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Thrombin is the pivotal enzyme in the biochemistry of secondary hemostasis crucial to maintaining homeostasis of hemostasis. In contrast to routine coagulation tests (PT or aPTT) or procoagulant or anticoagulant factor assays (e.g. fibrinogen, factor VIII, antithrombin or protein C), the thrombin generation assay (TGA), also named thrombin generation test (TGT) is a so-called "global assay" that provides a picture of the hemostasis balance though a continuous and simultaneous measurement of thrombin formation and inhibition. First described in the early 1950s, as a manual assay, efforts have been made in order to standardize and automate the assay to offer researchers, clinical laboratories and the pharmaceutical industry a versatile tool covering a wide range of clinical and non-clinical applications. This review describes technical options offered to properly run TGA, including a review of preanalytical and analytical items, performance, interpretation, and applications in physiology research and pharmacy.

Researchers and design engineers are increasingly interested in castellated beams because of their ability to provide greater flexural strength with lower dead loads, as well as provide services and cost-effective structures. The influence of castellation on the bending strength and stiffness of the hot-rolled steel Square Tubular Beams (STBs) and Castellated Tubular Beams (CTBs) with simply supported end conditions were investigated in this study. Totally eight bending tests were carried out on hollow tubular beams with and without castellation under three point bending. The STBs with a nominal steel tube thickness of 2.5 mm are castellated in a hexagonal pattern. The ultimate moments, moment versus mid-span deflection response curves, and failure patterns are provided as part of the test results. The bending tests show that the flexural capacities and stiffness of the hollow tubular sections significantly increased due to the castellation process. Finite element (FE) models of STBs and CTBs were established by including the material and geometric nonlinearity as well as the measured geometric imperfections. The FE models established show good agreement with the experimental test in terms of ultimate bending strength, moment vs. mid-span deflection response, and failure modes.

Determining patient's coagulation profile, i.e. detecting a bleeding tendency or the opposite, a thrombotic risk, is crucial for clinicians in many situations. Routine coagulation assays and even more specialized tests may not allow a relevant characterization of the hemostatic balance. In contrast, thrombin generation assay (TGA) is a global assay allowing the dynamic continuous and simultaneous recording of the combined effects of both thrombin generation and thrombin inactivation. TGA thus reflects the result of procoagulant and anticoagulant activities in blood and plasma. Because of this unique feature, TGA has been widely used in a wide array of settings from both research, clinical and pharmaceutical perspectives. This includes diagnosis, prognosis, prophylaxis, and treatment of inherited and acquired bleeding and thrombotic disorders. In addition, TGA has been shown to provide relevant information for the diagnosis of coagulopathies induced by infectious diseases, comprising also disturbance of the coagulation system in COVID-19, or for the assessment of early recurrence in breast cancer. This review article aims to document most clinical applications of TGA.

Sporotrichosis is usually a subcutaneous infection caused by thermodimorphic fungi of the genus Sporothrix. The disease occurs worldwide, but endemic areas are located in tropical and subtropical regions. The epidemiology of sporotrichosis in Brazil is peculiar because of the cat’s entry in the chain of transmission of this mycosis, associated with Sporothrix brasiliensis, the most virulent species in the genus. Sinusitis caused by Sporothrix species is unusual and may be underdiagnosed or confused with other fungal etiologies, like mucormycosis. We report a case of sinusitis due to a Sporothrix species in a 6-year renal transplant recipient. Direct examination of smears of exudate of the sinus specimen (aspirate, biopsy) revealed budding yeasts and cigar-shaped cells. Sporothrix was subsequently recovered from the patient’s exudate culture and identified as S. brasiliensis using species-specific polymerase chain reaction, and she was successfully treated with antifungal therapy. Her parents also developed the disease a week later, both only cutaneous involvement. Sporotrichosis sinusitis is a rare disease, even in immunocompromised patients. Diagnosis is crucial, and benefits from good epidemiological history.

Zusammenfassung Hintergrund Der Prozess des Studieneinschlusses von Teilnehmenden ist ein wichtiger Bestandteil und oftmals aufwendiger Arbeitsschritt in wissenschaftlichen Forschungsprojekten. Aufgrund unterschiedlicher finanzieller, organisatorischer und ethischer Rahmenbedingungen stellt die fristgerechte Gewinnung von Teilnehmenden haufig eine Herausforderung dar. In diesem Beitrag berichten wir uber unsere Erfahrungen hinsichtlich des Studieneinschlusses, die wir im Projekt „Psychoonkologische Versorgung von Krebspatienten mit Migrationshintergrund – eine Mixed-Methods-Studie“ (POM) gemacht haben. Methode Die Gewinnung von Teilnehmenden erfolgte uber ambulante hamato-onkologische Schwerpunktpraxen. Patient*innen und Angehorige wurden in erster Linie durch die behandelnden Arzt*innen auf das Projekt aufmerksam gemacht und fur eine Teilnahme an qualitativen Interviews gewonnen. Ergebnisse Es wurden bundesweit neun Patient*innen und Angehorige in qualitativen Einzelinterviews befragt. Abgesehen von der COVID-19-Pandemie gab es weitere Herausforderungen beim Studieneinschluss. In vielen Fallen wurde eine Teilnahme von Patient*innen abgelehnt. Grunde hierfur waren u.a. „kein Interesse“, der Gebrauch der Begriffe „Psychoonkologie“ oder „Mensch mit Migrationshintergrund“, ein Verbot der Teilnahme durch die Angehorigen, kein personliches Interview aufgrund der COVID-19-Pandemie sowie eine zu starke emotionale Belastung und Verschlechterung des Gesundheitszustands nach vorheriger Einwilligung. Diskussion Die Gewinnung von Studienteilnehmenden aus vulnerablen Gruppen fur ein sensibles Thema wie der Psychoonkologie bringt vielfache Herausforderungen mit sich. Um dennoch einen erfolgreichen Studieneinschluss zu erlangen, erwies sich ein regelmasiger telefonischer und schriftlicher Austausch mit den jeweils zustandigen Praxismitarbeitenden als hilfreich, wodurch ein Uberblick uber Herausforderungen erlangt und der Studieneinschluss evaluiert und zeitnah angepasst werden konnte. Schlussfolgerung In Forschungsprojekten mit vulnerablen Gruppen und zu sensiblen Themen sollten sowohl eine zielgruppenspezifische, feinfuhlige und laienverstandliche Ansprache als auch regelmasige Rucksprachen mit den Personen erfolgen, die fur den Studieneinschluss in Versorgungseinrichtungen verantwortlich sind, um ggf. im Laufe des Studieneinschlusses das bisherige Verfahren anzupassen. Basierend auf den Erfahrungen der POM-Studie werden Losungsansatze fur Versorgungsforschungsstudien mit vulnerablen Gruppen und bei sensiblen Themen aufgezeigt.

