Caregiver attitudes and beliefs associated with compliance to childhood immunization in Bamenda, Cameroon

Children who are up-to-date on their immunization schedule have a good chance of resisting diseases that are vaccine-preventable. The proper use of vaccines is one of the most cost-effective methods that can be used to control the spread of infectious diseases.The factors associated with children being up-to-date on their immunization schedule are many. The decision to immunize children is made by the caregiver, because a child cannot make this decision. Caregivers\u27 attitudes and beliefs about immunization and vaccine-preventable diseases influence the decisions they make.The purpose of this study was to analyze the relationship of caregivers\u27 beliefs and attitudes to childhood immunization compliance in Bamenda, Cameroon. The current rate of childhood immunization in Cameroon is 36%. This rate is very low and so the urgency to determine factors influencing immunization compliance. It is important to know caregiver beliefs and attitudes associated with compliance to childhood immunization so these could be addressed if they would lead to an increase in immunization compliance. The Health Belief Model and self-efficacy constructs were used as the theoretical framework.To access caregiver beliefs and attitudes a survey instrument based on constructs of the Health Belief Model and self-efficacy was modified, pilot tested and validated for use in this study. Participants were present with their children for admission into class one at randomly selected primary schools in Bamenda,Cameroon. The data for this study are presented in a descriptive and analytical format. Logistic regression, MANOVA and chi-square techniques were used for analysis.The following major conclusions are drawn from this study:Location of residence and level of education were associated with compliance to childhood immunization. Caregivers whose level of education was higher than classes seven were more likely to be compliant to childhood immunization than those whose level were lower than class seven. Perceived susceptibility, severity, and self efficacy were associated with compliance to childhood immunization. Self-efficacy increased the predictive ability of the Health Belief Model.Developing health education interventions to address these issues may improve immunization compliance in Bamenda, Cameroon. Further research is needed to address designing programs to reduce childhood mortality by increasing childhood compliance with immunization policie

Safety and feasibility of percutaneous retrograde coronary sinus delivery of autologous bone marrow mononuclear cell transplantation in patients with chronic refractory angina

<p>Abstract</p> <p>Background</p> <p>Chronic refractory angina is a challenging clinical problem with limited treatment options. The results of early cardiovascular stem cell trials using ABMMC have been promising but have utilized intracoronary or intramyocardial delivery. The goal of the study was to evaluate the safety and early efficacy of autologous bone marrow derived mononuclear cells (ABMMC) delivered via percutaneous retrograde coronary sinus perfusion (PRCSP) to treat chronic refractory angina (CRA).</p> <p>Methods</p> <p>From May 2005 to October 2006, 14 patients, age 68 +/- 20 years old, with CRA and ischemic stress-induced myocardial segments assessed by SPECT received a median 8.19*10⁸± 4.3*10⁸mononuclear and 1.65*10⁷± 1.42*10⁷CD34⁺cells by PRCSP..</p> <p>Results</p> <p>ABMMC delivery was successful in all patients with no arrhythmias, elevated cardiac enzymes or complications related to the delivery. All but one patient improved by at least one Canadian Cardiovascular Society class at 2 year follow-up compared to baseline (p < 0.001). The median baseline area of ischemic myocardium by SPECT of 38.2% was reduced to 26.5% at one year and 23.5% at two years (p = 0.001). The median rest left ventricular ejection fraction by SPECT at baseline was 31.2% and improved to 35.5% at 2 year follow up (p = 0.019).</p> <p>Conclusions</p> <p>PRCSP should be considered as an alternative method of delivery for cell therapy with the ability to safely deliver large number of cells regardless of coronary anatomy, valvular disease or myocardial dysfunction. The clinical improvement in angina, myocardial perfusion and function in this phase 1 study is encouraging and needs to be confirmed in randomized placebo controlled trials.</p

Structural basis of rotavirus RNA chaperone displacement and RNA annealing.

Rotavirus genomes are distributed between 11 distinct RNA molecules, all of which must be selectively copackaged during virus assembly. This likely occurs through sequence-specific RNA interactions facilitated by the RNA chaperone NSP2. Here, we report that NSP2 autoregulates its chaperone activity through its C-terminal region (CTR) that promotes RNA-RNA interactions by limiting its helix-unwinding activity. Unexpectedly, structural proteomics data revealed that the CTR does not directly interact with RNA, while accelerating RNA release from NSP2. Cryo-electron microscopy reconstructions of an NSP2-RNA complex reveal a highly conserved acidic patch on the CTR, which is poised toward the bound RNA. Virus replication was abrogated by charge-disrupting mutations within the acidic patch but completely restored by charge-preserving mutations. Mechanistic similarities between NSP2 and the unrelated bacterial RNA chaperone Hfq suggest that accelerating RNA dissociation while promoting intermolecular RNA interactions may be a widespread strategy of RNA chaperone recycling

