Middle East respiratory syndrome coronavirus vaccine based on a propagation-defective RNA replicon elicited sterilizing immunity in mice.

Self-amplifying RNA replicons are promising platforms for vaccine generation. Their defects in one or more essential functions for viral replication, particle assembly, or dissemination make them highly safe as vaccines. We previously showed that the deletion of the envelope (E) gene from the Middle East respiratory syndrome coronavirus (MERS-CoV) produces a replication-competent propagation-defective RNA replicon (MERS-CoV-ΔE). Evaluation of this replicon in mice expressing human dipeptidyl peptidase 4, the virus receptor, showed that the single deletion of the E gene generated an attenuated mutant. The combined deletion of the E gene with accessory open reading frames (ORFs) 3, 4a, 4b, and 5 resulted in a highly attenuated propagation-defective RNA replicon (MERS-CoV-Δ[3,4a,4b,5,E]). This RNA replicon induced sterilizing immunity in mice after challenge with a lethal dose of a virulent MERS-CoV, as no histopathological damage or infectious virus was detected in the lungs of challenged mice. The four mutants lacking the E gene were genetically stable, did not recombine with the E gene provided in trans during their passage in cell culture, and showed a propagation-defective phenotype in vivo. In addition, immunization with MERS-CoV-Δ[3,4a,4b,5,E] induced significant levels of neutralizing antibodies, indicating that MERS-CoV RNA replicons are highly safe and promising vaccine candidates.

The role of single nucleotide variant rs3819817 of the Histidine Ammonia-Lyase gene and 25-Hydroxyvitamin D on bone mineral density, adiposity markers, and skin pigmentation, in Mexican population.

PURPOSE: Vitamin D (VD) deficiency and osteoporosis have become a global public health problem. A variant in the Histidine Ammonia-Lyase (HAL) gene has been associated with VD levels and bone mineral density (BMD). However, whether this variant has an influence on VD levels and BMD in Mexican adults remain unclear. METHODS: This cross-sectional analysis included 1,905 adults participating in the Health Worker Cohort Study and 164 indigenous postmenopausal women from the Metabolic Analysis in an Indigenous Sample (MAIS) cohort. The rs3819817 variant was genotyped by TaqMan probe assay. Total 25 hydroxyvitamin D levels were measured by DiaSorin Liaison. BMD at the different sites was assessed through dual-energy X-ray absorptiometry. Linear and logistic regression models were performed to evaluate the associations of interest. RESULTS: The prevalence of VD deficiency was 41%, showing differences between sexes. Obesity and skin pigmentation were associated with lower levels of VD in males and females. rs3819817-T allele was associated with low levels of 25-hydroxyvitamin D, VD deficiency, and hip and femoral neck BMD values (g/cm2). We found two interactions with VD levels, one between adiposity and rs3819817-T allele (P = 0.017) and another between skin pigmentation and rs3819817-T allele (P = 0.019). In indigenous postmenopausal women, we observed higher VD levels in the southern region compared to the northern region (P < 0.001); however, we did not observe differences by genotype. CONCLUSION: Our findings confirm that the genetic variant rs3819817 has an essential function in VD levels and BMD and suggests a role in skin pigmentation in the Mexican population.

Fungal Planet description sheets: 1436-1477.

