Genetic Association of CYP1B1 4326 C>G Polymorphism with Disease-Free Survival in TNBC Patients Undergoing TAC Chemotherapy Regimen

Background: Triple negative breast cancer (TNBC) which is treated with taxane, adriamycin and cyclophosphamide (TAC) chemotherapy regimen show variation in treatment response. CYP1B1 4326 C>G polymorphism has been implicated in contributing to the differences in treatment response in various types of cancers. Aim: The objective of the present study was to investigate whether this polymorphism modulate the risk of disease recurrence in TNBC patients undergoing TAC chemotherapy regimen. Methods: Blood samples of 76 immunohistochemistry confirmed TNBC patients were recruited. The genotyping of CYP1B1 4326 C>G polymorphism was carried out using PCR-RFLP technique. The genotype patterns were categorized into homozygous wildtype, heterozygous and homozygous variant. Kaplan-Meier analysis followed by Cox proportional hazard regression model were performed to evaluate the TNBC patients’ recurrence risk. Results: Out of 76 TNBC patients, 25 (33.0%) showed disease recurrence after one-year evaluation. Kaplan Meier analysis showed that TNBC patients who are carriers of CYP1B1 4326 GG variant genotypes (37.0%) had a significantly lower probability of disease-free rates as compared to TNBC patients who are carriers of CYP1B1 4326 CC/CG genotypes (71.0%). Univariate and multivariate Cox analysis demonstrated that TNBC patients who carried CYP1B1 4326 GG variant genotype had a significantly higher risk of recurrence with HR: 2.50 and HR: 4.18 respectively, even after adjustment as compared to TNBC patients who were carriers of CYP1B1 4326 CC and CG genotypes. Conclusion: Our results demonstrate the potential use of CYP1B1 4325 GG variant genotype as a candidate biomarker in predicting risk of recurrence in TNBC patients undergoing TAC chemotherapy regimen.     

Racial and age-related disparities in obtaining screening mammography: results of a statewide database

BACKGROUND: This study compared mammography rates in Arkansas, based on race and age, to identify any disparities in obtaining mammography. METHODS: The Arkansas Mammography Data Collection Project contained data on 133,549 women, 87,680 of them aged 40 to 64 and 45,869 aged 65 years or older. Race data were available on 64,526 women. Mammography rates were compared by patient age and race. RESULTS: Women aged 65 years and older were less likely to obtain mammograms than younger women: 21.67% versus 23.30%. Mammograms were more likely to be classified as diagnostic in older women and as screening in younger women. Older African American women were less likely to obtain mammograms than younger women of the same race (7.23% vs 8.02%), while older white women were more likely to obtain mammograms than younger white women (11.64% vs 11.31%). African Americans were less likely to obtain mammograms in both age groups. CONCLUSIONS: Older African American women are less likely to obtain mammograms than white and younger women. The reasons for this disparity warrant further evaluation.     

Sample size calculation in physical medicine and rehabilitation: a systematic review of reporting, characteristics, and results in randomized controlled trials

Abdul Latif L, Daud Amadera JE, Pimentel D, Pimentel T, Fregni F. Sample size calculation in physical medicine and rehabilitation: a systematic review of reporting, characteristics, and results in randomized controlled trials.

Objective

To assess systematically the reporting of sample size calculation in randomized controlled trials (RCTs) in 5 leading journals in the field of physical medicine and rehabilitation (PM&R).

Data Sources

The data source was full reports of RCTs in 5 leading PM&R journals (Journal of Rehabilitation Medicine, Archives of Physical Medicine and Rehabilitation, American Journal of Physical Medicine and Rehabilitation, Clinical Rehabilitation, and Disability and Rehabilitation) between January and December of 1998 and 2008. Articles were identified in Medline.

Study Selection

A total of 111 articles met our inclusion criteria, which include RCTs of human studies in the 5 selected journals.

Data Extraction

Sample size calculation reporting and trial characteristics were collected for each trial by independent investigators.

Data Synthesis

In 2008, 57.3% of articles reported sample size calculation as compared with only 3.4% in 1998. The parameters that were commonly used were a power of 80% and alpha of 5%. Articles often failed to report effect size or effect estimates for sample size calculation. Studies reporting sample size calculation were more likely to describe the main outcome and to have a sample size greater than 50 subjects. The study outcome (positive vs negative) was not associated with the likelihood of sample size reporting. Trial characteristics of the 2 periods (1998 vs 2008) were similar except that in 1998 there were more negative studies compared with 2008.

Conclusions

Although sample size calculation reporting has improved dramatically in 10 years and is comparable with other fields in medicine, it is still not adequate given current publication guidelines.     