This study aimed to establish availability and characteristics of cardiac rehabilitation (CR) in Latin America and the Caribbean (LAC), where cardiovascular disease is highly prevalent. In this cross-sectional sub-analysis focusing on the 35 LAC countries, local cardiovascular societies identified CR programs globally. An online survey was administered to identified programs, assessing capacity and characteristics. CR need was computed relative to ischemic heart disease (IHD) incidence from the Global Burden of Disease study. ≥1 CR program was identified in 24 LAC countries (68.5% availability; median = 3 programs/country). Data were collected in 20/24 countries (83.3%); 139/255 programs responded (54.5%), and compared to responses from 1082 programs in 111 countries. LAC density was 1 CR spot per 24 IHD patients/year (vs 18 globally). Greatest need was observed in Brazil, Dominican Republic and Mexico (all with >150,000 spots needed/year). In 62.8% (vs 37.2% globally P < .001) of CR programs, patients pay out-of-pocket for some or all of CR. CR teams were comprised of a mean of 5.0 ± 2.3 staff (vs 6.0 ± 2.8 globally; P < .001); Social workers, dietitians, kinesiologists, and nurses were significantly less common on CR teams than globally. Median number of core components offered was 8 (vs 9 globally; P < .001). Median dose of CR was 36 sessions (vs 24 globally; P < .001). Only 27 (20.9%) programs offered alternative CR models (vs 31.1% globally; P < .01). In LAC countries, there is very limited CR capacity in relation to need. CR dose is high, but comprehensiveness low, which could be rectified with a more multidisciplinary team.

This paper presents a study on the development of a novel shear connector for usage on cold-formed steel–concrete composite beams. The connector consists of a bolt fixed to the steel profile by means of a tubular rivet with inner thread and can be installed with a single access, allowing usage on tubular sections. Four push-out tests and four full-scale beam tests were conducted, two with friction between the steel section and the slab and two without friction. A numerical analysis was also conducted to assess whether the beam behaviour could be simulated in the finite element commercial code ABAQUS. It was noted that the shear connectors were extremely flexible and presented very large slips. The connectors also presented enough strength to allow for the construction of composite beams with adequate shear interaction between the slab and the steel beam without an excessive number of connectors. Due to the high flexibility of the connectors, even though the beam was designed considering full shear interaction between the slab and the steel section, the observed values of strength and stiffness were not as high as calculated. Design codes should have their procedures reviewed to consider this flexibility, as only a strength requirement proved to be unsuitable, indicating that full shear interaction was not achieved. It was also observed that the presence of friction increased the interaction level of the beams.

BACKGROUND: The Centers for Medicare and Medicaid Services’ Hospital Value-Based Purchasing program uses 30-day mortality rates for acute myocardial infarction, heart failure, and pneumonia to evaluate US hospitals, but does not account for neighborhood socioeconomic disadvantage when comparing their performance. OBJECTIVE: To determine if neighborhood socioeconomic disadvantage is associated with worse 30-day mortality rates after a hospitalization for acute myocardial infarction (AMI), heart failure (HF), or pneumonia in the USA, as well as within the subset of counties with a high proportion of Black individuals. DESIGN AND PARTICIPANTS: This retrospective, population-based study included all Medicare fee-for-service beneficiaries aged 65 years or older hospitalized for acute myocardial infarction, heart failure, or pneumonia between 2012 and 2015. EXPOSURE: Residence in most socioeconomically disadvantaged vs. less socioeconomically disadvantaged neighborhoods as measured by the area deprivation index (ADI). MAIN MEASURE(S): All-cause mortality within 30 days of admission. KEY RESULTS: The study included 3,471,592 Medicare patients. Of these patients, 333,472 resided in most disadvantaged neighborhoods and 3,138,120 in less disadvantaged neighborhoods. Patients living in the most disadvantaged neighborhoods were younger (78.4 vs. 80.0 years) and more likely to be Black adults (24.6% vs. 7.5%) and dually enrolled in Medicaid (39.4% vs. 21.8%). After adjustment for demographics (age, sex, race/ethnicity), poverty, and clinical comorbidities, 30-day mortality was higher among beneficiaries residing in most disadvantaged neighborhoods for AMI (adjusted odds ratio 1.08, 95% CI 1.06–1.11) and pneumonia (aOR 1.05, 1.03–1.07), but not for HF (aOR 1.02, 1.00–1.04). These patterns were similar within the subset of US counties with a high proportion of Black adults (AMI, aOR 1.07, 1.03–1.11; HF 1.02, 0.99–1.05; pneumonia 1.03, 1.00–1.07). CONCLUSIONS: Neighborhood socioeconomic disadvantage is associated with higher 30-day mortality for some conditions targeted by value-based programs, even after accounting for individual-level demographics, clinical comorbidities, and poverty. These findings may have implications as policymakers weigh strategies to advance health equity under value-based programs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-07090-z.

Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551

The risk and potential consequences of mother-to-child transmission of severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) during pregnancy are still a matter of debate. We studied the impact of SARS-CoV-2 infection on 56 complete households, including 27 newborns whose mothers were pregnant when exposed to the virus. Two PCR-confirmed perinatal SARS-CoV-2 transmissions with mild symptoms in affected neonates were recorded. In addition, we observed a severe eye malformation (unilateral microphthalmia, optic nerve hypoplasia, and congenital retinopathy) associated with maternal SARS-CoV-2 infection in weeks 5 and 6 of embryonic development. This embryopathy could not be explained by other infectious agents, genetic factors, drug use, or maternal disease during pregnancy. Eight other women with a history of SARS-CoV-2 infection prior to gestational week 12, however, delivered healthy infants.Conclusion: The repeated occurrence of mother-to-child transmission in our cohort with risks that remain incompletely understood, such as long-term effects and the possibility of an embryopathy, should sensitize researchers and stimulate further studies as well as support COVID-19 vaccination recommendations for pregnant women. Trial registration number: NCT04741412. Date of registration: November 18, 2020 What is Known:•Materno-fetal transmission of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) during pregnancy has rarely been reported so far, but was demonstrated in isolated cases. What is New:•In a study of complete households with documented SARS-CoV-2 infection, including a cohort of pregnant women, we observed perinatal coronavirus transmission at a higher frequency than expected.•We also describe a newborn boy with an eye malformation reminiscent of rubella embryopathy but associated with early gestation SARS-CoV-2 infection of his mother.•A coronavirus-related embryopathy, reported here for the first time, is a finding that requires further investigation.

