Long-term effects of neuraxial analgesia.

PURPOSE OF REVIEW: This review article explores the potential longer-term implications of neuraxial analgesia in labour for both the mother and her child. RECENT FINDINGS: Neuraxial techniques for labour analgesia are well tolerated and effective, and long-term adverse sequelae are rare. Labour epidural analgesia is not independently associated with long-term headache, backache, postnatal depression or anal sphincter injury, and evidence supports that epidurals may offer protection against severe maternal morbidity, particularly in women at a higher risk of complications. However, there is an increasing awareness that postdural puncture headache may be associated with chronic headache, back pain and postnatal depression, emphasizing the need for adequate follow-up until symptoms resolve.For the neonate, a growing body of evidence refutes any association between epidural analgesia in labour and the later development of autism spectrum disorder. The clinical significance of epidural related maternal fever remains uncertain and is a research priority. SUMMARY: Women should continue to access the significant benefits of neuraxial analgesia in labour without undue concern about adverse sequelae for themselves or their offspring. Measures to prevent, appropriately manage and adequately follow-up women who have suffered complications of neuraxial analgesia, such as postdural puncture headache, are good practice and can mitigate the development of long-term sequelae.

Stepwise Oxidative C-C Coupling and/or C-N Fusion of Zn(II) meso-Pyridin-2-ylthio-porphyrins.

The synthesis and characterization of zinc(II) meso-pyridin-2-ylthio-porphyrins are presented in this manuscript. The (electro)chemical oxidation of [5-(pyridin-2-ylthio)-10,20-bis(p-tolyl)-15-phenylporphyrinato] zinc(II) or [5,15-bis(pyridin-2-ylthio)-10,20-bis(p-tolyl)porphyrinato] zinc(II) leads to the formation of one or two C-N bond(s) by intramolecular nucleophilic attack of the peripheral thiopyridinyl fragment(s) on the neighboring ß-pyrrolic position(s) (C-N fusion reaction). In addition, the chemical oxidation of [5-(pyridin-2-ylthio)-10,20-bis(p-tolyl)porphyrinato] zinc(II), i.e., bearing one free meso position, mainly affords the meso,meso-dimer. Further stepwise electrochemical oxidation selectively produces the mono and bis C-N fused meso,meso-dimer. The resulting pyridinium derivatives exhibit important changes in their physicochemical properties (NMR, UV-vis, CV) as compared to their initial unfused precursors. Also, the X-ray crystallographic structures of three unfused monomers, one unfused meso,meso-dimer, and two C-N fused monomers are presented.

Obstetric anaesthetic practice in the UK: a descriptive analysis of the National Obstetric Anaesthetic Database 2009-14.

BACKGROUND: Data on UK obstetric anaesthetic practice between 2009 and 2014 were collected by the Obstetric Anaesthetists' Association's National Obstetric Anaesthetic Database. This database provides information on workload, variation in practice, and complication rates. METHODS: During 2009-14, data were submitted by 190 UK hospitals. The number of hospitals that submitted data each year ranged between 114 and 145. During this 6 yr period, between 27 and 35 data items were requested, although not all hospitals submitted information on all data items. The dataset was assessed for quality and only those data items with acceptable quality were analysed. RESULTS: The dataset contains information on 3 030 493 deliveries, 770 545 Caesarean sections, 623 050 women with labour neuraxial analgesia, and 61 121 general anaesthetics for Caesarean section. There was increased use of patient-controlled regimens for labour neuraxial analgesia over the 6 yr period. The mean rate of general anaesthesia used for Caesarean section was 8.75% (95% confidence interval, 8.26-9.24%). The rate of failed intubation for general anaesthesia for Caesarean section was one in 379. Inadvertent dural puncture rates varied between hospitals with a mean of 1.2% (95% confidence interval, 1.02-1.37%). The rate of a high neuraxial block causing unconsciousness was one in 6667 for all blocks. CONCLUSIONS: This unique large dataset provides a valuable insight of obstetric anaesthetic activity in the UK. Although missing data may place limitations on interpretation, it provides comparative estimates for the rates of rare complications and highlights variations in practice in time and place.

Electrochemistry as an attractive and effective tool for the synthesis and immobilization of porphyrins on an electrode surface.

