes. This review explores the various physiological and pathophysiological roles, potential markers, and pathways that might be activated in different astrocytic phenotypes. Furthermore, we discuss the astrocyte heterogeneity in the main neurodegenerative diseases and identify potential therapeutic strategies. Understanding the underlying mechanisms in the differentiation and imbalance of the astrocytic population will allow the identification of specific biomarkers and timely therapeutic approaches in various neurodegenerative diseases.

Osteoporosis management in patients with chronic kidney disease (ERCOS Study): A challenge in nephrological care.

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the CKD-MBD ("Chronic Kidney Disease-Mineral and Bone Disorders") complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results can influence therapeutic decision-making. However, there is very little information on actual clinical practice in this population. The main objective of the ERCOS (ERC-Osteoporosis) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain. Fifteen centers participated and 162 patients (mostly women [71.2%] postmenopausal [98.3%]) with a median age of 77 years were included. Mean estimated glomerular filtration rate (eGFR) was 36 mL/min/1.73 m2 and 38% of the included patients were on dialysis. We highlight the high frequency of prevalent fragility fractures [37.7%), mainly vertebral (52.5%) and hip (24.6%)], the disproportionate history of patients with glomerular disease compared to purely nephrological series (corticosteroids) and undertreatment for fracture prevention, especially in nephrology consultations. This study is an immediate call to action with the dissemination of the new, more proactive, clinical guidelines, and underlines the need to standardize a coordinated and multidisciplinary care/therapeutic approach to these patients in an efficient way to avoid current discrepancies and therapeutic nihilism.

Digital Twin Platform for Water Treatment Plants Using Microservices Architecture.

The effects of climate change and the rapid growth of societies often lead to water scarcity and inadequate water quality, resulting in a significant number of diseases. The digitalization of infrastructure and the use of Digital Twins are presented as alternatives for optimizing resources and the necessary infrastructure in the water cycle. This paper presents a framework for the development of a Digital Twin platform for a wastewater treatment plant, based on a microservices architecture which optimized its design for edge computing implementation. The platform aims to optimize the operation and maintenance processes of the plant's systems, by employing machine learning techniques, process modeling and simulation, as well as leveraging the information contained in BIM models to support decision-making.

Soluble Klotho, a Potential Biomarker of Chronic Kidney Disease-Mineral Bone Disorders Involved in Healthy Ageing: Lights and Shadows.

Shortly after the discovery of Klotho, interest grew in its potential role in chronic kidney disease (CKD). There are three isoforms of the Klotho protein: αKlotho, ßKlotho and γKlotho. This review will focus on αKlotho due to its relevance as a biomarker in CKD. αKlotho is synthesized mainly in the kidneys, but it can be released into the bloodstream and urine as soluble Klotho (sKlotho), which undertakes systemic actions, independently or in combination with FGF23. It is usually accepted that sKlotho levels are reduced early in CKD and that lower levels of sKlotho might be associated with the main chronic kidney disease-mineral bone disorders (CKD-MBDs): cardiovascular and bone disease. However, as results are inconsistent, the applicability of sKlotho as a CKD-MBD biomarker is still a matter of controversy. Much of the inconsistency can be explained due to low sample numbers, the low quality of clinical studies, the lack of standardized assays to assess sKlotho and a lack of consensus on sample processing, especially in urine. In recent decades, because of our longer life expectancies, the prevalence of accelerated-ageing diseases, such as CKD, has increased. Exercise, social interaction and caloric restriction are considered key factors for healthy ageing. While exercise and social interaction seem to be related to higher serum sKlotho levels, it is not clear whether serum sKlotho might be influenced by caloric restriction. This review focuses on the possible role of sKlotho as a biomarker in CKD-MBD, highlighting the difference between solid knowledge and areas requiring further research, including the role of sKlotho in healthy ageing.

Customized Subperiosteal Implants for the Rehabilitation of Atrophic Jaws: A Consensus Report and Literature Review.

