The O-O coupling process in water oxidation on the gamma FeOOH hydroxide catalyst is simulated by means of density functional theory using model iron cubane cluster Fe4O4(OH)4. A key reactive intermediate is proposed to be the HO-FeIV-O• oxyl unit with terminal oxo radical formed from vertex HO-FeIV-OH moiety by withdrawal of proton-electron pair. The O-O coupling goes via water nucleophilic attack on the oxyl oxygen to form the O-O bond with a remarkably low barrier of 11 kcal/mol. This process is far more effective than alternative scenario based on direct interaction of two ferryl FeIV=O sites (with estimated barrier of 36 kcal/mol) and is comparable with the coupling between terminal oxo center and three-coordinated lattice oxo center (12 kcal/mol barrier). The process of hydroxylation of terminal oxygen inhibits the O-O coupling. Nevertheless, being more effective for ferryl oxygen, the hydroxylation in fact enhances selectivity of the O-O coupling initiated by the oxyl oxygen.

Aims: A prolonged PR interval may adversely affect ventricular filling and therefore cardiac function. AV delay can be corrected using right-ventricular-pacing (RVP) but this induces ventricular dyssynchrony, itself harmful. Therefore, in intermittent heart-block, pacing-avoidance algorithms are often implemented. We tested His-bundle pacing (HBP) as an alternative. Methods: Out-patients with a long PR interval(>200ms) and intermittent need for ventricular pacing were recruited. We measured within patient differences in high-precision haemodynamics between AV-optimized RVP, and HBP, as well as a pacing-avoidance algorithm [Managed Ventricular Pacing (MVP)]. Results We recruited 18 patients. Mean left ventricular ejection fraction was 44.3±9%. Mean intrinsic PR interval was 266±42ms and QRS duration was 123±29ms. RVP lengthened QRS duration(+54 ms, 95%CI 42 to 67ms, p<0.0001) whilst HBP delivered a shorter QRS duration than RVP(-56 ms, 95%CI -67 to -46ms, p<0.0001). HBP did not increase QRS duration(-2ms 95%CI -8 to 13ms, p=0.6). HBP improved acute systolic blood pressure by mean of 5.0 mmHg(95%CI 2.8 to 7.1mmHg, p<0.0001) compared to RVP and by 3.5 mmHg(95%CI 1.9 to 5.0mmHg, p=0.0002) compared to the pacing avoidance algorithm. There was no significant difference in haemodynamics between RVP and ventricular pacing avoidance (p=0.055). Conclusions HBP provides better acute cardiac function than pacing avoidance algorithms and RVP, in patients with prolonged PR intervals. HBP allows normalisation of prolonged AV delays (unlike pacing avoidance) and does not cause ventricular dyssynchrony (unlike RVP). Clinical trials may be justified to assess whether these acute improvements translate into longer term clinical benefits in patients with bradycardia indications for pacing.

Over the past 90 years, anthropogenic degradation of soil caused by alkaline, magnesium-rich dust deposit has presented a serious problem near magnesite processing factories in Jelšava and in Lubeník (Slovakia). The objective of this study was to investigate the chemical and biological soil properties in 14 sampling sites at different distances from factories, and based on the results, to propose further use of affected land. Results revealed that the available Mg 3–68 fold exceeded very high content for texturally medium soils at all grassland sampling sites, and areas close factory contained up to 14.4–17.4 g kg-1. Higher excess of available Mg caused significant increase of soil pH (up to 9.39) and worsened the conditions for the growth of vegetation. As a result, lower stock of newly formed organic matter (0.50–0.96 g kg-1 of labile carbon) with consequently weaker enzymatic activity occurred. Therefore, enrichment by organic matter provides a measure to support the biological activity of soil. The content of monitored heavy metals (Zn, Cu, Pb and Ni) was not related to Mg and did not influence the enzymatic activity of soil. Because alkaline emissions have decreased by 99.8% since 1970, the application of classical measures (mechanical removal of the Mg-rich crust, incorporation of gypsum and manure to the soil), or newer methods (growing of Mg hyper-accumulating plants) can offer more lasting positive effects than those of 50 years ago. This study concluded that Mg-rich, alkaline dust deposition causes long-lasting anthropogenic soil degradation.

