Association between coronary artery vitamin D receptor expression and select systemic risks factors for coronary artery atherosclerosis.

OBJECTIVE: The aim of this study is to analyze the association between coronary artery vitamin D receptor (VDR) expression and systemic coronary artery atherosclerosis (CAA) risk factors. METHODS: Female cynomolgus monkeys (n = 39) consumed atherogenic diets containing the women's equivalent of 1000 IU/day of vitamin D3. After 32 months consuming the diets, each monkey underwent surgical menopause. After 32 postmenopausal months, CAA and VDR expression were quantified in the left anterior descending coronary artery. Plasma 25OHD3, lipid profiles and serum monocyte chemotactic protein-1 (MCP-1) were measured. RESULTS: In postmenopausal monkeys receiving atherogenic diets, serum MCP-1 was significantly elevated compared with baseline (482.2 ± 174.2 pg/ml vs. 349.1 ± 163.2 pg/ml, respectively; p < 0.001; d = 0.79) and at the start of menopause (363.4 ± 117.2 pg/ml; p < 0.001; d = 0.80). Coronary VDR expression was inversely correlated with serum MCP-1 (p = 0.042). Additionally, the change of postmenopausal MCP-1 (from baseline to necropsy) was significantly reduced in the group with higher, compared to below the median, VDR expression (p = 0.038). The combination of plasma 25OHD3 and total plasma cholesterol/high-density lipoprotein cholesterol was subsequently broken into low-risk, moderate-risk and high-risk groups; as the risk increased, the VDR quantity decreased (p = 0.04). CAA was not associated with various atherogenic diets. CONCLUSION: Coronary artery VDR expression was inversely correlated with markers of CAA risk and inflammation, including MCP-1, suggesting that systemic and perhaps local inflammation in the artery may be associated with reduced arterial VDR expression.

Seroprevalence of SARS-CoV-2 antibodies, associated epidemiological factors and antibody kinetics among healthcare workers in Connecticut.

BACKGROUND: Healthcare workers (HCWs) are at the front line of the ongoing coronavirus 2019 (COVID-19) pandemic. Comprehensive evaluation of the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) among HCWs in a large healthcare system could help to identify the impact of epidemiological factors and the presence of symptoms on the immune response to the infection over time. AIM: To determine the seroprevalence of SARS-CoV-2-specific antibodies among HCWs, identify associated epidemiological factors and study antibody kinetics. METHODS: A longitudinal evaluation of the seroprevalence and epidemiology of SARS-CoV-2-specific antibodies was undertaken in approximately 30,000 HCWs in the largest healthcare system in Connecticut, USA. FINDINGS: At baseline, the prevalence of SARS-CoV-2 antibody among 6863 HCWs was 6.3% [95% confidence interval (CI) 5.7-6.9%], and was highest among patient care support (16.7%), medical assistants (9.1%) and nurses (8.2%), and lower for physicians (3.8%) and advanced practice providers (4.5%). Seroprevalence was significantly higher among African Americans [odds ratio (OR) 3.26 compared with Caucasians, 95% CI 1.77-5.99], in participants with at least one symptom of COVID-19 (OR 3.00, 95% CI 1.92-4.68), and in those reporting prior quarantine (OR 3.83, 95% CI 2.57-5.70). No symptoms were reported in 24% of seropositive participants. Among the 47% of participants who returned for a follow-up serological test, the seroreversion rate was 39.5% and the seroconversion rate was 2.2%. The incidence of re-infection in the seropositive group was zero. CONCLUSION: Although there is a decline in the immunoglobulin G antibody signal over time, 60.5% of seropositive HCWs had maintained their seroconversion status after a median of 5.5 months.

Development and evaluation of a novel taekwondo chest protector to improve mobility when performing axe kicks.

The axe kick, in Olympic style taekwondo, has been identified as the most popular scoring technique aimed to the head during full contact competition. The first purpose of this study was to identify and investigate design issues with the current World Taekwondo Federation approved chest protector. A secondary purpose was to develop a novel chest protector addressing the identified design issues and to conduct a biomechanical analysis. Fifteen male elite Taekwondo players were selected to perform three different styles of the axe kick, i.e., front, in-out, and out-in axe kick five times each for a total of 45 kicks. Two-way repeated measures ANOVA showed significant differences between the novel and existing chest protector conditions for vertical height of the toe, downward kicking foot speed, hip flexion angle and ipsilateral shoulder flexion extension range of motion (ROM) (p < 0.05). There were no significant differences between the control condition (no chest protector) and the novel chest protector condition for these variables (p > 0.05). These results indicate that the novel chest protector interferes less with both the lower and upper limbs during the performance of the axe kick and provides a more natural, free-moving alternative to the current equipment used.

