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Objective: Feeling depressed and lethargic are common side effects of prostate cancer (PCa) and its treatments. We examined the incidence and severity of feeling depressed and lack of energy in patients in a population based PCa registry., Methods: We included men diagnosed with PCa between 2015 and 2019 in Victoria, Australia, and enrolled in the Prostate Cancer Outcomes Registry. The primary outcome measures were responses to two questions on the Expanded Prostate Cancer Index Composite (EPIC-26) patient reported instrument: problems with feeling depressed and problems with lack of energy 12 months following treatment. We evaluated associations between these and age, cancer risk category, treatment type, and urinary, bowel, and sexual function., Results: Both outcome questions were answered by 9712 out of 12,628 (77%) men. 981 patients (10%) reported at least moderate problems with feeling depressed; 1563 (16%) had at least moderate problems with lack of energy and 586 (6.0%) with both. Younger men reported feeling depressed more frequently than older men. Lack of energy was more common for treatments that included androgen deprivation therapy than not (moderate/big problems: 31% vs. 13%), irrespective of disease risk category. Both outcomes were associated with poorer urinary, bowel, and sexual functional domain scores., Conclusions: Self-reported depressive feelings and lack of energy were frequent in this population-based registry. Problems with feeling depressed were more common in younger men and lack of energy more common in men having hormonal treatment. Clinicians should be aware of the incidence of these symptoms in these at-risk groups and be able to screen for them., (© 2021 John Wiley & Sons Ltd.)

Objective: The aim of the study was to understand the recovery phenomena and to explore participants' perspectives on the biopsychosocial facilitators and barriers affecting their recovery after a minor transport injury., Methods: A qualitative method was used involving semi-structured interviews with 23 participants who sustained a minor transport injury. Interviews and analysis were guided by the biopsychosocial model (BPS) of health. The outcomes were themes capturing biopsychosocial barriers to, and personal experiences of, recovery using a previously defined framework., Results: The themes indicate that recovery is a multifaceted phenomenon affected by comorbidities such as chronic pain, depression and anxiety. A range of subsequent complexities such as the inability to self-care and undertaking daily domestic duties, and incapacity to participate in recreational activities were major barriers to recovery. These barriers were found to be an on-going source of frustration, dissatisfaction and a perceived cause of depressive symptomatology in many participants. Most participants reported mixed feelings of the care received. Other common issues raised included a lack of understanding of the assessment time, regular follow-up, guidance and on-going support., Conclusion: This study revealed that recovery after a minor transport-related injury was a challenging, complex, demanding and a long-term process for the individuals in this study. Findings from this limited cohort suggested that, for participants to return to their pre-accident health status, a more coordinated approach to information and care delivery may be required., (© 2019 The Authors Health Expectations published by John Wiley & Sons Ltd.)

Objective: To assess the implications of increasing utilization of noninvasive prenatal screening (NIPS), which may reach 50% with the concomitant decrease in diagnostic procedures (DPs) for its impact on detection of chromosomal abnormalities., Methods: We studied our program's statistics over 5 years for DPs and utilization of array comparative genomic hybridization (aCGH). We then modeled the implications in our program if DP had not fallen and nationally of a 50% DP and aCGH testing rate using well-vetted expectations for the diagnosis of abnormal copy number variants (CNVs)., Results: Our DP fell 40% from 2013-2017. Utilization of aCGH for DP nearly tripled. We detected 28 abnormal CNVs. If DP had not fallen, we likely would have detected 60. With 4 million US births per year, 2 million DPs would detect 30 000 abnormal CNVs and 4000 standard aneuploidies. At a 1/500 complication-pregnancy loss rate, the detection/complication ratio is 8.5/1., Conclusions: Noninvasive prenatal screening has significantly changed the practice of prenatal screening. However, while increasing the detection of Down syndrome, the concomitant decrease in DP and lack of aCGH results in missing many more abnormalities than the increase in Down syndrome and complications of DP combined. From a public health perspective, such represents a missed opportunity for overall health care delivery., (© 2018 John Wiley & Sons, Ltd.)

