Complement-Mediated Thrombotic Microangiopathy after Kidney Transplant: Should Treatment with C5 Inhibitor Be Lifelong?

Complement-mediated thrombotic microangiopathy (CM-TMA) is a rare and life-threatening complication that can occur in kidney transplant recipients, with various potential triggers including immunosuppressive medications. The optimal management and duration of treatment with C5 inhibitors (C5i) for CM-TMA in this patient population remain areas of ongoing investigation. We present the case of a 38-year-old female with a history of IgA nephropathy who underwent preemptive living-related kidney transplantation and subsequently developed CM-TMA 7 years post-transplant. Treatment with ravulizumab led to a rapid hematologic response and stabilized platelet counts. Serial measurements of complement functional tests and clinical stability guided the discontinuation of C5i therapy. The case highlights the complexity of managing CM-TMA in kidney transplant recipients, particularly in determining the appropriate duration of C5i therapy. The absence of an established protocol for discontinuation necessitates a personalized approach based on clinical and laboratory stability, absence of complement gene variants, and serial complement functional tests. Further prospective investigations are warranted to define the optimal strategies for monitoring and safely discontinuing C5i therapy in this unique patient population. This case underscores the importance of individualized care in the management of CM-TMA post-kidney transplantation, offering insights into potential criteria for therapy discontinuation.

ChatGPT as an information tool in rhinology. Can we trust each other today?

PURPOSE: ChatGPT (Chat-Generative Pre-trained Transformer) has proven to be a powerful information tool on various topics, including healthcare. This system is based on information obtained on the Internet, but this information is not always reliable. Currently, few studies analyze the validity of these responses in rhinology. Our work aims to assess the quality and reliability of the information provided by AI regarding the main rhinological pathologies. METHODS: We asked to the default ChatGPT version (GPT-3.5) 65 questions about the most prevalent pathologies in rhinology. The focus was learning about the causes, risk factors, treatments, prognosis, and outcomes. We use the Discern questionnaire and a hexagonal radar schema to evaluate the quality of the information. We use Fleiss's kappa statistical analysis to determine the consistency of agreement between different observers. RESULTS: The overall evaluation of the Discern questionnaire resulted in a score of 4.05 (± 0.6). The results in the Reliability section are worse, with an average score of 3.18. (± 1.77). This score is affected by the responses to questions about the source of the information provided. The average score for the Quality section was 3.59 (± 1.18). Fleiss's Kappa shows substantial agreement, with a K of 0.69 (p < 0.001). CONCLUSION: The ChatGPT answers are accurate and reliable. It generates a simple and understandable description of the pathology for the patient's benefit. Our team considers that ChatGPT could be a useful tool to provide information under prior supervision by a health professional.

Cochlear dysfunction as an early biomarker of cognitive decline in normal hearing and mild hearing loss.

INTRODUCTION: Age-related hearing loss is an important risk factor for cognitive decline. However, audiogram thresholds are not good estimators of dementia risk in subjects with normal hearing or mild hearing loss. Here we propose to use distortion product otoacoustic emissions (DPOAEs) as an objective and sensitive tool to estimate the risk of cognitive decline in older adults with normal hearing or mild hearing loss. METHODS: We assessed neuropsychological, brain magnetic resonance imaging, and auditory analyses on 94 subjects > 64 years of age. RESULTS: We found that cochlear dysfunction, measured by DPOAEs-and not by conventional audiometry-was associated with Clinical Dementia Rating Sum of Boxes (CDR-SoB) classification and brain atrophy in the group with mild hearing loss (25 to 40 dB) and normal hearing (<25 dB). DISCUSSION: Our findings suggest that DPOAEs may be a non-invasive tool for detecting neurodegeneration and cognitive decline in the older adults, potentially allowing for early intervention.

Effectiveness of Omega-3 Fatty Acid Supplementation in Improving the Metabolic and Inflammatory Profiles of Mexican Adults Hospitalized with COVID-19.

