Sepsis expands a CD39+ plasmablast population that promotes immunosuppression via adenosine-mediated inhibition of macrophage antimicrobial activity.

Sepsis results in elevated adenosine in circulation. Extracellular adenosine triggers immunosuppressive signaling via the A2a receptor (A2aR). Sepsis survivors develop persistent immunosuppression with increased risk of recurrent infections. We utilized the cecal ligation and puncture (CLP) model of sepsis and subsequent infection to assess the role of adenosine in post-sepsis immune suppression. A2aR-deficient mice showed improved resistance to post-sepsis infections. Sepsis expanded a subset of CD39hi B cells and elevated extracellular adenosine, which was absent in mice lacking CD39-expressing B cells. Sepsis-surviving B cell-deficient mice were more resistant to secondary infections. Mechanistically, metabolic reprogramming of septic B cells increased production of ATP, which was converted into adenosine by CD39 on plasmablasts. Adenosine signaling via A2aR impaired macrophage bactericidal activity and enhanced interleukin-10 production. Septic individuals exhibited expanded CD39hi plasmablasts and adenosine accumulation. Our study reveals CD39hi plasmablasts and adenosine as important drivers of sepsis-induced immunosuppression with relevance in human disease.

Unveiling patterns in pediatric appendectomy: A comparative study on healthcare resource capacity and surgical decisions in Brazil.

BACKGROUND: Appendicitis is the most prevalent surgical emergency in children. This study examined hospital infrastructure, surgical techniques, patient demographics, and hospitalization parameters to assess the provision of safe and adequate care within the Brazilian public healthcare system. METHODS: Pediatric hospitalizations for acute appendicitis in 2022 were extracted from the Brazilian national database. We included all hospitalizations for patients aged 0-16 years with a primary ICD-10 diagnosis of acute appendicitis who underwent an operation. Parameters of interest were the type of surgical approach, mortality, and total cost of hospitalization. Facilities were defined as basic-facility, full-facility, and pediatric according to the level of pediatric resources available. RESULTS: In 2022, there were 29,983 pediatric appendectomies due to acute appendicitis. Of these, 90.2% were open appendectomies. Most occurred in basic-facility general hospitals (53.0%), followed by full-facility (35.2%) and pediatric hospitals (11.8%). Full-facility hospitals had a higher median cost (USD126.3, IQR 99.5-154.4) compared to basic (USD96.8, IQR 87.6-130.1) and pediatric hospitals (USD103.0, IQR 91.9-117.5), though the cost difference between basic and pediatric was not significant (p = 0.367). Death was a rare event across all levels of hospital infrastructure and for all types of procedures performed. CONCLUSIONS: The majority of hospitalizations for acute appendicitis occurred in hospitals with minimal pediatric infrastructure. Open appendectomies remain the most predominant procedure across all hospital types.

Pressing issues for oral care quality improvement: findings from the EU DELIVER project.

BACKGROUND: While oral health often takes a backseat to other health domains, it silently affects nearly half of the Worldwide population. The DELIVER project, funded by the EU's Horizon Europe program, seeks to develop a blueprint model for improving the quality of oral health care for everyone. METHODS: Applying the Nominal Group Technique (NGT), 17 stakeholders from various backgrounds participated in identifying pressing issues for oral care quality improvement across practice, community, and policy levels. RESULTS: The results revealed significant differences at the different levels, with accessibility emerging as a prominent issue, encompassing affordability, availability, and acceptability of oral healthcare services. CONCLUSIONS: These findings emphasizes the need for policy reforms, increased investments, and a shift towards preventive and patient-centered dental care practices. It highlights the importance of collaborative efforts with multi-stakeholders and prioritizing pressing issues on a multi-level to drive positive change in improving oral care quality.

Effect of m-Health-Based Interventions on Blood Pressure: An Updated Systematic Review with Meta-Analysis.

