Cellular and molecular mechanisms of skin wound healing.

Wound healing is a complex process that involves the coordinated actions of many different tissues and cell lineages. It requires tight orchestration of cell migration, proliferation, matrix deposition and remodelling, alongside inflammation and angiogenesis. Whereas small skin wounds heal in days, larger injuries resulting from trauma, acute illness or major surgery can take several weeks to heal, generally leaving behind a fibrotic scar that can impact tissue function. Development of therapeutics to prevent scarring and successfully repair chronic wounds requires a fuller knowledge of the cellular and molecular mechanisms driving wound healing. In this Review, we discuss the current understanding of the different phases of wound healing, from clot formation through re-epithelialization, angiogenesis and subsequent scar deposition. We highlight the contribution of different cell types to skin repair, with emphasis on how both innate and adaptive immune cells in the wound inflammatory response influence classically studied wound cell lineages, including keratinocytes, fibroblasts and endothelial cells, but also some of the less-studied cell lineages such as adipocytes, melanocytes and cutaneous nerves. Finally, we discuss newer approaches and research directions that have the potential to further our understanding of the mechanisms underpinning tissue repair.

Time Course of Mechanical Ventilation Driving Pressure Levels in Pediatric Acute Respiratory Distress Syndrome: Outcomes in a Prospective, Multicenter Cohort Study From Colombia, 2018-2022.

OBJECTIVES: High driving pressure (DP, ratio of tidal volume (Vt) over respiratory system compliance) is a risk for poor outcomes in patients with pediatric acute respiratory distress syndrome (PARDS). We therefore assessed the time course in level of DP (i.e., 24, 48, and 72 hr) after starting mechanical ventilation (MV), and its association with 28-day mortality. DESIGN: Multicenter, prospective study conducted between February 2018 and December 2022. SETTING: Twelve tertiary care PICUs in Colombia. PATIENTS: One hundred eighty-four intubated children with moderate to severe PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The median (interquartile range [IQR]) age of the PARDS cohort was 11 (IQR 3-24) months. A total of 129 of 184 patients (70.2%) had a pulmonary etiology leading to PARDS, and 31 of 184 patients (16.8%) died. In the first 24 hours after admission, the plateau pressure in the nonsurvivor group, compared with the survivor group, differed (28.24 [IQR 24.14-32.11] vs. 23.18 [IQR 20.72-27.13] cm H2O, p < 0.01). Of note, children with a Vt less than 8 mL/kg of ideal body weight had lower adjusted odds ratio (aOR [95% CI]) of 28-day mortality (aOR 0.69, [95% CI, 0.55-0.87]; p = 0.02). However, we failed to identify an association between DP level and the oxygenation index (aOR 0.58; 95% CI, 0.21-1.58) at each of time point. In a diagnostic exploratory analysis, we found that DP greater than 15 cm H2O at 72 hours was an explanatory variable for mortality, with area under the receiver operating characteristic curve of 0.83 (95% CI, 0.74-0.89); there was also increased hazard for death with hazard ratio 2.5 (95% CI, 1.07-5.92). DP greater than 15 cm H2O at 72 hours was also associated with longer duration of MV (10 [IQR 7-14] vs. 7 [IQR 5-10] d; p = 0.02). CONCLUSIONS: In children with moderate to severe PARDS, a DP greater than 15 cm H2O at 72 hours after the initiation of MV is associated with greater odds of 28-day mortality and a longer duration of MV. DP should be considered a variable worth monitoring during protective ventilation for PARDS.

Effect of monocultures and polycultures of Typha latifolia and Heliconia psittacorum on the treatment of river waters contaminated with landfill leachate/domestic wastewater in partially saturated vertical constructed wetlands.