Mini-commentary on BJOG-20-0142.R1: Acupuncture for recurrent urinary tract infection in women: A systematic review and meta-analysis

Background and aim: Revascularization guidelines support routine heart team (HT) discussion of appropriate patients. The effect of HT on decision making and clinical outcomes hasn’t been explored. The aim of our study is to investigate the impact of the HT on the mode and delay to revascularization. Methods: We compared data from a prospective cohort of consecutive patients with multivessel coronary artery disease referred for HT discussion between 2016-2017 (HT group) with a historic control group of patients matched according to clinical and angiographic characteristics treated between 2005-2015 (No HT group). Results: There were 93 patients in each group. The HT group and the No HT groups had a similar rate of ACS as well as cardiovascular risk factors and significant left ventricular (LV) dysfunction. No difference was observed in the mean Society of Thoracic Surgery (STS) score (2.5± 3 vs. 3 ±3 p=0.32) and the mean SYNTAX score was low and similar in both groups (21±6 vs. 19±6 p=0.59). The treatment recommendations changed greatly, with 63% of patients being referred for coronary artery bypass grafting (CABG) after HT discussion but only 23% in the no HT group (p<0.01). HT discussion led to a significant delay to PCI (8±5 vs. 1.8±4 days, p=0.02), while surgical revascularization times were not affected. Conclusion: HT discussion in patients with multivessel CAD was associated with an increased referral to CABG but led to a significant delay in revascularization by angioplasty. The impact of these findings on patient satisfaction and outcome should be further investigated.

Letter to the Editor, BJOG Exchange

Grazing exclusion (GE) has been applied as a suitable strategy to soil conservation worldwide, mainly in semiarid soils. However, it is unclear how GE management reduces the negative effects of overgrazing on the microbial community. In this study, we assessed the bacterial community in three different soil management belonged to a semiarid region from the Brazilian Caatinga biome, as follows: Native Caatinga (NC), Grazing exclusion (GE), and a highly degraded area by Overgrazing (OG). The bacterial community was assessed through the sequencing of the V4 region of the 16S rRNA gene. We also analyzed soil chemical and physical properties and correlated with bacterial community composition, and α- and β- diversities. Our results demonstrated that GE increases the content of soil C, N, and bacterial diversity. However, the changes in bacterial diversity were significant in a specific site (nº 1), suggesting that GE strategy could be a context-dependent and a complex approach to Caatinga soils. Moreover, overgrazing might restrain the potential of bacterial diversity to sustain ecosystem functions, since non-beneficial elements (e.g., Na+ and Al3+) increased in OG, which presented a negative correlation with the bacterial community. Our study provides novel evidence that high-intensity disturbance by overgrazing could not only reduce soil fertility, but it may also restrain bacterial composition, with implications on environmental functioning. Thus, the Caatinga soil microbiome may be unable to maintain ecosystem services such as plant and animals’ development under overgrazing management.

Objective: To define the prevalence of adverse outcomes according to the gestational age of maternal infection in a large cohort of ZIKV-infected Brazilian women and their infants. Design: Prospective, population-based cohort study. Setting: Ribeirão Preto’s region private and public health facilities. Population: All pregnant women with confirmed ZIKV-infection and their infants. Methods: Prenatal/early neonatal data were obtained for all pairs. A subgroup of infants had cranial ultrasonography, eye fundoscopy, hearing, neurological exam, and Bayley III screening test within 3 months of age. Main Outcome Measures: Prevalence of pregnancy losses, anomalies detected at birth or within 3 months according to the gestational age of infection. Results: 511 women with ZIKV were identified from a total of 1116 women with flavivirus-type symptoms. Pregnancy losses 24/511(4.7%) and/or ZIKV-related anomalies occurred in 43/511(8.4%) mothers. Microcephaly or other CNS malformations were diagnosed in 1/4(25.0%) of the stillbirths and 19/489[3.9%;CI95%:2.5-5.9] of the live-born infants, with 13/513[2.5%;CI95%:1.5-4.3] neonates presenting major signs of CZS. Fetal abnormalities were 14.0(CI95%:7.6-26.0) times more likely with gestational infection <11 weeks. Among 280 asymptomatic evaluated infants, 2/155(1.3%) had eye abnormalities, 1/207(0.5%) CNS imaging significant findings, and 16/199(8%) neurological alert signs. Conclusions: This prospective, population-based study represents the largest Brazilian cohort of ZIKV in pregnancy. Congenital anomalies potentially associated with CZS are less frequent than previously thought. There is a strong relationship between the gestational age of infection (<11 weeks) and worse early infant prognosis. A notable proportion of apparently asymptomatic newborns can present with subclinical findings within 3 months of age. Funding: FAEPA/SES-SP

