Miracle-dz/UniFAR-FTUs huggingface dataset:
Fixed versus removable orthodontic appliances to correct anterior crossbite in the mixed dentition--a randomized controlled trial.

OBJECTIVE To compare the effectiveness of fixed and removable orthodontic appliances in correcting anterior crossbite with functional shift in the mixed dentition. SUBJECTS AND METHODS Consecutive recruitment of 64 patients who met the following inclusion criteria: early to late mixed dentition, anterior crossbite with functional shift, moderate space deficiency in the maxilla, i.e. up to 4mm, a non-extraction treatment plan, the ANB angle > 0 degree, and no previous orthodontic treatment. Sixty-two patients agreed to participate. The study was designed as a randomized controlled trial with two parallel arms. After written consent was obtained, the patients were randomized, in blocks of 10, for treatment either with a removable appliance with protruding springs or a fixed appliance with multi-brackets. The main outcome measures assessed were success rate, duration of treatment, and changes in overjet, overbite, and arch length. The results were also analysed on an intention-to-treat basis. RESULTS The crossbite was successfully corrected in all patients in the fixed appliance group and all except one in the removable appliance group. The average duration of treatment was significantly less, 1.4 months, for the fixed appliance group (P < 0.05). There were significant increases in arch length and overjet in both treatment groups, but significantly more in the fixed appliance group (P < 0.05 and P < 0.01). CONCLUSION Anterior crossbite with functional shift in the mixed dentition can be successfully corrected by either fixed or removable appliance therapy in a short-term perspective.
Drosophila Rab14 mediates phagocytosis in the immune response to Staphylococcus aureus

Drosophila haemocytes are essential for the animal to resist Staphylococcus aureus infections. Phagocytosis is a central component of the haemocyte‐mediated immune response. It involves regulated interaction between the phagocytic and the endocytic compartments. RabGTPases are pivotal for the membrane trafficking and fusion events, and thus are often targets of intracellular pathogens that subvert phagocytosis. An in vivo screen identified Rab2 and Rab14 as candidates for proteins regulating phagosome maturation. Since Rab14 is often targeted by intracellular pathogens, an understanding of its function during phagocytosis and the overall immune response can give insight into the pathogenesis of intracellular microbes. We generated a Drosophila Rab14 mutant and characterized the resulting immune defects in animals and specifically in haemocytes in response to an S. aureus infection. Haemocyte based immunofluorescence studies indicate that Rab14 is recruited to the phagosome and like Rab7, a well‐characterized regulator of the phagocytic pathway, is essential for progression of phagosome maturation. Rab14 mutant haemocytes show impaired recruitment of Rab7 and of a lysosomal marker onto S. aureus phagosomes. The defect in phagocytosis is associated with higher bacterial load and increased susceptibility to S. aureus in the animal.
The natural alternative: protozoa as cellular models for Legionella infection

The severe pneumonia known as Legionnaires' disease occurs following infection by the Gram‐negative bacterium Legionella pneumophila. Normally resident in fresh‐water sources, Legionella are subject to predation by eukaryotic phagocytes such as amoeba and ciliates. To counter this, L. pneumophila has evolved a complex system of effector proteins which allow the bacteria to hijack the phagocytic vacuole, hiding and replicating within their erstwhile killers. These same mechanisms allow L. pneumophila to hijack another phagocyte, lung‐based macrophages, which thus avoids a vital part of the immune system and leads to infection. The course of infection can be divided into five main categories: pathogen uptake, formation of the replication‐permissive vacuole, intracellular replication, host cell response, and bacterial exit. L. pneumophila effector proteins target every stage of this process, interacting with secretory, endosomal, lysosomal, retrograde and autophagy pathways, as well as with mitochondria. Each of these steps can be studied in protozoa or mammalian cells, and the knowledge gained can be readily applied to human pathogenicity. Here we describe the manner whereby L. pneumophila infects host protozoa, the various techniques which are available to analyse these processes and the implications of this model for Legionella virulence and the pathogenesis of Legionnaires' disease.
Stress Fracture Influences Bone Resorption marker (u-NTX) in Female Long Distance Runners