Background: In recent years, the integration of mobile health (m-Health) interventions has garnered increasing attention as a potential means to improve blood pressure (BP) management in adults. This updated systematic review with meta-analysis aimed to identify the effect of m-Health-based interventions on BP in adults and to evaluate the effect of m-Health on BP according to the characteristics of subjects, interventions, and countries. Methods: The search was carried out in PubMed, Embase, ResearchGate, and Cochrane databases in January 2022. Study selection and data extraction were performed by two independent reviewers. For analysis, random effects models were used with a confidence interval (CI) of 95% and p < 0.05. Results: Fifty studies were included in this review and in the meta-analysis. Interventions with m-Health reduced systolic BP in 3.5 mmHg (95% CI -4.3; -2.7; p < 0.001; I2 = 85.8%) and diastolic BP in 1.8 mmHg (95% CI -2.3; -1.4; p < 0.001; I2 = 78.9%) compared to usual care. The effects of m-Health interventions on BP were more evident in men and in older adults, in interventions lasting 6-8 weeks, with medication reminders, with the possibility of insertion of BP values (p < 0.05). Conclusion: The results of this study support the effectiveness of m-Health in reducing BP when compared to standard care. However, these effects are dependent on the characteristics of the subjects and interventions. Given the substantial heterogeneity among the results of this systematic review with meta-analysis, its interpretation should be cautious. Future research on this topic is warranted.

A Mechanistic Analysis of the Neural Modulation of the Inflammatory System Through Vagus Nerve Stimulation: A Systematic Review and Meta-analysis.

OBJECTIVE: We aimed to conduct a systematic review and meta-analysis assessing the antiinflammatory effects of various VNS methods while exploring multiple antiinflammatory pathways. MATERIALS AND METHODS: We included clinical trials that used electrical stimulation of the vagus nerve and assessed inflammatory markers up to October 2022. We excluded studies lacking control groups, those with combined interventions, or abstracts without full text. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews. For each inflammatory marker, a random-effects meta-analysis using the inverse variance method was performed. Methods used include transcutaneous auricular VNS (taVNS), transcutaneous cervical VNS (tcVNS), invasive cervical VNS (iVNS), and electroacupuncture VNS (eaVNS). Main reported outcomes included tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß, C-reactive protein (CRP), and IL-10. Risk of bias was evaluated using the Cochrane Collaboration Tool (RoB 2.0). RESULTS: This review included 15 studies, involving 597 patients. No statistically significant general VNS effect was observed on TNF-α, IL-6, and IL-1ß. However, CRP, IL-10, and interferon (IFN)-γ were significantly modulated by VNS across all methods. Subgroup analysis revealed specific stimulation techniques producing significant results, such as taVNS effects in IL-1ß and IL-10, and iVNS in IL-6, whereas tcVNS and eaVNS did not convey significant pooled results individually. Cumulative exposure to VNS, higher risk of bias, study design, and pulse width were identified as effect size predictors in our meta-regression models. CONCLUSIONS: Pooling all VNS techniques indicated the ability of VNS to modulate inflammatory markers such as CRP, IL-10, and IFN-γ. Individually, methods such as taVNS were effective in modulating IL-1ß and IL-10, whereas iVNS modulated IL-6. However, different VNS techniques should be separately analyzed in larger, homogeneous, and powerful studies to achieve a clearer and more consistent understanding of the effect of each VNS method on the inflammatory system.

Macrophage-Derived MicroRNA-21 Drives Overwhelming Glycolytic and Inflammatory Response during Sepsis via Repression of the PGE2/IL-10 Axis.

Myeloid cells are critical for systemic inflammation, microbial control, and organ damage during sepsis. MicroRNAs are small noncoding RNAs that can dictate the outcome of sepsis. The role of myeloid-based expression of microRNA-21 (miR-21) in sepsis is inconclusive. In this study, we show that sepsis enhanced miR-21 expression in both peritoneal macrophages and neutrophils from septic C57BL/6J mice, and the deletion of miR-21 locus in myeloid cells (miR-21Δmyel mice) enhanced animal survival, decreased bacterial growth, decreased systemic inflammation, and decreased organ damage. Resistance to sepsis was associated with a reduction of aerobic glycolysis and increased levels of the anti-inflammatory mediators PGE2 and IL-10 in miR-21Δmyel in vivo and in vitro. Using blocking Abs and pharmacological tools, we discovered that increased survival and decreased systemic inflammation in septic miR-21Δmyel mice is dependent on PGE2/IL-10-mediated inhibition of glycolysis. Together, these findings demonstrate that expression of miR-21 in myeloid cells orchestrates the balance between anti-inflammatory mediators and metabolic reprogramming that drives cytokine storm during sepsis.

