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Open AccessArticle
Spiro Indane-Based Phosphine-Oxazolines as Highly Efficient P,N Ligands for Enantioselective Pd-Catalyzed Allylic Alkylation of Indoles and Allylic Etherification
Molecules 2019, 24(8), 1575; https://doi.org/10.3390/molecules24081575 (registering DOI) -
Abstract
A series of indane-based phosphine-oxazoline ligands with a spirocarbon stereogenic center were examined for palladium-catalyzed asymmetric allylic alkylation of indoles. Under optimized conditions, high yields (up to 98%) and enantioselectivities (up to 98% ee) were obtained with a broad scope of indole derivatives. [...] Read more.
A series of indane-based phosphine-oxazoline ligands with a spirocarbon stereogenic center were examined for palladium-catalyzed asymmetric allylic alkylation of indoles. Under optimized conditions, high yields (up to 98%) and enantioselectivities (up to 98% ee) were obtained with a broad scope of indole derivatives. The ligand was determined to be the most efficient P,N-ligand for this reaction. Moreover, the ligand was also efficient for Pd-catalyzed asymmetric allylic etherification with hard aliphatic alcohols as nucleophiles. Full article
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Herpes Simplex Virus Proctitis Masquerading as Rectal Cancer
Diseases 2019, 7(2), 36; https://doi.org/10.3390/diseases7020036 (registering DOI) -
Abstract
Herpes simplex virus (HSV) is the leading cause of proctitis in HIV-infected individuals. However, no cases of rectal masses secondary to HSV infection have been reported to date. Herein, we present the case of a 45-year-old man with HIV infection who developed rectal [...] Read more.
Herpes simplex virus (HSV) is the leading cause of proctitis in HIV-infected individuals. However, no cases of rectal masses secondary to HSV infection have been reported to date. Herein, we present the case of a 45-year-old man with HIV infection who developed rectal pain and bleeding, along with dysuria and voiding difficulty. Colonoscopy revealed proctitis and a rectal mass with features concerning for rectal cancer. Histologic sections of the rectal mass biopsy demonstrated colorectal mucosa with viral cytopathic changes, ulceration, granulation tissue, marked inflammatory infiltrate, and fibrinopurulent exudate. Immunohistochemistry for herpes simplex virus-1 was positive in epithelial cells demonstrating a viral cytopathic effect. The patient was treated with valacyclovir for 3 weeks, which led to complete resolution of his symptoms. Follow-up sigmoidoscopy at 6 months did not show any masses. Our case illustrates the importance of considering HSV in the differential diagnosis of rectal masses. We advocate the routine use of viral immunohistochemistry for the evaluation of rectal tumors, especially in patients with clinical manifestations and endoscopic findings consistent with proctitis. Full article
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Open AccessArticle
Music Training Positively Influences the Preattentive Perception of Voice Onset Time in Children with Dyslexia: A Longitudinal Study
Brain Sci. 2019, 9(4), 91; https://doi.org/10.3390/brainsci9040091 (registering DOI) -
Abstract
Previous results showed a positive influence of music training on linguistic abilities at both attentive and preattentive levels. Here, we investigate whether six months of active music training is more efficient than painting training to improve the preattentive processing of phonological parameters based [...] Read more.
