Obesity differs from diabetes mellitus in antibody and T-cell responses post-COVID-19 recovery.

OBJECTIVE: Obesity and type 2 diabetes (DM) are risk factors for severe coronavirus disease 2019 (COVID-19) outcomes, which disproportionately affect South Asian populations. This study aims to investigate the humoral and cellular immune responses to SARS-CoV-2 in adult COVID-19 survivors with overweight/obesity (Ov/Ob, BMI ≥ 23 kg/m2) and DM in Bangladesh. METHODS: In this cross-sectional study, SARS-CoV-2-specific antibody and T-cell responses were investigated in 63 healthy and 75 PCR-confirmed COVID-19 recovered individuals in Bangladesh, during the pre-vaccination first wave of the COVID-19 pandemic in 2020. RESULTS: In COVID-19 survivors, SARS-CoV-2 infection induced robust antibody and T-cell responses, which correlated with disease severity. After adjusting for age, sex, DM status, disease severity, and time since onset of symptoms, Ov/Ob was associated with decreased neutralizing antibody titers, and increased SARS-CoV-2 spike-specific IFN-γ response along with increased proliferation and IL-2 production by CD8 + T cells. In contrast, DM was not associated with SARS-CoV-2-specific antibody and T-cell responses after adjustment for obesity and other confounders. CONCLUSION: Ov/Ob is associated with lower neutralizing antibody levels and higher T-cell responses to SARS-CoV-2 post-COVID-19 recovery, while antibody or T-cell responses remain unaltered in DM.

Circadian genes and risk of prostate cancer in the prostate cancer prevention trial.

Circadian genes have been considered as a possible biological mechanism for the observed relationship between circadian rhythm disruptions and increased risk of hormone-related cancers. In the current study, we investigated the relationship between circadian gene variants and prostate cancer risk and whether reducing bioavailable testosterone modifies the circadian genes-prostate cancer relationship. We conducted a nested case-control study among Caucasian men in the Prostate Cancer Prevention Trial (PCPT), a randomized placebo-controlled clinical trial to assess if finasteride (an androgen bioactivation inhibitor) could prevent prostate cancer. We evaluated the associations between 240 circadian gene variations and prostate cancer risk among 1092 biopsy-confirmed prostate cancer cases and 1089 biopsy-negative controls in the study (642 cases and 667 controls from the placebo group; 450 cases and 422 controls from the finasteride group), stratified by treatment group. Among men in the finasteride group, there were suggestive associations between NPAS2 variants and total prostate cancer risk, with one SNP remaining statistically significant after Bonferroni correction (rs746924, odds ratio [OR] = 1.5, P = 9.6 × 10-5 ). However, we found little evidence of increased prostate cancer risk (overall or by low/high grade) associated with circadian gene variations in men of the placebo group, suggesting potential modification of genetic effects by treatment. We did not find strong evidence that circadian gene variants influenced prostate cancer risk in men who were not on finasteride treatment. There were suggestive associations between NPAS2 variants and prostate cancer risk among men using finasteride, which warrants further investigations.

Association of androgen metabolism gene polymorphisms with prostate cancer risk and androgen concentrations: Results from the Prostate Cancer Prevention Trial.

