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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. Centrioles are ancient organelles with a conserved architecture and their rigidity is thought to restrict microtubule sliding. Here authors show that, in mammalian sperm, the atypical distal centriole and its surrounding atypical pericentriolar matrix form a dynamic basal complex that facilitates a cascade of internal sliding deformations, coupling tail beating with asymmetric head kinking.

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.

Introduction: Currently, there is limited evidence for the relationship of Exosome-based Prostate Intelliscore (EPI) and multiparametric magnetic resonance imaging (mpMRI) in stratifying risk for clinically significant prostate cancer. Using a retrospective cohort study design, we sought to characterize the relationship between these two noninvasive metrics and prostate biopsy outcome. Methods: Data were collected via electronic medical record for all patients who underwent EPI testing from 1 January 2019 to 3 February 2022 and had available medical records at a single mid-western university medical center. Positive test result was defined as >15.6 for EPI, ≥3 PI-RADS score and ≥3 + 4 Gleason Score for biopsy findings. Utility of EPI, mpMRI and combined use was characterized through calculation of sensitivity, specificity, positive predictive value, negative predictive value, and ROC analysis. Results: A total of 226 patients were identified as receiving EPI testing for risk stratification of clinically significant prostate cancer. Sensitivity for EPI was 91%, mpMRI was 90%, and the highest was combined use at 96%. With ROC analysis, AUC for EPI alone was 0.57 (95% CI, 0.47–0.67) and 0.78 (95% CI, 0.70–0.87) for mpMRI alone. With prior positive EPI result, AUC for combined use with mpMRI was 0.80 (95% CI, 0.71–0.89). Further subgroup analysis resulted in increased AUC values of EPI 0.67 (95% CI, 0.48–0.87), mpMRI 0.90 (95% CI, 0.76–1.0), and combined 0.90 (95% CI, 0.75–1.0) in the African American population. Discussion: We observed that the combined use of EPI and mpMRI led to an avoided biopsy in 43% of patients. Using both parameters increased the overall sensitivity and diagnostic accuracy in detecting clinically significant prostate cancer. The best test performance was observed in the African American cohort. Identifying optimal noninvasive tools to assess risk for prostate cancer is crucial to providing accurate and cost-effective care. Future study should utilize a prospective study design to further support the combined use of these metrics.

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.

Introduction: We examined three patient characteristics: body mass index (BMI), the American Society of Anesthesiologists (ASA) status, and pre-admission testing (PAT), and their effect on total operating room (OR) time for six urologic procedures, including ureteroscopy, transurethral resection of the prostate (TURP), transurethral resection of bladder tumor (TURBT), prostatectomy, nephrectomy, and kidney transplants. Methods: We investigated the effect of these patient factors on OR time using linear regression for urologic procedures from The University of Toledo Medical Center from 2015 to 2020. Results: An increase in BMI was found to correlate with a statistically significant increase in total OR time for ureteroscopy, prostatectomy, and kidney transplant. The PAT showed a decrease in OR time for TURBT cases and an increase for kidney transplant cases. We found no correlation between the ASA status and changes in the total OR time. Conclusions: A higher BMI significantly increases the total OR time for robotic-assisted prostatectomy and kidney transplant but has a minimal effect on endoscopic procedures. Our results do not support ASA status as a predictor of total OR time. Due to the lack of consistency in results for PAT for the different procedures analyzed, further exploration of the effect of this patient factor on OR efficiency is needed.

The demand for transplantable organs has outpaced the supply. Thus, 20 Americans die every day while waiting for an organ. Although most adults support organ donation, 42% are not registered. The rate is even lower among young adults who are not enrolled in/never graduated from college. The aim of this study was to use the Integrated Behavior Model (IBM) to identify factors that predicted organ donation registration among a racially diverse sample of non-student young adults. The study was observational and cross-sectional. Proportional allocation was used to identify a racially diverse sample of 550 non-student, young adults from ten states in the U.S. with the lowest registration rates. A valid and reliable survey was designed, pilot-tested, and administered. A total of 407 young adults completed the survey (74%). Only 19% were registered donors. Caucasians were more likely to be registered donors than racial minorities, χ² (3, N = 407) = 15.19, p = 0.002. Those with more positive direct attitudes toward registration were 1.5 times more likely to be registered than those who had negative direct attitudes. Among non-registrants, indirect descriptive norm and direct attitude were statistically significant predictors of behavioral intention. Moreover, those who knew someone who donated an organ and knew someone who needed a transplant were nearly three times more likely to intend to register in the next year. The IBM proved useful in elucidating factors that predicted intention to register among non-student young adults. The IBM should be used by those who desire to increase registration rates.

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.

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.

Abstract Online education offers care providers flexibility and convenience. Applying the New World Kirkpatrick Model of training evaluation, this descriptive study evaluated the design and content of a 30-40 minute online training course that introduces direct-care workers to a multi-sensory device to help manage dementia symptoms in older adults. Following course completion, an online survey obtained ratings of engagement (i.e., aesthetics, ease of use, novelty, and involvement), relevance, and knowledge/skills gained from the training using a 5-point Likert scale. A convenience sample of 72 undergraduate students enrolled in health science and human service programs at a Midwestern university participated. The majority were white (83.3%), non-Hispanic (81.9%) females (88.9%). Most participants agreed or strongly agreed (median=4) with positive statements related to engagement with the course. Statements about relevance to their intended career were rated even higher (median=5). Wilcoxon signed-rank tests for matched pairs revealed statistically significant improvements on self-reported pre-post knowledge/skills scores (p<0.005). The results indicated that participants found the training aesthetically pleasing, easy to use, novel, and that it encouraged user involvement. Participants thought the topics covered were relevant to the professional career they are pursing, and they learned new knowledge/skills. Responses to open-ended questions suggested improvements to the design (e.g., color choice) and content (e.g., expanded topics and resources). Future research will evaluate a revised course with direct-care workers who will use the multi-sensory device in long term care facilities. Subsequently, an intervention study will determine the effectiveness of the device in increasing the well-being of people with dementia.

Abstract Osteosarcopenic Obesity (OSO) is the concurrent presence of obesity (excess body fat), sarcopenia (low muscle mass) and osteoporosis (low bone mineral density). Low levels of serum vitamin D (vitD) have been associated with each disease and their simultaneous presence. We examined this association in adults aged ≥50 years from the 2001-2006 survey cycles of the National Health and Nutrition Examination Survey (NHANES) (N=3791). SAS v9.4 complex survey procedures were used. Demographics and vitD status were compared across OSO components (0,1,2,3) by chi-squared tests and ANOVAs. Odds ratios and 95% confidence intervals for the association between vitD status and increasing number of OSO components were calculated using multinomial logistic regression (alpha=0.05). The mean age was 65.0 years (30% were older adults ≥ 65), 45.6% were female, and prevalences for obesity, osteoporosis, sarcopenia and OSO were 84.7%, 8.0%, 16.3%, and 1.8%, respectively. Additionally, 30.9% of the sample was vitD deficient. After adjusting for supplement use, and race, women with 1 or 2, and men with 1,2 or 3 OSO components were more likely to be vitD deficient than sufficient, compared to those with none [women: 2.8(1.4-5.7), 2.1(1.4-6.8), and men: 2.3 (1.5-3.6), 3.5(2.1-5.9) and 6.3(1.0-38.5), respectively]. Vitamin D status was associated with having one or two OSO components in women, and OSO and components in men, after adjusting for supplement use, sex, and race. These results suggest it is important to consider obesity, osteoporosis, and sarcopenia jointly with respect to vitamin D status in the chronic disease management of aging and older adults.