Parent-proxy pediatric CMT quality of life outcome measure: Validation of the Italian version.

BACKGROUND AND AIMS: The parent-proxy reports can offer complementary informations or be the only source of Quality of Life measurement in young children. The aim of this study was to provide and validate the Italian version of the recently published parent-proxy pCMT-QOL for patients aged 8-18 years old, making it available for possible trials in Italian speaking children. METHODS: The English-language instrument was translated and adapted into the Italian language using standard procedures: translation, transcultural adaptation, and back-translation. Parent-proxy pCMT-QOL was administered to parents of patients with a genetic diagnosis of CMT, aged 8-18 years old. All parents were retested 2 weeks later to assess reliability. RESULTS: A total of 21 parents of CMT patients (18 CMT1A, 2 CMT2A, 1 CMT2K) were assessed during their children clinical appointments. The Italian-pCMT-QOL showed a high test-retest reliability; none of the parents had any difficulties with the completion of the questionnaire and no further revisions were necessary after completion. INTERPRETATION: The Italian parent-proxy pCMT-QOL is a reliable, culturally adapted, and comparable version of the original English instrument. This questionnaire will improve the quality of the follow-up and will make it possible to monitor more accurately the severity of the disease in Italian-speaking families.

Neuropathy due to bi-allelic SH3TC2 variants: genotype-phenotype correlation and natural history.

Recessive SH3TC2 variants cause Charcot-Marie-Tooth disease type 4C (CMT4C). CMT4C is typically a sensorimotor demyelinating polyneuropathy, marked by early onset spinal deformities, but its clinical characteristics and severity are quite variable. Clear relationships between pathogenic variants and the spectrum of disease manifestations are to date lacking. Gene replacement therapy has been shown to ameliorate the phenotype in a mouse model of CMT4C, emphasizing the need for natural history studies to inform clinical trial readiness. Data, including both genetic information and clinical characteristics, were compiled from the longitudinal, prospective dataset of the Inherited Neuropathy Consortium, a member of the Rare Diseases Clinical Research Network (INC-RDCRN). The Charcot Marie Tooth Neuropathy Score (CMTNS), Examination Score (CMTES) and the Rasch-weighted CMTES (CMTES-R) were used to describe symptoms, neurological examinations and neurophysiological characteristics. Standardized response means were calculated at yearly intervals and a mixed model for repeated measures was used to estimate the change in CMTES and CMTES-R over time. Fifty-six individuals (59% female), median age 27 years (range 2-67 years) with homozygous or compound heterozygous variants in SH3TC2 were identified, including 34 unique variants, 14 of which have not previously been published. Twenty-eight participants had longitudinal data available. While there was no significant difference in the CMTES in those with protein truncating versus non-protein truncating variants, there were significant differences in the mean ulnar nerve compound muscle action potential amplitude, the mean radial sensory nerve action potential amplitude, and in the prevalence of scoliosis, suggesting the possibility of a milder phenotype in individuals with one or two non-protein-truncating variants. Overall, the mean value of the CMTES was 13, reflecting moderate clinical severity. There was a high rate of scoliosis (81%), scoliosis surgery (36%), and walking difficulty (94%) among study participants. The CMTES and CMTES-R appeared moderately responsive to change over extended follow-up, demonstrating a standardized response mean of 0.81 standard deviation units or 0.71 standard deviation units, respectively, over 3 years. Our analysis represents the largest cross-sectional and only longitudinal study to date, of the clinical phenotype of both adults and children with CMT4C. With the promise of upcoming genetic treatments, these data will further define the natural history of the disease and inform study design in preparation for clinical trials.

Metagenomic analysis examines oral microbiome changes and interplay with immune response following prenatal total oral rehabilitation.

