Abnormal centriolar biomarker ratios correlate with unexplained bull artificial insemination subfertility: a pilot study.

The mechanisms underlying male infertility are poorly understood. Most mammalian spermatozoa have two centrioles: the typical barrel-shaped proximal centriole (PC) and the atypical fan-like distal centriole (DC) connected to the axoneme (Ax). These structures are essential for fertility. However, the relationship between centriole quality and subfertility (reduced fertility) is not well established. Here, we tested the hypothesis that assessing sperm centriole quality can identify cattle subfertility. By comparing sperm from 25 fertile and 6 subfertile bulls, all with normal semen analyses, we found that unexplained subfertility and lower sire conception rates (pregnancy rate from artificial insemination in cattle) correlate with abnormal centriolar biomarker distribution. Fluorescence-based Ratiometric Analysis of Sperm Centrioles (FRAC) found only four fertile bulls (4/25, 16%) had positive FRAC tests (having one or more mean FRAC ratios outside of the distribution range in a group's high-quality sperm population), whereas all of the subfertile bulls (6/6, 100%) had positive FRAC tests (P = 0.00008). The most sensitive biomarker was acetylated tubulin, which had a novel labeling pattern between the DC and Ax. These data suggest that FRAC and acetylated tubulin labeling can identify bull subfertility that remains undetected by current methods and may provide insight into a novel mechanism of subfertility.

Do Stressful Events and Racial Discrimination Explain Racial Gaps in Exclusive Breastfeeding Duration? A Qualitative Interview Study with Black, Hispanic, and White Mothers Living in Ohio.

OBJECTIVES: This study aimed to understand why breastfeeding and exclusive breastfeeding rates substantially decrease shortly after birth among mothers in the USA. Specifically, we aimed to illuminate the impact of stressful life events and racial discrimination on mothers' breastfeeding behaviors and duration. METHODS: We conducted a qualitative analysis of semi-structured telephone interviews with women (N = 66; 47 White, 16 Black, and 3 Hispanic) who gave birth between 2019 and 2021 in Ohio. Interviews were conducted between March 2022 and May 2022. Interviews were digitally recorded, transcribed verbatim, analyzed, coded, and organized into themes. RESULTS: After thematic analysis of the data, five key themes were identified: (1) stress, (2) breastfeeding barriers, (3) policy and system change to support breastfeeding mothers, (4) racial discrimination, and (5) breastfeeding motivators. Our study found that the breastfeeding experience was both a positive bonding experience and a challenging practice, characterized by physical, mental, and sociocultural struggles. CONCLUSION FOR PRACTICE: Addressing stress during pregnancy, equitable access to culturally sensitive lactation support, improved parental leave, and enhanced workplace breastfeeding regulations are essential to increasing breastfeeding duration among racially marginalized women.

Sperm centriole assessment identifies male factor infertility in couples with unexplained infertility - a pilot study.

Unexplained infertility affects about one-third of infertile couples and is defined as the failure to identify the cause of infertility despite extensive evaluation of the male and female partners. Therefore, there is a need for a multiparametric approach to study sperm function. Recently, we developed a Fluorescence-Based Ratiometric Analysis of Sperm Centrioles (FRAC) assay to determine sperm centriole quality. Here, we perform a pilot study of sperm from 10 fertile men and 10 men in couples with unexplained infertility, using three centriolar biomarkers measured at three sperm locations from two sperm fractions, representing high and low sperm quality. We found that FRAC can identify men from couples with unexplained infertility as the likely source of infertility. Higher quality fractions from 10 fertile individuals were the reference population. All 180 studied FRAC values in the 10 fertile individuals fell within the reference population range. Eleven of the 180 studied FRAC values in the 10 infertile patients were outliers beyond the 95% confidence intervals (P = 0.0008). Three men with unexplained infertility had outlier FRAC values in their higher quality sperm fraction, while four had outlier FRAC values in their lower quality sperm fraction (3/10 and 4/10, P = 0.060 and P = 0.025, respectively), suggesting that these four individuals are infertile due, in part, to centriolar defects. We propose that a larger scale study should be performed to determine the ability of FRAC to identify male factor infertility and its potential contribution to sperm multiparametric analysis.

Serum bilirubin as a predictor of graft outcomes after renal transplant.