Previous results showed a positive influence of music training on linguistic abilities at both attentive and preattentive levels. Here, we investigate whether six months of active music training is more efficient than painting training to improve the preattentive processing of phonological parameters based on durations that are often impaired in children with developmental dyslexia (DD). Results were also compared to a control group of Typically Developing (TD) children matched on reading age. We used a Test–Training–Retest procedure and analysed the Mismatch Negativity (MMN) and the N1 and N250 components of the Event-Related Potentials to syllables that differed in Voice Onset Time (VOT), vowel duration, and vowel frequency. Results were clear-cut in showing a normalization of the preattentive processing of VOT in children with DD after music training but not after painting training. They also revealed increased N250 amplitude to duration deviant stimuli in children with DD after music but not painting training, and no training effect on the preattentive processing of frequency. These findings are discussed in view of recent theories of dyslexia pointing to deficits in processing the temporal structure of speech. They clearly encourage the use of active music training for the rehabilitation of children with language impairments. Full article
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Open AccessArticle
Convenient Asymmetric Synthesis of Fmoc-(S)-6,6,6-Trifluoro-Norleucine
Symmetry 2019, 11(4), 578; https://doi.org/10.3390/sym11040578 (registering DOI) -
Abstract
In this work we report a convenient asymmetric synthesis of Fmoc-(S)-6,6,6-trifluoro-norleucine via alkylation reaction of chiral glycine equivalent. The target amino acid of 99% enantiomeric purity was prepared with 82.4% total yield (three steps). Full article
Open AccessFeature PaperArticle
Group Method of Data Handling (GMDH) Lithology Identification Based on Wavelet Analysis and Dimensionality Reduction as Well Log Data Pre-Processing Techniques
Energies 2019, 12(8), 1509; https://doi.org/10.3390/en12081509 (registering DOI) -
Abstract
Although the group method of data handling (GMDH) is a self-organizing metaheuristic neural network capable of developing a classification function using influential input variables, the results can be improved by using some pre-processing steps. In this paper, we propose a joint principal component [...] Read more.
Although the group method of data handling (GMDH) is a self-organizing metaheuristic neural network capable of developing a classification function using influential input variables, the results can be improved by using some pre-processing steps. In this paper, we propose a joint principal component analysis (PCA) and GMDH (PCA-GMDH) classifier method. We investigated well log data pre-processing techniques composed of dimensionality reduction (DR) and wavelet analysis (WA), using the southern basin of the South Yellow Sea as a case study, with the aim of improving the lithology classification accuracy of the GMDH. Our results showed that the dimensionality reduction method, which is composed of PCA and linear discriminant analysis (LDA), minimized the complexity of the classifier by reducing the number of well log suites to the relevant components and factors. On the other hand, the WA decomposed the well log signals into time-frequency wavelets for the GMDH algorithm. Of all the pre-processing methods, only the PCA was able to significantly increase the classification accuracy rate of the GMDH. Finally, the proposed joint PCA-GMDH classifier not only increased the accuracy but also was able to distinguish between all the classes of lithofacies present in the southern basin of the South Yellow Sea. Full article
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Open AccessArticle
Identifying Optimal Irrigation Water Needs at District Scale by Using A Physically Based Agro-Hydrological Model
Water 2019, 11(4), 841; https://doi.org/10.3390/w11040841 (registering DOI) -
Abstract
This paper mainly aims to illustrate an irrigation management tool to simulate scheduling of district-level water needs over the course of an irrigation season. The tool is mostly based on a daily model for simulating flow of water (and solutes) in heterogeneous agri-environmental [...] Read more.