The treatment of atypical hemolytic uremic syndrome with eculizumab in pediatric patients: a systematic review.

BACKGROUND: The atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy associated with high morbidity and high mortality. Eculizumab, a humanized anti-C5 monoclonal antibody, was the first medication approved for treating aHUS in 2011. OBJECTIVE: The objective of this study is to evaluate the efficacy and safety of eculizumab treatment in pediatric patients with aHUS. DATA SOURCES: We consulted PubMed, Scopus, SciELO, and Cochrane Library databases in July 2021. The descriptors were as follows: "Atypical Hemolytic Uremic Syndrome," "aHUS," "eculizumab," "Pediatrics," "Pediatric," "Child," "Children," "Adolescent." STUDY ELIGIBILITY CRITERIA: The study eligibility criteria are as follows: clinical trials and observational studies that included pediatric patients with aHUS diagnosis and who were treated with eculizumab. PARTICIPANTS AND INTERVENTIONS: The participants are pediatric patients, up to 18 years old, with aHUS. The intervention was eculizumab treatment. STUDY APPRAISAL: For quality assessment, we used the Newcastle-Ottawa Scale, the National Institutes of Health (NIH) quality assessment tool for case series studies, and the Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool. RESULTS: The initial search retrieved 433 studies, from which 15 were selected after complete assessment: 9 cohorts, 4 case series, and 1 clinical trial. The publication date ranged from 2015 to 2021. In total, 940 pediatric patients were included, and 682 received eculizumab. All studies reported improvements in renal and hematological parameters in most of the patients treated with eculizumab. The mortality rate was 1.6% for all patients treated with eculizumab. LIMITATIONS: The number of studies is limited, and the included studies were methodologically heterogeneous. The studies were mostly observational and many had small sample sizes. CONCLUSIONS: Eculizumab appears to be safe and effective for the treatment of aHUS in pediatric patients. More research is necessary to establish long-term efficacy, safety, and time of discontinuation. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42021266255.

Phosphite Is More Effective Against Phytophthora Crown Rot and Leather Rot Caused by Phytophthora cactorum than P. nicotianae.

Phytophthora crown rot (PhCR) and leather rot (LR) caused by Phytophthora spp. are major threats to strawberry production worldwide. In the United States, these diseases are mainly caused by Phytophthora cactorum; however, P. nicotianae has also been recently reported causing PhCR. Growers have relied on three different chemical products (i.e., mefenoxam and phosphites for PhCR and LR, and azoxystrobin for LR). Because resistance to mefenoxam and azoxystrobin has been reported, this study aimed to assess the in vitro sensitivity of Phytophthora spp. isolates from strawberry to phosphites and investigate its efficacy on in vivo assays. In vitro sensitivity of P. cactorum (n = 128) and P. nicotianae (n = 24) isolates collected from 1997 to 2018 was assessed for phosphite at 10, 50, 100, 150, and 300 µg/ml. Regardless of the Phytophthora sp. and isolation organ, most of the isolates (75% for P. cactorum and 54.2% for P. nicotianae) had effective concentration that inhibits pathogen growth by 50% (EC50) values ranging from 50 to 100 µg/ml. In vivo tests with strawberry fruit and plants revealed that commercial formulations of phosphite applied at the highest field rate controlled P. cactorum isolates but failed to control PhCR and LR caused by some isolates of P. nicotianae. In this study, EC50 results from in vitro assay did not truly translate the efficacy of phosphites on controlling LR and PhCR caused by P. cactorum and P. nicotianae. Our findings support the hypothesis that the product acts in a dual way: direct on the pathogen and stimulating the plant immune system. Moreover, this has important implications for disease management, highlighting the importance of a correct diagnosis before phosphite recommendations, because its efficacy varies within Phytophthora spp.

The Analgesic Effect of Transcranial Direct Current Stimulation in Fibromyalgia: A Systematic Review, Meta-Analysis, and Meta-Regression of Potential Influencers of Clinical Effect.