BACKGROUND: Suboptimal maternal oral health during pregnancy is potentially associated with adverse birth outcomes and increased dental caries risks in children. This study aimed to assess the oral microbiome and immune response following an innovative clinical regimen, Prenatal Total Oral Rehabilitation (PTOR), that fully restores women's oral health to a "disease-free status" before delivery. METHODS: This prospective cohort study assessed 15 pregnant women at baseline and 3 follow-up visits (1 week, 2 weeks, and 2 months) after receiving PTOR. The salivary and supragingival plaque microbiomes were analyzed using metagenomic sequencing. Multiplexed Luminex cytokine assays were performed to examine immune response following PTOR. The association between salivary immune markers and oral microbiome was further examined. RESULTS: PTOR was associated with a reduction of periodontal pathogens in plaque, for instance, a lower relative abundance of Tannerella forsythia and Treponema denticola at 2 weeks compared to the baseline (p < 0.05). The alpha diversity of plaque microbial community was significantly reduced at the 1-week follow-up (p < 0.05). Furthermore, we observed significant changes in the Actinomyces defective-associated carbohydrate degradation pathway and Streptococcus Gordonii-associated fatty acid biosynthesis pathway. Two immune markers related to adverse birth outcomes significantly differed between baseline and follow-up. ITAC, negatively correlated with preeclampsia severity, significantly increased at 1-week follow-up; MCP-1, positively correlated with gestational age, was elevated at 1-week follow-up. Association modeling between immune markers and microbiome further revealed specific oral microorganisms that are potentially correlated with the host immune response. CONCLUSIONS: PTOR is associated with alteration of the oral microbiome and immune response among a cohort of underserved US pregnant women. Future randomized clinical trials are warranted to comprehensively assess the impact of PTOR on maternal oral flora, birth outcomes, and their offspring's oral health.

Model-based clustering of high-dimensional longitudinal data via regularization.

We propose a model-based clustering method for high-dimensional longitudinal data via regularization in this paper. This study was motivated by the Trial of Activity in Adolescent Girls (TAAG), which aimed to examine multilevel factors related to the change of physical activity by following up a cohort of 783 girls over 10 years from adolescence to early adulthood. Our goal is to identify the intrinsic grouping of subjects with similar patterns of physical activity trajectories and the most relevant predictors within each group. The previous analyses conducted clustering and variable selection in two steps, while our new method can perform the tasks simultaneously. Within each cluster, a linear mixed-effects model (LMM) is fitted with a doubly penalized likelihood to induce sparsity for parameter estimation and effect selection. The large-sample joint properties are established, allowing the dimensions of both fixed and random effects to increase at an exponential rate of the sample size, with a general class of penalty functions. Assuming subjects are drawn from a Gaussian mixture distribution, model effects and cluster labels are estimated via a coordinate descent algorithm nested inside the Expectation-Maximization (EM) algorithm. Bayesian Information Criterion (BIC) is used to determine the optimal number of clusters and the values of tuning parameters. Our numerical studies show that the new method has satisfactory performance and is able to accommodate complex data with multilevel and/or longitudinal effects.

Validation of the parent-proxy pediatric Charcot-Marie-Tooth disease quality of life outcome measure.

Charcot-Marie-Tooth disease (CMT) reduces health-related quality of life (QOL) in children. We have previously developed and validated the English and Italian versions of the pediatric CMT-specific QOL outcome measure (pCMT-QOL) for children aged 8 to 18. There is currently no parent-proxy CMT QOL outcome measure for use in clinical trials, which could provide complementary information in these children and adolescents. This study describes the validation studies conducted to develop the parent-proxy version of the pCMT-QOL outcome measure for children aged 8 to 18 years old. Development and validation of the parent-proxy version of the pCMT-QOL outcome measure for children aged 8 to 18 years old was iterative, involving identifying relevant domains, item pool generation, prospective pilot testing and clinical assessments, structured focus-group interviews, and psychometric testing, conducted on parents of children with CMT seen at participating sites from the USA, United Kingdom, and Australia. We utilized previously described methods to develop a working parent-proxy version of the pCMT-QOL measure. From 2010 to 2016, the parent-proxy pCMT-QOL working version was administered to 358 parents of children with CMT aged 8 to 18, seen at the participating study sites of the Inherited Neuropathies Consortium. The resulting data underwent rigorous psychometric analysis, including factor analysis, test-retest reliability, internal consistency, convergent validity, IRT analysis, and longitudinal analysis, to develop the final parent-proxy version of the pCMT-QOL outcome measure for children aged 8 to 18 years old. The parent-proxy version of the pCMT-QOL outcome measure is a reliable, valid, and sensitive proxy measure of health-related QOL for children aged 8 to 18 with CMT.

