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Aim: Solitary rectal ulcer syndrome (SRUS) is a benign and poorly understood disorder with complex management. Typical symptoms include straining during defaecation, rectal bleeding, tenesmus, mucoid secretion, anal pain and a sense of incomplete evacuation. Diagnosis is based on characteristic clinical symptoms and endoscopic/histological findings. Several treatments have been reported in the literature with variable ulcer healing rates. This study aimed to evaluate the efficacy of different treatments for SRUS. Materials and methods: A systematic review and network meta‐analysis were performed according to the PRISMA guidelines. Studies in English, French and Spanish languages were included. Papers written in other languages were excluded. Other exclusion criteria were reviews, case reports or clinical series enrolling less than five patients, study duplications, no clinical data of interest and no article available. A systematic literature search was conducted from January 2000 to March 2024 using the following databases: PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus. The biases of the studies were assessed using the Newcastle–Ottawa scale or the Jadad scale when appropriate. Types of treatment and their efficacy for the cure of SRUS were collected and critically assessed. The study's primary outcome was to estimate the rate of patients with ulcer healing. Results: A total of 22 studies with 911 patients (men 361, women 550) diagnosed with SRUS were analysed in the final meta‐analysis. The pooled effect estimates of treatment efficacy revealed that surgery showed the highest ulcer healing rate (70.5%; 95% CI 0.57–0.83). Surgery was superior in the cure of ulcers with respect to medical therapies and biofeedback (OR 0.09 and OR 0.14). Conclusion: Solitary rectal ulcer syndrome is a challenging clinical entity to manage. Proficient results have been reported with the surgical approach, suggesting its positive role in cases refractory to medical and biofeedback therapy. Further studies in homogeneous populations are required to evaluate the efficacy of surgery in this setting. (PROSPERO registration number CRD42022331422). [ABSTRACT FROM AUTHOR]

The new isotope module in HYDRUS‐1D can be used to infer the origin of root water uptake (RWU), a suitable dynamic indicator for agriculture and forest water management. However, evidence shows that the equilibrium fractionation between liquid water and water vapor within the soil is affected not only by soil temperature but also by soil tension. How soil tension affects isotope transport modeling and interpretations of the RWU origin is still unknown. In this study, we evaluated three fractionation scenarios on model performance for a field data set from Langeoog Island: (a) no fractionation (Non_Frac), (b) the soil temperature control on equilibrium fractionation as described by the standard Craig‐Gordon equation (CG_Frac), and (c) CG_Frac plus the soil tension control on equilibrium fractionation (CGT_Frac). The model simulations showed that CGT_Frac led to more depleted isotopic compositions of surface soil water than CG_Frac. The vertical origin of RWU was estimated using the water balance (WB) calculations and the Bayesian mixing model (SIAR). While the former directly used water flow outputs, the latter used as input simulated isotopic compositions (using different fractionation scenarios) of RWU and soil water. Both methods provided similar variation trends with time and depth in different soil layers' contributions to RWU. The contributions of all soil layers interpreted by the CGT_Frac scenario were always between Non_Frac and CG_Frac. The temporal origin of RWU was deduced from particle tracking (PT, releasing one hypothetical particle for individual precipitation event and tracking its movement based on the water balance between particles) and a virtual tracer experiment (VTE, assigning a known isotope composition to individual precipitation event and tracking its movement based on the cumulative isotope flux). Both methods revealed similar variation trends with time in drainage and root zone (RZ) travel times. The interpreted drainage and RZ travel times were generally ranked as Non_Frac > CGT_Frac > CG_Frac. Overall, the factors considered in the standard CG equation dominated isotope fractionation, transport, and interpretations of the RWU origin. Isotope transport‐based methods (SIAR, VTE) were more computationally demanding than water flow‐based methods (WB, PT). Key Points: While factors in the Craig‐Gordon equation dominate evaporation fractionation, soil tension effects deplete isotopic composition of surface soil waterRoot water uptake origin interpreted by considering tension effects is between no fractionation and Craig‐Gordon fractionation scenariosUsing the Bayesian isotope mixing model or the virtual tracer experiment is more demanding than water balance or particle tracking methods [ABSTRACT FROM AUTHOR]

Purpose: Fast and accurate thigh muscle segmentation from MRI is important for quantitative assessment of thigh muscle morphology and composition. A novel deep learning (DL) based thigh muscle and surrounding tissues segmentation model was developed for fully automatic and reproducible cross‐sectional area (CSA) and fat fraction (FF) quantification and tested in patients at 10 years after anterior cruciate ligament reconstructions. Methods: A DL model combining UNet and DenseNet was trained and tested using manually segmented thighs from 16 patients (32 legs). Segmentation accuracy was evaluated using Dice similarity coefficients (DSC) and average symmetric surface distance (ASSD). A UNet model was trained for comparison. These segmentations were used to obtain CSA and FF quantification. Reproducibility of CSA and FF quantification was tested with scan and rescan of six healthy subjects. Results: The proposed UNet and DenseNet had high agreement with manual segmentation (DSC >0.97, ASSD < 0.24) and improved performance compared with UNet. For hamstrings of the operated knee, the automated pipeline had largest absolute difference of 6.01% for CSA and 0.47% for FF as compared to manual segmentation. In reproducibility analysis, the average difference (absolute) in CSA quantification between scan and rescan was better for the automatic method as compared with manual segmentation (2.27% vs. 3.34%), whereas the average difference (absolute) in FF quantification were similar. Conclusions: The proposed method exhibits excellent accuracy and reproducibility in CSA and FF quantification compared with manual segmentation and can be used in large‐scale patient studies. [ABSTRACT FROM AUTHOR]

