Sustainable removal of nutrients (n and p) in a wastewater treatment plant, with eggshell (biocalcium).

Biological treatments have become insufficient to treat municipal wastewater with greater toxicity and excess nitrogen and phosphate species, thus affecting the organisms that consume the water. In this work, a process was implemented for the removal of nutrients through three stages: stage A, complete aeration (24 h, 43 months); stage B, decreased aeration (12 h, 17 months); and stage C, decreased aeration with biocalcium (12 h, 19 months). The addition of biocalcium from eggshell promoted the formation of flocks, which resulted in the removal of nitrites (61 %), nitrates (84 %), total nitrogen (57 %), total phosphorus (8.3 %), sedimentable solids (50 %), total suspended solids (69 %), BOD5 (76 %), helminth eggs (50 %) and fecal coliforms (54 %). The statistical analyses in the three stages indicated that there is a strong correlation between the concentration of fats and oils and the removal of sedimentable solids and total suspended solids, since these parameters were correlated by 97 and 89 %, respectively. Sedimentable solids were correlated with total suspended solids by 94 %, while nitrates and total nitrogen were correlated 92 %, which favors the removal of nutrients in wastewater. The increase in the concentration of nitrogen in the sludge in stage C generated a C:N ratio of 7.98. This ratio shows that the sludge is feasible for use as a mediator of soils and a biofertilizer because of the high contents of calcium, phosphorus and nitrogen. In addition, biocalcium promoted the precipitation of hydroxyapatite, struvite, calcite and quartz. In general, the three stages of the treatment contributed to the stabilization of the wastewater treatment plant (WWTP) in an efficient, economical, and safe way.

Preclinical Studies with Glioblastoma Brain Organoid Co-Cultures Show Efficient 5-ALA Photodynamic Therapy.

BACKGROUND: The high recurrence of glioblastoma (GB) that occurs adjacent to the resection cavity within two years of diagnosis urges an improvement of therapies oriented to GB local control. Photodynamic therapy (PDT) has been proposed to cleanse infiltrating tumor cells from parenchyma to ameliorate short long-term progression-free survival. We examined 5-aminolevulinic acid (5-ALA)-mediated PDT effects as therapeutical treatment and determined optimal conditions for PDT efficacy without causing phototoxic injury to the normal brain tissue. METHODS: We used a platform of Glioma Initiation Cells (GICs) infiltrating cerebral organoids with two different glioblastoma cells, GIC7 and PG88. We measured GICs-5-ALA uptake and PDT/5-ALA activity in dose-response curves and the efficacy of the treatment by measuring proliferative activity and apoptosis. RESULTS: 5-ALA (50 and 100 µg/mL) was applied, and the release of protoporphyrin IX (PpIX) fluorescence measures demonstrated that the emission of PpIX increases progressively until its stabilization at 24 h. Moreover, decreased proliferation and increased apoptosis corroborated the effect of 5-ALA/PDT on cancer cells without altering normal cells. CONCLUSIONS: We provide evidence about the effectiveness of PDT to treat high proliferative GB cells in a complex in vitro system, which combines normal and cancer cells and is a useful tool to standardize new strategic therapies.

Photodynamic therapy in glioblastoma: Detection of intraoperative inadvertent 5-ALA mediated photodynamic therapeutical effect after gross total resection.

Introduction: Glioblastoma (GBM) remains the most frequent and lethal primary brain tumor in adults, despite advancements in surgical resection techniques and adjuvant chemo- and radiotherapy. The most frequent recurrence pattern (75-90%) occurs in the form of continuous growth from the border of the surgical cavity, thus emphasizing the need for locoregional tumor control. Fluorescence-guided surgical resection using 5-ALA has been widely implemented in surgical protocols for such tumors. Recent literature also highlights the applicability of 5-ALA-mediated photodynamic therapy to obtain locoregional tumor control further. This study aims to identify if 5-ALA mediated photodynamic therapeutic effect after gross total glioblastoma resection has inadvertently occurred due to the exposition of protoporphyrin IX charged peripheral tumoral cells to operative room light sources. Methods: Of 146 patients who were intervened from glioblastoma between 2015 and 2020, 33 were included in the present study. Strict gross total resection (without supralocal resection) had been accomplished, and adjuvant chemoradiotherapy protocol was administered. Two comparison groups were created regarding the location of the recurrence (group A: up to 1 centimeter from the surgical cavity, and group B: beyond 1 centimeter from the surgical cavity). The cutoff point was determined to be 1 centimeter because of the visible light penetrance to the normal brain tissue. Results: In univariate analysis, both groups only differed regarding 5-ALA administration, which was significantly related to a minor relative risk of presenting the recurrence within the first centimeter from the surgical cavity (Relative Risk = 0,655 (95% CI 0,442-0,970), p-value=0,046). Results obtained in univariate analysis were corroborated posteriorly in multivariate analysis (RR=0,730 (95% CI 0,340-0,980), p=0,017). Discussion: In the present study, a probable inadvertent 5-ALA photodynamic therapeutical effect has been detected in vivo. This finding widely opens the door for further research on this promising theragnostic tool.

