Greater rate of weight loss predicts paediatric hospital admission in adolescent typical and atypical anorexia nervosa.

Hospital admissions for eating disorders (ED) are rapidly increasing. Limited research exists evidencing the factors that lead to hospital admissions or their outcomes. The current study aimed to identify predictors of hospital admission in adolescents with anorexia nervosa (AN) or atypical anorexia nervosa (AAN). Prospective observational study including participants (n = 205) aged 11-18 and diagnosed with AN or AAN at initial ED assessment, across eight London clinics. Physical health parameters at assessment, including heart rate, blood pressure, temperature and rate of weight loss, were compared between adolescents who were admitted to a paediatric ward following assessment and those who were not admitted. The mean rate of weight loss prior to assessment was significantly higher, and mean energy intake significantly lower, in the admitted vs not admitted groups (1.2 vs 0.6kg/week, p < 0.001 and 565 kcal/day vs 857 kcal/day, p < 0.001), independent of degree of underweight. No significant differences were identified between groups in all other parameters of physical risk. Underweight adolescents with AN were equally likely to be admitted as non-underweight adolescents with AAN.  Conclusion: This study provides evidence on predictors of hospital admission, from a sample representing the London area. The assessment of weight loss speed, duration and magnitude are recommended as priority parameters that inform the risk of deterioration and the likelihood of hospital admission in adolescent AN and AAN. Further research investigating outcomes of these hospital admission is needed. What is Known: • Hospital admissions for eating disorders (ED) are rapidly increasing. • Limited research exists evidencing the factors that lead to hospital admissions, or their outcomes. What is New: • This study provides evidence on predictors of hospital admission in young people with typical and atypical anorexia nervosa. • Weight loss speed, duration, and magnitude are recommended as priority parameters that inform the risk of deterioration and the likelihood of hospital admission in this patient group.

A prospective observational study comparing rates of medical instability between adolescents with typical and atypical anorexia nervosa.

BACKGROUND: Recognition of atypical anorexia nervosa (AAN) has challenged underweight as a defining factor of illness severity in anorexia nervosa (AN). The present study aimed to compare rates of medical instability in adolescents with underweight (AN) and non-underweight (AAN) anorexia nervosa. METHODS: The study examined assessment data from specialist eating disorder services in the UK between January and December 2022. Participants (n = 205) aged 11-18 years were recruited across eight eating disorder clinics and diagnosed with AN (n = 113) or AAN (n = 92) after clinical assessment. Parameters associated with risk of medical instability were compared between AN and AAN groups, using t tests and regression analysis. RESULTS: Rates of bradycardia and hypotension did not differ significantly between AN and AAN groups (p = 0.239 and p = 0.289). Although white blood cell counts were lower in the AN group, rates of leukopaenia could not be statistically compared as a result of there being too few counts in at least one group. No incidences of hypophosphataemia were found in the sample. A significant regression equation was found for percentage median body mass index, but not rate of weight loss, as a predictor of blood pressure, serum phosphorous and magnesium. CONCLUSIONS: Our findings indicate that medical instability occurs across a range of body weights in young people with AN and AAN. Although certain parameters of risk such as blood pressure, serum phosphorous and magnesium may be worsened at lower weight, both AN and AAN are serious mental health conditions that can lead to medical instability.

How Metal Ion Lewis Acidity and Steric Properties Influence the Barrier to Dioxygen Binding, Peroxo O-O Bond Cleavage, and Reactivity.

