Discriminative Power of Handwriting and Drawing Features in Depression.

This study contributes knowledge on the detection of depression through handwriting/drawing features, to identify quantitative and noninvasive indicators of the disorder for implementing algorithms for its automatic detection. For this purpose, an original online approach was adopted to provide a dynamic evaluation of handwriting/drawing performance of healthy participants with no history of any psychiatric disorders ([Formula: see text]), and patients with a clinical diagnosis of depression ([Formula: see text]). Both groups were asked to complete seven tasks requiring either the writing or drawing on a paper while five handwriting/drawing features' categories (i.e. pressure on the paper, time, ductus, space among characters, and pen inclination) were recorded by using a digitalized tablet. The collected records were statistically analyzed. Results showed that, except for pressure, all the considered features, successfully discriminate between depressed and nondepressed subjects. In addition, it was observed that depression affects different writing/drawing functionalities. These findings suggest the adoption of writing/drawing tasks in the clinical practice as tools to support the current depression detection methods. This would have important repercussions on reducing the diagnostic times and treatment formulation.

PYED-1 Overcomes Colistin Resistance in Acinetobacter baumannii.

Antibiotic resistance has become more and more widespread over the recent decades, becoming a major global health problem and causing colistin to be increasingly used as an antibiotic of last resort. Acinetobacter baumannii, an opportunistic pathogen that has rapidly evolved into a superbug exhibiting multidrug-resistant phenotypes, is responsible for a large number of hospital infection outbreaks. With the intensive use of colistin, A. baumannii resistance to colistin has been found to increase significantly. In previous work, we identified a deflazacort derivative, PYED-1 (pregnadiene-11-hydroxy-16,17-epoxy-3,20-dione-1), which exhibits either direct-acting or synergistic activity against Gram-positive and Gram-negative species and Candida spp., including A. baumannii. The aim of this study was to evaluate the antibacterial activity of PYED-1 in combination with colistin against both A. baumannii planktonic and sessile cells. Furthermore, the cytotoxicity of PYED-1 with and without colistin was assessed. Our results show that PYED-1 and colistin can act synergistically to produce a strong antimicrobial effect against multidrug-resistant populations of A. baumannii. Interestingly, our data reveal that PYED-1 is able to restore the efficacy of colistin against all colistin-resistant A. baumannii isolates. This drug combination could achieve a much stronger antimicrobial effect than colistin while using a much smaller dosage of the drugs, additionally eliminating the toxicity and resistance issues associated with the use of colistin.

Sems Sensibility: Biliary Stent Migration into the Oesophagus.

Endoprostheses are commonly used in the treatment of biliary and pancreatic disorders. Fully-covered metal stents are intended for the palliation of malignant strictures in the biliary tree. We report a case of a patient affected by cancer of the pancreas who was treated with a proximal metallic biliary stent. The stent migrated to the oesophagus and was endoscopically removed. Proximal migration, although rare, should be kept in mind as a potential complication of the procedure.

A Dynamic Probabilistic Model for Heterogeneous Data Fusion: A Pilot Case Study from Computer-Aided Detection of Depression.

The present paper, in the framework of a search for a computer-aided method to detect depression, deals with experimental data of various types, with their correlation, and with the way relevant information about depression delivered by different sets of data can be fused to build a unique body of knowledge about individuals' mental states facilitating the diagnosis and its accuracy. To this aim, it suggests the use of a recently introduced «limiting form¼ of the kinetic-theoretic language, at present widely used to describe complex systems of objects of the most diverse nature. In this connection, the paper mainly aims to show how a wide range of experimental procedures can be described as examples of this «limiting case¼ and possibly rendered by this description more effective as methods of prediction from experience. In particular, the paper contains a simple, preliminary application of the method to the detection of depression, to show how the consideration of statistical parameters connected with the analysis of speech can modify, at least in a stochastic sense, each diagnosis of depression delivered by the Beck Depression Inventory (BDI-II).

The Risk of Malignant Degeneration of Müllerian Derivatives in PMDS: A Review of the Literature.