BACKGROUND AND OBJECTIVES: The development of severe COVID-19 is related to the preexistence of comorbidities and an inadequate nutritional status. The latter is a critical factor for the development of infection and the progression of the disease. Notably, optimal nutrition impacts immune system function, as malnutrition is related to high cytokine levels in the late phase of the disease, correlating with a poor prognosis. In this sense, omega-3 fatty acids (O3FAs) have anti-inflammatory properties that may reduce morbidity and mortality from COVID-19 infection. O3FAs are linked to a better prognosis in COVID-19 patients. MATERIALS AND METHODS: In this randomized, double-blind clinical trial, we evaluate the administration of O3FAs to unvaccinated Mexican patients for two weeks starting after the first two hours of hospitalization. RESULTS: The findings support the notion that O3FAs (in a dose high enough to satisfy human physiological requirements in a short time, one capsule of 1.4 g O3FAs daily) exert a comprehensive multi-systemic modulatory influence, affecting inflammatory and metabolic pathways. Significant perturbations in biomarkers, including absolute neutrophil count, hematocrit, and platelet indices, underscore the compound's anti-inflammatory effect. Concurrently, the intervention modulates pivotal metabolic and hepatic parameters, attenuating cardiovascular risk profiles and expediting patient convalescence. These multifarious effects are likely orchestrated through intricate biochemical mechanisms and are subject to individual variations predicated on metabolic factors. CONCLUSIONS: The results of this trial support the notion that O3FA supplementation has beneficial effects on COVID-19 patients with moderate presentation by regulating metabolism and limiting inflammation.

Ir(III) Half-Sandwich Photosensitizers with a π-Expansive Ligand for Efficient Anticancer Photodynamic Therapy.

One approach to reduce the side effects of chemotherapy in cancer treatment is photodynamic therapy (PDT), which allows spatiotemporal control of the cytotoxicity. We have used the strategy of coordinating π-expansive ligands to increase the excited state lifetimes of Ir(III) half-sandwich complexes in order to facilitate the generation of 1O2. We have obtained derivatives of formulas [Cp*Ir(C∧N)Cl] and [Cp*Ir(C∧N)L]BF4 with different degrees of π-expansion in the C∧N ligands. Complexes with the more π-expansive ligand are very effective photosensitizers with phototoxic indexes PI > 2000. Furthermore, PI values of 63 were achieved with red light. Time-dependent density functional theory (TD-DFT) calculations nicely explain the effect of the π-expansion. The complexes produce reactive oxygen species (ROS) at the cellular level, causing mitochondrial membrane depolarization, cleavage of DNA, nicotinamide adenine dinucleotide (NADH) oxidation, as well as lysosomal damage. Consequently, cell death by apoptosis and secondary necrosis is activated. Thus, we describe the first class of half-sandwich iridium cyclometalated complexes active in PDT.

Host space, not energy or symbiont size, constrains feather mite abundance across passerine bird species.

Comprehending symbiont abundance among host species is a major ecological endeavour, and the metabolic theory of ecology has been proposed to understand what constrains symbiont populations. We parameterized metabolic theory equations to investigate how bird species' body size and the body size of their feather mites relate to mite abundance according to four potential energy (uropygial gland size) and space constraints (wing area, total length of barbs and number of feather barbs). Predictions were compared with the empirical scaling of feather mite abundance across 106 passerine bird species (26,604 individual birds sampled), using phylogenetic modelling and quantile regression. Feather mite abundance was strongly constrained by host space (number of feather barbs) but not by energy. Moreover, feather mite species' body size was unrelated to the body size of their host species. We discuss the implications of our results for our understanding of the bird-feather mite system and for symbiont abundance in general.

Evaluating the Thickness of the Root Canal Dentin Wall in Primary First Molars Using Cone-beam Computed Tomography.