BACKGROUND: There is tentative evidence to support the analgesic effect of transcranial direct current stimulation (tDCS) in fibromyalgia (FM), with large variability in the effect size (ES) encountered in different clinical trials. Understanding the source of the variability and exploring how it relates to the clinical results could characterize effective neuromodulation protocols and ultimately guide care in FM pain. The primary objective of this study was to determine the effect of tDCS in FM pain as compared with sham tDCS. The secondary objective was to explore the relationship of methodology, population, and intervention factors and the analgesic effect of tDCS in FM. MATERIALS AND METHODS: For the primary objective, a systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized clinical trials (RCTs) investigating tDCS as an intervention for FM pain were searched in MEDLINE, Embase, and the Web Of Science. Studies were excluded if they used cross-over designs or if they did not use tDCS as an intervention for pain or did not measure clinical pain. Analysis for the main outcome was performed using a random-effects model. Risk of bias and evidence certainty were assessed for all studies using Cochrane Risk of Bias and Grading of Recommendations Assessment, Development, and Evaluation tools. For the secondary objective, a meta-regression was conducted to explore methodology, population, and intervention factors potentially related to the ES. RESULTS: Sixteen RCTs were included. Six studies presented a high risk of bias. Significant reduction in pain scores were found for FM (standardized mean difference = 1.22, 95% CI = 0.80-1.65, p < 0.001). Subgroup analysis considering tDCS as a neural target revealed no differences between common neural sites. Meta-regression revealed that the duration of the tDCS protocol in weeks was the only factor associated with the ES, in which protocols that lasted four weeks or longer reported larger ES than shorter protocols. CONCLUSIONS: Results suggest an analgesic effect of tDCS in FM. tDCS protocols that last four weeks or more may be associated with larger ESs. Definite conclusions are inadequate given the large heterogeneity and limited quality of evidence of the included studies.

Neuroleptic intolerance in the context of anti-N-methyl-D-aspartate receptor encephalitis: A systematic review and synthesis of global case reports.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis presents commonly with psychiatric symptoms. One cohort of these patients reported that antipsychotic administration led to neuroleptic intolerance (NI) in 19% of them, which was preventable by a prompt encephalitis diagnosis. To date, there is no clear description of the "neuroleptic intolerance" spectrum in general or during anti-NMDAR encephalitis. We aimed to synthesize epidemiological and clinical characteristics of patients with NI and confirmed anti-NMDAR encephalitis, the time to the encephalitis diagnosis, the disease course, outcomes at discharge, and associated factors. We systematically searched three databases, to include clinical cases, case series, and observational studies. Additionally, we reported one clinical case. Results were summarized using narrative synthesis and the quality of the included studies was assessed. We included 22 records representing 40 patients (28 females; mean age, 24.6). Overall, the evidence quality was low. Initially, most cases were admitted in psychiatric wards (70%) with purely psychiatric symptoms (37.5%). However, most of them developed subtle concomitant neurological symptoms. The mean time to anti-NMDAR encephalitis diagnosis was 26.7 days, which was triggered by the NI in six patients. We found no association between clinical variables as delayed diagnosis, admission to psychiatric wards or the presence of malignancy with outcome variables as unfavorable outcomes at discharge, ICU, or mechanical ventilation requirement. A thorough neurological examination in young patients with new-onset psychiatric symptoms could help emergency physicians, neurologists, and psychiatrists suspect anti-NMDAR encephalitis earlier. Awareness of NI as a potential side effect during suspected or confirmed anti-NMDAR encephalitis is encouraged.

NLRP12 controls arthritis severity by acting as a checkpoint inhibitor of Th17 cell differentiation.

