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Article ; Online: The Clinical Impact of Obesity in Patients With Disorders of Defecation: A Cross-Sectional Study of 1,155 Patients.

Chaichanavichkij, Pam / Vollebregt, Paul F / Keshishian, Karekin / Knowles, Charles H / Scott, S Mark

The American journal of gastroenterology

2023 Volume 118, Issue 12, Page(s) 2247–2257

Abstract: ... 25, P = 0.0003), although the odds of anal hypertension were not significantly higher after Benjamini ...

Abstract	Introduction: Obesity is a global epidemic. Its clinical impact on symptoms of fecal incontinence (FI) and/or constipation and underlying anorectal pathophysiology remains uncertain. Methods: This is a cross-sectional study of consecutive patients meeting Rome IV criteria for FI and/or functional constipation, with data on body mass index (BMI), attending a tertiary center for investigation between 2017 and 2021. Clinical history, symptoms, and anorectal physiologic test results were analyzed according to BMI categories. Results: A total of 1,155 patients (84% female) were included in the analysis (33.5% normal BMI; 34.8% overweight; and 31.7% obese). Obese patients had higher odds of FI to liquid stools (69.9 vs 47.8%, odds ratio [OR] 1.96 [confidence interval: 1.43-2.70]), use of containment products (54.6% vs 32.6%, OR 1.81 [1.31-2.51]), fecal urgency (74.6% vs 60.7%, OR 1.54 [1.11-2.14]), urge FI (63.4% vs 47.3%, OR 1.68 [1.23-2.29]), and vaginal digitation (18.0% vs 9.7%, OR 2.18 [1.26-3.86]). A higher proportion of obese patients had Rome criteria-based FI or coexistent FI and functional constipation (37.3%, 50.3%) compared with overweight patients (33.8%, 44.8%) and patients with normal BMI (28.9%, 41.1%). There was a positive linear association between BMI and anal resting pressure (β 0.45, R 2 0.25, P = 0.0003), although the odds of anal hypertension were not significantly higher after Benjamini-Hochberg correction. Obese patients more often had a large clinically significant rectocele (34.4% vs 20.6%, OR 2.62 [1.51-4.55]) compared with patients with normal BMI. Discussion: Obesity affects specific defecatory (mainly FI) and prolapse symptoms and pathophysiologic findings (higher anal resting pressure and significant rectocele). Prospective studies are required to determine whether obesity is a modifiable risk factor of FI and constipation.
MeSH term(s)	Humans ; Female ; Male ; Defecation ; Rectocele/complications ; Cross-Sectional Studies ; Overweight/complications ; Overweight/epidemiology ; Manometry ; Constipation/etiology ; Constipation/complications ; Fecal Incontinence/etiology ; Fecal Incontinence/complications ; Anal Canal ; Obesity/complications ; Obesity/epidemiology
Language	English
Publishing date	2023-07-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	390122-1
ISSN	1572-0241 ; 0002-9270
ISSN (online)	1572-0241
ISSN	0002-9270
DOI	10.14309/ajg.0000000000002400
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Article ; Online: Botulinum toxin type A for the treatment of dyssynergic defaecation in adults: a systematic review.

Chaichanavichkij, P / Vollebregt, P F / Scott, S M / Knowles, C H

Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland

2020 Volume 22, Issue 12, Page(s) 1832–1841

Abstract: Aim: Dyssynergic defaecation (DD) is characterized by inappropriate coordination of the pelvic floor muscles during defaecation, resulting in impaired stool expulsion. The mainstay of treatment is biofeedback and alternative therapies are limited in ... ...