Partially Saturated Vertical Constructed Wetlands (PSV-CWs) are novel wastewater treatment systems that work through aerobic and anaerobic conditions that favor the removal of pollutants found in high concentrations, such as rivers contaminated with domestic wastewater and landfill leachate. The objective of the study was to evaluate the efficiency of PSV-CWs using monocultures and polycultures of Typha latifolia and Heliconia psittacorum to treat river waters contaminated with leachates from open dumps and domestic wastewater. Six experimental units of PSV-CWs were used; two were planted with Typha latifolia monoculture, two with Heliconia psittacorum monoculture and two with polycultures of both plants. The results indicated better organic matter and nitrogen removal efficiencies (p < 0.05) in systems with polycultures (TSS:95%, BOD5:83%, COD:89%, TN:82% and NH4+:99%). In general, the whole system showed high average removal efficiencies (TSS:93%, BOD5:79%, COD:85%, TN:79%, NH4+:98% and TP:85%). Regarding vegetation, both species developed better in units with monocultures, being Typha latifolia the one that reached a more remarkable development. However, both species showed high resistance to the contaminated environment. These results showed higher removals than those reported in the literature with conventional Free Flow Vertical Constructed Wetlands (FFV-CWs), so PSV-CWs could be a suitable option to treat this type of effluent.

The research addresses the contamination of water resources in developing countries by landfill leachate and domestic wastewater discharges. It proposes treatment through Partially Saturated Vertical Constructed Wetlands (PSV-CWs), which, despite the limited information available, have been shown to be effective in removing pollutants in effluents with high concentrations. In addition to evaluating PSV-CWs, the study examines the impact of different types of vegetation on pollutant removal efficiency, concluding that PSV-CWs are a promising and viable option for the treatment of these effluents.

Effectiveness of photobiomodulation with low-level lasers on the acceleration of orthodontic tooth movement: a systematic review and meta-analysis of split-mouth randomised clinical trials.

Although several studies have evaluated the effect of low-level laser therapy (LLLT) on orthodontic movement acceleration, results are still inconsistent. Such inconsistencies may be attributed to the differences in the LLLT application protocols, especially in terms of wavelength ranges. Objective: (i) to assess the clinical effects of LLLT on the acceleration of orthodontic movement and (ii) to establish the most effective LLLT wavelength to accelerate tooth movement during orthodontic treatments. MEDLINE (PubMed), Scopus, ScienceDirect, and LILACS were searched from inception to October 2022. Inclusion criteria: Split-mouth randomised clinical trials (RCTs) on systemically healthy patients reporting the effect of LLLT in accelerating orthodontic movements, specifically retraction of canines. The risk of bias was assessed using RoB-2. A random effect model was applied. Nineteen RCTs met the inclusion criteria for qualitative synthesis, and eighteen RCTs were included in the quantitative synthesis. Seventeen studies were rated as at some concerns of bias and two studies were classified as having a low risk of bias. In general terms, this systematic review and meta-analysis presents a moderate risk of bias. Findings of this systematic review and meta-analysis point to a tendency for faster orthodontic dental movement in the groups receiving LLLT treatment during the first (OR of 0.28 95% CI (0.07 to 0.48)), second (OR of 0.52 95% CI (0.31 to 0.73)), and third (OR of 0.41 95% CI (0.03 to 0.79)) month follow-up. Wavelengths ≤ 810 nm and energy density values ≤ 5.3 J/cm2 were associated with faster orthodontic tooth movement.

CXCL12a/CXCR4b acts to retain neutrophils in caudal hematopoietic tissue and to antagonize recruitment to an injury site in the zebrafish larva.

Neutrophils are a major component of the innate immune response and the most abundant circulating cell type in humans and zebrafish. The CXCL12/CXCR4 ligand receptor pair plays a key role in neutrophil homeostasis, controlling definitive hematopoiesis and neutrophil release into circulation. Neutrophils overexpressing CXCR4 respond by migrating towards sources of CXCL12, which is abundant in hematopoietic tissues. However, the physiological role of CXCL12/CXCR4 signaling during inflammatory responses remains unknown. Here, we show that zebrafish mutants lacking functional CXCL12a or CXCR4b show disrupted granulopoiesis in the kidney and increased number of circulating neutrophils. Additionally, CXCL12a and CXCR4b mutants display exacerbated recruitment of neutrophils to wounds and not to infections, and migrating neutrophils to wounds show increased directionality. Our results show that CXCL12a/CXCR4b signaling antagonizes wound-induced inflammatory signals by retaining neutrophils in hematopoietic tissues as a part of a balance between both inflammatory and anti-inflammatory cues, whose dynamic levels control neutrophils complex migratory behavior.