BACKGROUND: Prostate cancer is highly influenced by androgens and genes. The authors investigated whether genetic polymorphisms along the androgen biosynthesis and metabolism pathways are associated with androgen concentrations or with the risk of prostate cancer or high-grade disease from finasteride treatment. METHODS: A nested case-control study from the Prostate Cancer Prevention Trial using data from men who had biopsy-proven prostate cancer (cases) and a group of biopsy-negative, frequency-matched controls was conducted to investigate the association of 51 single nucleotide polymorphisms (SNPs) in 12 genes of the androgen pathway with overall (total), low-grade, and high-grade prostate cancer incidence and serum hormone concentrations. RESULTS: There were significant associations of genetic polymorphisms in steroid 5α-reductase 1 (SRD5A1) (reference SNPs: rs3736316, rs3822430, rs1560149, rs248797, and rs472402) and SRD5A2 (rs2300700) with the risk of high-grade prostate cancer in the placebo arm of the Prostate Cancer Prevention Trial; 2 SNPs were significantly associated with an increased risk (SRD5A1 rs472402 [odds ratio, 1.70; 95% confidence interval, 1.05-2.75; Ptrend = .03] and SRD5A2 rs2300700 [odds ratio, 1.94; 95% confidence interval, 1.19-3.18; Ptrend = .01]). Eleven SNPs in SRD5A1, SRD5A2, cytochrome P450 family 1, subfamily B, polypeptide 1 (CYP1B1), and CYP3A4 were associated with modifying the mean concentrations of serum androgen and sex hormone-binding globulin; and 2 SNPs (SRD5A1 rs824811 and CYP1B1 rs10012; Ptrend < .05) consistently and significantly altered all androgen concentrations. Several SNPs (SRD5A1 rs3822430, SRD5A2 rs2300700, CYP3A43 rs800672, and CYP19 rs700519; Ptrend < .05) were significantly associated with both circulating hormone levels and prostate cancer risk. CONCLUSIONS: Germline genetic variations of androgen-related pathway genes are associated with serum androgen concentrations and the risk of prostate cancer. Further studies to examine the functional consequence of novel causal variants are warranted. Cancer 2016;122:2332-2340. © 2016 American Cancer Society.

Serum androgens and prostate cancer risk: results from the placebo arm of the Prostate Cancer Prevention Trial.

BACKGROUND: Compelling and long-standing data suggest that androgens play an important role in the development of both normal prostate epithelium and prostate cancer. Although testosterone administration can induce prostate cancer (PCA) in laboratory animals, serum-based epidemiologic studies examining androgens in humans have not consistently supported a role for androgens in prostate carcinogenesis. We examined whether pre-diagnostic serum androgens were associated with PCA risk in the placebo arm of the Prostate Cancer Prevention Trial. METHODS: In this nested case-control study, cases (n = 1,032) were primarily local-stage, biopsy-detected cancers, and controls (n = 1,025) were biopsy-confirmed to be PCA-free. Pre-diagnostic serum androgens (total testosterone, 3α-androstanediol glucuronide, free testosterone), estrogen-to-testosterone ratio, and sex hormone-binding globulin (SHBG) concentrations were measured in pooled (baseline and year 3) blood samples. RESULTS: We found no significant associations between serum androgens, estrogen-to-testosterone ratios, or SHBG and risk of total, low (Gleason <7) or high-grade (Gleason 7-10) PCA. CONCLUSION: Much remains to be learned about the role of androgens in prostate carcinogenesis. Further research is needed to evaluate the role of androgens, timing of exposure, genetic modulators of androgen metabolism, or environmental exposures that may affect androgen influence on prostate carcinogenesis.

Prospective study of human herpesvirus type 8 serostatus and prostate cancer risk in the placebo arm of the Prostate Cancer Prevention Trial.

BACKGROUND: Human herpesvirus type 8 (HHV-8), a gamma herpesvirus associated with Kaposi's sarcoma, has been proposed as a candidate risk factor for prostate cancer (PCa) because of its detection in benign and malignant prostate specimens, and its relation with histologic prostatic inflammation. We investigated the possible relation between pre-diagnostic HHV-8 infection and PCa risk in a case-control study sampled from the placebo arm of the Prostate Cancer Prevention Trial. METHODS: We defined cases as men with a confirmed diagnosis of PCa after visit 2 (n = 315) and controls as men not diagnosed with PCa during the trial who also had a negative end-of-study prostate biopsy (n = 315). We tested sera from visit 2 for IgG antibodies against HHV-8 using a monoclonal antibody-enhanced immunofluorescence assay against multiple lytic HHV-8 antigens. RESULTS: The adjusted seroprevalence of HHV-8 infection was 11.6 % for cases and 11.0 % for controls (p = 0.81). No association was observed between HHV-8 seropositivity and PCa risk (OR 1.06, 95 % CI 0.65-1.76). CONCLUSION: Our findings of a null association between HHV-8 seropositivity and PCa risk do not support an association between HHV-8 infection and PCa development, consistent with the general tendency of the epidemiologic literature to date.