Association between proton pump inhibitors and spontaneous bacterial peritonitis in cirrhotic patients - a systematic review and meta-analysis.

Acid suppressive therapy, in the form of proton pump inhibitor (PPI), is widely used in cirrhotic patients, often in indications which are not clearly justified. PPI facilitates enteric bacterial colonisation, overgrowth and translocation, which might predispose to spontaneous bacterial peritonitis. However, observational studies evaluating the association of PPI and SBP in cirrhotic patients have yielded inconsistent results. We therefore conducted a meta-analysis of relevant clinical studies to determine the nature of this association. Observational studies assessing the association between SBP and PPI in cirrhosis, conducted in adult population and published in all languages, were identified through systematic search in the MEDLINE, EMBASE and manual reviews of all major gastroenterology meeting proceedings up to May 2010. The relevant studies were pooled using traditional meta-analytic techniques with a random-effects model. Four studies were identified and included in the meta-analysis. The pooled analysis, involving a total of 772 patients, found a significant association between the use of PPI and the development of SBP (OR 2.77, 95% CI 1.82-4.23). There was very little degree of heterogeneity as reflected by an I(2) value of 22% and the visual inspection of the funnel plot. There is a potential association between use of PPI and development of SBP. Therefore, PPIs should be used judiciously and only when clearly indicated in cirrhotics. Further studies are essential to clarify this relationship and elucidate the underlying mechanisms.

Mycobacterium tuberculosis DNA repair in response to subinhibitory concentrations of ciprofloxacin.

OBJECTIVES: To investigate how the SOS response, an error-prone DNA repair pathway, is expressed following subinhibitory quinolone treatment of Mycobacterium tuberculosis. METHODS: Genome-wide expression profiling followed by quantitative RT (qRT)-PCR was used to study the effect of ciprofloxacin on M. tuberculosis gene expression. RESULTS: Microarray analysis showed that 16/110 genes involved in DNA protection, repair and recombination were up-regulated. There appeared to be a lack of downstream genes involved in the SOS response. qRT-PCR detected an induction of lexA and recA after 4 h and of dnaE2 after 24 h of subinhibitory treatment. CONCLUSIONS: The pattern of gene expression observed following subinhibitory quinolone treatment differed from that induced after other DNA-damaging agents (e.g. mitomycin C). The expression of the DnaE2 polymerase response was significantly delayed following subinhibitory quinolone exposure.

The effect of oxidative stress on the mutation rate of Mycobacterium tuberculosis with impaired catalase/peroxidase function.

OBJECTIVES: To determine the effect of oxidative stress on isoniazid-resistant Mycobacterium tuberculosis deficient in catalase/peroxidase activity to varying degrees through mutation in katG. METHODS: The mutation rate was determined for a set of isogenic strains with different katG alleles giving different catalase and/or peroxidase activities following exposure to the oxidizing agent, hydrogen peroxide. Mutants were selected on rifampicin, and the location and nature of the mutation were identified by sequencing the rpoB gene. RESULTS: No evidence was found to suggest that strains that had impaired catalase/peroxidase activity were hypermutable, and the presence of excess hydrogen peroxide had no effect on the mutation rate. An unusual pattern of mutations in rpoB was observed in catalase-deficient strains with only 3 of 66 having mutations within the rifampicin resistance-determining region. CONCLUSIONS: The mutation rate of M. tuberculosis in response to oxidative stress is not increased in strains with significant deficits in catalase and peroxidase activity. Our data suggest that isoniazid-resistant strains compensate for their reduced ability to detoxify oxidative stress effectively. Interestingly, mutations were found in unusual locations at positions similar to those found in clinical isoniazid-resistant strains.

Evaluation of liquid culture for quantitation of Mycobacterium tuberculosis in murine models.

Quantitation of bacterial load in tissues is essential for experimental investigation of Mycobacterium tuberculosis infection and immunity. We have used an automated liquid culture system to determine the number of colony forming units (CFU) in murine tissues and compared the results to those obtained by conventional plating on Middlebrook agar. There is an overall good correlation between results obtained by the two methods. Although less consistency and more contamination was observed in the automated liquid culture, the method is more sensitive, less labour intensive and allows the processing of large numbers of samples.

Technique for cloning and sequencing the ends of bacterial artificial chromosome inserts.

Bacterial artificial chromosome (BAC) libraries are an important tool for positional cloning, gene analysis and physical mapping. During studies using BAC clones, it is often necessary to organize them into contiguous sequences (contigs). To finalize, join and extend the contigs, both cloning and sequencing of the ends of the inserts are required. Here, we describe a low-cost, accessible, fast and powerful method for the routine isolation of BAC ends. This method allows the isolation of 20 BAC clone ends in one day. The analysis of the ends reveals fragment sizes compatible with sequencing, and the structure of these clones allows the sequencing of both ends using the same plasmid. Moreover, long end fragments can be sequenced in both directions.

