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Article ; Online: Fibrin glue obliteration is safe, effective and minimally invasive as first line treatment for pilonidal sinus disease in children.

Hardy, Ejo / Herrod, Pjj / Sian, T / Boyd-Carson, H / Blackwell, Jem / Lund, J N / Quarmby, J W

2018 Volume 54, Issue 8, Page(s) 1668–1670

Abstract: Background / purpose: Sacrococcygeal pilonidal sinus disease (PSD) has an incidence of 1.2-2.5/1000 in children. Onset is around puberty. Symptoms of recurrent abscess and chronic suppuration may interfere with education and social integration. ... ...

Abstract	Background / purpose: Sacrococcygeal pilonidal sinus disease (PSD) has an incidence of 1.2-2.5/1000 in children. Onset is around puberty. Symptoms of recurrent abscess and chronic suppuration may interfere with education and social integration. Treatments should cause minimal disruption while having good cure and recurrence rates. Curettage and Fibrin glue obliteration (FGO) show promising results in adults. We present our experience of its use in children. Methods: Review of all pediatric patients receiving FGO of pilonidal sinus performed by a single surgeon from September 2014 to February 2018. Results: Eighteen patients were identified. Median age was 16 (range 15-17), 55.6% were male. All procedures were completed as day cases. Median operative duration was 14 .1 (6-29) min. Twelve patients required only 1 procedure, 4 required 2 procedures, 1 required 5 procedures and 1 elected for formal excision after 2 FGO treatments. Median return to normal activities was 3 days, with 1 day school absence. Two patients developed minor surgical site infections. Median follow-up was 52 weeks (17-102), during which time there was 1 recurrence (5.6%). Conclusion: This study demonstrates FGO is a safe, effective procedure for pediatric PNS, with results comparable to off-midline flap techniques and without the need for extensive tissue excision and the associated morbidity. Level of evidence: IV.
MeSH term(s)	Adolescent ; Female ; Fibrin Tissue Adhesive/adverse effects ; Fibrin Tissue Adhesive/therapeutic use ; Humans ; Male ; Operative Time ; Pilonidal Sinus/surgery ; Recurrence ; Reoperation ; Retrospective Studies ; Surgical Wound Infection/etiology ; Tissue Adhesives/adverse effects ; Tissue Adhesives/therapeutic use
Chemical Substances	Fibrin Tissue Adhesive ; Tissue Adhesives
Language	English
Publishing date	2018-09-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	80165-3
ISSN	1531-5037 ; 0022-3468
ISSN (online)	1531-5037
ISSN	0022-3468
DOI	10.1016/j.jpedsurg.2018.07.024
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Article ; Online: Fibrin glue is a quick and effective treatment for primary and recurrent pilonidal sinus disease.

Sian, T S / Herrod, P J J / Blackwell, J E M / Hardy, E J O / Lund, J N

Techniques in coloproctology

2018 Volume 22, Issue 10, Page(s) 779–784

Abstract: Background: Pilonidal sinus disease (PSD) is a common, chronic inflammatory condition involving hair follicles within the natal cleft. It mainly affects young males and creates a significant health, social and economic burden. Traditional surgery is ... ...