Novel species of fungi described in this study include those from various countries as follows: Argentina, Colletotrichum araujiae on leaves, stems and fruits of Araujia hortorum. Australia, Agaricus pateritonsus on soil, Curvularia fraserae on dying leaf of Bothriochloa insculpta, Curvularia millisiae from yellowing leaf tips of Cyperus aromaticus, Marasmius brunneolorobustus on well-rotted wood, Nigrospora cooperae from necrotic leaf of Heteropogon contortus, Penicillium tealii from the body of a dead spider, Pseudocercospora robertsiorum from leaf spots of Senna tora, Talaromyces atkinsoniae from gills of Marasmius crinis-equi and Zasmidium pearceae from leaf spots of Smilaxglyciphylla. Brazil, Preussia bezerrensis from air. Chile, Paraconiothyrium kelleni from the rhizosphere of Fragaria chiloensis subsp. chiloensis f. chiloensis. Finland, Inocybe udicola on soil in mixed forest with Betula pendula, Populus tremula, Picea abies and Alnus incana. France, Myrmecridium normannianum on dead culm of unidentified Poaceae. Germany, Vexillomyces fraxinicola from symptomless stem wood of Fraxinus excelsior. India, Diaporthe limoniae on infected fruit of Limonia acidissima, Didymella naikii on leaves of Cajanus cajan, and Fulvifomes mangroviensis on basal trunk of Aegiceras corniculatum. Indonesia, Penicillium ezekielii from Zea mays kernels. Namibia, Neocamarosporium calicoremae and Neocladosporium calicoremae on stems of Calicorema capitata, and Pleiochaeta adenolobi on symptomatic leaves of Adenolobus pechuelii. Netherlands, Chalara pteridii on stems of Pteridium aquilinum, Neomackenziella juncicola (incl. Neomackenziella gen. nov.) and Sporidesmiella junci from dead culms of Juncus effusus. Pakistan, Inocybe longistipitata on soil in a Quercus forest. Poland, Phytophthora viadrina from rhizosphere soil of Quercus robur, and Septoria krystynae on leaf spots of Viscum album. Portugal (Azores), Acrogenospora stellata on dead wood or bark. South Africa, Phyllactinia greyiae on leaves of Greyia sutherlandii and Punctelia anae on bark of Vachellia karroo. Spain, Anteaglonium lusitanicum on decaying wood of Prunus lusitanica subsp. lusitanica, Hawksworthiomyces riparius from fluvial sediments, Lophiostoma carabassense endophytic in roots of Limbarda crithmoides, and Tuber mohedanoi from calcareus soils. Spain (Canary Islands), Mycena laurisilvae on stumps and woody debris. Sweden, Elaphomyces geminus from soil under Quercus robur. Thailand, Lactifluus chiangraiensis on soil under Pinus merkusii, Lactifluus nakhonphanomensis and Xerocomus sisongkhramensis on soil under Dipterocarpus trees. Ukraine, Valsonectria robiniae on dead twigs of Robinia hispida. USA, Spiralomyces americanus (incl. Spiralomyces gen. nov.) from office air. Morphological and culture characteristics are supported by DNA barcodes. Citation: Tan YP, Bishop-Hurley SL, Shivas RG, et al. 2022. Fungal Planet description sheets: 1436-1477. Persoonia 49: 261-350. https://doi.org/10.3767/persoonia.2022.49.08.

Evidence of possible SARS-CoV-2 vertical transmission according to World Health Organization criteria in asymptomatic pregnant women.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vertical transmission has been investigated extensively. Recently, the World Health Organization (WHO) published strict criteria to classify the timing of mother-to-child transmission of SARS-CoV-2 into different categories. The aim of this study was to investigate the possibility of vertical transmission in asymptomatic SARS-CoV-2-positive women. METHODS: Pregnant women attending for delivery at a perinatology center in Mexico City, Mexico, who had a SARS-CoV-2-positive nasopharyngeal swab 24-48 h before delivery, were asymptomatic at the time of the test and had an obstetric indication for Cesarean section were eligible for inclusion in this study. Amniotic fluid was collected during Cesarean delivery, and neonatal oral and rectal swabs were collected at birth and at 24 h after birth. SARS-CoV-2 detection was carried out using real-time reverse-transcription polymerase chain reaction in all samples. Relevant medical information was retrieved from clinical records. The WHO criteria for classifying the timing of mother-to-child transmission of SARS-CoV-2 were applied to the study population. RESULTS: Forty-two SARS-CoV-2-positive asymptomatic pregnant women fulfilled the inclusion criteria. Twenty-five (59%) women developed mild disease after discharge. Neonatal death occurred in three (7%) cases, of which one had a positive SARS-CoV-2 test at birth and none had coronavirus disease 2019-related symptoms. There were five (12%) cases with strong evidence of intrauterine transmission of SARS-CoV-2, according to the WHO criteria, as amniotic fluid samples and neonatal samples at birth and at 24 h after birth were positive for SARS-CoV-2. Our results also showed that 40-60% of infected neonates would have been undetected if only one swab (oral or rectal) was tested. CONCLUSION: This study contributes evidence to reinforce the potential for vertical transmission of SARS-CoV-2 even in asymptomatic women and highlights the importance of testing more than one neonatal sample in order to increase the detection rate of SARS-CoV-2 in affected cases. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

COL1A1, CCDC170, and ESR1 single nucleotide polymorphisms associated with distal radius fracture in postmenopausal Mexican women.