(1) Background: The aim was to perform a literature review on customized subperiosteal implants (CSIs) and provide clinical guidelines based on the results of an expert consensus meeting held in 2023. (2) Methods: A literature search was performed in Pubmed (MEDLINE) in July 2023, including case series and cohort studies with a minimum follow-up of 6 months that analyzed totally or partially edentulous patients treated with CSIs. Previously, an expert consensus meeting had been held in May 2023 to establish the most relevant clinical guidelines. (3) Results: Six papers (four case series and two retrospective cohort studies) were finally included in the review. Biological and mechanical complication rates ranged from 5.7% to 43.8% and from 6.3% to 20%, respectively. Thorough digital planning to ensure the passive fit of the CSI is mandatory to avoid implant failure. (4) Conclusions: CSIs are a promising treatment option for rehabilitating edentulous patients with atrophic jaws; they seem to have an excellent short-term survival rate, a low incidence of major complications, and less morbidity in comparison with complex bone grafting procedures. As the available data on the use of CSIs are very scarce, it is not possible to establish clinical recommendations based on scientific evidence.

New Short RNA Motifs Potentially Relevant in the SARS-CoV-2 Genome.

Background: The coronavirus disease has led to an exhaustive exploration of the SARS-CoV-2 genome. Despite the amount of information accumulated, the prediction of short RNA motifs encoding peptides mediating protein-protein or protein-drug interactions has received limited attention. Objective: The study aims to predict short RNA motifs that are interspersed in the SARS-CoV-2 genome. Methods: A method in which 14 trinucleotide families, each characterized by being composed of triplets with identical nucleotides in all possible configurations, was used to find short peptides with biological relevance. The novelty of the approach lies in using these families to search how they are distributed across genomes of different CoV genera and then to compare the distributions of these families with each other. Results: We identified distributions of trinucleotide families in different CoV genera and also how they are related, using a selection criterion that identified short RNA motifs. The motifs were reported to be conserved in SARS-CoVs; in the remaining CoV genomes analysed, motifs contained, exclusively, different configurations of the trinucleotides A, T, G and A, C, G. Eighty-eight short RNA motifs, ranging in length from 12 to 49 nucleotides, were found: 50 motifs in the 1a polyprotein-encoding orf, 27 in the 1b polyprotein-encoding orf, 5 in the spike-encoding orf, and 6 in the nucleocapsid-encoding orf. Although some motifs (~27%) were found to be intercalated or attached to functional peptides, most of them have not yet been associated with any known functions. Conclusion: Some of the trinucleotide family distributions in different CoV genera are not random; they are present in short peptides that, in many cases, are intercalated or attached to functional sites of the proteome.

Advancing Alzheimer's Therapeutics: Exploring the Impact of Physical Exercise in Animal Models and Patients.

Alzheimer's disease (AD) is the main neurodegenerative disorder characterized by several pathophysiological features, including the misfolding of the tau protein and the amyloid beta (Aß) peptide, neuroinflammation, oxidative stress, synaptic dysfunction, metabolic alterations, and cognitive impairment. These mechanisms collectively contribute to neurodegeneration, necessitating the exploration of therapeutic approaches with multiple targets. Physical exercise has emerged as a promising non-pharmacological intervention for AD, with demonstrated effects on promoting neurogenesis, activating neurotrophic factors, reducing Aß aggregates, minimizing the formation of neurofibrillary tangles (NFTs), dampening inflammatory processes, mitigating oxidative stress, and improving the functionality of the neurovascular unit (NVU). Overall, the neuroprotective effects of exercise are not singular, but are multi-targets. Numerous studies have investigated physical exercise's potential in both AD patients and animal models, employing various exercise protocols to elucidate the underlying neurobiological mechanisms and effects. The objective of this review is to analyze the neurological therapeutic effects of these exercise protocols in animal models and compare them with studies conducted in AD patients. By translating findings from different approaches, this review aims to identify opportune, specific, and personalized therapeutic windows, thus advancing research on the use of physical exercise with AD patients.

Impact of the workforce allocation on the technical performance of mental health services: the collective case of Helsinki-Uusimaa (Finland).