Blue Rubber Bleb Nevus Syndrome, is a rare condition characterized by skin lesions caused by vascular malformations most frequently associated with lesions of the gastrointestinal tract, although rare, it can present with lesions in the central nervous system, thyroid, liver, spleen and lungs; common symptoms are: digestive tract bleeding and iron deficiency anemia. The main manifestation are skin lesions that are characterized by being button-like, with a bluish tint, covered by skin, called blue nevus with a rubbery consistency due to its rubber-like consistency. We present a case of Blue Rubber Bleb Nevus Syndrome with involvement in the central nervous and gastrointestinal systems.

OBJECTIVE Type 2 diabetes is a risk factor for cognitive impairment. We examined the relation of glycemia, lipids, blood pressure (BP), hypertension history, and statin use with cognition in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). RESEARCH DESIGN AND METHODS Cross-sectional analyses from GRADE at baseline examined the association of glycemia (hemoglobin A1c [HbA1c]), LDL, systolic BP (SBP) and diastolic BP (DBP), hypertension history, and statin use with cognition assessed by the Spanish English Verbal Learning Test, letter and animal fluency tests, and Digit Symbol Substitution Test (DSST). RESULTS Among 5,047 GRADE participants, 5,018 (99.4%) completed cognitive assessments. Their mean age was 56.7 ± 10.0 years, and 36.4% were women. Mean diabetes duration was 4.0 ± 2.7 years. HbA1c was not related to cognition. Higher LDL was related to modestly worse DSST scores, whereas statin use was related to modestly better DSST scores. SBP between 120 and 139 mmHg and DBP between 80 and 89 mmHg were related to modestly better DSST scores. Hypertension history was not related to cognition. CONCLUSIONS In people with type 2 diabetes of a mean duration of

Information concerning medications is a necessity for nurse practitioners and other clinicians. Pharmaceutical companies’ Medical Information services are an option for evidence-based, scientifically balanced information. This survey elicited clinicians’ opinions regarding the use and utility of Medical Information services. The top reasons cited for not using the services included bias, awareness, and lack of transparency. Awareness of availability and quality of information from Medical Information services and addressing bias and transparency issues are needed. Clinicians who requested information from Medical Information services indicated receiving high-quality and useful information that had a clinical impact or provided a patient benefit.

The role of innate immunity in COVID-19 is not completely understood. Therefore, this study explored the impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on the expression of Pattern Recognition Receptors (PRRs) in peripheral blood cells and their correlated cytokines. Seventy-nine patients with severe COVID-19 on admission, according to World Health Organization (WHO) classification, were divided into two groups: patients who needed mechanical ventilation and/or deceased (SEVERE, n = 50) and patients who used supplementary oxygen but not mechanical ventilation and survived (MILD, n = 29); a control group (CONTROL, n = 17) was also enrolled. In the peripheral blood, gene expression (mRNA) of Toll-like receptors (TLRs) 3, 4, 7, 8, and 9, retinoic-acid inducible gene I (RIGI), NOD-like receptor family pyrin domain containing 3 (NLRP3), interferon alpha (IFN-α), interferon beta (IFN-β), interferon gamma (IFN-γ), interferon lambda (IFN-λ), pro-interleukin(IL)-1β (pro-IL-1β), and IL-18 was determined on admission, between 5–9 days, and between 10–15 days. Circulating cytokines in plasma were also measured. When compared to the COVID-19 MILD group, the COVID-19 SEVERE group had lower expression of TLR3 and overexpression of TLR4.

An emerging approach with potential in improving the treatment of neurodegenerative diseases and brain tumors is the use of focused ultrasound (FUS) to bypass the blood–brain barrier (BBB) in a non-invasive and localized manner. A large body of pre-clinical work has paved the way for the gradual clinical implementation of FUS-induced BBB opening. Even though the safety profile of FUS treatments in rodents has been extensively studied, the histological and behavioral effects of clinically relevant BBB opening in large animals are relatively understudied. Here, we examine the histological and behavioral safety profile following localized BBB opening in non-human primates (NHPs), using a neuronavigation-guided clinical system prototype. We show that FUS treatment triggers a short-lived immune response within the targeted region without exacerbating the touch accuracy or reaction time in visual-motor cognitive tasks. Our experiments were designed using a multiple-case-study approach, in order to maximize the acquired data and support translation of the FUS system into human studies. Four NHPs underwent a single session of FUS-mediated BBB opening in the prefrontal cortex. Two NHPs were treated bilaterally at different pressures, sacrificed on day 2 and 18 post-FUS, respectively, and their brains were histologically processed. In separate experiments, two NHPs that were earlier trained in a behavioral task were exposed to FUS unilaterally, and their performance was tracked for at least 3 weeks after BBB opening. An increased microglia density around blood vessels was detected on day 2, but was resolved by day 18. We also detected signs of enhanced immature neuron presence within areas that underwent BBB opening, compared to regions with an intact BBB, confirming previous rodent studies. Logistic regression analysis showed that the NHP cognitive performance did not deteriorate following BBB opening. These preliminary results demonstrate that neuronavigation-guided FUS with a single-element transducer is a non-invasive method capable of reversibly opening the BBB, without substantial histological or behavioral impact in an animal model closely resembling humans. Future work should confirm the observations of this multiple-case-study work across animals, species and tasks.