Herein we quantitatively investigate how metal ion Lewis acidity and steric properties influence the kinetics and thermodynamics of dioxygen binding versus release from structurally analogous Mn-O2 complexes, as well as the barrier to Mn peroxo O-O bond cleavage, and the reactivity of Mn oxo intermediates. Previously we demonstrated that the steric and electronic properties of MnIII-OOR complexes containing N-heterocyclic (NAr) ligand scaffolds can have a dramatic influence on alkylperoxo O-O bond lengths and the barrier to alkylperoxo O-O bond cleavage. Herein, we examine the dioxygen reactivity of a new MnII complex containing a more electron-rich, less sterically demanding NAr ligand scaffold, and compare it with previously reported MnII complexes. Dioxygen binding is shown to be reversible with complexes containing the more electron-rich metal ions. The kinetic barrier to O2 binding and peroxo O-O bond cleavage is shown to correlate with redox potentials, as well as the steric properties of the supporting NAr ligands. The reaction landscape for the dioxygen chemistry of the more electron-rich complexes is shown to be relatively flat. A total of four intermediates, including a superoxo and peroxo species, are observed with the most electron-rich complex. Two new intermediates are shown to form following the peroxo, which are capable of cleaving strong X-H bonds. In the absence of a sacrificial H atom donor, solvent, or ligand, serves as a source of H atoms. With TEMPOH as sacrificial H atom donor, a deuterium isotope effect is observed (kH/kD = 3.5), implicating a hydrogen atom transfer (HAT) mechanism. With 1,4-cyclohexadiene, 0.5 equiv of benzene is produced prior to the formation of an EPR detected MnIIIMnIV bimetallic species, and 0.5 equiv after its formation.

Electronic Structure of a Cu(II)-Alkoxide Complex Modeling Intermediates in Copper-Catalyzed Alcohol Oxidations.

In the copper-catalyzed oxidation of alcohols to aldehydes, a Cu(II)-alkoxide (Cu(II)-OR) intermediate is believed to modulate the αC-H bond strength of the deprotonated substrate to facilitate the oxidation. As a structural model for these intermediates, we characterized the electronic structure of the stable compound Tp(tBu)Cu(II)(OCH2CF3) (Tp(tBu) = hydro-tris(3-tert-butyl-pyrazolyl)borate) and investigated the influence of the trifluoroethoxide ligand on the electronic structure of the complex. The compound exhibits an electron paramagnetic resonance (EPR) spectrum with an unusually large gzz value of 2.44 and a small copper hyperfine coupling Azz of 40 × 10(-4) cm(-1) (120 MHz). Single-crystal electron nuclear double resonance (ENDOR) spectra show that the unpaired spin population is highly localized on the copper ion (≈68%), with no more than 15% on the ethoxide oxygen. Electronic absorption and magnetic circular dichroism (MCD) spectra show weak ligand-field transitions between 5000 and 12,000 cm(-1) and an intense ethoxide-to-copper charge transfer (LMCT) transition at 24,000 cm(-1), resulting in the red color of this complex. Resonance Raman (rR) spectroscopy reveals a Cu-O stretch mode at 592 cm(-1). Quantum chemical calculations support the interpretation and assignment of the experimental data. Compared to known Cu(II)-thiolate and Cu(II)-alkylperoxo complexes from the literature, we found an increased σ interaction in the Cu(II)-OR bond that results in the spectroscopic features. These insights lay the basis for further elucidating the mechanism of copper-catalyzed alcohol oxidations.

Reimagining care: effectiveness of modifying an adolescent eating disorder intensive service.

AIMS AND METHOD: The COVID-19 pandemic prompted a surge in adolescent eating disorders and rapid changes in the delivery of intensive community treatments. This study investigates the modification from a group-based day programme to an intensive family treatment approach. A retrospective chart review was performed on data from 190 patients who accessed the intensive service for anorexia nervosa in the past 6 years. Outcomes from the traditional model were compared with the new intensive family model, namely length of admission, percentage median body mass index difference and transfers to in-patient services. RESULTS: There was a significant reduction in the length of intensive treatment (from 143.19 to 97.20 days). The number of transfers to specialist eating disorder in-patient services also significantly reduced, and is decreasing year on year. CLINICAL IMPLICATIONS: The findings hold particular relevance as intensive services for adolescent eating disorders continue to be established within health services, with no clear unified approach to treatment.

Vibrational Stark effect spectroscopy reveals complementary electrostatic fields created by protein-protein binding at the interface of Ras and Ral.