Objective: To describe how a partnered evaluation of the Whole Health (WH) system of care—comprised of the WH pathway, clinical care, and well‐being programs—produced patient outcomes findings, which informed Veterans Health Administration (VA) policy and system change. Data Sources: Electronic health records (EHR)‐based cohort of 1,368,413 patients and a longitudinal survey of Veterans receiving care at 18 WH pilot medical centers. Study Design: In partnership with VA operations, we focused the evaluation on the impact of WH services utilization on Veterans' (1) use of opioids and (2) care experiences, care engagement, and well‐being. Outcomes were compared between Veterans who did and did not use WH services identified from the EHR. Data Collection: Pharmacy records and WH service data were obtained from the VA EHR, including WH coaching, peer‐led groups, personal health planning, and complementary, integrative health therapies. We surveyed veterans at baseline and 6 months to measure patient‐reported outcomes. Principal Findings: Opioid use decreased 23% (31.5–6.5) to 38% (60.3–14.4) among WH users depending on level of WH use compared to a secular 11% (12.0–9.9) decrease among Veterans using Conventional Care. Compared to Conventional Care users, WH users reported greater improvements in perceptions of care (SMD = 0.138), engagement in health care (SMD = 0.118) and self‐care (SMD = 0.1), life meaning and purpose (SMD = 0.152), pain (SMD = 0.025), and perceived stress (SMD = 0.191). Conclusions: Evidence developed through this partnership yielded key VA policy changes to increase Veteran access to WH services. Findings formed the foundation of a congressionally mandated report in response to the Comprehensive Addiction and Recovery Act, highlighting the value of WH and complementary, integrative health and well‐being programs for Veterans with pain. Findings subsequently informed issuance of an Executive Decision Memo mandating the integration of WH into mental health and primary care across VA, now one lane of modernization for VA. [ABSTRACT FROM AUTHOR]

Background: Brachydactylies are a group of inherited conditions, characterized mainly by the presence of shortened fingers and toes. Based on the patients' phenotypes, brachydactylies have been subdivided into 10 subtypes. In this study, we have identified a family with two members affected by brachydactyly type A2 (BDA2). BDA2 is caused by mutations in three genes: BMPR1B, BMP2 or GDF5. So far only two studies have reported the BDA2 cases caused by mutations in the BMPR1B gene. Methods: We employed next‐generation sequencing to identify mutations in culpable genes. Results and Conclusion: In this paper, we report a case of BDA2 resulting from the presence of a heterozygous c.1456C>T, p.Arg486Trp variant in BMPR1B, which was previously associated with BDA2. The next generation sequencing analysis of the patients' family revealed that the mutation occurred de novo in the proband and was transmitted to his 26‐month‐old son. Although the same variant was confirmed in both patients, their phenotypes were different with more severe manifestation of the disease in the adult. [ABSTRACT FROM AUTHOR]

Introduction: Progressive arthropathy is the main cause of morbidity in patients with severe haemophilia. Diagnostic imaging can detect even subclinical arthropathy and impact prophylactic treatment. However, in most clinical settings the regular joint evaluation and follow‐up are based on clinical evaluation and patient's personal reporting of problems, while diagnostic imaging is not regularly employed. Aim: The aim of our prospective study was to assess how ultrasound (US), clinical examination, patient's subjective assessment and certain laboratory biomarkers correlate with magnetic resonance imaging (MRI) for detection and evaluation of haemophilic arthropathy in order to determine which tool is the most reliable. Methods: The study included 30 patients with severe haemophilia (age range 16‐49 years). MRI (IPSG), US (HEAD‐US), clinical examination (HJHS 2.1) and patient's subjective assessment of elbows, knees and ankles were performed; additionally, blood samples for laboratory analysis were taken (s‐25‐OH vitamin D, s‐ferritin, s‐C‐terminal telopeptide of type I collagen, s‐N‐terminal propeptide of type I procollagen and s‐cartilage oligomeric matrix protein). MRI results were used as a reference standard for joint status. Pearson's r was used to assess correlation of other methods with MRI. Results: The correlation with MRI was the highest for US (r =.92), considerably higher than for clinical evaluation (r =.62) and patient's subjective assessment (r =.66). There was no correlation between the presence or degree of haemophilic arthropathy and any of the laboratory biomarkers. Conclusion: The results of our study warrant the inclusion of US into the regular follow‐up of patients with severe haemophilia, where the equipment and staffing permit. [ABSTRACT FROM AUTHOR]