This paper mainly aims to illustrate an irrigation management tool to simulate scheduling of district-level water needs over the course of an irrigation season. The tool is mostly based on a daily model for simulating flow of water (and solutes) in heterogeneous agri-environmental systems (called FLOWS-HAGES). The model produces information on the daily evolution of: soil water contents and pressure potentials in the soil profile; water uptake and actual evapotranspiration; stress periods for each crop; return fluxes to the groundwater and their quality in terms of solute concentrations (e.g., nitrates). FLOWS-HAGES provides a daily list of hydrants to be operated according to water or crop-based criteria. The daily optimal sequence of hydrant use may thus be established by passing the volumes to be delivered on to the model for simulating the hydraulics of the irrigation network, in order to ensure that the discharges flowing inside the network of distribution pipes are delivered under optimal pressure head distribution in the system. All the above evaluations can be carried out in a stochastic framework to account for soil heterogeneity and climate changes. To illustrate the potential of FLOWS-HAGES, a case study was considered for a selected sector of the Irrigation District 10 in the “Sinistra Ofanto” irrigation system (southern Italy, Apulia region). In a 139 ha area (Sector 6 of the Irrigation District), soil profiles were analyzed for characterization of hydraulic properties variability. Hydraulic properties were determined by a combination of field and laboratory measurements. Model simulations were validated by comparing soil water storage simulated and measured by a sensor based on electromagnetic induction technique. Irrigation water volumes and frequency calculated by the model were compared to the volumes actually supplied by the farmers. Compared to the farmers behavior, the model simulates more frequent irrigations with lower irrigation volumes. Finally, some indexes of irrigation performance were calculated for each farm under study. The resulting maps provide useful information on the spatial distribution of farmer behavior, indicating the abuse or underuse of water as well as the fraction of the water lost by drainage following the irrigation method applied. Full article
Open AccessFeature PaperArticle
Assessing the Effectiveness of the WFD as a Tool to Address Different Levels of Water Scarcity Based on Two Case Studies of the Mediterranean Region
Water 2019, 11(4), 840; https://doi.org/10.3390/w11040840 (registering DOI) -
Abstract
Despite being a natural phenomenon, water scarcity is, to a great extent, human-induced, particularly affected by climate change and by the increased water resources vulnerability. The Water Framework Directive (WFD), an ‘umbrella’ directive that aims to provide holistic approaches to the management of [...] Read more.
Despite being a natural phenomenon, water scarcity is, to a great extent, human-induced, particularly affected by climate change and by the increased water resources vulnerability. The Water Framework Directive (WFD), an ‘umbrella’ directive that aims to provide holistic approaches to the management of water resources and is supported by a number of Communication documents on water scarcity, requires for prompt responses to ensure ‘healthy’ water bodies of good ecological status. The current paper presents a multidisciplinary approach, developed and engaged within the Globaqua Project, to provide an assessment of the main challenges towards addressing water scarcity with emphasis on the climate change projections, in two Mediterranean regions. The current paper attempts to critically assess the effectiveness of the WFD as a tool to address water scarcity and increase sustainability in resource use. Criticism lies on the fact that the WFD does not directly refer to it, still, water scarcity is recognized as a factor that increases stress on water resources and deteriorates their status. In addition, the Program of Measures (PoMs) within the WFD clearly contribute to reducing vulnerability of water resources and to ensure current and future water use, also under the impact of the projected climate change. Full article
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Open AccessArticle
Bariatric Procedures in Older Adults in the United States: Analysis of a Multicenter Database
Geriatrics 2019, 4(2), 32; https://doi.org/10.3390/geriatrics4020032 (registering DOI) -
Abstract
Background: Bariatric procedures help reduce obesity-related comorbidities and thus improve survival. Clinical characteristics and outcomes after bariatric procedures in older adults were investigated. Methods: A multi-institutional Nationwide Inpatient Sample (NIS) database was queried from years 2005 through 2012. Older adults >60 [...] Read more.
