Evaluation of the Thermal, Chemical, Mechanical, and Microbial Stability of New Nanohybrids Based on Carboxymethyl-Scleroglucan and Silica Nanoparticles for EOR Applications.

Scleroglucan (SG) is resistant to harsh reservoir conditions such as high temperature, high shear stresses, and the presence of chemical substances. However, it is susceptible to biological degradation because bacteria use SG as a source of energy and carbon. All degradation effects lead to viscosity loss of the SG solutions, affecting their performance as an enhanced oil recovery (EOR) polymer. Recent studies have shown that nanoparticles (NPs) can mitigate these degradative effects. For this reason, the EOR performance of two new nanohybrids (NH-A and NH-B) based on carboxymethyl-scleroglucan and amino-functionalized silica nanoparticles was studied. The susceptibility of these products to chemical, mechanical, and thermal degradation was evaluated following standard procedures (API RP 63), and the microbial degradation was assessed under reservoir-relevant conditions (1311 ppm and 100 °C) using a bottle test system. The results showed that the chemical reactions for the nanohybrids obtained modified the SG triple helix configuration, impacting its viscosifying power. However, the nanohybrid solutions retained their viscosity during thermal, mechanical, and chemical degradation experiments due to the formation of a tridimensional network between the nanoparticles (NPs) and the SG. Also, NH-A and NH-B solutions exhibited bacterial control because of steric hindrances caused by nanoparticle modifications to SG. This prevents extracellular glucanases from recognizing the site of catalysis, limiting free glucose availability and generating cell death due to substrate depletion. This study provides insights into the performance of these nanohybrids and promotes their application in reservoirs with harsh conditions.

Dietary metabarcoding reveals the simplification of bird-pest interaction networks across a gradient of agricultural cover.

Agriculture is vital for supporting human populations, but its intensification often leads to landscape homogenization and a decline in non-provisioning ecosystem services. Ecological intensification and multifunctional landscapes are suggested as nature-based alternatives to intensive agriculture, using ecological processes like natural pest regulation to maximize food production. Birds are recognized for their role in increasing crop yields by consuming invertebrate pests in several agroecosystems. However, the understanding of how bird species, their traits and agricultural land cover influence the structure of bird-pest interactions remains limited. We sampled bird-pest interactions monthly for 1 year, at four sites within a multifunctional landscape, following a gradient of increasing agricultural land cover. We analysed 2583 droppings of 55 bird species with DNA metabarcoding and detected 225 pest species in 1139 samples of 42 bird species. As expected, bird-pest interactions were highly variable across bird species. Dietary pest richness was lower in the fully agricultural site, while predation frequency remained consistent across the agricultural land cover gradient. Network analysis revealed a reduction in the complexity of bird-pest interactions as agricultural coverage increased. Bird species abundance affected the bird's contribution to the network structure more than any of the bird traits analysed (weight, phenology, invertebrate frequency in diet and foraging strata), with more common birds being more important to network structure. Overall, our results show that increasing agricultural land cover increases the homogenization of bird-pest interactions. This shows the importance of maintaining natural patches within agricultural landscapes for biodiversity conservation and enhanced biocontrol.

