Optimizing cryopreservation conditions for use of fucosylated human mesenchymal stromal cells in anti-inflammatory/immunomodulatory therapeutics.

Mesenchymal stem/stromal cells (MSCs) are being increasingly used in cell-based therapies due to their broad anti-inflammatory and immunomodulatory properties. Intravascularly-administered MSCs do not efficiently migrate to sites of inflammation/immunopathology, but this shortfall has been overcome by cell surface enzymatic fucosylation to engender expression of the potent E-selectin ligand HCELL. In applications of cell-based therapies, cryopreservation enables stability in both storage and transport of the produced cells from the manufacturing facility to the point of care. However, it has been reported that cryopreservation and thawing dampens their immunomodulatory/anti-inflammatory activity even after a reactivation/reconditioning step. To address this issue, we employed a variety of methods to cryopreserve and thaw fucosylated human MSCs derived from either bone marrow or adipose tissue sources. We then evaluated their immunosuppressive properties, cell viability, morphology, proliferation kinetics, immunophenotype, senescence, and osteogenic and adipogenic differentiation. Our studies provide new insights into the immunobiology of cryopreserved and thawed MSCs and offer a readily applicable approach to optimize the use of fucosylated human allogeneic MSCs as immunomodulatory/anti-inflammatory therapeutics.

The role of B-1 cells in cancer progression and anti-tumor immunity.

In recent years, in addition to the well-established role of T cells in controlling or promoting tumor growth, a new wave of research has demonstrated the active involvement of B cells in tumor immunity. B-cell subsets with distinct phenotypes and functions play various roles in tumor progression. Plasma cells and activated B cells have been linked to improved clinical outcomes in several types of cancer, whereas regulatory B cells have been associated with disease progression. However, we are only beginning to understand the role of a particular innate subset of B cells, referred to as B-1 cells, in cancer. Here, we summarize the characteristics of B-1 cells and review their ability to infiltrate tumors. We also describe the potential mechanisms through which B-1 cells suppress anti-tumor immune responses and promote tumor progression. Additionally, we highlight recent studies on the protective anti-tumor function of B-1 cells in both mouse models and humans. Understanding the functions of B-1 cells in tumor immunity could pave the way for designing more effective cancer immunotherapies.

Mounier-Kuhn syndrome in poorly controlled asthma.

INTRODUCTION: Mounier-Kuhn syndrome or tracheobronchomegaly, is a rare condition that consists of abnormal dilation of the trachea and main bronchi due to a pathological arrangement of smooth muscle fibers in this area. CASE REPORT: We present the case of a 46-year-old woman with poorly controlled asthma and recurrent infections, who was diagnosed with Mounier-Kuhn syndrome through a computed tomography scan revealing an unusual enlargement of the trachea with associated bronchiectasis. RESULTS: The diagnosis of Mounier-Kuhn syndrome is radiological, involving measurement of the trachea where a diameter >25 mm in men and >21 mm in women is observed. While diagnosis is sometimes incidental, there is an association with respiratory diseases such as asthma or COPD, hence clinical suspicion is important in patients with poorly controlled underlying conditions who present with recurrent infections, inadequate secretion management, or even hemoptysis. CONCLUSIONS: Despite its rarity, this syndrome significantly impacts patients' quality of life. Diagnosis and management involve comprehensive evaluations including computed tomography, with a multidisciplinary approach including pulmonologists and radiologists. Exploring its clinical features, associations with other respiratory diseases and treatment options is crucial in managing this rare respiratory condition.

What Technological and Economic Elements Must be Addressed to Support the Affordability, Accessibility, and Desirability of Alternative Proteins in LMIC?

Populations in low- and middle-income countries (LMIC) typically consume less than the recommended daily amount of protein. Alternative protein (AP) sources could help combat malnutrition, but this requires careful consideration of elements needed to further establish AP products in LMIC. Key considerations include technological, nutritional, safety, social, and economic challenges. This perspective analyzes these considerations in achieving dietary diversity in LMIC, using a combination of traditional and novel protein sources with high nutritional value, namely, soy, mycoprotein, and cultivated meat. Technological approaches to modulate the technofunctionality and bitter off-tastes of plant-sourced proteins facilitate processing and ensure consumer acceptance. Economic considerations for inputs, infrastructure for production, and transportation represent key elements to scale up AP. Dietary diversification is indispensable and LMIC cannot rely on plant proteins alone to provide adequate protein intake sustainably. Investments in infrastructure and innovation are urgently needed to offer diverse sources of protein in LMIC.