Abstract	Background: Pilonidal sinus disease (PSD) is a common, chronic inflammatory condition involving hair follicles within the natal cleft. It mainly affects young males and creates a significant health, social and economic burden. Traditional surgery is often radical resulting in pain, wound complications, long recovery times and poor cosmesis. The aim of our study was to evaluate fibrin glue as a primary treatment for PSD. Methods: Fibrin glue procedures for a single surgeon at our institution were identified from operative coding databases and the logbook from January 2011 to January 2016. Patients had curettage of the sinus with fibrin glue obliteration. Recurrence data was collected retrospectively. Results: One hundred and forty-six patients were identified; (115 (79%) males, mean age 30 (range 16-78 years). One hundred and forty-four (99%) were discharged the same day. Four (2.7%) were treated conservatively for wound discharge. Median operating time was 9 (range 4-28) min. There were 40 (27%) recurrences after one glue application. Median time to recurrence was 4 (range 0.25-36) months. Twenty-four (60%) of the recurrences had repeat glue treatment with 4 (16.6%) recurrences. After 2 rounds of treatment with glue alone, 126 out of 130 (96.9%) patients had healed. Conclusions: Fibrin glue application following curettage of the sinus is a quick and effective procedure for first and second line treatment of PSD.
MeSH term(s)	Adolescent ; Adult ; Aged ; Curettage/methods ; Female ; Fibrin Tissue Adhesive/therapeutic use ; Humans ; Male ; Middle Aged ; Operative Time ; Pilonidal Sinus/surgery ; Recurrence ; Retrospective Studies ; Tissue Adhesives/therapeutic use ; Treatment Outcome ; Young Adult
Chemical Substances	Fibrin Tissue Adhesive ; Tissue Adhesives
Language	English
Publishing date	2018-11-09
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2083309-X
ISSN	1128-045X ; 1123-6337
ISSN (online)	1128-045X
ISSN	1123-6337
DOI	10.1007/s10151-018-1864-4
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Article ; Online: Clinical Outcomes of the Modified Broström Technique in the Management of Chronic Ankle Instability After Early, Intermediate, and Delayed Presentation.

Hassan, Sami / Thurston, Daniel / Sian, Tanvir / Shah, Rohi / Aziz, Abdul / Kothari, Paresh

The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons

2018 Volume 57, Issue 4, Page(s) 685–688

Abstract: The modified Broström technique (MBT) is considered the reference standard for surgical management of ankle instability, with good short-term outcomes. However, limited evidence is available regarding outcomes for delayed presentations of instability. We ...

Abstract	The modified Broström technique (MBT) is considered the reference standard for surgical management of ankle instability, with good short-term outcomes. However, limited evidence is available regarding outcomes for delayed presentations of instability. We report our outcomes for patients who underwent ligament repair using the MBT, from a single-surgeon retrospective study of consecutive patients. The minimum postoperative follow-up period was 6 months during a 5-year study period. The patients were retrospectively divided into 3 groups according to the delay in presentation: group 1, 6 months to 2 years; group 2, 2 to 4 years; and group 3, >4 years. We collected data on patient demographics, injury pattern, and intraoperative surgeon findings. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale (AHS) was used to evaluate patient outcomes and satisfaction with surgery. Twenty-six patients were treated with MBT. The mean follow-up period was 36.9 (range 6-42) months. Twenty-five (96.2%) patients had unilateral injuries, and 1 (3.85%) had bilateral repairs. Of the 26 patients, 21 (80.8%) completed the AOFAS-AHS, with a mean score of 87.4 (range 12 to 100). The mean interval from injury to surgery was 47.9 months. The results were excellent in 15 (71.4%), good in 3 (14.3%), fair in 1 (4.8%), and poor in 2 (9.5%) using the AOFAS-AHS. We found no significant difference in the overall AOFAS-AHS score or postoperative satisfaction among the groups (p > .05). All patients had a stable ankle joint at their final follow-up visit. In conclusion, patients with persistent or chronic ankle instability have good clinical outcomes and satisfaction after the MBT, irrespective of the time from injury to presentation.
MeSH term(s)	Adolescent ; Adult ; Ankle Joint ; Chronic Disease ; Female ; Humans ; Joint Instability/surgery ; Lateral Ligament, Ankle/surgery ; Male ; Middle Aged ; Patient Satisfaction ; Reproducibility of Results ; Retrospective Studies ; Time-to-Treatment ; Treatment Outcome ; Young Adult
Language	English
Publishing date	2018-04-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1146972-9
ISSN	1542-2224 ; 1067-2516
ISSN (online)	1542-2224
ISSN	1067-2516
DOI	10.1053/j.jfas.2017.12.003
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Article ; Online: Pharmacological hypogonadism impairs molecular transducers of exercise-induced muscle growth in humans.