Nucleotide oligomerization domain (NOD)-like receptor-12 (NLRP12) has emerged as a negative regulator of inflammation. It is well described that the Th17 cell population increases in patients with early Rheumatoid Arthritis (RA), which correlates with the disease activity. Here, we investigated the role of NLRP12 in the differentiation of Th17 cells and the development of experimental arthritis, using the antigen-induced arthritis (AIA) murine model. We found that Nlrp12-/- mice develop severe arthritis characterized by an exacerbated Th17-mediated inflammatory response with increases in the articular hyperalgesia, knee joint swelling, and neutrophil infiltration. Adoptive transfer of Nlrp12-/- cells into WT mice recapitulated the hyperinflammatory response seen in Nlrp12-/- mice and the treatment with anti-IL-17A neutralizing antibody abrogated arthritis development in Nlrp12-/- mice, suggesting that NLRP12 works as an inhibitor of Th17 cell differentiation. Indeed, Th17 cell differentiation markedly increases in Nlrp12-/- T cells cultured under the Th17-skewing condition. Mechanistically, we found that NLRP12 negatively regulates IL-6-induced phosphorylation of STAT3 in T cells. Finally, pharmacological inhibition of STAT3 reduced Th17 cell differentiation and abrogated hyperinflammatory arthritis observed in Nlrp12-/- mice. Thus, we described a novel role for NLRP12 as a checkpoint inhibitor of Th17 cell differentiation, which controls the severity of experimental arthritis.

Influence of the production environment on the cultivation of lettuce and arugula with spent mushroom substrate.

After mushroom production, the substrate plus the cultivated mycelium represents a byproduct, the so-called "spent mushroom substrate" (SMS). We evaluated different SMS types in fresh form, recently taken from the cultivation rooms, for the production of lettuce and arugula in the open field, greenhouse and greenhouse in pot. Three kinds of SMS were used (i - SMS of ABL (Agaricus subrufescens), ii - SMS of POS (Pleurotus ostreatus) and iii - 50% SMS of ABL + 50% SMS of POS) at three doses (1, 2 and 4 kg m-2). For comparison purposes, two commercial soil conditioners, Forth Condicionador® and Visa Fértil Orgânico®, were used. Finally, chicken manure with reference as international organic material was used. A control treatment consisted of a soil plot without any organic material. The application of fresh SMS in the production of LE (lettuce) and AR (arugula) is feasible considering several agronomic parameters evaluated, therefore that in F (field) the superior results were obtained by the ABL dose of 4 kg m-2, in the GR (green house) at a lower dose ABL with 1 kg m-2, POS with 2 kg m-2 and mix with ABL + POS at doses of 2-4 kg m-2, and finally in GR/P (greenhouse pot) it was proved that in a protected environment by rain the combination ABL + POS at dose of 4 kg m-2 is recommended.

Linking assessment instruments for brachial plexus injury to the international classification of functioning, disability and health.

BACKGROUND: Brachial plexus injuries (BPI) affect not only body structure and function, but also several aspects of individual's well-being. Considering the crescent need for assessing such patients through a biopsychosocial perspective, linking meaningful concepts of BPI instruments to the International Classification of Functioning, Disability and Health (ICF) provides a useful overview of how the ICF components are contemplated on the current measurements available. PURPOSE: To identify patient-reported outcome measures (PROMs) specifically designed for BPI assessment and link the content with the ICF. STUDY DESIGN: Content Analysis through ICF linking. METHODS: The study was conducted in two steps: the first one encompassed a literature review to identify questionnaires specifically designed for assessing patients with BPI, where two PROMs were eligible: the Brachial Assessment Tool (BrAT) and the Impact of Brachial Plexus Injury Questionnaire (IBPIQ); in the second phase, the items of such instruments were linked to the ICF by two independent reviewers, in accordance to the methodology proposed by Cieza et al. RESULTS: 54 different significant concepts were identified from the 74 questionnaire items and linked to 49 distinct ICF categories. The categories were mostly related to the activities and participation component (56.9%, n = 29), followed by body functions (27.45%, n = 14), body structures (9.8%, n = 5) and environmental factors component (1.96%, n = 1). CONCLUSION: The questionnaires developed for adults with BPI were BrAT and IBPIQ. Although both instruments presented with a diverse coverage of ICF components, their content had a major focus on activities and participation domain and poorly or did not addressed environmental factors. Thus, other instruments could be considered in a complementary way for clinical assessment.

CariesCare International adapted for the pandemic in children: Caries OUT multicentre single-group interventional study protocol.