Correction: Integrated biosensors for monitoring microphysiological systems.

Correction for 'Integrated biosensors for monitoring microphysiological systems' by Lei Mou et al., Lab Chip, 2022, 22, 3801-3816, https://doi.org/10.1039/D2LC00262K.

Acute and chronic sleep restriction differentially modify maternal behavior and milk macronutrient composition in the postpartum rat.

BACKGROUNDS: Sleep restriction is considered a stressful condition itself, causing a wide variety of physiological alterations, from cognitive and hormonal to immunological status. In addition, it is established that stress in mother rats can modify milk ejection, milk composition, and maternal care of the pups. Also, sleep disturbances during the early stages of motherhood are a common feature of all studied species. In this context, while the impacts of sleep disruption in non-lactating animals were extensively investigated, its repercussions during the initial phases of motherhood have been poorly explored. Therefore, we wonder if maternal behavior, milk ejection and its macronutrient composition would be disrupted when mother rats are subjected to an additional acute or chronic sleep restriction to the already existing sleep disturbances. METHODS: Lactating rats were implanted with unilateral electrodes for polysomnographic recordings and for deep brain electrical stimulation into mesopontine waking-promoting area (for sleep deprivation). During the early postpartum period (postpartum day 5-9), mother rats were randomly assigned into one of three groups: chronic sleep restriction group (CSR; 6 h of sleep deprivation/day for five consecutive days), acute sleep restriction group (ASR; 6 h of sleep deprivation only for one day), or undisturbed group (control group). Active maternal behaviors (retrievals of the pups into the nest, mouthing, lickings [corporal and anogenital] and sniffing the pups) and passive maternal behaviors (kyphotic and supine nursing postures) were evaluated during a 30 min period without sleep restriction immediately after the sleep restriction or control period. The litter weight gain was assessed every day, and on the last experimental session mothers were milked for posterior macronutrients analysis (protein, carbohydrates and fat). RESULTS: When compared to control group, CSR decreased the amount of milk ejected in the middle days of the sleep restriction period, while ASR did not affect this parameter. Moreover, ASR reduced milk protein content compared to control and CSR groups. Finally, compared to the control group, CSR reduced active maternal behaviors towards the end of the treatment days. CONCLUSIONS: We demonstrated that not only acute but also chronic sleep restriction impacts on the postpartum period, each one affecting different aspects of maternal behavior and lactation. Our results suggest the existence of a homeostatic recovery mechanism in breastfeeding during CSR, possibly ensuring the survival of the litter, while the decline in active maternal behaviors appears to be cumulative.

Brain metabolism response to intrahospital transfers in neurocritical ill patients and the impact of microdialysis probe location.

Intrahospital transfer (IHT), a routine in the management of neurocritical patients requiring imaging or interventions, might affect brain metabolism. Studies about IHT effects using microdialysis (MD) have produced conflicting results. In these studies, only the most damaged hemisphere was monitored, and those may not reflect the impact of IHT on overall brain metabolism, nor do they address differences between the hemispheres. Herein we aimed to quantify the effect of IHT on brain metabolism by monitoring both hemispheres with bilateral MD. In this study, 27 patients with severe brain injury (10 traumatic brain injury and 17 subarachnoid hemorrhage patients) were included, with a total of 67 IHT. Glucose, glycerol, pyruvate and lactate were measured by MD in both hemispheres for 10 h pre- and post-IHT. Alterations in metabolite levels after IHT were observed on both hemispheres; although these changes were more marked in hemisphere A (most damaged) than B (less damaged). Our results suggest that brain metabolism is altered after an IHT of neurocritical ill patients particularly but not limited to the damaged hemisphere. Bilateral monitorization may be more sensitive than unilateral monitorization for detecting metabolic disturbances not directly related to the course of the disease.

