Targeted development and optimization of small-molecule ice recrystallization inhibitors (IRIs) for the cryopreservation of biological systems.

Despite the routine use of cryopreservation for the storage of biological materials, its outcomes are often sub-optimal (including reduced post-thaw viability, recovery, and functionality) due to the damage caused by uncontrolled ice growth. Traditional cryoprotective agents (CPAs), including dimethyl sulfoxide (DMSO), fail to prevent damage caused by ice growth and concerns over CPA cytotoxicity have fostered an increased interest in developing improved CPAs and cryoprotection strategies. The inhibition of ice recrystallization by natural antifreeze (glyco)proteins [AF(G)Ps] to improve cryopreservation outcomes has been examined; however, the ice binding properties of these substances and their challenging large-scale production make them poor CPA candidates. Therefore, the development and deployment of biocompatible, small-molecule ice recrystallization inhibitors (IRIs) for use as CPAs is a worthwhile objective. Extensive structure-activity relationship studies on AF(G)Ps revealed that simple carbohydrate derivatives could inhibit ice recrystallization. It was later discovered that this activity could be fine-tuned by delicately balancing the molecule's hydrophobicity and hydrophilicity. Current generation small-molecule IRIs have been meticulously designed to avoid binding to the surface of ice and subsequent biological testing (for both cytotoxicity and cryopreservation efficacy) has demonstrated significant improvements to the cryopreservation outcomes of several cell types. However, an individualized cell-specific approach for the simultaneous assessment of multiple cryopreservation outcomes is necessary to realize the full potential of IRIs as CPAs. This article provides a detailed overview of the development of small-molecule carbohydrate-based IRIs and highlights the crucial cell-specific biological considerations that must be taken into account when assessing cryopreservation outcomes. https://doi.org/10.54680/fr24210110112.

Effects of gonadal steroids on reward circuitry function and anhedonia in women with a history of postpartum depression.

BACKGROUND: Reward system dysfunction is evident across neuropsychiatric conditions. Here we present data from a double-blinded pharmaco-fMRI study investigating the triggering of anhedonia and reward circuit activity in women. METHODS: The hormonal states of pregnancy and parturition were simulated in euthymic women with a history of postpartum depression (PPD+; n = 15) and those without such a history (PPD-; n = 15) by inducing hypogonadism, adding back estradiol and progesterone for 8 weeks ("addback"), and then withdrawing both steroids ("withdrawal"). Anhedonia was assessed using the Inventory of Depression and Anxiety Symptoms (IDAS) during each hormone phase. Those who reported a 30 % or greater increase in IDAS anhedonia, dysphoria, or ill temper during addback or withdrawal, compared with pre-treatment, were identified as hormone sensitive (HS+) and all others were identified as non-hormone sensitive (HS-). The monetary incentive delay (MID) task was administered during fMRI sessions at pre-treatment and during hormone withdrawal to assess brain activation during reward anticipation and feedback. RESULTS: On average, anhedonia increased during addback and withdrawal in PPD+ but not PPD-. During reward feedback, both HS+ (n = 10) and HS- (n = 18) showed decreased activation in clusters in the right putamen (p < .031, FWE-corrected) and left postcentral and supramarginal gyri (p < .014, FWE-corrected) at the withdrawal scans, relative to pre-treatment scans. LIMITATIONS: A modest sample size, stringent exclusion criteria, and relative lack of diversity in study participants limit the generalizability of results. CONCLUSION: Although results do not explain differential hormone sensitivity in depression, they demonstrate significant effects of reproductive hormones on reward-related brain function in women.

Mobile meditation for improving quality of life, anxiety and depression among surgical residents and faculty.

BACKGROUND: Burnout, anxiety and depression are commonly reported among surgical residents and faculty members. Resident training programmes are encouraged to implement structured wellness initiatives, to address emotional stress. METHODS: Thirty otolaryngology residents and faculty members were invited to participate in this prospective pilot trial. Participants were randomised to either the intervention group, which involved completing 10 mobile meditation sessions, or the control group. Outcomes were measured with the Generalized Anxiety Disorder scale-7, Patient Health Questionnaire and Professional Quality of Life scale. RESULTS: Nineteen participants completed the study. Participants in the intervention group had a significantly greater mean change in Generalized Anxiety Disorder scale-7 score (-2.7 ± 3.335 vs 0.33 ± 1.225; p = 0.04). There was no significant difference in average change in Patient Health Questionnaire-9 scores or Professional Quality of Life scale sub-scores between the intervention and control groups. CONCLUSION: Short meditation sessions can significantly improve anxiety in surgical residents and faculty members, and they offer a simple, attainable and effective wellness intervention.

