Correlations between sleep architecture and sleep-related masseter muscle activity in children with sleep bruxism.

BACKGROUND: Sleep bruxism (SB) occurring during No-REM (nREM) sleep and increase in microarousals per hour have been described in adults, but not in children. OBJECTIVE: To assess the correlation between sleep architecture and masseter muscle activity related to sleep bruxism (SB/MMA) in children. MATERIALS AND METHODS: Forty-three children aged 7-12 years (mean age: 9.4 ± 1.3) with confirmed SB underwent a two-night polysomnographic (PSG) study in a sleep laboratory, for accommodation (first night) and data collection (second night). Data on sleep architecture (total sleep duration (TSD), sleep efficiency (SE), sleep onset latency (SOL), REM and nREM sleep duration and proportion and microarousals/hour during REM and nREM sleep) and episodes/hour of SB/MMA were recorded. Single and multiple-variable linear regression analyses were performed to assess the correlation between data on sleep architecture (predictors) and SB/MMA (dependent variable). RESULTS: Shorter TSD, REM and nREM stage 1 sleep duration, longer SOL and more microarousals/hour during REM and nREM sleep were found to be positive predictors of SB/MMA in children in the multiple-variable regression analysis (R2  = 0.511). CONCLUSION: Within the limitations of this study, it can be concluded that SB/MMA is correlated with altered sleep architecture in children (shorter total sleep duration (TSD), shorter nREM and REM sleep and higher microarousals during REM and nREM sleep). Nevertheless, the clinical significance of these findings need to be demonstrated in future studies.

Therapeutic Use of the Antimicrobial Peptide PNR20 to Resolve Disseminated Candidiasis in a Murine Model.

Invasive fungal infections (IFIs) caused by Candida species are an emerging threat globally, given that patients at-risk and antifungal resistance are increasing. Antimicrobial peptides (AMPs) have shown good therapeutic capacity against different multidrug-resistant (MDR) microorganisms. This study evaluated the activity of the synthetic peptide, PNR20, against Candida albicans ATCC 10231 and a MDR Colombian clinical isolate of Candida auris. Perturbation of yeast cell surface was evaluated using scanning electron microscopy. Cell viability of Vero cells was determined to assess peptide toxicity. Additionally, survival, fungal burden, and histopathology of BALB/c mice infected intravenously with each Candida species and treated with PNR20 were analyzed. Morphological alterations were identified in both species, demonstrating the antifungal effect of PNR20. In vitro, Vero cells' viability was not affected by PNR20. All mice infected with either C. albicans or C. auris and treated with PNR20 survived and had a significant reduction in the fungal burden in the kidney compared to the control group. The histopathological analysis in mice infected and treated with PNR20 showed more preserved tissues, without the presence of yeast, compared to the control groups. This work shows that the utilization of PNR20 is a promising therapeutic alternative against disseminated candidiasis.

In Vitro Antifungal Activity of Three Synthetic Peptides against Candida auris and Other Candida Species of Medical Importance.

Candidiasis is an opportunistic infection affecting immunosuppressed and hospitalized patients, with mortality rates approaching 40% in Colombia. The growing pharmacological resistance of Candida species and the emergence of multidrug-resistant Candida auris are major public health problems. Therefore, different antimicrobial peptides (AMPs) are being investigated as therapeutic alternatives to control candidiasis effectively and safely. This work aimed to evaluate the in vitro antifungal activity of three synthetic AMPs, PNR20, PNR20-1, and 35409, against ATCC reference strains of Candida albicans, Candida glabrata, Candida parapsilosis, Candida krusei, and Candida tropicalis, and clinical isolates of C. auris. Antifungal susceptibility testing, determined by broth microdilution, showed that the AMPs have antifungal activity against planktonic cells of all Candida species evaluated. In C. auris and C. albicans, the peptides had an effect on biofilm formation and cell viability, as determined by the XTT assay and flow cytometry, respectively. Also, morphological alterations in the membrane and at the intracellular level of these species were induced by the peptides, as observed by transmission electron microscopy. In vitro, the AMPs had no cytotoxicity against L929 murine fibroblasts. Our results showed that the evaluated AMPs are potential therapeutic alternatives against the most important Candida species in Colombia and the world.