Ionic Liquid-Assisted Thermal Evaporation of Bimetallic Ag-Au Nanoparticle Films as a Highly Reproducible SERS Substrate for Sensitive Nanoplastic Detection in Complex Environments.

Nanoplastic particles are emerging as an important class of environmental pollutants in the atmosphere that have adverse effects on our ecosystems and human health. While many methods have been developed to quantitatively detect nanoplastics; however, sensitive detection at low concentrations in a complex environment remains elusive. Herein, we demonstrate a greener method to fabricate a surface-enhanced Raman spectroscopy (SERS) substrate consisting of self-assembled plasmonic Ag-Au bimetallic nanoparticle (NP) films for quantitative SERS detection of nanoplastics in complex media. The self-assembly of Ag-Au bimetallic NPs was achieved through thermal evaporation onto a vapor-phase compatible ionic liquid based on deep eutectic solvent over the growth substrate. The finite-difference time-domain simulation revealed that the localized field enhancement is strong in the gaps, which generate uniform SERS "hotspots" in the obtained substrate. Benefiting from highly accessible SERS "hotspots" at the gaps, the SERS substrate exhibits excellent sensitivity for detecting crystal violet with a limit of detection (LOD) as low as 10-14 M and excellent reproducibility (RSD of 5.8%). The SERS substrate is capable of detecting PET nanoplastics with LOD as low as 1 µg/mL and about 100 µg/mL in real samples such as tap water, lake water, diluted milk, and wine. Moreover, we also validated the feasibility of the designed SERS substrate for the practical detection of PET nanoplastics collected from commercial drinking water bottles, and it showed great potential applications for sensitive detection in actual environments.

A Systematic Review of the Psychosocial Impact of Endometriosis before and after Treatment.

While endometriosis is a common gynecologic disease associated with infertility, the psychosocial impact of endometriosis has not been evaluated against various quality of life (QoL) instruments and compared with other chronic illnesses. We rigorously analyzed the psychosocial burden of endometriosis in adult women and compared standardized and validated QoL scores of women with and without endometriosis, before and following treatment, and against other chronic illnesses. We searched PubMed, PsychINFO Embase, and Cochrane Reviews and ClinicalTrials.gov from January 1990 to December 2022 for publications using a detailed list of search terms related to QoL, endometriosis, and questionnaires. Only English-language publications that evaluated the association between Endometriosis and QoL using standardized and validated questionnaires measured at baseline and following treatment were considered. Four reviewers first performed a title and abstract screening followed by full text-review to finalize included articles. QoL scores of women with endometriosis were measured at baseline and analyzed against women without endometriosis and women with endometriosis who had undergone treatment. Additionally, baseline endometriosis scores were assessed against the published QoL scores of populations with other chronic conditions. Assessment of risk of bias was performed in accordance with Cochrane and Newcastle-Ottawa Scale guidelines. A total of 30 articles were included in this review: 4 randomized trials and 26 observational studies. The diagnosis and experience of women with symptomatic endometriosis had an equal or worse QoL score than that of other chronic conditions including heart disease, diabetes, and breast cancer when compared using the 36-Item Short Form Survey and World Health Organization Quality of Life questionnaires. Evidence showed association between low QoL and infertility, sexual dysfunction, mental health struggles, physical pain, poor sleep and fatigue. QoL scores were lower at baseline compared to following treatment in the majority of these domains. Endometriosis is associated with significant psychosocial burden and impaired QoL scores across baseline measurements in comparison to controls and other chronic illnesses. Medical and surgical interventions significantly decreased experienced burdens and improved QoL of women with endometriosis.

Parenthood and neurosurgery in Europe, a white paper from the European association of neurosurgical societies' diversity in neurosurgery committee, part II - practice with children.