Purpose: Fully automatic tissue segmentation is an essential step to translate quantitative MRI techniques to clinical setting. The goal of this study was to develop a novel approach based on the generative adversarial networks for fully automatic segmentation of knee cartilage and meniscus. Theory and Methods: Defining proper loss function for semantic segmentation to enforce the learning of multiscale spatial constraints in an end‐to‐end training process is an open problem. In this work, we have used the conditional generative adversarial networks to improve segmentation performance of convolutional neural network, such as UNet alone by overcoming the problems caused by pixel‐wise mapping based objective functions, and to capture cartilage features during the training of the network. Furthermore, the Dice coefficient and cross entropy losses were incorporated to the loss functions to improve the model performance. The model was trained and tested on 176, 3D DESS (double‐echo steady‐state) knee images from the Osteoarthritis Initiative data set. Results: The proposed model provided excellent segmentation performance for cartilages with Dice coefficients ranging from 0.84 in patellar cartilage to 0.91 in lateral tibial cartilage, with an average Dice coefficient of 0.88. For meniscus segmentation, the model achieves 0.89 Dice coefficient for lateral meniscus and 0.87 Dice coefficient for medial meniscus. The results are superior to previously published automatic cartilage and meniscus segmentation methods based on deep learning models such as convolutional neural network. Conclusion: The proposed UNet‐conditional generative adversarial networks based model demonstrated a fully automated segmentation method with high accuracy for knee cartilage and meniscus. [ABSTRACT FROM AUTHOR]

Rationale: The stable isotope compositions of hydrogen and oxygen in water (δ2H and δ18O values) have been widely used to investigate plant water sources, but traditional isotopic measurements of plant waters are expensive and labor intensive. Recent work with direct vapor equilibration (DVE) on laser spectroscopy has shown potential to side step limitations imposed by traditional methods. Here, we evaluate DVE analysis of plants with a focus on spectral contamination introduced by organic compounds. We present 17O‐excess as a way of quantifying organic compound interference in DVE. Methods: We performed isotopic analysis using the δ2H, δ18O and δ17O values of water on an Off‐Axis Integrated Cavity Output Spectroscopy (IWA‐45EP OA‐ICOS) instrument in vapor mode. We used a set of methanol (MeOH) and ethanol (EtOH) solutions to assess errors in isotope measurements. We evaluated how organic compounds affect the 17O‐excess. DVE was used to measure the isotopic signatures in natural plant material from Pinus banksiana, Picea mariana, and Larix laricina, and soil from boreal forest for comparison with solutions. Results: The 17O‐excess was sensitive to the presence of organic compounds in water. 17O‐excess changed proportionally to the concentration of MeOH per volume of water, resulting in positive values, while EtOH solutions resulted in smaller changes in the 17O‐excess. Soil samples did not show any spectral contamination. Plant samples were spectrally contaminated on the narrow‐band and were enriched in 1H and 16O compared with source water. L. laricina was the only species that did not show any evidence of spectral contamination. Xylem samples that were spectrally contaminated had positive 17O‐excess values. Conclusions: 17O‐excess can be a useful tool to identify spectral contamination and improve DVE plant and soil analysis in the laboratory and in situ. The 17O‐excess flagged the presence of MeOH and EtOH. Adding measurement of δ17O values to traditional measurement of δ2H and δ18O values may shed new light on plant water analysis for source mixing dynamics using DVE. [ABSTRACT FROM AUTHOR]

Aim: In the current Anthropocene, many ecosystems are being simultaneously invaded by multiple alien species. Some of these invasive species become more dominant and have greater environmental impacts than others. If two potentially dominant species invade the same area, the combined impact has been reported to be either (a) domination by one species, that is, the competitive dominance of one invader, or (b) invasion meltdown, where the combined impact is much greater, that is, a synergistic effect. We studied the effects of the invasion of two alien plant species that are known to strongly decrease native plant species diversity: the Persian walnut Juglans regiaand goldenrod Solidago canadensis. Location: We examined native vegetation diversity in abandoned fields (in Poland) where neither species had invaded, only one species had invaded, and both species had invaded. Methods: Field survey data were analysed using generalized linear mixed models and ordination techniques. Results: When goldenrod invaded alone, it caused a larger decrease in species richness and cover (74%) than when walnut invaded alone (58%). When walnut and goldenrod co‐occurred in abandoned fields, walnut was dominant and strongly decreased goldenrod density by 87%. However, the combined impact on native species diversity was much lower (15% decrease in native plant diversity) than when either goldenrod or walnut invaded alone. Main conclusions: In contrast to many other studies, our study does not support the occurrence of an invasion meltdown. Instead, our results show that even when one invader dominates, its negative effect on plant diversity can be strongly modified by the presence of another invasive species. [ABSTRACT FROM AUTHOR]