Aim: To evaluate the thickness of the root canal dentin wall in the cervical, middle, and apical third of primary first molars. Materials and methods: Cross-sectional study consisting of 30 cone-beam computed tomography (CBCT) images of primary maxillary and mandibular first molars, with crown, and root integrity. The wall dentin thickness of each canal was measured in three axial views, divided into distal (D), mesial, lingual/palatine, and buccal surfaces. Results: The smallest dentin wall thickness of the maxillary molar was located on the mesial surface of the mesiobuccal (MB) canal apical third (mean 0.55 ± 0.04 mm). The buccal and palatal (P) surfaces of the distobuccal (DB) and P canals showed the smallest dentin thickness on the cervical third (0.62 ± 0.02 mm). On the mandibular molar, we found the smallest dentin thickness on the apical third [lingual surface of the MB canal and buccal surface of the mesiolingual (ML) canal] with a mean of 0.41 ± 0.07 mm. Additionally, the dentin thickness is average of the D canal was about 0.67 ± 0.11 mm. Conclusion: It is essential to understand the primary first molar's anatomy to reduce possible complications in pediatric patients from instrumentation during root canal treatments. Clinical significance: Pulpectomy is among the most challenging procedures in pediatric dentistry and the knowledge of the root anatomy of primary teeth allows the professional to make better clinical decisions and reduce possible risks during root canal treatment. How to cite this article: Justiniano-Navarro C, Caballero-García S, López-Rodriguez G, et al. Evaluating the Thickness of the Root Canal Dentin Wall in Primary First Molars using Cone-beam Computed Tomography. Int J Clin Pediatr Dent 2023;16(S-2):S122-S127.

Neuropsychological assessment protocol in an ongoing randomized controlled trial on posterior subthalamic area vs. ventral intermediate nucleus deep brain stimulation for essential tremor.

Objective: Patients with essential tremor (ET) may experience cognitive-affective impairment. Deep brain stimulation (DBS) of different targets, such as the ventral intermediate nucleus (VIM) of the thalamus or the posterior subthalamic area (PSA), has been shown to be beneficial for refractory ET. However, there is little evidence regarding the possible neuropsychological effects of PSA-DBS on patients with ET, and there are few studies comparing it with VIM-DBS in this population.In this study, we aim to present the evaluation protocol and neuropsychological battery as used in an ongoing trial of DBS for ET comparing the already mentioned targets. Methods: As part of a randomized, double-blind, crossover clinical trial comparing the effectiveness and safety of PSA-DBS vs. VIM-DBS, 11 patients with refractory ET will undergo a multi-domain neuropsychological battery assessment. This will include a pre-/post-implantation assessment (3 months after the stimulation of each target and 6 months after an open stage of DBS on the most optimal target). Conclusion: Evidence on the neuropsychological effects of DBS in patients with refractory ET is very scarce, particularly in lesser-explored targets such as PSA. This study could contribute significantly in this field, particularly on pre-procedure safety analysis for tailored patient/technique selection, and to complete the safety analysis of the procedure. Moreover, if proven useful, this proposed neuropsychological assessment protocol could be extensible to other surgical therapies for ET.

Cross-species transmission and PB2 mammalian adaptations of highly pathogenic avian influenza A/H5N1 viruses in Chile.

H5N1 highly pathogenic avian influenza viruses (HPAIV) emerged in wild birds in Chile in December 2022 and spilled over into poultry, marine mammals, and one human. Between December 9, 2022 - March 14, 2023, a coordinated government/academic response detected HPAIV by real-time RT-PCR in 8.5% (412/4735) of samples from 23 avian and 3 mammal orders. Whole-genome sequences obtained from 77 birds and 8 marine mammals revealed that all Chilean H5N1 viruses belong to lineage 2.3.4.4b and cluster monophyletically with viruses from Peru, indicating a single introduction from North America into Peru/Chile. Mammalian adaptations were identified in the PB2 segment: D701N in two sea lions, one human, and one shorebird, and Q591K in the human and one sea lion. Minor variant analysis revealed that D701N was present in 52.9 - 70.9% of sequence reads, indicating the presence of both genotypes within hosts. Further surveillance of spillover events is warranted to assess the emergence and potential onward transmission of mammalian adapted H5N1 HPAIV in South America.

Bioconsolidation of Damaged Construction Calcarenites and Evaluation of the Improvement in Their Petrophysical and Mechanical Properties.