Introduction: In the first part of this White Paper, the European Association of Neurosurgical Societies (EANS) Diversity in Neurosurgery Committee (DC) addressed the obstacles faced by neurosurgeons when planning to have a family and practice during pregnancy, attempting to enumerate potential, easily implementable solutions for departments to be more family-friendly and retain as well as foster talent of parent-neurosurgeons, regardless of their gender identity and/or sexual orientation. Attrition avoidance amongst parent-neurosurgeons is at the heart of these papers. Research question: In this second part, we address the obstacles posed by practice with children and measures to mitigate attrition rates among parent-neurosurgeons. For the methodology employed to compose this White Paper, please refer to Supplementary Electronic Materials (SEM) 1. Materials and methods: For composing these white papers, the European Association of Neurosurgical Societies (EANS)'s Diversity Committee (DC) recruited neurosurgeon volunteers from all member countries, including parents, aspiring parents, and individuals without any desire to have a family to create a diverse and representative working group (WG). Results: In spite of the prevailing heterogeneity in policies across the continent, common difficulties can be identified for both mothers and fathers considering the utilization of parental leave. Discussion and conclusion: Reconciliation of family and a neurosurgical career is challenging, especially for single parents. However, institutional support in form of childcare facilities and/or providers, guaranteed lactation breaks and rooms, flexible schedule models including telemedicine, and clear communication of policies can improve working conditions for parent-neurosurgeons, avoid their attrition, and foster family-friendly work environments.

Blood pressure targets after successful reperfusion in mechanical thrombectomy for acute ischemic stroke: an updated systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: This study sought to determine whether intensive blood pressure (BP) control for patients with successful reperfusion following acute ischemic stroke (AIS) is beneficial, compared to conventional BP management. METHODS: PubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials (RCTs) on the subject. The studied outcomes included dependency or death at 90 days (modified Rankin Scale [mRS] 3-6); severe disability at 90 days (mRS 3-5); mortality at 90 days; and symptomatic intracranial hemorrhage. Odds ratios (OR) with 95% confidence intervals were used to compare the treatment effects for categorical outcomes. We employed a fixed-effect model for analyses with low heterogeneity (I2 < 25%) and a random-effects model for analyses with higher heterogeneity. RESULTS: A total of 1519 patients were included, with 50% (n = 760) receiving intensive BP control (systolic BP < 140 mmHg). Functional disability or death at 90 days was significantly higher in the intensive group (54.9%) compared to the conventional treatment group (44.1%) (OR = 1.51; 95% Confidence Interval [CI]: 1.15-1.96; p = 0.003; I2 = 29%). Severe functional disability (mRS 3-5) was significantly higher in the intensive group (30.6% vs. 43.5%, OR = 1.75; 95%CI = 1.36-2.25; p < 0.0001; I2 = 0%). There was no difference in symptomatic intracranial hemorrhage (OR = 1.13; 95%CI = 0.76-1.67) or mortality (OR = 1.22; 95%CI = 0.9-1.64). CONCLUSIONS: Intensive BP control is harmful in patients who underwent EVT for AIS and achieved successful reperfusion. It yields higher rates of functional dependence, with no differences in mortality or symptomatic intracranial hemorrhage.

European Medical Students' Views on Neurosurgery, with Emphasis on South-East Europe (Albania, Greece, Serbia, and Turkey).

BACKGROUND: Neurosurgery, an intricate and dynamic surgical specialty, faces challenges in attracting medical graduates. Despite its potential appeal, a decreasing trend in medical students opting for surgical specialties, including neurosurgery, is noted. This study aims to assess European medical students' perceptions of neurosurgery, focusing on South-East Europe, and address concerns about the declining interest in this field. METHODS: A comprehensive digital survey, comprising 33 questions, was distributed to 1115 medical students across 17 European countries. The survey, conducted over 9 months, gathered responses through European neurosurgical societies, the European Association of Neurosurgical Societies (EANS), and university channels. Statistical analysis utilized IBM Statistical Package for the Social Sciences, presenting data through counts, proportions, and χ2 tests. RESULTS: The study reveals that, over the survey period, 834 medical students completed the questionnaire, with a predominant representation from South-East Europe. While 43.2% of participants were considering a surgical career, neurosurgery emerged as the most preferred specialty (26.37%). Despite this interest, 80.2% reported insufficient knowledge about pursuing a neurosurgical career, with limited exposure during medical education. Concerns about work-life balance, heavy workload, and hierarchical structures were prominent among respondents. CONCLUSIONS: The findings underscore the need for targeted interventions to address concerns influencing medical students' decisions regarding neurosurgery. Improving neurosurgical education, dispelling misconceptions, and creating a supportive work environment are crucial steps to attract and retain diverse talented individuals in neurosurgery. These efforts will be vital in narrowing the gap between the demand for neurosurgeons and the number of medical graduates entering the field, ensuring a sustainable future for this essential surgical specialty.