Plasmodium falciparum rhoptry neck protein 4 has conserved regions mediating interactions with receptors on human erythrocytes and hepatocyte membrane.

Plasmodium falciparum-related malaria represents a serious worldwide public health problem due to its high mortality rates. P. falciparum expresses rhoptry neck protein 4 (PfRON4) in merozoite and sporozoite rhoptries, it participates in tight junction-TJ formation via the AMA-1/RON complex and is refractory to complete genetic deletion. Despite this, which PfRON4 key regions interact with host cells remain unknown; such information would be useful for combating falciparum malaria. Thirty-two RON4 conserved region-derived peptides were chemically synthesised for determining and characterising PfRON4 regions having high host cell binding affinity (high activity binding peptides or HABPs). Receptor-ligand interaction/binding assays determined their specific binding capability, the nature of their receptors and their ability to inhibit in vitro parasite invasion. Peptides 42477, 42479, 42480, 42505 and 42513 had greater than 2% erythrocyte binding activity, whilst peptides 42477 and 42480 specifically bound to HepG2 membrane, both of them having micromolar and submicromolar range dissociation constants (Kd). Cell-peptide interaction was sensitive to treating erythrocytes with trypsin and/or chymotrypsin and HepG2 with heparinase I and chondroitinase ABC, suggesting protein-type (erythrocyte) and heparin and/or chondroitin sulphate proteoglycan receptors (HepG2) for PfRON4. Erythrocyte invasion inhibition assays confirmed HABPs' importance during merozoite invasion. PfRON4 800-819 (42477) and 860-879 (42480) regions specifically interacted with host cells, thereby supporting their inclusion in a subunit-based, multi-antigen, multistage anti-malarial vaccine.

Identification of Babesia bovis MSA-1 functionally constraint regions capable of binding to bovine erythrocytes.

Merozoite surface antigen-1 is a glycoprotein expressed by Babesia bovis and is considered a vaccine candidate given that antibodies against it are able to partially block in vitro invasion of bovine erythrocytes. Despite this, no study to date has confirmed the target cell binding properties of the full MSA-1 or its fragments. This research has thus been focused on identifying protein regions playing a role in erythrocyte attachment, based on genetic diversity and natural selection analysis. Two regions under functional constraint (nucleotides 134-428 and 464-629) having a preponderance of negatively-selected signals were identified in silico. Three non-overlapping peptides derived from functionally constraint regions (42422 (39PEGSFYDDMSKFYGAVGSFD58), 42424 (91NALIKNNPMIRPDLFNATIV110) and 42426 (150TDIVEEDREKAVEYFKKHVY169)) were able to specifically bind to a sialoglycoprotein located on the bovine erythrocyte surface as confirmed by sensitive and specific peptide-cell interaction competition assays using both enzymatically treated and untreated red blood cells. Interestingly, it was predicted that peptides 42422 and 42426 have a helical structure and conserved motifs in all strain/isolates. These findings provide evidence, for the first time, related to B. bovis MSA-1 short regions used by the parasite in erythrocyte binding which could be predicted using natural selection analysis. Future work focused on evaluating these peptides' antigenic ability during natural infection, and their ability to induce protection in immunisation assays are needed to confirm their usefulness as synthetic vaccine candidates.

How to Combat Gram-Negative Bacteria Using Antimicrobial Peptides: A Challenge or an Unattainable Goal?