[Persistent abdominal pain caused by superior mesenteric artery and celiac trunk dissection that does not respond to conservative treatment]. / Dolor abdominal persistente por disección de arteria mesentérica superior y tronco celiaco, que no responde a tratamiento conservador.

We report the case of a 32 year old male with recurrent colic abdominal pain due to superior mesenteric artery (SMA) and celiac trunk dissection, which resolved after placing 3 stents in SMA. The patient presented atypical clinical signs and symptoms, which made the diagnosis difficult. Clinical presentation, diagnostic methods and treatment options are discussed. We started with conservative management with pain medication, anticoagulation, antihypertensive drugs and image control, but on the seventh day, after restarting oral ingestion, he presented with abdominal angina, after which we proceeded to endovascular treatment with successful results and with an uneventfully 2 year follow up.

Macrophage Recruitment Contributes to Regeneration of Mechanosensory Hair Cells in the Zebrafish Lateral Line.

In vertebrates, damage to mechanosensory hair cells elicits an inflammatory response, including rapid recruitment of macrophages and neutrophils. While hair cells in amniotes usually become permanently lost, they readily regenerate in lower vertebrates such as fish. Damage to hair cells of the fish lateral line is followed by inflammation and rapid regeneration; however the role of immune cells in this process remains unknown. Here, we show that recruited macrophages are required for normal regeneration of lateral line hair cells after copper damage. We found that genetic ablation or local ablation using clodronate liposomes of macrophages recruited to the site of injury, significantly delays hair cell regeneration. Neutrophils, on the other hand, are not needed for this process. We anticipate our results to be a starting point for a more detailed description of extrinsic signals important for regeneration of mechanosensory cells in vertebrates. J. Cell. Biochem. 117: 1880-1889, 2016. © 2016 Wiley Periodicals, Inc.

Electroablation: a method for neurectomy and localized tissue injury.

BACKGROUND: Tissue injury has been employed to study diverse biological processes such as regeneration and inflammation. In addition to physical or surgical based methods for tissue injury, current protocols for localized tissue damage include laser and two-photon wounding, which allow a high degree of accuracy, but are expensive and difficult to apply. In contrast, electrical injury is a simple and inexpensive technique, which allows reproducible and localized cell or tissue damage in a variety of contexts. RESULTS: We describe a novel technique that combines the advantages of zebrafish for in vivo visualization of cells with those of electrical injury methods in a simple and versatile protocol which allows the study of regeneration and inflammation. The source of the electrical pulse is a microelectrode that can be placed with precision adjacent to specific cells expressing fluorescent proteins. We demonstrate the use of this technique in zebrafish larvae by damaging different cell types and structures. Neurectomy can be carried out in peripheral nerves or in the spinal cord allowing the study of degeneration and regeneration of nerve fibers. We also apply this method for the ablation of single lateral line mechanosensory neuromasts, showing the utility of this approach as a tool for the study of organ regeneration. In addition, we show that electrical injury induces immune cell recruitment to damaged tissues, allowing in vivo studies of leukocyte dynamics during inflammation within a confined and localized injury. Finally, we show that it is possible to apply electroablation as a method of tissue injury and inflammation induction in adult fish. CONCLUSIONS: Electrical injury using a fine microelectrode can be used for axotomy of neurons, as a general tissue ablation tool and as a method to induce a powerful inflammatory response. We demonstrate its utility to studies in both larvae and in adult zebrafish but we expect that this technique can be readily applied to other organisms as well. We have called this method of electrical based tissue ablation, electroablation.

Comparison of dynamic cyclic fatigue resistance of Reciproc® Blue and WaveOne® Gold after sterilization and/or immersion in sodium hypochlorite.