[Impact of diabetes on cardiovascular risk in patients with dyslipidemia]. / Impacto de la diabetes en el riesgo cardiovascular en pacientes con dislipidemia.

Objective: To determine the impact of diabetes on cardiovascular risk in patients with dyslipidemia. Method: Observational, cross-sectional and comparative study in which cardiovascular risk was determined at 10 years in 100 patients with dyslipidemia, of these, 50 non-diabetic patients and 50 diabetic patients. Results: Both groups had similar characteristics in terms of age, blood pressure figures, average body mass index, and HDL and LDL levels. It was observed that the diabetic group has almost double the risk compared to the dyslipidemia group, 13.7 vs. 7.9 (p = 0.014), and the calculated heart age is also higher in patients with diabetes, 80 vs. 66 years (p = 0.003). Even in patients with diabetes there is a greater difference between the real age and the age of the heart, 24 years vs. 15 years of patients without diabetes (p = 0.000). Conclusion: Having diabetes and dyslipidemia doubles the cardiovascular risk of patients. Little metabolic control was found in the population studied, which significantly increases complications at an early age and the economic burden on the health system and the families of patients, so it is necessary to rethink treatment strategies to improve metabolic control and with it the prognosis for the patient in the long term.

Objetivo: Determinar el impacto de la diabetes en el riesgo cardiovascular en pacientes con dislipidemia. Método: Estudio observacional, transversal y comparativo, en el que se determinó el riesgo cardiovascular en 100 pacientes con dislipidemia, de los cuales 50 eran diabéticos, sin complicaciones crónicas. Resultados: Ambos grupos tenían características similares en cuanto a edad, presión arterial, índice de masa corporal, niveles de c-HDL y c-LDL. Sin embargo, al comparar el porcentaje de riesgo cardiovascular, observamos que el grupo de diabéticos tenía casi el doble de riesgo cardiovascular, 13.7 contra 7.9 (p = 0.014), y la edad del corazón calculada también fue mayor en los pacientes con diabetes, 80 contra 66 años (p = 0.003). Incluso, en los pacientes diabéticos la diferencia entre la edad real y la edad del corazón fue mayor, 24 años contra 15 años (p = 0.000). Conclusión: Padecer diabetes y dislipidemia duplica el riesgo cardiovascular. En la población estudiada se encontró poco control metabólico, lo que aumenta significativamente las complicaciones en edades tempranas y la carga económica al sistema de salud y a las familias de los pacientes; por tanto, es necesario replantear las estrategias de tratamiento para mejorar el control metabólico y el pronóstico del paciente a largo plazo.

Chemical Multiverse and Diversity of Food Chemicals.

Food chemicals have a fundamental role in our lives, with an extended impact on nutrition, disease prevention, and marked economic implications in the food industry. The number of food chemical compounds in public databases has substantially increased in the past few years, which can be characterized using chemoinformatics approaches. We and other groups explored public food chemical libraries containing up to 26,500 compounds. This study aimed to analyze the chemical contents, diversity, and coverage in the chemical space of food chemicals and additives and, from here on, food components. The approach to food components addressed in this study is a public database with more than 70,000 compounds, including those predicted via omics techniques. It was concluded that food components have distinctive physicochemical properties and constitutional descriptors despite sharing many chemical structures with natural products. Food components, on average, have large molecular weights and several apolar structures with saturated hydrocarbons. Compared to reference databases, food component structures have low scaffold and fingerprint-based diversity and high structural complexity, as measured by the fraction of sp3 carbons. These structural features are associated with a large fraction of macronutrients as lipids. Lipids in food components were decompiled by an analysis of the maximum common substructures. The chemical multiverse representation of food chemicals showed a larger coverage of chemical space than natural products and FDA-approved drugs by using different sets of representations.