Gharahdaghi, Nima / Rudrappa, Supreeth / Brook, Matthew S / Farrash, Wesam / Idris, Iskandar / Aziz, Muhammad Hariz Abdul / Kadi, Fawzi / Papaioannou, Konstantinos / Phillips, Bethan E / Sian, Tanvir / Herrod, Philip J / Wilkinson, Daniel J / Szewczyk, Nathaniel J / Smith, Kenneth / Atherton, Philip J

Journal of cachexia, sarcopenia and muscle

2022 Volume 13, Issue 2, Page(s) 1134–1150

Abstract: Background: The relative role of skeletal muscle mechano-transduction in comparison with systemic hormones, such as testosterone (T), in regulating hypertrophic responses to exercise is contentious. We investigated the mechanistic effects of chemical ... ...

Abstract	Background: The relative role of skeletal muscle mechano-transduction in comparison with systemic hormones, such as testosterone (T), in regulating hypertrophic responses to exercise is contentious. We investigated the mechanistic effects of chemical endogenous T depletion adjuvant to 6 weeks of resistance exercise training (RET) on muscle mass, function, myogenic regulatory factors, and muscle anabolic signalling in younger men. Methods: Non-hypogonadal men (n = 16; 18-30 years) were randomized in a double-blinded fashion to receive placebo (P, saline n = 8) or the GnRH analogue, Goserelin [Zoladex (Z), 3.6 mg, n = 8], injections, before 6 weeks of supervised whole-body RET. Participants underwent dual-energy X-ray absorptiometry (DXA), ultrasound of m. vastus lateralis (VL), and VL biopsies for assessment of cumulative muscle protein synthesis (MPS), myogenic gene expression, and anabolic signalling pathway responses. Results: Zoladex suppressed endogenous T to within the hypogonadal range and was well tolerated; suppression was associated with blunted fat free mass [Z: 55.4 ± 2.8 to 55.8 ± 3.1 kg, P = 0.61 vs. P: 55.9 ± 1.7 to 57.4 ± 1.7 kg, P = 0.006, effect size (ES) = 0.31], composite strength (Z: 40 ± 2.3% vs. P: 49.8 ± 3.3%, P = 0.03, ES = 1.4), and muscle thickness (Z: 2.7 ± 0.4 to 2.69 ± 0.36 cm, P > 0.99 vs. P: 2.74 ± 0.32 to 2.91 ± 0.32 cm, P < 0.0001, ES = 0.48) gains. Hypogonadism attenuated molecular transducers of muscle growth related to T metabolism (e.g. androgen receptor: Z: 1.2 fold, P > 0.99 vs. P: 1.9 fold, P < 0.0001, ES = 0.85), anabolism/myogenesis (e.g. IGF-1Ea: Z: 1.9 fold, P = 0.5 vs. P: 3.3 fold, P = 0.0005, ES = 0.72; IGF-1Ec: Z: 2 fold, P > 0.99 vs. P: 4.7 fold, P = 0.0005, ES = 0.68; myogenin: Z: 1.3 fold, P > 0.99 vs. P: 2.7 fold, P = 0.002, ES = 0.72), RNA/DNA (Z: 0.47 ± 0.03 to 0.53 ± 0.03, P = 0.31 vs. P: 0.50 ± 0.01 to 0.64 ± 0.04, P = 0.003, ES = 0.72), and RNA/ASP (Z: 5.8 ± 0.4 to 6.8 ± 0.5, P > 0.99 vs. P: 6.5 ± 0.2 to 8.9 ± 1.1, P = 0.008, ES = 0.63) ratios, as well as acute RET-induced phosphorylation of growth signalling proteins (e.g. AKT Conclusions: We conclude that endogenous T sufficiency has a central role in the up-regulation of molecular transducers of RET-induced muscle hypertrophy in humans that cannot be overcome by muscle mechano-transduction alone.
MeSH term(s)	Exercise/physiology ; Humans ; Hypogonadism/etiology ; Male ; Muscle, Skeletal/physiology ; Resistance Training ; Transducers
Language	English
Publishing date	2022-03-01
Publishing country	Germany
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2586864-0
ISSN	2190-6009 ; 2190-5991
ISSN (online)	2190-6009
ISSN	2190-5991
DOI	10.1002/jcsm.12843
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Article ; Online: Cell surface rescue of kidney anion exchanger 1 mutants by disruption of chaperone interactions.

