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- Galluzzi, L, et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes.
- 2009
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In: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 16:8, s. 1093-107
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Research review (peer-reviewed)abstract
- Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells.
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- Abrams, G. D., et al.
(author)
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Pronator teres is an appropriate donor muscle for restoration of wrist and thumb extension
- 2005
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In: J Hand Surg [Am]. ; 30:5, s. 1068-73
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To compare the detailed architectural properties of the pronator teres (PT), extensor carpi radialis brevis (ECRB), and extensor pollicis longus (EPL) muscles to evaluate the suitability of PT-to-ECRB and PT-to-EPL surgical procedures. METHODS: Muscle physiologic cross-sectional areas and region-specific muscle fiber lengths were measured in cadaveric PT, ECRB, and EPL muscles (n = 10 muscles of each type). One-way repeated-analyses of variance measures and post hoc t tests with Bonferroni corrections were used for statistical comparisons. RESULTS: The ulnar head of the PT was present in 8 of 10 specimens. The average PT fiber length was similar to that of the ECRB (7.02 +/- 0.49 cm vs 6.17 +/- 0.27 cm) but was significantly longer than that of the EPL (5.44 +/- 0.25 mm). Fiber length in the humeral head of the PT was longer compared with the ulnar head (7.19 +/- 0.52 cm vs 4.14 +/- 0.25 cm). The average physiologic cross-sectional area of the PT was similar to that of the ECRB (3.5 +/- 0.4 cm2 vs 3.3 +/- 0.3 cm2) but was significantly larger than that of the EPL (3.5 +/- 0.4 cm2 vs 1.1 +/- 0.1 cm2). CONCLUSIONS: From an architectural point of view the PT is an excellent donor choice for transfer to the ECRB for restoration of wrist extension or to the EPL for restoration of thumb extension. Because there is fiber length heterogeneity within the PT, however, when the ulnar head is present it may limit the total excursion of the donor muscle. These data suggest that releasing the ulnar head of the PT before transfer may result in larger excursions of this important motor in tendon transfer surgery.
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- Irwin, D. E., et al.
(author)
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Impact of overactive bladder symptoms on employment, social interactions and emotional well-being in six European countries
- 2006
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In: BJU Int. - 1464-4096. ; 97:1, s. 96-100
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine the impact of overactive bladder (OAB) symptoms on issues related to employment, social interactions, and emotional well-being in a population aged 40-64 years. SUBJECTS AND METHODS: The study comprised a cross-sectional population-based survey of 11 521 individuals aged 40-64 years, conducted in France, Germany, Italy, Spain, Sweden, and the UK. The survey involved a two-stage screening procedure. Initially, individuals with any lower urinary tract symptoms were identified. Those whose only symptom/(s) was suggestive of a urinary tract infection, stress incontinence, or prostate obstruction were excluded from further study. Respondents were asked questions about the impact that their symptoms had on their emotional well-being, social interactions and productivity at home and at work. RESULTS: Of those with OAB, approximately 32% (1272) reported that having these symptoms made them feel depressed, and 28% reported feeling very stressed. There were statistically significant differences in reported feelings of stress and depression when OAB symptoms were stratified by OAB with incontinence (OAB+) vs those with OAB with no incontinence (OAB-), with values for emotional stress of OAB+ 36.4% vs OAB- 19.6%, for depression of OAB+ 39.8% vs OAB- 23.3%. Participants with OAB+ were significantly more likely than those with OAB- to express worry about having accidents and concern about participating in activities away from home because of their bladder symptoms. In addition, those with OAB+ were significantly more likely to report that these bladder symptoms were a source of great concern and made them feel uncomfortable in social situations compared to those with OAB-. Men were significantly more likely than women to report OAB+ having an impact on their daily work life, including worry about interrupting meetings, impact on decisions about work location and hours, and voluntary termination or early retirement. This effect was primarily in men reporting OAB+. CONCLUSION: OAB symptoms have a significant effect on the emotional well-being and productivity of those affected, both at home and at work.
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- Irwin, D. E., et al.