ADAMTS13 RECOVERY IN ACUTE THROMBOTIC THROMBOCYTOPENIC PURPURA AFTER CAPLACIZUMAB THERAPY. THE SPANISH REGISTRY.

Caplacizumab prevents the interaction between von Willebrand factor and platelets, and is used to treat immune thrombotic thrombocytopenic purpura (iTTP). Its administration has been associated with a delay in ADAMTS13 activity restoration after plasma exchange (PEX) suspension. We analyzed the outcomes of 113 iTTP episodes, 75 of which were treated with caplacizumab, in 108 patients from the Spanish Registry of Thrombotic Thrombocytopenic Purpura. Caplacizumab shortened the time to platelet count normalization and reduced PEX requirement, exacerbations and relapses. There was no difference in the time to achieve ADAMTS13 activity ≥20% after PEX end between caplacizumab-treated and non-treated episodes (14.5 [7.7-27.2] vs. 13.0 [8.0-29.0] days, median [IQR], P=.653). However, considering the 36 episodes where caplacizumab started <=3 days after iTTP diagnosis, the time to ADAMTS13 restoration from PEX end was higher than in those episodes where caplacizumab started >3 days after iTTP diagnosis (20.0 [12.0-43.0] vs. 11.0 [3.5-20.0] days, P = .003), or than in non-caplacizumab-treated episodes (P=.033). This finding could be related to a significantly shorter duration of PEX in early caplacizumab-treated episodes than in late caplacizumab-treated episodes (5.5 [4.0-9.0] vs. 15.0 [11.0-21.5] days, P <.001) or non-caplacizumab-treated episodes (11.0 [6.0-26.0] days, P < .001). There were no differences in time to ADAMTS-13 restoration from PEX start (28.0 [17.2-47.5], 27.0 [19.0-37.5] and 29.5 [15.2-45.0] days in early caplacizumab-treated, late caplacizumab-treated and non-caplacizumab-treated episodes). Early administered caplacizumab does not prevent the requirement for immunosuppression but has beneficial effects by shortening PEX requirement without major safety concerns.

Clinical and molecular characterization of children and adults with respiratory bocavirus infection in Mexico: a cross-sectional nested study within the ILI002 prospective observational study.

Background: Human Bocaviruses (HBoV) can cause acute respiratory tract infections. High coinfection rates cloud its pathogenicity. This study sought to describe the clinical features of HBoV1 disease in children and adults with Influenza-like illness (ILI), exploring associations between viral load, clinical features, and seasonality. Methods: Patients who tested positive for HBoV1 by polymerase chain reaction, enrolled from April 2010 to March 2014 in the ILI002 prospective observational cohort study were included in this cross-sectional nested study. Participants were included in ILI002 if they presented with signs and/or symptoms suggestive of influenza-like illness. Samples were tested for viral load, and NP1 and VP1/VP2 phylogenetic analyses, except for the samples lacking suitable and viable clinical material for genotyping. Findings: We identified HBoV1 in 157 (2.8%) of participants. Prevalence was 4.5% in children and 1.8% in adults. Single HBoV1 detection occurred in 41.1% and 46.3% of children and adults, respectively. Children commonly experienced fever (83.3%), cough with sputum (74.4%), and shortness of breath (72.2%). In the multivariate analysis of children, significant positive associations were detected between viral loads and age (0.20 [95% CI: 0.07, 0.33]), and the presence of fever (2.64 [95% CI: 1.35, 3.94]), nasal congestion (1.03 [95% CI: 0.07, 1.99]), dry cough (1.32 [95% CI: 0.42, 2.22]), chest congestion (1.57 [95% CI: 0.33, 2.80]), red eyes (1.25 [95% CI: 0.35, 2.14]), cough with sputum (1.79 [95% CI: 0.80, 2.78]), and other signs and symptoms such as chills, dizziness, and diaphoresis (1.73 [95% CI: 0.19, 3.27]). In contrast, significant negative associations were found between viral loads and percent neutrophils on the blood count (-0.04 [95% CI: -0.06, -0.02]), fatigue (-1.60 [95% CI: -2.46, -0.74]) and the presence of other symptoms or signs, including adenopathy and rash (-1.26 [95% CI: -2.31, -0.21]). Adults commonly experienced sore throat (73.1%), fatigue (77.4%), and headache (73.1%). In the multivariate analysis of adults, significant positive associations were detected between viral load and body mass index (0.13 [95% CI: 0.04, 0.21]), and the presence of confusion (1.54 [95% CI: 0.55, 2.53]), and sore throat (1.03 [95% CI: 0.20, 1.85]), and significant negative associations were detected between viral load and chest congestion (-1.16 [95% CI: -2.07, -0.24]). HBoV1 was detected throughout the year irrespective of season, temperature, and humidity. Interpretation: This study demonstrated the importance of detecting HBoV1 in patients with influenza-like illness either as single infection or co-infection, in both adults and children, and improves the characterization of HBoV1 seasonality, clinical features, and viral load. Phylogenetic analyses show a high conservation. Funding: The Mexican Emerging Infectious Diseases Clinical Research Network (LaRed), CONACYT (Fondo Sectorial SSA/IMSS/ISSSTE, Projects No. 71260 and No. 127088), Fondos federales no. HIM/2015/006, NIAID, NIH through a contract with Westat, Inc. (HHSN2722009000031, HHSN27200002), NCI, NIH (75N91019D00024, 75N91019F00130). Additional information at the end of the manuscript.

