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Matthew A Bartlett, Karen F Mauck, Paul R Daniels Division of General Internal Medicine, Mayo Clinic Thrombophilia Center, Department of Medicine, Mayo Clinic, Rochester, MN, USA Abstract: Bariatric surgical procedures are now a common method of obesity treatment with established effectiveness. Venous thromboembolism (VTE) events, which include deep vein thrombosis and pulmonary embolism, are an important source of postoperative morbidity and mortality among bariatric surgery patients. Due to an understanding of the frequency and seriousness of these complications, bariatric surgery patients typically receive some method of VTE prophylaxis with lower extremity compression, pharmacologic prophylaxis, or both. However, the optimal approach in these patients is unclear, with multiple open questions. In particular, strategies of adjusted-dose heparins, postdischarge anticoagulant prophylaxis, and the role of vena cava filters have been evaluated, but only to a limited extent. In contrast to other types of operations, the literature regarding VTE prophylaxis in bariatric surgery is notable for a dearth of prospective, randomized clinical trials, and current professional guidelines reflect the uncertainties in this literature. Herein, we summarize the available evidence after systematic review of the literature regarding approaches to VTE prevention in bariatric surgery. Identification of risk factors for VTE in the bariatric surgery population, analysis of the effectiveness of methods used for prophylaxis, and an overview of published guidelines are presented. Keywords: bariatric surgery, venous thromboembolism, prophylaxis, vena cava filter, heparin

Abstract Background MLL2, an epigenetic regulator in mammalian cells, mediates histone 3 lysine 4 tri-methylation (H3K4me3) through the formation of a multiprotein complex. MLL2 shares a high degree of structural similarity with MLL, which is frequently disrupted in leukemias via chromosomal translocations. However, this structural similarity is not accompanied by functional equivalence. In light of this difference, and previous reports on involvement of epigenetic regulators in malignancies, we investigated MLL2 expression in established cell lines from breast and colon tissues. We then investigated MLL2 in solid tumors of breast and colon by immunohistochemistry, and evaluated potential associations with established clinicopathologic variables. Results We examined MLL2 at both transcript and protein levels in established cell lines from breast and colon cancers. Examination of these cell lines showed elevated levels of MLL2. Furthermore, we also identified incomplete proteolytic cleavage of MLL2 in the highly invasive tumor cell lines. To corroborate these results, we studied tumor tissues from patients by immunohistochemistry. Patient samples also revealed increased levels of MLL2 protein in invasive carcinomas of the breast and colon. In breast, cytoplasmic MLL2 was significantly increased in tumor tissues compared to adjacent benign epithelium (p < 0.05), and in colon, both nuclear and cytoplasmic immunostaining was significantly increased in tumor tissues compared to adjacent benign mucosa (p < 0.05). Conclusion Our study indicates that elevated levels of MLL2 in the breast and colon cells are associated with malignancy in these tissues, in contrast to MLL involvement in haematopoietic cancer. In addition, both abnormal cellular localization of MLL2 and incomplete proteolytic processing may be associated with tumor growth/progression in breast and colonic tissues. This involvement of MLL2 in malignancy may be another example of the role of epigenetic regulators in cancer.

Abstract Background Pneumocystis carinii causes pneumonia in immunocompromised patients with a high morbidity and mortality rate, but the interaction between this organism and the host cell is not well understood. The purpose of this research was to study the response of host cells to P. carinii infection on a molecular level. Results The technique of mRNA differential display was used to detect genes whose expression may be affected by P. carinii infection. The nucleotide sequence of one differentially displayed DNA fragment was found to be identical to that of the rat mitochondrial ATPase 6 gene, which is a subunit of the F0F1-ATP synthase complex. A four-fold increase in expression of this gene was verified by Northern blot analysis of total RNA extracted from P. carinii-infected rat lung versus that from mock-infected rat lung. Localization of the cells containing ATPase 6 mRNA was accomplished by in situ hybridization. In sections of non-infected rat lung, these cells were found lining the distal parts of the respiratory tree and in apical areas of the alveoli. Histological location of these cells suggested that they were Clara cells and type II pneumocytes. This hypothesis was confirmed by co-localizing the mRNAs for ATPase 6 and surfactant protein B (SP-B) to the same cells by two-color fluorescent in situ hybridization. Conclusions The ATPase 6 gene is over expressed during P. carinii infection, and type II pneumocytes and Clara cells are the cell types responsible for this over-expression.