Validation of the parent-proxy version of the pediatric Charcot-Marie-Tooth disease quality of life instrument for children aged 0-7 years.

OBJECTIVE: To evaluate the parent-proxy version of the pediatric Charcot Marie Tooth specific quality of life (pCMT-QOL) outcome instrument for children aged 7 or younger with CMT. We have previously developed and validated the direct-report pCMT-QOL for children aged 8-18 years and a parent proxy version of the instrument for children 8-18 years old. There is currently no CMT-QOL outcome measure for children aged 0-7 years old. METHODS: Testing was conducted in parents or caregivers of children aged 0-7 years old with CMT evaluated at participating INC sites from the USA, United Kingdom, and Australia. The development of the instrument was iterative, involving identification of relevant domains, item pool generation, prospective pilot testing and clinical assessments, structured focus group interviews, and psychometric testing. The parent-proxy instrument was validated rigorously by examining previously identified domains and undergoing psychometric tests for children aged 0-7. RESULTS: The parent-proxy pCMT-QOL working versions were administered to 128 parents/caregivers of children aged 0-7 years old between 2010 and 2016. The resulting data underwent rigorous psychometric analysis, including factor analysis, internal consistency, and convergent validity, and longitudinal analysis to develop the final parent-proxy version of the pCMT-QOL outcome measure for children aged 0-7 years old. CONCLUSIONS: The parent-proxy version of the pCMT-QOL outcome measure, known as the pCMT-QOL (0-7 years parent-proxy) is a valid and sensitive proxy measure of health-related QOL for children aged 0-7 years with CMT.

Effects of Nystatin oral rinse on oral Candida species and Streptococcus mutans among healthy adults.

OBJECTIVES: To examine the effect of Nystatin oral rinse on oral Candida species and Streptococcus mutans carriage. MATERIALS AND METHODS: Twenty healthy adults with oral candidiasis participated in the single-arm clinical trial and received Nystatin oral rinse for 7 days, 4 applications/day, and 600,000 International Units/application. Demographic-socioeconomic-oral-medical conditions were obtained. Salivary and plaque Candida species and Streptococcus mutans were assessed at baseline and 1-week and 3-month follow-ups. Twenty-four salivary cytokines were assessed. Candida albicans isolates underwent Nystatin susceptibility test. RESULTS: Half of participants (10/20) were free of salivary C. albicans after using Nystatin rinse. Salivary S. mutans was significantly reduced at 3-month follow-up (p < 0.05). Periodontal status reflected by bleeding-on-probing was significantly improved at 1-week and 3-month follow-ups (p < 0.05). Plaque accumulation was significantly reduced at 1-week follow-up (p < 0.05). Interestingly, the responses to Nystatin oral rinse were not associated with race, gender, age, oral hygiene practice, adherence to Nystatin rinse, or sweet consumption (p > 0.05). No C. albicans isolates were resistant to Nystatin. Furthermore, salivary cytokine eotaxin and fractalkine were significantly reduced at 3-month follow-up among participants who responded to Nystatin rinse (p < 0.05). CONCLUSIONS: The study results indicate that oral antifungal treatment had an effect on S. mutans salivary carriage. Future clinical trials are warranted to comprehensively assess the impact of antifungal treatment on the oral flora other than S. mutans and Candida. CLINICAL RELEVANCE: Due to the potential cariogenic role of oral Candida species, antifungal approaches shed new light on the prevention and management of dental caries from a fungal perspective.

Effect of Probiotic Lactobacillus plantarum on Streptococcus mutans and Candida albicans Clinical Isolates from Children with Early Childhood Caries.