A agricultura é essencial para suportar a população humana, mas a sua intensificação geralmente leva à homogeneização da paisagem e à redução dos serviços do ecossistema que não sejam de provisão. A intensificação ecológica e paisagens multifuncionais são sugeridas como alternativas naturais à agricultura intensiva, utilizando processos ecológicos como a regulação natural de pragas para maximizar a produção de alimentos. As aves são conhecidas pelo seu papel no aumento da produtividade das culturas por consumirem pragas em diversos agroecossistemas. Contudo, o conhecimento de como as espécies de aves, as suas características e a cobertura agrícola influenciam as interações entre aves e pragas são limitados. Nós amostrámos estas interações mensalmente durante um ano, em quatro locais, numa paisagem multifuncional, ao longo um gradiente de aumento da cobertura agrícola. Analisamos 2583 dejetos de 55 espécies de aves com DNA metabarcoding e detetamos 225 espécies praga em 1139 amostras de 42 espécies de aves. Como esperado, as interações entre aves e pragas foram muito distintas entre as várias espécies de aves. A riqueza de pragas na dieta foi menor no local completamente dominado por área agrícola, enquanto a frequência de predação de pragas foi constante ao longo do gradiente de cobertura agrícola. A análise de redes demonstrou uma redução na complexidade das interações entre aves e pragas à medida que a cobertura agrícola aumenta. A abundância das espécies de aves influenciou mais a contribuição das aves para a estrutura da rede do que qualquer uma das características analisadas (peso, fenologia, frequência de invertebrados na dieta e estrato de alimentação), sendo as aves mais comuns as mais importantes na estrutura da rede. De forma geral, os nossos resultados indicam que o aumento da cobertura agrícola aumenta a homogeneização das interações entre aves e pragas. Isto demonstra a importância de preservar áreas naturais em paisagem agrícolas para a conservação de biodiversidade e melhor controlo biológico.

Synthesis and Characterization of New Nanohybrids Based on Carboxymethyl Scleroglucan and Silica Nanoparticles.

In this study, two new nanohybrids (NH-A and NH-B) were synthesized through carbodiimide-assisted coupling. The reaction was performed between carboxymethyl-scleroglucans (CMS-A and CMS-B) with different degrees of substitution and commercial amino-functionalized silica nanoparticles using 4-(dimethylamino)-pyridine (DMAP) and N,N'-dicyclohexylcarbodiimide (DCC) as catalysts. The morphology and properties of the nanohybrids were investigated by using transmission (TEM) and scanning electron microscopy (SEM), electron-dispersive scanning (EDS), attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FT-IR), X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (XRD), inductively coupled plasma atomic emission spectroscopy (ICP-OES), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic light scattering (DLS). The nanohybrids exhibited differences in structure due to the incorporation of polyhedral oligomeric silsesquioxane (POSS) materials. The results reveal that hybrid nanomaterials exhibit similar thermal properties but differ in morphology, chemical structure, and crystallinity properties. Finally, a viscosity study was performed on the newly obtained nanohybrid materials; viscosities of nanohybrids increased significantly in comparison to the carboxymethyl-scleroglucans, with a viscosity difference of 7.2% for NH-A and up to 32.6% for NH-B.

Photoimmuno-antimicrobial therapy for Staphylococcus aureus implant infection.

INTRODUCTION: Implant infections caused by Staphylococcus aureus are responsible for high mortality and morbidity worldwide. Treatment of these infections can be difficult especially when bacterial biofilms are involved. In this study we investigate the potential of infrared photoimmunotherapy to eradicate staphylococcal infection in a mouse model. METHODS: A monoclonal antibody that targets Wall Teichoic Acid surface components of both S. aureus and its biofilm (4497-IgG1) was conjugated to a photosensitizer (IRDye700DX) and used as photoimmunotherapy in vitro and in vivo in mice with a subcutaneous implant pre-colonized with biofilm of Staphylococcus aureus. A dose of 400 µg and 200 µg of antibody-photosensitizer conjugate 4497-IgG-IRDye700DXwas administered intravenously to two groups of 5 mice. In addition, multiple control groups (vancomycin treated, unconjugated IRDye700DX and IRDye700DX conjugated to a non-specific antibody) were used to verify anti-microbial effects. RESULTS: In vitro results of 4497-IgG-IRDye700DX on pre-colonized (biofilm) implants showed significant (p<0.01) colony-forming units (CFU) reduction at a concentration of 5 µg of the antibody-photosensitizer conjugate. In vivo, treatment with 4497-IgG-IRDye700DX showed no significant CFU reduction at the implant infection. However, tissue around the implant did show a significant CFU reduction with 400 µg 4497-IgG-IRDye700DX compared to control groups (p = 0.037). CONCLUSION: This study demonstrated the antimicrobial potential of photoimmunotherapy for selectively eliminating S. aureus in vivo. However, using a solid implant instead of a catheter could result in an increased bactericidal effect of 4497-IgG-IRDye700DX and administration locally around an implant (per operative) could become valuable applications in patients that are difficult to treat with conventional methods. We conclude that photoimmunotherapy could be a potential additional therapy in the treatment of implant related infections, but requires further improvement.