Magnesium(II) 10-phenyl-5,15-p-ditolylporphyrin is easily and cleanly transformed by electrolysis. A nitro group is first introduced at the free meso position by anodic substitution. Hydrogenation into the amine is then carried out electrocatalytically under ambient conditions with water as a hydrogen supplier. The synthesized porphyrin under the nickel(II) form can be covalently grafted onto a platinum electrode by electrochemical reduction of the diazonium cation, generated in situ by a reaction of the nickel(II) aminoporphyrin with sodium nitrite and trifluoroacetic acid. The electrosynthesized thin film gives an electrochemical response typical of a porphyrin material. Films grown under our conditions have a maximum surface coverage of approximately 5×10(-10)  mol cm(-2). The modified electrode exhibits a reproducible electrochemical behavior and a good level of stability over potential cycling and exposition to air.

Aromatic nucleophilic substitution (S(N)Ar) of meso-nitroporphyrin with azide and amines as an alternative metal catalyst free synthetic approach to obtain meso-N-substituted porphyrins.

Aromatic nucleophilic substitution reaction of the nitro group of meso-nitroporphyrins with azide and various amines was achieved and represents an alternative procedure to C-N coupling reactions usually needed to obtain such meso-N-substituted porphyrins in good yields.

Kinetic and electrochemical studies of the oxidative addition of demanding organic halides to Pd(0): the efficiency of polyphosphane ligands in low palladium loading cross-couplings decrypted.

Oxidative addition (OA) of organic halides to palladium(0) species is a fundamental reaction step which initiates the C-C bond formation catalytic processes typical of Pd(0)/Pd(II) chemistry. The use of structurally congested polyphosphane ligands in palladium-catalyzed C-C bond formation has generated very high turnover numbers (TONs) in topical reactions such as Heck, Suzuki, Sonogashira couplings, and direct sp(2)C-H functionalization. Herein, the OA of aryl bromides to Pd(0) complexes stabilized by ferrocenylpolyphosphane ligands L1 (tetraphosphane), L2 (triphosphane), and L3 (diphosphane) is considered. The investigation of kinetic constants for the addition of Ph-Br to Pd(0) intermediates (generated by electrochemical reduction of Pd(II) complexes coordinated by L1-L3) is reported. Thus, in the OA of halides to the Pd(0) complex coordinated by L1 the series of rate constants kapp is found (mol(-1) L s(-1)): kapp(Ph-Br) = 0.48 > kapp(ClCH2-Cl) = 0.25 ≫ kapp(p-MeC6H4-Br) = 0.08 ≈ kapp(o-MeC6H4-Br) = 0.07 ≫ kapp(Ph-Cl). Kinetic measurements clarify the influence that the presence of four, three, or two phosphorus atoms in the coordination sphere of Pd has on OA. The presence of supplementary phosphorus atoms in L1 and L2 unambiguously stabilizes Pd(0) species and thus slows down the OA of Ph-Br to Pd(0) of about 2 orders of magnitude compared to the diphosphane L3. The electrosynthesis of the complexes resulting from the OA of organic halides to [Pd(0)/L] is easily performed and show the concurrent OA to Pd(0) of the sp(3)C-Cl bond of dichloromethane solvent. The resulting unstable Pd/alkyl complex is characterized by NMR and single crystal X-ray structure. We additionally observed the perfect stereoselectivity of the OA reactions which is induced by the tetraphosphane ligand L1. Altogether, a clearer picture of the general effects of congested polydentate ligands on the OA of organic halides to Pd(0) is given.

Consensus Practice Guidelines on Postdural Puncture Headache From a Multisociety, International Working Group: A Summary Report.