Cystic kidney diseases such as autosomal recessive or dominant polycystic kidney disease (ARPKD and ADPKD) are associated with high prevalence of arterial hypertension. On the contrary, studies on hypertension in children with renal cysts and diabetes (RCAD) syndrome caused by abnormalities in the HNF1B gene are rare. Therefore, the primary aim of our study was to investigate the prevalence of high blood pressure in children with RCAD syndrome due to HNF1B gene abnormalities and secondary to search for possible risk factors for development of high blood pressure. Data on all children with genetically proven RCAD syndrome from three pediatric nephrology tertiary centers were retrospectively reviewed (office blood pressure (BP), ambulatory blood pressure monitoring (ABPM), creatinine clearance, renal ultrasound, echocardiography, albuminuria/proteinuria). High blood pressure was defined as BP ≥ 95th percentile of the current ESH 2016 guidelines and/or by the use of antihypertensive drugs. Thirty-two children with RCAD syndrome were investigated. Three children received ACE inhibitors for hypertension and/or proteinuria. High blood pressure was diagnosed using office BP in 22% of the children (n = 7). In the 7 performed ABPM, 1 child (14%) was diagnosed with hypertension and one child with white-coat hypertension. Creatinine clearance, proteinuria, albuminuria, body mass index, enlargement, or hypodysplasia of the kidneys and prevalence of HNF1B-gene deletion or mutation were not significantly different between hypertensive and normotensive children. Conclusion: High blood pressure is present in 22% of children with RCAD syndrome.

BACKGROUND Atrial fibrillation (AF) ablation is alternative treatment to medical therapy. Most feared complication is atrioesophageal fistula METHODS: Observational, retrospective analysis of consecutive 355 patients undergoing first AF ablation. Low-power long-duration (LPLD) group contained 158 patients, with 121 (76.58%) having paroxysmal AF who underwent ablation with power 20/30W (anterior and posterior left atrial wall), 17 mL/min flow, and a contact force of 10-30 g for 30 s. High-power short-duration group (HPSD) contained 197 patients, with 113 (57.36%) having paroxysmal AF who underwent ablation at 45/50W of power with a contact force of 8-15 g/10-20 g and a 35 mL/min flow rate for 6-8 s on the anterior and the posterior left atrial wall, respectively. Both groups had pulmonary veins isolated and atrial flutter was ablated when needed. For patients not in sinus rhythm, cardioversion was performed before ablation RESULTS: There were no complications. LPLD group: Left atrial time 118.74 min, total 145.32 min, radiofrequency time 4317.99s, X-ray 13.42 min, and elevation of luminal esophageal temperature (LET) in 132 (84.53%) patients. HPSD group: Left atrial time 72.16 min, total 93.76 min, radiofrequency time 1511.29s, X-ray 7.6 min, and LET elevation in only 75 (38.07%) patients. A markedly higher rate of first-pass isolation was observed in HPSD compared to LPLD, 77.16% versus 13.29%, respectively. Recurrence occurred in 64 (40.50%) and 32 (16.24%) in 28.45 and 22.35 months in LPLD and HPSD patients, respectively. In LPLD, 10 patients were submitted to endoscopy, and one (10%) had mild erythema and in HPSD, 13 performed the endoscopy, with two (15.38%) patients showing mild erythema CONCLUSION: HPSD technique compared to the LPLD technique showed significant reduced radiofrequency and fluoroscopy times, higher rate of first-pass isolation, lower recurrence rate, and esophageal temperature elevation and may also have a protective effect avoiding incidental esophageal injury due to these findings.

La diabetes mellitus es una enfermedad crónica endocrina que se considera como un factor de riesgo importante para el desarrollo de las enfermedades periodontales y periimplantarias debido a su naturaleza inflamatoria. El Objetivo de esta revisión es la de argumentar qué evidencia científica existe acerca de la diabetes mellitus como factor de riesgo para el desarrollo de la periimplantitis. Se realizó una revisión bibliográfica de los últimos 10 años (enero 2011 a enero 2021) usando términos de búsqueda que incluyeron las palabras clave en inglés: (dental implants OR oral implants) AND (diabetes OR diabetic), en los motores de búsqueda: PubMed y Embase (electronic databases). Concluyendo en que a pesar que no existe una evidencia concluyente, se debe considerar que existe relación entre la presencia de la diabetes mellitus y la periimplantitis; en tal razón se debe considerar a esta enfermedad como un factor de riesgo para la periimplantitis, siendo aconsejable que el paciente diabético debe mantener siempre controlado su nivel de glucosa.

OBJECTIVES Network analysis is an innovative, analytic approach that enables visual representation of variables as nodes and their corresponding statistical associations as edges. It also provides a new way of framing oral health-related questions as complex systems of variables. We aimed to generate networks of oral health variables using epidemiological data of Indigenous children, and to compare network structures of oral health variables among participants who received immediate or delayed delivery of an oral health intervention. METHODS Epidemiological data from 448 mother-child dyads enrolled in a randomized controlled trial of dental caries prevention in South Australia, Australia, were obtained. Networks were estimated with nodes representing study variables and edges representing partial correlation coefficients between variables. Data included dental caries, impact on quality of life, self-rated general health, self-rated oral health, dental service utilization, knowledge of oral health, fatalism and self-efficacy in three time points. Communities of nodes, centrality, clustering coefficient and network stability were estimated. RESULTS The oral health intervention interacted with the network through self-rated general health and knowledge of oral health. Networks depicting groups shortly after receiving the intervention presented higher clustering coefficients and a similar arrangement of nodes. Networks tended to return to a preintervention state. CONCLUSION The intervention resulted in increased connectivity and changes in the structure of communities of variables in both intervention groups. Our findings contribute to elucidating dynamics between variables depicting oral health networks over time.

Introduction: Long-term freedom from atrial fibrillation (AF) after catheter ablation and, consequently, the potential for stroke reduction remain unpredictable. Recently, left atrial appendage closure (LAAC) became an effective mechanical alternative to oral anticoagulation (OAC) for stroke prevention in AF patients. Objective: This study aims to evaluate the feasibility and safety of combined treatment for AF with catheter ablation (CA) with the high-power short duration technique associated with LAAC in one single procedure. Methods: Patients with non-valvular AF who underwent combined CA and LAAC procedure were included in the retrospective observational study. Between April 2018 and October 2020, 13 patients with AF were included, eight (61,54%) males, eight (61.54%) with persistent AF (PersAF), mean age 68.54 (65–84) years old, mean time from AF diagnosis to treatment 13.08 (3–33) months, mean CHA2VASC2 5.08 (3–7), all patients with coronary or vascular disease, 12 (92.31%) with hypertension, five (38.46%) with left ventricular dysfunction, four (30.77%) prior strokes using OAC and four (30.77%) patients with diabetes. Indications for LAAC included history of contraindication to OAC because of severe bleeding in eight (61.54%), previous stroke in four (30.77%) and two (13.08%) patients with LAA thrombus, despite the use of two different OAC (one associated with bleeding). One patient had a pseudoaneurysm in femoral artery, and two patients died of non-procedure complications after 30 days. At six months, angiotomography showed successful complete sealing of the LAA in seven (77.72%) of nine patients evaluated, and the two patients without it had a leak of less than 2 mm. After mean follow-up of 14 months (five to 33), 10 (90.91%) of the 11 patients were in sinus rhythm. Three (27.27%) patients, one in blanking period, recovered sinus rhythm after amiodarone. No cardioembolic or bleeding events occurred. Conclusion: In this small observational study, we showed the feasibility and safety of the combined therapy with AF catheter ablation with LAAC with a high rate of sinus rhythm and no cardioembolic event.

