Hybrid Amyloid-Chitin Nanofibrils for Magnetic and Catalytic Aerogels.

In the quest for a sustainable and circular economy, it is essential to explore environmentally friendly alternatives to traditional petroleum-based materials. A promising pathway toward this goal lies in the leveraging of biopolymers derived from food waste, such as proteins and polysaccharides, to develop advanced sustainable materials. Here, we design versatile hybrid materials by hybridizing amyloid nanofibrils derived by self-assembly of whey, a dairy byproduct, with chitin nanofibrils exfoliated from the two distinct allomorphs of α-chitin and ß-chitin, extracted from seafood waste. Various hydrogels and aerogels were developed via the hybridization and reassembly of these biopolymeric nanobuilding blocks, and they were further magnetized upon biomineralization with iron nanoparticles. The pH-phase diagram highlights the significant role of electrostatic interactions in gel formation, between positively charged amyloid fibrils and negatively charged chitin nanofibrils. Hybrid magnetic aerogels exhibit a ferromagnetic response characterized by a low coercivity (<50 Oe) and a high specific magnetization (>40 emu/g) at all temperatures, making them particularly suitable for superparamagnetic applications. Additionally, these aerogels exhibit a distinct magnetic transition, featuring a higher blocking temperature (200 K) compared to previously reported similar nanoparticles (160 K), indicating enhanced magnetic stability at elevated temperatures. Finally, we demonstrate the practical application of these hybrid magnetic materials as catalysts for carbon monoxide oxidation, showcasing their potential in environmental pollution control and highlighting their versatility as catalyst supports.

Antiviral activity of nitazoxanide against Morbillivirus infections.

The measles virus (MeV) and canine distemper virus (CDV) belong to the genus Morbillivirus of the Paramyxoviridae family. They are enveloped viruses harboring a non-segmented negative-sense RNA. Morbilliviruses are extremely contagious and transmitted through infectious aerosol droplets. Both MeV and CDV may cause respiratory infections and fatal encephalitis, although a high incidence of brain infections is unique to CDV. Despite the availability of a safe and effective vaccine against these viruses, in recent years we are witnessing a strong resurgence of Morbillivirus infection. Measles still kills more than 100,000 people each year, and CDV causes widespread outbreaks, especially among wild animals, including non-human primates. No drugs are currently approved for MeV and CDV. Therefore, the identification of effective antiviral agents represents an unmet medical need. Here, we have investigated the potential antiviral properties of nitazoxanide (NTZ) against MeV and CDV. Antiviral activity was explored with live virus and cell-based assays. NTZ is a thiazolide that is approved by the FDA as an antiprotozoal agent for the treatment of Giardia intestinalis and Cryptosporidium parvum. Further, nitazoxanide and its metabolite tizoxanide have recently emerged as broad-spectrum antiviral agents. We found that NTZ blocks the MeV and CDV replication, acting at the post-entry level. Moreover, we showed that NTZ affects the function of the viral fusion protein (F), impairing viral spread. Our results indicate that NTZ should be further explored as a therapeutic option in measles and canine distemper virus treatment.

Instantaneous and time-averaged intensity flow measurements in scale models.

Current methods of representing energy flows in rooms have been limited to stationary pressure contour maps or intensity vectors derived from finite-element modeling (FEM) software. Despite recent advances in FEM analysis, such models are at best approximations of real-world phenomena because of the assumptions made in obtaining these results. This paper presents an energy flow visualization tool that combines the well-accepted practice of scale modeling in performance venue acoustics design and recent advances in sensor technology to provide rapid and accurate real-time maps of intensity flows derived from simultaneously-measured pressure and velocity quantities in the studied space.

Attentional enhancement predicts individual differences in visual working memory under go/no-go search conditions.

Attention-control processes transfer relevant information to visual working memory (WM) and prevent irrelevant information from consuming WM resources. Although event-related potentials (ERPs) have revealed attention-control processes associated with enhancement of relevant stimuli (targets) and suppression of irrelevant stimuli (distractors), only the suppressive processes have been found to predict WM capacity. We hypothesised a link between target-enhancement processes and WM capacity would be revealed in a task that requires more control than the conventional visual search paradigms used to study target selection. Here, participants searched for a pop-out target on Go trials and withheld responses on an equal number of randomly intermixed No-Go trials, depending on the colour of the stimulus array. Magnitudes of ERP indices associated with target enhancement (the singleton detection positivity, SDP, and N2pc) were positively correlated with individual differences in WM capacity. These relationships vanished when participants searched for the pop-out target on every trial, regardless of stimulus-array colour. Inhibitory processes associated with suppressing distractors (PD) and withholding responses (no-go P3) on No-Go trials did not predict WM capacity. These findings indicate that target-enhancement mechanisms control access to WM in search tasks that require dynamic control and disconfirm the view that the gateway to WM is entirely inhibitory by nature.