Importance: Postdural puncture headache (PDPH) can follow unintentional dural puncture during epidural techniques or intentional dural puncture during neuraxial procedures, such as a lumbar puncture or spinal anesthesia. Evidence-based guidance on the prevention, diagnosis, and management of this condition is, however, currently lacking. Objective: To fill the practice guidelines void and provide comprehensive information and patient-centric recommendations for preventing, diagnosing, and managing PDPH. Evidence Review: With input from committee members and stakeholders of 6 participating professional societies, 10 review questions that were deemed important for the prevention, diagnosis, and management of PDPH were developed. A literature search for each question was performed in MEDLINE on March 2, 2022. Additional relevant clinical trials, systematic reviews, and research studies published through March 2022 were also considered for practice guideline development and shared with collaborator groups. Each group submitted a structured narrative review along with recommendations that were rated according to the US Preventive Services Task Force grading of evidence. Collaborators were asked to vote anonymously on each recommendation using 2 rounds of a modified Delphi approach. Findings: After 2 rounds of electronic voting by a 21-member multidisciplinary collaborator team, 47 recommendations were generated to provide guidance on the risk factors for and the prevention, diagnosis, and management of PDPH, along with ratings for the strength and certainty of evidence. A 90% to 100% consensus was obtained for almost all recommendations. Several recommendations were rated as having moderate to low certainty. Opportunities for future research were identified. Conclusions and Relevance: Results of this consensus statement suggest that current approaches to the treatment and management of PDPH are not uniform due to the paucity of evidence. The practice guidelines, however, provide a framework for individual clinicians to assess PDPH risk, confirm the diagnosis, and adopt a systematic approach to its management.

Evidence-based clinical practice guidelines on postdural puncture headache: a consensus report from a multisociety international working group.

INTRODUCTION: Postdural puncture headache (PDPH) can follow unintentional dural puncture during epidural techniques or intentional dural puncture during neuraxial procedures such as a lumbar puncture or spinal anesthesia. Evidence-based guidance on the prevention, diagnosis or management of this condition is, however, currently lacking. This multisociety guidance aims to fill this void and provide practitioners with comprehensive information and patient-centric recommendations to prevent, diagnose and manage patients with PDPH. METHODS: Based on input from committee members and stakeholders, the committee cochairs developed 10 review questions deemed important for the prevention, diagnosis and management of PDPH. A literature search for each question was performed in MEDLINE (Ovid) on 2 March 2022. The results from each search were imported into separate Covidence projects for deduplication and screening, followed by data extraction. Additional relevant clinical trials, systematic reviews and research studies published through March 2022 were also considered for the development of guidelines and shared with contributors. Each group submitted a structured narrative review along with recommendations graded according to the US Preventative Services Task Force grading of evidence. The interim draft was shared electronically, with each collaborator requested to vote anonymously on each recommendation using two rounds of a modified Delphi approach. RESULTS: Based on contemporary evidence and consensus, the multidisciplinary panel generated 50 recommendations to provide guidance regarding risk factors, prevention, diagnosis and management of PDPH, along with their strength and certainty of evidence. After two rounds of voting, we achieved a high level of consensus for all statements and recommendations. Several recommendations had moderate-to-low certainty of evidence. CONCLUSIONS: These clinical practice guidelines for PDPH provide a framework to improve identification, evaluation and delivery of evidence-based care by physicians performing neuraxial procedures to improve the quality of care and align with patients' interests. Uncertainty remains regarding best practice for the majority of management approaches for PDPH due to the paucity of evidence. Additionally, opportunities for future research are identified.

Aqua Walking as an Appropriate and Healthy Winter and Summer Physical Practice? An Exploratory Study.

(1) Background: Aqua-walking in a natural environment is a health promoting physical activity that is gaining popularity and appropriate for a variety of populations, however, to date, there is little scientific evidence supporting the efficacy and safety of this activity for older adults. The objective was to propose a preliminary exploration of psychometric and metabolic responses to an acute Aqua walking session either during winter or summer in older adults Aqua walking exercisers. (2) Methods: Heart rate, body temperature, glycemia, and blood pressure were monitored in 37 (30 women, 7 men) participants aged 52 to 83 years old in two Aqua walking sessions (water at 13 °C and 18.5 °C, respectively). Anthropometry (body weight, waist, and hip circumferences), body composition, physical activity level, sedentary time, sleep quality, quality of life, physical self-perception, and perceived health and feelings on various parameters were also assessed. (3) Results: Present results revealed a greater quality of life, physical self-perception, and perceived health in aging Aqua walking exercisers compared to those found in the literature in younger populations. None of the metabolic or psychometric measurements were found to be different between classically calibrated Aqua walking sessions performed in winter compared to summer. By contrast, there was a time effect during the sessions for body temperature (p < 0.001), SBP (p = 0.17), perceived mental and physical well-being (p = 0.006 and p < 0.001, respectively), and anxiety (p < 0.001). Leg discomfort also showed a time effect (p = 0.0009) and interaction effect (p = 0.025). (4) Conclusion: Aqua walking appears here to be an accessible practice that can be performed all year long with a range of physical and mental benefits for older adults. Future studies should investigate the metabolic responses of Aqua walking in different populations.