Assessment of treatment outcomes of multidrug-resistant tuberculosis patients in D R Congo: A study based on drug regimens used between 2007 to 2017: Évaluation des issues thérapeutiques des patients atteints de la tuberculose à bacilles multi résistants : étude basée sur les régimes de médicaments utilisés en République Démocratique du Congo de 2007 à 2017

Context. Little is known about therapeutic successes in MDR-TB patients under regimens containing second-line molecules. The present study aimed to assess therapeutic outcomes in patients under therapeutic regimens applied in DR Congo. Methods. This historical cohort study has included confirmed MDR-TB patients who received treatment between 2007 and 2017 in 218 TB centers in DR Congo. Treatment outcome and survival at 36 months were analyzed using Zscore and chi square test. Kaplan-Meier method was performed to describe survival and Log Rank test helped in comparing curve based on the therapeutical regimen. Factors associated with therapeutic success and mortality predictors were assessed using multivariate logistic regression and Cox regression analysis, respectively. Results. The therapeutic success in the study group (n=1,724) was 72% (range 68-74%) for all regimen combined. The average death rate was 12.8% although the group of patients receiving Cyclosérine and Ofloxacine was the most affected (16%). The death rate was significantly higher in patients living in urban areas (15.2% versus 14.9%, p = 0.013) and also among MDR-TB/HIV co-infected patients (28.4% vs 15.7%, p&lt;0.001) patients. The median survival of the study group was 722.7 days compared to 601.1 days for MDR-TB/HIV co-infected patients, and 736.7 days for HIV negative patients (p&lt;0.001). Conclusion. Therapeutic successes are significant for the short regimen. However, the death rate remains high when Cycloserine and Ofloxacin are included in the regimen. The predictors of mortality are HIV infection and living in urban areas. Contexte. L’issue thérapeutique de la tuberculose multi résistante (TB-MR) sous les molécules de deuxième intention n’est pas très bien connue. La présente étude a évalué les régimes thérapeutiques appliqués, en termes de succès thérapeutique et de survie. Méthodes. L’étude de cohorte historique a inclu les patients TB-MR confirmés et traités entre 2007 et 2017 dans 218 centres de tuberculose en RD Congo. L’issue thérapeutique et la survie à 36 mois ont été analysées. Le score Z ou le test de chi carré ont comparé des issues. La méthode de Kaplan-Meier a décrit les courbes de survie et le test de Log Rank a comparé la survie en fonction du regime therapeutique. Les facteurs associés au succès thérapeutique et les prédicteurs de mortalité ont été analysés respectivement, par l’analyse multivariée de régression logistique et de Cox. Résultats. Dans le groupe étudié (n=1724), le succès thérapeutique a été de 72% (68-74%) pour l’ensemble des régimes. Le taux était plus élevé pour le régime court (74%) et plus faible pour le régime contenant la Cyclosérine et l’Ofloxacine (68%). La moyenne de décès était de 12,8% ; mais plus élevée dans le groupe sous regime contenant la Cyclosérine et l’Ofloxacine (16%). Le taux de décès était significativement plus élevé en milieu urbain (15,2% versus 14,9 %, p = 0,013) et également chez les sujets co-infectés par la MDR-TB&nbsp; et le VIH (28.4% vs 15.7%, p &lt;0,001). La survie médiane dans le groupe était de 722,7 jours contre 601,1 jours chez les co-infectés MDR-TB/VIH, et de 736,7 jours) chez les patients VIH négatifs (p&lt;0,001). Conclusion. Les succès thérapeutiques sont acceptables en particulier, pour le régime court ; toutefois, le taux de décès demeure encore très élevé dans le groupe sous Cyclosérine et Ofloxacine. Les prédicteurs de mortalité sont l’infection à VIH et la vie citadine. &nbsp

Tale proteins bind to both active and inactive chromatin

TALE (transcription activator-like effector) proteins can be tailored to bind to any DNA sequence of choice and thus are of immense utility for genome editing and the specific delivery of transcription activators. However, to perform these functions, they need to occupy their sites in chromatin. In the present study, we have systematically assessed TALE binding to chromatin substrates and find that in vitro TALEs bind to their target site on nucleosomes at the more accessible entry/exit sites, but not at the nucleosome dyad. We show further that in vivo TALEs bind to transcriptionally repressed chromatin and that transcription increases binding by only 2-fold. These data therefore imply that TALEs are likely to bind to their target in vivo even at inactive loci

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Truncating mutations in the Wilson disease gene ATP7B are associated with very low serum ceruloplasmin oxidase activity and an early onset of Wilson disease