Validation of Presurgical Simulation of White Matter Damage Using Diffusion Tensor Imaging.

BACKGROUND: The understanding of white matter (WM) was revolutionized by the emergence of tractography based on diffusion tensor imaging (DTI). Currently, DTI simulations are implemented in preoperative planning to optimize surgical approaches. The reliability of these simulations has been questioned and investigated seeking for correlation between neurological performance and anomalies in DTI parameters. However, the ability of preoperative WM simulations to predict a surgical injury has not been thoroughly evaluated. Our objective was to assess the reliability of preoperatively simulated WM injuries for conventional neurosurgical procedures. METHODS: WM surgical damage was preoperatively simulated by creating a 3-dimensional volume representing the endoscope or the surgical trajectory. This volume was used as an additional region of interest in the fascicle reconstruction to be subtracted from the original fascicle. Simulated, injured fascicles were compared in terms of the number of fibers and volume to those created from postoperative DTI studies. Reliability was assimilated into the correlation between the simulation and the postoperative reconstruction; evaluated using the intraclass correlation coefficient or Lin's Concordance correlation coefficient (CCC), and represented on Bland-Altman plots. RESULTS: The preoperative and postoperative DTI studies of 30 patients undergoing various neurosurgical approaches were processed. The correlation between simulated injuries and postoperative studies was high in terms of fibers (Concordance correlation coefficient = Rho.C = 0.989 [95% confidence interval = 0.979-0.995]) and volume (intraclass correlation coefficient = 0.95 [95% CI = 0.89-0.97]). Bland-Altman plots demonstrated that the great majority of cases fell within the mean ± 2 Standard deviations. CONCLUSIONS: Presurgical simulation of WM fascicles based on DTI is consistent with postoperative DTI studies. These findings require further validation by neurophysiological and clinical correlation.

Current and Future Frontiers of Molecularly Defined Oligodendrogliomas.

Oligodendrogliomas are a subtype of adult diffuse glioma characterized by their better responsiveness to systemic chemotherapy than other high-grade glial tumors. The World Health Organization (WHO) 2021 brain tumor classification highlighted defining molecular markers, including 1p19q codeletion and IDH mutations which have become key in diagnosing and treating oligodendrogliomas. The management for patients with oligodendrogliomas includes observation or surgical resection potentially followed by radiation and chemotherapy with PCV (Procarbazine, Lomustine, and Vincristine) or Temozolomide. However, most of the available research about oligodendrogliomas includes a mix of histologically and molecularly diagnosed tumors. Even data driving our current management guidelines are based on post-hoc subgroup analyses of the 1p19q codeleted population in landmark prospective trials. Therefore, the optimal treatment paradigm for molecularly defined oligodendrogliomas is incompletely understood. Many questions remain open, such as the optimal timing of radiation and chemotherapy, the response to different chemotherapeutic agents, or what genetic factors influence responsiveness to these agents. Ultimately, oligodendrogliomas are still incurable and new therapies, such as targeting IDH mutations, are necessary. In this opinion piece, we present relevant literature in the field, discuss current challenges, and propose some studies that we think are necessary to answer these critical questions.

Review of SGLT2i for the Treatment of Renal Complications: Experience in Patients with and Without T2D.