Antimicrobial peptides (AMPs) represent a promising and effective alternative for combating pathogens, having some advantages compared to conventional antibiotics. However, AMPs must also contend with complex and specialised Gram-negative bacteria envelops. The variety of lipopolysaccharide and phospholipid composition in Gram-negative bacteria strains and species are decisive characteristics regarding their susceptibility or resistance to AMPs. Such biological and structural barriers have created delays in tuning AMPs to deal with Gram-negative bacteria. This becomes even more acute because little is known about the interaction AMP-Gram-negative bacteria and/or AMPs' physicochemical characteristics, which could lead to obtaining selective molecules against Gram-negative bacteria. As a consequence, available AMPs usually have highly associated haemolytic and/or cytotoxic activity. Only one AMP has so far been FDA approved and another two are currently in clinical trials against Gram-negative bacteria. Such a pessimistic panorama suggests that efforts should be concentrated on the search for new molecules, designs and strategies for combating infection caused by this type of microorganism. This review has therefore been aimed at describing the currently available AMPs for combating Gram-negative bacteria, exploring the characteristics of these bacteria's cell envelop hampering the development of new AMPs, and offers a perspective regarding the challenges for designing new AMPs against Gram-negative bacteria.

Sleep bruxism in children: relationship with screen-time and sugar consumption.

OBJECTIVE/BACKGROUND: Consumption of added sugar and excessive screen-time is increasing worldwide and is associated with sleeping and behavior disorders, which are related with possible Sleep Bruxism (SB) in children. Therefore, the objective of this investigation was to examine the relationship between screen-time and sugar-consumption and possible SB in children. PATIENTS/METHODS: A cross-sectional study, including parents of 460 4- to 8-year-old children, was performed. Frequency of possible SB was assessed with the Children's Sleep Habits Questionnaire; sugar consumption with the Health Behaviour in School-Aged Children Food-Frequency Questionnaire. Comprehensive measures of screen-time (including cell phones, computers, electronic devices, electronic games, and TV) were taken. The time was recorded in hour/day. All data were analyzed with STATA© data analysis and statistical software version 13.0 (Copyright 1996-2016; Stata-Corp LP, College Station, TX, USA). Spearman correlation test and ordinal-multiple-variable regression analyses were used. RESULTS: Data of 440 subjects Mean age 6.2 years (S.D. 1.8) were analyzed. Prevalence of possible SB was 35% and screen-time was available for 92.9% of the children. Mean screen-time was 2.1 h/day. Parents reported 73% of the children (n = 319) to consume added sugar once a day every day and 20% more than once every day. Correlations of possible SB were statistically significant with screen-time (Rho = 0.8; p = 0.002) and sugar-consumption (Rho = 0.7; p = 0.03). Associations were found between possible SB and increase-to-increase screen-time and sugar-consumption (OR > 2). CONCLUSION: The results of this study demonstrated that as screen-time and sugar consumption increased, the frequency of bruxism in children increased.

Shorter Antibacterial Peptide Having High Selectivity for E. coli Membranes and Low Potential for Inducing Resistance.

Antimicrobial peptides (AMPs) have been recognised as a significant therapeutic option for mitigating resistant microbial infections. It has been found recently that Plasmodium falciparum-derived, 20 residue long, peptide 35409 had antibacterial and haemolytic activity, making it an AMP having reduced selectivity, and suggesting that it should be studied more extensively for obtaining new AMPs having activity solely targeting the bacterial membrane. Peptide 35409 was thus used as template for producing short synthetic peptides (<20 residues long) and evaluating their biological activity and relevant physicochemical characteristics for therapeutic use. Four of the sixteen short peptides evaluated here had activity against E. coli without any associated haemolytic effects. The 35409-1 derivative (17 residues long) had the best therapeutic characteristics as it had high selectivity for bacterial cells, stability in the presence of human sera, activity against E. coli multiresistant clinical isolates and was shorter than the original sequence. It had a powerful membranolytic effect and low potential for inducing resistance in bacteria. This peptide's characteristics highlighted its potential as an alternative for combating infection caused by E. coli multiresistant bacteria and/or for designing new AMPs.