The purpose of this study was to provide in-depth insight into men's experiences of prostate cancer, specifically: perceived stigma and self-blame, social isolation, unmet need and help-seeking. A qualitative descriptive approach was used. Semi-structured interviews were undertaken with 20 men diagnosed with prostate cancer, and thematic analysis was undertaken. Some participants perceived a stigma associated with prostate cancer and cancer in general, which sometimes acted as a barrier to disclosure. Self-blame and internalisation of cause was not a prominent issue. Participants' descriptions of emotional distress, social isolation and anxiety demonstrated the impact of prostate cancer. Social isolation was most commonly reported as a physical consequence of treatment and/or side effects. Participants felt both support and ongoing care were limited at post-treatment. Most did not seek or receive help for emotional or psychosocial problems from a formal source due to anticipated awkwardness, autonomous coping, not burdening others, unwanted sympathy and retaining privacy. Prostate cancer can cause considerable emotional and social burden for some men, and many are unlikely to seek or receive help. Men, and their support networks, require active encouragement throughout diagnosis, treatment and follow-up to overcome barriers and access additional support, particularly for sexual, emotional and psychosocial issues., (© 2017 John Wiley & Sons Ltd.)

Background: Prostate cancer is commonly diagnosed in men worldwide. Surgery, in the form of radical prostatectomy, is one of the main forms of treatment for men with localised prostate cancer. Prostatectomy has traditionally been performed as open surgery, typically via a retropubic approach. The advent of laparoscopic approaches, including robotic-assisted, provides a minimally invasive alternative to open radical prostatectomy (ORP)., Objectives: To assess the effects of laparoscopic radical prostatectomy or robotic-assisted radical prostatectomy compared to open radical prostatectomy in men with localised prostate cancer., Search Methods: We performed a comprehensive search using multiple databases (CENTRAL, MEDLINE, EMBASE) and abstract proceedings with no restrictions on the language of publication or publication status, up until 9 June 2017. We also searched bibliographies of included studies and conference proceedings., Selection Criteria: We included all randomised controlled trials (RCTs) with a direct comparison of laparoscopic radical prostatectomy (LRP) and robotic-assisted radical prostatectomy (RARP) to ORP, including pseudo-RCTs., Data Collection and Analysis: Two review authors independently classified studies and abstracted data. The primary outcomes were prostate cancer-specific survival, urinary quality of life and sexual quality of life. Secondary outcomes were biochemical recurrence-free survival, overall survival, overall surgical complications, serious postoperative surgical complications, postoperative pain, hospital stay and blood transfusions. We performed statistical analyses using a random-effects model and assessed the quality of the evidence according to GRADE., Main Results: We included two unique studies with 446 randomised participants with clinically localised prostate cancer. The mean age, prostate volume, and prostate-specific antigen (PSA) of the participants were 61.3 years, 49.78 mL, and 7.09 ng/mL, respectively. Primary outcomes We found no study that addressed the outcome of prostate cancer-specific survival. Based on data from one trial, RARP likely results in little to no difference in urinary quality of life (MD -1.30, 95% CI -4.65 to 2.05) and sexual quality of life (MD 3.90, 95% CI -1.84 to 9.64). We rated the quality of evidence as moderate for both quality of life outcomes, downgrading for study limitations. Secondary outcomes We found no study that addressed the outcomes of biochemical recurrence-free survival or overall survival.Based on one trial, RARP may result in little to no difference in overall surgical complications (RR 0.41, 95% CI 0.16 to 1.04) or serious postoperative complications (RR 0.16, 95% CI 0.02 to 1.32). We rated the quality of evidence as low for both surgical complications, downgrading for study limitations and imprecision.Based on two studies, LRP or RARP may result in a small, possibly unimportant improvement in postoperative pain at one day (MD -1.05, 95% CI -1.42 to -0.68 ) and up to one week (MD -0.78, 95% CI -1.40 to -0.17). We rated the quality of evidence for both time-points as low, downgrading for study limitations and imprecision. Based on one study, RARP likely results in little to no difference in postoperative pain at 12 weeks (MD 0.01, 95% CI -0.32 to 0.34). We rated the quality of evidence as moderate, downgrading for study limitations.Based on one study, RARP likely reduces the length of hospital stay (MD -1.72, 95% CI -2.19 to -1.25). We rated the quality of evidence as moderate, downgrading for study limitations.Based on two study, LRP or RARP may reduce the frequency of blood transfusions (RR 0.24, 95% CI 0.12 to 0.46). Assuming a baseline risk for a blood transfusion to be 8.9%, LRP or RARP would result in 68 fewer blood transfusions per 1000 men (95% CI 78 fewer to 48 fewer). We rated the quality of evidence as low, downgrading for study limitations and indirectness.We were unable to perform any of the prespecified secondary analyses based on the available evidence. All available outcome data were short-term and we were unable to account for surgeon volume or experience., Authors' Conclusions: There is no high-quality evidence to inform the comparative effectiveness of LRP or RARP compared to ORP for oncological outcomes. Urinary and sexual quality of life-related outcomes appear similar.Overall and serious postoperative complication rates appear similar. The difference in postoperative pain may be minimal. Men undergoing LRP or RARP may have a shorter hospital stay and receive fewer blood transfusions. All available outcome data were short-term, and this study was unable to account for surgeon volume or experience.