Persistent Müllerian Duct Syndrome (PMDS) is a rare autosomal recessive disorder of sex development characterized by the presence of fallopian tubes, uterus and upper one-third of the vagina in individuals with XY genotype and normal male phenotype. The main complications of PMDS are infertility and the rare risk of malignant degeneration of both testicular and Müllerian derivatives. We report the case of a 49-year-old man who, during repair of an incisional hernia, was incidentally found to have a uterine-like structure posterior to the bladder. In the past at the age of 18 months, he had undergone bilateral orchidopexies for bilateral cryptorchidism. The intraoperative decision was to preserve the uterine-like structure and make a more accurate diagnosis postoperatively. Evaluation revealed an XY chromosome and imaging consistent with PMDS. The patient was informed about the risk of neoplastic transformation of the residual Müller ducts and was offered surgical treatment, which he declined. Subsequent follow-up imaging studies, including testicular and pelvic ultrasound, were negative for findings suggestive of malignant testicular and Mullerian derivative degeneration. A review of the international literature showed that, when a decision is taken to remove the Mullerian derivatives, laparoscopy and especially robotic surgery allow for the successful removal of Müllerian derivatives. Whenever the removal of these structures is not possible or the patient refuses to undergo surgery, it is necessary to inform the patient of the need for adequate follow-up. Patients should undergo regular pelvic imaging examination and MRI might be a better method for that purpose.

N-Substituted l-Iminosugars for the Treatment of Sanfilippo Type B Syndrome.

Sanfilippo syndrome comprises a group of four genetic diseases due to the lack or decreased activity of enzymes involved in heparan sulfate (HS) catabolism. HS accumulation in lysosomes and other cellular compartments results in tissue and organ dysfunctions, leading to a wide range of clinical symptoms including severe neurodegeneration. To date, no approved treatments for Sanfilippo disease exist. Here, we report the ability of N-substituted l-iminosugars to significantly reduce substrate storage and lysosomal dysfunctions in Sanfilippo fibroblasts and in a neuronal cellular model of Sanfilippo B subtype. Particularly, we found that they increase the levels of defective α-N-acetylglucosaminidase and correct its proper sorting toward the lysosomal compartment. Furthermore, l-iminosugars reduce HS accumulation by downregulating protein levels of exostosin glycosyltransferases. These results highlight an interesting pharmacological potential of these glycomimetics in Sanfilippo syndrome, paving the way for the development of novel therapeutic approaches for the treatment of such incurable disease.

Reciprocity versus Self-Interest in a Competitive Interaction Context: An Experimental Study.

In social interactions, the reciprocity norm implies to adjust one's behavior to that of the other agents. Conversely, behaving according to self-interest involves taking into account the reciprocity principle only if it does not hinder the achievement of one's goals. However, reciprocity and self-interest may conflict with each other, as when returning a kind action involves sacrificing the possibility to achieve a personal objective. The conflict could be exacerbated by some contextual factors, such as competitive pressures. This study investigated, in a competitive interaction context, which principle prevails when the two conflict. To this end, 276 unpaid participants (M = 138) took part in a two-stage experiment entailing a simulated interaction with a fictitious opponent, which behaved selfishly, fairly or altruistically toward them during the first stage. Participants had to decide whether or not to reciprocate the opponent's previous behavior, which in the critical experimental conditions conflicted with the goal to successfully complete the experiment. So, they were faced with a moral dilemma. Competition degree was manipulated to make the conflict between reciprocity and self-interest more or less harsh. Moreover, we tested whether the putative effect of experimental manipulation was mediated by changes in context-related affective states and personal beliefs about morality. Results showed that decision-making was principally influenced by reciprocity. Regardless of the competition degree, participants preferred to engage in reciprocal behavior even when this compromised their personal interest. Affective states and beliefs changed in response to the experimental manipulation, but they did not mediate the effect of the independent variable on decision-making.

Synthesis and antiviral properties of biomimetic iminosugar-based nucleosides.

Herein we report the synthesis, conformational analysis and the evaluation of the antiviral activity of six-membered nucleoside analogues having a piperidine ring as the preorganized (deoxy)ribose bioisostere. Mutagenic nucleobase-containing nucleosides 1 and 2 were obtained by appropriate manipulation of the well-known glycomimetic agent deoxynojirimycin as easily accessible starting material. In vitro assays revealed activity of 5-iododeoxyuridine analogue 1 against all DNA viruses tested. As suggested by DFT analysis and pH-dependent NMR experiments, antiviral activity was correlated to the biomimetic character of the piperidine ring, as it is able to resemble the deoxyribose conformations adopted by natural nucleosides when interacting with viral enzymes.

Alarm fatigue in nurses working in intensive care units: A multicenter study.