Prevalence of dental caries in primary and permanent teeth and its relation with tooth brushing habits among schoolchildren in Eastern Saudi Arabia

Objectives:

To determine the prevalence of dental caries in the primary and permanent teeth, and evaluate the brushing habits of school children in Dammam, Kingdom of Saudi Arabia (KSA).

Methods:

This study was conducted at Dammam, KSA. Oral examination of the participants was conducted from February to May 2014. The total sample size for this cross-sectional study was 711. There were 397 children between the age of 6-9 years, who were examined for primary teeth caries, and 314 between the age 10-12 years were examined for permanent teeth caries. Primary and permanent dentitions were studied for decayed, missing, and filled teeth (dmft [primary teeth], DMFT [permanent teeth]).

Results:

The overall prevalence of dental caries in primary and permanent teeth was almost 73% (n=711). Among the 6-9-year-old, the prevalence of caries was approximately 78% (n=397) whereas, among the 10-12-year-old children, it was approximately 68% (n=314). Mean dmft value among the 6-9-year-olds was 3.66±3.13 with decayed (d) component of 3.28±2.92, missing (m) component of 0.11±0.69, and filled (f) component of 0.26±0.9. Mean DMFT value among the 10-12-year-old children was 1.94±2.0 with decayed (D) component of 1.76±1.85, missing (M) component of 0.03±0.22, and filled (F) of component 0.15±0.73. Daily tooth brushing had a positive effect on caries prevention, and this effect was statistically significant for caries in primary teeth.

Conclusion:

Although the prevalence of dental caries in primary and permanent teeth was not found to be as high as other researchers reported from different cities of KSA, still the prevalence was high considering the World Health Organization future oral health goals. Awareness should be provided to students, as well as, teachers and parents regarding the importance of good brushing habits and regular dental visits.Dental caries is one of the most common cause of extraction of primary teeth in Saudi Arabia.1 In the past few decades, an increase in the prevalence of dental caries has been observed, which can be attributed to a change in lifestyle of Saudis, involving increased consumption of sugary food, carbonated drinks, and lack of awareness towards proper oral health maintenance.2,3 Generally, the prevalence of dental caries in developed countries is decreasing, while in underdeveloped and developing countries, the prevalence is on the rise.4 According to the statistics available from the World Health Organization (WHO), caries prevalence among the 12-year-old children from many European Union states (EU) has decreased considerably from 1970’s to 2006.5 This decline in the caries’ prevalence among EU countries over a period of 35 years could be attributed to an increased awareness of oral hygiene maintenance, and use of fluoridated toothpaste.6 However, among underdeveloped countries where fluoridated toothpaste is not easily available, or not affordable in some cases, caries prevalence is still high.7 The area of dental caries prevalence is of great interest to local and international researchers, which can be indicated by a number of studies that have been performed in developed and developing countries regarding caries’ prevalence.8-10 A study conducted in the urban and rural areas of Lahore, Pakistan to determine whether urbanization and family earnings are related to dental caries reported caries prevalence of 40.5%, and decayed (d), missing (m), and filled (f) teeth (dmft [primary teeth]) score of 1.85 ± 3.26 in preschool children aged 3-5 years,11 while another cross-sectional study performed in Chikar, Pakistan with convenience sampling of 311 schoolchildren revealed an overall DMFT (permanent teeth) score of 3.3 in 5-20-year-olds.12 Several studies have been conducted in different parts of the Kingdom of Saudi Arabia (KSA) to report the prevalence of dental caries in schoolchildren. A study performed in Riyadh reported a dmft score of 6.1, decayed factor of 4.6, and no significant difference in the prevalence of caries in relation to gender among 789 pre-school children.13 Farsi14 conducted a study to develop an association between enamel defects and caries occurrence in Jeddah, KSA, and reported a dmft score of 3.9, and a strong association between enamel defects and caries prevalence among 4-5-year-olds.14 In 2012, caries prevalence in the maxillary and mandibular first molar in the age group of 7-10 years schoolchildren was determined in Abha city, and a mean DMFT of 2.74 was reported.15 It was also concluded in the same study that caries prevalence in the first permanent molars from this region is higher than the recommended standards of the WHO.15 Extensive literature search was carried out to find studies regarding caries’ prevalence from Dammam, KSA. The search resulted in only one study, which was conducted in 2008 on children with cleft lip and palate aged 1-6 years, and it reported a high dmft of 10.54 from Dammam region.16 Since Dammam is one of the largest cities of the Eastern province of KSA, it would be interesting to observe caries’ prevalence among schoolchildren from this city. Therefore, the aim of the present study was to determine the prevalence of dental caries in schoolchildren aged 6-12 years in Dammam, KSA using the dmft/DMFT index of dental caries.     