As a milestone in soft and hard tissue engineering, a precise control over the micropatterns of scaffolds have lightened new opportunities for the recapitulation of native body organs through 3D bioprinting approaches. Well-printable bioinks are pre-requisites for the bioprinting of tissues/organs where hydrogels play a critical role. Despite the outstanding developments in 3D engineered microstructures, current printer devices, suffer from the risk of exposing loaded living agents to mechanical (nozzle-based) and thermal (nozzle-free) stresses. Thus, tuning the rheological, physical, and mechanical properties of hydrogels are promising solutions to address these issues. The relationship between the mechanical characteristics of hydrogels and their printability is important to control printing quality and fidelity. Recent developments in defining this relationship have highlighted the decisive role of main additive manufacturing strategies. These strategies are applied to enhance the printing quality of scaffolds and determine the nurture of cellular morphology. In this regard, it is beneficial to use external and internal stabilization, photo curable biopolymers, and cooling substrates containing the printed scaffolds. The objective of this study was to review cutting-edge developments in hydrogel-type bioinks and discuss the optimum simulation of the zonal stratification in osteochondral and cartilage units.

Background: Socioeconomic and health care coverage disparities are established as poor prognostic markers in adults with sarcoma, but few studies examine these differences among pediatric, adolescent and young adults (AYA). This study examines the association between socioeconomic status (SES), insurance status, and disease presentation among children and AYA patients with sarcoma. Methods: This is a retrospective cohort study of patients aged 0-25 years with bone or soft tissue sarcoma from the National Cancer Database. SES assignments were based on estimated median income and education-level. Patient demographics and clinical factors were compared by SES and insurance status. Multivariate logistic regression models were fitted to determine adjusted odds ratios of SES and insurance status on metastatic disease or tumor size ≥5cm at time of presentation. Results: In a cohort of 9112 patients, 2932 (32.1%) had low, 2084 (22.8%) middle, and 4096 (44.9%) high SES. For insurance status, 5864 (64.3%) had private, 2737 (30.0%) public, and 511 (5.6%) were uninsured. Compared to high SES, patients with low SES were more likely to have metastatic disease (OR=1.16, p=0.03) and tumors ≥5cm (OR=1.29, p<0.01). Compared to private insurance, public and no insurance were associated with metastatic disease (OR=1.35, p<0.01 and OR=1.32, p=0.02) and increased tumors ≥5cm (OR=1.28, p<0.01 and OR=1.67, p<0.01). Conclusions: SES disparities exist among children and AYA patients with sarcoma. Low SES and public or no insurance are associated with advanced disease at presentation. Further studies are needed to identify interventions to improve earlier detection of sarcomas in at-risk children and young adults.

More than 1.2 million people died from chronic kidney damage (CKD) globally, in 2017. Anemia is a common complication of CKD. Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Roxadustat is often used to treat anemia caused by renal diseases. Its adverse effects include high blood pressure, myocardial infarction, heart failure, high potassium, and dizziness; however, there are no reports about rhabdomyolysis associated with roxadustat. One of our patients developed rhabdomyolysis after he was administered roxadustat to treat anemia caused by chronic renal failure. Physicians should be alert about the occurrence of rhabdomyolysis when roxadustat is used.