The stable isotopes of hydrogen and oxygen (δ2H and δ18O) are useful conservative tracers for tracking the movement of water in soil. But although the tracking of water infiltrating through the soil profile and its movement as run‐off and groundwater recharge are well developed, water movement through the soil can also include evaporative fractionation. Soil water fractionation factors have, until now, been largely empirical. Unlike open water evaporation where temperature, humidity, and vapour pressure gradient define fractionation, soil water evaporation includes fractionation by soil matrix effects. These effects are still poorly characterized. Here, we present preliminary results from a simple laboratory experiment with four soil admixtures with grain sizes that range from sand to silt and clay. Our results show that soil tension seems to control the isotope fractionation of resident soil water. The relationship between soil tension and equilibrium fractionation appears to be independent of soil texture and appears well supported by thermodynamic theory. Although these results are preliminary, they suggest that future work should go after soil tension effects as a possible explanatory factor of soil water and water vapour fractionation. [ABSTRACT FROM AUTHOR]

Core Ideas: Matric potential controls the equilibrium fractionation factor between soil water and water vapor.Surface chemistry determined by X‐ray spectroscopy affects the equilibrium fractionation factor.A conceptual isotope retention characteristic approach is presented. Soil water stable isotopes are widely used for geo‐ and ecohydrological applications. However, the signature of the soil water isotopic composition in the environment depends on various factors. While recent work has shown matric potential effects on equilibrium fractionation, little work has examined other soil parameters concerning soil water energy status like the surface wettability, usually quantified in terms of contact angle. We simultaneously explored the role of matric potential, contact angle, and soil surface chemistry effects on the equilibrium fractionation factor during soil water evaporation. We present a simple laboratory experiment with four different soils of various textures. Subsamples of each texture class were treated with dichlorodimethylsilane to modify surface wetting properties. Additionally, we tested two natural soil samples to explore wettability effects. Samples were dried at temperatures between 40 and 550°C to produce chemically modified surface properties. All samples were spiked with water of known isotopic composition at different water contents. The isotopic signature was determined using the vapor‐bag equilibration method. The matric potential of each sample was measured with a soil water potential meter, the contact angle was determined with the sessile drop method, and the surface chemistry by X‐ray photoelectron spectroscopy. In addition to temperature and soil matric potential, the elemental composition has apparently some control on the equilibrium fractionation factor. Based on findings, we introduce a new soil water isotope retention characteristic approach to summarize how these factors (matric potential, contact angle, and soil surface chemistry) each control the equilibrium fractionation factor for 18O/16O and 2H/H. Corresponding retention curve approach parameters are promising to be applied in the future to predict soil water fractionation effects under natural and non‐stationary conditions. [ABSTRACT FROM AUTHOR]

The article discusses the coronavirus disease 2019 pandemic has biggest concerns worldwide and in Italy, the first European country to face the pandemic and all dramatic consequences. Topics include primary prevention, for older persons with comorbidities, has involved physical distancing and isolation; and the COVID-19 pandemic has required joint efforts to identify strategies and guidelines for infection prevention.

RATIONALE: The ability to recover the isotopic signature of water added to soil samples that have previously been ovendried decreases with the increasing presence of silt and clay. The effects on the isotopic signature of water associated with physicochemical soil properties are not yet fully understood, for either hydration or dehydration of soil samples. METHODS: The soil sample chemistry and the crystallinity of minerals were measured by X-ray fluorescence and X-ray diffraction. The organic carbon and the cation-exchange capacity were also determined. Water of known isotopic signature was used to spike an oven-dried substrate and subsequently extracted by cryogenic vacuum extraction at a temperature of 105°C. In addition, the soils were oven-dried at 205°C and water extractions were also performed at 205°C. The isotopic signatures of the water samples were determined by cavity-ring-down spectrometry. RESULTS: The isotope effects caused by the cryogenic vacuum extraction method applied to soils with elevated clay content were reduced. First, by increasing the extraction temperature to 205°C, we improved the precision of the cryogenic vacuum extraction method and the recovery of the known isotopic signature of the spike water. Secondly, the postcorrection of data based on the physicochemical soil properties and a common extraction temperature of 105°C improved the measurement trueness. CONCLUSIONS: The isotopic signature of soil water is influenced by mineral-water interaction. During the hydration of clay, different minerals deplete free water in heavy isotopes. The extracted soil water (dehydration water) gathered from clay-rich soils is generally more depleted in the heavy isotopes than the spike water, making results obtained for different soil types difficult to compare. Isotope effects observed at the mineral-water interface highlight potential explanations for eco-hydrological separation of water pools. [ABSTRACT FROM AUTHOR]