Designing and optimizing new antimicrobial peptides: all targets are not the same.

Because the resistance of microorganisms to the available antibiotics is a growing healthcare problem worldwide, the search for new antimicrobial peptides (AMPs) that provide useful therapeutic options has been increasing in importance. Many initial candidates have had to be discarded after having advanced to the preclinical and clinical stages. This has led to substantial losses in terms of time and money. For that reason, the essential characteristics of AMPs (i.e. their activity, selectivity, stability in physiological conditions and low production cost) must be considered in their design. In addition, peptides could be active against several kinds of cells with activity and selectivity resulting from interaction with multiple target cell components, which sometimes are present in mammalian cells as well. Thus, the cellular composition is important in the AMP-target cell interaction and must be considered in the design of AMPs, too. This review describes general aspects of AMP design, limitations concerning their therapeutic application, and optimization strategies for overcoming such limitations.

Effect of face mask therapy on mandibular rotation considering initial and final vertical growth pattern: A longitudinal study.

Objectives: To evaluate the effect of maxillary protraction with facemask therapy on mandibular rotation taking into account the initial and final vertical growth pattern of each participant in order to evaluate our null hypothesis: The use of facemask in these patients does not modify their initial vertical growth pattern. Material and Methods: A prospective single cohort study included children with Class III malocclusion treated with rapid palatal expansion and maxillary protraction with facemask. Cephalograms were taken before commencement and after completion of the facemask therapy with standardized equipment and magnification. Intraindividual cephalometric measurements were compared, and the vertical growth patterns were classified according to cephalometric standards. Potential changes in vertical growth pattern before and after completion of the facemask therapy was assessed by measuring Pearson's chi­square and by multiple correspondence analysis. Results: Thirty­eight study participants were recruited, aged between 5.2 to 9.5 years (mean 7.5) at the commencement of facemask therapy, which lasted on average 1.6 years. Differences on pretherapy and posttherapy cephalograms were seen for linear rotational and sagittal measurements (p < .01) as well as angular measurements of the cranial base, including an average palatal plane rotation of 0.45° (standard deviation: 1.78) and an average mandibular rotation of 0.39° (standard deviation: 2.19). The majority of participants maintained their initial vertical growth pattern after facemask therapy according to the multiple correspondence analysis (p < .001). Conclusion: Facemask therapy does not modify vertical growth pattern. The observed changes suggest a trend of maintaining each patient's initial growth direction after therapy.

Agreement between jaw-muscle activity measurement with portable single-channel electromyography and polysomnography in children.

BACKGROUND: Polysomnography (PSG) is the gold standard for sleep bruxism (SB) assessment. High economical costs, complex technical equipment, and unfamiliar laboratory setting limit its use in children. AIM: To determine the night-to-night variability of electromyography (EMG) episodes during a five-night recording with the GrindCare Measure (GCM), and the agreement in the assessment of masticatory muscle activity (MMA) between GCM and PSG in children. DESIGN: Forty-seven children from clinics of Universidad CES participated. Each participant was assessed with GCM for five consecutive nights. The last night, children underwent a single-night PSG study, together with the GCM. Spearman correlation coefficients were used to analyze data. RESULTS: The frequency of SB occurrence was 'sometimes' in 12 (25.5%) and 'usually' in 19 (40.4%) children. Simultaneous measurements with GCM and PSG obtained during the fifth night of measurement were not significantly correlated. Correlation between GCM total EMG episodes and EMG episodes/h and PSG total SB episodes, SB episodes/h, total bursts and burst/h measured with PSG was also not significant. CONCLUSION: EMG measurement with GCM was not accurate to detect PSG/SB in children. There was not advantage of multiple assessment for five nights with GCM, reducing the impact of night-to-night EMG episodes' variability on the GCM/PSG correlation.