Perioperative medicine is an evolving field with important publications each year across multiple disciplines. Staying up to date in the field is complicated due to the wide range of journals that publish relevant articles. This review summarizes the most noteworthy perioperative publications in 2023. We conducted a multi-database search of the literature from January to December 2023 and included all original research articles, meta-analyses, systematic reviews, and guidelines. Abstracts, case reports, letters, protocols, pediatric and obstetric articles, and cardiac surgery publications were excluded. Two authors reviewed each reference using the Distiller SR systematic review software (Evidence Partners Inc., Ottawa, Ontario, Canada). A modified Delphi technique was used to identify eight practice-changing articles as well as another eight articles for table-based summary., Competing Interests: Declaration of competing interest Matthew A. Bartlett, M.B., B.Ch., B.A.O. reports stock ownership in Johnson and Johnson and received honoraria from Elsevier Clinical Key as an expert contributor on “Dual Antiplatelet Therapy, Perioperative Management”. No other authors report conflicts of interest. All authors had access to the data and a role in writing the manuscript., (Copyright © 2024. Published by Elsevier Inc.)

The i-propyl + O2 reaction mechanism has been investigated by definitive quantum chemical methods to establish this system as a benchmark for the combustion of secondary alkyl radicals. Focal point analyses extrapolating to the ab initio limit were performed based on explicit computations with electron correlation treatments through coupled cluster single, double, triple, and quadruple excitations and basis sets up to cc-pV5Z. The rigorous coupled cluster single, double, and triple excitations/cc-pVTZ level of theory was used to fully optimize all reaction species and transition states, thus, removing some substantial flaws in reference geometries existing in the literature. The vital i-propylperoxy radical (MIN1) and its concerted elimination transition state (TS1) were found 34.8 and 4.4 kcal mol-1 below the reactants, respectively. Two β-hydrogen transfer transition states (TS2, TS2') lie above the reactants by (1.4, 2.5) kcal mol-1 and display large Born-Oppenheimer diagonal corrections indicative of nearby surface crossings. An α-hydrogen transfer transition state (TS5) is discovered 5.7 kcal mol-1 above the reactants that bifurcates into equivalent α-peroxy radical hanging wells (MIN3) prior to a highly exothermic dissociation into acetone + OH. The reverse TS5 → MIN1 intrinsic reaction path also displays fascinating features, including another bifurcation and a conical intersection of potential energy surfaces. An exhaustive conformational search of two hydroperoxypropyl (QOOH) intermediates (MIN2 and MIN3) of the i-propyl + O2 system located nine rotamers within 0.9 kcal mol-1 of the corresponding lowest-energy minima., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Objective: To determine whether anticoagulation therapy is associated with an increased risk of complications after initiation of intrauterine contraception (IUC)., Patients and Methods: We retrospectively reviewed records of women receiving anticoagulation therapy at the time of IUC placement from 2000 to 2017 and records of controls (no anticoagulation), matched by race, age, and body mass index. The primary outcome was the cumulative incidence of bleeding (more than spotting [World Health Organization bleeding grades 2 to 4]), IUC expulsion, and IUC removal. Secondary outcomes included treatment for bleeding and bleeding patterns stratified by medication and IUC type. Outcomes were assessed at 24 hours, 30 days, and 6 months after IUC placement., Results: We matched 208 women taking anticoagulants with 421 controls. The most common anti-coagulant agents were aspirin (60.1%) and warfarin (36.1%). Most women received the levonorgestrel IUC. No complications occurred within 24 hours. Patients receiving anticoagulants had higher rates of the primary composite outcome at 30 days (odds ratio, 1.77 [95% CI, 1.04 to 3.04]; P =.04) and at 6 months (odds ratio, 2.05 [95% CI, 1.29 to 3.26]; P =.002). Primary complications did not differ by IUC type among control patients, but among women receiving anticoagulants, nonhormonal IUC was associated with an increased rate of complications ( P =.04)., Conclusion: Anticoagulation therapy was associated with higher rates of bleeding at 30 days and 6 months, and nonhormonal IUC plus anticoagulation therapy was associated with higher rates of primary complications. Our findings support current periprocedural anticoagulation guidelines, which state that anticoagulation and antiplatelet therapy can be continued at the time of IUC insertion., (© 2022 The Authors.)