BACKGROUND: Comprehensive caries care has shown effectiveness in controlling caries progression and improving health outcomes by controlling caries risk, preventing initial-caries lesions progression, and patient satisfaction. To date, the caries-progression control effectiveness of the patient-centred risk-based CariesCare International (CCI) system, derived from ICCMS™ for the practice (2019), remains unproven. With the onset of the COVID-19 pandemic a previously planned multi-centre RCT shifted to this "Caries OUT" study, aiming to assess in a single-intervention group in children, the caries-control effectiveness of CCI adapted for the pandemic with non-aerosols generating procedures (non-AGP) and reducing in-office time. METHODS: In this 1-year multi-centre single-group interventional trial the adapted-CCI effectiveness will be assessed in one single group in terms of tooth-surface level caries progression control, and secondarily, individual-level caries progression control, children's oral-health behaviour change, parents' and dentists' process acceptability, and costs exploration. A sample size of 258 3-5 and 6-8 years old patients was calculated after removing half from the previous RCT, allowing for a 25% dropout, including generally health children (27 per centre). The single-group intervention will be the adapted-CCI 4D-cycle caries care, with non-AGP and reduced in-office appointments' time. A trained examiner per centre will conduct examinations at baseline, at 5-5.5 months (3 months after basic management), 8.5 and 12 months, assessing the child's CCI caries risk and oral-health behaviour, visually staging and assessing caries-lesions severity and activity without air-drying (ICDAS-merged Epi); fillings/sealants; missing/dental-sepsis teeth, and tooth symptoms, synthetizing together with parent and external-trained dental practitioner (DP) the patient- and tooth-surface level diagnoses and personalised care plan. DP will deliver the adapted-CCI caries care. Parents' and dentists' process acceptability will be assessed via Treatment-Evaluation-Inventory questionnaires, and costs in terms of number of appointments and activities. Twenty-one centres in 13 countries will participate. DISCUSSION: The results of Caries OUT adapted for the pandemic will provide clinical data that could help support shifting the caries care in children towards individualised oral-health behaviour improvement and tooth-preserving care, improving health outcomes, and explore if the caries progression can be controlled during the pandemic by conducting non-AGP and reducing in-office time. TRIAL REGISTRATION: Retrospectively-registered-ClinicalTrials.gov-NCT04666597-07/12/2020: https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000AGM4&selectaction=Edit&uid=U00019IE&ts=2&cx=uwje3h . Protocol-version 2: 27/01/2021.

Influence of grape seed extract in adhesion on dentin surfaces conditioned with Er,Cr:YSGG laser.

The proanthocyanidin (PA)-rich grape seed extract (GSE) is a collagen cross-linking agent that can perform a chemical bond with the dentin's collagen. The objective of this study was to evaluate the influence on shear bond strength (SBS) of the pre-conditioning of GSE, on human dentin surfaces conditioned with Er,Cr:YSGG laser. The sample consisted of 64 non-carious human teeth, divided into eight groups, four groups conditioned with Er,Cr:YSGG laser (4.5 W, 50 Hz, 50 µs, 70% air, 90% water) and four prepared with conventional methods (control). In both groups, a GSE solution was applied before using the two adhesives tested: Clearfil™ SE Bond (CSE) and Scotchbond™ Universal (SU). Subsequently, a SBS test, a scanning electron microscopy, and a statistical analysis were performed. In the laser groups, the best SBS mean (20.08 ± 4.01 MPa) was achieved in the group treated with GSE and CSE. The control group with the application of CSE showed the highest SBS mean (24.27 ± 10.28 MPa), and the group treated with laser and SU showed the lowest SBS mean (12.94 ± 6.51 MPa). Between these two groups there was a statistically significant difference (p = 0.05). However, this was not observed among the laser or control groups. The type of dentin surface preparation can influence the SBS. The CSE showed better SBS in laser and control groups. The presence of GSE did not improve the adhesion on surfaces conditioned with laser, but more studies should be carried out in the future to confirm this conclusion.