What Kind of Dressing Is Important to Ensure Wound Healing With the Application of Platelet-Rich Plasma in Chronic Ulcers?

Wound healing is an intricate process of tissue regeneration that depends on the simultaneous presence of immunological and microenvironmental factors. The significant role of platelets and their granules in the wound-healing process has led to extensive research on their potential as a therapeutic intervention in different areas, including chronic wounds and aesthetic therapies. Saltwater aids in purification and promotes healing by utilizing osmosis. Sodium chloride, the chemical component present in salt, induces the extrusion of fluids from cells upon contact. If the liquids in issue are bacterial, they will also be ejected, assisting in the cleansing of the skin. Desiccation, often known as the drying out of injured cells, is well-known for its antibacterial properties and subsequent ability to reduce inflammation. This case series aims to investigate the advantages of using saltwater dressing following platelet-rich plasma therapy for chronic wounds.

Assessing Trace Metal-Based Human Health Risks for Commonly Used Body Soaps in Bangladesh.

In Bangladesh, body soaps are very popular among consumers due to their flavors and low alkali content. The current study assesses the contamination of several trace metals (TMs) such as iron (Fe), copper (Cu), zinc (Zn), chromium (Cr), manganese (Mn), nickel (Ni), cadmium (Cd), and lead (Pb) in some of the body soaps most commonly used in Bangladesh. The concentrations of Fe, Cu, Zn, Cr, and Mn were found within the acceptable limits stipulated by the World Health Organization (WHO); however, in contrast, the concentrations of Ni, Cd, and Pb remained below the detection limit. Notably, the concentration of Cr in two soap samples (S-2, S-3) out of twenty-one soap samples exceeded the permissible limit stipulated by the WHO. Health risks associated with the TM intake via dermal routes were evaluated in terms of chronic daily intake (CDI) and hazard quotient (HQ). The results indicated that no non-carcinogenic risks (NCR) are likely to occur owing to the use of those body soaps. The carcinogenic risk (CR) estimated for Cr revealed no possibility of probable carcinogenic diseases. Though the NCR and CR are unlikely to occur resulting from the long-term uses of these soaps, the present study provides baseline information on the possible contaminations of TMs in the beauty soaps that do not seem to have been reported so far in Bangladesh. In light of the above information, it can be concluded that the presence of TMs in the body soaps could be a warning for people in general thereby suggesting continuous monitoring.

Inhibition of farnesoid X receptor controls esophageal cancer cell growth in vitro and in nude mouse xenografts.

BACKGROUND: Gastroesophageal reflux is a risk factor for esophageal adenocarcinoma, and bile acid and its farnesoid X receptor (FXR) have been implicated in esophageal tumorigenesis. The authors investigated the role of FXR expression and activity in esophageal cancer initiation and growth. METHODS: FXR expression in esophageal adenocarcinoma tissues was assessed by immunohistochemistry. Knockdown of FXR expression in esophageal cancer cells in vitro and in nude mice xenografts was suppressed by FXR small hairpin RNA (shRNA) and guggulsterone (a natural FXR inhibitor). Esophageal cancer cells were treated with bile acids to demonstrate their effects on growth-promoting genes. RESULTS: FXR was expressed in 48 of 59 esophageal adenocarcinoma tissues (81.3%), and this overexpression was associated with higher tumor grade, larger tumor size, and lymph node metastasis; however, was inversely associated with retinoic acid receptor-ß2 (RAR-ß2 ) expression. Knockdown of FXR expression suppressed tumor cell growth in vitro and in nude mouse xenografts. Guggulsterone reduced the viability of esophageal cancer cells in a time-dependent and dose-dependent manner, whereas this effect was diminished after knockdown of FXR expression. Guggulsterone induced apoptosis through activation of caspase-8, caspase-9, and caspase-3 in tumor cells. FXR mediated bile acid-induced alterations of gene expression, eg, RAR-ß2 and cyclooxygenase-2 (COX-2). CONCLUSIONS: Inhibition of FXR by FXR shRNA or guggulsterone suppressed tumor cell viability and induced apoptosis in vitro, and it reduced tumor formation and growth in nude mouse xenografts. FXR also mediated bile acid-induced alterations of cell growth-related genes in esophageal cancer cells.