Bilirubin is a signaling molecule that alters the immune response and metabolism. While bilirubin has been employed as a marker of renal and cardiovascular health, its role in renal transplant recipients is not known. In this study, we sought to determine the impact of bilirubin (total, direct and indirect) on the estimated glomerular filtration rate (eGFR) after renal transplantation. We conducted a retrospective review of pre- and postoperative bilirubin levels in 457 renal transplant recipients at a single center. Pre- and post-rejection bilirubin levels were also assessed in those patients who experienced a rejection episode. No statistically significant differences were found in bilirubin levels during the pre-transplant to post-rejection period among patients who experienced rejection with kidney allograft survival. No statistically significant associations were observed between baseline bilirubin and post-transplant eGFR in the full patient group or within the gender- or race-stratified groups. Baseline bilirubin was not correlated with time to rejection. Our results suggest that bilirubin may not offer renoprotection in renal transplant recipients.

Renal Displacement with Supine to Prone Positional Change: Effect of Sex and Body Mass Index.

Objective: To determine patterns of kidney and retroperitoneal organ movement during positional change between the supine and prone positions as seen on CT scans. Methods: Axial CT scans of 75 subjects who underwent supine and prone positions were retrospectively analyzed. A total of 1650 measurements were taken for anterior/posterior, medial/lateral, cranial/caudal, skin-to-calix distance, kidney-to-liver distance, and kidney-to-colon distance in both positions. Results: Pronation shortens the distance from the skin to renal calix for both the right (99.62 mm vs 85.14 mm; p < 0.00001) and left (96.67 mm vs 90.80 mm; p < 0.00001) sides. The reduction in left-side tract length for obese patients is significantly greater than that of normal weight patients (11.88 mm vs -5.02 mm; p = 0.001). The left kidney displaces ventrally (11.12 mm vs 18.59 mm; p < 0.00001), while the right kidney does not (14.26 mm vs 15.30 mm; p = 0.30). The right kidney displaces cranially (62.76 mm vs 79.51 mm; p < 0.00001), while the left kidney does not (64.35 mm vs 66.52 mm; p = 0.14). The left kidney in females moves medially, while no change is seen in males (4.22 mm vs -0.48 mm; p = 0.0004). The left kidney in females displaces toward the descending colon, while it moves farther away in males (2.73 mm vs -2.01 mm; p = 0.011). Conclusions: Both sex and body mass index had effects on the movement of the kidneys upon pronation. The differences can be clinically useful to help pre- and intraoperative planning.

Urine versus stent cultures and clinical UTIs.

PURPOSE: Current American Urological Association guidelines recommend pre-operative antimicrobial therapy based on prior urine cultures (UC); however, the role of stent culture (SC) in urologic practice is unclear. We examined whether UC and SC differed at the time of stent removal, as well as the association, microbiology, and timing of subsequent UTIs as related to SC. METHODS: This was a retrospective review of 159 patients with ureteral stents for indications of urolithiasis, benign stricture, malignant obstruction, and kidney transplant. UC and SC were analyzed at the time of stent removal. Patients were followed for 12 months after stent removal for development, concordance, and timing of clinical UTIs. RESULTS: In 159 patients, 15% had positive UC and 45% had positive SC. Of patients who had positive SC, 66% had negative UC. All patients with positive UC had identical micro-organisms on SC; however, 33% of these had SC with additional micro-organisms. Relative to those with both negative UC and SC, patients with negative UC and positive SC had a 5.7 odds, and those with both positive UC and SC had a 13.6 odds of developing a clinical UTI within 12 months. Concordance of SC and future UTI was highest in those with post-operative sepsis, and those with Candida species on SC. CONCLUSIONS: SC was a unique risk factor for development of UTI within 12 months of stent removal. Clinicians should consider SC results when empirically treating those with post-operative sepsis or those with UTI after Candida on SC.

A dynamic basal complex modulates mammalian sperm movement.

Reproductive success depends on efficient sperm movement driven by axonemal dynein-mediated microtubule sliding. Models predict sliding at the base of the tail - the centriole - but such sliding has never been observed. Centrioles are ancient organelles with a conserved architecture; their rigidity is thought to restrict microtubule sliding. Here, we show that, in mammalian sperm, the atypical distal centriole (DC) and its surrounding atypical pericentriolar matrix form a dynamic basal complex (DBC) that facilitates a cascade of internal sliding deformations, coupling tail beating with asymmetric head kinking. During asymmetric tail beating, the DC's right side and its surroundings slide ~300 nm rostrally relative to the left side. The deformation throughout the DBC is transmitted to the head-tail junction; thus, the head tilts to the left, generating a kinking motion. These findings suggest that the DBC evolved as a dynamic linker coupling sperm head and tail into a single self-coordinated system.