Totally implantable active middle-ear implants: a large, single-surgeon cohort.

OBJECTIVES: This study aimed to evaluate hearing outcomes and device safety in a large, single-surgeon experience with the totally implantable active middle-ear implants. METHODS: This was a retrospective case series review of 116 patients with moderate-to-severe sensorineural hearing loss undergoing implantation of active middle-ear implants. RESULTS: Mean baseline unaided pure tone average improved from 57.6 dB before surgery to 34.1 dB post-operatively, signifying a mean gain in pure tone average of 23.5 dB (p = 0.0002). Phonetically balanced maximum word recognition score improved slightly from 70.5 per cent to 75.8 per cent (p = 0.416), and word recognition score at a hearing level of 50 dB values increased substantially from 14.4 per cent to 70.4 per cent (p < 0.0001). Both revision and explant rates were low and dropped with increasing surgeon experience over time. CONCLUSION: This study showed excellent post-operative hearing results with active middle-ear implants with regard to pure tone average and word recognition score at a hearing level of 50 db. Complication rates in this case series were significantly lower with increasing experience of the surgeon. Active middle-ear implants should be considered in appropriate patients with moderate-to-severe sensorineural hearing loss who have struggled with conventional amplification and are good surgical candidates.

Men's experiences of radiotherapy treatment for localized prostate cancer and its long-term treatment side effects: a longitudinal qualitative study.

PURPOSE: To investigate men's experiences of receiving external-beam radiotherapy (EBRT) with neoadjuvant Androgen Deprivation Therapy (ADT) for localized prostate cancer (LPCa) in the ProtecT trial. METHODS: A longitudinal qualitative interview study was embedded in the ProtecT RCT. Sixteen men with clinically LPCa who underwent EBRT in ProtecT were purposively sampled to include a range of socio-demographic and clinical characteristics. They participated in serial in-depth qualitative interviews for up to 8 years post-treatment, exploring experiences of treatment and its side effects over time. RESULTS: Men experienced bowel, sexual, and urinary side effects, mostly in the short term but some persisted and were bothersome. Most men downplayed the impacts, voicing expectations of age-related decline, and normalizing these changes. There was some reticence to seek help, with men prioritizing their relationships and overall health and well-being over returning to pretreatment levels of function. Some unmet needs with regard to information about treatment schedules and side effects were reported, particularly among men with continuing functional symptoms. CONCLUSIONS: These findings reinforce the importance of providing universal clear, concise, and timely information and supportive resources in the short term, and more targeted and detailed information and care in the longer term to maintain and improve treatment experiences for men undergoing EBRT.

Anemochory of diapausing stages of microinvertebrates in North American drylands.

1. Dry, ephemeral, desert wetlands are major sources of windblown sediment, as well as repositories for diapausing stages (propagules) of aquatic invertebrates. Zooplankton propagules are of the same size range as sand and dust grains. They can be deflated and transported in windstorm events. This study provides the evidence that dust storms aid in dispersal of microinvertebrate propagules via anemochory (aeolian transport). 2. We monitored 91 windstorms at six sites in the southwestern U.S. over a 17-year period. The primary study site was located in El Paso, Texas in the northern Chihuahuan Desert. Additional samples were collected from the Southern High Plains region. Dust carried by these events was collected and rehydrated to hatch viable propagules transported with it. 3. Using samples collected over a six-year period, 21 m above the ground which included 59 storm events, we tested the hypothesis that transport of propagules is correlated with storm intensity by monitoring meteorological conditions such as storm duration, wind direction, wind speed, and PM10 (fine dust concentration). An air quality monitoring site located adjacent to the dust samplers provided quantitative hourly measurements. 4. Rehydration results from all events showed that ciliates were found in 92% of the samples, rotifers in 81%, branchiopods in 29%, ostracods in 4%, nematodes in 13%, gastrotrichs in 16%, and tardigrades in 3%. Overall, four bdelloid and 11 monogonont rotifer species were identified from rehydrated windblown dust samples. 5. PCA results indicated gastrotrichs, branchiopods, nematodes, tardigrades, and monogonont rotifer occurrence positively correlated with PM10 and dust event duration. Bdelloid rotifers were correlated with amount of sediment deposited. NMDS showed a significant relationship between PM10 and occurrence of some taxa. Zero-inflated, general linear models with mixed-effects indicated significant relationships with bdelloid and nematode transport and PM10. 6. Thus, windstorms with high particulate matter concentration and long duration are more likely to transport microinvertebrate diapausing stages in drylands.