Lateral ventricle injection of orexin-A ameliorates central precocious puberty in rat via inhibiting the expression of MEG3

Background: Central precocious puberty (CPP) is characterized as increasing gonadotropin-releasing hormone (GnRH) release. Orexin-A has also been shown to affect GnRH release. However, there are few reports about the effect of orexin A on the treatment of CPP. Methods: After establishing the precocious puberty model, the rats were divided into four groups: normal control, precocious puberty rats, precocious puberty rats treated with normal saline and precocious puberty rats treated with orexin-A. The vaginal opening time, second estrus cycle, ovarian index and uterus index of rats in each group were detected. qRT-PCR was performed to examine the expression of MEG3 and kisspeptin in rats. HT22 cells were transfected with pcDNA-MEG3 to detect the expression of Kisspeptin. Results: In this study, we found that orexin-A not only delayed the day of vaginal opening and regular estrus cycle days but also decreased the ovarian index and uterus index in rats with CPP. In addition, orexin-A reversed the up-regulation of MEG3 and kisspeptin in rats with CPP. In HT22 cells, the mRNA and protein level of kisspeptin were enhanced by pcDNA-MEG3. Conclusion: Our results suggest that orexin-A ameliorates central precocious puberty in rat and MEG3 might be involved in this effect, suggesting that MEG3 might be a novel target in treating central precocious puberty.     

Evaluation of Pyrosequencing for Detecting Extensively Drug-Resistant Mycobacterium tuberculosis among Clinical Isolates from Four High-Burden Countries

Reliable molecular diagnostics, which detect specific mutations associated with drug resistance, are promising technologies for the rapid identification and monitoring of drug resistance in Mycobacterium tuberculosis isolates. Pyrosequencing (PSQ) has the ability to detect mutations associated with first- and second-line anti-tuberculosis (TB) drugs, with the additional advantage of being rapidly adaptable for the identification of new mutations. The aim of this project was to evaluate the performance of PSQ in predicting phenotypic drug resistance in multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB) clinical isolates from India, South Africa, Moldova, and the Philippines. A total of 187 archived isolates were run through a PSQ assay in order to identify M. tuberculosis (via the IS6110 marker), and to detect mutations associated with M/XDR-TB within small stretches of nucleotides in selected loci. The molecular targets included katG, the inhA promoter and the ahpC-oxyR intergenic region for isoniazid (INH) resistance; the rpoB core region for rifampin (RIF) resistance; gyrA for fluoroquinolone (FQ) resistance; and rrs for amikacin (AMK), capreomycin (CAP), and kanamycin (KAN) resistance. PSQ data were compared to phenotypic mycobacterial growth indicator tube (MGIT) 960 drug susceptibility testing results for performance analysis. The PSQ assay illustrated good sensitivity for the detection of resistance to INH (94%), RIF (96%), FQ (93%), AMK (84%), CAP (88%), and KAN (68%). The specificities of the assay were 96% for INH, 100% for RIF, FQ, AMK, and KAN, and 97% for CAP. PSQ is a highly efficient diagnostic tool that reveals specific nucleotide changes associated with resistance to the first- and second-line anti-TB drug medications. This methodology has the potential to be linked to mutation-specific clinical interpretation algorithms for rapid treatment decisions.     

The 11-item Medication Adherence Reasons Scale: reliability and factorial validity among patients with hypertension in Malaysian primary healthcare settings

INTRODUCTION

The aim of this study was to assess the reliability and validity of a modified Malaysian version of the Medication Adherence Reasons Scale (MAR-Scale).

METHODS

In this cross-sectional study, the 15-item MAR-Scale was administered to 665 patients with hypertension who attended one of the four government primary healthcare clinics in the Hulu Langat and Klang districts of Selangor, Malaysia, between early December 2012 and end-March 2013. The construct validity was examined in two phases. Phase I consisted of translation of the MAR-Scale from English to Malay, a content validity check by an expert panel, a face validity check via a small preliminary test among patients with hypertension, and exploratory factor analysis (EFA). Phase II involved internal consistency reliability calculations and confirmatory factor analysis (CFA).

RESULTS

EFA verified five existing factors that were previously identified (i.e. issues with medication management, multiple medications, belief in medication, medication availability, and the patient’s forgetfulness and convenience), while CFA extracted four factors (medication availability issues were not extracted). The final modified MAR-Scale model, which had 11 items and a four-factor structure, provided good evidence of convergent and discriminant validities. Cronbach’s alpha coefficient was > 0.7, indicating good internal consistency of the items in the construct. The results suggest that the modified MAR-Scale has good internal consistencies and construct validity.

CONCLUSION

The validated modified MAR-Scale (Malaysian version) was found to be suitable for use among patients with hypertension receiving treatment in primary healthcare settings. However, the comprehensive measurement of other factors that can also lead to non-adherence requires further exploration.