Fluorescence-Based Ratiometric Analysis of Sperm Centrioles (FRAC) Finds Patient Age and Sperm Morphology Are Associated With Centriole Quality.

A large proportion of infertility and miscarriage causes are unknown. One potential cause is a defective sperm centriole, a subcellular structure essential for sperm motility and embryonic development. Yet, the extent to which centriolar maladies contribute to male infertility is unknown due to the lack of a convenient way to assess centriole quality. We developed a robust, location-based, ratiometric assay to overcome this roadblock, the Fluorescence-based Ratiometric Assessment of Centrioles (FRAC). We performed a case series study with semen samples from 33 patients, separated using differential gradient centrifugation into higher-grade (pellet) and lower-grade (interface) sperm fractions. Using a reference population of higher-grade sperm from infertile men with morphologically standard sperm, we found that 79% of higher-grade sperm of infertile men with substandard sperm morphology have suboptimal centrioles (P = 0.0005). Moreover, tubulin labeling of the sperm distal centriole correlates negatively with age (P = 0.004, R = -0.66). These findings suggest that FRAC is a sensitive method and that patient age and sperm morphology are associated with centriole quality.

Healthcare providers attitudes towards risk stratification of adopted patients with limited family history information: a cross-sectional survey.

Familial medical history (FMH) is crucial for patient risk stratification; however, adopted patients' FMH knowledge may be limited. This can be problematic when determining steps in screening and management of patients. Little is known about providers' opinions and practices regarding adopted patients with limited FMH. This study explored healthcare providers' attitudes towards these patients and explored whether they interact differently with these individuals. We assessed providers' opinions regarding earlier screening, more aggressive management techniques, and genetic testing for this population. Surveys were mailed to 300 Family Practice Medical Doctors (M.D.s) and Doctors of Osteopathic Medicine (D.O.s), in the state of Ohio. Descriptive statistics were calculated, and chi-squared or Fisher's exact tests assessed relationships between provider characteristics and screening and management practices (alpha = 0.05). There was no association between years of practice or provider sex and how they screened, managed, or interacted with adopted patients. Providers that had adopted patients did not hold any statistically different opinions on how adopted patients should be managed versus providers that did not. Most providers did not initiate earlier screening for patients with unknown FMH, with the exception of D.O.s initiating earlier mammographic screening. However, all providers took more extensive personal histories and carried out more extensive monitoring. Although family medical history is only a piece of the puzzle when determining what medical care is right for a particular patient, it still remains an important aspect that needs to be addressed. Providers need to ensure that they are correctly managing patients with unknown familial risk factors.

State Tested Nursing Assistants' Workplace Experiences That Threaten or Support Intent to Stay.

PURPOSE: Over 1 million Americans utilize skilled nursing facilities (SNFs) annually. Within SNFs, State Tested Nursing Assistants (STNAs) are primary caregivers; however, low retention rates are notable and threaten patient care. DESIGN: A phenomenological, qualitative study was conducted to explore intrinsic factors that influence STNAs' intent to stay in their positions. METHODS: Ten STNAs employed at for-profit SNFs participated in semistructured face-to-face interviews. Data were analyzed to identify broad concepts and recurrent themes. FINDINGS: Findings suggest that intrinsic factors supporting and threatening intent to stay included the fulfillment of basic psychological needs. Supporting themes included self-confidence, appreciation, positive relationships, and a willingness to go beyond required duties. Threatening themes included frustration, lack of support, and career advancement opportunities. CONCLUSIONS: Findings provide an understanding of factors that influence STNAs' intent to stay. CLINICAL RELEVANCE: The results may help guide the development of responsive strategies that improve quality and continuity of care in SNFs.

Same-Day Discharge for Laparoscopic Donor Nephrectomy.