Bacterial community structure and response to nitrogen amendments in Lake Shenandoah (VA, USA).

Microbial processes are critical to the function of freshwater ecosystems, yet we still do not fully understand the factors that shape freshwater microbial communities. Furthermore, freshwater ecosystems are particularly susceptible to effects of environmental change, including influx of exogenous nutrients such as nitrogen and phosphorus. To evaluate the impact of nitrogen loading on the microbial community structure of shallow freshwater lakes, water samples collected from Lake Shenandoah (Virginia, USA) were incubated with two concentrations of either ammonium, nitrate, or urea as a nitrogen source. The potential impact of these nitrogen compounds on the bacterial community structure was assessed via 16S rRNA amplicon sequencing. At the phylum level, the dominant taxa in Lake Shenandoah were comprised of Actinobacteria and Proteobacteria, which were not affected by exposure to the various nitrogen treatments. Overall, there was not a significant shift in the diversity of the bacterial community of Lake Shenandoah with the addition of nitrogen sources, indicating this shallow system may be constrained by other environmental factors.

Oxidative stress, inflammation and risk of neurodegeneration in a population sample.

BACKGROUND AND PURPOSE: Inflammation and oxidative stress (OS) have been clearly linked to neurodegeneration. However, studies investigating the associations between peripheral markers of inflammation and cognitive decline have produced mixed results. This is possibly due to the fact that markers are typically tested individually despite the fact that biologically they function interactively. Thus, the aim of this study was to investigate the association between a combination of OS/inflammation markers and outcomes including mild cognitive impairment (MCI) diagnosis, cognitive decline and hippocampal atrophy. METHODS: Oxidative stress/inflammation status was assessed in 380 older community-living individuals. Thirteen blood markers were assayed. Principal component analysis (PCA) of all markers was conducted to identify the more salient inflammatory components. Associations between significant principal components, MCI diagnosis, previous change in Mini-Mental State Examination (MMSE) score and hippocampal atrophy were investigated through logistic and linear multiple regression. RESULTS: Two factors (PC1 and PC2) reflecting predominantly broad pro-inflammatory activity and two factors (PC3 and PC4) reflecting predominantly OS activity were identified by PCA analysis. PC3 and PC4 were predictive of MCI. PC3 was also predictive of prior MMSE change. PC1, PC2 and PC3 were significantly associated with hippocampal atrophy. CONCLUSIONS: Combined analysis of complex and interacting biomarkers revealed a protective association between antioxidant activity and MCI that is consistent with lifestyle factors shown to reduce risk of cognitive decline. OS and broad systemic inflammation were also found to be associated with hippocampal atrophy further highlighting the benefits of the PCA methodology applied in this study.

The impact of type 2 diabetes and body mass index on cerebral structure is modulated by brain reserve.

BACKGROUND AND PURPOSE: Body mass index (BMI), hyperglycaemia and type 2 diabetes and their interactive effects are associated with brain volume atrophy in ageing. It remains to be established if these risk factors are particularly concerning in individuals with high or low brain volumes. METHODS: Demographics, venous blood and magnetic resonance imaging data were collected for 494 healthy community-living adults aged 53-78 (mean 65) years, as part of the Personality and Total Health Through Life study. Associations between BMI, blood glucose, diabetes status and brain volume (whole brain, grey matter, white matter and subcortical structures) were investigated using quantile regression. RESULTS: Quantile regression revealed vulnerability to BMI × glucose interactions particularly in lower volumes and significant main effects for type 2 diabetes particularly in higher volumes. Diabetes was most strongly associated with brain volumes. The association between BMI, blood glucose and diabetes was not consistent across the full range of brain volumes. CONCLUSION: Explicit investigation of the upper and lower boundaries of brain volume distributions was valuable. We found evidence of protective reserve from higher brain volumes and that a combination of high BMI and higher blood glucose was particularly concerning for individuals with lower brain volumes.