Flow Behavior through Porous Media and Displacement Performance of a SILICA/PAM Nanohybrid: Experimental and Numerical Simulation Study.

Nanoparticles (NPs) have been proposed as additives to improve the rheological properties of polymer solutions and reduce mechanical degradation. This study presents the results of the retention experiment and the numerical simulation of the displacement efficiency of a SiO2/hydrolyzed polyacrylamide (HPAM) nanohybrid (CSNH-AC). The CSNH-AC was obtained from SiO2 NPs (synthesized by the Stöber method) chemically modified with HPAM chains. Attenuated total reflection-Fourier transform infrared spectroscopy, field emission gun-scanning electron microscopy, X-ray diffraction, and thermogravimetric analysis were used to characterize the nanohybrid. The injectivity and dynamic retention tests were performed at 56 °C in a sandstone core with a porosity of ∼26% and a permeability of 117 and 287 mD. A history matching of the dynamic retention test was performed to determine the maximum and residual adsorption, IPV, and residual resistance factor (RRF). A laboratory-scale model was used to evaluate the displacement efficiency of CSNH-AC and HPAM through numerical simulation. According to the results, the nanohybrid exhibits better rheological behavior than the HPAM solution at a lower concentration. The nanopolymer sol adsorption and IPV (29,7 µg/grock, 14,5) are greater than those of the HPAM solution (9,2 µg/grock, 10), which was attributed to the difference between the rock permeabilities used in the laboratory tests (HPAM: 287 mD and CSNH-AC: 117 mD). The RF of both samples gradually increases with the increase in shear rate, while the RRF slightly decreases and tends to balance. However, the nanopolymer sol exhibits greater RF and RRF values than that of the polymer solution due to the strong flow resistance of the nanohybrid (higher retention in the porous media). According to the field-scale simulation, the incremental oil production could be 295,505 and 174,465 barrels for the nanopolymer sol and the HPAM solution, respectively (compared to waterflooding). This will represent an incremental recovery factor of 11.3% for the nanopolymer sol and 6.7% for the HPAM solution.

Prolonged hypothermic machine perfusion enables daytime liver transplantation - an IDEAL stage 2 prospective clinical trial.

Background: Liver transplantation is traditionally performed around the clock to minimize organ ischemic time. However, the prospect of prolonging preservation times holds the potential to streamline logistics and transform liver transplantation into a semi-elective procedure, reducing the need for nighttime surgeries. Dual hypothermic oxygenated machine perfusion (DHOPE) of donor livers for 1-2 h mitigates ischemia-reperfusion injury and improves transplant outcomes. Preclinical studies have shown that DHOPE can safely extend the preservation of donor livers for up to 24 h. Methods: We conducted an IDEAL stage 2 prospective clinical trial comparing prolonged (≥4 h) DHOPE to conventional (1-2 h) DHOPE for brain-dead donor livers, enabling transplantation the following morning. Liver allocation to each group was based on donor hepatectomy end times. The primary safety endpoint was a composite of all serious adverse events (SAE) within 30 days after transplantation. The primary feasibility endpoint was defined as the number of patients assigned and successfully receiving a prolonged DHOPE-perfused liver graft. Trial registration at: WHO International Clinical Trial Registry Platform, number NL8740. Findings: Between November 1, 2020 and July 16, 2022, 24 patients were enrolled. The median preservation time was 14.5 h (interquartile range [IQR], 13.9-15.5) for the prolonged group (n = 12) and 7.9 h (IQR, 7.6-8.6) for the control group (n = 12; p = 0.01). In each group, three patients (25%; 95% CI 3.9-46%, p = 1) experienced a SAE. Markers of ischemia-reperfusion injury and oxidative stress in both perfusate and recipients were consistently low and showed no notable discrepancies between the two groups. All patients assigned to either the prolonged group or control group successfully received a liver graft perfused with either prolonged DHOPE or control DHOPE, respectively. Interpretation: This first-in-human clinical trial demonstrates the safety and feasibility of DHOPE in prolonging the preservation time of donor livers to enable daytime transplantation. The ability to extend the preservation window to up to 20 h using hypothermic oxygenated machine preservation at a 10 °C temperature has the potential to reshape the landscape of liver transplantation. Funding: University Medical Center Groningen, the Netherlands.