Background: Bariatric procedures help reduce obesity-related comorbidities and thus improve survival. Clinical characteristics and outcomes after bariatric procedures in older adults were investigated. Methods: A multi-institutional Nationwide Inpatient Sample (NIS) database was queried from years 2005 through 2012. Older adults >60 years of age with procedure codes for bariatric procedures and a diagnosis of obesity/morbid obesity were selected to compare clinical characteristics/outcomes between those undergoing closed versus open procedures and identify risk factors associated with in-hospital mortality and increased hospital length of stay (LOS). Results:Over the study period, 79,122 bariatric procedures were performed. Those undergoing open procedures compared to closed procedures had a higher in-hospital mortality (0.8% vs. 0.2%) and a longer hospital LOS (4.8 days vs. 2.2 days). Risk factors significantly associated with in-hospital mortality were open procedures, the Western region, and the Elixhauser comorbidity index. Risk factors associated with increased LOS were Medicaid insurance type, an open procedure, a higher Elixhauser comorbidity score, a required skilled nursing facility (SNF) discharge, and died in hospital. Conclusion: Closed bariatric procedures are increasingly being preferred in older adults, with a four-fold lower mortality compared to open procedures. Besides choice of procedure, the presence of specific comorbidities is associated with increased mortality in older adults. Full article
Open AccessArticle
Oncogenic Role of ZFAS1 lncRNA in Head and Neck Squamous Cell Carcinomas
Cells 2019, 8(4), 366; https://doi.org/10.3390/cells8040366 (registering DOI) -
Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with high mortality. The identification of specific HNSCC biomarkers will increase treatment efficacy and limit the toxicity of current therapeutic strategies. Long non-coding RNAs (lncRNAs) are promising biomarkers. Accordingly, here we [...] Read more.
Background: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with high mortality. The identification of specific HNSCC biomarkers will increase treatment efficacy and limit the toxicity of current therapeutic strategies. Long non-coding RNAs (lncRNAs) are promising biomarkers. Accordingly, here we investigate the biological role of ZFAS1 and its potential as a biomarker in HNSCC. Methods: The expression level of ZFAS1 in HNSCC cell lines was analyzed using qRT-PCR. Based on the HNSCC TCGA data, the ZFAS1 expression profile, clinicopathological features, and expression of correlated genes were analyzed in patient tissue samples. The selected genes were classified according to their biological function using the PANTHER tool. The interaction between lncRNA:miRNA and miRNA:mRNA was tested using available online tools. All statistical analyses were accomplished using GraphPad Prism 5. Results: The expression of ZFAS1 was up-regulated in the metastatic FaDu cell line relative to the less aggressive SCC-25 and SCC-040 and dysplastic DOK cell lines. The TCGA data indicated an up-regulation of ZFAS1 in HNSCCs compared to normal tissue samples. The ZFAS1 levels typically differed depending on the cancer stage and T-stage. Patients with a lower expression of ZFAS1 presented a slightly longer disease-free survival and overall survival. The analysis of genes associated with ZFAS1, as well its targets, indicate that they are linked with crucial cellular processes. In the group of patients with low expression of ZFAS1, we detected the up-regulation of suppressors and down-regulation of genes associated with epithelial-to-mesenchymal transition (EMT) process, metastases, and cancer-initiating cells. Moreover, the negative correlation between ZFAS1 and its host gene, ZNFX1, was observed. The analysis of interactions indicated that ZFAS1 has a binding sequence for miR-150-5p. The expression of ZFAS1 and miR-150-5p is negatively correlated in HNSCC patients. miR-150-5p can regulate the 3′UTR of EIF4E mRNA. In the group of patients with high expression of ZFAS1 and low expression of miR-150-5p, we detected an up-regulation of EIF4E. Conclusions: In HNSCC, ZFAS1 displays oncogenic properties, regulates important processes associated with EMT, cancer-initiating cells, and metastases, and might affect patients’ clinical outcomes. ZFAS1 likely regulates the cell phenotype through miR-150-5p and its downstream targets. Following further validation, ZFAS1 might prove a new and valuable biomarker. Full article
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Open AccessReview
Plasma Transthyretin as A Biomarker of Sarcopenia in Elderly Subjects
Nutrients 2019, 11(4), 895; https://doi.org/10.3390/nu11040895 (registering DOI) -
Abstract
Skeletal muscle (SM) mass, the chief component of the structural compartment belonging to lean body mass (LBM), undergoes sarcopenia with increasing age. Decreased SM in elderly persons is a naturally occurring process that may be accelerated by acute or chronic nutritional deficiencies and/or [...] Read more.