Does First-Use Syndrome Happen During Apheresis? A Case Report.

Steam, dry heat, radiation, ethylene oxide gas, evaporated hydrogen peroxide, and many other sterilization methods are used to sanitize medical equipment (e.g., chlorine dioxide gas, nitrogen dioxide, and vaporized peracetic acid). The benefits of ethylene oxide (EO) are its great processing capabilities, high ionic conductivity, high flexibility, low cost, and exceptional adhesive qualities. Patients on hemodialysis, those undergoing extracorporeal photopheresis, and plasmapheresis donors have all reported allergic reactions to EO. Differentiating between IgE-mediated anaphylaxis and anaphylactoid reactions is often impossible in practice due to the wide range of clinical symptoms. The infrequency of EO reactions coupled with healthcare personnel's lack of familiarity with this clinical phenomenon may result in their underdiagnosis. We describe the case of a platelet donor who developed an allergy, while donating at a transfusion facility, due to an ethylene oxide-sterilized apheretic kit. We aim to draw attention to the fact that care should be given while handling cases of this nature as they can become life-threatening.

Outcome of Intra-articular Injection of Total Stromal Cells and Platelet-Rich Plasma in Primary Knee Osteoarthritis: A Randomized Clinical Trial.

INTRODUCTION:  Mesenchymal stem cell (MSC) therapy appeared promising in knee osteoarthritis (OA). We examined if a single intra-articular (IA) autologous total stromal cells (TSC) and platelet-rich plasma (PRP) injection improved knee pain, physical function, and articular cartilage thickness in knee OA. METHODS:  The study was performed in the physical medicine and rehabilitation department of Bangabandhu Shaikh Mujib Medical University, Dhaka, Bangladesh. Knee OA was diagnosed according to the American College of Rheumatology criteria and randomly assigned to treatment (received TSC and PRP) and control groups. Kallgreen-Lawrance (KL) scoring system was used to grade primary knee OA. The Visual Analogue Scale (VAS, 0-10 cm) for pain, WOMAC (Western Ontario and McMaster Universities Arthritis Index) for physical function, and medial femoral condylar cartilage (MFC) thickness (millimeters) under ultrasonogram (US) were documented and compared between groups before and after treatment. Statistical Package analyzed data for Social Scientists (SPSS 22.0; IBM Corp, Armonk, NY) was used for data analysis. Pre- and post-intervention outcomes were measured using the Wilcoxon-sign test, whereas Mann-Whitney U-test calculated the difference between groups; a p-value <0.05 was considered statistically significant.  Result: In the treatment group, 15 received IA-TSC and PRP preparation, and in the control group, 15 patients received no injection, but quadricep muscle-strengthening exercise. There was no significant difference between groups regarding VAS for pain, WOMAC physical function, and cartilage thickness before starting the treatment and two weeks after intervention. VAS for pain and WOMAC physical function scores improved profoundly in the treatment group after 12 and 24 weeks of intervention; the pain and physical function scores difference between groups was also significant. However, significant mean femoral cartilage thickness was not changed until the end of 24 weeks (U=175.00, p=0.009 two-tailed and U= 130.00, p=0.016 two-tailed, respectively, for right and left knee). CONCLUSION:  Single TSC and PRP injection reduces knee pain and improves physical function and cartilage thickness in knee OA. While pain and physical function improvement happen earlier, cartilage thickness change takes more time.