Patterson, Sian T / Reithmeier, Reinhart A F

The Journal of biological chemistry

2010 Volume 285, Issue 43, Page(s) 33423–33434

Abstract: Mutations in the human kidney anion exchanger 1 (kAE1) membrane glycoprotein cause impaired urine acidification resulting in distal renal tubular acidosis (dRTA). Dominant and recessive dRTA kAE1 mutants exhibit distinct trafficking defects with ... ...

Abstract	Mutations in the human kidney anion exchanger 1 (kAE1) membrane glycoprotein cause impaired urine acidification resulting in distal renal tubular acidosis (dRTA). Dominant and recessive dRTA kAE1 mutants exhibit distinct trafficking defects with retention in the endoplasmic reticulum (ER), Golgi, or mislocalization to the apical membrane in polarized epithelial cells. We examined the interaction of kAE1 with the quality control system responsible for the folding of membrane glycoproteins and the retention and degradation of misfolded mutants. Using small molecule inhibitors to disrupt chaperone interactions, two functional, dominant kAE1 mutants (R589H and R901stop), retained in the ER and targeted to the proteasome for degradation by ubiquitination, were rescued to the basolateral membrane of Madin-Darby canine kidney cells. In contrast, the Golgi-localized, recessive G701D and the severely misfolded, ER-retained dominant Southeast Asian ovalocytosis (SAO) mutants were not rescued. These results show that functional dRTA mutants are retained in the ER due to their interaction with molecular chaperones, particularly calnexin, and that disruption of these interactions can promote their escape from the ER and cell surface rescue.
MeSH term(s)	Amino Acid Substitution ; Animals ; Anion Exchange Protein 1, Erythrocyte/genetics ; Anion Exchange Protein 1, Erythrocyte/metabolism ; Calnexin/genetics ; Calnexin/metabolism ; Cell Line ; Cell Membrane/genetics ; Cell Membrane/metabolism ; Dogs ; Elliptocytosis, Hereditary/genetics ; Elliptocytosis, Hereditary/metabolism ; Endoplasmic Reticulum/genetics ; Endoplasmic Reticulum/metabolism ; Genes, Dominant ; Golgi Apparatus/genetics ; Golgi Apparatus/metabolism ; Humans ; Kidney/metabolism ; Molecular Chaperones/genetics ; Molecular Chaperones/metabolism ; Mutation ; Mutation, Missense ; Proteasome Endopeptidase Complex/genetics ; Proteasome Endopeptidase Complex/metabolism ; Protein Folding
Chemical Substances	Anion Exchange Protein 1, Erythrocyte ; Molecular Chaperones ; SLC4A1 protein, human ; Calnexin (139873-08-8) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
Language	English
Publishing date	2010-07-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M110.144261
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Article: Cell Surface Rescue of Kidney Anion Exchanger 1 Mutants by Disruption of Chaperone Interactions