Diagnostic accuracy of the use of parental-reported sleep bruxism in a polysomnographic study in children.

BACKGROUND: Polysomnography (PSG) is the gold standard for sleep bruxism (SB) diagnosis. PSG/SB children's criteria are not available; thus, parental-report SB is widely used. AIM: Assessing the diagnostic accuracy of parental report of sleep tooth grinding (STG) with a PSG/SB diagnosis in children, adopting adult criteria. DESIGN: Thirty-seven children from clinics of Universidad CES were included. Parents filled the Children's Sleep Habits Questionnaire (CSHQ) assessing the single-observation report - CSHQ - of STG with a No/Yes answer and five ordinal answers. A 5-day diary reporting the presence/absence of STG (multiple-observation report) was also completed. Each child underwent a single-night PSG study. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, likelihood ratios, Spearman correlation coefficient, and Cohen's kappa coefficient were used to analyze data. RESULTS: Single observation, using No/Yes answer, showed acceptable specificity and NPV, while low PPV and sensitivity. Accuracy and likelihood ratios were low. When using the five ordinal answers, weak correlation and fair agreement (r = 0.34 and κ = 0.40) with PSG/SB adult criteria were found. Multiple-observation evaluation of STG presented moderate correlation and agreement (r = 0.50 and κ = 0.48). CONCLUSIONS: Although multiple-observation report achieved better agreement than single-observation report, our results failed supporting the validity of report strategies for the diagnosis of SB in children, as an equivalent of PSG/SB adult criteria.

A New Synthetic Peptide Having Two Target of Antibacterial Action in E. coli ML35.

The increased resistance of microorganisms to the different antimicrobials available to today has highlighted the need to find new therapeutic agents, including natural and/or synthetic antimicrobial peptides (AMPs). This study has evaluated the antimicrobial activity of synthetic peptide 35409 (RYRRKKKMKKALQYIKLLKE) against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 15442 and Escherichia coli ML 35 (ATCC 43827). The results have shown that peptide 35409 inhibited the growth of these three bacterial strains, having 16-fold greater activity against E. coli and P. aeruginosa, but requiring less concentration regarding E. coli (22 µM). When analyzing this activity against E. coli compared to time taken, it was found that this peptide inhibited bacterial growth during the first 60 min and reduced CFU/mL 1 log after 120 min had elapsed. This AMP permeabilized the E. coli membrane by interaction with membrane phospholipids, mainly phosphatidylethanolamine, inhibited cell division and induced filamentation, suggesting two different targets of action within a bacterial cell. Cytotoxicity studies revealed that peptide 35409 had low hemolytic activity and was not cytotoxic for two human cell lines. We would thus propose, in the light of these findings, that the peptide 35409 sequence should provide a promising template for designing broad-spectrum AMPs.

El menor de seis años: Situación de caries y conocimientos y prácticas de cuidado bucal de sus madres / Caries prevalence of six year old children and knowledge of oral hygiene health practices of their mothers

Con el objetivo de identificar la frecuencia de la caries dental en niños y niñas menores de seis años residentes en la ciudad de Medellín y describir los conocimientos y las practicas de cuidado bucal de sus madres, se realizó un examen clínico bucal a 365 niños de los estratos socioeconómicos medio-alto (MA) y bajo (B) y se entrevistaron con base en una encuesta estructurada, 346 madres. El diagnóstico de caries se basó en la propuesta de clasificación de Pitts y Fyffe. La prevalencia de caries en el estrato MA fue del 48.4 por ciento y en el B del 58.3 por ciento. Se encontró caries dental desde el primer año de edad, en ambos estratos. El promedio de superficies afectada por caries es de 3.4 y 6.6 para el estrato MA y B respectivamente. Se encontró una diferencia significativa en el nivel de escolaridad de las madres. El 42 por ciento de las madres del MA Y el 50 por ciento del B afirman no haber recibido información sobre el cuidado bucal de sus hijos. En el momento del estudio se encontró que el 18 por ciento de los niños presentaban hábito prolongado del biberón y el 50 por ciento de las madres tenían la costumbre de dejar dormir el niño con el tetero. Los hallazgos de este estudio sugieren que la caries dental sigue siendo un problema frecuente en los menores de seis años en Medellín; por lo tanto es indispensable asumir con continuidad la educación de las madres y cuidadoras para la verdadera promoción de la salud bucal, con temáticas específicas que trasciendan la acción educativa de la transmisión de información a prácticas de instrucción y adiestramiento para el desarrollo de destrezas...