Probiotics interfere with pathogenic microorganisms or reinstate the natural microbiome. Streptococcus mutans and Candida albicans are well-known emerging pathogenic bacteria/fungi for dental caries. In this study, three probiotic Lactobacilli strains (Lactobacillus plantarum 8014, L. plantarum 14917, and Lactobacillus salivarius 11741) were tested on S. mutans and C. albicans clinical isolates using a multispecies biofilm model simulating clinical cariogenic conditions. The ten pairs of clinical isolates of S. mutans and C. albicans were obtained from children with severe early childhood caries. Our study findings show a remarkable inhibitory effect of L. plantarum 14917 on S. mutans and C. albicans clinical isolates, resulting in significantly reduced growth of S. mutans and C. albicans, a compromised biofilm structure with a significantly smaller microbial and extracellular matrix and a less virulent microcolony structure. FurTre, plantaricin, an antimicrobial peptide produced by L. plantarum, inhibited the growth of S. mutans and C. albicans. The mechanistic assessment indicated that L. plantarum 14917 had a positive inhibitory impact on the expression of S. mutans and C. albicans virulence genes and virulent structure, such as C. albicans hypha formation. Future utilization of L. plantarum 14917 and/or its antimicrobial peptide plantaricin could lead to a new paradigm shift in dental caries prevention.

Development and Validation of the Pediatric Charcot-Marie-Tooth Disease Quality of Life Outcome Measure.

OBJECTIVE: Charcot-Marie-Tooth disease (CMT) reduces health-related quality of life (QOL), especially in children. Defining QOL in pediatric CMT can help physicians monitor disease burden clinically and in trials. We identified items pertaining to QOL in children with CMT and conducted validation studies to develop a pediatric CMT-specific QOL outcome measure (pCMT-QOL). METHODS: Development and validation of the pCMT-QOL patient-reported outcome measure were iterative, involving identifying relevant domains, item pool generation, prospective pilot testing and clinical assessments, structured focus-group interviews, and psychometric testing. Testing was conducted in children with CMT seen at participating sites from the USA, United Kingdom, and Australia. RESULTS: We conducted systematic literature reviews and analysis of generic QOL measures to identify 6 domains relevant to QOL in children with CMT. Sixty items corresponding to those domains were developed de novo, or identified from literature review and CMT-specific modification of items from the pediatric Neuro-QOL measures. The draft version underwent prospective feasibility and face content validity assessments to develop a working version of the pCMT-QOL measure. From 2010 to 2016, the pCMT-QOL working version was administered to 398 children aged 8 to 18 years seen at the participating study sites of the Inherited Neuropathies Consortium. The resulting data underwent rigorous psychometric analysis, including factor analysis, test-retest reliability, internal consistency, convergent validity, item response theory analysis, and longitudinal analysis, to develop the final pCMT-QOL patient-reported outcome measure. INTERPRETATION: The pCMT-QOL patient-reported outcome measure is a reliable, valid, and sensitive measure of health-related QOL for children with CMT. ANN NEUROL 2021;89:369-379.

Validation of the Italian version of the pediatric CMT quality of life outcome measure.

The pediatric Charcot-Marie-Tooth (CMT) specific quality of life (QOL) outcome measure (pCMT-QOL) is a recently developed and validated patient-reported measure of health QOL for children with CMT. The aim of this study was to provide and validate an Italian version of the pCMT-QOL. The original English version was translated and adapted into Italian using standard procedures. pCMT-QOL was administered to patients genetically diagnosed with CMT, aged 8 to 18 years. A retest was given 2 weeks later to assess reliability in all patients. A total of 22 patients (median age 14 years, DS 2.5; M:F 1:1) affected with CMT (19 CMT1A, 2 CMT2A, 1 CMT2K) were assessed as part of their clinical visit. The Italian-pCMT-QOL demonstrate a high test-retest reliability. None of the patients experienced difficulty in completing the questionnaire, no further corrections were needed after administration in patients. The Italian-pCMT-QOL is a reliable, culturally adapted and comparable version of the original English pCMT-QOL. This questionnaire is expected to be valuable in monitoring disease progression and useful for future clinical trials in Italian-speaking children with CMT.