The management of type 2 diabetes (T2D) involves decreasing plasma glucose levels and reducing cardiovascular and microvascular complications. Diabetic kidney disease (DKD), defined as presence of albuminuria, impaired glomerular filtration, or both, is an insidious microvascular complication of diabetes that generates a substantial personal and clinical burden. The progressive reduction in renal function and increased albuminuria results in an increase of cardiovascular events. Thus, patients with DKD require exhaustive control of the associated cardiovascular risk factors. People with diabetes and renal impairment have fewer options of antidiabetic drugs because of contraindications, adverse effects, or altered pharmacokinetics. Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) reduce blood glucose concentrations by blocking the uptake of sodium and glucose in the proximal tubule and promoting glycosuria, and these agents now have an important role in the management of T2D. The results of several cardiovascular outcomes trials suggested that SGLT2i are associated with improvements in renal endpoints in addition to their reduction in cardiovascular events and mortality, which represents a major advance in the care of this population. The dedicated kidney outcomes trials have confirmed the renoprotective action of SGLT2i across different glomerular filtration and albuminuria values, even in patients with non-diabetic chronic kidney disease. Notably, this improvement in kidney function may indirectly benefit cardiac function through multifaceted interorgan cross talk, which can break the cardiorenal vicious circle linked to T2D. In this article, we briefly review the different mechanisms of action that may explain the renal beneficial effects of SGLT2i and disclose the results of the key renal outcome trials and the subsequent update of related clinical guidelines.

High-dose corticosteroid pulse therapy increases the survival rate in COVID-19 patients at risk of hyper-inflammatory response.

OBJECTIVE: Test whether high dose corticosteroid pulse therapy (HDCPT) with either methylprednisolone or dexamethasone is associated with increased survival in COVID-19 patients at risk of hyper-inflammatory response. Provide some initial diagnostic criteria using laboratory markers to stratify these patients. METHODS: This is a prospective observational study, 318 met the inclusion criteria. 64 patients (20.1%) were treated with HDCPT by using at least 1.5mg/kg/24h of methylprednisolone or dexamethasone equivalent. A multivariate Cox regression (controlling for co-morbidities and other therapies) was carried out to determine whether HDCPT (among other interventions) was associated with decreased mortality. We also carried out a 30-day time course analysis of laboratory markers between survivors and non-survivors, to identify potential markers for patient stratification. RESULTS: HDCPT showed a statistically significant decrease in mortality (HR = 0.087 [95% CI 0.021-0.36]; P < 0.001). 30-day time course analysis of laboratory marker tests showed marked differences in pro-inflammatory markers between survivors and non-survivors. As diagnostic criteria to define the patients at risk of developing a COVID-19 hyper-inflammatory response, we propose the following parameters (IL-6 > = 40 pg/ml, and/or two of the following: C-reactive protein > = 100 mg/L, D-dimer > = 1000 ng/ml, ferritin > = 500 ng/ml and lactate dehydrogenase > = 300 U/L). CONCLUSIONS: HDCPT can be an effective intervention to increase COVID-19 survival rates in patients at risk of developing a COVID-19 hyper-inflammatory response, laboratory marker tests can be used to stratify these patients who should be given HDCPT. This study is not a randomized clinical trial (RCT). Future RCTs should be carried out to confirm the efficacy of HDCPT to increase the survival rates of COVID-19.

Cost-Effectiveness of Low-Field Intraoperative Magnetic Resonance in Glioma Surgery.

OBJECT: Low-field intraoperative magnetic resonance (LF-iMR) has demonstrated a slight increase in the extent of resection of intra-axial tumors while preserving patient`s neurological outcomes. However, whether this improvement is cost-effective or not is still matter of controversy. In this clinical investigation we sought to evaluate the cost-effectiveness of the implementation of a LF-iMR in glioma surgery. METHODS: Patients undergoing LF-iMR guided glioma surgery with gross total resection (GTR) intention were prospectively collected and compared to an historical cohort operated without this technology. Socio-demographic and clinical variables (pre and postoperative KPS; histopathological classification; Extent of resection; postoperative complications; need of re-intervention within the first year and 1-year postoperative survival) were collected and analyzed. Effectiveness variables were assessed in both groups: Postoperative Karnofsky performance status scale (pKPS); overall survival (OS); Progression-free survival (PFS); and a variable accounting for the number of patients with a greater than subtotal resection and same or higher postoperative KPS (R-KPS). All preoperative, procedural and postoperative costs linked to the treatment were considered for the cost-effectiveness analysis (diagnostic procedures, prosthesis, operating time, hospitalization, consumables, LF-iMR device, etc). Deterministic and probabilistic simulations were conducted to evaluate the consistency of our analysis. RESULTS: 50 patients were operated with LF-iMR assistance, while 146 belonged to the control group. GTR rate, pKPS, R-KPS, PFS, and 1-year OS were respectively 13,8% (not significative), 7 points (p < 0.05), 17% (p < 0.05), 38 days (p < 0.05), and 3.7% (not significative) higher in the intervention group. Cost-effectiveness analysis showed a mean incremental cost per patient of 789 € in the intervention group. Incremental cost-effectiveness ratios were 111 € per additional point of pKPS, 21 € per additional day free of progression, and 46 € per additional percentage point of R-KPS. CONCLUSION: Glioma patients operated under LF-iMR guidance experience a better functional outcome, higher resection rates, less complications, better PFS rates but similar life expectancy compared to conventional techniques. In terms of efficiency, LF-iMR is very close to be a dominant technology in terms of R-KPS, PFS and pKPS.