Abstract In this study, we aim to clarify the influence based on bone resorption markers at onset of stress fracture. Also, we will clarify the state of the bone resorption markers of female long distance runners who have a history of stress fracture and also ones who routinely practices running long distances. Participants comprised 19 female long distance athletes. The survey period was 2011–2014, and we measured u-NTX as a bone resorption marker at least twice a year, taking the mean±SD of the periodic measured values without stress fracture as the mean value. Measurements were collected sample when stress fractures developed. 132 u-NTX measurements were taken from 19 participants. As a result, the average was 41.03±12.31 nmolBCE/mmolCRE (Q1: 33.15, Q2: 40.55, Q3: 47.95). In six of the 19 participants, u-NTX could be measured following a stress fracture. The mean value of u-NTX for those participants was 40.16±9.10 nmolBCE/mmolCRE, increasing to 64.08±16.07 nmolBCE/mmol CRE with the stress fracture (p<0.01). The findings showed that, in adult female long distance runners, u-NTX values when there was no stress fracture were within the standard value for mean premenopausal women, but increased when the athletes suffered from a stress fracture.
Antibody-Based and and Cellular Therapies of Type 1 Diabetes

Type 1 diabetes (T1D) is an insulin-dependent diabetes because of insufficient insulin pro‐ duction by the pancreatic islet β cells. Although the pathogenic mechanism of T1D is not yet completely clear, the current view of T1D pathogenesis is that under certain genetic back‐ ground, exogenous and/or endogenous factors trigger autoimmunity against islet β cells in the pancreas causing β cell damage and subsequent insufficiency of insulin production [1, 2]. About two decades ago, it was first demonstrated that T cells specific to β cell antigens were activated and participated in the pathogenesis of T1D [3, 4]. A great deal of work fol‐ lowing these reports in both animal models and humans has provided convincing data fur‐ ther supporting T1D is a T cell-mediated autoimmune disease. On the other hand, the evidence showing that majority of T1D patients have high titers of autoantibodies against islet β cells [5, 6] suggests that self-reactive B cells must also be involved in the autoimmune process. The role of B cells in the pathogenesis of T1D was further supported by the recent research and clinical data demonstrating B cell depletion by anti-CD20 antibodies delayed the disease process.
Prevalence and repair of intraoperatively diagnosed patent foramen ovale and association with perioperative outcomes and long-term survival.

CONTEXT A recent survey suggested that cardiothoracic surgeons may alter planned procedures to repair incidentally discovered patent foramen ovale (PFO). How frequently this occurs and the impact on outcomes remain unknown. OBJECTIVE To measure the frequency of incidentally discovered PFO closure during cardiothoracic surgery and determine its perioperative and long-term impact. DESIGN, SETTING, AND PATIENTS We reviewed the intraoperative transesophageal echocardiograms of 13,092 patients without prior diagnosis of PFO or atrial septal defect undergoing surgery at the Cleveland Clinic, Cleveland, Ohio, from 1995 through 2006. Postoperative outcomes were prospectively collected until discharge. MAIN OUTCOME MEASURES All-cause hospital mortality and stroke were predetermined primary outcomes; length of hospital stay, length of intensive care unit stay, and time on cardiopulmonary bypass were secondary outcomes. RESULTS Intraoperative PFO was diagnosed in 2277 patients in the study population (17%), and risk factors for stroke were similar in patients with and without PFO. After propensity matching was performed with the comparator groups, patients with PFO demonstrated similar rates of in-hospital death (3.4% vs 2.6%, P = .11) and postoperative stroke (2.3% vs 2.3%, P = .84). Surgical closure was performed in 639 PFO patients (28%), and surgeons were more likely to close defects in patients who were younger (mean [SD] age, 61.1 [14] vs 64.4 [13] years; P < .001), were undergoing mitral or tricuspid valve surgery (51% vs 32%, P < .001), or had history of transient ischemic attack or stroke (16% vs 10%, P < .001). Patients with repaired PFO demonstrated a 2.47-times greater odds (95% confidence interval, 1.02-6.00) of having a postoperative stroke compared with those with unrepaired PFO (2.8% vs 1.2%, P = .04). Long-term analysis demonstrated that PFO repair was associated with no survival difference (P = .12). CONCLUSIONS Incidental PFO is common in patients undergoing cardiothoracic surgery but is not associated with increased perioperative morbidity or mortality. Surgical closure appears unrelated to long-term survival and may increase postoperative stroke risk.
Lipid kinases are essential for apicoplast homeostasis in Toxoplasma gondii