Over the past 10 years, the multitude of highly constrained applications such as radio-frequency identification and sensor networks has led to a new trend in the development of cryptographic primitives. Many algorithms categorized as lightweight cryptographic algorithms have been developed specifically for these new applications. Comparing them is very important but also very challenging because every application has its own constraints. This fact leads to a different choice of design strategies, and the best algorithm for one application is not necessarily the best for all applications. Moreover, the definition of what is lightweight is not always the same because lightweight covers a reduction in power and energy consumption just as well as a reduction in area for hardware. This article proposes and compares lightweight hardware implementations of four recent block ciphers (Klein, Led, Lilliput, and Ktantan). This work is included in a large project that aims to protect the hardware against cloning and counterfeiting. The main constraint in this field is the area required by the protection scheme. As a result, we chose to target only the smallest possible area for each selected algorithm. Consequently, two strategies are presented: full width and serial hardware implementations. All results were generated and verified for Xilinx Spartan-6 and Spartan-3 field-programmable gate arrays and also for application-specific integrated circuit. Additionally, all the design files are available online. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Introduction: The probability and degree of muscle recovery after lesions of long peripheral nerves have not been assessed quantitatively.Methods: Twelve adults with closed injuries of the fibular division of the sciatic nerve with complete denervation of associated muscles were followed-up for 2-10 years. The onset of reinnervation was detected electromyographically. Calf circumference and maximum voluntary isometric contraction (MVIC) of foot dorsiflexion were measured on both sides during 2-4 visits.Results: Reinnervation occurred in 11 patients after an average of 13 months. MVIC on the affected side was 2%-27% of that on the unaffected side (average 11%) and remained stable for the following 2-3 years. Correlations and mixed-model regressions confirmed that the degree of recovery was negatively associated with duration of denervation.Conclusions: Reinnervation occurs in about 90% of patients within about 1 year. About 10% of baseline dorsiflexion strength is permanently recovered, which is functionally relevant. Muscle Nerve, 2016 Muscle Nerve 54: -, 2016 Muscle Nerve 54: 702-708, 2016. [ABSTRACT FROM AUTHOR]

Groundwater recharge estimations are necessary for sustainable management of groundwater resources. Among various hydraulic, hydrogeological and hydrological approaches, tracer methods are proposed to improve groundwater recharge estimations. Soil water isotope-based estimates of groundwater recharge rates were developed in the 1960s and have been applied in more than 40 studies reviewed within this manuscript. This comprehensive review research distinguishes three fundamental research approaches: (1) labelling method with tritium or deuterium, which can be used to trace unsaturated zone water movement, (2) tracing soil water movement using a seasonal signal of stable isotopes in precipitation, mainly applied in humid zones, and (3) interpretation of an evaporation signal that impacts soil water stable isotope composition, mainly applicable in arid and semiarid regions. More recently, advances in soil water extraction and analytical methods allow a higher sampling resolution and in situ measurements of soil water stable isotopes. Analytical advances may strengthen and improve the applicability of stable isotope methods for quantitative recharge. We present, compare and discuss studies of unsaturated zone isotope profiles with an emphasis on necessary prerequisites, such as a substantial thick porous sedimentary layer, or negative influences through high clay and silt contents or dry soil conditions. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims: The aims of this study were to assess the attitudes of Slovene paediatricians to aspects of end-of-life (EOL) care and compare these attitudes between paediatric intensivists, paediatric specialists and paediatric residents.Methods: We performed a cross-sectional survey, using a specifically designed 43-item anonymous questionnaire.Results: We included 323 out of 586 Slovene paediatricians and residents, while 46.7% (151 of 323) of them responded to our questionnaire. More than half of intensivists (54.2%) had sought counsel from the Committee for Medical Ethics in the past as compared with 12.0% and 12.1% of specialists and residents, respectively (P < 0.001). The decision to limit life-sustaining treatment (LST) was found to be ethically acceptable in all groups of respondents. The highest level of agreement was found in residents (90.2%), followed by 83.3% among intensivists and 73.8% among specialists (P = not statistically significant (NS)). Disagreement with termination of hydration was highest among residents (85%) and intensivists (79.2%) while it was lower among specialists (66.7%) (P = NS). Patient's best interest, good clinical practice and patient's autonomous decision were graded as the top three aspects of the EOL care, while cost effectiveness and availability of patient's bed in intensive care were the least important.Conclusions: The decision to limit LST measures was found to be ethically acceptable for Slovene paediatricians. No major differences were found among paediatric intensivists, specialist paediatricians and paediatric residents in the attitudes towards the EOL care. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) is the most common cause of congenital infection. This pathogen exhibits extensive genetic variability in the genes that encode structural envelope glycoproteins, regulatory proteins, and proteins that contribute to immune evasion. However, the role of specific viral strains in the outcome of congenital CMV infection is unclear. Variation in the UL55 gene encoding glycoprotein B (gB), the UL144 gene encoding TNF α-like receptor, and the US28 gene encoding β-chemokine receptor was determined in 60 newborn infants with congenital CMV infection and 90 infants with postnatal or undefined CMV infection. CMV polymorphisms were studied in relation to disease outcome and viral load. Genotyping was performed by a sequencing analysis of PCR-amplified fragments, and the viral load was measured by quantitative real-time PCR. The results demonstrated that (1) the UL55 and US28 genotype distributions were similar among the group of congenital and postnatal CMV infection; (2) the UL144 B1 genotype was more prevalent in congenital than in postnatal infection and was detected in 70% of newborns with asymptomatic congenital infection; and (3) none of the examined genotype was significantly linked with symptomatic CMV infection. No relationship was observed between genotype and viral load. The results revealed that UL55, UL144, and US28 polymorphisms are not associated with the outcome of CMV infection in infants, but the presence of UL144 B1 genotype might be virological marker of asymptomatic infection at birth. J. Med. Virol. 87:1737-1748, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A sustainable D-glucosamine ligand is successfully introduced into iron-catalysed C C for the first time. The Fe(acac)2/ D-glucosamine·HCl/Et3N catalytic system was effective at 5 mol% loading in of Grignard reagents with organic bromides. Moderate to high efficiency was achieved with preserved stereochemistry when allyl (Csp3) or alkenyl (Csp2) bromides were coupled with phenylmagnesium (Csp2) or benzylmagnesium (Csp3) bromides. The catalytic system developed was also successfully applied for the novel and economic preparation of a Michael-acceptor-like starting material used in an alternative synthesis of the drug sitagliptin, a known blockbuster for the treatment of type II diabetes mellitus. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background The Matthew-Wood syndrome is associated with mutations of the STRA6 gene. It combines a pulmonary agenesis/hypoplasia; microphthalmia/anophthalmia; congenital cardiac, digestive, and urogenital malformations; and diaphragmatic defects. Case A 23-year-old nulliparous woman was referred to our center after a fetal ultrasound examination at 26 weeks of pregnancy revealed an abnormal head shape, a heart malformation, multiple cysts in both kidneys, and dilated ureters. A male baby (46, XY; 3600g; Apgar score 1) was delivered at 38 weeks of gestation and died 1 hr later due to respiratory failure. The diagnosis of Matthew-Wood syndrome was suspected given the association of bilateral anophthalmia, agenesis of the left lung, and heart and kidney defects. It was confirmed by the identification of two deleterious mutations of the STRA6 gene. RESULTS The child was a compound heterozygote for two previously reported mutations, a paternally inherited missense mutation (c.878C>T [p.Pro293Leu] and a maternally inherited frameshift mutation (c.50_52delACTinsCC [p. Asp17Alafs*55]), producing a premature stop codon. CONCLUSION The diagnosis of Matthew-Wood syndrome should be considered in all fetuses with microphthalmia/anophthalmia. It requires an extensive ultrasound/MRI examination of the lung, heart, and diaphragm. Birth Defects Research 109:251-253, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Conjugation to human serum albumin (HSA) has emerged as a powerful approach for extending the in vivo half-life of many small molecule and peptide/protein drugs. Current HSA conjugation strategies, however, can often yield heterogeneous mixtures with inadequate pharmacokinetics, low efficacies, and variable safety profiles. Here, we designed and synthesized analogues of TAK-242, a small molecule inhibitor of Toll-like receptor 4, that primarily reacted with a single lysine residue of HSA. These TAK-242-based cyclohexene compounds demonstrated robust reactivity, and Lys64 was identified as the primary conjugation site. A bivalent HSA conjugate was also prepared in a site-specific manner. Additionally, HSA-cyclohexene conjugates maintained higher levels of stability both in human plasma and in mice than the corresponding maleimide conjugates. This new conjugation strategy promises to broadly enhance the performance of HSA conjugates for numerous applications. [ABSTRACT FROM AUTHOR]