Salivary mutans streptococci and caries development in the primary and mixed dentitions of children.

OBJECTIVES: For more than 25 years, both cross-sectional and longitudinal studies of dental caries have focused on the role of salivary mutans streptococci (SMS) as a predictor of caries risk. This study examined the relationship between SMS and longitudinal caries development in the primary and mixed dentitions. METHODS: Eighty-five children, initial mean age 3.8 years, were examined for dental caries at baseline and once annually for 6 years. Children's SMS were sampled with a tongue blade, which was impressed onto plates containing a medium selective for SMS. After incubation, colony forming units of SMS were determined semi-quantitatively and categorized as low, moderate or high. RESULTS: Children classified as high caries risk at baseline had significantly greater (P<0.05) dmfs scores for all teeth, and in the primary molars, than children classified as moderate or low caries risk at every age but 9 (P<0.10). Children classified as high risk at age 3 had the greatest DMFS increment through age 8. Based on annual examinations, there was a trend towards increasing mean dmfs/DMFS scores among children classified as high risk in every year. CONCLUSIONS: The current study is among the first to report on the ability of annual measurements of SMS to identify long-term caries risk in both the primary and the mixed dentitions. Despite limitations in predicting caries risk using microbiological methods, this longitudinal study supports the overall benefits of this type of testing.

Failure of intense preventive efforts to arrest early childhood and rampant caries: three case reports.

This report presents the first three children who developed dental caries despite being enrolled in a randomized, control trial to test methods to prevent early childhood caries. The children's caretakers received education on decreasing frequent and prolonged feeding with a nursing bottle and other sugar containing foods, as well as brushing the children's teeth daily with 0.4% SnF2 gel. One of the child's caretaker additionally received training sessions to improve confidence in eliminating the child's nursing bottle habit and in performing daily tooth brushing. The two other children received monthly topical fluoride treatments with 2% NaF. Despite these intensive preventive efforts, these three children developed dental caries. Two of the children had mutans streptococci colonization at the time of initial visit, (12 and 14 months of age, respectively). All had high mutans streptococci levels at the time that caries was detected. Incorrigible, high-frequency sugar consumption from a bottle or from solid foods was suggested in all three cases. In one case, dental caries was associated with defects of the tooth enamel. Conceivably, the cariogenic challenge and harmful behaviors in certain children may be so extreme that they can overwhelm even extraordinary preventive efforts.

The relationship between bottle usage/content, age, and number of teeth with mutans streptococci colonization in 6-24-month-old children.

OBJECTIVES: Mutans streptococci (MS) are the primary pathogens involved in the development of early childhood caries. However, factors that may affect their acquisition in the mouths of young children are not well understood, and the period of initial colonization remains controversial. This study investigated the relationship of age, number of teeth, and bottle usage/content with regard to the isolation of MS in 6-24-month-old children. METHODS: A total of 122 children from low-income families attending a nutritional supplement program, and their mothers, participated in this study. Children were examined for dental caries and number of erupted teeth and were sampled for MS. Mothers were administered a questionnaire to obtain details of baby bottle use, including what food items were put in the bottle during the last week. RESULTS: MS was detected in more than one-third of the 6-24-month-olds. Unlike some studies that suggest a later period of infectivity, approximately 20% of children under 14 months of age, including 4 of 22 infants aged 6-9 months, were colonized with MS. When examined separately, age, number of teeth, and bottle usage/content were each found to be related to the presence of MS. Mutans streptococci colonization was more likely with increasing age and number of teeth, and children whose bottles contained sweetened beverages were more likely to be colonized than children whose bottles contained milk. Logistic regression models that controlled for both age and number of teeth indicated that children who consumed sweetened beverages in their baby bottle had a statistically significant, four-fold increase in the odds of colonization by MS relative to children who consumed milk. CONCLUSIONS: The finding that approximately 20% of the children under 14 months of age were infected with MS indicates that colonization in this sample of low-income preschool children may begin earlier than suggested by some investigations. Additionally, the risk of MS colonization appears lower among infants who consume milk rather than sweetened beverages in the bottle.

Colonization of mutans streptococci in 8- to 15-month-old children.

OBJECTIVE: The age at which a child becomes colonized with mutans streptococci (MS) is important for understanding early childhood caries. The aim of this study was to explore the relationship of age with MS colonization in infants. METHODS: Inner-city children (n = 149) between the ages of 8 months and 15 months, inclusive, who reportedly were still using a baby bottle, were sampled for MS. RESULTS: Evidence of MS colonization was seen as early at 10 months of age. For children 12 months old or younger (n = 80), 25 percent had detectable levels of MS; in the 15-month age group, 60 percent were colonized. CONCLUSION: This study suggests that prevention of MS colonization in some populations may need to be initiated prior to the child's first birthday.