Phosphoinositides regulate numerous cellular processes by recruiting cytosolic effector proteins and acting as membrane signalling entities. The cellular metabolism and localization of phosphoinositides are tightly regulated by distinct lipid kinases and phosphatases. Here, we identify and characterize a unique phosphatidylinositol 3 kinase (PI3K) in Toxoplasma gondii, a protozoan parasite belonging to the phylum Apicomplexa. Conditional depletion of this enzyme and subsequently of its product, PI(3)P, drastically alters the morphology and inheritance of the apicoplast, an endosymbiotic organelle of algal origin that is a unique feature of many Apicomplexa. We searched the T. gondii genome for PI(3)P‐binding proteins and identified in total six PX and FYVE domain‐containing proteins including a PIKfyve lipid kinase, which phosphorylates PI(3)P into PI(3,5)P2. Although depletion of putative PI(3)P‐binding proteins shows that they are not essential for parasite growth and apicoplast biology, conditional disruption of PIKfyve induces enlarged apicoplasts, as observed upon loss of PI(3)P. A similar defect of apicoplast homeostasis was also observed by knocking down the PIKfyve regulatory protein ArPIKfyve, suggesting that in T. gondii, PI(3)P‐related function for the apicoplast might mainly be to serve as a precursor for the synthesis of PI(3,5)P2. Accordingly, PI3K is conserved in all apicomplexan parasites whereas PIKfyve and ArPIKfyve are absent in Cryptosporidium species that lack an apicoplast, supporting a direct role of PI(3,5)P2 in apicoplast homeostasis. This study enriches the already diverse functions attributed to PI(3,5)P2 in eukaryotic cells and highlights these parasite lipid kinases as potential drug targets.
The actin and Rho‐modifying toxins PTC3 and PTC5 of Photorhabdus luminescens: enzyme characterization and induction of MAL/SRF‐dependent transcription

PTC3 and PTC5 are tripartite Tc (toxin complex) toxins from Photorhabdus luminescens, which consist of the binding component TcdA1, the linker component TcdB2 and the enzyme components TccC3 and TccC5 respectively. While PTC5 adenosine diphosphate (ADP)‐ribosylates Rho proteins at Gln61/63 resulting in constitutive activation of the GTPases, PTC3 ADP‐ribosylates actin at Thr148 thereby inducing actin polymerization. Here, we identified amino acids involved in ADP‐ribosyltransferase activity of TccC3 and TccC5 and analysed the substrate specificity of Rho‐activating TccC5. We compared the time dependency of Rho protein activation by PTC5 in HeLa cells with the effects of Escherichia coli cytotoxic necrotizing factor 1, which activates Rho GTPases by deamidation of Gln61/63. Using a luciferase reporter assay, we show that PTC5 and PTC3 stimulated gene transcription via myocardin‐related transcription factor A (also called MAL) and AP1. MAL activation by PTC5 involved Rho kinase and formins. Activation of AP1 by PTC5 occurred via two MAP kinase pathways involving extracellular signal‐regulated kinase and Jun kinase respectively.
Neisseria meningitidis causes cell cycle arrest of human brain microvascular endothelial cells at S phase via p21 and cyclin G2

Microbial pathogens have developed several mechanisms to modulate and interfere with host cell cycle progression. In this study, we analysed the effect of the human pathogen Neisseria meningitidis on cell cycle in a brain endothelial cell line as well as in primary brain endothelial cells. We found that N. meningitidis causes an accumulation of cells in the S phase early at 3 and at 24 h post‐infection that was paralleled by a decrease of cells in G2/M phase. Importantly, the outer membrane proteins of the colony opacity‐associated (Opa) protein family as well as the Opc protein proved to trigger the accumulation of cells in the S phase. A focused cell cycle reverse transcription quantitative polymerase chain reaction‐based array and integrated network analysis revealed changes in the abundance of several cell cycle regulatory mRNAs, including the cell cycle inhibitors p21WAF1/CIP1 and cyclin G2. These alterations were reflected in changes in protein expression levels and/or relocalization in N. meningitidis‐infected cells. Moreover, an increase in p21WAF1/CIP1 expression was found to be p53 independent. Genetic ablation of p21WAF1/CIP1 and cyclin G2 abrogated N. meningitidis‐induced S phase accumulation. Finally, by measuring the levels of the biomarker 8‐hydroxydeoxyguanosine and phosphorylation of the histone variant H2AX, we provide evidence that N. meningitidis induces oxidative DNA damage in infected cells.
BigA is a novel adhesin of Brucella that mediates adhesion to epithelial cells