Bioconsolidation treatment using bacterial carbonatogenesis has been proposed as an environmentally friendly strategy for the efficient preservation of damaged stones, particularly suitable for carbonate stones. The study presented here deals with the evaluation of the performance of this treatment, applied to damaged carbonate stones in two historical buildings in Spain. The methodology applied in this research serves as a reference for future similar studies. Results showed significant improvement in the petrophysical and mechanical properties of the damaged stone following the treatment through the production of calcite and vaterite by the abundant carbonatogenic bacteria inhabiting the stone. These bacteria were able to effectively consolidate weathered areas if an adequate nutritional solution was employed, thereby augmenting the stone's resistance, as evidenced by the Drilling Resistance Measurement System (DRMS). FESEM images showed calcified bacteria and calcified exopolymeric substances (EPS) consolidating stone minerals without blocking their pores. In addition to consolidation, this biotreatment improves the stone's behavior against water absorption and increases the contact angle of water droplets without significant modifications in the pore size or diminishing vapor permeability. No color changes are observed. Overall, these results show that the application of the nutritional solution (M-3P) for in situ consolidation of different types of porous carbonate building stones is a highly effective conservation method, with no modification of the chemical composition of the treated materials.

Smart education system to improve the learning system with CBR based recommendation system using IoT.

Over the last few years, the research fields of intelligent learning systems have been improving the process of learning systems. Smart Tutoring System-(STS) applications have been used in e-learning. The results signify the importance of the learner's engagement in customizing a model. The design outcomes of this IoT-based personalized learning system purely work on the audience's learning requirements, their keyword search, their learning experience levels, proficiency level of subjects, and the type of the course being taught. Students spent an average of 25.67 h accessing textual materials weekly, 27.4 h accessing video assets weekly, and similarly 6.5 h accessing visual learning materials. The research analysis part concludes participants' percentage of learning as per evaluations assessment, which increases whenever the outcome analysis comes with Case-Based Reasoning classifiers-CBR based search model. The findings displayed significant differences before and after learning case by case for every learner as per chosen topic and quiz assessments: 42.57% of the students responded before learning the first question assessments whereas 74.82%, of the students responded, after completion of learning from online resources based on their choice with CBR. Recommendation Model Analysis discussed root means square error-RMSE lies from 10% to 20% for 550 students group size. The RMSE result is 24% for a size of 1600, which is low performance compared to other group sizes. This study focuses on the STS recommendation model for the slow learner group to identify required learning from various online resources.

Fate of concomitant tricuspid regurgitation in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Owing to a lack of supportive data, tricuspid regurgitation (TR) is usually not addressed in patients undergoing coronary artery bypass grafting (CABG). Here we evaluated changes in TR degrees over time and its impact on survival in patients undergoing CABG. METHODS: We reviewed the data of 9726 patients who underwent isolated CABG between January 2000 and January 2021. According to preoperative TR severity, patients were stratified into nonsignificant (none to trivial, mild) and significant (moderate to severe) TR groups. We excluded patients who had undergone previous tricuspid valve surgery, pacemaker placement, and concomitant valve or ablative surgery. Propensity score matching and Cox proportional hazards models were used to identify associations between TR grade and the primary outcome of all-cause mortality. The secondary outcome was change in TR severity on the last echocardiogram. RESULTS: After propensity score matching, 380 patients in each group were identified. At baseline, 359 patients had moderate TR (94.5%) and 21 (5.5%) had severe TR. On the last follow-up echocardiogram, TR had improved in 40.5% of the patients in the significant TR group. Kaplan-Meier survival curves showed significantly lower survival in patients with significant preoperative TR compared to those with nonsignificant TR (P < .001). After adjusting for other confounders, survival was no worse in the patients with significant TR group (hazard ratio, 1.05; 95% confidence interval, 0.80-1.38; P = .70). CONCLUSIONS: Significant preoperative TR improved in 40.5% of patients after isolated CABG. After adjusting for other factors, significant TR did not affect long-term survival.

Frequency of Autoantibodies on Non-Hodgkin Lymphoma.

