Structural Changes in the Cervical Facet Capsular Ligament: Potential Contributions to Pain Following Subfailure Loading

While studies have demonstrated the cervical facet capsule is at risk for tensile injury during whiplash, the relationship between joint loading, changes in the capsule’s structure, and pain is not yet fully characterized. Complementary approaches were employed to investigate the capsule’s structure-function relationship in the context of painful joint loading. Isolated C6/C7 facet joints (n=8) underwent tensile mechanical loading, and measures of structural modification were compared for two distraction magnitudes: 300 μm (PV) and 700 μm (SV). In a matched in vivo study, C6/C7 facet joints (n=4) were harvested after the same SV distraction and the tissue was sectioned to analyze collagen fiber organization using polarized light microscopy. Laxity following SV distraction (7.30±3.01%) was significantly greater (p\u3c0.001) than that produced following PV distraction (0.99±0.44%). Also, SV distractions produced significantly higher maximum principal strain (p\u3c0.001) in the capsule and resulted in significantly greater decreases in stiffness (p=0.002) when compared to PV distraction. After SV distraction in vivo, mean angular deviation of the fiber direction (16.8±2.6º) was significantly increased (p=0.004) relative to naive samples in the lateral region of the capsule, indicating collagen fiber disorganization. These findings demonstrate that certain subfailure loading conditions are associated with altered joint mechanics and collagen fiber disorganization and imply ligament damage. Substructural damage in the capsule has the potential to both directly modulate nerve fiber signaling and produce sustained physiologic modifications that may initiate persistent pain

Circumcision of Male Children for Reduction of Future Risk for HIV: Acceptability among HIV Serodiscordant Couples in Kampala, Uganda

The ultimate success of medical male circumcision for HIV prevention may depend on targeting male infants and children as well as adults, in order to maximally reduce new HIV infections into the future.We conducted a cross-sectional study among heterosexual HIV serodiscordant couples (a population at high risk for HIV transmission) attending a research clinic in Kampala, Uganda on perceptions and attitudes about medical circumcision for male children for HIV prevention. Correlates of willingness to circumcise male children were assessed using generalized estimating equations methods.318 HIV serodiscordant couples were interviewed, 51.3% in which the female partner was HIV uninfected. Most couples were married and cohabiting, and almost 50% had at least one uncircumcised male child of ≤18 years of age. Overall, 90.2% of male partners and 94.6% of female partners expressed interest in medical circumcision for their male children for reduction of future risk for HIV infection, including 79.9% of men and 87.6% of women who had an uncircumcised male child. Among both men and women, those who were knowledgeable that circumcision reduces men's risk for HIV (adjusted prevalence ratio [APR] 1.34 and 1.14) and those who had discussed the HIV prevention effects of medical circumcision with their partner (APR 1.08 and 1.07) were significantly (p≤0.05) more likely to be interested in male child circumcision for HIV prevention. Among men, those who were circumcised (APR 1.09, p = 0.004) and those who were HIV seropositive (APR 1.09, p = 0.03) were also more likely to be interested in child circumcision for HIV prevention.A high proportion of men and women in Ugandan heterosexual HIV serodiscordant partnerships were willing to have their male children circumcised for eventual HIV prevention benefits. Engaging both parents may increase interest in medical male circumcision for HIV prevention

Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer

Background Apalutamide, a competitive inhibitor of the androgen receptor, is under development for the treatment of prostate cancer. We evaluated the efficacy of apalutamide in men with nonmetastatic castration-resistant prostate cancer who were at high risk for the development of metastasis. Methods We conducted a double-blind, placebo-controlled, phase 3 trial involving men with nonmetastatic castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less. Patients were randomly assigned, in a 2:1 ratio, to receive apalutamide (240 mg per day) or placebo. All the patients continued to receive androgen-deprivation therapy. The primary end point was metastasis-free survival, which was defined as the time from randomization to the first detection of distant metastasis on imaging or death. Results A total of 1207 men underwent randomization (806 to the apalutamide group and 401 to the placebo group). In the planned primary analysis, which was performed after 378 events had occurred, median metastasis-free survival was 40.5 months in the apalutamide group as compared with 16.2 months in the placebo group (hazard ratio for metastasis or death, 0.28; 95% confidence interval [CI], 0.23 to 0.35;

A 'snip' in time: what is the best age to circumcise?

<p>Abstract</p> <p>Background</p> <p>Circumcision is a common procedure, but regional and societal attitudes differ on whether there is a need for a male to be circumcised and, if so, at what age. This is an important issue for many parents, but also pediatricians, other doctors, policy makers, public health authorities, medical bodies, and males themselves.</p> <p>Discussion</p> <p>We show here that infancy is an optimal time for clinical circumcision because an infant's low mobility facilitates the use of local anesthesia, sutures are not required, healing is quick, cosmetic outcome is usually excellent, costs are minimal, and complications are uncommon. The benefits of infant circumcision include prevention of urinary tract infections (a cause of renal scarring), reduction in risk of inflammatory foreskin conditions such as balanoposthitis, foreskin injuries, phimosis and paraphimosis. When the boy later becomes sexually active he has substantial protection against risk of HIV and other viral sexually transmitted infections such as genital herpes and oncogenic human papillomavirus, as well as penile cancer. The risk of cervical cancer in his female partner(s) is also reduced. Circumcision in adolescence or adulthood may evoke a fear of pain, penile damage or reduced sexual pleasure, even though unfounded. Time off work or school will be needed, cost is much greater, as are risks of complications, healing is slower, and stitches or tissue glue must be used.</p> <p>Summary</p> <p>Infant circumcision is safe, simple, convenient and cost-effective. The available evidence strongly supports infancy as the optimal time for circumcision.</p

p53 Pro72Arg polymorphism and prostate cancer in men of African descent.