Background: This study aims to compare the cyclic fatigue resistance (CFR) of the Reciproc Blue and WaveOne Gold instruments under a dynamic cyclical fatigue test. Material and Methods: 210 Reciproc Blue "R25" and WaveOne Gold "primary" files were assigned into 7 groups (n =15) for each brand. Groups G: Files were not exposed to NaOCl or sterilization. Groups A and D: files were immersed for 3 minutes in NaOCl 1 and 3 times, respectively. Groups B and E: Files were autoclaved 1 and 3 times, respectively. Groups C and F: files were exposed to both, NaOCl immersion and autoclaving 1 and 3 times, respectively. Subsequently, files underwent a dynamic CFR test. The chemical composition of the files' surface from Group G was analysed by energy-dispersive X-ray spectroscopy (EDS). Cyclic fatigue resistance time was statistically analysed using 1-way and 2-way analyses of variance (ANOVA) and T-test. A p-value ≤0,05 was set to be statistically significant. Results: There was a significantly higher CFR of RB files than WOG in groups A, B, C, D and G (p<0.05). WOG files were superior to RB in group E (p>0.05). There were no statistically significant differences between files in group F (p>0.05). RB files from groups B, C, D, E and F had significantly lower resistance than new ones (Group G) (p<0.05). WaveOne Gold files exposed to 5 % NaOCl immersion in combination with sterilization cycles (Groups C and F) had significantly lower CFR than new ones (p<0.05). Reciproc Blue and WaveOne Gold NiTi alloys differed in atomic wt % of carbon, oxygen, nickel and titanium. Conclusions: The Reciproc Blue files outperformed the WaveOne Gold files in terms of CFR. The Reciproc Blue files were more vulnerable to the cycles of NaOCl immersion or autoclave sterilisation. The combined autoclaving and NaOCl cycles had the most significant impact on the mechanical properties of both files. Key words:Cyclic fatigue, Reciproc blue, Wave one gold, Dynamic test, Simulated channels, Sodium hypochlorite, Sterilization.

Eligibility of sodium-glucose cotransporter-2 inhibitors in heart failure with preserved ejection fraction: Insights from the Colombian heart failure registry (RECOLFACA).

Background: The value of Sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitor) therapy in individuals with heart failure with preserved EF (HFpEF) was unknown until the EMPEROR-Preserved trial. We aimed to assess the proportion of patients with HFpEF that are eligible for empagliflozin therapy within the Colombian Heart Failure Registry (RECOLFACA). Methods: RECOLFACA enrolled adult patients with a HF diagnosis during 2017-2019 from 60 medical centers in Colombia. Criteria of the EMPEROR-Preserved Trial were used to recruit participants. The main outcome was individual eligibility with N-terminal pro-B-type natriuretic peptide (NT-proBNP) criteria, while the secondary outcome was eligibility without NT-proBNP data. Results: RECOLFACA had 799 patients with HFpEF (mean age70.7 ± 13.5; 50.7 % males). According to the major selection criteria of the EMPEROR Preserved Trial, 73.7 % patients would be eligible for empagliflozin therapy initiation when considering the NT-proBNP threshold. The NT-proBNP threshold represented the main determinant of ineligibility in patients with this biomarker measure (13.6 %; n = 16). In patients without NT-proBNP data, the main reasons for exclusion were the diagnosis of symptomatic hypotension or a systolic blood pressure below 100 mmHg (7.5 %), having an eGFR < 20 ml/min/1.73 m2 (4.3 %), and haemoglobin < 9 g/dl (3.1 %). Excluding NT-proBNP criteria increased empagliflozin eligibility to 80.6 %. Conclusion: Most patients with HFpEF from RECOLFACA are potential candidates for empagliflozin therapy initiation according to the EMPEROR-Preserved trial criteria. These findings favor the utilization of SGLT-2 inhibitor medications in daily medical practice, which may further decrease morbidity and mortality in HF patients, regardless of their EF classification.

Secondary haemophagocytic lymphohistiocytosis in a patient with new-onset systemic lupus erythematosus: the challenges of timely diagnosis and successful treatment.