(1) Background: Non-Hodgkin Lymphoma is a neoplasm that can significantly compromise the immune system, but timely assessment can change the patient outcome. In cancer, the activation of the immune system could lead to the secretion of autoantibodies. (2) Methods: A retrospective cohort study was performed from 2017 to 2019 in patients with Non-Hodgkin Lymphoma diagnosed with a biopsy. (3) Results: We included 39 patients who were newly diagnosed, untreated, and without any autoimmune disease previously reported. Thirty patients had the presence of autoantibodies (antiphospholipid antibodies, anti-cytoplasmic neutrophils antibodies, antinuclear antibodies), and nine were without autoantibodies. There were no statistical differences among groups regarding clinical, demographic, staging, and prognosis characteristics. Also, there were no differences in the outcomes of the patients after finishing chemotherapy and one year after initiating treatment. (4) Conclusions: Further investigations must be conducted regarding an extended panel of autoantibodies because the panel of autoantibodies in this study did not show a relationship between the presence and the clinical outcome of the patients.

Lateral pterygoid muscle ultrasound-guided injection: A technical note.

BACKGROUND: Temporomandibular disorders (TMDs) are a frequent cause of orofacial pain, causing functional disability and a negative impact on quality of life. Botulinum toxin (BTX-A) injection in lateral pterygoid muscle (LPM) is one of the treatment modalities proposed, but the blind puncture guided by EMG carries a risk of vascular puncture or diffusion of the toxin to nearby muscles. We describe an ultrasound-guided approach and evaluate the spread of the injection in a fresh human cadaver. METHODS: A fresh human cadaver was injected. An out-of-plane approach was performed using a convex probe, injecting 1.0 ml of 0.25% methylene blue dye into the LPM. After, a dissection was performed to isolate the lateral pterygoid muscle and assess the spread of the dye. RESULTS: Ultrasound-guided injection allowed to visualize in real-time the spread of the dye within the LPM. The deep and superficial muscles nearby to LPM were not stained by the dye, but upper and lower head of LPM was heavily stained. CONCLUSION: Ultrasound-guided approach for the injection of BTX-A into the LPM could be considered a successful and safe treatment for myofascial pain related to TMD. Therefore, further clinical studies are needed to study the reproducibility of ultrasound guided LPM injection and to evaluate the clinical results.

Zein-based nanospheres and nanocapsules for the encapsulation and oral delivery of quercetin.

In this study, the ability of zein nanospheres (NS) and zein nanocapsules containing wheat germ oil (NC) to enhance the bioavailability and efficacy of quercetin was evaluated. Both types of nanocarriers had similar physico-chemical properties, including size (between 230 and 250 nm), spherical shape, negative zeta potential, and surface hydrophobicity. However, NS displayed a higher ability than NC to interact with the intestinal epithelium, as evidenced by an oral biodistribution study in rats. Moreover, both types of nanocarriers offered similar loading efficiencies and release profiles in simulated fluids. In C. elegans, the encapsulation of quercetin in nanospheres (Q-NS) was found to be two twice more effective than the free form of quercetin in reducing lipid accumulation. For nanocapsules, the presence of wheat germ oil significantly increased the storage of lipids in C. elegans; although the incorporation of quercetin (Q-NC) significantly counteracted the presence of the oil. Finally, nanoparticles improved the oral absorption of quercetin in Wistar rats, offering a relative oral bioavailability of 26% and 57% for Q-NS and Q-NC, respectively, compared to a 5% for the control formulation. Overall, the study suggests that zein nanocarriers, particularly nanospheres, could be useful in improving the bioavailability and efficacy of quercetin.

Are all ventilators for NIV performing the same? A bench analysis.

Global pandemic due to COVID-19 has increased the interest for ventilators´ use worldwide. New devices have been developed and older ones have undergone a renewed interest, but we lack robust evidence about performance of each ventilator to match appropriate device to a given patient and care environment. The aim of this bench study was to investigate the performance of six devices for noninvasive ventilation, and to compare them in terms of volume delivered, trigger response, pressurization capacity and synchronization in volume assisted controlled and pressure support ventilation. All ventilators were tested under thirty-six experimental conditions by using the lung model ASL5000® (IngMar Medical, Pittsburgh, PA). Two leak levels, two muscle inspiratory efforts and three mechanical patterns were combined for simulation. Trigger function was assessed by measurement of trigger-delay time. Pressurization capacity was evaluated as area under the pressure-time curve over the first 500 ms after inspiratory effort onset. Synchronization was evaluated by the asynchrony index and by incidence and type of asynchronies in each condition. All ventilators showed a good performance, even if pressurization capacity was worse than expected. Leak level did not affect their function. Differences were found during low muscle effort and obstructive pattern. In general, Philips Trilogy Evo/EV300 and Hamilton C3 showed the best results. NIV devices successfully compensate air leaks but still underperform with low muscle effort and obstructive lungs. Clinicians´ must have a clear understanding of the goals of NIV both for devices´ choice and set main parameters to achieve therapy success.