Chlorthalidone with potassium citrate decreases calcium oxalate stones and increases bone quality in genetic hypercalciuric stone-forming rats.

To study human idiopathic hypercalciuria we developed an animal model, genetic hypercalciuric stone-forming rats, whose pathophysiology parallels that of human idiopathic hypercalciuria. Fed the oxalate precursor, hydroxyproline, every rat in this model develops calcium oxalate stones. Using this rat model, we tested whether chlorthalidone and potassium citrate combined would reduce calcium oxalate stone formation and improve bone quality more than either agent alone. These rats (113 generation) were fed a normal calcium and phosphorus diet with hydroxyproline and divided into four groups: diets plus potassium chloride as control, potassium citrate, chlorthalidone plus potassium chloride, or potassium citrate plus chlorthalidone. Urine was collected at six, 12, and 18 weeks and kidney stone formation and bone parameters were determined. Compared to potassium chloride, potassium citrate reduced urinary calcium, chlorthalidone reduced it further and potassium citrate plus chlorthalidone even further. Potassium citrate plus chlorthalidone decreased urine oxalate compared to all other groups. There were no significant differences in calcium oxalate supersaturation in any group. Neither potassium citrate nor chlorthalidone altered stone formation. However, potassium citrate plus chlorthalidone significantly reduced stone formation. Vertebral trabecular bone increased with chlorthalidone and potassium citrate plus chlorthalidone. Cortical bone area increased with chlorthalidone but not potassium citrate or potassium citrate plus chlorthalidone. Mechanical properties of trabecular bone improved with chlorthalidone, but not with potassium citrate plus chlorthalidone. Thus in genetic hypercalciuric stone-forming rats fed a diet resulting in calcium oxalate stone formation, potassium citrate plus chlorthalidone prevented stone formation better than either agent alone. Chlorthalidone alone improved bone quality, but adding potassium citrate provided no additional benefit.

Myocardial tissue-specific Dnmt1 knockout in rats protects against pathological injury induced by Adriamycin.

Novel molecular mechanisms of the pathophysiology of heart failure (HF) are continuously being discovered, including epigenetic regulation. Among epigenetic marks, the role of DNA hypomethylation in shaping heart morphology and function in vivo and the pathogenesis of cardiomyopathy and/or HF, especially in adults, has not been clearly established. Here we show that the strong expression of DNA methyltransferase 1 (Dnmt1) is obviously downregulated in the WT adult rat heart with age. By contrast, the expression of Dnmt1 is upregulated suddenly in heart tissues from pressure overload-induced HF mice and adriamycin-induced cardiac injury and HF mice, consistent with the increased expression of Dnmt1 observed in familial hypertrophic cardiomyopathy (FHCM) patients. To further assess the role of Dnmt1, we generated myocardium-specific Dnmt1 knockout (Dnmt1 KO) rats using CRISPR-Cas9 technology. Echocardiographic and histopathological examinations demonstrated that Dnmt1 deficiency is associated with resistance to cardiac pathological changes and protection at the global and organization levels in response to pathological stress. Furthermore, Dnmt1 deficiency in the myocardium restricts the expressional reprogramming of genes and activates pathways involved in myocardial protection and anti-apoptosis in response to pathological stress. Transcriptome and genome-wide DNA methylation analyses revealed that these changes in regulation are linked to alterations in the methylation status of genes due to Dnmt1 knockout. The present study is the first to investigate in vivo the impact of genome-wide cardiac DNA methyltransferase deficiency on physiological development and the pathological processes of heart tissues in response to stress. The exploration of the role of epigenetics in the development, modification, and prevention of cardiomyopathy and HF is in a very preliminary stage but has an infinite future.

Multifunctional aggregation-based fluorescent probe for visualizing intracellular calcium dynamic fluctuations.