Abstract	Aim: Dyssynergic defaecation (DD) is characterized by inappropriate coordination of the pelvic floor muscles during defaecation, resulting in impaired stool expulsion. The mainstay of treatment is biofeedback and alternative therapies are limited in those who do not respond. This systematic review evaluated botulinum toxin type A injection (BTXA) as a treatment option for dyssynergia. Methods: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched for studies evaluating adult patients with DD treated with BTXA injection into the puborectalis and/or external anal sphincter. All study designs, except case reports, were included in the review with no language restriction. Studies limited to patients with specific neurological diagnoses or with a follow-up period under 1 month were excluded. Study selection, assessment and data extraction were performed by two reviewers and results were synthesized narratively. Results: Eleven studies (three randomized control trials) involving 248 participants were included. All studies used the transanal approach to deliver the injection, most commonly at the 3 and 9 o'clock positions using digital palpation for guidance. The most commonly used patient position was left lateral, and most studies did not use any anaesthesia. The dose of BTXA varied (Botox 12-100 units, Dysport 100-500 units), and outcomes measured were heterogeneous (global rating ± up to five investigations). Symptomatic improvement varied between 29.2% and 100% and adverse effects occurred in 0% to 70%. Conclusion: The evidence to support using BTXA for DD is poor and only covers a transanal approach. Future studies should redress these limitations: heterogeneity of design, dose and outcome measures.
MeSH term(s)	Adult ; Ataxia ; Biofeedback, Psychology ; Botulinum Toxins, Type A/therapeutic use ; Defecation ; Humans ; Neuromuscular Agents/therapeutic use ; Randomized Controlled Trials as Topic
Chemical Substances	Neuromuscular Agents ; Botulinum Toxins, Type A (EC 3.4.24.69)
Language	English
Publishing date	2020-06-11
Publishing country	England
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	1440017-0
ISSN	1463-1318 ; 1462-8910
ISSN (online)	1463-1318
ISSN	1462-8910
DOI	10.1111/codi.15120
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Zs.A 5799: Show issues

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Article ; Online: Slow-transit constipation and criteria for colectomy: a cross-sectional study of 1568 patients.

Chaichanavichkij, P / Vollebregt, P F / Tee, S Z Y / Scott, S M / Knowles, C H

BJS open

2021 Volume 5, Issue 3

Abstract: Background: Colectomy remains a treatment option for a minority of patients with slow-transit constipation (STC) refractory to conservative treatment. However careful patient selection is essential to maximize benefits and minimize risk of adverse ... ...

Abstract	Background: Colectomy remains a treatment option for a minority of patients with slow-transit constipation (STC) refractory to conservative treatment. However careful patient selection is essential to maximize benefits and minimize risk of adverse outcome. This study determined the proportion of patients with chronic constipation that would meet criteria for colectomy based on recent European graded practice recommendations derived by expert consensus. Methods: Retrospective application of graded practice recommendations was undertaken on a prospectively maintained data set of consecutive adult patients with chronic constipation who underwent whole-gut transit studies using radio-opaque markers. Primary analysis applied contraindications achieving high level of expert consensus (normal whole-gut transit as an absolute contraindication and faecal incontinence as a relative contraindication for colectomy). Secondary analysis applied contraindications with less certain consensus. Results: Primary analysis of 1568 patients undergoing a whole-gut transit study between January 2004 and March 2016 found 208 (13.3 per cent) met published criteria to be selected for colectomy, with 974 excluded for normal whole-gut transit and 386 for faecal incontinence. Secondary analysis demonstrated high prevalence of other relative contraindications to colectomy: 165 concomitant upper gastrointestinal symptoms, 216 abdominal pain (including 126 irritable bowel syndrome), and 446 evacuation disorder. The majority of patients (416 of 594) had two or more relative contraindications. If these patients were excluded, only 26 (1.7 per cent) chronically constipated patients retrospectively met selection criteria for colectomy. Conclusions: The retrospective application of selection criteria is a limitation. However, the data highlight the high prevalence of factors associated with poor postoperative outcome and provide further caution to surgeons undertaking colectomy for STC.
MeSH term(s)	Adult ; Colectomy ; Constipation/epidemiology ; Constipation/surgery ; Cross-Sectional Studies ; Gastrointestinal Transit ; Humans ; Retrospective Studies ; Treatment Outcome
Language	English
Publishing date	2021-05-24
Publishing country	England
Document type	Journal Article
ISSN	2474-9842
ISSN (online)	2474-9842
DOI	10.1093/bjsopen/zrab049
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Article ; Online: Single-Molecule Sizing through Nanocavity Confinement.