Skeletal muscle (SM) mass, the chief component of the structural compartment belonging to lean body mass (LBM), undergoes sarcopenia with increasing age. Decreased SM in elderly persons is a naturally occurring process that may be accelerated by acute or chronic nutritional deficiencies and/or inflammatory disorders, declining processes associated with harmful complications. A recently published position paper by European experts has provided an overall survey on the definition and diagnosis of sarcopenia in elderly persons. The present review describes the additional contributory role played by the noninvasive transthyretin (TTR) micromethod. The body mass index (BMI) formula is currently used in clinical studies as a criterion of good health to detect, prevent, and follow up on the downward trend of muscle mass. The recent upsurge of sarcopenic obesity with its multiple subclasses has led to a confused stratification of SM and fat stores, prompting workers to eliminate BMI from screening programs. As a result, investigators are now focusing on indices of protein status that participate in SM growth, maturation, and catabolism that might serve to identify sarcopenia trajectories. Plasma TTR is clearly superior to all other hepatic biomarkers, showing the same evolutionary patterns as those displayed in health and disease by both visceral and structural LBM compartments. As a result, this TTR parameter maintains positive correlations with muscle mass downsizing in elderly persons. The liver synthesis of TTR is downregulated in protein-depleted states and suppressed in cytokine-induced inflammatory disorders. TTR integrates the centrally-mediated regulatory mechanisms governing the balance between protein accretion and protein breakdown, emerging as the ultimate indicator of LBM resources. This review proposes the adoption of a gray zone defined by cut-off values ranging from 200 mg/L to 100 mg/L between which TTR plasma values may fluctuate and predict either the best or the worst outcome. The best outcome occurs when appropriate dietary, medicinal and surgical decisions are undertaken, resuming TTR synthesis which manifests rising trends towards pre-stress levels. The worst occurs when all therapeutic means fail to succeed, leading inevitably to complete exhaustion of LBM and SM metabolic resources with an ensuing fatal outcome. Some patients may remain unresponsive in the middle of the gray area, combining steady clinical states with persistent stagnant TTR values. Using the serial measurement of plasma TTR values, these last patients should be treated with the most aggressive and appropriate therapeutic strategies to ensure the best outcome. Full article
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Open AccessArticle
MSC.sTRAIL Has Better Efficacy than MSC.FL-TRAIL and in Combination with AKTi Blocks Pro-Metastatic Cytokine Production in Prostate Cancer Cells
Cancers 2019, 11(4), 568; https://doi.org/10.3390/cancers11040568 (registering DOI) -
Abstract
Cell therapy is a promising new treatment option for cancer. In particular, mesenchymal stem cells (MSCs) have shown potential in delivering therapeutic genes in various tumour models and are now on the verge of being tested in the clinic. A number of therapeutic [...] Read more.
Cell therapy is a promising new treatment option for cancer. In particular, mesenchymal stem cells (MSCs) have shown potential in delivering therapeutic genes in various tumour models and are now on the verge of being tested in the clinic. A number of therapeutic genes have been examined in this context, including the death ligand TRAIL. For cell therapy, it can be used in its natural form as a full-length and membrane-bound protein (FL-TRAIL) or as an engineered version commonly referred to as soluble TRAIL (sTRAIL). As to which is more therapeutically efficacious, contradicting results have been reported. We discovered that MSCs producing sTRAIL have significantly higher apoptosis-inducing activity than cells expressing FL-TRAIL and found that FL-TRAIL, in contrast to sTRAIL, is not secreted. We also demonstrated that TRAIL does induce the expression of pro-metastatic cytokines in prostate cancer cells, but that this effect could be overcome through combination with an AKT inhibitor. Thus, a combination consisting of small-molecule drugs specifically targeting tumour cells in combination with MSC.sTRAIL, not only provides a way of sensitising cancer cells to TRAIL, but also reduces the issue of side-effect-causing cytokine production. This therapeutic strategy therefore represents a novel targeted treatment option for advanced prostate cancer and other difficult to treat tumours. Full article
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