Evidence for regional aeolian transport of freshwater micrometazoans in arid regions.

While separated by large expanses of dry terrain unsuitable for aquatic biota, aridland waters possess high biodiversity. How aquatic micrometazoans disperse to, and colonize, these isolated ephemeral habitats are not well understood. We used a multi-faceted approach including wind tunnel and rehydration experiments, and next-generation sequencing to assess potential movement of diapausing propagules of aquatic invertebrates by anemochory across regional scales (102-105 km). Wind tunnel experiments using dry playa sediments with added micrometazoan propagules demonstrated that after entrainment by saltation and downwind transport were subsequently recoverable as viable animals when rehydrated. Further, rehydration of fallen natural dust yielded micrometazoans, including rotifers, gastrotrichs, microcrustaceans, and nematodes. Using conserved DNA primers, we identified >3,300 eukaryotic Operational Taxonomic Units (excluding fungi) in the dust including some taxa found in rehydration experiments. Thus, we provide strong evidence that anemochory can disperse micrometazoans among isolated, ephemeral ecosystems in North American deserts and likely elsewhere.

T-Cell Responses in Adults During Natural Respiratory Syncytial Virus Infection.

Background: The pathogenesis of respiratory syncytial virus (RSV) in older adults may be due to age-related T-cell immunosenescence. Thus, we evaluated CD4 and CD8 T-cell responses during RSV infection in adults across the age spectrum. Methods: Peripheral blood mononuclear cells collected during RSV infection in adults, age 26-96 years, were stimulated with live RSV and peptide pools representing F, M, NP, and G proteins and analyzed by flow cytometry. Results: There were no significant age-related differences in frequency of CD4+ T cells synthesizing interferon (IFN)γ, interleukin (IL)2, IL4, IL10, or tumor necrosis factor (TNF)α or in CD8+IFNγ+ T cells. IL4+CD4+ T-cell numbers were low, as were IL13 and IL17 responses. However, in univariate analysis, CD4 T-cell IFNγ, IL2, IL4, IL10, and TNFα responses and CD8+IFNγ+ T cells were significantly increased with more severe illness requiring hospitalization. In multivariate analysis, viral load was also associated with increased T-cell responses. Conclusions: We found no evidence of diminished RSV-specific CD4 or CD8 T-cell responses in adults infected with RSV. However, adults with severe disease seemed to have more robust CD4 and CD8 T-cell responses during infection, suggesting that disease severity may have a greater association with T-cell responses than age.

Quality of life and social functioning of former long-stay psychiatric patients transferred into the community: a 10 year follow up study.

PURPOSE: Deinstitutionalisation in Ireland began following the impetus of the successful transfer of psychiatric patients into the community in other countries. This study sought to evaluate the quality of life (QoL) and social functioning (SF) of former long-stay institutionalised patients with severe and enduring mental illness who had been relocated into local community settings and followed up 10 years later. METHOD: One month prior to hospital closure, 87 former long-stay psychiatric patients, the majority of whom had a diagnosis of schizophrenia, were assessed on a range of QoL and SF measures. Patients were followed-up 10 years later in the community, to evaluate baseline predictors of quality of life and social functioning. RESULTS: Study completers (n = 35) improved significantly on a range of QoL and SF measures over the 10 year period. Specific improvements were noted in domestic skills (t = - 2.8, p < 0.0008), community skills (t = - 4.9, p < 0.001), as well as the activity and social relations measure (t = - 4.1, p < 0.001). Increased social function (t = - 6.3, p < 0.001) and improvement on the social behaviour scale (t = 7.6, p < 0.001) were noted at follow-up. Linear regression analysis found that less social behaviour problems at baseline predicted QoL 10 years later (t = - 2.6, p < 0.02). CONCLUSION: This study demonstrated that transfer into the community from an institutional environment was associated with long-term improvements in quality of life and social functioning, even in those who spent many years in the institution. Those who demonstrated the greatest improvement in QoL had less social behavioural problems at baseline assessment, providing further evidence of the success of community living for former long-stay patients.