INTRODUCTION: Laparoscopic donor nephrectomy has provided advantages of decreased postoperative pain and length of stay when compared to the open approach. We provide our results of same-day discharge for laparoscopic donor nephrectomy. CASE PRESENTATION: We examined the safety and efficacy of same-day discharge for laparoscopic donor nephrectomy in a retrospective cohort analysis. This institutional review board-approved study began in July 2015, when all consecutive patients who underwent laparoscopic donor nephrectomy were offered same-day discharge. Experimental and control groups were analyzed for differences in sex, age, body mass index, surgery time, estimated blood loss, procedure, complications, length of stay, and distance lived from hospital. Statistical analyses were completed with Mann-Whitney U or Fisher's exact test, as appropriate. MANAGEMENT AND OUTCOME: Eight patients underwent laparoscopic donor nephrectomy during the study period. Of the 8 donors, 4 were discharged on the same day as surgery. The other 4 were discharged the following day. No significant differences were found between the 2 groups with respect to the aforementioned variables. At a median follow-up of 206 days, no complications have been reported. DISCUSSION: The results of our pilot study revealed that same-day discharge is safe and feasible, could have a significant impact on patient satisfaction and healthcare costs, and warrants further study.

Same-Day Discharge for Patients Undergoing Robot-Assisted Laparoscopic Radical Prostatectomy Is Safe and Feasible: Results of a Pilot Study.

INTRODUCTION: With healthcare reform, cost and patient satisfaction will directly affect hospital reimbursement. We present data on same-day discharge (SDD) for patients who underwent robot-assisted laparoscopic radical prostatectomy (RALP). METHODS: Patient data were gathered in an IRB-approved database. In April 2015, the surgeon (S.J.) began SDD. The SDD protocol for RALP includes multimodal anesthesia/analgesia and extended recovery. Interim analysis revealed that government insurance (CMS) refused hospital reimbursement for SDD. As of that time, only patients with commercial insurance were offered SDD. The demographic and peri-operative data were compared between the two cohorts (Group 1, SDD; Group 2, Admitted patients) by using Mann-Whitney U, chi-squared, or fisher exact tests, where appropriate. RESULTS: During the study period, 21 patients had undergone RALP. Eleven of 21 patients were offered SDS, and nine (81.8%) were discharged. Both those who elected to stay were successfully discharged on the next day. Patient age, body mass index (BMI), prostate-specific antigen, operative time, estimated blood loss (EBL), prostate weight, distance from home to hospital, margin status, marital status, and household income were not statistically significantly different between the two groups. The same is true between patients who underwent RALP both before and after initiation of the SDD protocol with the exception of EBL (greater in the SDD group). There have been no reported complications or readmissions for any of the patients in Group 1. CONCLUSION: Our novel pilot study reveals that SDS is safe and feasible. We are currently conducting a further evaluation of patient satisfaction. Future research is needed to verify these conclusions.

Comparison of Urologic Complications Between Ureteroneocystostomy and Ureteroureterostomy in Renal Transplant: A Meta-Analysis.

OBJECTIVES: Transplant surgeons use a myriad of ureteral anastomotic techniques in renal transplant. Although the Lich-Gregoir extravesical anastomosis is the most common, ureteroureterostomy also is used. In this meta-analysis, our objective was to compare the complication rates of these 2 techniques as reported in the literature. MATERIALS AND METHODS: A systematic review of the literature revealed 44 articles, 6 of which met our inclusion criteria. Studies were compiled using Review Manager (RevMan version 5.3, Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen, Denmark). Forest plots were generated to assess relative risk. A fixed-effects model was used for low heterogeneity, and a random-effects model was used for high heterogeneity. RESULTS: Overall complications were similar for both procedures (relative risk, 1.22; 95% confidence interval, 0.9-1.65), as were rates of urine leak and fistula (relative risk, 0.79; 95% confidence interval, 0.17-3.64) and hematuria (relative risk, 0.24; 95% confidence interval, 0.001-4.84). Stricture, obstruction, and stone formation were more common after ureteroureterostomy (relative risk, 0.63; 95% confidence interval, 0.45-0.88), whereas vesicoureteral reflux (relative risk, 6.82; 95% confidence interval, 1.68-27.61) and urinary tract infection (relative risk, 2.29; 95% confidence interval, 1.3-4.03) were more common after ureteroneocystostomy. CONCLUSIONS: With similar overall complication rates, both procedures can be viewed as being acceptable primary anastomotic techniques. In light of differing individual complication rates and the scarcity of data comparing the 2 methods, no specific recommendation regarding that technique should be used can currently be elucidated. We believe that further prospective studies comparing ureteroneocystostomy and primary ureteroureterostomy may reveal which is superior regarding complication rates.