Venous thromboembolism (VTE) is a preventable cause of postoperative morbidity and mortality; however, audits suggest that the use of thromboprophylaxis is underused. In this review, we describe our approach to prevention of postoperative VTE and provide guidance on how to formulate an optimal VTE prophylaxis plan. We recommend that all patients undergo thrombosis- and bleeding-risk assessment as part of their preoperative evaluation. The risk of thrombosis can be estimated based on patient- and procedure-specific factors, using validated risk-assessment models such as the Caprini score. There are no validated models to predict perioperative bleeding; however, several risk factors have been proposed. Patients should ambulate early and frequently after surgery. We recommend no additional prophylaxis in patients at very low risk of VTE (Caprini score 0). Patients at low risk of VTE (Caprini 1 to 2) are recommended to receive either mechanical or pharmacological prophylaxis. Patients at moderate (Caprini 3 to 4) to high risk of VTE (Caprini ≥5) are recommended pharmacological prophylaxis either alone or combined with mechanical prophylaxis. Patients at high risk of bleeding should receive mechanical prophylaxis until their risk of bleeding is reduced and pharmacological prophylaxis can be reconsidered. Populations for which the Caprini score has not been validated (such as orthopedic surgery) are recommended prophylaxis based on individual and procedure-specific risk factors. Prophylaxis is typically continued until the patient is ambulatory or until hospital dismissal; however, longer durations can be considered in certain circumstances (high-risk patients undergoing malignant abdominopelvic operations, bariatric operations, and certain orthopedic operations)., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

We report the first preparation of the s - cis , s - cis conformer of dihydroxycarbene ( 1 cc ) by means of pyrolysis of oxalic acid, isolation of the lower-energy s - trans , s - trans ( 1 tt ) and s - cis , s - trans ( 1 ct ) product conformers at cryogenic temperatures in a N 2 matrix, and subsequent narrow-band near-infrared (NIR) laser excitation to give 1 cc . Carbene 1 cc converts quickly to 1 ct via quantum-mechanical tunneling with an effective half-life of 22 min at 3 K. The potential energy surface features around 1 were pinpointed by convergent focal point analysis targeting the AE-CCSDT(Q)/CBS level of electronic structure theory. Computations of the tunneling kinetics confirm the time scale of the 1 cc → 1 ct rotamerization and suggest that direct 1 cc → H 2 + CO 2 decomposition may also be a minor pathway. The intriguing latter possibility cannot be confirmed spectroscopically, but hints of it may be present in the measured kinetic profiles.

A single thiocatecholate group has been combined with a phthalocyanine and used to coordinate a [Ni(dppe)]2+ fragment to give the unprecedented title complex [(dppe)Ni(S2PcH2)]. UV-Vis spectroscopy shows new strong transitions in the Q-band, which TDDFT calcualtions predict result from internal charge transfer processes. Insights are gained with respect to designing future photocatalytic systems.

A 56-year-old truck driver with a history of tobacco use presented with acute onset digital ischaemia in the ulnar distribution of his dominant hand, associated with severe pain. Occupational exposures included extensive manual labour and prolonged vibratory stimuli. Workup with Doppler and angiography confirmed the diagnosis of hypothenar hammer syndrome (HHS). After the failure of medical management, he underwent ulnar artery thrombectomy with reconstruction and arterial bypass grafting. His pain improved significantly postsurgically, and he was able to return to a normal routine. This case illustrates the classic presentation, examination, imaging findings and management options of HHS. HHS should be considered in patients with digital ischaemia and associated occupational exposures. Diagnosing the condition appropriately allows for optimal management, aiming at minimising symptoms and maximising quality of life., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The hydridotrioxygen (HO 3 ) radical has been investigated in many previous theoretical and experimental studies over several decades, originally because of its possible relevance to the tropospheric HO x cycle but more recently because of its fascinating chemical bonding, geometric structure, and vibrational dynamics. We have executed new, comprehensive research on this vexing molecule via focal point analyses (FPA) to approach the ab initio limit of optimized geometric structures, relative energies, complete quartic force fields, and the entire reaction path for cis-trans isomerization. High-order coupled cluster theory was applied through the CCSDT(Q) and even CCSDTQ(P) levels, and CBS extrapolations were performed using cc-pVXZ (X = 2-6) basis sets. The cis isomer proves to be higher than trans by 0.52 kcal mol -1 , but this energetic ordering is achieved only after the CCSDT(Q) milestone is reached; the barrier for cis → trans isomerization is a minute 0.27 kcal mol -1 . The FPA central r e (O-O) bond length of trans-HO 3 is astonishingly long (1.670 Å), consistent with the semiexperimental r e distance we extracted from microwave rotational constants of 10 isotopologues using FPA vibration-rotation interaction constants (α i ). The D 0 (HO-O 2 ) dissociation energy converges to a mere 2.80 ± 0.25 kcal mol -1 . Contrary to expectation for such a weakly bound system, vibrational perturbation theory performs remarkably well with the FPA anharmonic force fields, even for the torsional fundamental near 130 cm -1 . Exact numerical procedures are applied to the potential energy function for the torsional reaction path to obtain energy levels, tunneling rates, and radiative lifetimes. The cis → trans isomerization occurs via tunneling with an inherent half-life of 1.4 × 10 -11 s and 8.6 × 10 -10 s for HO 3 and DO 3 , respectively, thus resolving the mystery of why the cis species has not been observed in previous experiments executed in dissipative environments that allow collisional cooling of the trans-HO 3 product. In contrast, the pure ground eigenstate of the cis species in a vacuum is predicted to have a spontaneous radiative lifetime of about 1 h and 5 days for HO 3 and DO 3 , respectively.