Dental caries prevalence and treatment levels in Arizona preschool children.

OBJECTIVES: To assess the prevalence of dental caries in a large group of preschool children, to determine the extent to which the children received dental treatment, to examine the association between demographic and socioeconomic factors and the prevalence of caries, and to compare these findings with those from previous studies of preschool populations in the United States. METHODS: Dental caries exams were performed on 5171 children ages 5 months through 4 years, and a parent or other caregiver was asked to complete a questionnaire giving information about the child and her or his household. The children were recruited from Head Start programs; Women, Infants, and Children (WIC) nutrition programs; health fairs; and day care centers in a representative sample of Arizona communities with populations of more than 1000 people. RESULTS: Of the 994 one-year-old children examined, 6.4% had caries, with a mean dmft (decayed, missing [extracted due to caries], and filled teeth) score of 0.18. Nearly 20% of the 2-year-olds had caries, with a mean dmft of 0.70. Thirty-five percent of the 3-year-olds had caries, with a mean dmft of 1.35, and 49% of the 4-year-olds had caries, with a mean dmft of 2.36. Children whose caregivers fell into the lowest education category had a mean dmft score three times higher than those with caregivers in the highest education category. Children with caregivers in the lowest income category had a mean dmft score four times higher than those with caregivers in the highest category. Children younger than age 3 had little evidence of dental treatment, and most of the children with caries in each age group had no filled or extracted teeth. CONCLUSIONS: The data show that dental caries is highly prevalent in this preschool population, with little of the disease being treated. Timing of diagnostic examinations and prevention strategies for preschool children need to be reconsidered, especially for children identified as having a high risk of caries.

Early childhood caries: overview and recent findings.

Early childhood caries is of epidemic proportions in some U.S. minority populations and in developing countries, yet a review of the literature reveals numerous conflicting reports and unanswered questions regarding the etiology and prevention of the disease. Better knowledge of the cause of early childhood caries and effective strategies to reduce its risk should produce enormous reductions in initial and long-term dental treatment costs, as well as the pain and suffering of affected children.

Caries experience and mutans streptococci as indicators of caries incidence.

Studies indicate that previous caries experience can influence future caries development; however, caries-free individuals also may develop caries. The aim of this study was to examine the relationship between baseline caries experience and salivary mutans streptococci (SMS) levels as an indicator for predicting caries incidence in pre-school children. One hundred forty-eight preschool children (mean baseline age, 3-8 years) of low socioeconomic status were examined for dental caries and SMS levels at baseline and annually for 2 years. All children were identified at baseline as either caries free or caries positive. The 2-year delta dmfs scores for both groups were evaluated as 0, 1-2, 3-4, or > 4. The children's baseline SMS levels were categorized as low (0 CFU), moderate (1-50 CFU), or high (> 50 CFU), and were recoded to assigned ranges of 1, 2, and 3, respectively, in each year for longitudinal analysis. Both the caries-free and caries-positive groups had high SMS levels associated with the greatest delta dmfs, and when SMS ranges were added for the three examination years (minimum = 3, maximum = 9), the mean second-year dmfs scores varied directly as the sum of the ranges. Results from this study suggest that SMS levels may be useful in identifying and predicting future caries in preschool children, independent of baseline caries experience.

Salivary mutans streptococci and dental caries patterns in pre-school children.

Recent studies have suggested that the identification of caries as discrete patterns may be valuable in describing and predicting caries experience on an individual basis. The purpose of this study was to assess the association between levels of salivary mutans streptococci and the prevalence, incidence and distribution of caries patterns in the primary dentition. A cohort of pre-school children (n = 146, mean age 3.8 yr) were examined for dental caries and sampled for salivary mutans streptococci (SMS) at baseline and once annually for 2 yr. Children's tooth surfaces were categorized into four patterns: pit/fissure, maxillary anterior, posterior proximal, and buccal/lingual smooth surface. Salivary mutans streptococci were enumerated using a tongue blade technique, and were categorized as low (0 CFU), moderate (1-50 CFU) and high (> 50 CFU). At year 2, children with high baseline SMS had the 1) highest prevalence of caries (87%) and the highest dmfs (9.15); 2) highest prevalence of each pattern, and 3) greatest number of patterns. Among children with the pit/fissure pattern, those with high baseline SMS had the greatest pit/fissure dmfs after 2 yr. Results show that baseline SMS levels were associated with both cross-sectional and longitudinal caries experience, numbers of caries patterns, and the prevalence and severity of those patterns.