Genetic variation in the bioactivation pathway for polycyclic hydrocarbons and heterocyclic amines in relation to risk of colorectal neoplasia.

Animal work implicates chemical carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HAAs) as contributing to the development of colorectal cancer (CRC). The epidemiologic evidence, however, remains inconsistent possibly due to intra-individual variation in bioactivation of these compounds. We conducted a case-control study of colorectal adenoma (914 cases, 1185 controls) and CRC (496 cases, 607 controls) among Japanese Americans, European Americans and Native Hawaiians to investigate the association of genetic variation in the PAH and HAA bioactivation pathway (CYP1A1, CYP1A2, CYP1B1, AHR and ARNT) identified through sequencing with risk of colorectal neoplasia, as well as their interactions with smoking and intakes of red meat and HAAs. The A allele for ARNT rs12410394 was significantly inversely associated with CRC [odds ratios (ORs) and 95% confidence intervals (CIs) for GG, AG and AA genotypes: 1.00, 0.66 (0.48-0.89), 0.54 (0.37-0.78), P(trend) = 0.0008] after multiple comparison adjustment. CYP1A2 rs11072508 was marginally significantly associated with CRC, where each copy of the T allele was associated with reduced risk (OR: 0.72, 95% CI: 0.58-0.88, P(trend) = 0.0017). No heterogeneity of genetic effects across racial/ethnic groups was detected. In addition, no significant interaction was observed after adjusting for multiple testing between genetic variants and pack-years of smoking, intake of red meat or HAAs (PhIP, MeIQx, Di-MeIQx or total HAAs) or NAT2 genotype (Rapid versus Slow or Intermediate). This study suggests that the genomic region around ARNT rs12410394 may harbor variants associated with CRC.

Serum CRP and IL-6, genetic variants and risk of colorectal adenoma in a multiethnic population.

Chronic inflammation, which is suspected to play a role in the development of colorectal cancer (CRC), has rarely been studied in colorectal adenoma. We investigated the inter-relationships of serum levels of the inflammatory proteins CRP and in IL-6, single nucleotide polymorphisms (SNPs) in the CRP (rs1205, rs1130864, rs1800947) and IL6 (rs1800795) genes, and lifestyle factors with colorectal adenoma in a sigmoidoscopy-based case-control study of 271 adenoma cases and 539 age-, sex-, and race/ethnicity-matched controls in Hawaii. We found no association of serum CRP or IL-6 levels with the risk of adenoma. A multiple regression with stepwise selection identified elevated BMI, Caucasian and Native Hawaiian versus Japanese race/ethnicity, and current smoking as being associated with significantly higher serum CRP and IL-6 levels. Female versus male gender was also associated with higher CRP levels and older age with higher IL-6 levels. The C allele of rs1205 and the A allele of rs1130864 were significantly associated with higher serum CRP levels (p (trend): 0.0002 and 0.01, respectively), as well as with a decreased adenoma risk [rs1205: OR for CT and CC vs. TT = 0.69 (95% CI: 0.48-0.98) and 0.53 (0.34-0.83), respectively, p (trend) = 0.008; rs1130864: OR for GA and AA versus GG = 0.65 (0.45-0.93) and 0.74 (0.31-1.76), respectively, p (trend) = 0.04]. The findings of lower serum CRP and IL-6 levels in Japanese (a group with a high CRC risk) and of a decreased adenoma risk observed for alleles associated with higher circulating CRP levels suggest a protective effect for CRP in early colorectal neoplasia that warrants further study.

Vitamin D receptor polymorphisms and breast cancer risk: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.