Purity in water: An interesting course of developmENt took place recENtly in the area of boron additions to unsaturated precursors. The first CuII and Cu0 catalyzed B2pin2 additions to alkENes and alkynes in/on pure aqueous media evolved from discovery on racemic versions to asymmetric variants and pharmaceutical applications. All presENted methods provide significantly simplified catalytic systems and perform with high efficiENcy and stereoselectivity in/on pure water. [ABSTRACT FROM AUTHOR]

Outlier detection among over-dispersed proportions is important in healthcare quality monitoring. We had previously introduced control limits for double-square-root chart on the basis of prediction intervals from regression-through-origin and compared our approach to common outlier detection tests. In this study, we develop our approach further by adjusting the confidence level (in the spirit of Chauvenet's criterion and Bayesian thinking) and transforming the chart into an asymmetric funnel plot. We compare it to Laney's approach ( p'-chart adapted for cross-sectional data), Spiegelhalter's approach (funnel plots based on multiplicative or additive regression models) and Carling's median rule. Comparisons are performed on simulated and real data. The simulations comprise 'small' (<0.2; highly right-skewed) and 'large' (>0.5; symmetrically distributed) proportions, drawn in samples of size 10-100 from lognormal distribution either without outliers or with one outlier added. The real data comprise hospital readmissions from the UK (used by Laney and Spiegelhalter) and business indicators of healthcare quality for Slovenian hospitals. In the simulations, Spiegelhalter's approach tended to yield very high false alarm rates, except the multiplicative version in very small samples. Laney's approach produced fewest false alarms but could not detect the outlier in very small samples among small proportions, and regardless of sample size among large proportions. Median rule performed similarly. Our approach performed the best overall, although it is slightly less liberal than median rule for small proportions, it appears to be the only generally useful approach for large proportions. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A metal-free reaction system of air, NH4NO3(cat), 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)(cat), and H+(cat) is introduced as a simple, safe, inexpensive, efficient and chemoselective mediator for aerobic oxidation of various primary and secondary benzyl and alkyl alcohols, including those bearing oxidizable heteroatoms (N, S, O) to the corresponding aldehydes or ketones. Air oxygen under slight overpressure plays the role of the terminal oxidant, which is catalytically activated by redox cycles of nitrogen oxides released from a catalytic amount of NH4NO3 and cocatalyzed by TEMPO (nitroxyl radical compound), under acidic conditions, which are essential for an overall activation of the reaction system. The synthetic value of this reaction system and its green chemical profile was illustrated by a 10 g scale-up experiment, performed in an open-air system by using a renewable and reusable polymer-supported form of TEMPO (OXYNITROX®S100). The reaction solvent was recovered by distillation under atmospheric pressure, and the pure final product was isolated under reduced pressure; the acid activators (HCl or H2SO4) were recovered as ammonium salts. [ABSTRACT FROM AUTHOR]