Objective: The aim of this study was to analyze the genetic association of five ESR1 single nucleotide polymorphisms (SNPs) (rs3020331, rs851982, rs1999805, rs2234693, rs3020404), four COL1A1 SNPs (rs1800012, rs2075555, rs2412298, rs1107946), and two SNPs on the CCDC170 gene (rs9479055, rs4870044) with distal radius fracture (DRF) in a group of postmenopausal Mexican women.Methods: A case-control study was conducted. Cases (n = 182) were women above the age of 38 years with low-energy DRF, and controls (n = 201) were women without. Analysis was done through real-time polymerase chain reaction. Frequencies and Hardy-Weinberg equilibrium were calculated. A multivariate analysis including bone mass index, age, menarche, and menopause as covariables was carried out. Finally, haplotype and linkage disequilibrium (LD) analyses were performed.Results:COL1A1 rs1107946 was strongly associated with DRF. Both CCDC170 SNPs showed strong association with DRF. For the ESR1 gene, four SNPs (rs2234693, 3020404, rs3020331, and rs851982) showed very strong association with DRF. Additionally, the region between the latter two showed strong LD.Conclusions: A strong association of DRF with variants in these genes was found, including haplotypes and a region with strong LD on ESR1. The results suggest that these SNPs could be useful to detect the population at risk of presenting DRF among Mexican perimenopausal women.

Association between vitamin D deficiency and common variants of Vitamin D binding protein gene among Mexican Mestizo and indigenous postmenopausal women.

PURPOSE: Vitamin D deficiency (VDD) and polymorphisms in the group-specific component (GC) gene are known to be associated in different populations. However, the effects of such genetic variants may vary across different populations. Thus, the objective of this study was to estimate the association between Vitamin D-Binding Protein (VDBP) haplotypes and VDD in mestizo postmenopausal women and Mexican Amerindian ethnic groups. METHODS: This was a cross-sectional study of 726 postmenopausal Mexican women from the Health Workers Cohort Study (HWCS) and 166 postmenopausal women from the Metabolic Analysis in an Indigenous Sample (MAIS) cohort in Mexico. GC polymorphisms (rs7045 and rs4588) were analyzed by TaqMan probes. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured by Chemiluminescent Microparticle Immuno Assay. RESULTS: The prevalence of VDD serum 25(OH)D < 20 ng/mL was 43.7% in mestizo women and 44.6% in indigenous women. In HWCS, the single nucleotide polymorphisms (SNPs) rs7041 and rs4588 were associated with VDD. In addition, women from the HWCS, carrying the haplotypes GC2/2 and GC1f/2 had higher odds of VDD (OR = 2.83, 95% CI 1.14, 7.02; and OR = 2.30, 95% CI 1.40, 3.78, respectively) compared to women with haplotype 1f/1 s. These associations were not statistically significant in the MAIS cohort. CONCLUSIONS: Our results show genetic association of the analyzed SNPs and related haplotypes, on the GC gene, with VDD in mestizo Mexican postmenopausal women. Moreover, a high prevalence of VDD with high genetic variability within the country was observed. Our results support the need for national policies for preventing VDD.

Association of RMND1/CCDC170-ESR1 single nucleotide polymorphisms with hip fracture and osteoporosis in postmenopausal women.

OBJECTIVE: This study aimed to investigate the association of seven single nucleotide polymorphisms (SNPs) on the RMND1, CCDC170, and ESR1 genes with osteoporosis or hip fracture in a postmenopausal Mexican population. METHODS: We included a group of 400 postmenopausal women from the Health Workers Cohort Study from the Mexican Institute of Social Security. As a replication sample, we recruited 423 postmenopausal women from the National Institute of Rehabilitation. Demographic data were collected through a structured questionnaire. Bone mineral density was assessed using dual X-ray absorptiometry. Individuals were classified as normal, osteopenia, osteoporosis, and fracture, according to World Health Organization criteria. Genotyping was performed using predesigned TaqMan Probes. Linear regression analysis was used to investigate association. RESULTS: All of the analyzed SNPs showed association with at least one of the phenotypes of the study groups. In addition, we observed a region with linkage disequilibrium within the ESR1 gene in all groups. CONCLUSION: This study shows that an association of the SNPs can exist with osteopenia, osteoporosis, or fragility fracture. Our results agree with data published elsewhere, supporting the potential of these loci for the identification of the population at risk. However, additional studies are required to determine the extent of this association for other geographic regions of Mexico.

Limited performance of MALDI-TOF for identification of fish Aeromonas isolates at species level.

The aim of this study was to evaluate the usefulness of the MALDI-TOF MS to identify 151 isolates of Aeromonas obtained mostly from diseased fish. MALDI-TOF MS correctly identified all isolates to the genus level but important differences in the percentage of isolates correctly identified depending on the species were observed. Considering exclusively the first identification option, Aeromonas bestiarum, Aeromonas hydrophila, Aeromonas salmonicida, Aeromonas veronii and Aeromonas sobria were the best identified with results >95%. However, considering the first and second identification options, the only species that showed values >90% was A. hydrophila. Overall, when the database was supplemented with 14 new spectra, the number of accurate identifications increased (41% vs. 55%) and the number of inconclusive identifications decreased (45% vs. 29%), but great differences in the success of species-level identifications were found. Species-distinctive mass peaks were identified only for A. hydrophila and A. bestiarum (5003 and 7360 m/z in 95.5% and 94.1% of their isolates, respectively). This work demonstrates the utility of MALDI-TOF MS for Aeromonas identification to the genus level, but there is no consistency for the accurate identification of some of the most prevalent species implicated in fish disease.