<p>Abstract</p> <p>Background</p> <p>Mutations in the gene ATP7B cause Wilson disease, a copper storage disorder with a high phenotypic and genetic heterogeneity. We aimed to evaluate whether 'severe' protein-truncating ATP7B mutations (SMs) are associated with low serum ceruloplasmin oxidase activities and an early age of onset when compared to missense mutations (MMs).</p> <p>Methods</p> <p>The clinical phenotype of 59 genetically confirmed WD patients was analyzed retrospectively. Serum ceruloplasmin was measured by its oxidase activity with <it>o</it>-dianisidine dihydrochloride as substrate and immunologically.</p> <p>Results</p> <p>Thirty-nine patients had two MMs, 15 had the genotype SM/MM, and 5 patients had two SMs on their ATP7B alleles. Enzymatic and immunologic serum ceruloplasmin levels differed significantly between the three groups (P < 0.001 and P < 0.01, respectively). The lowest levels were measured in patients with two SMs (0.0 U/L; IQR, 0.0-0.0 U/L and 0.02 g/L; IQR, 0.01-0.02 g/L, respectively) and the highest in patients with two MMs (17.8 U/L; IQR, 5.8-35.1 U/L and 0.11 g/L; IQR,0.10-0.17 g/L, respectively). The age of onset was also significantly different between the three patient groups (P < 0.05), with SM/SM patients showing the earliest onset (13 years; IQR, 9-13 years) and patients with two MMs showing the latest onset (22 years; IQR, 14-27 years). By ROC curve analysis a ceruloplasmin oxidase level ≤ 5 U/L can predict the presence of at least one SM with a sensitivity of 80% and a specificity of 79.5%.</p> <p>Conclusions</p> <p>In our German study cohort truncating ATP7B mutations were associated with lower ceruloplasmin serum oxidase levels and an earlier age of onset when compared to MMs. Measurement of serum ceruloplasmin oxidase might help to predict presence of truncating ATP7B mutations and might facilitate the mutation analysis.</p

NOTCH3 Expression Is Linked to Breast Cancer Seeding and Distant Metastasis

Background: Development of distant metastases involves a complex multistep biological process termed the invasion-metastasis cascade, which includes dissemination of cancer cells from the primary tumor to secondary organs. NOTCH developmental signaling plays a critical role in promoting epithelial-to-mesenchymal transition, tumor stemness, and metastasis. Although all four NOTCH receptors show oncogenic properties, the unique role of each of these receptors in the sequential stepwise events that typify the invasion-metastasis cascade remains elusive. Methods: We have established metastatic xenografts expressing high endogenous levels of NOTCH3 using estrogen receptor alpha-positive (ERα+) MCF-7 breast cancer cells with constitutive active Raf-1/mitogen-associated protein kinase (MAPK) signaling (vMCF-7Raf-1) and MDA-MB-231 triple-negative breast cancer (TNBC) cells. The critical role of NOTCH3 in inducing an invasive phenotype and poor outcome was corroborated in unique TNBC cells resulting from a patient-derived brain metastasis (TNBC-M25) and in publicly available claudin-low breast tumor specimens collected from participants in the Molecular Taxonomy of Breast Cancer International Consortium database. Results: In this study, we identified an association between NOTCH3 expression and development of metastases in ERα+ and TNBC models. ERα+ breast tumor xenografts with a constitutive active Raf-1/MAPK signaling developed spontaneous lung metastases through the clonal expansion of cancer cells expressing a NOTCH3 reprogramming network. Abrogation of NOTCH3 expression significantly reduced the self-renewal and invasive capacity of ex vivo breast cancer cells, restoring a luminal CD44low/CD24high/ERαhigh phenotype. Forced expression of the mitotic Aurora kinase A (AURKA), which promotes breast cancer metastases, failed to restore the invasive capacity of NOTCH3-null cells, demonstrating that NOTCH3 expression is required for an invasive phenotype. Likewise, pharmacologic inhibition of NOTCH signaling also impaired TNBC cell seeding and metastatic growth. Significantly, the role of aberrant NOTCH3 expression in promoting tumor self-renewal, invasiveness, and poor outcome was corroborated in unique TNBC cells from a patient-derived brain metastasis and in publicly available claudin-low breast tumor specimens. Conclusions: These findings demonstrate the key role of NOTCH3 oncogenic signaling in the genesis of breast cancer metastasis and provide a compelling preclinical rationale for the design of novel therapeutic strategies that will selectively target NOTCH3 to halt metastatic seeding and to improve the clinical outcomes of patients with breast cancer

Bacteriophage MS2 genomic RNA encodes an assembly instruction manual for its capsid

Using RNA-coat protein crosslinking we have shown that the principal RNA recognition surface on the interior of infectious MS2 virions overlaps with the known peptides that bind the high affinity translational operator, TR, within the phage genome. The data also reveal the sequences of genomic fragments in contact with the coat protein shell. These show remarkable overlap with previous predictions based on the hypothesis that virion assembly is mediated by multiple sequences-specific contacts at RNA sites termed Packaging Signals (PSs). These PSs are variations on the TR stem-loop sequence and secondary structure. They act co-operatively to regulate the dominant assembly pathway and ensure cognate RNA encapsidation. In MS2, they also trigger conformational change in the dimeric capsomere creating the A/B quasi-conformer, 60 of which are needed to complete the T=3 capsid. This is the most compelling demonstration to date that this ssRNA virus, and by implications potentially very many of them, assemble via a PS-mediated assembly mechanism