In this study, the synthesis of biopolyols derived from castor oil and glycerol was performed by enzymatic glycerolysis in a solvent-free system applying the lipases: Novozym® 435 (N435), from Candida antarctica fraction B, immobilized on macroporous anionic resin, and Eversa® Transform 2.0, a soluble formulation from Thermomyces lanuginosus. The biopolyols presented different conversion into mono- and diacylglycerol (MAG and DAG) owing to regioselectivity of the lipases. The resulting biopolyols were employed for the synthesis of polyurethane foams using different amounts of chemical blowing agent (water). The NCO source employed was polymeric methylene diphenyl diisocyanate (pMDI). The foams were compared, and the results showed that the PU foams obtained by using the biopolyol from lipase N435 presented uniform pore size and more desirable mechanical characteristics. Although this has arisen, the results obtained by using the lipase Eversa® Transform 2.0 showed the possibility of applying a low-cost enzyme to obtain biopolyols and foams, and there may be a possibility of competition with chemical catalysts.

Objective: Alcohol use disorder (AUD) is a leading cause of global disease burden. Chronic, heavy use increases the likelihood of alcohol withdrawal symptoms and associated secondary outcomes of al...

Objective:Given the high disease burden associated with the low intake of whole grains, modelling studies that estimate the impact of dietary strategies to increase more healthful grain foods consumption are essential to inform evidence-based and culturally specific policies. The current study investigated the potential nutritional impact of replacing staple grain foods with more healthful options.Design:Based on the 2015 Health Survey of São Paulo, a cross-sectional, population-based study, we modelled the substitution of white rice and white bread with brown rice and whole-wheat bread. Outcomes included changes in more healthful grain foods, energy and nutrient intakes.Setting:Urban area of São Paulo, Brazil.Participants:Participants aged over 12 years who completed a semi-structured questionnaire and one 24-h recall (n 1741).Results:The substitution of all white rice and white bread with brown rice and whole-wheat bread, respectively, would result in more than 5 % increases in Zn (+9·1 %), Ca (+9·3 %), vitamin E (+18·8 %), dietary fibre (+27·0 %) and Mg (+52·9 %) intake, while more than a 5 % decrease would be seen for total carbohydrate (–6·1 %), folate (–6·6 %), available carbohydrate (–8·5 %), Fe (–8·6 %), vitamin B6 (–12·5 %), vitamin B2 (–17·4 %), and vitamin B1 (–20·7 %). A substantial increase in the amount of more healthful grain foods consumed would be seen (10 g/d to 220 g/d, or from 4 % to 69 % of total grain intake).Conclusions:Replacing white rice and white bread with their whole-grain versions has the potential to improve diet quality, suggesting they are prime targets for policy actions aiming at increasing intake of more healthful grain foods.

Zusammenfassung Hintergrund Menschen mit Migrationshintergrund stellen eine heterogene Bevölkerungsgruppe dar mit einer Vielfalt an Ethnien, kulturellen und religiösen Ansichten und Erfahrungen. Die Diagnose und anschließende Behandlung einer Krebserkrankung gehen mit vielfältigen psychosozialen Belastungen einher. Daher war es Ziel dieser Studie, die aktuelle Perspektive von Ärzt/innen bezüglich Barrieren bei der psychoonkologischen Versorgung von MMH zu untersuchen sowie benötigte Hilfestellungen zu analysieren. Methode Es wurden bundesweit acht niedergelassene Ärzt/innen aus der hämatologisch-onkologischen Versorgung in qualitativen Einzelinterviews befragt. Die Interviews wurden digital aufgezeichnet und transkribiert. Die Auswertung erfolgte nach der inhaltlich strukturierenden Inhaltsanalyse mithilfe des Softwareprogramms MAXQDA 2020. Ergebnisse Identifiziert wurden 255 Codes in den Hauptkategorien „Definition Menschen mit Migrationshintergrund“, „Kommunikation“, „Kulturelle Unterschiede“, „Psychoonkologische Versorgung“, „Koordinierung & Vermittlung von psychoonkologischen Versorgungsangeboten“ sowie „Optimale psychoonkologische Versorgung“. Die Ergebnisse geben einen aktuellen Einblick in alltägliche und praxisrelevante Probleme, die sich in der transkulturellen Kommunikation, Barrieren hinsichtlich der Identifizierung von Bedürfnissen, in der psychoonkologischen Weiterversorgung oder auch während der Übersetzung durch Angehörige erkennen lassen. Diskussion Bereits die Identifizierung von Bedürfnissen während der ärztlichen Behandlung ist mit diversen Barrieren verbunden. Screening-Instrumente für Menschen mit Migrationshintergrund und Angehörige auf verschiedenen Sprachen und für unterschiedliche Kulturkreise könnten die Identifizierung unterstützen. Zudem müssten Netzwerke geschaffen werden, um Patient/innen anschließend auch psychoonkologisch versorgen zu können.

Adaptation to environments with constant fluctuations imposes challenges that are only overcome with sophisticated strategies that allow bacteria to perceive environmental conditions and develop an appropriate response. The gastrointestinal environment is a complex ecosystem that is home to trillions of microorganisms. Termed microbiota, this microbial ensemble plays important roles in host health and provides colonization resistance against pathogens, although pathogens have evolved strategies to circumvent this barrier. Among the strategies used by bacteria to monitor their environment, one of the most important are the sensing and signalling machineries of two-component systems (TCSs), which play relevant roles in the behaviour of all bacteria. Salmonella enterica is no exception, and here we present our current understanding of how this important human pathogen uses TCSs as an integral part of its lifestyle. We describe important aspects of these systems, such as the stimuli and responses involved, the processes regulated, and their roles in virulence. We also dissect the genomic organization of histidine kinases and response regulators, as well as the input and output domains for each TCS. Lastly, we explore how these systems may be promising targets for the development of antivirulence therapeutics to combat antibiotic-resistant infections.