[Cardiovascular preventive recommendations. PAPPS 2020 update]. / Recomendaciones preventivas cardiovasculares. Actualización PAPPS 2020.

The recommendations of the semFYC's Program for Preventive Activities and Health Promotion (PAPPS) for the prevention of cardiovascular diseases (CVD) are presented. The following sections are included: Epidemiological review, where the current morbidity and mortality of CVD in Spain and its evolution as well as the main risk factors are described; Cardiovascular (CV) risk tables and recommendations for the calculation of CV risk; Main risk factors such as arterial hypertension, dyslipidemia and diabetes mellitus, describing the method for their diagnosis, therapeutic objectives and recommendations for lifestyle measures and pharmacological treatment; Indications for antiplatelet therapy, and recommendations for screening of atrial fibrillation. The quality of testing and the strength of the recommendation are included in the main recommendations.

Facial Nerve Preservation for Supraorbital Approaches: Anatomical Mapping Based on Consistent Landmarks.

BACKGROUND: The supraorbital keyhole approach (SOKA) provides a safe and advantageous access to the anterior cranial fossa. The implemented skin incision varies depending on surgeon's preferences and requirements. Facial nerve (FN) injury might appear in up to 5.6% of patients. There is a lack of validated tenets for avoiding FN injury. OBJECTIVE: To define a safety area for FN preservation during a SOKA. METHODS: Ten dried skulls and 5 injected cadaveric heads (10 sides) were used. A Cartesian frame was created with its horizontal axis at the level of the supraorbital notch and the vertical axis just lateral to the frontozygomatic junction (FZj). FNs were dissected and points along their course were registered and transferred to the Cartesian frame. RESULTS: Ten microscopic dissections of the FN were performed preserving all branches. A safety area could be defined 8 mm superior and 10 mm inferior to the FZj extending medially to the supraorbital notch and beyond. A 20 mm2 area superior and lateral to the FZj provided low probability (≤10%) of injuring the FN. Similarly, starting 4 mm inferior to the FZj, a lateral safety area was also found. A probabilistic colored heat map was built to represent the results. CONCLUSION: We provide a "safety zone" for a SOKA incision in which the probability to encounter the FN is low. Clinical studies following our method may validate our findings and add evidence to the tenets for minimizing morbidity related to the SOKA incision.

Presurgical simulation for neuroendoscopic procedures: Virtual study of the integrity of neurological pathways using diffusion tensor imaging tractography.

BACKGROUND: White matter (WM) transgression is an unexplored concept in neuroendoscopy. Diffusion tensor image (DTI) tractography could be implemented as a planning and postoperative evaluation tool in functional disconnection procedures (FDPs), which are, currently, the subject of technological innovations. We intend to prove the usefulness of this planning method focused on the assessment of WM injury that is suitable for planning FDPs. METHODS: Ten cranial magnetic resonance studies (20 sides) without pathological findings were processed. Fascicles were defined by two regions of interest (ROIs) using the fiber assignment method by the continuous tracking approach. Using three-dimensional (3D) simulation and DTI tractography, we created an 8-mm virtual endoscope and an uninjured inferior fronto-occipital fasciculus (IFOF) from two ROIs. The injured tract was generated using a third ROI built from the 3D model of the intersection of the oriented trajectory of the endoscope with the fascicle. Data and images were quantitatively and qualitatively analyzed. RESULTS: The average percentage of the injured fibers was 32.0% (range: 12.4%-70%). The average intersected volume was 1.1 cm3 (range: 0.3-2.3 cm3). Qualitative analysis showed the inferior medial quadrant of the inferior fronto-occipital fasciculus (IFOF) as the most frequently injured region. No hemispherical asymmetry was found (P > 0.5). CONCLUSION: DTI tractography is a useful surgical planning tool that could be implemented in several endoscopic procedures. Together with a functional atlas, the presented technique provides a noninvasive method to assess the potential sequelae and thus to optimize the surgical route. The suggested method could be implemented to analyze pathological WM fascicles and to assess the surgical results of FDP such as hemispherotomy or amygdalohippocampectomy. More studies are needed to overcome the limitations of the tractography based information and to develop more anatomically and functionally reliable planning systems.