Electrostatic fields at the interface of the GTPase H-Ras (Ras) docked with the Ras binding domain of the protein Ral guanine nucleoside dissociation stimulator (Ral) were measured with vibrational Stark effect (VSE) spectroscopy. Nine residues on the surface of Ras that participate in the protein-protein interface were systematically mutated to cysteine and subsequently converted to cyanocysteine in order to introduce a nitrile VSE probe into the protein-protein interface. The absorption energy of the nitrile was measured both on the surface of Ras in its monomeric state, then after incubation with the Ras binding domain of Ral to form the docked complex. Boltzmann-weighted structural snapshots of the nitrile-labeled Ras protein were generated both in monomeric and docked configurations from molecular dynamics simulations using enhanced sampling of the cyanocysteine side chain's χ2 dihedral angle. These snapshots were used to determine that on average, most of the nitrile probes were aligned along the Ras surface, parallel to the Ras-Ral interface. The average solvent-accessible surface areas (SASA) of the cyanocysteine side chain were found to be <60 Å(2) for all measured residues, and was not significantly different whether the nitrile was on the surface of the Ras monomer or immersed in the docked complex. Changes in the absorption energy of the nitrile probe at nine positions along the Ras-Ral interface were compared to results of a previous study examining this interface with Ral-based probes, and found a pattern of low electrostatic field in the core of the interface surrounded by a ring of high electrostatic field around the perimeter of the interface. These data are used to rationalize several puzzling features of the Ras-Ral interface.

The morbidly adherent placenta: diagnosis and management options.

PURPOSE OF REVIEW: Randomized controlled trials and large cohort studies regarding the diagnosis and management of placenta accreta are lacking. This review examines the available evidence. RECENT FINDINGS: Avoiding the placenta and leaving it attached at time of elective caesarean section to proceed with either delayed hysterectomy or conservative management is currently recommended. Recent literature has focussed on conservative management. Routine use of methotrexate in conservative management is no longer advocated. Use of emergency balloon catheter placement and embolization in tertiary centres where access to interventional radiology is immediately available may be favourable to prophylactic balloon catheter placement. Follow-up of patients undergoing conservative management should include ultrasonographic follow-up, human chorionic gonadotropin levels have been shown not to correlate with rate of placental resorption. SUMMARY: Women with an antenatal diagnosis of placenta accreta should be managed in a tertiary facility with multidisciplinary input. To determine optimum management strategies, it is imperative that larger studies are carried out in the future. It is essential that the continual monitoring and containment of rising caesarean section rates becomes a priority to prevent a further increase in the incidence of placenta accreta.

Sterically directed nitronate complexes of 2,6-di-tert-butyl-4-nitrophenoxide with Cu(ii) and Zn(ii) and their H-atom transfer reactivity.

The bulky 2,6-di-tert-butyl-4-nitrophenolate ligand forms complexes with [TptBuCuII]+ and [TptBuZnII]+ binding via the nitro group in an unusual nitronato-quinone resonance form (TptBu = hydro-tris(3-tert-butyl-pyrazol-1-yl)borate). The Cu complex in the solid state has a five-coordinate κ2-nitronate structure, while the Zn analogue has a four-coordinate κ1-nitronate ligand. 4-Nitrophenol, without the 2,6-di-tert-butyl substituents, instead binds to [TptBuCuII]+ through the phenolate oxygen. This difference in binding is very likely due to the steric difficulty in binding a 2,6-di-tert-butyl-phenolate ligand to the [TptBuMII]+ unit. TptBuCuII(κ2-O2NtBu2C6H2O) reacts with the hydroxylamine TEMPO-H (2,2,6,6-tetramethylpiperidin-1-ol) by abstracting a hydrogen atom. This system thus shows an unusual sterically enforced transition metal-ligand binding motif and a copper-phenolate interaction that differs from what is typically observed in biological and chemical catalysis.

EPR Study of UV-Irradiated Thymidine Microcrystals Supports Radical Intermediates in Spore Photoproduct Formation.

Spore photoproduct is a thymidine dimer formed when bacterial endospore DNA is exposed to ultraviolet (UV) radiation. The mechanism of formation of this thymidine dimer has been proposed to proceed through a radical-pair intermediate. The intermediate forms when a methyl-group hydrogen atom of one thymidine nucleobase is transferred to the C6 position of an adjacent thymidine nucleobase, forming two species, the TCH2 and TH radicals, respectively. Using a series of thymidine isotopologues and electron paramagnetic resonance (EPR) spectroscopy, we show that microcrystals of thymidine exposed to UV radiation produce these two radical species. We observe three sources that donate the additional hydrogen at the C6 position of the TH radical. One of the three sources is the methyl group of another thymidine molecule in a significant fraction of the TH species. This lends support to the radical-pair intermediate proposed in the formation of spore photoproduct.