Calcium ion (Ca2+) is an indispensable second messenger in living organisms. The impaired Ca2+ handling can induce many diseases. In this paper, we developed a simple and effective method to encapsulate a coumarin-based Ca2+ probe ((E)-2-hydroxy-N'-((7-hydroxy-2-oxo-2H-chromen-8-yl)methylene)-2-phenylacetohydrazide, CPM) into nanoparticles (NPs), and CPM NPs with blue fluorescence were obtained, whose maximum excitation and maximum emission wavelengths were characterized at 365 nm and 450 nm, respectively. The CPM NPs show significant fluorescence enhancement toward Ca2+ over other metal ions, with a limit of determination (LOD) of 0.04 µM. To optimize the optical property of the NPs, CPM and curcumin, which were introduced as the Förster resonance energy transfer (FRET) donor and acceptor, respectively, were co-encapsulated, and bright green CPM@Cur NPs with large stokes shift and narrow emission band width were constructed. Due to their low cytotoxicity and excellent stability, CPM NPs and CPM@Cur NPs were further successfully used to discriminate the primary aortic smooth muscle cells isolated from mice with abnormal Ca2+ homeostasis from their littermate controls. It is worth noting that CPM@Cur NPs exhibit stronger fluorescence signal and diminished background interference, which make them have great potential in the Ca2+ monitoring during biological processes. This strategy opens a new way to synthesize NPs with high brightness and has a potential application prospect in composite sensing and intracellular imaging. CPM@Cur NPs are developed and applied in biological sensing and intracellular Ca2+ imaging, as well as discriminating the cells with abnormal calcium homeostasis.

Chlorthalidone Is Superior to Potassium Citrate in Reducing Calcium Phosphate Stones and Increasing Bone Quality in Hypercalciuric Stone-Forming Rats.

BACKGROUND: The pathophysiology of genetic hypercalciuric stone-forming rats parallels that of human idiopathic hypercalciuria. In this model, all animals form calcium phosphate stones. We previously found that chlorthalidone, but not potassium citrate, decreased stone formation in these rats. METHODS: To test whether chlorthalidone and potassium citrate combined would reduce calcium phosphate stone formation more than either medication alone, four groups of rats were fed a fixed amount of a normal calcium and phosphorus diet, supplemented with potassium chloride (as control), potassium citrate, chlorthalidone (with potassium chloride to equalize potassium intake), or potassium citrate plus chlorthalidone. We measured urine every 6 weeks and assessed stone formation and bone quality at 18 weeks. RESULTS: Potassium citrate reduced urine calcium compared with controls, chlorthalidone reduced it further, and potassium citrate plus chlorthalidone reduced it even more. Chlorthalidone increased urine citrate and potassium citrate increased it even more; the combination did not increase it further. Potassium citrate, alone or with chlorthalidone, increased urine calcium phosphate supersaturation, but chlorthalidone did not. All control rats formed stones. Potassium citrate did not alter stone formation. No stones formed with chlorthalidone, and rats given potassium citrate plus chlorthalidone had some stones but fewer than controls. Rats given chlorthalidone with or without potassium citrate had higher bone mineral density and better mechanical properties than controls, whereas those given potassium citrate did not. CONCLUSIONS: In genetic hypercalciuric stone-forming rats, chlorthalidone is superior to potassium citrate alone or combined with chlorthalidone in reducing calcium phosphate stone formation and improving bone quality.

Patients with advanced chronic kidney disease and vascular calcification have a large hydrodynamic radius of secondary calciprotein particles.