Contralateral Transfalcine Versus Ipsilateral Anterior Interhemispheric Approach for Midline Arteriovenous Malformations: Surgical and Anatomical Assessment.

BACKGROUND: The contralateral anterior interhemispheric approach (CAIA) is considered to provide surgical advantages to access deep midline lesions: wider working angle, gravity enhanced dissection and retraction, more efficient lighting, and ergonomics. Our team has previously published on the merits of using a contralateral trajectory for medial frontoparietal arteriovenous malformations (AVMs) compared with the conventional anterior interhemispheric approach (IAIA). In this article, we compare the IAIA and CAIA for the resection of medial frontoparietal AVMs using quantitative surgical and anatomical analysis. METHODS: Two models were designed mimicking the most common features of midline AVMs. The CAIA and IAIA were performed bilaterally in 10 specimens. Variables to compare technical feasibility (surgical window [SW] and surgical freedom [SF], target exposure, and angle of attack) were independently assessed using stereotactic navigation. The average SW, SF, and angle of attack were compared with the Student t test. Significance threshold was set at 0.05. RESULTS: The CITA and IAIA were similar in terms of SW, target exposure, and SF in the superior aspect of the AVM. In the depth of the interhemispheric fissure, the CAIA was significantly superior to IAIA in both AVM models: 77% wider AA for the inferior aspect of the AVM (P < 0.01) and greater SF for the draining vein (54%, P = 0.01), ipsilateral (98%, P = 0.02), and contralateral ACA (117%, P < 0.01). CONCLUSIONS: This study suggests technical superiority of the CAIA for the resection of deep midline AVMs. No objective difference was noted in the superficial areas of our models, denoting that IAIA is a safer choice for superficial AVMs. Our results set the foundation for further clinical analysis comparing both approaches.

Austerity Policies and Mortality in Spain After the Financial Crisis of 2008.

OBJECTIVES: To analyze mortality in Spain and the United States before and after these countries implemented divergent policies in response to the financial crisis of 2008. METHODS: We examined mortality statistics in both countries in the years 2000 to 2015. Spain started austerity policies in 2010. We compared differences in mortality ratios, on the basis of trends and effect size analysis. RESULTS: During 2000 to 2010, overall mortality rates (r = 0.98; P < .001; Cohen's d = -0.228) decreased in both countries. In 2011, this trend changed abruptly in Spain, where observed mortality surpassed expected mortality by 29% in 2011 and by 41% in 2015. By contrast, observed mortality surpassed expected mortality in the United States by only 8% in 2015. As the mortality statistics diverged, the effect size greatly increased (d = 7.531). During this 5-year period, there were 505 559 more deaths in Spain than the expected number, while in the United States the difference was 431 501 more deaths despite the 7-fold larger population in the United States compared with Spain. CONCLUSIONS: The marked excess mortality in 2011 to 2015 in Spain is attributable to austerity policies.

Recomendaciones preventivas cardiovasculares. Actualización PAPPS 2018 / No disponible

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Anterior clinoidectomy using an extradural and intradural 2-step hybrid technique.

In Brief: The authors found a practical intraoperative landmark to localize the optic strut during anterior clinoidectomy and used it as the basis for performing anterior clinoidectomy in two steps: extradural phase and intradural phase. This anatomically based technique can increase the safety of anterior clinoidectomy by providing easily identifiable landmarks and reducing intradural bone drilling, which could put the adjacent neurovauscular structures at risk.

Is gout an easy-to-treat disease? The importance of health determinants / ¿Es la gota una enfermedad fácil de tratar? La importancia de los determinantes de salud

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