Correction to: Distal Doppler-guided transanal hemorrhoidal dearterialization with mucopexy versus conventional hemorrhoidectomy for grade III and IV hemorrhoids: postoperative morbidity and long-term outcomes.

The article "Distal Doppler-guided transanal hemorrhoidal dearterialization with mucopexy versus conventional hemorrhoidectomy for grade III and IV hemorrhoids: postoperative morbidity and long-term outcomes", written by L. Trenti, S. Biondo, A. Galvez, A. Bravo, J. Cabrera, E. Kreisler, was originally published electronically on the publisher's internet portal (currently SpringerLink) on [27 April 2017] without open access. With the author(s)' decision to opt for Open Choice the copyright of the article changed on 7 June, 2018 to

Vapour-liquid interfacial properties of square-well chains from density functional theory and Monte Carlo simulation.

The statistical associating fluid theory for attractive potentials of variable range (SAFT-VR) density functional theory (DFT) developed by [Gloor et al., J. Chem. Phys., 2004, 121, 12740-12759] is used to predict the interfacial behaviour of molecules modelled as fully-flexible square-well chains formed from tangentially-bonded monomers of diameter σ and potential range λ = 1.5σ. Four different model systems, comprising 4, 8, 12, and 16 monomers per molecule, are considered. In addition to that, we also compute a number of interfacial properties of molecular chains from direct simulation of the vapour-liquid interface. The simulations are performed in the canonical ensemble, and the vapour-liquid interfacial tension is evaluated using the wandering interface (WIM) method, a technique based on the thermodynamic definition of surface tension. Apart from surface tension, we also obtain density profiles, coexistence densities, vapour pressures, and critical temperature and density, paying particular attention to the effect of the chain length on these properties. According to our results, the main effect of increasing the chain length (at fixed temperature) is to sharpen the vapour-liquid interface and to increase the width of the biphasic coexistence region. As a result, the interfacial thickness decreases and the surface tension increases as the molecular chains get longer. The interfacial thickness and surface tension appear to exhibit an asymptotic limiting behaviour for long chains. A similar behaviour is also observed for the coexistence densities and critical properties. Agreement between theory and simulation results indicates that SAFT-VR DFT is only able to predict qualitatively the interfacial properties of the model. Our results are also compared with simulation data taken from the literature, including the vapour-liquid coexistence densities, vapour pressures, and surface tension.

Distal Doppler-guided transanal hemorrhoidal dearterialization with mucopexy versus conventional hemorrhoidectomy for grade III and IV hemorrhoids: postoperative morbidity and long-term outcomes.

BACKGROUND: Distal Doppler-guided transanal hemorrhoidal dearterialization with mucopexy (Doppler-guided THD) seems to be associated with better short-term outcomes than conventional hemorrhoidectomy, but there are little data about long-term recurrence. The aim of this study was to compare Doppler-guided THD for grade III-IV hemorrhoids with conventional hemorrhoidectomy with regard to long-term postoperative morbidity and recurrence. METHODS: This was a single-center longitudinal and comparative study of a cohort of patients who underwent either distal Doppler-guided THD with low ligation of the hemorrhoidal artery and mucopexy or conventional excisional hemorrhoidectomy (Milligan and Morgan or Ferguson) for grade III and IV hemorrhoids. Short- and long-term postoperative morbidity was recorded. Severity of hemorrhoid symptoms (bleeding, prolapse, manual reduction, discomfort or pain and impact on quality of life) and fecal continence status (Vaizey score) were evaluated before surgery and at minimum of 1 year after surgery. RESULTS: Eighty-three patients were included in the study. Forty-nine patients (59%) underwent Doppler-guided THD, and 34 (41%) patients underwent conventional hemorrhoidectomy. The 30-day postoperative surgical morbidity was 26.5% in the Doppler-guided THD group and 8.82% in the conventional hemorrhoidectomy group (p = 0.085). No significant differences between the groups were observed in terms of persistence of bleeding, prolapse, need for manual reduction in prolapse and pain. One (2%) patient in the THD group and 2 (5.4%) patients in the conventional hemorrhoidectomy group needed further surgical procedures. Minor fecal incontinence occurred only after conventional hemorrhoidectomy in 2 (5.4%) patients. CONCLUSIONS: Our results showed that Doppler-guided THD is not inferior to conventional excisional hemorrhoidectomy for advanced hemorrhoidal disease in terms of postoperative complications and long-term recurrence of symptoms.