A diet rich in omega-3 fatty acid improves periodontitis and tissue destruction by MMP2- and MMP9-linked inflammation in a murine model.

Periodontitis is an oral-cavity inflammatory disease and is the principal cause associated with tooth loss. Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are important proteases involved in periodontal tissue destruction. The omega-3 polyunsaturated fatty acids (ω-3 PUFA) have been demonstrated to possess immunoregulatory properties in periodontitis. The aim of the study was to investigate the effects of ω-3 PUFA on inflammation and on the expression of MMP-2 and -9 in a murine periodontitis model. Twenty-four male C57BL/6 mice were divided into control mice (Control), control mice treated with ω-3 PUFA (O3), mice with periodontitis (P), and mice with periodontitis treated with ω-3 PUFA (P + O3). ω-3 PUFA were administered orally once a day for 70 days. Periodontitis in mice was induced by Porphyromonas gingivalis-infected ligature placement around the second maxillary molar. The mice were sacrificed, and blood and maxillary samples were collected. Flow cytometry was used to quantify tumor necrosis factor-alpha (TNFα), interleukin (IL)-2, IL-4, IL-5, and interferon-gamma. Histologic analysis and immunohistochemistry for MMP-2 and -9 were performed. The data were statistically evaluated using analysis of variance (ANOVA) and the Tukey post hoc test. Histological analysis showed that ω-3 PUFA supplementation prevented inflammation and tissue destruction and revealed that bone destruction was more extensive in the P group than in the P + O3 group (p < 0.05). Also, it decreased the serum expressions of TNFα and IL-2 and the tissue expression of MMP-2 and -9 in the periodontitis-induced model (p < 0.05). ω-3 PUFA supplementation prevented alveolar bone loss and periodontal destruction, probably by decreasing the expression of MMP-2 and MMP-9 and its immunoregulatory properties.

Tailored electrocardiographic-based criteria for different pacing locations within the left bundle branch.