Direct arylation of heteroaromatic compounds with congested, functionalised aryl bromides at low palladium/triphosphane catalyst loading.

A new ferrocenyl triphosphane ligand associated to palladium was found to be an efficient catalyst for the direct coupling of highly congested, functionalised aryl bromides with a variety of heteroarenes. These coupling reactions can generally be performed by using a low-loading (0.1-0.5 mol%) of the catalyst. The present protocol tolerates important and useful functional groups, which allows for further elaboration into more sophisticated heterocyclic molecules. The straightforward arylation of heteroaromatic compounds with congested ortho-substituted aryl bromides may permit further convergent syntheses of diverse ligands, biologically active molecules and molecular materials in only a few steps.

Gold(I) Complexes Nuclearity in Constrained Ferrocenyl Diphosphines: Dramatic Effect in Gold-Catalyzed Enyne Cycloisomerization.

Di-tert-butylated-bis(phosphino)ferrocene ligands bearing phosphino substituents R (R=phenyl, cyclohexyl, iso-propyl, mesityl, or furyl) allow tuning the selective formation of Au(I) halide complexes. Thus, dinuclear linear two-coordinate, but also rare mononuclear trigonal three-coordinate and tetrahedral four-coordinate complexes were formed upon tuning of the conditions. Both Au(I) chloride and rarer Au(I) iodide complexes were synthesized, and their X-ray diffraction analysis are reported. The significance of the control of structure and nuclearity in Au(I) complexes is further illustrated herein by its strong effect on the efficiency and selectivity of gold-catalysed cycloisomerization. Cationic linear digold(I) bis(dicyclohexylphosphino) ferrocenes outperform other catalysts in the demanding regioselective cycloisomerization of enyne sulphonamides into cyclohexadienes. Conversely, tetrahedral and trigonal cationic monogold(I) complexes were found incompetent for enyne cycloaddition. We used the two-coordinate linear electron-rich Au(I) complex 2 b (R=Cy) to extend the scope of selective intramolecular cycloaddition of different 1,6-enyne sulfonylamines with high activity and excellent selectivity to the endo cyclohexadiene products.

Reduction of ferricytochrome c catalyzed by optically active chromium(III) complexes.

The reduction rates of horse heart ferricytochrome c by amalgamated zinc or by electrolysis at fixed potential on a mercury pool as the cathode have been measured in a buffered solution at pH 7.5 by absorption spectrophotometry. In both cases, the reaction was strongly accelerated by the presence of the optically active complexes Lambda-[Cr(III)((S,S)-promp)H(2)O](+) (H(2)promp = N,N'-[(pyridine-2,6-diyl)bis(methylene)]-bis[(S)-proline]), Delta-[Cr(III)((R,R)-alamp)H(2)O](+) (H(2)alamp = N,N'-[(pyridine-2,6-diyl)bis(methylene)]-bis[(R)-alanine]) and Lambda-[Cr(III)((S,S)-alamp)(H(2)O)(2)](+). These were shown to undergo reversible one-electron reduction to the corresponding labile chromium(II) species by cyclic voltammetry (CV), although the diaquo Lambda-[Cr(III)((S,S)-alamp)(H(2)O)(2)](+) compound behaved differently than the two others. The cyclic voltammogram evidenced a strong catalytic reduction wave below -1.1 V/SHE overlapping with the Cr(3+)/Cr(2+) couple, which has been attributed to the catalytic reduction of hydroxonium ions to molecular hydrogen. Although stable in the second time range as demonstrated by CV, the chromium(II) complexes exist in solution only as short-lived species in the absence of protein and are rapidly reoxidized to the initial trivalent state, thus preventing their isolation even under anaerobic conditions. However, their lifetime was found to be long enough to catalyze the reduction of the ferric heme moiety of cytochrome c according to an electron-transfer-mediated reaction. Both chemical and electrochemical processes were found to follow zero-order kinetics. It could therefore be safely concluded that the rate-determining step is associated to the electron transfer from transient chromium(II) complexes to the protein and not to the in situ generation of the metallic reducing agent.