Elementos de análisis para la estructuración de un programa docente asistencial. Vereda el Zancudo (Fredonia, Antioquia), 1998. I Parte: Estado de Salud Bucal de Población / Elements of analysis for the design and implementation of a teaching assistance program, in the communities of El Zancudo y Fredonia in Colombia. Part I: Oral health status of the population

En este estudio se describe el estado de salud bucal de la población de la vereda el Zancudo (Fredonia- Antioquia). Se realizó examen clínico bucal a una muestra de 150 personas para determinar los niveles de caries dental, enfermedad periodontal y las necesidades de prótesis. En términos generales puede afirmarse que la situación de salud bucal de la población estudiada es un nivel aceptable principalmente en la población joven. Las personas menores de 20 años tienen alto grado de conservación dentaria, baja historia de caries dental y buena salud gingival. En los mayores de 20 años hay un deterioro evidente de estas condiciones pero los indicadores de enfermedad son más bajos que los reportados en el último estudio Nacional de salud bucal. Con base en estos resultados puede afirmarse que el programa docente asistencial debe estructurarse para responder a tres retos: -Mantener los buenos niveles de salud bucal encontrados en la población escolar, -Reformular programas educativos y de mercadeo social que tengan efectos sobre las conductas, hábitos y comportamiento de la población y -Garantizar actividades de recuperación de la salud para todos los grupos de edad...

Descripción de la mortalidad por leucemia en Bogotá: enero-diciembre de 1987 / Description of mortality due to leukemia in Bogotá: January 1 to December 31 1986

Se realizó un estudio descriptivo sobre la mortalidad por leucemia en Bogotá, de Enero 1 a Diciembre 31 de 1987, teniendo como universo el total de fallecidos cuya causa de muerte en el certificado médico de defunción fue "Leucemia". A partir de esta información se obtuvo un universo de 269 casos de los cuales 213 fallecieron en institución y 55 en casa. Con el fin de confrontar y complementar la información obtenida se revisaron y analizaron las historias clínicas respectivas en 24 instituciones. Al tabular los datos se tuvieron en cuenta las variables: edad, sexo, residencia en Bogotá, estrato socioeconómico, tipo de Leucemia y causa desencadenante de muerte. A partir de los datos obtuvimos indicadores epidemiologícos que incluyen tasas, proporciones y concordancia diagnóstica. Dentro de los hallazgos más sobresalientes para nuestro estudio encontramos que la mortalidad por leucemia en Bogotá no esta disminuyendo proporcionalmente con la mortalidad general. Se presentaron más defunciones por Leucemias Agudas que por crónicas y predominaron las Linfoides sobre las Mieloides. Las leucemias crónicas de acuerdo a nuestro estudio y a la literatura no se presentan en menores de 15 años; a diferencia de las leucemias agudas que se presentaron en todos los grupos etáreos. Se destaca una mayor mortalidad en hombres que en mujeres por todos los tipos de leucemia, siendo más notoria la diferencia en las leucemias linfoide que en mieloides. La principal causa desencadenante de muerte para LLC es por la infiltración leucémica propiamente dicha, mientras que para los otros tipos se presentan en igual proporción hemorragias, infecciones e infiltración leucémica propiamente dicha