Prospective study of cytomegalovirus serostatus and prostate cancer risk in the Prostate Cancer Prevention Trial.

PURPOSE: To investigate serologic evidence of infection by cytomegalovirus (CMV), a herpesvirus with known oncogenic potential that has been detected in malignant prostate tissue, in relation to prostate cancer (PCa) risk in a large case-control study nested in the Prostate Cancer Prevention Trial (PCPT). METHODS: Cases were men with a confirmed diagnosis of PCa after visit 2 (n = 614), and controls were men not diagnosed with PCa during the trial who also had a negative end-of-study biopsy (n = 616). Controls were frequency-matched to cases by age, treatment arm, and family history of PCa. Sera from visit 2 were tested for CMV IgG antibodies. RESULTS: No association was observed between CMV serostatus and PCa risk (adjusted CMV seroprevalence = 67.9 % for cases and 65.2 % for controls, odds ratio = 1.13, 95 % CI 0.89-1.45). CONCLUSIONS: Considering our null findings in the context of the full CMV literature, CMV infection, as measured by serostatus, does not appear to increase PCa risk.

Repeat polymorphisms in estrogen metabolism genes and prostate cancer risk: results from the Prostate Cancer Prevention Trial.

The etiology of prostate cancer remains elusive, although steroid hormones probably play a role. Considering the carcinogenic potential of estrogen metabolites as well as altered intraprostatic estrogen biosynthesis during the development of prostate cancer, we investigated associations between repeat polymorphisms of three key estrogen-related genes (CYP11A1, CYP19A1, UGT1A1) and risk of prostate cancer in the Prostate Cancer Prevention Trial (PCPT), designed to test finasteride versus placebo as a chemoprevention agent. Using data and specimens from 1154 cases and 1351 controls who were frequency matched on age, family history of prostate cancer and PCPT treatment arm, we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) separately in the placebo and finasteride arms. Among men in the placebo arm, CYP19A1 7/8 genotype carriers had a significantly higher risk of prostate cancer compared with those with the 7/7 genotype (OR = 1.70, 95% CI = 1.16-2.5), regardless of Gleason grade. This genotype was also associated with elevated serum estrogen levels. For the (TA)(n) repeat polymorphism in UGT1A1, the heterozygous short (<7 repeats)/long (≥7 repeats) genotype was significantly associated with the risk of low-grade prostate cancer (OR = 1.34, 95% CI = 1.05-1.70) compared with the short/short genotype. No significant association was found with CYP11A1. These associations were not observed among men in the finasteride arm. The results indicate that repeat polymorphisms in genes involved in estrogen biosynthesis and metabolism may influence risk of prostate cancer but that their effects may be modified by factors altering hormone metabolism, such as finasteride treatment.

Prognostic significance of differentially expressed miRNAs in esophageal cancer.

Altered microRNA (miRNA) expression has been found to promote carcinogenesis, but little is known about the role of miRNAs in esophageal cancer. In this study, we selected 10 miRNAs and analyzed their expression in 10 esophageal cancer cell lines and 158 tissue specimens using Northern blotting and in situ hybridization, respectively. We found that Let-7g, miR-21 and miR-195p were expressed in all 10 cell lines, miR-9 and miR-20a were not expressed in any of the cell lines, and miR-16-2, miR-30e, miR-34a, miR-126 and miR-200a were expressed in some of the cell lines but not others. In addition, transient transfection of miR-34a inhibited c-Met and cyclin D1 expression and esophageal cancer cell proliferation, whereas miR-16-2 suppressed RAR-ß(2) expression and increased tumor cell proliferation. Furthermore, we found that miR-126 expression was associated with tumor cell dedifferentiation and lymph node metastasis, miR-16-2 was associated with lymph node metastasis, and miR-195p was associated with higher pathologic disease stages in patients with esophageal adenocarcinoma. Kaplan-Meier analysis showed that miR-16-2 expression and miR-30e expression were associated with shorter overall and disease-free survival in all esophageal cancer patients. In addition, miR-16-2, miR-30e and miR-200a expression were associated with shorter overall and disease-free survival in patients with esophageal adenocarcinoma; however, miR-16-2, miR-30e and miR-200a expression were not associated with overall or disease-free survival in squamous cell carcinoma patients. Our data indicate that further evaluation of miR-30e and miR-16-2 as prognostic biomarkers is warranted in patients with esophageal adenocarcinoma. In addition, the role of miR-34a in esophageal cancer also warrants further study.