Micropropagation of Stevia (Stevia rebaudiana Bert.) in RITA®.

Stevia rebaudiana Bert. is a plant that contains noncaloric sweeteners highly appreciated in the food industry. However, there is a high demand for propagules to establish commercial plantations, and the conventional reproduction types for this species are inefficient. Micropropagation is a technique that allows obtaining a large number of plants and can be used to meet the demand in the field. However, it requires in vitro propagation techniques such as temporary immersion systems (SIT) to increase yield and reduce production costs. This chapter describes an effective protocol for the large-scale micropropagation of S. rebaudiana using a TIS.

Large-Scale Micropropagation of Vanilla (Vanilla planifolia Jacks.) in a Temporary Immersion Bioreactor (TIB).

The cultivation of vanilla (Vanilla planifolia) is of economic interest because vanillin is extracted from the fruits of this species. Vanillin is a natural flavoring highly valued in the food market. However, there is a short supply of propagules available for establishing commercial plantations and good-quality plants with phytosanitary certification. Plant tissue culture represents a viable option to supply large amounts of healthy plants to vanilla producers. In addition, the use of temporary immersion systems will allow commercial scale-up and the establishment of biofactories dedicated to in vitro vanilla propagation. This chapter describes a large-scale micropropagation protocol for vanilla using temporary immersion bioreactors (TIB).

Experimental Investigation of the Viscosity and Stability of Scleroglucan-Based Nanofluids for Enhanced Oil Recovery.

Biopolymers emerge as promising candidates for enhanced oil recovery (EOR) applications due to their molecular structures, which exhibit better stability than polyacrylamides under harsh conditions. Nonetheless, biopolymers are susceptible to oxidation and biological degradation. Biopolymers reinforced with nanoparticles could be a potential solution to the issue. The nanofluids' stability and performance depend on the nanoparticles' properties and the preparation method. The primary objective of this study was to evaluate the effect of the preparation method and the nanoparticle type (SiO2, Al2O3, and TiO2) on the viscosity and stability of the scleroglucan (SG). The thickening effect of the SG solution was improved by adding all NPs due to the formation of three-dimensional structures between the NPs and the SG chains. The stability test showed that the SG + Al2O3 and SG + TiO2 nanofluids are highly unstable, but the SG + SiO2 nanofluids are highly stable (regardless of the preparation method). According to the ANOVA results, the preparation method and standing time influence the nanofluid viscosity with a statistical significance of 95%. On the contrary, the heating temperature and NP type are insignificant. Finally, the nanofluid with the best performance was 1000 ppm of SG + 100 ppm of SiO2_120 NPs prepared by method II.

Carboxymethyl Scleroglucan Synthesized via O-Alkylation Reaction with Different Degrees of Substitution: Rheology and Thermal Stability.

This paper presents the methodology for synthesizing and characterizing two carboxymethyl EOR-grade Scleroglucans (CMS-A and CMS-B). An O-Alkylation reaction was used to insert a hydrophilic group (monochloroacetic acid-MCAA) into the biopolymer's anhydroglucose subunits (AGUs). The effect of the degree of the carboxymethyl substitution on the rheology and thermal stability of the Scleroglucan (SG) was also evaluated. Simultaneous thermal analysis (STA/TGA-DSC), differential scanning calorimetry (DSC), X-ray Diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Scanning Electron Microscopy, and Energy Dispersive Spectroscopy (SEM/EDS) were employed to characterize both CMS products. FTIR analysis revealed characteristic peaks corresponding to the carboxymethyl functional groups, confirming the modification. Also, SEM analysis provided insights into the structural changes in the polysaccharide after the O-Alkylation reaction. TGA results showed that the carboxymethylation of SG lowered its dehydroxylation temperature but increased its thermal stability above 300 °C. The CMS products and SG exhibited a pseudoplastic behavior; however, lower shear viscosities and relaxation times were observed for the CMS products due to the breakage of the SG triple helix for the chemical modification. Despite the viscosity results, the modified Scleroglucans are promising candidates for developing new engineering materials for EOR processes.