Patterson, Sian T / Reithmeier, Reinhart A.F

Journal of biological chemistry. 2010 Oct. 22, v. 285, no. 43

2010

Abstract	Mutations in the human kidney anion exchanger 1 (kAE1) membrane glycoprotein cause impaired urine acidification resulting in distal renal tubular acidosis (dRTA). Dominant and recessive dRTA kAE1 mutants exhibit distinct trafficking defects with retention in the endoplasmic reticulum (ER), Golgi, or mislocalization to the apical membrane in polarized epithelial cells. We examined the interaction of kAE1 with the quality control system responsible for the folding of membrane glycoproteins and the retention and degradation of misfolded mutants. Using small molecule inhibitors to disrupt chaperone interactions, two functional, dominant kAE1 mutants (R589H and R901stop), retained in the ER and targeted to the proteasome for degradation by ubiquitination, were rescued to the basolateral membrane of Madin-Darby canine kidney cells. In contrast, the Golgi-localized, recessive G701D and the severely misfolded, ER-retained dominant Southeast Asian ovalocytosis (SAO) mutants were not rescued. These results show that functional dRTA mutants are retained in the ER due to their interaction with molecular chaperones, particularly calnexin, and that disruption of these interactions can promote their escape from the ER and cell surface rescue.
Language	English
Dates of publication	2010-1022
Size	p. 33423-33434.
Publishing place	American Society for Biochemistry and Molecular Biology
Document type	Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
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Article: Intramolecular C-H...Ccarbene hydrogen bonds and competing interactions in monoprotonated tripodal carbenes.

Howard, Siân T / Abernethy, Colin D

Journal of computational chemistry

2004 Volume 25, Issue 5, Page(s) 649–659

Abstract: The anionic tripodal N-heterocyclic carbene (C3N2H3)3BH- first prepared by Fehlhammer, together with three neutral variants, (C3N2H3)3CH, (C3N2H3)3P, and (C3N2H3)3SiH, have been studied using quantum chemical methods. Isodesmic reactions are used to ... ...

Abstract	The anionic tripodal N-heterocyclic carbene (C3N2H3)3BH- first prepared by Fehlhammer, together with three neutral variants, (C3N2H3)3CH, (C3N2H3)3P, and (C3N2H3)3SiH, have been studied using quantum chemical methods. Isodesmic reactions are used to deduce that the phosphine-bridgehead species in particular has a large-resonance stabilization energy. All the podands undergo substantial conformational change on excitation to the lowest triplet electronic state, with effective localization of the excitation on one of the heterocyclic rings, dearomatizing it. On monoprotonation of the ground states, three of these species display intramolecular C-H...Ccarbene hydrogen bonding: The nature and strength of these interactions is explored using model (intermolecularly hydrogen-bonded) complexes, isodesmic reactions, and GIAO calculations of chemical shifts. One surprising result is that C-H...Ccarbene hydrogen bonds involving ethenic hydrogens can be almost as strong as those involving the imidazolium proton (first identified by Arduengo). The case of the monoprotonated carbon bridgehead species is in particular intriguing. It is stabilized by a competitive Ccarbene...N interaction of sufficient strength to override the C-H...Ccarbene bonding motif observed in the other structures.
Language	English
Publishing date	2004-04-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	1479181-x
ISSN	1096-987X ; 0192-8651
ISSN (online)	1096-987X
ISSN	0192-8651
DOI	10.1002/jcc.20004
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Article: A new orbital-based model for the analysis of experimental molecular charge densities: an application to (Z)-N-methyl-C-phenylnitrone.

Hibbs, David E / Howard, Siân T / Huke, Jeremy P / Waller, Mark P

Physical chemistry chemical physics : PCCP

2008 Volume 7, Issue 8, Page(s) 1772–1778

Abstract: An alternative to the usual atom-centred multipole expansion is presented for the analysis of high resolution, low-temperature X-ray scattering data. The molecular electron density is determined in a fixed basis of molecular orbitals with variable ... ...