ABSTRACT Site-specific recombinases are tremendously valuable tools for basic research and genetic engineering. By promoting high-fidelity DNA modifications, site-specific recombination systems have empowered researchers with unprecedented control over diverse biological functions, enabling countless insights into cellular structure and function. The rigid target specificities of many sites-specific recombinases, however, have limited their adoption in fields that require highly flexible recognition abilities. As a result, intense effort has been directed toward altering the properties of site-specific recombination systems by protein engineering. Here, we review key developments in the rational design and directed molecular evolution of site-specific recombinases, highlighting the numerous applications of these enzymes across diverse fields of study. Biotechnol. Bioeng. 2014;111: 1-15. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The efficient 'on water' β-borylation using bis(pinacolato)diboron agent was achieved with a newly developed catalytic system based on basic copper carbonate and various ligands. The catalytic system was used for β-borylation of various Michael acceptors, alkenes and alkynes. The presented methodology was successfully applied to the novel synthesis of β-alcohol type sitagliptin side chain precursor via water-based highly enantioselective β-borylation followed by an oxidation process. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Healthcare quality monitoring by the Ministry of Health in Slovenia includes over 100 business indicators of economy, efficiency and funding allocation, which are analysed annually for over 20 hospitals. Most of these indicators are random-denominator same-quantity ratios with a strongly correlated numerator and denominator, and the goal is the identification of outliers. A large simulation study was performed to study the performance of three types of methods: common outlier detection tests for small samples-Grubbs, Dean and Dixon, and Nalimov tests-applied unconditionally and conditionally upon results of Shapiro-Wilk normality test; the boxplot rule; and the double-square-root control chart, for which we introduced regression-through-origin-based control limits. Pert, Burr and three-parameter loglogistic distributions, which fitted the real data best, were used with no, one or two outliers in the simulated samples of sizes 5 to 30. Small (below 0.2, right skewed) and large (above 0.5, more symmetrical) ratios were simulated. Performance of the methods varied greatly across the conditions. Formal small-sample tests proved virtually useless if applied conditionally upon passed normality pre-test in the presence of outliers. Boxplot rule performed most variedly but was the only useful one for tiny samples. Our variant of the double-square-root control chart proved too conservative in tiny samples and too liberal for samples of size 20 or more without outliers but appeared the most useful to detect actual outliers in samples of the latter size. As a possibility for future improvement and research, we propose pre-testing of normality by using a class of robustified Jarque-Bera tests. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We present a general protocol for processing cost-beneficial, environmentally benign aqueous-type suspensions containing metal-oxide nanostructured particles, and their patterning with piezoelectric ink-jet printing technology. The critical issues relevant to ink-jet printing are the preparation and stabilization of nanosized particles in a fluid and adjusting its physical properties to the values appropriate for a particular ink-jet printer mechanism. We discuss and illustrate, on a model titania system, the processing of a highly stable, colloidal, water-based suspension containing particles not bigger than 570 nm, prepared by a ball-milling process. For the ink-jet printing experiments, the surface tension and the viscosity of the suspension were modified by the addition of a small amount of the appropriate non-ionic amphiphiles and glycerol. The formation of droplets, their positioning on the substrate, and the shape and uniformity of the dots on the substrate are discussed and correlated with the fluid properties via the inverse Ohnesorge number Z. It was shown successfully that uniform, regular-shaped TiO2 dots with a diameter of 30 μm and a good positioning accuracy on Si/SiO2 substrates could be obtained by jetting a fluid with Z values of 5 and 9 using a piezoelectric ink-jet printer with a nozzle diameter of 21 μm operating at an amplitude of 13 V and a frequency of 5 kHz. [ABSTRACT FROM AUTHOR]

Melatonin was recently shown to have protective effects against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) by diminishing bladder oxidative stress. HC is accompanied by destruction of the bladder urothelium and followed by apoptosis and rapid regeneration via proliferation and differentiation of urothelial cells, reaching complete restoration of normal urothelium in three weeks. Therefore, the effect of melatonin on apoptosis, proliferation and differentiation of urothelial cells, during destruction and regeneration of the urothelium three-weeks after a single dose CP treatment, was studied. F344 male rats were injected intraperitoneally with saline (control group) or melatonin (Mel group) or a single dose of CP (100 mg/kg; CP group) or melatonin (10 mg/kg) with CP (Mel + CP group). Melatonin co-treatment with CP significantly reduced apoptosis and increased proliferation of urothelial cells at day 1 and thus prevented extensive loss of cells from the urothelium. However, proliferation indices at days 4 and 7 after melatonin and CP co-treatment suddenly dropped and therefore the development of hyperplasia was prevented. Melatonin co-treatment with CP also resulted in earlier differentiation of superficial urothelial cells. Melatonin seems to have protective effect against CP-induced urothelial damage and a favorable impact on regeneration and restoration of normal urothelium, since it reduces the number of apoptotic and proliferating urothelial cells and results in their earlier differentiation. [ABSTRACT FROM AUTHOR]