Adhesion to cells is the initial step in the infectious cycle of basically all pathogenic bacteria, and to do so, microorganisms have evolved surface molecules that target different cellular receptors. Brucella is an intracellular pathogen that infects a wide range of mammals whose virulence is completely dependent on the capacity to replicate in phagocytes. Although much has been done to elucidate how Brucella multiplies in macrophages, we still do not understand how bacteria invade epithelial cells to perform a replicative cycle or what adhesion molecules are involved in the process. We report the identification in Brucella abortus of a novel adhesin that harbours a bacterial immunoglobulin‐like domain and demonstrate that this protein is involved in the adhesion to polarized epithelial cells such as the Caco‐2 and Madin–Darby canine kidney models targeting the bacteria to the cell–cell interaction membrane. While deletion of the gene significantly reduced adhesion, over‐expression dramatically increased it. Addition of the recombinant protein to cells induced cytoskeleton rearrangements and showed that this adhesin targets proteins of the cell–cell interaction membrane in confluent cultures.
Decreased UDP‐GlcNAc levels abrogate proliferation control in EMeg32‐deficient cells

The hexosamine pathway provides UDP‐N‐acetylhexosamine donor substrates used in cytosolic and Golgi‐mediated glycosylation of proteins and for formation of glycosylphosphatidylinositol (GPI) anchors, which tether proteins to the outer plasma membrane. We have recently identified the murine glucosamine‐6‐phosphate (GlcN6P) acetyltransferase, EMeg32, as a developmentally regulated enzyme on the route to UDP‐N‐acetylglucosamine (UDP‐GlcNAc). Here we describe embryos and cells that have the EMeg32 gene inactivated by homologous recombination. Homozygous mutant embryos die at around embryonic day (E) 7.5 with a general proliferative delay of development. In vitro differentiated EMeg32−/− ES cells show reduced proliferation. Mouse embryonic fibroblasts (MEFs) deficient for EMeg32 exhibit defects in proliferation and adhesiveness, which could be complemented by stable re‐expression of EMeg32 or by nutritional restoration of intracellular UDP‐GlcNAc levels. Reduced UDP‐GlcNAc levels predominantly translated into decreased O‐GlcNAc modifications of cytosolic and nuclear proteins. Interestingly, growth‐impaired EMeg32−/− MEFs withstand a number of apoptotic stimuli and express activated PKB/AKT. Thus, EMeg32‐dependent UDP‐GlcNAc levels influence cell cycle progression and susceptibility to apoptotic stimuli.
On Becoming Culturally Competent: HIV Nursing in the 21st Century : Best Practices for Nursing Care of HIV-Infected Patients

Tampereen ammattikorkeakoulu Tampere University of Applied Sciences Degree Programme in Nursing Option of Medical-Surgical Nursing UUSI-TARKKA, HANNA & WINCH, PAULA: On Becoming Culturally Competent: HIV Nursing in the 21st Century Best Practices for Nursing Care of HIV-Infected Patients Bachelor's thesis 57 pages, appendices 4 pages November 2013 The goal of this study was to illuminate the current state of knowledge about culturally competent nursing care of Human Immunodeficiency Virus (HIV) focusing on the Current Care Guidelines, culture, cultural competence, stigma, education, medication adherence, and patient experience. This thesis presents and reviews the most up-to-date methods for nurses to provide culturally competent care to their HIV-infected patients. The literature review in this thesis demonstrates how culturally competent nursing care can help nurses provide optimal care for their culturally diverse HIV-infected patients. The thesis also provides evidence-based recommendations for culturally competent nursing strategies for nurses’ culturally diverse HIV-infected patients. This analysis was formulated through a rigorous review of the relevant literature in the field and is based on the recognized, current, and culturally competent best practices of nursing for HIVinfected patients. The synthesis and analysis of this research revealed unquestionably that culturally-competent nursing care improves the quality of life of HIV-infected individuals. It would be valuable for further research to explore and develop an understanding of if, and how, gender roles impact a patient’s management of his/her HIV-infected status. In addition, further research on the effect of stigma experienced in Finland by culturally diverse HIV-infected patients could improve nursing care practices as well as the patient’s medication adherence and self-care.
Effects of care coordination on hospitalization, quality of care, and health care expenditures among Medicare beneficiaries: 15 randomized trials.