Hydrogen sulfide (H2S) together with polysulfides (H2Sn, n>2) are signaling molecules like nitric oxide (NO) with various physiological roles including regulation of neuronal transmission, vascular tone, inflammation, oxygen sensing etc. H2S and H2Sn diffuse to the target proteins to S-sulfurate their cysteine residues to induce the conformational changes to alter the activity. On the other hand, 3-mercaptopyruvate sulfurtransferase transfers sulfur from a substrate 3-mercaptopyruvate to the cysteine residues of acceptor proteins. A similar mechanism has also been identified in S-nitrosylation. S-sulfuration and S-nitrosylation by enzymes proceed only inside the cell, while reactions induced by H2S, H2Sn and NO even extend to the surrounding cells. Disturbance of signaling by these molecules as well as S-sulfuration and S-nitrosylation causes many neuronal diseases. This review focuses on the signaling by H2S and H2Sn with S-sulfuration compared with those of NO and S-nitrosynation, and discuss on their roles in physiology and pathophysiology.

Expanding Clinical Spectrum of Female X-linked Lymphoproliferative Syndrome 2Shruthi Suryaprakash, MD1, Mohammad El-Baba2, MD, Kelly J. Walkovich, MD3, Süreyya Savaşan, MD41Children’s Hospital of Michigan2Division of Gastroenterology, Children’s Hospital of Michigan3Division of Hematology/Oncology, Immuno-Hematology Comprehensive Program, C.S. Mott Children’s Hospital, University of Michigan4Division of Hematology/Oncology and Blood and Marrow Transplant Program, Children’s Hospital of Michigan, Carman and Ann Adams Department of Pediatrics, Barbara Ann Karmanos Cancer Center, Central Michigan University College of MedicineCorrespondence: Süreyya Savaşan, MD3901 Beaubien Blvd.Division of Hematology/OncologyBlood and Marrow Transplant ProgramChildren’s Hospital of MichiganDetroit, Michigan 48201E-mail: [email protected]: 313-745-5516 Fax: 313-745-5237Text word count: 495Reference count: 4Tables and figures: 1Short running title: Spectrum of Symptomatic Female XLP2Key words: Female XLP2, EBV reactivation, Vitamin B12 deficiency, B-cell lymphopenia, clonal T-LGL proliferationDear Editor:X-linked lymphoproliferative syndrome type 2 (XLP2) due to pathogenic variants in the X-linked inhibitor of apoptosis (XIAP) gene is a rare cause of primary immunodeficiency. Symptomatic patients, primarily males, present with hemophagocytic lymphohistiocytosis (HLH), inflammatory bowel disease (IBD) and/or transient hypogammaglobinaemia.1 However, XLP2 in female patients is complicated with the rarity of symptomatic cases and clinical heterogeneity.2 We report a female affected by XLP2 with previously unreported findings.A currently 18-year-old female presented with fever, abdominal pain, diffuse lymphadenopathy, splenomegaly, and pancytopenia three years ago. She was diagnosed with HLH, treated with steroids and found to have low B-cells and borderline hypogammaglobinemia. Additionally, a single pathogenic variant in XIAP (c.389_392delACAG [p.Asp130Glyfs*11]) was identified. Further workup showed presence of EBV IgG, and normal expression of XIAP protein in only 8-19% of various white blood cell types by flow cytometry indicating skewed X chromosome inactivation. She had intermittent infections, one resulting in an additional HLH flare with elevated IL-18 and CXCL9 levels that was treated with steroids and intravenous immunoglobulin (IVIG). Repeated EBV PCR testing had been negative.However, she was found to have EBV reactivation with positive EBV VCA-IgM, high titer VCA-IgG and EA-IgG levels while EBV-PCR was negative when she presented to our clinic with diarrhea. There was ongoing history of headaches, abdominal pain, joint pain, and ADHD at that time. Later, she underwent work up for recurrent abdominal pain, diarrhea, urgency and elevated fecal calprotectin. MRI-enterography and capsule endoscopy were negative. Endoscopy was remarkable for chronic active proctitis. She was prescribed mesalamine with significant improvement in abdominal pain and resolution of mucuosy stools.Due to persistent knee/ankle pain, she was investigated for peripheral neuropathy and was found to have low vitamin B12 levels (112-145pg/mL; N:180-914) without dietary restrictions, absent anti-intrinsic factor antibodies and negative family history. Her pain improved significantly on vitamin B12 injections and gabapentin with normalization of vitamin B12 levels.She continued to have fluctuating and borderline low levels of serum immunoglobulins with persistently low B-cells. She was given IVIG supplementation when serum IgG levels were low. No additional HLH flares have occurred. Mild increase in CD5-dim T-cells (9%) representing T-large granular lymphocytes (T-LGL) and clonal T-cell receptor (TCR) rearrangement pattern were identified in peripheral blood. She continues to have migraine episodes and very high EA-IgG at >150U/mL (N <9).Female carriers are at risk for extra hematopoietic manifestations, if they have an extremely skewed X chromosome inactivation.3 She was EBV-PCR negative, but EBV VCA-IgM positive repeatedly suggesting a recent reactivation at presentation to our institution. Persistent high EBV EA-IgG titers is suggestive of ongoing EBV challenge due to immune deficiency and emphasizes the significance of EBV serology testing. Clonal T-LGL expansion may be related to EBV and/or immune deficiency.4 Low vitamin B12 raises the possibility of impairment in absorption; the presence of proctitis raises possible subclinical inflammation in the distal ileum. Observed conditions in this case add to the spectrum of this rare entity (Table1).