BACKGROUND: The size of secondary calciprotein particles (CPP2) and the speed of transformation (T50) from primary calciprotein particles (CPP1) to CPP2 in serum may be associated with vascular calcification (VC) in patients with chronic kidney disease (CKD). METHODS: We developed a high throughput, microplate-based assay using dynamic light scattering (DLS) to measure the transformation of CPP1 to CPP2, hydrodynamic radius (Rh) of CPP1 and CPP2, T50 and aggregation of CPP2. We used this DLS assay to test the hypothesis that a large Rh of CPP2 and/or a fast T50 are associated with VC in 45 participants with CKD Stages 4-5 (22 without VC and 23 with VC) and 17 healthy volunteers (HV). VC was defined as a Kauppila score >6 or an Adragao score ≥3. RESULTS: CKD participants with VC had larger cumulants Rh of CPP2 {370 nm [interquartile range (IQR) 272-566]} compared with CKD participants without VC [212 nm (IQR 169-315)] and compared with HV [168 nm (IQR 145-352), P < 0.01 for each]. More CPP2 were in aggregates in CKD participants with VC than those without VC (70% versus 36%). The odds of having VC increased by 9% with every 10 nm increase in the Rh of CPP2, after adjusting for age, diabetes, serum calcium and phosphate [odds ratio 1.09, 95% confidence interval (CI) 1.03, 1.16, P = 0.005]. The area under the receiver operating characteristic curve for VC of CPP2 size was 0.75 (95% CI 0.60, 0.90). T50 was similar in CKD participants with and without VC, although both groups had a lower T50 than HV. CONCLUSIONS: Rh of CPP2, but not T50, is independently associated with VC in patients with CKD Stages 4-5.

Oral health and Candida carriage in socioeconomically disadvantaged US pregnant women.

BACKGROUND: Despite the well-documented associations between poor maternal oral health and increased risk for adverse birth outcomes and dental caries in children after birth, prenatal oral health care is under-utilized, especially among the underserved population. In addition, oral Candida has recently been suggested as a potential culprit for children's dental caries, with evident maternal contributions. Therefore, this study aimed to obtain epidemiological data on the oral health and oral Candida carriage in a cohort of underserved US pregnant women, and reveal factors associated with their oral Candida carriage. METHODS: Demographic-medical-oral hygiene practice data were collected. Comprehensive oral examination was conducted. Caries status and plaque index were recorded. Oral samples (saliva, plaque and swab) were processed to identify Candida species and Streptococcus mutans by culturing-dependent and -independent methods. Multiple logistic regression analyses were used to identify factors associated with oral Candida carriage and caries severity. RESULTS: Eighty-two socioeconomically disadvantaged women (48 pregnant and 34 non-pregnant) were enrolled. More pregnant women (79.1%) had > = 1 untreated decayed tooth when compared to their non-pregnant counterparts (47.1%) (p = 0.01). The average number of decayed teeth in pregnant and non-pregnant women was 3.9 and 3.1 (p > 0.05). Caries severity was positively associated with race (African American vs. white), plaque index and salivary Candida albicans level. C. albicans was the most predominant/abundant Candida strain, with cheek and tonsil as the most common colonized sites. The detection of C. albicans was 56%/56% in saliva and 40%/47% in plaque of the pregnant and non-pregnant groups, respectively. Study women's oral Candida carriage is positively associated with hypertension [p = 0.03, odds ratio = 14.47(1.28, 163.51)], decayed teeth number [p = 0.04, odds ratio = 1.31 (1.01,1.69)] and salivary S. mutans level [p = 0.03, odds ratio = 4.80 (1.18-19.43)]. CONCLUSIONS: Socioeconomically disadvantaged US women are in need of improved prenatal oral health, a large proportion of them have untreated decayed teeth and high carriage of oral Candida. Due to the observed significant association between the decayed teeth number and oral Candida carriage, providing oral health care during pregnancy (including limiting decayed teeth) will not only improve women's oral health, but also present as a promising approach to reduce oral Candida carriage in women.

Prenatal Oral Health Care and Early Childhood Caries Prevention: A Systematic Review and Meta-Analysis.