(author)
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Overactive bladder is associated with erectile dysfunction and reduced sexual quality of life in men
- 2008
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In: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6109 .- 1743-6095. ; 5:12, s. 2904-10
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Journal article (peer-reviewed)abstract
- Introduction. The prevalence of sexual dysfunction, including erectile dysfunction (ED), is greater in men with lower urinary tract symptoms (LUTS), including overactive bladder (OAB), than in men without LUTS. Aim. To evaluate the prevalence of ED, the impact of urinary symptoms on sexual activity and sexual enjoyment, and sexual satisfaction in men with OAB. Methods. A nested case-control analysis was performed on data from a subset of men with (cases) and without (controls) OAB frequency-matched for age (5-year age strata) and country from the EPIC study. Respondents were asked about OAB symptoms (using the 2002 International Continence Society [ICS] definitions) and sexual activity. Sexually active respondents were asked about ED, sexual enjoyment, and overall satisfaction with their sex lives. Conditional logistic regression was used to assess factors associated with ED. Main Outcome Measures. The percentage of cases and controls reporting ED, a reduction in the frequency of sexual activity or enjoyment of sexual activity because of urinary symptoms, and overall satisfaction with their sex lives was determined for cases and controls. Results. A total of 502 cases and 502 controls were matched for age strata and country. Significantly more cases (14%) reported reduced sexual activity because of urinary symptoms compared with controls (4%; P
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- Irwin, D. E., et al.
(author)
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Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study
- 2006
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In: Eur Urol. - : Elsevier BV. - 0302-2838. ; 50:6
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Estimate the prevalence of urinary incontinence (UI), overactive bladder (OAB), and other lower urinary tract symptoms (LUTS) among men and women in five countries using the 2002 International Continence Society (ICS) definitions. METHODS: This population-based, cross-sectional survey was conducted between April and December 2005 in Canada, Germany, Italy, Sweden, and the United Kingdom using computer-assisted telephone interviews. A random sample of men and women aged >/= 18 yr residing in the five countries and who were representative of the general populations in these countries was selected. Using 2002 ICS definitions, the prevalence estimates of storage, voiding, and postmicturition LUTS were calculated. Data were stratified by country, age cohort, and gender. RESULTS: A total of 19,165 individuals agreed to participate; 64.3% reported at least one LUTS. Nocturia was the most prevalent LUTS (men, 48.6%; women, 54.5%). The prevalence of storage LUTS (men, 51.3%; women, 59.2%) was greater than that for voiding (men, 25.7%; women, 19.5%) and postmicturition (men, 16.9%; women, 14.2%) symptoms combined. The overall prevalence of OAB was 11.8%; rates were similar in men and women and increased with age. OAB was more prevalent than all types of UI combined (9.4%). CONCLUSIONS: The EPIC study is the largest population-based survey to assess prevalence rates of OAB, UI, and other LUTS in five countries. To date, this is the first study to evaluate these symptoms simultaneously using the 2002 ICS definitions. The results indicate that these symptoms are highly prevalent in the countries surveyed.
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- Irwin, D. E., et al.
(author)
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Prevalence, Severity, and Symptom Bother of Lower Urinary Tract Symptoms among Men in the EPIC Study: Impact of Overactive Bladder
- 2009
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In: European Urology. - : Elsevier BV. - 0302-2838. ; 56:1, s. 14-20
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Journal article (peer-reviewed)abstract
- BACKGROUND: Lower urinary tract symptoms (LUTS) are prevalent among men. OBJECTIVE: To describe the prevalence, severity, and symptom bother of LUTS in all men and men with overactive bladder (OAB) symptoms in the EPIC study. DESIGN, SETTING, AND PARTICIPANTS: A secondary analysis of data from EPIC, a multinational population-based survey of 19 165 adults, was performed. Current International Continence Society definitions were used for individual LUTS and OAB; OAB cases were defined as men reporting urgency. MEASUREMENTS: Participants were asked about the presence of individual LUTS and associated symptom bother. LUTS severity was measured using the International Prostate Symptom Score (IPSS). RESULTS AND LIMITATIONS: There was substantial overlap of storage, voiding, and postmicturition symptoms among all men (n=7210) and in men with OAB symptoms (n=502); men with OAB symptoms were more likely to experience multiple LUTS subtypes. Among both populations, nocturia was the most commonly reported symptom, except for urgency (the hallmark symptom) among men with OAB symptoms; terminal dribble and sensation of incomplete emptying were the most common voiding and postmicturition symptoms. The prevalence of all LUTS increased with age among the general population; only storage LUTS increased with age among men with OAB symptoms. Number of LUTS and mean IPSS increased with age in both populations but were higher among men with OAB symptoms at all ages; the proportion reporting moderate-severe LUTS was higher than the general population (30% vs 6%). The proportion of men with OAB symptoms reporting symptom bother increased with urgency severity and severity and number of LUTS. LUTS severity may have been underestimated by the IPSS, which does not assess incontinence. CONCLUSIONS: Men with LUTS commonly experience coexisting storage, voiding, and postmicturition symptoms, emphasizing the need for comprehensive urologic assessments. Men with OAB symptoms reported more LUTS and greater severity than the general population. Symptom bother was related to number of LUTS and urgency severity.