A unique case of subcutaneous panniculitis-like T-cell lymphoma presenting as an abscess following an arthropod bite.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of low-grade cutaneous lymphoma that usually presents with multifocal non-tender subcutaneous nodules over the trunk and extremities. We present an exceptional case of SPTCL masquerading as a solitary abscess which developed following an antecedent arthropod bite. Unique histological features encountered include foci of neutrophilic aggregation and admixed eosinophils within the neoplastic lymphomatous subcuticular infiltrate. As SPTCL rarely presents as an abscess, the authors wish to highlight this diagnostic pitfall and suggest excluding SPTCL as a cause of pseudo-pyoderma in patients who are afebrile with a discordant inflammatory marker profile. In addition, this condition should be suspected in non-diabetic patients who experience a rapid clinical course with suppuration and demonstrate a poor response to appropriate antibiotics. As such, we recommend sending tissue for histopathological examination for patients with atypical presentations.

Searching for Visual Singletons Without A Feature to Guide Attention.

RT studies have provided evidence for a singleton-detection strategy that is used to search for salient targets when there is no additional featural knowledge that would help guide attention. Despite this behavioral evidence, there have been few ERP studies of singleton detection mode because it was reported early on that the ERP signature of attentional selection (the N2pc) is absent without feature guidance. Recently, however, it was discovered that a small and relatively late N2pc occurs in singleton detection mode along with a previously unreported component called the singleton detection positivity (SDP). Here, we show that both components are influenced by the number of items in the display, as one might expect in a salience-based search mode. Specifically, the N2pc and SDP were larger when the set size was increased to make the singleton "pop out" more easily, when participants responded more quickly regardless of set size, and when RT search slopes were negative (Experiment 1). The latency of the SDP also depended on set size. In Experiment 2, EEG was recorded with a higher density electrode array to better characterize the scalp topography of the components and to estimate their neural sources. Regional sources near the ventral surface of extrastriate cortex in the occipital lobe explained over 96% of N2pc and SDP activities. These results indicate that searching in singleton detection mode selectively modulates processing within perceptual regions of visual cortex.

Isolating the Neural Substrates of Visually Guided Attention Orienting in Humans.

The neural processes that enable healthy humans to orient attention to sudden visual events are poorly understood because they are tightly intertwined with purely sensory processes. Here we isolated visually guided orienting activity from sensory activity using event-related potentials (ERPs). By recording ERPs to a lateral stimulus and comparing waveforms obtained under conditions of attention and inattention, we identified an early positive deflection over the ipsilateral visual cortex that was associated with the covert orienting of visual attention to the stimulus. Across five experiments with male and female adult participants, this ipsilateral visual orienting activity (VOA) could be distinguished from purely sensory-evoked activity and from other top-down spatial attention effects. The VOA was linked with behavioral measures of orienting, being significantly larger when the stimulus was detected rapidly than when it was detected more slowly, and its presence was independent of saccadic eye movements toward the targets. The VOA appears to be a specific neural index of the visually guided orienting of attention to a stimulus that appears abruptly in an otherwise uncluttered visual field.SIGNIFICANCE STATEMENT The study of visual attention orienting has been an important impetus for the field of cognitive neuroscience. Seminal reaction-time studies demonstrated that a suddenly appearing visual stimulus attracts attention involuntarily, but the neural processes associated with visually guided attention orienting have been difficult to isolate because they are intertwined with sensory processes that trigger the orienting. Here, we disentangled orienting activity from sensory activity using scalp recordings of event-related electrical activity in the human brain. A specific neural index of visually guided attention orienting was identified. Surprisingly, whereas peripheral sensory stimulation is processed initially and predominantly by the contralateral visual cortex, this electrophysiological index of visual orienting was recorded over the cerebral hemisphere that was ipsilateral to the attention-capturing stimulus.

Dynamic inhibitory control prevents salience-driven capture of visual attention.