Focused ultrasound (FUS)-based viscoelastic imaging techniques using high frame rate (HFR) ultrasound to track tissue displacement can be used for mechanistic monitoring of FUS neuromodulation. However, a majority of techniques avoid imaging during the active push transmit (interleaved or postpush acquisitions) to mitigate ultrasound interference, which leads to missing temporal information of ultrasound effects when FUS is being applied. Furthermore, critical for clinical translation, use of both axial steering and real-time (1 s) capabilities for optimizing acoustic parameters for tissue engagement are largely missing. In this study, we describe a method of noninterleaved, single Vantage imaging displacement within an active FUS push with simultaneous axial steering and real-time capabilities using a single ultrasound acquisition machine. Results show that the pulse sequence can track micron-sized displacements using frame rates determined by the calculated time-of-flight (TOF), without interleaving the FUS pulses and imaging acquisition. Decimation by 3-7 frames increases signal-to-noise ratio (SNR) by 15.09±7.03 dB. Benchmarking tests of CUDA-optimized code show increase in processing speed of 35- and 300-fold in comparison with MATLAB parallel processing GPU and CPU functions, respectively, and we can estimate displacement from steered push beams ±10 mm from the geometric focus. Preliminary validation of displacement imaging in humans shows that the same driving pressures led to variable nerve engagement, demonstrating important feedback to improve transducer coupling, FUS incident angle, and targeting. Regarding the use of our technique for neuromodulation, we found that FUS altered thermal perception of thermal pain by 0.9643 units of pain ratings in a single trial. Additionally, 5 [Formula: see text] of nerve displacement was shown in on-target versus off-target sonications. The initial feasibility in healthy volunteers warrants further study for potential clinical translation of FUS for pain suppression.

A Klebsiella pneumoniae carbapenemase (KPC), conhecida como "superbactéria", desempenha um papel importante em relação í s infecções hospitalares. Objetivos: Identificar a incidência de Klebsiella pneumoniae com fator de resistência KPC em adultos nos hospitais das regiões Centro-Oeste, Sudeste e Sul do Brasil entre os anos de 2006 e 2016, observando também, o perfil de resistência aos antimicrobianos. Método: Pesquisa retrospectiva com base descritiva e qualitativa, sendo uma revisão bibliográfica literária sistemática realizada por meio das bases de dados: SciELO, Medline, LILACS e Pubmed. Resultados: Localizou-se 95 artigos, dos quais 58 foram incluí­dos. A região Sul obteve a maior prevalência para isolados KPC nos hospitais, sendo a Klebsiella pneumoniae. Em relação aos antimicrobianos o Ertapenem teve quase 100% de resistência em todos os estados. Conclusão: É necessário que sejam implementadas precauções e o controle da disseminação desse tipo de mecanismo de resistência.

Objetivo. El entrenamiento físico se ha asociado a un incremento en la supervivencia de pacientes cardiopatas, sin embargo, su papel en la disminución de las arritmias inducidas por ejercicio (AIE) en esta población aún no ha sido demostrado. El objetivo del estudio fue evaluar el efecto del entrenamiento físico en la ocurrencia de AIE en pacientes con cardiopatía. Metodología. Se evaluó una cohorte retroprospectiva y autocontrolada de pacientes mayores de 18 años con cardiopatía, que ingresaron al programa de rehabilitación cardíaca del Instituto Nacional de Cardiología Ignacio Chávez de México durante enero del 2005 a diciembre 2016. En todos los pacientes se estratificó el riesgo cardiovascular, incluyendo una prueba de ejercicio cardiopulmonar al inicio y al finalizar el programa. Se evaluó la ocurrencia de arritmias antes y después del programa de entrenamiento. Resultados. Se analizaron 160 pacientes, de los cuales 126 (79%) fueron varones. La proporción de pacientes que desarrollaron AIE en la primera prueba de ejercicio fue de 56% y en la segunda de 48%. Del primer grupo 35% ( n=31) no hizo arritmia en la segunda prueba. De los 71 pacientes que no presentaron AIE al inicio del programa, veinte (28%) las presentaron en la segunda prueba, asociado con un incremento del porcentaje de la frecuencia cardiaca máxima alcanzado. En relación con el efecto del programa de entrenamiento en la ocurrencia de arritmias, pudimos observar que tuvo un efecto protector, con un RR= 0.49 (IC 95%:0.35- 0.67, p

Accurate maps of species ranges are essential to inform conservation, but time-consuming to produce and update. Given the pace of change of knowledge about species distributions and shifts in ranges under climate change and land use, a need exists for timely mapping approaches that enable batch processing employing widely available data. We develop a systematic approach of batch-processing range maps and derived Area of Habitat maps for terrestrial bird species with published ranges below 125,000 km2 in Central and South America. (Area of Habitat is the habitat available to a species within its range.) We combine existing range maps with the rapidly expanding crowd-sourced eBird data of presences and absences from frequently surveyed locations, plus readily accessible, high resolution satellite data on forest cover and elevation to map the Area of Habitat available to each species. Users can interrogate the maps produced to see details of the observations that contributed to the ranges. Previous estimates of Areas of Habitat were constrained within the published ranges and thus were, by definition, smaller—typically about 30%. This reflects how little habitat within suitable elevation ranges exists within the published ranges. Our results show that on average, Areas of Habitat are 12% larger than published ranges, reflecting the often-considerable extent that eBird records expand the known distributions of species. Interestingly, there are substantial differences between threatened and non-threatened species. Some 40% of Critically Endangered, 43% of Endangered, and 55% of Vulnerable species have Areas of Habitat larger than their published ranges, compared with 31% for Near Threatened and Least Concern species. The important finding for conservation is that threatened species are generally more widespread than previously estimated.