A systematic review and meta-analysis of the treatment of anal fissure.

BACKGROUND: Anal fissure has a very large number of treatment options. The choice is difficult. In an effort to assist in that, choice presented here is a systematic review and meta-analysis of all published treatments for anal fissure that have been studied in randomized controlled trials. METHODS: Randomized trials were sought in the Cochrane Controlled Trials Register, Medline, EMBASE and the trials registry sites clinicaltrials.gov and who/int/ictrp/search/en. Abstracts were screened, full-text studies chosen, and finally eligible studies selected and abstracted. The review was then divided into those studies that compared two or more surgical procedures and those that had at least one arm that was non-surgical. Studies were further categorized by the specific interventions and comparisons. The outcome assessed was treatment failure. Negative effects of treatment assessed were headache and anal incontinence. Risk of bias was assessed for each study, and the strength of the evidence of each comparison was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS: One hundred and forty-eight eligible trials were found and assessed, 31 in the surgical group and 117 in the non-surgical group. There were 14 different operations described in the surgical group and 29 different non-surgical treatments in the non-surgical group along with partial lateral internal sphincterotomy (LIS). There were 61 different comparisons. Of these, 47 were reported in 2 or fewer studies, usually with quite small patient samples. The largest single comparison was glyceryl trinitrate (GTN) versus control with 19 studies. GTN was more effective than control in sustained cure (OR 0.68; 95% CI 0.63-0.77), but the quality of evidence was very poor because of severe heterogeneity, and risk of bias due to inadequate clinical follow-up. The only comparison to have a GRADE quality of evidence of high was a subgroup analysis of LIS versus any medical therapy (OR 0.12; CI 0.07-0.21). Most of the other studies were downgraded in GRADE due to imprecision. CONCLUSIONS: LIS is superior to non-surgical therapies in achieving sustained cure of fissure. Calcium channel blockers were more effective than GTN and with less risk of headache, but with only a low quality of evidence. Anal incontinence, once thought to be a frequent risk with LIS, was found in various subgroups in this review to have a risk between 3.4 and 4.4%. Among the surgical studies, manual anal stretch performed worse than LIS in the treatment of chronic anal fissure in adults. For those patients requiring surgery for anal fissure, open LIS and closed LIS appear to be equally efficacious, with a moderate GRADE quality of evidence. All other GRADE evaluations of procedures were low to very low due mostly to imprecision.

Uterosome-like vesicles prompt human sperm fertilizing capability.

STUDY QUESTION: Does the rapid transit through the uterine environment modulate the sperm physiological state? SUMMARY ANSWER: The uterosome-like vesicles (ULVs) secreted by endometrial epithelial cells (EECs) in vitro are able to fuse with human spermatozoa, prompting their fertilizing capacity. WHAT IS KNOWN ALREADY: Early studies suggest that sperm capacitation begins in the uterus and ends in the oviduct, and that a synergistic effect of both female organs may accelerate this process. Although it has been reported that co-incubation of human spermatozoa with endometrial cell-conditioned medium (CM) stimulates sperm capacitation, the mechanism mediating this communication is unknown. STUDY DESIGN, SIZE, DURATION: Human ULVs secreted by EECs were characterized and their effect on human sperm physiology was analysed. Spermatozoa were incubated with EEC-derived CM or ULV, after which sperm capacitation was evaluated at different time points. In addition, the interaction of spermatozoa with ULV was analysed. PARTICIPANTS/MATERIALS, SETTING, METHODS: ULVs were isolated by ultracentrifugation and identified using electron microscopy and Western blotting to assess the presence of specific protein markers. Following seminal plasma removal, human spermatozoa were incubated CM or ULV, after which sperm capacitation was evaluated as the ability of the sperm to undergo the induced acrosome reaction and the level of protein tyrosine phosphorylation (PY) determined by Western blot and immunocytochemistry. The interaction of spermatozoa with labelled ULV was analysed by fluorescence microscopy. In all cases, at least three biological replicates from different sperm donors were performed for each set of experiments. Significant differences between mean values were determined by one-way ANOVA followed by Tukey's post hoc test. Differences between treatments were considered statistically significant at P ≤ 0.05. MAIN RESULTS AND THE ROLE OF CHANCE: The level of capacitated spermatozoa and those recruited by chemotaxis increased 3- to 4-fold when spermatozoa were incubated in the presence of CM for 4 h. Even a 15 min incubation of spermatozoa with CM was also enough to increase the level of capacitated cells 3- to 4-fold (P < 0.05). Furthermore, a short co-incubation of spermatozoa with ULV stimulates sperm capacitation, as determined by the increase in the level of induced acrosome reaction and the induction of PY. In addition, after the co-incubation of spermatozoa with fluorescent labelled ULV, the sperm cells acquired the fluorescent staining which indicates that ULV might be transferred to the sperm surface by a fusion mechanism. LIMITATIONS, REASONS FOR CAUTION: This is an in vitro study performed with human biological material, spermatozoa and endometrial derived cells; the latter being a cell line originally isolated from a uterine adenocarcinoma. WIDER IMPLICATIONS OF THE FINDINGS: The capability of spermatozoa to briefly interact with ULVs supports the hypothesis that any step of sperm transport may have physiological consequences, despite the interaction lasting for only a limited period of time. This way of communication of spermatozoa with cell products of uterine origin opens new frontiers of investigation (e.g. the signalling molecules involved), shedding light on the sperm processes that prepare the male gamete for fertilization, which might have implications for human infertility treatment. LARGE SCALE DATA: N/A. STUDY FUNDING AND COMPETING INTERESTS: The project was financially supported by SECyT-UNC. The authors declare no conflict of interest.