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- Irwin, D. E., et al.
(author)
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Symptom bother and health care-seeking behavior among individuals with overactive bladder
- 2008
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In: European Urology. - : Elsevier BV. - 0302-2838. ; 53:5, s. 1029-37
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To estimate symptom bother and health care seeking among individuals with overactive bladder (OAB; ie, cases) using current International Continence Society definitions. METHODS: This was a nested case-controlled analysis of data from the EPIC study, a population-based, cross-sectional survey of adults in five countries. Cases and matched controls were asked about risk factors, use of coping techniques, and health care seeking for urinary symptoms. Cases were asked about symptom bother and assessed with the Overactive Bladder-Validated 8 and Patient Perception of Bladder Condition instruments. RESULTS: Among cases (n=1434), 54% reported symptom bother; rates were similar between men (54%) and women (53%). Significantly more men with urinary incontinence (UI) reported bother (77%) than women with UI (67%; p
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- Irwin, D. E., et al.
(author)
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Understanding the elements of overactive bladder: questions raised by the EPIC study
- 2008
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In: BJU International. - 1464-410X. ; 101:11, s. 1381-7
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To compare the prevalence of frequency and nocturia and the bother they impose in a population-based sample of men and women using current International Continence Society (ICS) definitions of lower urinary tract symptoms (LUTS) and commonly used alternative definitions of these LUTS to emphasize the importance of standardizing the definitions when evaluating overactive bladder (OAB) syndrome; we also describe the spectrum of LUTS and bother they impose in this population with OAB. SUBJECTS AND METHODS: Several validated disease-specific measures were used in a population-based, cross-sectional telephone survey of adults aged >or=18 years in five countries. The population with OAB was defined as those participants who answered 'yes' to questions about urgency or urgency urinary incontinence according to ICS standards. The prevalence of daytime frequency and nocturia within the OAB population was examined using two different criteria for each symptom. Frequency was defined using the current ICS definition (i.e. subject's perception of whether they urinated too often during the day) or more than eight daytime voids. Nocturia was defined according to the ICS definition of having to wake once or more per night to void and using the threshold of waking twice or more per night to urinate. Urinary symptom bother within the OAB population was compared using the different criteria for frequency and nocturia. RESULTS: In all, 1434 participants (502 men and 932 women) were classified as having OAB; 31% of men and 25% of women with OAB had daytime frequency consistent with the ICS definition. The ICS-defined frequency identified a population with a varied distribution of reported daytime voiding frequencies; most respondents reported frequencies below the threshold of nine daytime voids. The ICS-defined daytime frequency was reported as bothersome by more than half of the OAB population (46% of men, 66% of women). Of the OAB population, approximately 75% reported one or more nocturia episodes per night, and approximately 40% reported two or more per night. The proportion of the OAB population that was bothered by nocturia increased markedly as the number of nocturia episodes increased. Among those with OAB, the most prevalent combination of OAB symptoms was urgency and nocturia. More than half of those with OAB reported urgency combined with three or more other LUTS (including voiding and postmicturition symptoms), and the number of LUTS reported increased with age. The proportion of the population reporting symptom bother increased as the number of reported LUTS in that population increased. CONCLUSIONS: The ICS definitions for daytime frequency as 'the subject's perception of urinating too often' and for nocturia as 'one or more episodes per night' adequately described bladder symptoms within the OAB population when assessed by the level of symptom bother. Urgency was uncommon in isolation and did not alone impose as high a level of bother as when combined with other LUTS. In this population, the most predominant manifestation of OAB was a combination of urgency with one or more other OAB symptoms. Symptom bother became more common as the number of symptoms reported increased. LUTS other than the defining symptoms of OAB were also highly prevalent within the OAB population.
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