BACKGROUND: Technological progress improves health care efficiency, quality, safety, and cost, supporting clinical activity in various scenarios, such as Intensive Care Unit (ICU). A timely response to alarms from monitors and other ICU electromedical devices is therefore crucial. The number of false alarms tend to desensitize care providers increasing the risk of experiencing alarm fatigue and, at times, lead to severe consequences for patients. OBJECTIVES: To assess the psychometric properties of the Italian version of the Alarm Fatigue Questionnaire and to explore the phenomenon of alarm fatigue among nurses working in intensive care settings. METHODS: The CVI-I was calculated to evaluate the validity of the content of the tool. Construct validity was investigated through exploratory factor analysis. Cronbach's alpha coefficient (α) was used to examine the internal consistency of the scale and Spearman's rho coefficient to test for stability.We designed a multicentre cross-sectional survey. A convenience sample of nurses from 4 Major Italian hospitals was recruited. The nurses completed the Italian version of the Alarm Fatigue Questionnaire. RESULTS: The content validity index CVI-S of the scale (CVI-S) was 91.11%; Cronbach's alpha coefficient was 0.71. The Italian version of the tool explained 67.18%of the overall variance. 396 nurses were enrolled (79.84%). The overall level of alarm fatigue was Me = 29 [22;30]. 42.17%of the sample reported prior experience with alarm fatigue incidents. CONCLUSIONS: The extension of alarm fatigue requires the adoption of a preventive intervention plan. The Italian version of the Alarm Fatigue Questionnaire shows promising psychometric properties.

Digging into protein metalation differences triggered by fluorine containing-dirhodium tetracarboxylate analogues.

The catalytic and biological properties of dirhodium tetracarboxylates ([Rh2(µ-O2CR)4L2], L = axial ligand and R = CH3-, CH3CH2-, etc.) largely depend on the nature of bridging carboxylate equatorial µ-O2CR ligands, which can be easily exchanged by solvent molecules when R is CF3 (i.e. µ-O2CR is trifluoroacetate, tfa). Here, we prepared the [Rh2(OAc)(tfa)3] compound and investigated its interaction with bovine pancreatic ribonuclease and lysozyme under the same conditions used to study the reactivity of these proteins with [Rh2(OAc)4] and [cis-Rh2(OAc)2(tfa)2]. UV-vis absorption spectroscopy and 19F nuclear magnetic resonance studies indicate that [Rh2(OAc)(tfa)3] rapidly loses tfa ligands and interacts with the proteins. Crystallographic data demonstrate that the reaction of [Rh2(OAc)(tfa)3] with proteins can lead to products that are significantly different when compared to those obtained with [Rh2(OAc)4] and [cis-Rh2(OAc)2(tfa)2]: the dirhodium centre can bind the side chain of His residues at both axial and equatorial sites, at variance with what is found in the case of [Rh2(OAc)4] and [cis-Rh2(OAc)2(tfa)2]. These data indicate that the hydrolysis of dirhodium tetracarboxylates plays a significant role in defining their reaction with proteins allowing the formation of unexpected reaction products. These results suggest that [cis-Rh2(OAc)2(tfa)2] and [Rh2(OAc)(tfa)3] can be used to obtain different dirhodium/peptide and dirhodium/protein adducts with distinct catalytic properties and can explain the different cytotoxicity exhibited by tfa-containing dirhodium tetracarboxylates.

Mesenchymal Stem Cells for Cryptoglandular Anal Fistula: Current State of Art.

Anal fistula is a common disease that needs surgical treatment to be resolved. Despite a variety of surgical options, the major problem is still to cure complex fistulas without any recurrence in the long-term follow-up but, at the same time, to avoid an impairment of continence. In recent years, one solution has been the application of mesenchymal stem cells derived from adipose tissue, especially in association with other treatments, such as the use of fibrin glue or the previous application of a seton. Their initial use in fistulas associated with Crohn's disease has shown encouraging results. In this non-systematic review our aim is to analyze the use in cryptoglandular fistulas: the rate of healing is not so high, and the number of studies is limited. Therefore, further randomized controlled trials are needed to establish their efficacy in the case of complex cryptoglandular anal fistulas and their possible complications.

Mood State Detection in Handwritten Tasks Using PCA-mFCBF and Automated Machine Learning.