Protective outcomes of low-dose doxycycline on renal function of Wistar rats subjected to acute ischemia/reperfusion injury.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute renal failure. Doxycycline (Dc) belongs to the tetracycline-class of antibiotics with demonstrated beneficial molecular effects in the brain and heart, mainly through matrix metalloproteinases inhibition (MMP). However, Dc protection of renal function has not been demonstrated. We determined whether low doses of Dc would prevent decreases in glomerular filtration rate (GFR) and maintain tubular Na+ handling in Wistar rats subjected to kidney I/R. Male Wistar rats underwent bilateral kidney ischemia for 30min followed by 24h reperfusion (I/R). Doxycycline (1, 3, and 10mg/kg, i.p.) was administered 2h before surgery. Untreated I/R rats showed a 250% increase in urine volume and proteinuria, a 60% reduction in GFR, accumulation of urea-nitrogen in the blood, and a 60% decrease in the fractional Na+ excretion due to unbalanced Na+ transporter activity. Treatment with Dc 3mg/kg maintained control levels of urine volume, proteinuria, GFR, blood urea-nitrogen, fractional Na+ excretion, and equilibrated Na+ transporter activities. The Dc protection effects on renal function were associated with kidney structure preservation and prevention of TGFß and fibronectin deposition. In vitro, total MMP activity was augmented in I/R and inhibited by 25 and 50µM Dc. In vivo, I/R augmented MMP-2 and -9 protein content without changing their activities. Doxycycline treatment downregulated total MMP activity and MMP-2 and -9 protein content. Our results suggest that treatment with low dose Dc protects from IRI, thereby preserving kidney function.

Postoperative Immobilization following Occipitocervical Fusion in the Pediatric Population: Outcome Evaluation and Review of Literature.

The scientific literature does not have a consensus about the role and method of postoperative immobilization after occipitocervical fusion in the pediatric population. The primary goal of this study is to review the medical literature and evaluate different immobilization methods and their impact on fusion, following the surgical management of craniocervical instability in children. It started with an extensive research of randomized controlled trials, series of cases and case reports, describing occipitocervical junction pathologies, clinical, epidemiological characteristics, and treatment. The search was performed using the Pubmed database evaluating all the literature involving postoperative immobilization after occipitocervical fusion in pediatric patients. The results showed that most cases of occipitocervical stabilization were due to congenital spinal instability followed by trauma in most series. The most common type of surgery performed was occipitocervical fusion using screw and rod constructs. The different methods of postoperative immobilization did not affect outcomes. Then, we can conclude that screw-and-rod constructions in occipitocervical fusion augment the rates of fusion, independently from which immobilization was used, even when none was used at all.

Morphology of the Dentin-resin Interface yielded by Two-step Etch-and-rinse Adhesives with Different Solvents.

AIM: The study aimed to analyze the morphology of the dentin-resin interface yielded by two-step etch-and-rinse adhesive systems with different solvents and compositions. MATERIALS AND METHODS: A total of 32 dentine disks were prepared and randomly assigned to four groups of one-bottle etch-and-rinse adhesive systems containing different solvents: group I, Adper Scotchbond-IXT™ (ethanol/water); group II, XP-Bond™ (tertiary butanol); group III, Prime and Bond NT® (acetone); and group IV, One Coat bond® (5% water). Adhesive systems were applied onto dentin disks, which were then thermal cycled, divided into two hemi-disks (n = 16), and prepared for field-emission scanning electron microscopy to examine the dentin-resin interdiffusion zone. Microphotographs were scanned and data were processed. Data were compared with analysis of variance multivariant test after Kolmogorov-Smirnov and Shapiro-Wilk tests using Statistic Package for the Social Sciences. RESULTS: The adhesive layer thickness average found was group I: 45.9 ± 13.41 urn, group II: 20.6 ± 16.32 urn, group III: 17.7 ± 11.75 urn, and group IV: 50.7 ± 27.81 urn. Significant differences were found between groups I and IV and groups II and III (p < 0.000). Groups I (3.23 ± 0.53 µm) and II (3.13 ± 0.73 µm) yielded significantly thicker hybrid layers than groups III (2.53 ± 0.50 µm) and IV (1.84 ± 0.27 µm) (p < 0.003). Group III presented a less homogeneous hybrid layer, with some gaps. Tag length average was greater in groups II (111.0 ± 36.92 µm) and IV (128.9 ± 78.38 µm) than in groups I (61.5 ± 18.10 µm) and III (68.6 ± 15.84 µm) (p < 0.008). CONCLUSION: Adhesives systems with different solvents led to significant differences in the dentin-resin interface morphology. Solvents role in adhesives bond strength should be considered together with the other adhesive system components. CLINICAL SIGNIFICANCE: The adhesive containing tertiary butanol, in addition, seems to originate a good-quality hybrid layer and long, entangled tags and also appears to have greater ability to originate microtags, which may indicate higher bond strength.