Zusammenfassung Einleitung Palliativ versorgte Patientinnen und Patienten haben zu einem hohen Anteil onkologische Diagnosen. Die spezialisierte ambulante Palliativversorgung (SAPV) richtet sich an Erkrankte mit komplexem Symptomgeschehen und intensivem Betreuungsbedarf und soll eine Betreuung im häuslichen Umfeld bis zum Lebensende ermöglichen. In Hessen wurden ab 2009 die ersten SAPV-Angebote geschaffen. Entsprechend untersucht diese Studie (i) die Inanspruchnahme von SAPV und spezialisierten stationären palliativen Leistungen im letzten Lebensjahr von Krebserkrankten, (ii) die SAPV verordnende Arztgruppe und (iii) den Sterbeort und Krankenhausaufenthalte in den letzten 91 Lebenstagen. Methoden In der retrospektiven Sekundärdatenanalyse wurden Daten der AOK Hessen für 2009–2014 deskriptiv ausgewertet. Studienpopulation waren an Brust-, Prostata- oder Darmkrebs Erkrankte, die im jeweiligen Beobachtungsjahr (2010–2014) verstarben und 360 Tage vor ihrem Tod durchgängig versichert waren. Ergebnisse In die Studie konnten je nach Beobachtungsjahr 492–545 Personen mit Brust-, 546–625 mit Prostata- und 709–752 mit Darmkrebs eingeschlossen werden. In allen 3 Gruppen Krebserkrankter stieg zwischen 2010 und 2014 der Anteil mit Inanspruchnahme von mindestens einer Palliativleistung. Die Häufigkeit der Inanspruchnahme von SAPV-Leistungen lag bei den betrachteten Krebserkrankten meist höher im Vergleich zu Palliativstationen bzw. stationären Hospizen. SAPV wurde bei den 3 Krebsdiagnosen zu über 90 % von Hausärztinnen bzw. -ärzten verordnet. Sowohl der Anteil von Personen mit einem Krankenhausaufenthalt in den letzten 91 Lebenstagen als auch der im Krankenhaus Verstorbenen ging von 2010 bis 2014 bei allen 3 Krebsarten zurück. Schlussfolgerung Die Ergebnisse sind vor dem Hintergrund des Aufbaus der SAPV in Hessen zu bewerten. Die Zunahme an SAPV-Leistungen und der Rückgang an Krankenhauseinweisungen am Lebensende weist auf eine gelungene Etablierung der SAPV in Hessen hin.

Aims This short communication aims to review the treatment of cardiogenic shock in patients with yew poisoning based on two case reports from our institution, focusing on the use of extracorporeal life support (ECLS). Methods and results We report two cases of Taxus baccata poisoning treated with ECLS at our institution and review the literature based on a search in PubMed and Google Scholar on the topic of yew poisoning and ECLS. All cases were combined for analysis of demographics, ECLS therapy, and outcome. Case 1: A 35‐year‐old woman developed polymorphic ventricular tachycardia followed by cardiovascular arrest 5 h after orally ingesting a handful of yew needles. Successful resuscitation required ECLS for 72 h due to ongoing cardiac arrhythmias and cardiogenic shock. The patient left the hospital without neurological sequelae after 10 days. Case 2: A 30‐year‐old woman developed refractory cardiac arrhythmias and circulatory arrest. Resuscitation included ECLS for 71 h. T. baccata needles found by gastroscopy confirmed the diagnosis. The patient had no neurologic deficits and was transferred to psychiatry after 11 days. Review of the literature: Nine case reports were found and analysed along with our two cases. Five out of the 11 (45%) patients were female. Median (range) age was 28 (19–46) years. T. baccata needles were ingested with a suicidal intention in all patients. Median (range) duration of ECLS was 70 h (24–120 h). Eight (73%) patients had full neurological recovery. Conclusions Yew poisoning is a differential diagnosis in young psychiatric patients presenting with polymorphic ventricular tachycardia and cardiogenic shock. A characteristic cardiac contraction pattern in echocardiography may present a diagnostic clue. The early use of ECLS is a valuable bridge to recovery in most of these patients.

The aim of this work was to analyse the behaviour of the dental lamina during the development process of first molar teeth. The offspring of female mice were analysed at the 16th day of intra-uterine life and since birth till 17 days old with the aim to evaluate the dental lamina evolution of upper and lower first molars. The animals were sacrificed, and the heads embedded in paraffin in order to get frontal or sagittal sections whose were stained by hematoxylin and eosin method. The results showed a very clear presence of the dental lamina in all periods under analysis, without the occurrence of its disorganization, in other words, it was permanently connecting the developing tooth germ to the oral epithelium until advanced dental eruption.

Background Frailty is a geriatric syndrome of decreased physiologic reserve and resistance to stressors that results in increased vulnerability to adverse health outcomes with aging. Diabetes and hyperglycemia are established risk factors for frailty. We sought to examine whether the odds of frailty among individuals at high risk of diabetes randomized to treatment with intensive lifestyle (ILS), metformin, or placebo differed after long-term follow-up. Method The sample comprised participants in the Diabetes Prevention Program (DPP) clinical trial, who continued follow-up in the DPP Outcomes Study (DPPOS) and completed frailty assessments in DPPOS Years 8 (n = 2385) and 10 (n = 2289), approximately 12 and 14 years after DPP randomization. Frailty was classified using Fried Frailty Phenotype criteria. GEE models adjusting for visit year with repeated measures pooled for Years 8 and 10 were used to estimate pairwise odds ratios (ORs) between ILS, metformin, and placebo for the outcomes of frail and prefrail versus nonfrail. Results Frailty prevalence by treatment group was ILS = 3.0%, metformin = 5.4%, placebo = 5.7% at Year 8, and ILS = 3.6%, metformin = 5.3%, placebo = 5.4% at Year 10. Odds ratios (95% CI) estimated with GEE models were ILS versus placebo, 0.62 (0.42–0.93), p = .022; metformin versus placebo, 0.99 (0.69–1.42), p = .976; and ILS versus metformin, 0.63 (0.42–0.94), p = .022. Odds of being frail versus nonfrail were 37% lower for ILS compared to metformin and placebo. Conclusions Early ILS intervention, at an average age of about 50 years, in persons at high risk of diabetes may reduce frailty prevalence in later life. Metformin may be ineffective in reducing frailty prevalence. Clinical Trials Registration Numbers NCT00004992 (DPP) and NCT00038727 (DPPOS).