Jacquat, Raphaël P B / Krainer, Georg / Peter, Quentin A E / Babar, Ali Nawaz / Vanderpoorten, Oliver / Xu, Catherine K / Welsh, Timothy J / Kaminski, Clemens F / Keyser, Ulrich F / Baumberg, Jeremy J / Knowles, Tuomas P J

Nano letters

2023 Volume 23, Issue 5, Page(s) 1629–1636

Abstract: An approach relying on nanocavity confinement is developed in this paper for the sizing of nanoscale particles and single biomolecules in solution. The approach, termed nanocavity diffusional sizing (NDS), measures particle residence times within ... ...

Abstract	An approach relying on nanocavity confinement is developed in this paper for the sizing of nanoscale particles and single biomolecules in solution. The approach, termed nanocavity diffusional sizing (NDS), measures particle residence times within nanofluidic cavities to determine their hydrodynamic radii. Using theoretical modeling and simulations, we show that the residence time of particles within nanocavities above a critical time scale depends on the diffusion coefficient of the particle, which allows the estimation of the particle's size. We demonstrate this approach experimentally through the measurement of particle residence times within nanofluidic cavities using single-molecule confocal microscopy. Our data show that the residence times scale linearly with the sizes of nanoscale colloids, protein aggregates, and single DNA oligonucleotides. NDS thus constitutes a new single molecule optofluidic approach that allows rapid and quantitative sizing of nanoscale particles for potential applications in nanobiotechnology, biophysics, and clinical diagnostics.
Language	English
Publishing date	2023-02-24
Publishing country	United States
Document type	Journal Article
ISSN	1530-6992
ISSN (online)	1530-6992
DOI	10.1021/acs.nanolett.1c04830
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Article ; Online: Author Correction: Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues.

Feng, Zijie / He, Xin / Zhang, Xuyao / Wu, Yuan / Xing, Bowen / Knowles, Alison / Shan, Qiaonan / Miller, Samuel / Hojnacki, Taylor / Ma, Jian / Katona, Bryson W / Gade, Terence P F / Siegel, Don L / Schrader, Jörg / Metz, David C / June, Carl H / Hua, Xianxin

Nature cancer

2024 Volume 5, Issue 4, Page(s) 691

Language	English
Publishing date	2024-04-11
Publishing country	England
Document type	Published Erratum
ISSN	2662-1347
ISSN (online)	2662-1347
DOI	10.1038/s43018-024-00766-5
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Article: Fracture load of zirconia crowns based on preparation and cement type.

Jenista, John S / Hoopes, Wyeth L / Knowles, James F / Vandewalle, Kraig S

General dentistry

2022 Volume 70, Issue 5, Page(s) 22–27

Abstract: ... found based on both AWH and cement type (P < 0.05). Regardless of cement type, the median fracture loads ...