Deterioration of the intervertebral discs is an unfortunate consequence of aging. The intervertebral disc in mammals is composed of three parts: a jelly-like center called the nucleus pulposus, the cartilaginous annulus fibrosus, and anterior and posterior endplates that attach the discs to vertebrae. To understand the origin of the disc, we have investigated the intervertebral region of chickens. Surprisingly, our comparison of mouse and chicken discs revealed that chicken discs lack nuclei pulposi. In addition, the notochord, which in mice forms nuclei pulposi, was found to persist as a rod-like structure and express Shh throughout chicken embryogenesis. Our fate mapping data indicate that cells originating from the rostral half of each somite are responsible for forming the avian disc while cells in the caudal region of each somite form vertebrae. A histological analysis of mammalian and nonmammalian organisms suggests that nuclei pulposi are only present in mammals., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: The purpose of this study was to define the effects of external beam radiation (EBR) on AlloDerm (LifeCell Corp) through the analysis of graft thickness, fibroblast recellularization, and neovascularization as a function of time., Methods and Material: Thirty-six male Sprague-Dawley rats (n = 36) were randomly assigned to 1 of 4 groups (A, B, C, and D). AlloDerm was implanted subcutaneously into the hind legs of each rat, and 20 Gy of EBR was administered to one side. Grafts harvested 1, 2, 4, and 12 weeks after radiation were subjected to blinded histologic analysis., Results: In groups A, B, and C, the irradiated grafts showed a significant decrease in recellularization versus nonirradiated (P < 0.001). At 12 weeks (group D), recellularization equalized, but neovascularization was significantly less (P = 0.048) in the irradiated group. Graft thickness was unaffected., Conclusions: In the rat model, EBR of the implanted AlloDerm graft hinders recellularization in the early posttreatment period. However, EBR did not adversely affect graft thickness, recellularization or ultimate graft survival.

1. The role of nitric oxide (NO) formed by the inducible isoform of NO synthase (NOS) in the generation of indomethacin-induced intestinal microvascular leakage was investigated in the rat. 2. Indomethacin (10 mg kg-1, s.c.) provoked an elevation of vascular leakage of radiolabelled human serum albumin in the jejunum over 48 h, commencing 18 h after its administration. This was associated with the induction of a calcium-independent NOS, as assessed by the conversion of radiolabelled L-arginine to citrulline. 3. Pretreatment with the glucocorticoid, dexamethasone (1 mg kg-1 day-1, s.c.) inhibited the induction of NOS and reduced jejunal microvascular leakage, determined 24 and 48 h after indomethacin. 4. Administration of the broad-spectrum antibiotic, ampicillin (800 mg kg-1 day-1, p.o.) likewise inhibited both the induction of NOS and the plasma leakage observed 24 and 48 h after indomethacin. 5. Ampicillin pretreatment did not, however, inhibit the induction of NOS, determined 5 h following endotoxin (3 mg kg-1 i.v.) challenge. Furthermore, incubation with ampicillin (1 mM, 10 min) did not inhibit the activity of the calcium-independent isoform in vitro. 6. Administration of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 2-10 mg kg-1, s.c.), at the time of the detectable expression of the inducible NOS (18 h after indomethacin), dose-dependently attenuated the plasma leakage, determined 6 later. This effect was reversed by pretreatment with L-arginine (300 mg kg-1, s.c.) 15 min before L-NAME. 7. These findings suggest that induction of a calcium-independent NOS following indomethacin administration involves gut bacteria and leads to microvascular injury in the rat jejunum.