Aim: To describe the pattern of paediatric soft tissue sarcomas with emphasis on the grade and stage at the first surgical or medical oncologic intervention. Methods: We retrospectively reviewed all cases of histologically confirmed paediatric Soft Tissue Sarcomas in the Department of Pathology, University College Hospital (UCH), Ibadan, Nigeria in children age 0-14 years. The study period was January 1991 to December 2016. Information obtained included age, gender, morphology and site of the tumours. The tumour grade and pathologic/clinical staging of all cases that had surgical biopsy or surgical resection were also obtained and verified from the clinical records. Tumour grading was carried out using the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) Sarcoma group grading system and staging was done using TNM. Results: One hundred and twelve cases were seen with an almost equal male-to-female ratio and age range from 5 months to 14 years (median 8.5 years). The peak age group was 5-9 years. Rhabdomyosarcoma was by far the most common histological type (73.2%). Other types were undifferentiated sarcomas (6.3%), fibrosarcoma (5.4%), Kaposi sarcoma (4.5%), and 2.7% each for synovial sarcoma, dermatofibrosarcoma protuberans. The common primary sites were the head and neck (including the orbit) 51(45.5%), and the abdominopelvic 27(24.1%) regions. Other sites included the lower limb 13(11.6%), trunk 12(10.7%), upper limb 6(5.4%). Majority (67.9%) had histologic grade 3 at presentation based on the FNCLCC grading system. About 48.2% had Stage T2b while 9.8% were stage T2a based on American Joint Committee on Cancer Staging (AJCC) system. Conclusion: Rhabdomyosarcoma, undifferentiated sarcomas and Kaposi sarcoma are the commonest paediatric malignant soft tissue tumours in our practice. Majority of our patients present with late stage tumour and with high histologic grade thereby conferring poor prognosis at presentation/first surgical or medical oncologic intervention.

Aim Doppler echocardiography has become the standard imaging modality for diastolic function and provide pathophysiological insight into systolic and diastolic heart failure. In this study we aimed to obtain normal echocardiographic Doppler parameters of healthy Turkish population. Methods Among 31 collaborating institutions from all regions of Turkey, 1154 healthy volunteers were enrolled in this study. Predefined protocols were used for all participants during echocardiographic examination and The American Society of Echocardiography and European Association of Cardiovascular Imaging recommendations were used for echocardiographic Doppler measurements. Results A total of 967 healthy participants were enrolled in this study after applying exclusion criteria. Echocardiographic examination was obtained from all subjects following predefined protocols. Mitral E wave velocity and E/A ratio were higher in females and decreased progressively in advancing ages. E wave deceleration time and A wave velocity were increased with aging. Assessment of tissue Doppler velocities showed that left ventricular lateral e’, septal e’ and septal s’ were higher in younger subjects and in females. E/e’ ratio was increased progressively with advancing decades. Right ventricular e’and s’ were decreased but a’ was increased with increasing age. Septal e’ lower than 8 cm/s was 1.9% in the fifth decade and 13.7% in ages older than 50-years. The E/e’ ratio greater than 15 (and also 13) was not found. Conclusion This study, for the first time, provides echocardiographic reference ranges for normal cardiac Doppler data in healthy Turkish population which will be useful in routine clinical practice as well as in future clinical trials.