Abstract	Limited research has been published evaluating the failure of zirconia crowns with less retentive tooth preparations. The purpose of this study was to evaluate the effect of axial wall height (AWH) and cement type on the fracture load of cubic phase-containing zirconia crowns. Standardized crown preparations with an AWH of 0, 2, or 4 mm (n = 10) were made in 90 extracted human maxillary third molars. The preparations were scanned, and crown restorations were designed. Cubic phase-containing zirconia crowns were milled and cemented with a resin-modified glass ionomer cement, a self-adhesive resin cement, or an adhesive resin cement. The specimens were subjected to thermocycling and cyclic loading. Each crown specimen was positioned in a universal testing machine so that the long axis of the tooth was at a 60° angle to the testing fixture and loaded until failure using a stainless steel rod resting on the buccal incline of the palatal cusp. Data were found to have a nonnormal distribution and were analyzed with Kruskal-Wallis and Mann-Whitney U tests (α = 0.05). Statistically significant differences in the median fracture loads of the groups were found based on both AWH and cement type (P < 0.05). Regardless of cement type, the median fracture loads were significantly lower in the 0-mm AWH groups than in the 2-mm and 4-mm AWH groups, which were not significantly different from each other. Compared to the other cement types, adhesive resin cement resulted in a significantly greater median fracture load when the AWH was 0 mm. The use of an adhesive resin cement with a cubic phase-containing zirconia crown may provide greater fracture resistance for preparations with minimal AWH.
MeSH term(s)	Crowns ; Dental Cements/therapeutic use ; Dental Materials ; Dental Prosthesis Design ; Dental Restoration Failure ; Dental Stress Analysis ; Glass Ionomer Cements/therapeutic use ; Humans ; Materials Testing ; Resin Cements/therapeutic use ; Zirconium/therapeutic use
Chemical Substances	Dental Cements ; Dental Materials ; Glass Ionomer Cements ; Resin Cements ; Zirconium (C6V6S92N3C) ; zirconium oxide (S38N85C5G0)
Language	English
Publishing date	2022-08-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	603650-8
ISSN	0363-6771
ISSN	0363-6771
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Article ; Online: Abnormal Perception of Urge to Defecate: An Important Pathophysiological Mechanism in Women With Chronic Constipation.

Vollebregt, Paul F / Wiklendt, Lukasz / Burgell, Rebecca E / Chaichanavichkij, Pam / Dinning, Phil G / Knowles, Charles H / Scott, S Mark

The American journal of gastroenterology

2022 Volume 117, Issue 7, Page(s) 1125–1136

Abstract: ... 3% vs 41.4%; P < 0.0001), and the viscerosensory referral area was 81% larger (median pixels ... anterior: 1,849 vs 1,022; P < 0.0001) compared to women with CC and normal urge perception. Abnormal (vs ... score: 19 vs 15 P < 0.0001), irritable bowel syndrome (45.7% vs 22.9% P < 0.0001), and a functional ...

Abstract	Introduction: Although the association of absent or attenuated "call to stool" with constipation is well-recognized, no studies have systematically evaluated the perception of urge to defecate in a well-defined cohort of patients with chronic constipation (CC). Methods: A prospective study of 43 healthy adult women and 140 consecutive adult women attending a tertiary center for investigation of CC. All participants completed a 5-day viscerosensory questionnaire, and all women with CC also underwent anorectal physiologic investigations. Normal urge perception and abnormal urge perception were defined using a Naive Bayes model trained in healthy women (95% having normal urge). Results: In total, 181 toilet visits in healthy women and 595 in women with CC were analyzed. Abnormal urge perception occurred in 70 (50.0%) women with CC. In this group, the urge to defecate was more often experienced as abdominal sensation (69.3% vs 41.4%; P < 0.0001), and the viscerosensory referral area was 81% larger (median pixels anterior: 1,849 vs 1,022; P < 0.0001) compared to women with CC and normal urge perception. Abnormal (vs normal) urge in women with CC was associated with more severe constipation (Cleveland Clinic constipation score: 19 vs 15 P < 0.0001), irritable bowel syndrome (45.7% vs 22.9% P < 0.0001), and a functional evacuation disorder on defecography (31.3% vs 14.3% P = 0.023). A distinct pattern of abnormal urge was found in women with CC and rectal hyposensitivity. Discussion: Abnormal urge perception was observed in 50% of women with CC and was frequently described as abdominal sensation, supporting the concept that sensory dysfunction makes an important contribution to the pathophysiology of constipation.
MeSH term(s)	Adult ; Bayes Theorem ; Constipation ; Defecation/physiology ; Female ; Humans ; Male ; Manometry ; Perception ; Prospective Studies ; Rectum
Language	English
Publishing date	2022-04-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	390122-1
ISSN	1572-0241 ; 0002-9270
ISSN (online)	1572-0241
ISSN	0002-9270
DOI	10.14309/ajg.0000000000001794
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Article ; Online: An octameric PqiC toroid stabilises the outer-membrane interaction of the PqiABC transport system.