Haemophagocytic lymphohistiocytosis (HLH) is an immune-mediated disease driven by abnormal macrophage activation and regulatory cell dysfunction. HLH can be primary due to genetic mutations or secondary due to infection, malignancy or autoimmune conditions. We describe a woman in her early 30s who developed HLH while being treated for newly diagnosed systemic lupus erythematosus (SLE) complicated by lupus nephritis as well as concomitant cytomegalovirus (CMV) reactivation from a dormant infection. The trigger for this secondary form of HLH may have been either aggressive SLE and/or CMV reactivation. Despite prompt treatment with immunosuppressive therapies for SLE consisting of high-dose corticosteroids, mycophenolate mofetil, tacrolimus, etoposide for HLH and ganciclovir for CMV infection, the patient developed multiorgan failure and passed away. We demonstrate the difficulty in identifying a specific cause for secondary HLH when multiple conditions are present (SLE and CMV) and the fact that, despite aggressive treatment for both conditions, the mortality for HLH remains high.

Comparative outcomes of platelet concentrates and blood clot scaffolds for regenerative endodontic procedures: A systematic review of randomized controlled clinical trials.

Background: The main objective of this systematic review is to evaluate the effectiveness of platelet concentrates -Platelet-rich plasma (PRP) or Fibrin-rich plasma (PRF)- compared with blood clot (BC) as scaffolds for maturogenesis, in patients with immature permanent teeth with or without AP, in terms of the criteria for pulp revascularization success. Material and Methods: We reviewed randomized controlled clinical trials comparing regenerative endodontic therapies (maturogenesis) based on PRP or PRF versus the conventional BC approach, in necrotic teeth with or without apical periodontitis (AP) under clinical and radiographic criteria. We performed a strategic search in MEDLINE (PUBMED), EMBASE, and ISI Web of Science from inception to October 2022. This systematic review of the literature was developed following the Cochrane Collaboration and PRISMA statement recommendations. We used the Cochrane risk of bias tool v2 to assess the included studies' quality. We performed a qualitative synthesis of the evidence. Results: Ten randomized controlled clinical trials were included in this systematic review. Analyses of these studies suggest that maturogenesis is a successful therapy regardless of the method employed. However, further research should be conducted with more suitable research methodologies and more homogenous data for meta-analysis. Conclusions: Results from this systematic review suggest that BC maturogenesis approaches yield similar clinical and radiographic outcomes when compared to Platelet-concentrates based therapies (PRP and PRF). Key words:Maturogenesis, Revascularization, Platelet-rich plasma, Fibrin-rich plasma, blood clot, systematic review.

Association between cigarette smoking and the prevalence of post-endodontic periapical pathology: a systematic review and meta-analysis.

Objectives: This systematic review and meta-analysis aimed to assess the association of cigarette smoking with the prevalence of post-endodontic apical periodontitis in humans. Materials and Methods: We searched through PubMed/Medline, Web of Science, and Scopus from inception to December 2020. Risk of bias was performed by using the Newcastle-Ottawa Scale for cross-sectional, cohort, and case-control studies. We performed the statistical analysis in Review Manager 5.3 (RevMan 5.3). Results: 6 studies met the inclusion criteria for qualitative and quantitative synthesis. Statistical analysis of these studies suggests that there were no differences in the prevalence of post endodontic apical periodontitis (AP) when comparing non-smokers vs smoker subjects regarding patients (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.31-1.49; I2 = 58%) and teeth (OR, 1.71; 95% CI, 0.99-2.93; I2 = 72%). Conclusions: Our findings suggest that there was no association between cigarette smoking and post-endodontic apical periodontitis, as we did not find statistical differences in the prevalence of post-endodontic AP when comparing non-smokers vs smoker subjects. Therefore, smoking should not be considered a risk factor associated with endodontic failure.

A high-throughput chemically induced inflammation assay in zebrafish.

BACKGROUND: Studies on innate immunity have benefited from the introduction of zebrafish as a model system. Transgenic fish expressing fluorescent proteins in leukocyte populations allow direct, quantitative visualization of an inflammatory response in vivo. It has been proposed that this animal model can be used for high-throughput screens aimed at the identification of novel immunomodulatory lead compounds. However, current assays require invasive manipulation of fish individually, thus preventing high-content screening. RESULTS: Here we show that specific, noninvasive damage to lateral line neuromast cells can induce a robust acute inflammatory response. Exposure of fish larvae to sublethal concentrations of copper sulfate selectively damages the sensory hair cell population inducing infiltration of leukocytes to neuromasts within 20 minutes. Inflammation can be assayed in real time using transgenic fish expressing fluorescent proteins in leukocytes or by histochemical assays in fixed larvae. We demonstrate the usefulness of this method for chemical and genetic screens to detect the effect of immunomodulatory compounds and mutations affecting the leukocyte response. Moreover, we transformed the assay into a high-throughput screening method by using a customized automated imaging and processing system that quantifies the magnitude of the inflammatory reaction. CONCLUSIONS: This approach allows rapid screening of thousands of compounds or mutagenized zebrafish for effects on inflammation and enables the identification of novel players in the regulation of innate immunity and potential lead compounds toward new immunomodulatory therapies. We have called this method the chemically induced inflammation assay, or ChIn assay. See Commentary article: http://www.biomedcentral.com/1741-7007/8/148.