CONTEXT Medicare expenditures of patients with chronic illnesses might be reduced through improvements in care, patient adherence, and communication. OBJECTIVE To determine whether care coordination programs reduced hospitalizations and Medicare expenditures and improved quality of care for chronically ill Medicare beneficiaries. DESIGN, SETTING, AND PATIENTS Eligible fee-for-service Medicare patients (primarily with congestive heart failure, coronary artery disease, and diabetes) who volunteered to participate between April 2002 and June 2005 in 15 care coordination programs (each received a negotiated monthly fee per patient from Medicare) were randomly assigned to treatment or control (usual care) status. Hospitalizations, costs, and some quality-of-care outcomes were measured with claims data for 18 309 patients (n = 178 to 2657 per program) from patients' enrollment through June 2006. A patient survey 7 to 12 months after enrollment provided additional quality-of-care measures. INTERVENTIONS Nurses provided patient education and monitoring (mostly via telephone) to improve adherence and ability to communicate with physicians. Patients were contacted twice per month on average; frequency varied widely. MAIN OUTCOME MEASURES Hospitalizations, monthly Medicare expenditures, patient-reported and care process indicators. RESULTS Thirteen of the 15 programs showed no significant (P<.05) differences in hospitalizations; however, Mercy had 0.168 fewer hospitalizations per person per year (90% confidence interval [CI], -0.283 to -0.054; 17% less than the control group mean, P=.02) and Charlestown had 0.118 more hospitalizations per person per year (90% CI, 0.025-0.210; 19% more than the control group mean, P=.04). None of the 15 programs generated net savings. Treatment group members in 3 programs (Health Quality Partners [HQP], Georgetown, Mercy) had monthly Medicare expenditures less than the control group by 9% to 14% (-$84; 90% CI, -$171 to $4; P=.12; -$358; 90% CI, -$934 to $218; P=.31; and -$112; 90% CI, -$231 to $8; P=.12; respectively). Savings offset fees for HQP and Georgetown but not for Mercy; Georgetown was too small to be sustainable. These programs had favorable effects on none of the adherence measures and only a few of many quality of care indicators examined. CONCLUSIONS Viable care coordination programs without a strong transitional care component are unlikely to yield net Medicare savings. Programs with substantial in-person contact that target moderate to severe patients can be cost-neutral and improve some aspects of care. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00627029.
Failure rate of atraumatic restorative treatment using high-viscosity glass-ionomer cement compared to conventional amalgam restorative treatment in primary and permanent teeth : a systematic review of Chinese trials [ protocol ]

Wang Xiao-yan*, Nie Jie *, Cai Xue *Veerasamy Yengopal**, Steffen Mickenautsch** *Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Street, Haidian District, Beijing, China **SYSTEM Initiative / Department of Community Dentistry, Faculty of Health Sciences, University of the Witwatersrand, 7 York Rd., Parktown/Johannesburg 2193, South Africa.
Setting Up a Buprenorphine Clinic: One Year Later

Buprenorphine is a new FDA-approved medication for treating opioid dependence. There has been little described about the practical aspects of setting up such a practice or clinic. This article describes the practical aspects of using buprenorphine in an outpatient setting based on the one-year experience of a clinic which is housed within a busy outpatient substance abuse clinic in a Veterans Hospital setting. The spectrum of treatment from induction to maintenance and stabilization and, when appropriate, discharge as well as other treatment challenges is discussed. Overall both patients and staff report a positive experience. The purpose of describing this process is to encourage those practitioners that are considering starting buprenorphine clinics to do so. This in turn will make this pharmacotherapeutic option for patients with opioid addiction more widely available.