BACKGROUND: p53 is a transcription factor that regulates the cell cycle, DNA repair, and apoptosis. A variant at codon 72, rs1042522, results in altered activities for p53 and is, notably, differentially distributed among different ethnic populations. However, associations of this variant with cancer in men of African descent have not been explored. Herein, we tested the hypothesis that rs1042522 was associated with prostate cancer (PCa) risk. MATERIALS AND METHODS: Genotypes were determined by PCR-RFLP methods in a study population of African descent consisting of 266 PCa patients and 196 male controls. RESULTS: Our results indicate that the p53 polymorphism may be associated with increased risk of PCa. Genotypes were significantly and marginally associated with PCa risk using the dominant and log-additive genetic models (OR=1.53, 95% CI: 1.02-2.29, P=0.04; OR=1.33, 95% CI: 0.99-1.78, P=0.06, respectively). After adjusting for age, the associations with PCa remained, but results were not statistically significant (OR=1.48, 95% CI: 0.95-2.31, P=0.08; OR=1.30, 95% CI: 0.95-1.80, P=0.10, respectively). CONCLUSIONS: The present study demonstrates that population-dependent differences in allele frequencies associated with health disparities provide a valuable framework for the interrogation of complex diseases in all populations. © 2010 Wiley-Liss, Inc

Identification of genetic risk associated with prostate cancer using ancestry informative markers

BACKGROUND: Prostate cancer (PCa) is a common malignancy and a leading cause of cancer death among men in the United States with African-American (AA) men having the highest incidence and mortality rates. Given recent results from admixture mapping and genome-wide association studies for PCa in AA men, it is clear that many risk alleles are enriched in men with West African genetic ancestry.METHODS: A total of 77 ancestry informative markers (AIMs) within surrounding candidate gene regions were genotyped and haplotyped using Pyrosequencing in 358 unrelated men enrolled in a PCa genetic association study at the Howard University Hospital between 2000 and 2004. Sequence analysis of promoter region single-nucleotide polymorphisms (SNPs) to evaluate disruption of transcription factor-binding sites was conducted using in silico methods.RESULTS: Eight AIMs were significantly associated with PCa risk after adjusting for age and West African ancestry. SNP rs1993973 (intervening sequences) had the strongest association with PCa using the log-additive genetic model (P0.002). SNPs rs1561131 (genotypic, P0.007), rs1963562 (dominant, P0.01) and rs615382 (recessive, P0.009) remained highly significant after adjusting for both age and ancestry. We also tested the independent effect of each significantly associated SNP and rs1561131 (P0.04) and rs1963562 (P0.04) remained significantly associated with PCa development. After multiple comparisons testing using the false discovery rate, rs1993973 remained significant. Analysis of the rs156113-, rs1963562-rs615382l and rs1993973-rs585224 haplotypes revealed that the least frequently found haplotypes in this population were significantly associated with a decreased risk of PCa (P0.032 and 0.0017, respectively).CONCLUSIONS: The approach for SNP selection utilized herein showed that AIMs may not only leverage increased linkage disequilibrium in populations to identify risk and protective alleles, but may also be informative in dissecting the biology of PCa and other health disparities. © 2012 Macmillan Publishers Limited All rights reserved

Factors associated with mothers’ decisions on male neonatal circumcision in Swaziland

Neonatal male circumcision is safer, easier and cheaper than adult male circumcision, but is not widely practised in Swaziland. It has been suggested as one of several ways of controlling the spread of HIV. We conducted research aimed at assessing mothers' knowledge, attitudes and perceptions towards circumcision and reasons why mothers have their newly born male children circumcised. A cross-sectional study was conducted at Hlatikulu Government Hospital, a rural hospital in Shiselweni region, Swaziland. The target population was mothers with children younger than 6 months old who presented at the hospital. Of the 392 participants who were interviewed, 43 (11.2%) had circumcised their children. The participants' ages ranged from 15 to 44 with a mean age of 25.3 years. All the respondents had a mean knowledge score of 7.8 out of a maximum possible of 11, a mean attitudes score of 3.6 out of 6 and a mean perception score of 1.8 out of 3. The main reasons for mothers circumcising their children were to keep the penile organ clean (97.7%), to reduce sexually transmitted infections when one is sexually active (97.7%) and to reduce HIV transmission (97.7%). Participants who did not circumcise their children cited mainly that their spouses did not approve (84.5%), that they were anxious about complications after the operation (44.4%) and fear that their newborns would feel pain (54.4%). The mothers in this study had high knowledge, positive attitudes and perceptions towards male neonatal circumcision, but the circumcision levels are still very low. Interventions need to be directed towards providing accurate information and resources that facilitate mothers, and to a greater extend fathers, in making the decision to circumcise their male children and being able to act on that decision.