Objective: To evaluate the behavioral, subjective, and reinforcing effects of immediate-release (IR) alprazolam and extended-release (XR) alprazolam to assess the effect of release rate on laboratory measures of abuse liability., Methods: Fourteen healthy men with histories of sedative abuse participated as subjects in a double-blind crossover study. All subjects received placebo, 1 and 2 mg immediate-release alprazolam, and 2 and 3 mg extended-release alprazolam in random order. Behavioral performance, subjective effects, and alprazolam plasma concentrations were assessed repeatedly 1/2 hour before and 1/2, 1, 3, 5, 7, 9, 12, and 24 hours after drug administration., Results: Mean peak alprazolam plasma concentrations occurred 1.7 and 9.2 hours after immediate-release alprazolam and extended-release alprazolam, respectively. Compared to placebo, 2 mg immediate-release alprazolam impaired all measures of psychomotor and cognitive performance (Digit Symbol Substitution Test), motor coordination (circular lights and balance), and memory (digit entry and recall); 2 mg extended-release alprazolam did not affect any of these measures and 3 mg extended-release alprazolam impaired circular lights only. Immediate-release alprazolam, 2 mg, increased all six measures of positive drug effects (e.g., ratings of liking or good effects); none of these measures were increased by 2 mg extended-release alprazolam and only three of the six measures were increased by 3 mg extended-release alprazolam. A drug versus money multiple-choice procedure designed to assess the relative reinforcing effects of each condition was administered 24 hour after the drug. The amount of money subjects were willing to "pay" to take the drug was significantly greater than placebo for both doses of immediate-release alprazolam but for neither dose of extended-release alprazolam., Conclusions: These data indicate that extended-release alprazolam has less potential for abuse than immediate-release alprazolam.

1. The effect of endotoxin (E. coli lipopolysaccharide) on the induction of nitric oxide synthase (NOS) and the changes in vascular permeability in the colon and jejunum over a 5 h period have been investigated in the rat. 2. Under resting conditions, a calcium-dependent constitutive NOS, determined by the conversion of radiolabelled L-arginine to citrulline, was detected in homogenates of both colonic and jejunal tissue. 3. Administration of endotoxin (3 mg kg-1, i.v.) led, after a 2 h lag period, to the appearance of calcium-independent NOS activity in the colon and jejunum ex vivo, characteristic of the inducible NOS enzyme. 4. Administration of endotoxin led to an increase in colonic and jejunal vascular permeability after a lag period of 3 h, determined by the leakage of radiolabelled albumin. 5. Pretreatment with dexamethasone (1 mg kg-1 s.c., 2 h prior to challenge) inhibited both the induction of NOS and the vascular leakage induced by endotoxin. 6. Administration of the NO synthase inhibitor NG-monomethyl-L-arginine (12.5-50 mg kg-1, s.c.) 3 h after endotoxin injection, dose-dependently reduced the subsequent increase in vascular permeability in jejunum and colon, an effect reversed by L-arginine (300 mg kg-1, s.c.). 7. These findings suggest that induction of NOS is associated with the vascular injury induced by endotoxin in the rat colon and jejunum.

1. The effects of the monoamine oxidase inhibitors pargyline and nialamide on the Ca2+-dependency of [3H]-5-hydroxytryptamine release from superfused rat brain synaptosomes has been studied in order to evaluate the discrepancies that have occasionally been observed in studying transmitter release by in vivo and in vitro techniques. 2. The application of K+ pulses of low concentration (12.5-20 mM) caused an essentially Ca2+-dependent release of [3H]-5-HT. However, at K+ concentrations above 30 mM, a small non-Ca2+-dependent component appeared. 3. At high concentrations of K+ (30-55 mM), nialamide (18 microM) or pargyline (7 microM) increased the amount of [3H]-5-HT released which could be accounted for by an increase in the non-Ca2+-dependent component of release. 4. The elevation of the non-Ca2+-dependent component of release caused by the monoamine oxidase inhibitors was totally abolished by the inhibitors of the plasma membrane 5-HT carrier, chlomipramine (500 nM), citalopram (50 nM) and fluoxetine (1 microM). 5. The results suggest that the non-Ca2+-dependent component of release seen with high depolarizing concentrations of K+, particularly in the presence of monoamine oxidase inhibitors, is caused by the efflux of [3H]-5-HT through the plasma membrane carrier which seems to be activated during depolarization. 6. The significance of these findings to the physiological in vivo situation, and to the use of in vitro preparations in the study of transmitter release is discussed.