Serum estrogen levels and prostate cancer risk in the prostate cancer prevention trial: a nested case-control study.

OBJECTIVE: Finasteride reduces prostate cancer risk by blocking the conversion of testosterone to dihydrotestosterone. However, whether finasteride affects estrogens levels or change in estrogens affects prostate cancer risk is unknown. METHODS: These questions were investigated in a case-control study nested within the prostate cancer prevention trial (PCPT) with 1,798 biopsy-proven prostate cancer cases and 1,798 matched controls. RESULTS: Among men on placebo, no relationship of serum estrogens with risk of prostate cancer was found. Among those on finasteride, those in the highest quartile of baseline estrogen levels had a moderately increased risk of Gleason score < 7 prostate cancer (for estrone, odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.06-2.15; for estradiol, OR = 1.50, 95% CI = 1.03-2.18). Finasteride treatment increased serum estrogen concentrations; however, these changes were not associated with prostate cancer risk. CONCLUSION: Our findings confirm those from previous studies that there are no associations of serum estrogen with prostate cancer risk in untreated men. In addition, finasteride results in a modest increase in serum estrogen levels, which are not related to prostate cancer risk. Whether finasteride is less effective in men with high serum estrogens, or finasteride interacts with estrogen to increase cancer risk, is uncertain and warrants further investigation.

Antibody Response to ChAdOx1-nCoV-19 Vaccine Among Recipients in Bangladesh: A Prospective Observational Study.

PURPOSE: The aim of the study was to assess the antibody response to the ChAdOx1-nCoV vaccine in individuals who were not previously infected by COVID-19. PATIENTS AND METHODS: All people aged 18-65 years who received their first vaccination with ChAdOx1-nCoV from March to May 2021 were approached for inclusion. Individuals with sufficient antibody titers against SARS-CoV-2 infection before vaccination were considered previously infected and were excluded from the analysis. We observed viral spike protein RBD-S1-specific IgG antibody levels at day 28 of the first dose of vaccination and day 14 of the second dose of vaccination (74 days from index vaccination). An optical density ratio (ODR) of >1.1 was considered to have a positive antibody response, 0.8 to 1.1 borderline and <0.8 was denoted as negative. Informed consent was ensured before enrollment, and ethical principles conformed with the current Declaration of Helsinki. RESULTS: This observational study comprised 769 infection-naïve individuals (mean age 40.5 years, 38.9% female). Spike-specific IgG antibody responses elicited after the first and second doses of vaccine were 99.9% and 100%, respectively. The median ODR was 5.43 (interquartile range [IQR]: 4.32-6.98) and 10.90 (IQR 9.02-11.90) after the first and second doses. Higher age was associated with lower antibody levels after both dosages. However, no sex-specific variation was seen. People with comorbidity had a lower antibody level after the second dose. Tenderness (51.46%) and fever (19.30%) were the most common local and systemic side effects after vaccination. CONCLUSION: This study was one of the earlier attempts in the country to assess the antibody response to ChAdOx1-nCoV vaccine recipients. The results imply that general people should be encouraged to take the vaccine at their earliest.

Knowledge, Attitude, and Practices on Antimicrobial Use and Antimicrobial Resistance among Commercial Poultry Farmers in Bangladesh.