Cooper, Benjamin F / Ratkevičiūtė, Giedrė / Clifton, Luke A / Johnston, Hannah / Holyfield, Rachel / Hardy, David J / Caulton, Simon G / Chatterton, William / Sridhar, Pooja / Wotherspoon, Peter / Hughes, Gareth W / Hall, Stephen Cl / Lovering, Andrew L / Knowles, Timothy J

EMBO reports

2024 Volume 25, Issue 1, Page(s) 82–101

Abstract: The E. coli Paraquat Inducible (Pqi) Pathway is a putative Gram-negative phospholipid transport system. The pathway comprises three components: an integral inner membrane protein (PqiA), a periplasmic spanning MCE family protein (PqiB) and an outer ... ...

Abstract	The E. coli Paraquat Inducible (Pqi) Pathway is a putative Gram-negative phospholipid transport system. The pathway comprises three components: an integral inner membrane protein (PqiA), a periplasmic spanning MCE family protein (PqiB) and an outer membrane lipoprotein (PqiC). Interactions between all complex components, including stoichiometry, remain uncharacterised; nevertheless, once assembled into their quaternary complex, the trio of Pqi proteins are anticipated to provide a continuous channel between the inner and outer membranes of diderms. Here, we present X-ray structures of both the native and a truncated, soluble construct of the PqiC lipoprotein, providing insight into its biological assembly, and utilise neutron reflectometry to characterise the nature of the PqiB-PqiC-membrane interaction. Finally, we employ phenotypic complementation assays to probe specific PqiC residues, which imply the interaction between PqiB and PqiC is less intimate than previously anticipated.
MeSH term(s)	Escherichia coli/genetics ; Escherichia coli/metabolism ; Escherichia coli Proteins/chemistry ; Membrane Proteins/metabolism ; Biological Transport ; Lipoproteins/metabolism
Chemical Substances	Escherichia coli Proteins ; Membrane Proteins ; Lipoproteins
Language	English
Publishing date	2024-01-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2020896-0
ISSN	1469-3178 ; 1469-221X
ISSN (online)	1469-3178
ISSN	1469-221X
DOI	10.1038/s44319-023-00014-4
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Zs.A 5433: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 41: Show issues

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Article: Interspecific Hybridizations of Bromus.

Knowles, P F

Genetics

2007 Volume 29, Issue 2, Page(s) 128–140

Language	English
Publishing date	2007-01-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2167-2
ISSN	1943-2631 ; 0016-6731
ISSN (online)	1943-2631
ISSN	0016-6731
DOI	10.1093/genetics/29.2.128
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Article ; Online: Addressing end-of-life care in the chronically ill: Conversations in the emergency department.

Hughes, Katarina / Achauer, Samantha / Baker, Eileen F / Knowles, Heidi C / Clayborne, Elizabeth P / Goett, Rebecca R / Moussa, Mohamad

Journal of the American College of Emergency Physicians open

2021 Volume 2, Issue 5, Page(s) e12569

Abstract: Patients present to the emergency department in various stages of chronic illness. Advance directives (ADs) aid emergency physicians in making treatment decisions, but only a minority of Americans have completed an AD, and the percentage of those who ... ...

Abstract	Patients present to the emergency department in various stages of chronic illness. Advance directives (ADs) aid emergency physicians in making treatment decisions, but only a minority of Americans have completed an AD, and the percentage of those who have discussed their end-of-life wishes may be even lower. This article addresses the use of common ADs and roadblocks to their use from the perspectives of families, patients, and physicians. Cases to examine new approaches to optimizing end-of-life conversations in patients who are chronically ill, such as the Improving Palliative Care in Emergency Medicine Project, a decision-making framework that opens discussion for patients to gain understanding and determine preferences, and the Brief Negotiated Interview, a 7-minute, scripted, motivational interview that determines willingness for behavior change and initiates care planning, are used.
Language	English
Publishing date	2021-10-01
Publishing country	United States
Document type	Journal Article
ISSN	2688-1152
ISSN (online)	2688-1152
DOI	10.1002/emp2.12569
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