Objective: To compare the clinical efficacy and safety of apixaban with those of rivaroxaban for the treatment of acute venous thromboembolism (VTE)., Patients and Methods: Consecutive patients enrolled in the Mayo Thrombophilia Clinic Registry (between March 1, 2013, and January 30, 2018) and treated with apixaban or rivaroxaban for acute VTE were followed forward in time. The primary efficacy outcome was VTE recurrence. The primary safety outcome was major bleeding; the second safety outcome was clinically relevant nonmajor bleeding (CRNMB); and the third was a composite of major bleeding or CRNMB., Results: Within the group of 1696 patients with VTE enrolled, 600 (38%) were treated either with apixaban (n=302, 50%) or rivaroxaban (n=298, 50%) within the first 14 days of VTE diagnosis and who completed at least 3 months of therapy or had a study event. Recurrent VTE was diagnosed in 7 patients (2.3%) treated with apixaban and in 6 (2%) treated with rivaroxaban (adjusted hazard ratio [aHR], 1.4; 95% CI, 0.5-3.8). Major bleeding occurred in 11 patients (3.6%) receiving apixaban and in 9 patients (3.0%) receiving rivaroxaban (aHR, 1.2; 95% CI, 0.5-3.2). Clinically relevant nonmajor bleeding was diagnosed in 7 patients (2.3%) receiving apixaban and in 20 (6.7%) receiving rivaroxaban (aHR, 0.4; 95% CI, 0.2-0.9). The rates of composite major bleeding or CRNMB were similar (aHR, 0.6; 95% CI, 0.3-1.2). Most study events occurred in patients with cancer., Conclusion: In the setting of a standardized, guideline-directed, patient-oriented clinical practice, the efficacy and safety of apixaban and rivaroxaban for the treatment of acute VTE were comparable., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

A new and facile method of generating thiolate groups at the phthalocyanine (Pc) β-position is presented as well the unique properties that these groups confer on the Pc ligand upon coordination of group 10 metals Ni, Pd and Pt(dppe) or SnMe3. In particular, the Q-band is shifted to almost 800 nm for all group 10 metals used, and the complexes show panchromatic absorption owing to new absorbance bands that appear between 400 and 650 nm. Enhanced intersystem-crossing for all transition metal coordinated Mg(Pc) complexes was demonstrated by the moderate to very high singlet oxygen quantum yields of 0.36, 0.76 and 0.91 for the Ni, Pd and Pt coordinating complexes, respectively, which show that the heavy metals have direct influence on the Pc π-system and inter-system-crossing (ISC). This was further confirmed by MO calculations, which show mixing of metal and ligand orbitals, as well as suggest that the Q-band transition has both π → π* and ligand-to-metal charge transfer characteristics. Furthermore, the origin of the Q-band red-shift was shown to be due to greater destabilization of the HOMO compared to LUMO/LUMO+1, thus decreasing the HOMO-LUMO band gap.

Venous thromboembolism (VTE) management is rapidly evolving and staying up-to-date is challenging. We identified the most practice-informing articles published in 2017 relevant to the nonspecialist provider managing VTE. We performed a systematic search of the literature (Appendix A), limiting the search to a publication date of 2017. Two reviewers screened the 2735 resulting abstracts to identify high-quality, clinically relevant publications related to VTE management. One-hundred and six full-text articles were considered for inclusion. The five authors used a modified Delphi method to reach consensus on inclusion of seven articles for in-depth appraisal, following predetermined criteria of clinical relevance to nonspecialist providers, potential for practice change, and strength of the evidence.