Die Internistische Intensivmedizin ist fur die intensivmedizinische Diagnostik, Uberwachung, Therapie, Pflege und Nachsorge von Patienten mit schweren, potenziell lebensbedrohlichen Erkrankungen aus dem gesamten Bereich der Inneren Medizin verantwortlich. Die Qualifikation in Internistischer Intensivmedizin erfordert breite Kenntnisse und praktische Fahigkeiten, zum einen im gesamten Fach Innere Medizin und zum anderen in der konservativen (Internistischen) Intensivmedizin einschlieslich der Einbeziehung spezieller Diagnostik- und Therapieoptionen der angrenzenden Fachgebiete. Die Patientenbetreuung darf sich deshalb nicht nur auf lebenserhaltende Masnahmen beschranken, sondern muss wahrend der intensivmedizinischen Behandlungsphase auch die zugrunde liegenden internistischen Erkrankungen in bestmoglicher Weise einschliesen. Das Fundament der Internistischen Intensivmedizin beinhaltet theoretische Kenntnisse, praktische Fahigkeiten (Kompetenzlevel I–III) und eine adaquate beruflich-professionelle Einstellung. Fur die Zusatz-Weiterbildung (ZWB) (Internistische) Intensivmedizin der Bundesarztekammer soll dieses Curriculum der Deutschen Gesellschaft fur Internistische Intensivmedizin und Notfallmedizin (DGIIN) dem intensivmedizinisch weiterzubildenden Internisten die Moglichkeit geben, seine Weiterbildungszeit so effizient wie moglich zu strukturieren, sich gut auf die Prufung vorzubereiten und das Erlernte anschliesend im Sinne eines „berufslebenslangen“ Qualifizierens zu bewahren. Das Curriculum mochte aber auch die Weiterbilder und Weiterbildungsausschusse der Arztekammern erreichen und aufzeigen, welche Kenntnisse und Fertigkeiten nach Ansicht der DGIIN in der ZWB zum Internistischen Intensivmediziner vermittelt werden sollen.

To evaluate the frequency and characteristics of trunk and upper limb pain in women diagnosed with breast cancer, in different movement planes, during task-oriented training (TOT) 3, 6, and 9 months after surgery. A prospective cohort study with 20 women. The body pain diagram (BPD), VAS, and McGill questionnaire were used. The TOT consisted of 20 exercises based on the Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH) questionnaire. BPD overlay was performed in GIMP® image editor. The chi-square test was applied to the relationship between population characteristics and pain. Freedman's ANOVA and the Cochran's Q test were used in the comparison of pain site frequencies and intensity over time. In total, 297 BPDs were generated, which identified the affected upper limb as the body area with the highest frequency of pain at the three moments. However, at 9 months, the unaffected upper limb presented the same frequency as the affected limb. Radiotherapy presented a statistically significant relationship (p

Background: Cathelicidins are ancient and well-conserved antimicrobial peptides (AMPs) with intriguing immunomodulatory properties in both infectious and non-infectious inflammatory diseases. In addition to direct antimicrobial activity, cathelicidins also participate in several signaling pathways inducing both pro-inflammatory and anti-inflammatory effects. Acute kidney injury (AKI) is common in critically ill patients and is associated with high mortality and morbidity. Rhabdomyolysis is a major trigger of AKI. Objectives: Here, we investigated the role of cathelicidins in non-infectious Acute kidney Injury (AKI). Method: Using an experimental model of rhabdomyolysis, we induced AKI in wild-type and cathelicidin-related AMP knockout (CRAMP-/-) mice. Results: We previously demonstrated that CRAMP-/- mice, as opposed wild-type mice, are protected from AKI during sepsis induced by cecal ligation and puncture. Conversely, in the current study, we show that CRAMP-/- mice are more susceptible to the rhabdomyolysis model of AKI. A more in-depth investigation of wild-type and CRAMP-/- mice revealed important differences in the levels of several inflammatory mediators. Conclusion: Cathelicidins can induce a varied and even opposing repertoire of immune-inflammatory responses depending on the subjacent disease and the cellular context.

In this study, zinc phthalocyanine (ZnPc) was encapsulated in liposomes (Phosphatidylcholine (PC) from soybean lecithin (95% phosphatidylcholine, 5% lysophosphatidylcholine), and phosphatidic acid) obtained by a reverse-phase evaporation method. Liposomes were characterized and cytotoxicity and phototoxicity assays were performed using mouse embryo fibroblast (NIH3T3) and human breast cancer (MDAMB231), respectively. ZnPc was successfully encapsulated in liposomes ([Formula: see text]80%), presenting single populations with sizes of [Formula: see text]300 nm and negative zeta potential (-35 to -40 mV). The release profile at different pH presented a biphasic release controlled by the Fickian diffusion mechanism. The cytotoxicity assays carried out on NIH3T3 cells showed that the liposomes provided good protection for ZnPc, and did not affect the viability of non-cancerous cells. In contrast, free ZnPc significantly reduced non-cancerous cell viability at higher concentrations. ZnPc loaded in liposomes ensured a higher phototoxic effect on the MDAMB231 cells at all concentrations tested when exposed to low light dose.

Dystrophin deficiency makes the sarcolemma fragile and susceptible to degeneration in Duchenne muscular dystrophy. The proteasome is a multimeric protease complex and is central to the regulation of cellular proteins. Previous studies have shown that proteasome inhibition improved pathological changes in mdx mice. Ixazomib is the first oral proteasome inhibitor used as a therapy in multiple myeloma. This study investigated the effects of ixazomib on the dystrophic muscle of mdx mice. MDX mice were treated with ixazomib (7.5 mg/kg/wk by gavage) or 0.2 mL of saline for 12 weeks. The Kondziela test was performed to measure muscle strength. The tibialis anterior (TA) and diaphragm (DIA) muscles were used for morphological analysis, and blood samples were collected for biochemical measurement. We observed maintenance of the muscle strength in the animals treated with ixazomib. Treatment with ixazomib had no toxic effect on the mdx mouse. The morphological analysis showed a reduction in the inflammatory area and fibres with central nuclei in the TA and DIA muscles and an increase in the number of fibres with a diameter of 20 µm(2) in the DIA muscle after treatment with ixazomib. There was an increase in the expression of dystrophin and utrophin in the TA and DIA muscles and a reduction in the expression of osteopontin and TGF‐β in the DIA muscle of mdx mice treated with ixazomib. Ixazomib was thus shown to increase the expression of dystrophin and utrophin associated with improved pathological and functional changes in the dystrophic muscles of mdx mice.