BACKGROUND: Electrocardiographic (ECG)-based criteria are used to confirm left bundle branch (LBB) pacing (LBBP), but current cutoff values have never been validated for different pacing locations. OBJECTIVE: The purpose of this study was to describe diagnostic performance of V6-R wave peak time (RWPT), V6-V1 interpeak interval, and aVL-RWPT for different pacing sites within the LBB and to determine 100% specific values for each criterion at each pacing location. METHODS: Consecutive patients with confirmed LBBP were selected. Population was divided into subgroups based on the site of pacing: left bundle trunk pacing (LBTP), left septal fascicular pacing (LSFP), left posterior fascicular pacing (LPFP), and left anterior fascicular pacing (LAFP). RESULTS: A total of 147 patients with unequivocal LBB capture were analyzed. Left fascicular pacing was more frequently achieved (82.8%) than LBTP (17.2%). Diagnostic performance of V6-RWPT, V6-V1 interpeak interval, and aVL-RWPT for discrimination of LBBP was good in all subgroups. V6-RWPT cutoff values with 100% specificity (SP) for LBBP discrimination were 75 ms in LBTP, 68 ms in LPFP, 81 ms in LAFP, and 79.5 ms in LSFP. V6-V1 interpeak interval cutoff values with 100% SP for LBBP discrimination were 35.5 ms in LBTP, 53.5 ms in LPFP, 41 ms in LAFP, and 46 ms in LSFP. In LAFP, aVL-RWPT cutoff value with 100% SP for LBBP discrimination was 68 ms, but was 74 ms in LBTP, 74.5 ms in LSFP, and 73.5 ms in LPFP. CONCLUSIONS: Tailored ECG-based criteria might be useful to confirm LBBP at different pacing locations within the LBB.

Synthesis of α3ß4 Nicotinic Acetylcholine Receptor Modulators Derived from Aristoquinoline That Reduce Reinstatement of Cocaine-Seeking Behavior.

Growing evidence suggests that inhibition of the α3ß4 nicotinic acetylcholine receptor (nAChR) represents a promising therapeutic strategy to treat cocaine use disorder. Recently, aristoquinoline (1), an alkaloid from Aristotelia chilensis, was identified as an α3ß4-selective nAChR inhibitor. Here, we prepared 22 derivatives of 1 and evaluated their ability to inhibit the α3ß4 nAChR. These studies revealed structure-activity trends and several compounds with increased potency compared to 1 with few off-target liabilities. Additional mechanistic studies indicated that these compounds inhibit the α3ß4 nAChR noncompetitively, but do not act as channel blockers, suggesting they are negative allosteric modulators. Finally, using a cocaine-primed reinstatement paradigm, we demonstrated that 1 significantly attenuates drug-seeking behavior in an animal model of cocaine relapse. The results from these studies further support a role for the α3ß4 nAChR in the addictive properties of cocaine and highlight the possible utility of aristoquinoline derivatives in treating cocaine use disorder.

3D Accuracy of a Conventional Method Versus Three Digital Scanning Strategies for Completely Edentulous Maxillary Implant Impressions.

PURPOSE: To compare the 3D accuracy of three scanning strategies and conventional impressions using an edentulous model with six implants. MATERIALS AND METHODS: An edentulous maxillary master model was fabricated with six equigingival internal connection implants at 0 degrees of angulation. Ten conventional open-tray splinted implant-level impressions were made and poured in stone. A master model and conventional casts were digitized with a reference scanner. Digital impressions were made by calibrated clinicians with a TRIOS 3 intraoral scanner ([IOS] 3Shape) according to three scanning strategies: DIG1 (occlusal-palatal-lingual), DIG2 (S-type motion from buccal to palatal), and DIG3 (scanning two half arches and connecting them at the midline). Each technique was repeated 10 times on the master model. Deviations from the STL datasets (N = 40) were compared to those of the reference master model using the Hexagon Metrology software system PC-DMIS CAD++. Linear distortions (dX, dY, dZ), global linear distortion (dR), and angular distortions (Absdθx, Absdθy) were calculated. Kruskal-Wallis test and mixed linear and logistic regression models were used to compare the original and binary distortion measures between the techniques. RESULTS: The mean dR ranged from 91 µm (conventional method) to 183 µm (DIG1). The mean angular distortion ranged from 0.20 degrees (Absdθx for DIG2) to 0.69 degrees (Absdθy for DIG3). No scan pattern resulted in a more accurate reproduction in any of the measured parameters than the conventional impression method. There were significant differences between the methods for all distortion measures. CONCLUSIONS: No group reproduced the 3D position of the six-implant master model below the thresholds for both global linear and angular distortions. All the digital strategies tested were less accurate than the conventional open-tray splinted implant-level impression technique.