On interfacial properties of tetrahydrofuran: Atomistic and coarse-grained models from molecular dynamics simulation.

We have determined the interfacial properties of tetrahydrofuran (THF) from direct simulation of the vapor-liquid interface. The molecules are modeled using six different molecular models, three of them based on the united-atom approach and the other three based on a coarse-grained (CG) approach. In the first case, THF is modeled using the transferable parameters potential functions approach proposed by Chandrasekhar and Jorgensen [J. Chem. Phys. 77, 5073 (1982)] and a new parametrization of the TraPPE force fields for cyclic alkanes and ethers [S. J. Keasler et al., J. Phys. Chem. B 115, 11234 (2012)]. In both cases, dispersive and coulombic intermolecular interactions are explicitly taken into account. In the second case, THF is modeled as a single sphere, a diatomic molecule, and a ring formed from three Mie monomers according to the SAFT-γ Mie top-down approach [V. Papaioannou et al., J. Chem. Phys. 140, 054107 (2014)]. Simulations were performed in the molecular dynamics canonical ensemble and the vapor-liquid surface tension is evaluated from the normal and tangential components of the pressure tensor along the simulation box. In addition to the surface tension, we have also obtained density profiles, coexistence densities, critical temperature, density, and pressure, and interfacial thickness as functions of temperature, paying special attention to the comparison between the estimations obtained from different models and literature experimental data. The simulation results obtained from the three CG models as described by the SAFT-γ Mie approach are able to predict accurately the vapor-liquid phase envelope of THF, in excellent agreement with estimations obtained from TraPPE model and experimental data in the whole range of coexistence. However, Chandrasekhar and Jorgensen model presents significant deviations from experimental results. We also compare the predictions for surface tension as obtained from simulation results for all the models with experimental data. The three CG models predict reasonably well (but only qualitatively) the surface tension of THF, as a function of temperature, from the triple point to the critical temperature. On the other hand, only the TraPPE united-atoms models are able to predict accurately the experimental surface tension of the system in the whole temperature range.

Liquid-liquid interfacial properties of a symmetrical Lennard-Jones binary mixture.

We determine the interfacial properties of a symmetrical binary mixture of equal-sized spherical Lennard-Jones molecules, σ11 = σ22, with the same dispersive energy between like species, ϵ11 = ϵ22, but different dispersive energies between unlike species low enough to induce phase separation. We use the extensions of the improved version of the inhomogeneous long-range corrections of Janec̆ek [J. Phys. Chem. B 110, 6264 (2006)], presented recently by MacDowell and Blas [J. Chem. Phys. 131, 074705 (2009)] and Martínez-Ruiz et al. [J. Chem. Phys. 141, 184701 (2014)], to deal with the interaction energy and microscopic components of the pressure tensor. We perform Monte Carlo simulations in the canonical ensemble to obtain the interfacial properties of the symmetrical mixture with different cut-off distances rc and in combination with the inhomogeneous long-range corrections. The pressure tensor is obtained using the mechanical (virial) and thermodynamic route. The liquid-liquid interfacial tension is also evaluated using three different procedures, the Irving-Kirkwood method, the difference between the macroscopic components of the pressure tensor, and the test-area methodology. This allows to check the validity of the recent extensions presented to deal with the contributions due to long-range corrections for intermolecular energy and pressure tensor in the case of binary mixtures that exhibit liquid-liquid immiscibility. In addition to the pressure tensor and the surface tension, we also obtain density profiles and coexistence densities and compositions as functions of pressure, at a given temperature. According to our results, the main effect of increasing the cut-off distance rc is to sharpen the liquid-liquid interface and to increase the width of the biphasic coexistence region. Particularly interesting is the presence of a relative minimum in the total density profiles of the symmetrical mixture. This minimum is related with a desorption of the molecules at the interface, a direct consequence of a combination of the weak dispersive interactions between unlike species of the symmetrical binary mixture, and the presence of an interfacial region separating the two immiscible liquid phases in coexistence.