Practical Implementation of Evidence-Based Dentistry Into Daily Dental Practice Through a Short Time Dependent Searching Method.

INTRODUCTION: Despite the fact that the benefits of implementation of Evidence-Based Dentistry (EBD) into clinical practice is increasingly being highlighted, there are still clear limitations in its implementation into daily dental practice. One potentially important barrier to effective implementation into practice is the perception of EBD as a time-consuming process. The aim of the present study is to increase the familiarity of dental practitioners with the benefits of different time-dependent 'practical' search strategies important to EBD using a clinical question from the field of dental implantology as an example. MATERIALS AND METHODS: The PICO (population, intervention, comparison, outcome) question used in this study was: "In young adults with anterior single-tooth implant what is the effect of immediate or delayed loading on success?" A bibliographic search according to the Haynes 5S pyramid, together with 3 different time-dependent strategies (5-min, 30-min and more than 60-min), were applied. RESULTS: Both the Haynes 5S Pyramid and time-dependent search strategies revealed promising results for enhancing decision-making for determining the feasibility of immediate or conventional loading of anterior single dental implants. Results clearly showed that selection of the loading protocol would be case (patient)-specific and also indicated high primary implant stability and bone quality as the most important prerequisites for a successful immediate/early loading. From among the 3 different time-dependent strategies (5 min, 30 min and more than 60 min), the 60+ min search results were quite comparable with the Haynes pyramid search results. CONCLUSION: It is likely that the different time-dependent search strategies may have the potential to support the clinical decision making process and may improve the implementation of EBD into daily dental practice. Increased time spent searching naturally seems to increase the extent of this support. However, even with short time-dependent searches, busy dental clinicians may get an improved idea/opinion regarding a clinical question.

Target Inhibition of IL-1 Receptor Prevents Ifosfamide Induced Hemorrhagic Cystitis in Mice.

PURPOSE: Hemorrhagic cystitis is an important dose limiting side effect of ifosfamide based cancer chemotherapy. Despite chemoprophylaxis inflammation can still be found in cystoscopy guided biopsies. Previous studies confirmed the role of TNF-α and IL-1ß. We evaluated the protective effect of the IL-1R antagonist anakinra and the anti-TNF-α antibody infliximab in experimental ifosfamide induced hemorrhagic cystitis. MATERIALS AND METHODS: Hemorrhagic cystitis was induced by an injection of ifosfamide (400 mg/kg intraperitoneally) in Swiss wild-type C57Bl/6, IL-1R-/-, TNFR1-/- or TNFR1/R2-/- mice. Mice were treated 30 minutes before ifosfamide with anakinra (100 mg/kg intraperitoneally), infliximab (5 mg/kg intraperitoneally) or vehicle. Visceral nociception was evaluated after hemorrhagic cystitis induction. At 12 hours the animals were sacrificed. Bladders were harvested to assess bladder wet weight, vascular permeability, macroscopic and microscopic findings, muscle contractility, and for cystometrography. Inflammatory cell infiltration was assessed by myeloperoxidase assay and flow cytometry. RESULTS: Anakinra attenuated hemorrhage, edema, neutrophil infiltration, visceral hyperalgesia and bladder dysfunction. IL-1R-/- mice also showed milder hemorrhagic cystitis. Infliximab inhibited bladder edema and visceral hyperalgesia without preventing hemorrhage, bladder dysfunction, neutrophils or accumulation. Additionally, the lack of TNFR1 decreased bladder edema but not cell infiltration whereas concomitant deficiency of TNFR1 and TNFR2 resulted in worse hemorrhagic cystitis. CONCLUSIONS: Anakinra is effective for preventing experimentally ifosfamide induced hemorrhagic cystitis. It seems that neutrophil and macrophage infiltration in this circumstance depends on IL-1 signaling through IL1R. Possibly TNFR2 has a protective role in hemorrhagic cystitis.