The salience-driven selection theory is comprised of three main tenets: (a) the most salient stimulus within a monitored region of the visual field captures attention, (b) the only way to prevent salience-driven distraction is by narrowly focusing attention elsewhere, and (c) all other goal-driven processes are possible only after the most salient item has been attended. Evidence for and against this theory has been provided from two experimental paradigms. Here, event-related potentials (ERPs) recorded in a novel Go/No-Go paradigm disconfirmed all three of tenets of the theory. Participants were instructed to search cyan-item displays for a salient orientation singleton (Go trials) and to ignore randomly intermixed yellow-item displays that could also contain an orientation singleton (No-Go trials). ERP components associated with attentional orienting (posterior contralateral N2; N2pc), distractor suppression (distractor positivity; PD), and stimulus relevance (P2a) were isolated to test predictions stemming from the salience-driven selection theory. On No-Go trials, the salient oddball elicited a PD rather than an N2pc, indicating that it was suppressed, not attended. Moreover, a P2a emerged before the N2pc on Go trials, demonstrating that observers first evaluated the global color of each display and then decided to search for the oddball (Go trials) or to ignore it (No-Go trials). We conclude that goal-driven processes can lead to the prevention of salience-driven attention capture by salient visual objects within the attentional window. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Electrophysiological correlates of visual singleton detection.

Identifying a fixed-feature singleton that pops out from an otherwise uniform array of distractors elicits an ERP component called the N2pc over the posterior scalp. The N2pc has been used to track attention with millisecond accuracy, inform theories of visual selection, and test for specific attention deficits in clinical populations, yet it is still unclear what neuro-cognitive process gives rise to the component. One hypothesis is that the N2pc reflects a spatial filtering process that suppresses irrelevant distractors. In support of this hypothesis, Luck and Hillyard (1994a) showed that the N2pc is eliminated when the features of the target and distractors switch unpredictably across trials (so that participants cannot prepare to filter out irrelevant items). The present study aimed to replicate Luck and Hillyard's singleton detection experiment but with modifications to enhance the N2pc signal and to gain statistical power. We show that orientation singletons do, in fact, elicit the N2pc as well as an earlier-onset and longer-lasting singleton detection positivity over the occipital scalp when the target and distractor orientations swap randomly across trials. We conclude that spatial filtering might not play a major role in the generation of the N2pc and that the selection processes required to search for fixed-feature targets (in feature-search mode) are also engaged in the detection of variable-feature singletons (in singleton detection mode).

Palladium-meta-terarylphosphine catalyst for the Mizoroki-Heck reaction of (hetero)aryl bromides and functional olefins.

The evolutionary meta-terarylphosphine ligand architecture of Cy*Phine was recently shown to be a key feature that imposed outstanding performance in palladium-catalyzed copper-free Sonogashira applications. Herein, the Pd-Cy*Phine combination has similarly proven to be a powerful catalyst system for the Mizoroki-Heck reaction. Using high-throughput screening (HTS) methodology, DMF and NaHCO3 were rapidly identified as the most effective solvent and base pair for the cross-coupling catalysis of challenging and industrially valuable substrates including highly electron-rich heteroaryl bromides and unactivated olefins. Unprotected functional groups were well tolerated using low catalyst loadings, and the simple protocol produced excellent yields (up to 99%) with unprecedented substrate diversity. The Pd-Cy*Phine system broadly outperformed many state-of-the-art commercial alternatives, which demonstrated its potential as a next-generation cross-coupling catalyst.

Immunoglobulin G4-related aortitis mimicking an intramural hematoma.

Immunoglobulin G4-related systemic disease is a rare entity with various presenting symptoms. We report the case of a 34-year-old Chinese male who presented with immunoglobulin G4-related aortitis and the unusual symptom of hoarseness of voice. He underwent distal ascending aorta and total aortic arch replacement.

Prospective audit and feedback in antimicrobial stewardship: is there value in early reviewing within 48 h of antibiotic prescription?

Antimicrobial stewardship programme (ASP) methodologies are not well defined, with most preferring to wait ≥72-96 h following antibiotic prescription before reviewing patients. However, we hypothesise that early ASP reviews and interventions are beneficial and do not adversely impact patient safety. This study aimed to evaluate the impact of early ASP interventions within 48 h of antibiotic prescription on patient outcomes and safety. A prospective review of ASP interventions made within 48 h of antibiotic prescription in Singapore General Hospital (SGH) from January to December 2012 was conducted. Patient demographics and outcomes were extracted from the database maintained by the ASP team. For culture-directed treatment, there was a shorter mean duration of therapy (DOT) in the accepted group compared with the rejected group (2.26 days vs. 5.56 days; P<0.001). ASP interventions did not alter the length of hospital stay (LOS), 30-day mortality, 14-day Clostridium difficile infection (CDI), 30-day re-admissions and 14-day re-infection (all P>0.05). For empirical treatment, a shorter DOT (3.61 days vs. 6.25 days; P<0.001) and decreased 30-day all-cause mortality (P=0.003) and infection-related mortality (P=0.002) were observed among patients in the accepted group compared with the rejected group. There was no significant difference in LOS, 14-day CDI and 30-day re-admission (all P>0.05). In conclusion, acceptance of early interventions recommended by ASP in SGH was associated with a reduction in DOT without compromising patient safety. This is evident even during empirical therapy when not all clinical information was available.