The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder.

BACKGROUND: Intranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, thus, has received considerable interest as a potential ASD therapeutic agent. Although preclinical research indicates that OT modulates the functional output of the mesocorticolimbic dopamine system that processes rewards, no clinical brain imaging study to date has examined the effects of OT on this system using a reward processing paradigm. To address this, we used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD. METHODS: In this placebo-controlled double-blind study, 28 children and adolescents with ASD (age: M = 13.43 years, SD = 2.36) completed two fMRI scans, one after intranasal OT administration and one after PLC administration. During both scanning sessions, participants completed social and nonsocial incentive delay tasks. Task-based neural activation and connectivity were examined to assess the impact of OT relative to PLC on mesocorticolimbic brain responses to social and nonsocial reward anticipation and outcomes. RESULTS: Central analyses compared the OT and PLC conditions. During nonsocial reward anticipation, there was greater activation in the right nucleus accumbens (NAcc), left anterior cingulate cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal cortex, and right frontal pole (FP) during the OT condition relative to PLC. Alternatively, during social reward anticipation and outcomes, there were no significant increases in brain activation during the OT condition relative to PLC. A Treatment Group × Reward Condition interaction revealed relatively greater activation in the right NAcc, right caudate nucleus, left ACC, and right OFC during nonsocial relative to social reward anticipation during the OT condition relative to PLC. Additionally, these analyses revealed greater activation during nonsocial reward outcomes during the OT condition relative to PLC in the right OFC and left FP. Finally, functional connectivity analyses generally revealed changes in frontostriatal connections during the OT condition relative to PLC in response to nonsocial, but not social, rewards. CONCLUSIONS: The effects of intranasal OT administration on mesocorticolimbic brain systems that process rewards in ASD were observable primarily during the processing of nonsocial incentive salience stimuli. These findings have implications for understanding the effects of OT on neural systems that process rewards, as well as for experimental trials of novel ASD treatments developed to ameliorate social communication impairments in ASD.

Trajectories of BMI change impact glucose and insulin metabolism.

BACKGROUND AND AIMS: The aim of this study was to examine, in a community setting, whether trajectory of weight change over twelve years is associated with glucose and insulin metabolism at twelve years. METHODS AND RESULTS: Participants were 532 community-living middle-aged and elderly adults from the Personality and Total Health (PATH) Through Life study. They spanned the full weight range (underweight/normal/overweight/obese). Latent class analysis and multivariate generalised linear models were used to investigate the association of Body Mass Index (BMI, kg/m2) trajectory over twelve years with plasma insulin (µlU/ml), plasma glucose (mmol/L), and HOMA2 insulin resistance and beta cell function at follow-up. All models were adjusted for age, gender, hypertension, pre-clinical diabetes status (normal fasting glucose or impaired fasting glucose) and physical activity. Four weight trajectories were extracted; constant normal (mean baseline BMI = 25; follow-up BMI = 25), constant high (mean baseline BMI = 36; follow-up BMI = 37), increase (mean baseline BMI = 26; follow-up BMI = 32) and decrease (mean baseline BMI = 34; follow-up BMI = 28). At any given current BMI, individuals in the constant high and increase trajectories had significantly higher plasma insulin, greater insulin resistance, and higher beta cell function than those in the constant normal trajectory. Individuals in the decrease trajectory did not differ from the constant normal trajectory. Current BMI significantly interacted with preceding BMI trajectory in its association with plasma insulin, insulin resistance, and beta cell function. CONCLUSION: The trajectory of preceding weight has an independent effect on blood glucose metabolism beyond body weight measured at any given point in time.

Is chemotherapy always required for cancer in pregnancy? An observational study.