A 67-year-old woman presented with 5 days of myalgias and fevers on completion of a 21-day course of amoxicillin for Lyme disease ( Borrelia burgdorferi infection). She was found to have profound thrombocytopenia, as well as new anaemia and leucopenia. Workup revealed Babesia microti as the causative agent of her symptoms. The patient quickly improved after appropriate antimicrobial therapy directed against babesiosis was started. This case illustrates the importance of basic microbiology, including epidemiology and common vectors, when creating a differential diagnosis. Because the Ixodes scapularis tick can harbour and transmit multiple parasites simultaneously, the possibility of coinfection should be considered in any patient not responding to appropriate initial medical therapy., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Disentangling internal and external effects is a key requirement for understanding conformational tunneling processes. Here we report the s- trans/ s- cis tunneling rotamerization of carbonic acid monomethyl ester (1) under matrix isolation conditions and make comparisons to its parent carbonic acid (3). The observed tunneling rate of 1 is temperature-independent in the 3-20 K range and accelerates when using argon instead of neon as the matrix material. The methyl group increases the effective half life (τ eff ) of the energetically disfavored s- trans-conformer from 3-5 h for 3 to 11-13 h for 1. Methyl group deuteration slows the rotamerization further (τ eff ≈ 35 h). CCSD(T)/cc-pVQZ//MP2/aug-cc-pVTZ computations of the tunneling probability suggest that the rate should be almost unaffected by methyl substitution or its deuteration. Thus the observed relative rates are puzzling, and they disagree with previous explanations involving fast vibrational relaxation after the tunneling event facilitated by the alkyl rotor.

While ring-walking is a critical step in transition metal catalyzed cross-coupling reactions, the associated metastable intermediates are often difficult to isolate and characterize. In this work, theoretical structures and energetics for ring-walking and oxidative addition of zerovalent nickel with 1-bromo-2-methylbenzene, 2-bromopyridine, 2-bromo-3-methyl-thiophene, and 2-bromopyrrole were computed at the B3LYP-D3/TZ2P-LANL2TZ(f)-LANL08d level. The mechanisms vary qualitatively with substrate ring size and type-the catalyst weaves along the edges of the benzene and pyridine rings, cuts through the interior of the thiophene ring, and arcs along the bond opposite the nitrogen atom in the pyrrole ring. Analogous computations on the ring-walking and oxidative addition of zerovalent palladium with 1-bromo-2-methylbenzene reveal an energetic profile similar to that of Ni but with much weaker overall binding to the arene. In all cases, dispersion corrections are found to be very important for computing accurate metal-substrate binding energies.

Continuous-wave measurement-based methods offer a rapid cost-effective way to determine optical properties in turbid media. This method requires a measure of the refractive index of the medium, which is often unknown a priori. Whereas previous studies have reported that the refractive index has little impact on the measurement of optical properties, here we show a significant effect of refractive indices on measurements, using both simulations and experiments. In addition we propose a noniterative method to determine the refractive index of the medium. This method can also provide an optimal initial guess of the optical properties for the standard iterative method for determining optical properties in turbid media. Our method is confirmed by simulations and experiments with latex spheres and Intralipid suspensions.

Background: Despite the possible overall health benefits of a vegetarian diet, there is concern that some vegetarians and infrequent meat eaters, particularly females, may have inadequate iron status because of low or no heme-iron intakes., Objective: The objective was to investigate the nutritional intake and iron status of vegetarian women., Design: The nutritional intakes of 50 free-living vegetarian women aged 18-45 y and 24 age-matched omnivorous control women were assessed by using 12-d weighed dietary records. Iron status was assessed by measuring hemoglobin and serum ferritin concentrations., Results: There was no significant difference between mean (+/-SD) daily iron intakes of vegetarians and omnivores (10.7 +/- 4.4 and 9.9 +/- 2.9 mg, respectively), although heme-iron intakes were low in the vegetarians. Vegetarians had significantly lower intakes of protein (P < 0.01), saturated fat (P < 0.01), and cholesterol (P < 0.001), and significantly higher intakes of dietary fiber (P < 0.001) and vitamin C (P < 0.05). Mean serum ferritin concentrations were significantly lower (P = 0.025) in vegetarians (25.0 +/- 16.2 microg/L) than in omnivores (45.5 +/- 42.5 microg/L). However, similar numbers of vegetarians (18%) and omnivores (13%) had serum ferritin concentrations <12 microg/L, which is a value often used as an indicator of low iron stores. Hemoglobin concentrations were not significantly different., Conclusion: It is important that both vegetarian and omnivorous women maintain an adequate iron status and follow dietary practices that enhance iron absorption.