Background: Duodenogastro-esophageal reflux (DGER) is an important factor in the pathogenesis of reflux esophagitis. Animal studies have demonstrated that the injurious effect of duodenal juice components depends on pH. The purpose of the present study was to investigate the temporal relationship between DGER and esophageal pH. Methods: Seventy-six children with symptoms of gastro-esophageal reflux disease (27 without, 31 with mild, 18 with severe esophagitis) underwent 24 h simultaneous esophageal pH and bilirubin monitoring with Bilitec 2000. The recordings were analyzed for (i) pH at the beginning of DGER episodes; (ii) relative duration of DGER in eight defined pH intervals of 1 pH unit; and (iii) differences in relative duration of DGER between the three groups of children. Results: DGER episodes most frequently began at pH between 6 and 7. DGER was present in the esophagus across the spectrum of esophageal pH, with the biggest relative duration between pH 3 and 5. However, in children without esophagitis relative duration of DGER was longest between pH 5 and 6, in children with mild esophagitis between pH 4 and 5, while in those with severe esophagitis it was between pH 2 and 4 ( P < 0.001). Conclusions: DGER appears across the whole esophageal pH spectrum. The more severe the esophagitis, the lower the pH at which DGER occurs, resulting in simultaneous damaging effects of acid and duodenal juice components. [ABSTRACT FROM AUTHOR]

The article offers information on the psychological intervention with elderly people during the Covid-19 pandemic, along with mentions the experience of a nursing home amid the pandemic in Italy. It discusses that nursing homes people with physical or mental disabilities, neurological diseases or older people with different levels of cognitive functioning live together, closely with healthcare personnel.

Screening combinatorial libraries of conformationally constrained peptides against macromolecular targets is utilized in identifying novel drug leads and in developing new reagents for chemical biology. In methods such as phage-display selections, biotinylated macromolecular targets are often immobilized on avidin- and streptavidin-functionalized supports. Thus, the characterization of peptides that bind avidin and streptavidin is necessary for accurate interpretation of screening and selection results. Toward this goal, we panned a phage-displayed cyclic peptide library against NeutrAvidin, a chemically deglycosylated version of avidin. The selection produced a highly homologous consensus motif (Asp-Arg/Leu-Ala-Ser/Thr-Pro-Tyr/Trp). Two of these cyclic peptides, CDRATPYC and CDRASPYC, bound both NeutrAvidin and avidin with low-micromolar dissociation constants, whereas their acyclic counterparts had negligible affinity (<80-fold). Moreover, these cyclic peptides were very specific for their targets and did not bind the structurally and functionally similar protein, streptavidin. Thus, we have identified a new class of cyclic peptides, distinct from the much-studied streptavidin-binding His-Pro-Gln peptide motif. These results will not only allow for discriminating between desired and background cyclic peptide motifs in selections and screens but also provide a new protein/peptide model system and a useful reagent in chemical biology that can have utility in protein immobilization, purification, and chemical tagging. [ABSTRACT FROM AUTHOR]

Deposition of conformationally altered proteins prominently characterizes pathogenesis and pathomorphology of a number of neurodegenerative disorders. 2-(1-{6-[(2-[F-18]fluoroethyl) (methyl)amino]-2-naphthyl} ethylidene) malononitrile ([F-18]FDDNP), a hydrophobic, viscosity-sensitive, solvent-sensitive, fluorescent imaging probe has been used with positron emission tomography to visualize brain pathology in the living brain of Alzheimer disease (AD) patients. Its non-radiofluorinated analog FDDNP was shown to label senile plaques and neurofibrillary tangles (NFTs) in brain tissue sections. This work aimed at evaluating FDDNP labeling of various protein deposits in fixed, paraffin-embedded brain tissue sections of selected neurodegenerative disorders: AD, cerebral amyloid angiopathy (CAA), transmissible spongiform encephalopathies, progressive supranuclear palsy (PSP), Pick disease (PiD), Parkinson disease, dementia with Lewy bodies, multiple system atrophy (MSA). Cerebral hypertensive vascular hyalinosis (HVH) was used as negative control. Significant agreement between amyloid histochemical properties and FDDNP labeling of the deposits was established. FDDNP labeling showed high positive predictive value for birefringence in senile plaques and NFTs in AD, prion plaques and amyloid deposits in CAA. No FDDNP labeled structures were observed in HVH, PSP, PiD or MSA tissue sections. Our findings may be of significant value for the detection of neuropathological aggregates with [F-18]FDDNP in some of these disorders in the living brain of human subjects. [ABSTRACT FROM AUTHOR]