Antimicrobial resistance (AMR) has become an emerging health issue globally, posing a threat to zoonotic pathogens and foodborne diseases. In Bangladesh, the poultry sector supplies the majority of the demand for animal-source protein. The irrational and excessive use of antimicrobials (AMU) has been observed in the poultry sector. The development of AMR is associated with many factors, including the knowledge and attitudes of poultry farmers. Therefore, AMR reduction requires intervention from all the stockholders, including the farmers who are considered as end users of antimicrobials. This current research conducted a cross-sectional study to assess the knowledge, attitudes, and practices (KAP) of poultry farmers on AMU and AMR in Bangladesh. We determined the KAP of poultry farmers (broiler and layer farmers) of some selected districts of the country using a tested and paper-based questionnaire. The results demonstrated that most of the respondents have insufficient KAP regarding AMU and AMR. The respondents used a variety of antimicrobials primarily in the treatment of various diseases in poultry. One-third of the farmers did not seek antimicrobials from registered vets. Instead, they depended on others or themselves. The factor score analysis further revealed that the farmers' demographic and socioeconomic variables were significant factors influencing the KAP. An adjusted logistic regression analysis showed that older farmers with 9-12 years of farming experience and graduate-level education, engaging in medium-sized layer farming, were more likely to have correct KAP on AMU and AMR. Further, farmers from the Cox's Bazar region showed correct knowledge, whereas farmers of the Chattogram region showed a correct attitude towards AMU and AMR. A Spearman's rank-order correlation revealed a positive association between knowledge-attitudes and knowledge-practices. The findings of the current investigation provide baseline evidence about the KAP of poultry farmers from low-income resources and offer insights into designing interventions and policies for the use of AMU and AMR in Bangladesh.

Knowledge, Attitude, and Practices on Antimicrobial Use and Antimicrobial Resistance among Poultry Drug and Feed Sellers in Bangladesh.

Poultry production has boomed in Bangladesh in recent years. The poultry sector has contributed significantly to meet the increased demand for animal source proteins in the country. However, increased use of antimicrobials appeared to be a significant threat to food safety in the poultry sector. The poultry drug and feed sellers are at the frontline position involving selecting and delivering the antimicrobials to the poultry farmers. Studies assessing the poultry drug and feed sellers' knowledge, attitudes, and practices (KAPs) are limited. The current study aimed to assess the community poultry drug and feed sellers' KAPs of antimicrobial use (AMU) and antimicrobial resistance (AMR) in some selected areas of Bangladesh. We determined the respondents' (drug and the feed sellers) KAPs of AMU and AMR using a tested and paper-based questionnaire. The study demonstrated that most respondents have insufficient knowledge, less positive attitudes, and inappropriate practices regarding AMU and AMR. The factor score analysis further showed that the type of respondents and their years of experience, level of education, and training on the drug were the significant factors impacting the current knowledge, attitudes, and practices of AMU and AMR. The adjusted logistic regression analysis revealed that the drug sellers who completed their education up to 12th grade and had training on the drug had adequate knowledge of AMU and AMR. The data also showed that the drug sellers belong to the age group 31-35 and 36-40 years and who completed 12th grade had good attitudes on the same. Likewise, the analysis further determined that drug sellers belonging to the age category 18-25 and 26-30 years, and interestingly, the respondents who completed education up to 12th grade, had better practices. Spearman's rank-order correlation revealed a positive association between each pair of the KAPs scores for the respondents. The correlation was fair between knowledge-attitudes, knowledge-practices, and attitudes-practices. Based on the current study results, we recommend educational interventions and appropriate training for the poultry drug and feed sellers to raise awareness and to upgrade their current knowledge on the appropriate use of antimicrobials. This will ultimately lead to reducing the chances of developing AMR in the poultry sectors of the country.

Single nucleotide differences (SNDs) in the dbSNP database may lead to errors in genotyping and haplotyping studies.