Application of Dermal Skin Substitutes for Hand and Finger Palmar Soft Tissue Loss.

Restoring function after traumatic defects of the palm is a reconstructive challenge, considering the need for flexible, elastic, and resistant skin. Dermal skin substitutes are biologically engineered materials composed of collagen and glycosaminoglycan, devoid of cellular structures. These biodegradable materials act as artificial dermis and stimulate neovascularization: they have been used for many years, mainly on the dorsal side of the hand and fingers, whereas the palmar side of the hand has been generally addressed by local flaps. In this study, we described our experience with dermal skin substitutes in two cases of palmar defects associated with exposed tendinous structures. Coverage of palmar defects in hand and fingers with dermal substitute and split thickness skin graft was performed on two patients. Both patients presented palmar-only loss of tissue (traumatic palmar amputation in the first patient and degloving-type injury in the second patient). Range of motion, functional outcomes, and satisfaction and aesthetical results were evaluated. The resulting skin showed good quality, thickness, pliability, and Disabilities of the Arm, Shoulder, and Hand (DASH) score. Additionally, the patients regained full range of motion and reported high satisfaction. The association of split thickness skin graft with dermal substitutes in palmar traumatic hand showed optimal functional and aesthetic outcomes. Although being more adapted to dorsal loss of substance, collagen-based dermal substitutes can also be useful reconstructive tools in palmar defects with exposed structures and could be used to a larger extent in the future.

Oxidative C-N fusion of pyridinyl-substituted porphyrins.

The mild (electro)chemical oxidation of pyridin-2-ylthio-meso substituted Ni(ii) porphyrins affords C-N fused cationic and dicationic pyridinium-based derivatives. These porphyrins are fully characterized and the molecular structure of one of them was confirmed by X-ray crystallography. A mechanism for the intramolecular oxidative C-N coupling is proposed based on theoretical calculations and cyclic voltammetry analyses.

A general diastereoselective synthesis of highly functionalized ferrocenyl ambiphiles enabled on a large scale by electrochemical purification.

A general synthesis of highly functionalized ferrocenes, which include (P,B)- and (N,B)-ambiphiles, has been developed at a multigram scale. Diastereoselective stepwise modification of di-tert-butylated ferrocenes included the unprecedented separation of electroactive species. Bulky alkyl groups on ferrocenes ensure planar chirality of ambiphiles and enforce closer proximity of antagonist Lewis functions.

Versatile redox reactivity of triaryl-meso-substituted Ni(II) porphyrin.

The electrochemical oxidation of nickel(ii) 5,15-p-ditolyl-10-phenylporphyrin () leads to the formation of different coupling products, with the distribution depending on the nature of the solvent (CH2Cl2-CH3CN, CH2Cl2, DMF), the cell configuration (2 or 3 compartments) and the number of electrons abstracted. In a two compartment configuration (anode and cathode in the same compartment) in a CH2Cl2-CH3CN mixture, nickel(ii) 5-chloro-10,20-p-ditolyl-15-phenylporphyrin () was isolated in good yield and its mechanism of formation is proposed. Switching to the three compartment configuration, the meso-ß/meso-ß doubly fused dimer () is detected as the major product whereas in pure CH2Cl2, the singly bonded meso-ß dimer () is the major product; in both cases a significant amount of is also produced. These results are in accordance with the cyclic voltammetry analysis of measured in CH2Cl2-CH3CN and CH2Cl2 from which the voltammetric trace of is, respectively, appearing or not. In DMF the hydroxyporphyrin was detected as the major product. Furthermore, meso-functionalization of was performed by controlled potential electrolysis with triphenylphosphine as the nucleophile leading to the phosphonium substituted derivative () in good yield. Finally, unprecedented X-ray crystallographic structures of , , and are presented and their respective structural parameters compared.