In this research, we analyse data obtained from sensors when a user handwrites or draws on a tablet to detect whether the user is in a specific mood state. First, we calculated the features based on the temporal, kinematic, statistical, spectral and cepstral domains for the tablet pressure, the horizontal and vertical pen displacements and the azimuth of the pen's position. Next, we selected features using a principal component analysis (PCA) pipeline, followed by modified fast correlation-based filtering (mFCBF). PCA was used to calculate the orthogonal transformation of the features, and mFCBF was used to select the best PCA features. The EMOTHAW database was used for depression, anxiety and stress scale (DASS) assessment. The process involved the augmentation of the training data by first augmenting the mood states such that all the data were the same size. Then, 80% of the training data was randomly selected, and a small random Gaussian noise was added to the extracted features. Automated machine learning was employed to train and test more than ten plain and ensembled classifiers. For all three moods, we obtained 100% accuracy results when detecting two possible grades of mood severities using this architecture. The results obtained were superior to the results obtained by using state-of-the-art methods, which enabled us to define the three mood states and provide precise information to the clinical psychologist. The accuracy results obtained when detecting these three possible mood states using this architecture were 82.5%, 72.8% and 74.56% for depression, anxiety and stress, respectively.

Reactivity of a fluorine-containing dirhodium tetracarboxylate compound with proteins.

Dirhodium complexes of general formula [Rh2(O2CR)4]L2 are a well-known class of bimetallic compounds that are used as efficient catalysts for a variety of reactions and have been shown to be potent antibacterial and anticancer agents. The catalytic and biological properties of these complexes largely depend on the nature of the bridging carboxylate ligands. Trifluoroacetate (tfa)-containing dirhodium compounds have been used to build artificial metalloenzymes upon reaction with peptides and have been shown to be more cytotoxic than dirhodium tetraacetate. However, there is no structural information on the interaction between these compounds and proteins. Here, cis-Rh2(µ-O2CCH3)2(µ-O2CCF3)2 ([cis-Rh2(OAc)2(tfa)2]) has been synthesized and its reaction with bovine pancreatic ribonuclease (RNase A) and hen egg white lysozyme (HEWL) was analyzed using a combination of different techniques, including Fluorine-19 nuclear magnetic resonance spectroscopy and macromolecular X-ray crystallography, with the aim to unveil the differences in the reactivity of tfa-containing dihrodium complexes with proteins when compared to [Rh2(OAc)4]. [cis-Rh2(OAc)2(tfa)2] and [Rh2(OAc)4] bind the N atoms of His side chains of RNase A at the axial position; however the fluorine-containing compound rapidly loses its tfa ligands, while [Rh2(OAc)4] can retain the acetate ligands upon protein binding. The reactivity of [cis-Rh2(OAc)2(tfa)2] with HEWL is slightly distinct when compared to that of [Rh2(OAc)4] under the same experimental conditions; however, both [cis-Rh2(OAc)2(tfa)2] and [Rh2(OAc)4] degrade when soaked within HEWL crystals. These results provide a structural-based guide for the design of new heterogenous chiral dirhodium/peptide and dirhodium/protein adducts with application in the fields of organic synthesis and asymmetric catalysis.

Lung Tumor Skin Metastasis: Case Report of a Solitary Cutaneous Ulcerated Lesion as Initial Manifestation of Lung Carcinoma.

Lung cancer has the highest cancer incidence, and it is the most common cause of cancer death worldwide. Cutaneous metastases are infrequent compared to hilar nodes, adrenal glands, liver, brain, and bones. However, unusual skin lesions in patients at high risk of lung cancer should be regarded carefully to rule out a metastatic manifestation of an occult primary site tumor. Surgical excision, or incisional biopsy when the former is deemed unfeasible, should be performed to allow histopathological examination in case of occult primary site. In patients affected by advanced lung tumors, surgical excision could be beneficial in terms of pain control and improvement of the quality of life. We report a case of a solitary large skin lesion as an early manifestation of a lung adenocarcinoma.

The Glucocorticoid PYED-1 Disrupts Mature Biofilms of Candida spp. and Inhibits Hyphal Development in Candida albicans.

Invasive Candida infections have become a global public health problem due to the increase of Candida species resistant against antifungal therapeutics. The glucocorticoid PYED-1 (pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1) has antimicrobial activity against various bacterial taxa. Consequently, it might be considered for the treatment of Candida infections. The antifungal activity of PYED-1 was evaluated against several fungal strains that were representative of the five species that causes the majority of Candida infections-namely, Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis and Candida krusei. PYED-1 exhibited a weak antifungal activity and a fungistatic effect on all five Candida species. On the other hand, PYED-1 exhibited a good anti-biofilm activity, and was able to eradicate the preformed biofilms of all Candida species analyzed. Moreover, PYED-1 inhibited germ tube and hyphae formation of C. albicans and reduced adhesion of C. albicans to abiotic surfaces by up to 30%.