Differential Requirement of Gata2a and Gata2b for Primitive and Definitive Myeloid Development in Zebrafish.

Germline loss or mutation of one copy of the transcription factor GATA2 in humans leads to a range of clinical phenotypes affecting hematopoietic, lymphatic and vascular systems. GATA2 heterozygous mice show only a limited repertoire of the features observed in humans. Zebrafish have two copies of the Gata2 gene as a result of an additional round of ancestral whole genome duplication. These genes, Gata2a and Gata2b, show distinct but overlapping expression patterns, and between them, highlight a significantly broader range of the phenotypes observed in GATA2 deficient syndromes, than each one alone. In this manuscript, we use mutants for Gata2a and Gata2b to interrogate the effects on hematopoiesis of these two ohnologs, alone and in combination, during development in order to further define the role of GATA2 in developmental hematopoiesis. We define unique roles for each ohnolog at different stages of developmental myelopoiesis and for the emergence of hematopoietic stem and progenitor cells. These effects are not additive in the haploinsufficient state suggesting a redundancy between these two genes in hematopoietic stem and progenitor cells. Rescue studies additionally support that Gata2b can compensate for the effects of Gata2a loss. Finally we show that adults with loss of combined heterozygosity show defects in the myeloid compartment consistent with GATA2 loss in humans. These results build on existing knowledge from other models of GATA2 deficiency and refine our understanding of the early developmental effects of GATA2. In addition, these studies shed light on the complexity and potential structure-function relationships as well as sub-functionalization of Gata2 genes in the zebrafish model.

State and parameter estimation for a class of Nonlinear Systems based on Sliding Mode Approach.

In this paper, simultaneous state estimation and parameters identification for a class of nonlinear systems are addressed. With the aim of solving this problem, an adaptive observer based on the sliding mode (AOSM) approach is designed. The main advantage of the proposed adaptive observer design is that it combines the robustness and finite time convergence of the sliding mode observers, with the simplicity of tuning of high-gain observers, reducing tuning effort. The finite time convergence of the proposed adaptive observer is established using a Lyapunov approach. Furthermore, a comparative study of the proposed adaptive observer against schemes from literature is presented, in order to show the advantages of the proposed approach. Finally, numerical results are provided to demonstrate the effectiveness and performance of the proposed approach under noise and external disturbances.

Observer-based super twisting design: A comparative study on quadrotor altitude control.

This paper addresses the design of a continuous super twisting control combined with a high-order sliding mode observer for a class of nonlinear systems. An analysis of closed-loop stability is provided by means of Lyapunov approach, where sufficient conditions are given to ensure the convergence and to select the gains of the proposed controller. Numerical simulation and experimental results illustrate the performance of the proposed control-observer scheme for controlling the altitude of a quad-rotor aircraft. Furthermore, a comparative study against similar approaches from literature is included for illustrating that proposed methodology requires less control effort while shows the best performance.

TLR7 ligation augments hematopoiesis in Rps14 (uS11) deficiency via paradoxical suppression of inflammatory signaling.