BACKGROUND: Long-term mental health (MH) policies in Finland aimed at investing in community care and promoting reforms have led to a reduction in the number of psychiatric hospital beds. However, most resources are still allocated to hospital and community residential services due to various social, economic and political factors. Despite previous research focussing on the number and cost of these services, no study has evaluated the emerging patterns of use, their technical performance and the relationship with the workforce structure. OBJECTIVE: The purpose of this study was to observe the patterns of use and their technical performance (efficiency) of the main types of care of MH services in the Helsinki-Uusimaa region (Finland), and to analyse the potential relationship between technical performance and the corresponding workforce structure. METHODS: The sample included acute hospital residential care, non-hospital residential care and outpatient care services. The analysis was conducted using regression analysis, Monte Carlo simulation, fuzzy inference and data envelopment analysis. RESULTS: The analysis showed a statistically significant linear relationship between the number of service users and the length of stay, number of beds in non-hospital residential care and number of contacts in outpatient care services. The three service types displayed a similar pattern of technical performance, with high relative technical efficiency on average and a low probability of being efficient. The most efficient acute hospital and outpatient care services integrated multidisciplinary teams, while psychiatrists and nurses characterized non-hospital residential care. CONCLUSIONS: The results indicated that the number of resources and utilization variables were linearly related to the number of users and that the relative technical efficiency of the services was similar across all types. This suggests homogenous MH management with small variations based on workforce allocation. Therefore, the distribution of workforce capacity should be considered in the development of effective policies and interventions in the southern Finnish MH system.

Serum phosphate is associated with increased risk of bone fragility fractures in hemodialysis patients.

BACKGROUND: Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of CKD-MBD and bone fragility fractures in the COSMOS project. METHODS: COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 hemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and PTH (exposure), was assessed using Standard Cox proportional hazards regression and Cox proportional hazards regression for recurrent events. Additional analyses were performed considering all-cause mortality as a competitive event for bone fragility fracture occurrence. Multivariable models were used in all strategies, with the fully adjusted model including a total of 24 variables. RESULTS: During a median follow-up of 24 months 252 (4%) patients experienced at least one bone fragility fracture (incident bone fragility fracture rate 28.5 per 1000 patient-years). In the fractured and non-fractured patients, the percentage of men was 43.7% and 61.4%, mean age 68.1 and 63.8 years and a haemodialysis vintage of 55.9 and 38.3 months respectively. Baseline serum phosphate > 6.1 mg/dL (reference value 4.3-6.1 mg/dL) was significantly associated with a higher bone fragility fracture risk in both regression models (HR: 1.53[95%CI: 1.10-2.13] and HR: 1.44[95%CI: 1.02-2.05]. The significant association persisted after competitive risk analysis (subHR: 1.42[95%CI: 1.02-1.98]) but the finding was not confirmed when serum phosphate was considered as a continuous variable. Baseline serum calcium showed no association with bone fragility fracture risk in any regression model. Baseline serum PTH > 800 pg/mL was significantly associated with a higher bone fragility fracture risk in both regression models, but the association disappeared after a competitive risk analysis. CONCLUSIONS: Hyperphosphatemia was independently and consistently associated with an increased bone fracture risk, suggesting serum phosphate could be a novel risk factor for bone fractures in hemodialysis patients.

Transition of patients with metabolic bone disease from paediatric to adult healthcare services: current situation and proposals for improvement.

BACKGROUND: There are currently no models for the transition of patients with metabolic bone diseases (MBDs) from paediatric to adult care. The aim of this project was to analyse information on the experience of physicians in the transition of these patients in Spain, and to draw up consensus recommendations with the specialists involved in their treatment and follow-up. METHODS: The project was carried out by a group of experts in MBDs and included a systematic review of the literature for the identification of critical points in the transition process. This was used to develop a questionnaire with a total of 48 questions that would determine the degree of consensus on: (a) the rationale for a transition programme and the optimal time for the patient to start the transition process; (b) transition models and plans; (c) the information that should be specified in the transition plan; and (d) the documentation to be created and the training required. Recommendations and a practical algorithm were developed using the findings. The project was endorsed by eight scientific societies. RESULTS: A total of 86 physicians from 53 Spanish hospitals participated. Consensus was reached on 45 of the 48 statements. There was no agreement that the age of 12 years was an appropriate and feasible point at which to initiate the transition in patients with MBD, nor that a gradual transition model could reasonably be implemented in their own hospital. According to the participants, the main barriers for successful transition in Spain today are lack of resources and lack of coordination between paediatric and adult units. CONCLUSIONS: The TEAM Project gives an overview of the transition of paediatric MBD patients to adult care in Spain and provides practical recommendations for its implementation.