Treatment of vaginal agglutination associated with chronic graft-versus-host disease.

OBJECTIVE: To describe the presentation and clinical course of two patients after development of vaginal agglutination associated with chronic graft-versus-host disease. DESIGN: Case report. SETTING: Tertiary referral center for pelvic reconstructive surgery. PATIENT(S): Two patients with the diagnosis of chronic graft-versus-host disease who later developed vaginal agglutination requiring treatment. INTERVENTION(S): Surgical lysis of vaginal adhesions and postoperative use of vaginal dilators. MAIN OUTCOME MEASURE(S): Successful treatment of vaginal adhesions. RESULT(S): Both patients underwent successful surgical lysis of vaginal adhesions and maintained vaginal patency with postoperative use of vaginal dilators. CONCLUSION(S): Prompt diagnosis of vaginal agglutination in patients with chronic graft-versus-host disease and appropriate surgical correction of this complication rather than prophylaxis is the correct treatment course.

COX-2 inhibitors and their role in gynecology.

UNLABELLED: This review summarizes current knowledge about the roles of cyclooxygenases and prostaglandins in reproductive medicine. With the development of COX-2 specific inhibitors, new therapeutic options are available to obstetricians and gynecologists, offering better-tolerated alternatives to conventional NSAIDs. The analgesic effectiveness of COX-2 specific inhibitors is well established, and they are already in use in a range of painful conditions. Both celecoxib and valdecoxib are indicated for the treatment of primary dysmenorrhea, and may be effective in postoperative pain, including hysterectomy, and pain associated with endometriosis. There is also speculation that COX-2 specific inhibitors may be effective tocolytic agents without the risks to the fetus seen with conventional NSAIDs. The role of COX-2 in oncogenesis is also under investigation, and COX-2 specific inhibitors may eventually be used in the prevention and treatment of gynecologic malignancies. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to describe the two types of cylooxygenase enzymes (COX), to list the effects and side effects of NSAIDs and COX-2 medications, and to outline the various changes in COX expression during pregnancy.

The importance of a travel history in the preoperative assessment of an elective surgical patient.

The authors present the case of a 43-year-old gentleman who was admitted for an elective surgical removal of an eroded gastric band. The patient reported no medical concerns and other than a mild anaemia of haemoglobin of 10.6, his preoperative assessment was non-significant. Postoperatively, the patient spiked temperatures on multiple occasions. When a travel history was subsequently taken, the patient revealed he had returned from Nigeria the night before his elective surgery. The patient tested positive for Plasmodium falciparum malaria for which he was successfully managed with oral quinine and doxycycline, and recuperated well both from malaria and the surgery. P falciparum malaria is a medical emergency and increases the morbidity and mortality of anaesthesia and surgery. Travel histories are not currently routinely taken as part of the preoperative assessment for elective surgical admissions; the authors argue that it should become a mandatory part.

Effect of glycodelin on the production of vascular endothelial growth factor in cumulus cells.

Glycodelin modulates vascular endothelial growth factor (VEGF) production in cumulus cells in vitro. Patients with normal gonadotropin responses who were undergoing IVF demonstrated increased VEGF production to glycodelin, whereas poor responders had a decreased response to glycodelin.

A comparison of medical induction and dilation and evacuation for second-trimester abortion.

OBJECTIVE: The purpose of this study was to compare complication rates of patients who undergo dilation and evacuation or medical abortion between 14 and 24 weeks of gestation. STUDY DESIGN: We present a retrospective cohort study of 297 women who underwent either dilation and evacuation or medical abortion. Statistical methods included the Student t test, the chi(2) test, the Fisher exact test (where appropriate), and logistic regression. RESULTS: The overall complication rate was significantly lower in patients who underwent dilation and evacuation than in patients who underwent medical abortion (4% vs 29%; P <.001). Medical abortions with misoprostol resulted in a lower complication rate than abortions with other medications (odds ratio, 0.2; 95% CI, 0.1-0.4). More Laminaria was associated with a decreased risk of complications with surgical abortions (odds ratio, 0.9; 95% CI, 0.7-1.0). CONCLUSION: Dilation evacuation is the safest method of second-trimester abortion. Misoprostol is safer than other methods for medical abortion. Maximal use of Laminaria will decrease complication rates in surgical abortion.