The structure, energetic and quantum chemical descriptors of Cs+ complexes of calix[4]arene-crown-6 (C4C6) and substituted C4C6 i.e 1,3 alternate-diethoxy C4C6 are reported here based on the analysis of results using density functional theory. Substitution of benzo group to both C4C6 and 1,3 alternate-diethoxy C4C6 resulted in reduction of binding energy (BE). Further substitution on benzo group with methyl, methoxy and amino groups leads to increase in BE and nitro substitution leads to decrease in BE for C4C6, whereas in the case of 1,3 alternate-diethoxy calix[4]arenebenzocrown-6, methoxy substitution leads to highest BE compared to other complexes. The calculated Gibbs free energy, ΔGgas also followed the same order as BE in the case of 1,3 alternate-diethoxy C4C6 and their substituted ligands. Furthermore, the ΔG of complexation were computed using thermodynamic cycle with conductor like screening model (COSMO) in different solvents: toluene, chloroform, octanol and nitrobenzene. The values of ΔGext are found to be increased with increase in the dielectric constant of the solvent and found to be highest in the nitrobenzene. The Atoms in Molecule (AIM) analysis reveals partial ionic character in Cs-O bond. Among all the studied complexes, 1,3 alternate-diethoxy calix[4]arene 3’-methoxy benzo crown-6 displays highest ΔGext in nitrobenzene. The calculated value of ∆∆Gext (∆∆G= ∆GCs+-∆GNa+) is found to be -41.82 kcal/mol with 1,3 alternate-diethoxy calix[4]arene 3’-methoxy benzocrown-6 which is higher than that obtained with calix [4] bis-crown-6 (-5.24 kcal/mol). The newly designed ligand might be suitable for the selective extraction of Cs+ over Na+ in the reprocessing of nuclear waste and thus invites the experimentalists for testing this DFT finding in the laboratory.

To cope with the energy crisis and global warming issues, researcher are rendering their efforts and paying their attentions to analyze and fabricate hydrogen storage devices. In this regard, we report a comprehensive study on the structural, vibrational, and optoelectronic properties of Lithium Borohydride (LiBH4), a hydrogen storage material. For this purpose, calculations of structural properties have been made using the local, non-local and hybrid functionals within the framework of density functional theory (DFT). The lattice constants for the orthorhombic phase are determined by applying LDA, PBE and HSE06 density functionals and their results are compared with available experimental and theoretical studies. In order to determine IR and Raman active modes of vibrations, vibrational spectroscopy has been utilized through Density Functional Perturbation Theory (DFPT) approach. Li, B and H atoms are noticed to be contributing in the modes of vibrations between different ranges of frequencies, i.e., 0 to 400 cm-1, 1100 to 1300 cm-1 and 2250 -2400 cm-1. The respective values of band gaps are found to be 6.35 eV, 6.81 eV and 7.58 eV for LDA, PBE and HSE06 functionals, respectively, leading to indicate insulating nature of LiBH4 which makes it a promising candidate for applications in optoelectronic devices. The mechanical analysis reveals that LiBH4 is a brittle material. The optical properties such as dielectric constant, refractive index, reflectivity, absorptivity, conductivity and loss function are also calculated with the aid of well-recognized relation of Kramer-Kronig. The plasma frequency is noted at the highest peak (13.7 eV) of the energy loss function.

Exploring the space generated by the self-assembly of known metal oxides computationally and the ability to predict new architectures is a challenging task. Narrowing it down to a family of all-inorganic porous materials, composed of ring-shaped tungsten oxide building blocks connected with transition metal linkers forming zero to three dimensional frameworks. Structurally like zeolites (213 recognized structures), but an order of magnitude smaller, the POMzite library has only 14 members. Applying the concept of ‘materials by design’ applied to molecular metal oxide chemistry synthesis, and their assembly into frameworks. Structures with new topologies, but aiming for pure inorganic systems, will be targeted from the beginning.