Myelodysplastic syndrome (MDS) is a hematological malignancy characterized by blood cytopenias and predisposition to acute myeloid leukemia (AML). Therapies for MDS are lacking, particularly those that have an impact in the early stages of disease. We developed a model of MDS in zebrafish with knockout of Rps14, the primary mediator of the anemia associated with del(5q) MDS. These mutant animals display dose- and age-dependent abnormalities in hematopoiesis, culminating in bone marrow failure with dysplastic features. We used Rps14 knockdown to undertake an in vivo small-molecule screening, to identify compounds that ameliorate the MDS phenotype, and we identified imiquimod, an agonist of Toll-like receptor-7 (TLR7) and TLR8. Imiquimod alleviates anemia by promoting hematopoietic stem and progenitor cell expansion and erythroid differentiation, the mechanism of which is dependent on TLR7 ligation and Myd88. TLR7 activation in this setting paradoxically promoted an anti-inflammatory gene signature, indicating cross talk via TLR7 between proinflammatory pathways endogenous to Rps14 loss and the NF-κB pathway. Finally, in highly purified human bone marrow samples from anemic patients, imiquimod led to an increase in erythroid output from myeloerythroid progenitors and common myeloid progenitors. Our findings have both specific implications for the development of targeted therapeutics for del(5q) MDS and wider significance identifying a potential role for TLR7 ligation in modifying anemia.

Effect of Electronic Health Record Reminders for Routine Immunizations and Immunizations Needed for Chronic Medical Conditions.

BACKGROUND: Immunization reminders in electronic health records (EHR) provide clinical decision support (CDS) that can reduce missed immunization opportunities. Little is known about using CDS rules from a regional immunization information system (IIS) to power local EHR immunization reminders. OBJECTIVE: This study aimed to assess the impact of EHR reminders using regional IIS CDS-provided rules on receipt of immunizations in a low-income, urban population for both routine immunizations and those recommended for patients with chronic medical conditions (CMCs). METHODS: We built an EHR-based immunization reminder using the open-source resource used by the New York City IIS in which we overlaid logic regarding immunizations needed for CMCs. Using a randomized cluster-cross-over pragmatic clinical trial in four academic-affiliated clinics, we compared captured immunization opportunities during patient visits when the reminder was "on" versus "off" for the primary immunization series, school-age boosters, and adolescents. We also assessed coverage of CMC-specific immunizations. Up-to-date immunization was measured by end of quarter. Rates were compared using chi square tests. RESULTS: Overall, 15,343 unique patients were seen for 26,647 visits. The alert significantly impacted captured opportunities to complete the primary series in both well-child and acute care visits (57.6% on vs. 54.3% off, p = 0.001, and 15.3% on vs. 10.1% off, p = 0.02, respectively), among most age groups, and several immunization types. Captured opportunities for CMC-specific immunizations remained low regardless of alert status. The alert did not have an effect on up-to-date immunization overall (89.1 vs. 88.3%). CONCLUSION: CDS in this population improved captured immunization opportunities. Baseline high rates may have blunted an up-to-date population effect. Converting Centers for Disease Control and Prevention (CDC) rules to generate sufficiently sensitive and specific alerts for CMC-specific immunizations proved challenging, and the alert did not have an impact on CMC-specific immunizations, potentially highlighting need for more work in this area.

Association between type 2 diabetes mellitus and the evolution of endodontic pathology.

OBJECTIVE: The purpose of the present study was to assess the influence of type 2 diabetes mellitus (DM) on the evolution of pulpal and periapical pathology. METHOD AND MATERIALS: Two reviewers independently conducted a systematic search for articles published between 1 January 2001 and 31 December 2018 on MEDLINE/PubMed, ISI Web of Science, and Scopus databases. An additional manual search was also carried out. RESULTS: Ten studies fulfilling the inclusion criteria were included in the review (two longitudinal studies with 1-year follow-up comparing the success of primary root canal treatment between type 2 diabetic patients and non-diabetic patients, and eight cross-sectional studies). Analysis of the ten studies showed that inadequate control of type 2 DM may predispose and influence the inflammatory pulpal and periapical disease evolution. CONCLUSIONS: The present systematic review suggests that there are biologic bases to suggest that type 2 DM may act as a risk factor for developing an endodontic pathology, affecting the course of the disease in terms of susceptibility, prevalence, progression, and tissue healing capacity as a consequence of a disrupted immune response. However, more well-designed clinical investigations carrying out suitable research methodologies are needed to elucidate the influence of type 2 DM on the pulpal and periapical disease evolution.