BACKGROUND: Cancer in pregnancy is relatively rare, but the incidence is increasing. Several studies show that cytotoxic agents are safe to use in pregnancy from the second trimester onwards. AIMS: This study assesses the maternal and foetal outcomes of cancers diagnosed during pregnancy. In particular, it focuses on a subset of women who elected to defer systemic chemotherapy until after delivery. This study examines if all cancers need to be treated during pregnancy or if, in certain cases, treatment can be safely deferred until after full-term delivery. METHODS: This is a retrospective observational study of women diagnosed with cancer during pregnancy in an Irish cancer centre over a 27-year period. All women diagnosed with cancer during pregnancy who were referred to the medical oncology department for consideration of chemotherapy were included in this study. Medical and pharmacy records were extensively reviewed. RESULTS: Twenty-five women were diagnosed with cancer in pregnancy and referred to medical oncology for consideration of systemic chemotherapy. Sixteen women (64%) commenced chemotherapy during pregnancy, seven women (28%) did not receive chemotherapy while pregnant, but commenced treatment immediately after delivery, and two (8%) did not receive any systemic chemotherapy at all. Of the seven women who commenced chemotherapy after delivery, six (85.7%) were diagnosed before 30/40 gestation. There were three cases of Hodgkin's lymphoma, two breast cancers and one ovarian cancer. After a median follow-up of 12 years, all six mothers remain disease-free. CONCLUSIONS: This study identified a select cohort of patients that did not receive chemotherapy during pregnancy. There were no adverse outcomes to mothers due to delayed treatment.

Root-Knot Nematode Parasitism Suppresses Host RNA Silencing.

Root-knot nematodes damage crops around the world by developing complex feeding sites from normal root cells of their hosts. The ability to initiate and maintain this feeding site (composed of individual "giant cells") is essential to their parasitism process. RNA silencing pathways in plants serve a diverse set of functions, from directing growth and development to defending against invading pathogens. Influencing a host's RNA silencing pathways as a pathogenicity strategy has been well-documented for viral plant pathogens, but recently, it has become clear that silencing pathways also play an important role in other plant pathosystems. To determine if RNA silencing pathways play a role in nematode parasitism, we tested the susceptibility of plants that express a viral suppressor of RNA silencing. We observed an increase in susceptibility to nematode parasitism in plants expressing viral suppressors of RNA silencing. Results from studies utilizing a silenced reporter gene suggest that active suppression of RNA silencing pathways may be occurring during nematode parasitism. With these studies, we provide further evidence to the growing body of plant-biotic interaction research that suppression of RNA silencing is important in the successful interaction between a plant-parasitic animal and its host.

Prescribing error at hospital discharge: a retrospective review of medication information in an Irish hospital.

BACKGROUND: Prescribing error may result in adverse clinical outcomes leading to increased patient morbidity, mortality and increased economic burden. Many errors occur during transitional care as patients move between different stages and settings of care. AIM: To conduct a review of medication information and identify prescribing error among an adult population in an urban hospital. METHODS: Retrospective review of medication information was conducted. Part 1: an audit of discharge prescriptions which assessed: legibility, compliance with legal requirements, therapeutic errors (strength, dose and frequency) and drug interactions. Part 2: A review of all sources of medication information (namely pre-admission medication list, drug Kardex, discharge prescription, discharge letter) for 15 inpatients to identify unintentional prescription discrepancies, defined as: "undocumented and/or unjustified medication alteration" throughout the hospital stay. RESULTS: Part 1: of the 5910 prescribed items; 53 (0.9%) were deemed illegible. Of the controlled drug prescriptions 11.1% (n = 167) met all the legal requirements. Therapeutic errors occurred in 41% of prescriptions (n = 479) More than 1 in 5 patients (21.9%) received a prescription containing a drug interaction. Part 2: 175 discrepancies were identified across all sources of medication information; of which 78 were deemed unintentional. Of these: 10.2% (n = 8) occurred at the point of admission, whereby 76.9% (n = 60) occurred at the point of discharge. CONCLUSIONS: The study identified the time of discharge as a point at which prescribing errors are likely to occur. This has implications for patient safety and provider work load in both primary and secondary care.

Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.

BACKGROUND: Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. METHODS: We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. RESULTS: The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. CONCLUSIONS: In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).