Key features of puberty onset and progression can help distinguish self-limited delayed puberty from congenital hypogonadotrophic hypogonadism.

Introduction: Delayed puberty (DP) is a frequent concern for adolescents. The most common underlying aetiology is self-limited DP (SLDP). However, this can be difficult to differentiate from the more severe condition congenital hypogonadotrophic hypogonadism (HH), especially on first presentation of an adolescent patient with DP. This study sought to elucidate phenotypic differences between the two diagnoses, in order to optimise patient management and pubertal development. Methods: This was a study of a UK DP cohort managed 2015-2023, identified through the NIHR clinical research network. Patients were followed longitudinally until adulthood, with a definite diagnosis made: SLDP if they had spontaneously completed puberty by age 18 years; HH if they had not commenced (complete, cHH), or had commenced but not completed puberty (partial, pHH), by this stage. Phenotypic data pertaining to auxology, Tanner staging, biochemistry, bone age and hormonal treatment at presentation and during puberty were retrospectively analysed. Results: 78 patients were included. 52 (66.7%) patients had SLDP and 26 (33.3%) patients had HH, comprising 17 (65.4%) pHH and 9 (34.6%) cHH patients. Probands were predominantly male (90.4%). Male SLDP patients presented with significantly lower height and weight standard deviation scores than HH patients (height p=0.004, weight p=0.021). 15.4% of SLDP compared to 38.5% of HH patients had classical associated features of HH (micropenis, cryptorchidism, anosmia, etc. p=0.023). 73.1% of patients with SLDP and 43.3% with HH had a family history of DP (p=0.007). Mean first recorded luteinizing hormone (LH) and inhibin B were lower in male patients with HH, particularly in cHH patients, but not discriminatory. There were no significant differences identified in blood concentrations of FSH, testosterone or AMH at presentation, or in bone age delay. Discussion: Key clinical markers of auxology, associated signs including micropenis, and serum inhibin B may help distinguish between SLDP and HH in patients presenting with pubertal delay, and can be incorporated into clinical assessment to improve diagnostic accuracy for adolescents. However, the distinction between HH, particularly partial HH, and SLDP remains problematic. Further research into an integrated framework or scoring system would be useful in aiding clinician decision-making and optimization of treatment. .

Chemomechanical Properties and Biocompatibility of Various Premixed Putty-type Bioactive Ceramic Cements.

INTRODUCTION: This study aimed to evaluate the chemomechanical properties and biocompatibility of recently introduced premixed putty-type bioactive ceramic cements (PPBCs). METHODS: Including ProRoot MTA (PMTA) as a control, BC RRM fast-set putty (BCPT), Well-Root PT (WRPT), One-Fil PT (OFPT), and Endocem MTA premixed (ECPM) were compared to evaluate setting time, radiopacity, pH change, and microhardness. Biocompatibility on human dental pulp cells was compared using CCK-8 assay. Mineralization potential was evaluated using alkaline phosphatase activity, Alizarin Red S (ARS) staining, and quantitative real-time polymerase chain reaction with odontogenic gene marker. For data analysis, 1-way analysis of variance and Tukey's post hoc test were used at the significance level of 95%. RESULTS: Among the PPBCs, BCPT presented the longest (552 ± 27) setting time (minutes) and others showed significantly shorter time than PMTA (334 ± 22) (P < .05). WRPT (6.20 ± 0.54) and OFPT (5.82 ± 0.50) showed significantly higher radiopacity values (mmAl) and others showed similar value compared with PMTA (P > .05). All PPBCs showed high alkaline pH from fresh materials and tended to increase according to time periods from 30 minutes to 12 hours. ECPM showed the highest value of microhardness (81.62 ± 5.90), WRPT showed similar, and others showed lower than PMTA (P < .05). All PPBCs showed biocompatibility in CCK-8 assay. All PPBCs showed similar or better value compared with PMTA in ALP and ARS staining, and ALP and DSPP marker expression (P < .05). CONCLUSIONS: The PPBCs showed clinically acceptable chemomechanical properties and favorable mineralization potential.

Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial.

Background: The oncological safety of minimally invasive surgery has been questioned for several abdominal cancers. Concerns also exist regarding the use of minimally invasive distal pancreatectomy (MIDP) in patients with resectable pancreatic cancer as randomised trials are lacking. Methods: In this international randomised non-inferiority trial, we recruited adults with resectable pancreatic cancer from 35 centres in 12 countries. Patients were randomly assigned to either MIDP (laparoscopic or robotic) or open distal pancreatectomy (ODP). Both patients and pathologists were blinded to the assigned approach. Primary endpoint was radical resection (R0, ≥1 mm free margin) in patients who had ultimately undergone resection. Analyses for the primary endpoint were by modified intention-to-treat, excluding patients with missing data on primary endpoint. The pre-defined non-inferiority margin of -7% was compared with the lower limit of the two-sided 90% confidence interval (CI) of absolute difference in the primary endpoint. This trial is registered with the ISRCTN registry (ISRCTN44897265). Findings: Between May 8, 2018 and May 7, 2021, 258 patients were randomly assigned to MIDP (131 patients) or ODP (127 patients). Modified intention-to-treat analysis included 114 patients in the MIDP group and 110 patients in the ODP group. An R0 resection occurred in 83 (73%) patients in the MIDP group and in 76 (69%) patients in the ODP group (difference 3.7%, 90% CI -6.2 to 13.6%; pnon-inferiority = 0.039). Median lymph node yield was comparable (22.0 [16.0-30.0] vs 23.0 [14.0-32.0] nodes, p = 0.86), as was the rate of intraperitoneal recurrence (41% vs 38%, p = 0.45). Median follow-up was 23.5 (interquartile range 17.0-30.0) months. Other postoperative outcomes were comparable, including median time to functional recovery (5 [95% CI 4.5-5.5] vs 5 [95% CI 4.7-5.3] days; p = 0.22) and overall survival (HR 0.99, 95% CI 0.67-1.46, p = 0.94). Serious adverse events were reported in 23 (18%) of 131 patients in the MIDP group vs 28 (22%) of 127 patients in the ODP group. Interpretation: This trial provides evidence on the non-inferiority of MIDP compared to ODP regarding radical resection rates in patients with resectable pancreatic cancer. The present findings support the applicability of minimally invasive surgery in patients with resectable left-sided pancreatic cancer. Funding: Medtronic Covidien AG, Johnson & Johnson Medical Limited, Dutch Gastroenterology Society.

Metformin-associated lactic acidosis reported to the United Kingdom National Poisons Information Service (NPIS) between 2010 and 2019: a ten-year retrospective analysis.