VolumePeeler: a novel FIJI plugin for geometric tissue peeling to improve visualization and quantification of 3D image stacks.

MOTIVATION: Quantitative descriptions of multi-cellular structures from optical microscopy imaging are prime to understand the variety of three-dimensional (3D) shapes in living organisms. Experimental models of vertebrates, invertebrates and plants, such as zebrafish, killifish, Drosophila or Marchantia, mainly comprise multilayer tissues, and even if microscopes can reach the needed depth, their geometry hinders the selection and subsequent analysis of the optical volumes of interest. Computational tools to "peel" tissues by removing specific layers and reducing 3D volume into planar images, can critically improve visualization and analysis. RESULTS: We developed VolumePeeler, a versatile FIJI plugin for virtual 3D "peeling" of image stacks. The plugin implements spherical and spline surface projections. We applied VolumePeeler to perform peeling in 3D images of spherical embryos, as well as non-spherical tissue layers. The produced images improve the 3D volume visualization and enable analysis and quantification of geometrically challenging microscopy datasets. AVAILABILITY: ImageJ/FIJI software, source code, examples, and tutorials are openly available in https://cimt.uchile.cl/mcerda.

Silica-Functionalized Nanolimes for the Conservation of Stone Heritage.

The relatively recent development of nanolimes (i.e., alcoholic dispersions of Ca(OH)2 nanoparticles) has paved the way for new approaches to the conservation of important art works. Despite their many benefits, nanolimes have shown limited reactivity, back-migration, poor penetration, and lack of proper bonding to silicate substrates. In this work a novel solvothermal synthesis process is presented by which extremely reactive nanostructured Ca(OH)2 particles are obtained using calcium ethoxide as the main precursor species. Moreover, it is demonstrated that this material can be easily functionalized with silica-gel derivatives under mild synthesis conditions, thereby preventing particle growth, increasing total specific surface area, enhancing reactivity, modifying colloidal behavior, and functioning as self-integrated coupling agents. Additionally, the formation of calcium silicate hydrate (CSH) nanocement is promoted by the presence of water, resulting in optimal bonding when applied to silicate substrates, as evidenced by the higher reinforcement effect produced on treated Prague sandstone specimens as compared to those consolidated with nonfunctionalized commercial nanolime. The functionalization of nanolimes is not only a promising strategy for the design of optimized consolidation treatments for the cultural heritage, but may also have important implications for the development of advanced nanomaterials for building, environmental, or biomedical applications.

Unveiling the secret of ancient Maya masons: Biomimetic lime plasters with plant extracts.

Ancient Maya produced some of the most durable lime plasters on Earth, yet how this was achieved remains a secret. Here, we show that ancient Maya plasters from Copan (Honduras) include organics and have a calcite cement with meso-to-nanostructural features matching those of calcite biominerals (e.g., shells). To test the hypothesis that the organics could play a similar toughening role as (bio)macromolecules in calcium carbonate biominerals, we prepared plaster replicas adding polysaccharide-rich bark extracts from Copan's local trees following an ancient Maya building tradition. We show that the replicas display similar features as the organics-containing ancient Maya plasters and demonstrate that, as in biominerals, in both cases, their calcite cement includes inter- and intracrystalline organics that impart a marked plastic behavior and enhanced toughness while increasing weathering resistance. Apparently, the lime technology developed by ancient Maya, and likely other ancient civilizations that used natural organic additives to prepare lime plasters, fortuitously exploited a biomimetic route for improving carbonate binders performance.