The creation of single nucleotide polymorphism (SNP) databases (such as NCBI dbSNP) has facilitated scientific research in many fields. SNP discovery and detection has improved to the extent that there are over 17 million human reference (rs) SNPs reported to date (Build 129 of dbSNP). SNP databases are unfortunately not always complete and/or accurate. In fact, half of the reported SNPs are still only candidate SNPs and are not validated in a population. We describe the identification of SNDs (single nucleotide differences) in humans, that may contaminate the dbSNP database. These SNDs, reported as real SNPs in the database, do not exist as such, but are merely artifacts due to the presence of a paralogue (highly similar duplicated) sequence in the genome. Using sequencing we showed how SNDs could originate in two paralogous genes and evaluated samples from a population of 100 individuals for the presence/absence of SNPs. Moreover, using bioinformatics, we predicted as many as 8.32% of the biallelic, coding SNPs in the dbSNP database to be SNDs. Our identification of SNDs in the database will allow researchers to not only select truly informative SNPs for association studies, but also aid in determining accurate SNP genotypes and haplotypes.

Intra-individual variation in serum C-reactive protein over 4 years: an implication for epidemiologic studies.

BACKGROUND: Data on long-term intra-individual variability in high-sensitivity C-reactive protein (hsCRP) are needed to determine whether one measurement adequately reflects usual levels in prospective studies of on the etiology of cancer and other chronic diseases; when not reflective, the ability to statistically detect modest to moderate associations is reduced. The authors estimated the size of this source of variability and consequent attenuation of the relative risk (RR). METHODS: High-sensitivity C-reactive protein (hsCRP) concentration was measured using a high-sensitivity immunoturbidometric assay in sera collected at years 2, 4, and 6 from 50 men in the placebo arm of the Prostate Cancer Prevention Trial (PCPT). After natural logarithm-transformation of hsCRP, analysis of variance was used to estimate the within- and between-individual variances from which the intra-class correlation coefficient (ICC) was calculated. RESULTS: The observed RR due to an ICC < 1 was calculated by e((ln true RR*ICC)) for a range of true RRs. The 4-year ICC was 0.66. Measuring hsCRP once and assuming no other error, if the true RRs were 1.50, 2.00, and 3.00 when comparing high with low concentration, then the observed RRs would be 1.31, 1.58, and 2.06, respectively. CONCLUSION: Investigators planning to measure hsCRP only once should design adequately sized studies to preserve inferences for hypothesized modest to moderate RRs.

Androgen receptor CAG repeat length and association with prostate cancer risk: results from the prostate cancer prevention trial.

PURPOSE: We investigated the association between the length of the polymorphic trinucleotide CAG microsatellite repeats in exon 1 of the AR gene and the risk of prostate cancer. MATERIALS AND METHODS: This is a nested case-control study of 1,159 cases and 1,353 controls from the Prostate Cancer Prevention Trial, a randomized, placebo controlled trial testing whether the 5α-reductase inhibitor finasteride could decrease the 7-year prevalence of prostate cancer. During the course of the trial men underwent annual digital rectal examination and prostate specific antigen measurement. Prostate biopsy was recommended in all men with abnormal digital rectal examination or finasteride adjusted prostate specific antigen greater than 4.0 ng/ml. Cases were drawn from men with biopsy determined prostate cancer identified by for cause or end of study biopsy. Controls were selected from men who completed the end of study biopsy. RESULTS: Mean CAG repeat length did not differ between cases and controls. The frequency distribution of cases and controls for the AR CAG repeat length was similar. There were no significant associations of CAG repeat length with prostate cancer risk when stratified by treatment arm (finasteride or placebo), or when combined. There was also no significant association between CAG repeat length and the risk of low or high grade prostate cancer. CONCLUSIONS: There is no association of AR CAG repeat length with prostate cancer risk. Knowledge of AR CAG repeat length provides no clinically useful information to predict prostate cancer risk.