INTRODUCTION: Metformin toxicity following therapeutic use or overdose may result in metabolic acidosis with hyperlactatemia. This study aims to assess the relationship between serum lactate concentration, arterial pH, and ingested dose with severity of poisoning, and to identify if serum lactate concentration is a useful marker of severity in metformin toxicity. METHODS: A retrospective study of telephone enquiries relating to metformin exposures to the National Poisons Information Service between 2010 and 2019 from hospitals in the United Kingdom. RESULTS: Six-hundred and thirty-seven cases were identified; 117 involved metformin only and 520 involved metformin with other drugs. The majority of cases involved acute (87%) and intentional (69%) exposures. There was a statistically significant difference in doses between the Poisoning Severity Scores, as well as between intentional and unintentional or therapeutic error doses (P < 0.0001). The distribution of cases for each Poisoning Severity Score differed between the metformin only and metformin with other drugs cases (P < 0.0001). Lactic acidosis was reported in 232 cases. Serum lactate concentration and arterial pH differed across Poisoning Severity Scores. Arterial pH inversely correlated with ingested dose (r=-0.3, P = 0.003), and serum lactate concentration positively correlated with ingested dose (r = 0.37, P < 0.0001). Serum lactate concentration and arterial pH did not correlate with each other. Twenty-five deaths were recorded, all following intentional overdoses. DISCUSSION: The dataset focuses mostly on acute, intentional overdoses. Increasing ingested metformin dose, a higher serum lactate concentration and worsening arterial pH were all associated with an unfavourable Poisoning Severity Score in patients in both metformin only and metformin with other drugs groups. As serum lactate concentration did not correlate with arterial pH, it represents an independent marker of poisoning severity. CONCLUSIONS: Data from the present study suggest that serum lactate concentration can be used to assess severity of poisoning in patients who have reportedly ingested metformin.

Influencing the Insulin System by Placebo Effects in Patients With Diabetes Type 2 and Healthy Controls: A Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to investigate whether placebo effect induced by pharmacological conditioning with intranasal insulin can affect glucose, insulin, C-peptide, hunger, and memory in patients with diabetes type 2 and healthy controls. METHODS: Placebo effect was induced by pharmacological conditioning. Thirty-two older patients (mean age = 68.3 years) with diabetes type 2 and age- and sex-matched thirty-two healthy older adults (mean age = 67.8 years) were randomly assigned to a conditioned or a control group. On day 1, conditioned group received six administrations of intranasal insulin with a conditioned stimulus (CS; smell of rosewood oil), whereas the control group received a placebo with the CS. On day 2, both groups received a placebo spray with the CS. Glucose, insulin, and C-peptide were repeatedly measured in blood. Hunger and memory were assessed with validated measures. RESULTS: Intranasal insulin stabilized dropping glucose levels in patients ( B = 0.03, SE = 0.02, p = .027) and healthy men ( B = 0.046, SE = 0.02, p = .021), and decreased C-peptide levels in healthy controls ( B = 0.01, SE = 0.001, p = .008). Conditioning also prevented the drop of glucose levels but only in men (both healthy and patients; B = 0.001, SE = 0.0003, p = .024). Conditioning significantly decreased hunger in healthy participants ( B = 0.31, SE = 0.09, p < .001). No effects were found on other measures. CONCLUSIONS: Placebo effect induced by conditioning with intranasal insulin modifies blood glucose levels and decreases hunger in older adults, but its effects depend on health status and sex. Insulin conditioning might be beneficial for groups suffering from intensive hunger but seems not be particularly suitable for blood glucose reduction. TRIAL REGISTRATION: Netherlands Trial Register, NL7783 ( https://www.trialregister.nl/trial/7783 ).

Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/025, September 2022) - Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth.

Aim This revised guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). It aims to improve the prediction, prevention, and management of preterm birth, based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations. Methods The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote). Recommendations Part 1 of this short version of the guideline presents statements and recommendations on the epidemiology, etiology, prediction, and primary and secondary prevention of preterm birth.

Microsatellite-Based Genetic Diversity and Population Structure of Huacaya Alpacas (Vicugna pacos) in Southern Peru.

The alpaca population mostly consists of the Huacaya phenotype and is widely distributed in Southern Peru. This study aimed to estimate the genetic diversity and population structure of two Huacaya alpaca populations (Ajoyani and Quimsachata) using fourteen and twelve microsatellite markers for each population, respectively. A total of 168 alpaca biological samples were outsourced to Peruvian laboratories for DNA extraction and genotyping. For genetic diversity, observed heterozygosity (Ho), expected heterozygosity (He), polymorphism information content (PIC), and fixation indices values were estimated. An admixture analysis was performed for the population structure analysis. Different programs were used for these estimations. In total, 133 (Ajoyani) and 129 (Quimsachata) alleles were found, with a range of 4 to 17 by locus. The mean HO, HE, and PIC per marker for Ajoyani were 0.764 ± 0.112, 0.771 ± 0.1, and 0.736; for Quimsachata, they were 0.783 ± 0.087, 0.773 ± 0.095, and 0.738, respectively. The population structure showed no structure with K = 2. This study provides useful indicators for the creation of appropriate alpaca conservation programs.

Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, September 2022) - Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and on the Management of Preterm Premature Rupture of Membranes.

Aim The revision of this guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of the guideline is to improve the prediction, prevention and management of preterm birth based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations. Methods The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote). Recommendations Part 2 of this short version of the guideline presents statements and recommendations on the tertiary prevention of preterm birth and the management of preterm premature rupture of membranes.

Neurodevelopment in patients with biliary atresia up to toddler age: Outcomes and predictability.

AIM: To assess neurodevelopment in young patients with biliary atresia (BA) and to determine the predictive value of General Movement Assessment (GMA) at infant age for neurodevelopmental impairments at toddler age. METHOD: Infants diagnosed with BA were prospectively included in a longitudinal study. Neurodevelopmental status was previously assessed before Kasai porto-enterostomy (KPE) and one month after KPE using Prechtl's GMA, including motor optimality scores. At 2-3 years, neurodevelopment was assessed using the Bayley Scales of Infant Development, and compared to the Dutch norm population. The predictive value of GMA at infant age for motor skills and cognition at toddler age was determined. RESULTS: Neurodevelopment was assessed in 41 BA patients. At toddler age (n = 38, age 29 ± 5 months, 70 % liver transplantation), 13 (39 %) patients scored below-average on motor skills, and 6 (17 %) patients on cognition. Abnormal GMA after KPE predicted both below-average motor skills and cognitive score at toddler age (sensitivity, 91 % and 80 %; specificity 83 % and 67 %; negative predictive value, 94 % and 94 %; and, positive predictive value, 77 % and 33 %, resp.). INTERPRETATION: One-third of toddlers with BA show impaired motor skills. GMA post-KPE has a high predictive value to identify infants with BA at risk of neurodevelopmental impairments.

Doppler-ultrasound reference values after pediatric liver transplantation: a consecutive cohort study.

OBJECTIVES: Doppler ultrasound (DUS) is the main imaging modality to evaluate vascular complications of pediatric liver transplants (LT). The current study aimed to determine reference values and their change over time. METHODS: A consecutive cohort of pediatric patients undergoing an LT were retrospectively included between 2015 and 2020. Timepoints for standardized DUS were intra-operative and postoperative (day 0), days 1-7, months 1 and 3, and years 1 and 2. DUS measurements of the hepatic artery (HA), portal vein (PV), and hepatic vein(s) (HV) were included if there were no complications during 2 years follow-up. Measurements consisted of: peak systolic velocity (PSV) and resistive index (RI) for the HA, PSV for the PV, and venous pulsatility index (VPI) for the HV. Generalized estimating equations were used to analyze change over time. RESULTS: One hundred twelve pediatric patients with 123 LTs were included (median age 3.3 years, interquartile range 0.7-10.1). Ninety-five HAs, 100 PVs, and 115 HVs without complications were included. Reference values for HA PSV and RI, PV PSV, and HV VPI were obtained for all timepoints (4043 included data points in total) and presented using 5th-95th percentiles and threshold values. All reference values changed significantly over time (p = 0.032 to p < 0.001). CONCLUSIONS: DUS reference values of hepatic vessels in children after LT are presented, reference values change over time with specific vessel-dependent patterns. Timepoint-specific reference values improve the interpretation of DUS values and may help to better weigh their clinical significance. KEY POINTS: • Doppler ultrasound reference values of pediatric liver transplantations are not static but change over time. Applying the correct reference values for the specific timepoint may further improve the interpretation of the measurements. • The pattern of change over time of Doppler ultrasound measurements differs between the hepatic vessel and measurement; knowledge of these patterns may help radiologists to better understand normal postoperative hemodynamic changes.