Abstract	An alternative to the usual atom-centred multipole expansion is presented for the analysis of high resolution, low-temperature X-ray scattering data. The molecular electron density is determined in a fixed basis of molecular orbitals with variable orbital occupation numbers, i.e. the same form which is used to represent the density in ab initio electron-correlated calculations. The advantages of such an approach include linear scaling (in the sense that the number of parameters to be determined by fitting varies linearly with system size) and ease of property calculation. The method is applied to experimental high-resolution structure factors for a phenylnitrone, and compared to the results of a multipole model of the same data. Finally, the model is critically compared with several related, published orbital-based models.
MeSH term(s)	Benzene Derivatives/chemistry ; Nitrogen Oxides/chemistry ; Stereoisomerism ; Temperature
Chemical Substances	Benzene Derivatives ; N-methyl-C-phenylnitrone ; Nitrogen Oxides ; nitrones
Language	English
Publishing date	2008-09-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1476244-4
ISSN	1463-9084 ; 1463-9076
ISSN (online)	1463-9084
ISSN	1463-9076
DOI	10.1039/b416614k
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Article: Conformations, energies, and intramolecular hydrogen bonds in dicarboxylic acids: implications for the design of synthetic dicarboxylic acid receptors.

Nguyen, Thanh Ha / Hibbs, David E / Howard, Siân T

Journal of computational chemistry

2005 Volume 26, Issue 12, Page(s) 1233–1241

Abstract: The various conformers of the dicarboxylic acids HO2C--(CH2)n--CO2H, n = 1-4, were obtained using density functional methods (DFT), both in the gas phase and in the aqueous phase using a polarized continuum model (PCM). Several new conformers were ... ...

Abstract	The various conformers of the dicarboxylic acids HO2C--(CH2)n--CO2H, n = 1-4, were obtained using density functional methods (DFT), both in the gas phase and in the aqueous phase using a polarized continuum model (PCM). Several new conformers were identified, particularly for the two larger molecules glutaric (n = 3) and adipic acid (n =4). The PCM results show that the stability of most conformers were affected, many becoming unstable in the aqueous phase; and the energy ordering of conformers is also different. The results suggest that conformational preferences could be important in determining the design and stability of appropriate synthetic receptors for glutaric and adipic acid. Geometry changes between gas and aqueous phases were most marked in those conformers containing an intramolecular hydrogen bond. Additional calculations have probed the strength of intramolecular hydrogen bonds in these dicarboxylic acids. In the cases of glutaric and adipic acid, the strength of the intramolecular hydrogen bond were estimated to be around 28-29 kJ/mol, without any vibrational energy correction. The intramolecular hydrogen bond energies in malonic and succinic acid were also estimated from the calculated H-bond distances using an empirical relationship. Intramolecular H-bond redshifts of 170-250 cm(-1) have been estimated from the results of the harmonic frequency analyses.
MeSH term(s)	Adipates/chemistry ; Dicarboxylic Acids/chemistry ; Glutarates/chemistry ; Hydrogen Bonding ; Isomerism ; Malonates/chemistry ; Models, Molecular ; Molecular Conformation ; Molecular Structure ; Succinic Acid/chemistry ; Thermodynamics
Chemical Substances	Adipates ; Dicarboxylic Acids ; Glutarates ; Malonates ; adipic acid (76A0JE0FKJ) ; malonic acid (9KX7ZMG0MK) ; Succinic Acid (AB6MNQ6J6L) ; glutaric acid (H849F7N00B)
Language	English
Publishing date	2005-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1479181-x
ISSN	1096-987X ; 0192-8651
ISSN (online)	1096-987X
ISSN	0192-8651
DOI	10.1002/jcc.20259
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Article ; Online: Ab Initio Studies of Proton Sponges (V): 1,4,7,10-Tetraaza-tricyclo[5,5,2,2(4,10)]hexa- decane, a Tricyclic Proton Sponge.

Howard, Siân T. / Fallis, Ian A.

The Journal of organic chemistry

1998 Volume 63, Issue 20, Page(s) 7117–7119

Language	English
Publishing date	1998-10-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	123490-0
ISSN	1520-6904 ; 0022-3263
ISSN (online)	1520-6904
ISSN	0022-3263
DOI	10.1021/jo9809478
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