Synthesis of Piperidine Nucleosides as Conformationally Restricted Immucillin Mimics.

The de novo synthesis of piperidine nucleosides from our homologating agent 5,6-dihydro-1,4-dithiin is herein reported. The structure and conformation of nucleosides were conceived to faithfully resemble the well-known nucleoside drugs Immucillins H and A in their bioactive conformation. NMR analysis of the synthesized compounds confirmed that they adopt an iminosugar conformation bearing the nucleobases and the hydroxyl groups in the appropriate orientation.

Toward the Identification of Novel Antimicrobial Agents: One-Pot Synthesis of Lipophilic Conjugates of N-Alkyl d- and l-Iminosugars.

In the effort to improve the antimicrobial activity of iminosugars, we report the synthesis of lipophilic iminosugars 10a-b and 11a-b based on the one-pot conjugation of both enantiomeric forms of N-butyldeoxynojirimycin (NBDNJ) and N-nonyloxypentyldeoxynojirimycin (NPDNJ) with cholesterol and a succinic acid model linker. The conjugation reaction was tuned using the established PS-TPP/I2/ImH activating system, which provided the desired compounds in high yields (94-96%) by a one-pot procedure. The substantial increase in the lipophilicity of 10a-b and 11a-b is supposed to improve internalization within the bacterial cell, thereby potentially leading to enhanced antimicrobial properties. However, assays are currently hampered by solubility problems; therefore, alternative administration strategies will need to be devised.

N-Nonyloxypentyl-l-Deoxynojirimycin Inhibits Growth, Biofilm Formation and Virulence Factors Expression of Staphylococcus aureus.

Staphylococcus aureus is one of the major causes of hospital- and community-associated bacterial infections throughout the world, which are difficult to treat due to the rising number of drug-resistant strains. New molecules displaying potent activity against this bacterium are urgently needed. In this study, d- and l-deoxynojirimycin (DNJ) and a small library of their N-alkyl derivatives were screened against S. aureus ATCC 29213, with the aim to identify novel candidates with inhibitory potential. Among them, N-nonyloxypentyl-l-DNJ (l-NPDNJ) proved to be the most active compound against S. aureus ATCC 29213 and its clinical isolates, with the minimum inhibitory concentration (MIC) value of 128 µg/mL. l-NPDNJ also displayed an additive effect with gentamicin and oxacillin against the gentamicin- and methicillin-resistant S. aureus isolate 00717. Sub-MIC values of l-NPDNJ affected S. aureus biofilm development in a dose-dependent manner, inducing a strong reduction in biofilm biomass. Moreover, real-time reverse transcriptase PCR analysis revealed that l-NPDNJ effectively inhibited at sub-MIC values the transcription of the spa, hla, hlb and sea virulence genes, as well as the agrA and saeR response regulator genes.

PYED-1 Inhibits Biofilm Formation and Disrupts the Preformed Biofilm of Staphylococcus aureus.

Pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1 (PYED-1), a heterocyclic corticosteroid derivative of deflazacort, exhibits broad-spectrum antibacterial activity against Gram-negative and Gram-positive bacteria. Here, we investigated the effect of PYED-1 on the biofilms of Staphylococcus aureus, an etiological agent of biofilm-based chronic infections such as osteomyelitis, indwelling medical device infections, periodontitis, chronic wound infections, and endocarditis. PYED-1 caused a strong reduction in biofilm formation in a concentration dependent manner. Furthermore, it was also able to completely remove the preformed biofilm. Transcriptional analysis performed on the established biofilm revealed that PYED-1 downregulates the expression of genes related to quorum sensing (agrA, RNAIII, hld, psm, and sarA), surface proteins (clfB and fnbB), secreted toxins (hla, hlb, and lukD), and capsular polysaccharides (capC). The expression of genes that encode two main global regulators, sigB and saeR, was also significantly inhibited after treatment with PYED-1. In conclusion, PYED-1 not only effectively inhibited biofilm formation, but also eradicated preformed biofilms of S. aureus, modulating the expression of genes related to quorum sensing, surface and secreted proteins, and capsular polysaccharides. These results indicated that PYED-1 may have great potential as an effective antibiofilm agent to prevent S. aureus biofilm-associated infections.