Effect of mitochondrial calcium uniporter blocking on human spermatozoa.

Calcium (Ca(2+) ) regulates a number of essential processes in spermatozoa. Ca(2+) is taken up by mitochondria via the mitochondrial calcium uniporter (mCU). Oxygen-bridged dinuclear ruthenium amine complex (Ru360) has been used to study mCU because it is a potent and specific inhibitor of this channel. In bovine spermatozoa, it has been demonstrated that mitochondrial calcium uptake inhibition adversely affects the capacitation process. It has been demonstrated in human spermatozoa that mCU blocking, through Ru360, prevents apoptosis; however, the contribution of the mCU to normal human sperm function has not been studied. Therefore, the aim of this study was to evaluate the effect of mCU blocking on human sperm function. Spermatozoa obtained from apparently healthy donors were incubated with 5 and 10 µm Ru360 for 4 h at 37 °C. Viability was assessed using propidium iodide staining; motility was determined by computer-aided sperm analysis, adenosine triphosphate (ATP) levels using a luminescence-based method, mitochondrial membrane potential (ΔΨm) using JC-1 staining and reactive oxygen species (ROS) production using dihydroethidium dye. Our results show that mCU blocking significantly reduced total sperm motility and ATP levels without affecting sperm viability, ΔΨm and ROS production. In conclusion, mCU contributes to the maintenance of sperm motility and ATP levels in human spermatozoa.

Development of an Epstein-Barr virus-associated lymphoproliferative disorder in a patient treated with azacitidine for chronic myelomonocytic leukaemia.

Some chemotherapeutic agents can cause iatrogenic lymphoproliferative disorders. In analogy to what has been observed with other nucleoside analogues such as cladribine and fludarabine, we document the first case of an Epstein-Barr virus-positive, iatrogenic immunodeficiency-associated, lymphoproliferative disease, formally resembling polymorphic post-transplant lymphoproliferative disease in a patient treated with azacitidine (Vidaza) for chronic myelomonocytic leukaemia (CMML). A 78-year-old female patient was diagnosed with CMML in January 2012, and treatment with azacitidine was initiated, which lasted for five cycles from February until June 2012. The patient was hospitalized in June 2012 under the suspicion of pneumonia. Transformation of the CMML was suspected at that time too. During hospitalization, a generalized enlargement of the lymph nodes and the spleen was noticed. The patient rapidly deteriorated and finally died of respiratory insufficiency. At autopsy, an Epstein-Barr virus-associated lymphoproliferative disorder, resembling polymorphic post-transplant lymphoproliferative disease with involvement of the lymph nodes, the spleen and the lung and causing necrotizing pneumonia, was diagnosed. Diagnostic criteria for diffuse large B-cell lymphoma or infectious mononucleosis-like lymphoproliferative disease were not met. This is the first documented case of an azacitidine-associated lymphoproliferative disease, raising awareness for possible not yet known side effects of this drug, which should be kept in mind by oncologists and pathologists.

Effect of molecular flexibility of Lennard-Jones chains on vapor-liquid interfacial properties.

We have determined the interfacial properties of short fully flexible chains formed from tangentially bonded Lennard-Jones monomeric units from direct simulation of the vapor-liquid interface. The results obtained are compared with those corresponding to rigid-linear chains formed from the same chain length, previously determined in the literature [F. J. Blas, A. I. M.-V. Bravo, J. M. Míguez, M. M. Piñeiro, and L. G. MacDowell, J. Chem. Phys. 137, 084706 (2012)]. The full long-range tails of the potential are accounted for by means of an improved version of the inhomogeneous long-range corrections of Janecek [J. Phys. Chem. B 129, 6264 (2006)] proposed recently by MacDowell and Blas [J. Chem. Phys. 131, 074705 (2008)] valid for spherical as well as for rigid and flexible molecular systems. Three different model systems comprising of 3, 5, and 6 monomers per molecule are considered. The simulations are performed in the canonical ensemble, and the vapor-liquid interfacial tension is evaluated using the test-area method. In addition to the surface tension, we also obtained density profiles, coexistence densities, critical temperature and density, and interfacial thickness as functions of temperature, paying particular attention to the effect of the chain length and rigidity on these properties. According to our results, the main effect of increasing the chain length (at fixed temperature) is to sharpen the vapor-liquid interface and to increase the width of the biphasic coexistence region. As a result, the interfacial thickness decreases and the surface tension increases as the molecular chains get longer. Comparison between predictions for fully flexible and rigid-linear chains, formed by the same number of monomeric units, indicates that the main effects of increasing the flexibility, i.e., passing from a rigid-linear to a fully flexible chain, are: (a) to decrease the difference between the liquid and vapor densities; (b) to decrease the critical temperature and to increase the critical density; (c) to smooth the density profiles along the interfacial region; (d) to increase the interfacial thickness; and (e) to decrease the vapor-liquid surface tension.