BACKGROUND: Vitamin D is hypothesized to lower the risk of breast cancer by inhibiting cell proliferation via the nuclear vitamin D receptor (VDR). Two common single nucleotide polymorphisms (SNP) in the VDR gene (VDR), rs1544410 (BsmI), and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokI ff genotype, which encodes a less transcriptionally active isoform of VDR, and reduced risk has been reported for the BsmI BB genotype, a SNP in strong linkage disequilibrium with a 3'-untranslated region, which may influence VDR mRNA stability. METHODS: We pooled data from 6 prospective studies in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium to examine associations between these SNPs and breast cancer among >6,300 cases and 8,100 controls for each SNP using conditional logistic regression. RESULTS: The odds ratio (OR) for the rs2228570 (FokI) ff versus FF genotype in the overall population was statistically significantly elevated [OR, 1.16; 95% confidence interval (95% CI), 1.04-1.28] but was weaker once data from the cohort with previously published positive findings were removed (OR, 1.10; 95% CI, 0.98-1.24). No association was noted between rs1544410 (BsmI) BB and breast cancer risk overall (OR, 0.98; 95% CI, 0.89-1.09), but the BB genotype was associated with a significantly lower risk of advanced breast cancer (OR, 0.74; 95% CI, 0.60-0.92). CONCLUSIONS: Although the evidence for independent contributions of these variants to breast cancer susceptibility remains equivocal, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status.

Association of genetic variation in the transforming growth factor beta-1 gene with serum levels and risk of colorectal neoplasia.

In the normal intestinal epithelium transforming growth factor beta-1 (TGFbeta-1) acts as a growth inhibitor, but in malignant cells it may act as a tumor promoter. However, only limited information is available on genetic variation in the TGFB1 gene and its relationship to circulating levels and risk of colorectal cancer. To characterize associations of genetic variation [tagging single-nucleotide polymorphisms (tagSNP) and haplotypes with frequency >0.05] at the TGFB1 locus with circulating TGFbeta-1 and risk of colorectal neoplasia, we conducted two case-control studies (including 271 colorectal adenoma cases and 544 controls, and 535 colorectal adenocarcinoma cases and 656 controls) among Japanese Americans, Caucasians, and Native Hawaiians in Hawaii. Serum TGFbeta-1 was measured by sandwich ELISA among the subjects of the first study. The variant A allele for tagSNP rs6957 was associated with higher serum TGFbeta-1 [means (in ng/mL) and 95% confidence interval (95% CI) for AA or AG, 32.6 (30.6-34.7); GG, 29.0 (25.1-32.9); P(difference) = 0.05] after adjusting for age and other factors. Homozygous carriers of the variant G allele for tagSNP rs11466345 had a statistically significantly lower risk of adenocarcinoma [AG versus AA: odds ratio (OR), 0.9 (95% CI, 0.7-1.2); GG versus AA: OR, 0.4 (95% CI, 0.2-0.7); P(trend) = 0.01]. The haplotype carrying both variants was also statistically significantly associated with a reduced risk of adenocarcinoma (OR, 0.3; 95% CI, 0.1-0.8). Although not statistically significant, the direction and magnitude of the corresponding ORs were similar for adenoma. These results suggest that a haplotype containing SNP rs11466345 at the 3' end of TGFB1 is associated with genetic susceptibility to colorectal neoplasia.

Sun exposure, diet, and melanoma in Hawaii Caucasians.

Much uncertainty remains about the type of sunlight exposure that most increases risk of cutaneous melanoma and the role of diet. The authors conducted a population-based case-control study (1986-1992) of Caucasians living on Oahu, Hawaii; included were 278 cases and age- and sex-matched controls. Plasma samples were measured for retinol, carotenoids, and alpha-tocopherol by high-pressure liquid chromatography. Selenium was measured in blood and toenails by neutron activation. Celtic and English ancestries, migration to Hawaii before age 20 years, fair complexion, inability to tan, and family history of skin cancer, as well as height, hours spent in the summer sun, blistering sunburns during adolescence, and moles, all increased melanoma risk. With regard to diet and biomarkers, only alcohol was associated with risk. The odds ratios for increasing tertiles of lifetime ethanol intake were 1.0, 1.2 (95% confidence interval (CI): 0.6, 2.2), and 2.3 (95% CI: 1.2, 4.4) (p for trend = 0.01) for men and 1.0, 1.1 (95% CI: 0.5, 2.4), and 1.7 (95% CI: 0.7, 3.8) (p for trend = 0.19) for women. Dietary lipids were unrelated to risk, but polyunsaturated fat intake appeared to modify the effects of alcohol and toenail selenium on melanoma risk. These data provide additional evidence for the association of constitutional susceptibility factors, intense sun exposure (particularly before age 20 years), and alcohol consumption with melanoma risk.