Despite the advancement of early childhood caries (ECC) prediction and treatment, ECC remains a significant public health burden in need of more effective preventive strategies. Pregnancy is an ideal period to promote ECC prevention given the profound influence of maternal oral health and behaviors on children's oral health. However, studies have shown debatable results with respect to the effectiveness of ECC prevention by means of prenatal intervention. Therefore, this study systematically reviewed the scientific evidence relating to the association between prenatal oral health care, ECC incidence, and Streptococcus mutans carriage in children. Five studies (3 randomized control trials, 1 prospective cohort study, and 1 nested case-control study) were included for qualitative assessment. Tested prenatal oral health care included providing fluoride supplements, oral examinations/cleanings, oral health education, dental treatment referrals, and xylitol gum chewing. Four studies that assessed ECC incidence reduction were included in meta-analysis using an unconditional generalized linear mixed effects model with random study effects and age as a covariate. The estimated odds ratio and 95% confidence intervals suggested a protective effect of prenatal oral health care against ECC onset before 4 years of age: 0.12 (0.02, 0.77) at 1 year of age, 0.18 (0.05, 0.63) at 2 years of age, 0.25 (0.09, 0.64) at 3 years of age, and 0.35 (0.12, 1.00) at 4 years of age. Children's S. mutans carriage was also significantly reduced in the intervention group. Future studies should consider testing strategies that restore an expectant mother's oral health to a disease-free state during pregnancy.

Penalized Empirical Likelihood for the Sparse Cox Regression Model.

The current penalized regression methods for selecting predictor variables and estimating the associated regression coefficients in the sparse Cox model are mainly based on partial likelihood. In this paper, a bias-corrected empirical likelihood method is proposed for the sparse Cox model in conjunction with appropriate penalty functions when the dimensionality of data is high. Theoretical properties of the resulting estimator for the large sample are proved. Simulation studies suggest that penalized empirical likelihood works better than partial likelihood in terms of selecting correct predictors without introducing more model errors. The well-known primary biliary cirrhosis data set is used to illustrate the proposed penalized empirical likelihood method.

Candida albicans and Early Childhood Caries: A Systematic Review and Meta-Analysis.

Oral Candida albicans has been detected in children with early childhood caries (ECC) and has demonstrated cariogenic traits in animal models of the disease. Conversely, other studies found no positive correlation between C. albicans and caries experience in children, while suggesting it may have protective effects as a commensal organism. Thus, this study aimed to examine whether oral C. albicans is associated with ECC. Seven electronic databases were searched. The data from eligible studies were extracted, and the risk of bias was evaluated. A fixed effects model (Mantel-Haenszel estimate) was used for meta-analysis, and the summary effect measure was calculated by odds ratio (OR) and 95% confidence interval (CI). Fifteen cross-sectional studies were included for the qualitative assessment and 9 studies for meta-analysis. Twelve studies revealed higher oral C. albicans prevalence in ECC children than in caries-free children, while 2 studies indicated an equivalent prevalence. A pooled estimate, with OR = 6.51 and 95% CI = 4.94-8.57, indicated a significantly higher ECC experience in children with oral C. albicans than those without C. albicans (p < 0.01). The odds of experiencing ECC in children with C. albicans versus children without C. albicans were 5.26 for salivary, 6.69 for plaque, and 6.3 for oral swab samples. This systematic review indicates that children with oral C. albicans have >5 times higher odds of having ECC compared to those without C. albicans. Further prospective cohort studies are needed to determine whether C. albicans could be a risk factor for ECC, and whether it is dependent on different sample sources (saliva/plaque).

Matrix Completion Discriminant Analysis.

Matrix completion discriminant analysis (MCDA) is designed for semi-supervised learning where the rate of missingness is high and predictors vastly outnumber cases. MCDA operates by mapping class labels to the vertices of a regular simplex. With c classes, these vertices are arranged on the surface of the unit sphere in c - 1 dimensional Euclidean space. Because all pairs of vertices are equidistant, the classes are treated symmetrically. To assign unlabeled cases to classes, the data is entered into a large matrix (cases along rows and predictors along columns) that is augmented by vertex coordinates stored in the last c - 1 columns. Once the matrix is constructed, its missing entries can be filled in by matrix completion. To carry out matrix completion, one minimizes a sum of squares plus a nuclear norm penalty. The simplest solution invokes an MM algorithm and singular value decomposition. Choice of the penalty tuning constant can be achieved by cross validation on randomly withheld case labels. Once the matrix is completed, an unlabeled case is assigned to the class vertex closest to the point deposited in its last c - 1 columns. A variety of examples drawn from the statistical literature demonstrate that MCDA is competitive on traditional problems and outperforms alternatives on large-scale problems.