Effect of dispersive long-range corrections to the pressure tensor: the vapour-liquid interfacial properties of the Lennard-Jones system revisited.

We propose an extension of the improved version of the inhomogeneous long-range corrections of Janecek [J. Phys. Chem. B 110, 6264-6269 (2006)], presented recently by MacDowell and Blas [J. Chem. Phys. 131, 074705 (2009)] to account for the intermolecular potential energy of spherical, rigid, and flexible molecular systems, to deal with the contributions to the microscopic components of the pressure tensor due to the dispersive long-range corrections. We have performed Monte Carlo simulations in the canonical ensemble to obtain the interfacial properties of spherical Lennard-Jones molecules with different cutoff distances, r(c) = 2.5, 3, 4, and 5σ. In addition, we have also considered cutoff distances r(c) = 2.5 and 3σ in combination with the inhomogeneous long-range corrections proposed in this work. The normal and tangential microscopic components of the pressure tensor are obtained using the mechanical or virial route in combination with the recipe of Irving and Kirkwood, while the macroscopic components are calculated using the Volume Perturbation thermodynamic route proposed by de Miguel and Jackson [J. Chem. Phys. 125, 164109 (2006)]. The vapour-liquid interfacial tension is evaluated using three different procedures, the Irving-Kirkwood method, the difference between the macroscopic components of the pressure tensor, and the Test-Area methodology. In addition to the pressure tensor and the surface tension, we also obtain density profiles, coexistence densities, vapour pressure, critical temperature and density, and interfacial thickness as functions of temperature, paying particular attention to the effect of the cutoff distance and the long-range corrections on these properties. According to our results, the main effect of increasing the cutoff distance (at fixed temperature) is to sharpen the vapour-liquid interface, to decrease the vapour pressure, and to increase the width of the biphasic coexistence region. As a result, the interfacial thickness decreases, the width of the tangential microscopic component of the pressure tensor profile increases, and the surface tension increases as the cutoff distance is larger. We have also checked the effect of the impulsive contribution to the pressure due to the discontinuity of the intermolecular interaction potential when it is cut. If this contribution is not accounted for in the calculation of the microscopic components of the pressure tensor, incorrect values of both components as well as a wrong structure along the vapour-liquid interface are obtained.

[Antihypertensive prescription in type 2 diabetes patients in Andalusia and SEH-LELHA 2022 guidelines: An economic cost evaluation]. / Prescripción de antihipertensivos en personas con diabetes tipo 2 en Andalucía y recomendaciones SEH-LELHA 2022: evaluación del coste y uso.

OBJECTIVE: This study aims to analyze the prescription of antihypertensive drugs in patients with type 2 diabetes (T2D) in Andalusia, comparing it with the SEH-LELHA 2022 guidelines, and to assess the direct cost of these treatments. MATERIALS AND METHODS: A multicentric, cross-sectional, and descriptive study was conducted with 385 T2D patients. Participants were randomly selected from the patient lists of 120 primary care physicians from Andalusia. Inclusion criteria included a diagnosis of T2D and complete clinical records for the year 2022. Demographic data and drug prescription information were collected, with the average cost per patient being calculated. RESULTS: The mean age of the subjects was 70.72 years, with 53.51% being male. A total of 70.9% of the patients were taking antihypertensive drugs, the most common being ACE inhibitors/ARBs (70.9%), diuretics (70.1%), beta-blockers (40.0%), and calcium channel blockers (20.0%). Each patient took an average of 2.46±1.06 antihypertendsive, and fixed association of 2 or more antihypertensive drugs were used by 40.9% of the studied patients. The annual cost per patient was 141.45€/year. CONCLUSIONS: The study reveals strong adherence to the SEH-LELHA 2022 guidelines among physicians in Andalusia regarding the of antihypertensives for T2D patients, with a significant preference for Renin-Angiotensin System blockers, diuretics, and beta-blockers. However, a notable deviation in prescription practices was observed with the frequent choice of doxazosin over spironolactone, despite the latter being the recommended option for resistant hypertension. Although the overall expenditure on antihypertensives is moderate, their cost-effectiveness is enhanced by the efficacy of these treatments in preventing cardiovascular complications.