Desymmetrization of diolefinic diols by enantioselective amino-thiocarbamate-catalyzed bromoetherification: synthesis of chiral spirocycles.

A facile, efficient, and highly diastereo- and enantioselective bromoetherification of diolefinic diols has been developed using an amino-thiocarbamate catalyst. Further manipulations of the bromoether products enabled entry into a new class of spirocycles which are distinctively lacking in the literature.

Pyoderma gangrenosum: a commonly overlooked ulcerative condition.

BACKGROUND: Pyoderma ga ngrenosum (PG) is a rare, inflammatory, destructive neutrophilic dermatosis, which mimics other ulcerative conditions. MATERIALS AND METHODS: In a retrospective study based on patients diagnosed with PG over a 3-year period (2010-2013), we evaluated demographics, anatomical sites, number of lesions, subtypes, histopathology, associated conditions, treatment regimens, healing time, and recurrence. RESULTS: Of our five patients, there were three males and two females, age ranging between 19 and 58 years (mean age 38 years). Four had single lesions localized to the lower limbs while one had multiple lesions (more than five) over bilateral hands and legs. Ulcerative subtype was observed in all the patients. One exhibited pathergy. Skin biopsies were done in four patients, revealing dense neutrophilic infiltrates in three cases and leukocytoclastic vasculitis in one. Associated systemic diseases were observed in all patients, four having inflammatory bowel disease and one having both systemic lupus erythematosus and anti-phospholipid syndrome. The patients were all treated with systemic corticosteroids either alone or in combination with immunosuppressants (e.g., azathioprine, mycophenolate mofetil, tacrolimus), and wound dressing. Split-thickness skin graft was done in one patient. Complete healing was achieved in all patients, ranging from one to 3 months after diagnosis. No recurrence was reported. CONCLUSIONS: Systemic corticosteroids, either alone or in combination with steroid-sparing agents are the mainstay of treatment. Should family physicians encounter a rapidly progressing ulcer that has poor response to usual wound management, timely referral to dermatology should be made.

Lewis basic selenium catalyzed chloroamidation of olefins using nitriles as the nucleophiles.

A Lewis base catalyzed chloroamidation of olefinic substrates was achieved using diphenyl selenide as the catalyst. The reaction conditions are mild and suitable for a wide range of substrates including those which are acid labile.

Enantioselective synthesis of 2-substituted and 3-substituted piperidines through a bromoaminocyclization process.

A catalytic enantioselective bromocyclization of olefinic amides using amino-thiocarbamates as the catalysts has been developed. The resulting enantioenriched 2-substituted 3-bromopiperidines can readily be transformed to 3-substituted piperidines through a silver salt-mediated rearrangement. This process has been applied to the synthesis of a dopaminergic drug, Preclamol.

T3SEdb: data warehousing of virulence effectors secreted by the bacterial Type III Secretion System.

BACKGROUND: Effectors of Type III Secretion System (T3SS) play a pivotal role in establishing and maintaining pathogenicity in the host and therefore the identification of these effectors is important in understanding virulence. However, the effectors display high level of sequence diversity, therefore making the identification a difficult process. There is a need to collate and annotate existing effector sequences in public databases to enable systematic analyses of these sequences for development of models for screening and selection of putative novel effectors from bacterial genomes that can be validated by a smaller number of key experiments. RESULTS: Herein, we present T3SEdb http://effectors.bic.nus.edu.sg/T3SEdb, a specialized database of annotated T3SS effector (T3SE) sequences containing 1089 records from 46 bacterial species compiled from the literature and public protein databases. Procedures have been defined for i) comprehensive annotation of experimental status of effectors, ii) submission and curation review of records by users of the database, and iii) the regular update of T3SEdb existing and new records. Keyword fielded and sequence searches (BLAST, regular expression) are supported for both experimentally verified and hypothetical T3SEs. More than 171 clusters of T3SEs were detected based on sequence identity comparisons (intra-cluster difference up to ~60%). Owing to this high level of sequence diversity of T3SEs, the T3SEdb provides a large number of experimentally known effector sequences with wide species representation for creation of effector predictors. We created a reliable effector prediction tool, integrated into the database, to demonstrate the application of the database for such endeavours. CONCLUSIONS: T3SEdb is the first specialised database reported for T3SS effectors, enriched with manual annotations that facilitated systematic construction of a reliable prediction model for identification of novel effectors. The T3SEdb represents a platform for inclusion of additional annotations of metadata for future developments of sophisticated effector prediction models for screening and selection of putative novel effectors from bacterial genomes/proteomes that can be validated by a small number of key experiments.