ABSTRACT
Importance: Cellulitis is misdiagnosed in up to 30% of cases due to mimic conditions termed pseudocellulitis. The resulting overuse of antibiotics is a threat to patient safety and public health. Surface thermal imaging and the ALT-70 (asymmetry, leukocytosis, tachycardia, and age ≥70 years) prediction model have been proposed as tools to help differentiate cellulitis from pseudocellulitis. Objectives: To validate differences in skin surface temperatures between patients with cellulitis and patients with pseudocellulitis, assess the optimal temperature measure and cut point for differentiating cellulitis from pseudocellulitis, and compare the performance of skin surface temperature and the ALT-70 prediction model in differentiating cellulitis from pseudocellulitis. Design, Setting, and Participants: This prospective diagnostic validation study was conducted among patients who presented to the emergency department with acute dermatologic lower extremity symptoms from October 11, 2018, through March 11, 2020. Statistical analysis was performed from July 2020 to March 2021 with additional work conducted in September 2023. Main Outcomes and Measures: Temperature measures for affected and unaffected skin were obtained. Cellulitis vs pseudocellulitis was assessed by a 6-physician, independent consensus review. Differences in temperature measures were compared using the t test. Logistic regression was used to identify the temperature measure and associated cut point with the optimal performance for discriminating between cellulitis and pseudocellulitis. Diagnostic performance characteristics for the ALT-70 prediction model, surface skin temperature, and both combined were also assessed. Results: The final sample included 204 participants (mean [SD] age, 56.6 [16.5] years; 121 men [59.3%]), 92 (45.1%) of whom had a consensus diagnosis of cellulitis. There were statistically significant differences in all skin surface temperature measures (mean temperature, maximum temperature, and gradients) between cellulitis and pseudocellulitis. The maximum temperature of the affected limb for patients with cellulitis was 33.2 °C compared with 31.2 °C for those with pseudocellulitis (difference, 2.0 °C [95% CI, 1.3-2.7 °C]; P < .001). The maximum temperature was the optimal temperature measure with a cut point of 31.2 °C in the affected skin, yielding a mean (SD) negative predictive value of 93.5% (4.7%) and a sensitivity of 96.8% (2.3%). The sensitivity of all 3 measures remained above 90%, while specificity varied considerably (ALT-70, 22.0% [95% CI, 15.8%-28.1%]; maximum temperature of the affected limb, 38.4% [95% CI, 31.7%-45.1%]; combination measure, 53.9% [95% CI, 46.5%-61.2%]). Conclusions and Relevance: In this large diagnostic validation study, significant differences in skin surface temperature measures were observed between cases of cellulitis and cases of pseudocellulitis. Thermal imaging and the ALT-70 both demonstrated high sensitivity, but specificity was improved by combining the 2 measures. These findings support the potential of thermal imaging, alone or in combination with the ALT-70 prediction model, as a diagnostic adjunct that may reduce overdiagnosis of cellulitis.
Subject(s)
Cellulitis , Thermography , Adult , Aged , Female , Humans , Male , Middle Aged , Cellulitis/diagnosis , Diagnosis, Differential , Emergency Service, Hospital , Leukocytosis/diagnosis , Predictive Value of Tests , Prospective Studies , Skin Temperature , Thermography/methodsSubject(s)
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Receptors, Chimeric Antigen , Skin Neoplasms , Humans , Skin Neoplasms/pathology , Skin Neoplasms/immunology , Receptors, Chimeric Antigen/immunology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/immunology , Male , Immunotherapy, Adoptive/methods , FemaleABSTRACT
This review provides an in-depth analysis of recent advances and strategies employed in the Pd-catalysed asymmetric allylic alkylation (Pd-AAA) of nucleophilic prochiral heterocycles. The review is divided into sections each focused on a specific family of heterocycle, where optimisation data and reaction scope have been carefully analysed in order to bring forward specific reactivity and selectivity trends. The review eventually opens on how computer-based technologies could be used to predict an ideally matched catalytic system for any given substrate. This user-guide targets chemists from all horizons interested in running a Pd-AAA reaction for the preparation of highly enantioenriched heterocyclic compounds.
ABSTRACT
Stereoselective carbon-carbon bond formation via palladium-catalyzed asymmetric allylic alkylation is a crucial strategy to access chiral natural products and active pharmaceutical ingredients. However, catalysts based on the privileged Trost and Pfaltz-Helmchen-Williams PHOX ligands often require high loadings, specific preactivation protocols, and excess chiral ligand. This makes these reactions uneconomical, often unreproducible, and thus unsustainable. Here we report several chiral single-component Pd(0) precatalysts that are active and practically-applicable in a variety of asymmetric allylic alkylation reactions. Despite the decades-long history and widespread use of Trost-type ligands, the precatalysts in this work are the only reported examples of stable, isolable Pd(0) complexes with these ligands. Evaluating these precatalysts across nine asymmetric allylic alkylation reactions reveals high reactivity and selectivity at low Pd loading. Importantly, we also report an unprecedented Pd-catalyzed enantioselective allylation of a hydantoin, achieved on gram scale in high yield and enantioselectivity with only 0.2 mol% catalyst.
ABSTRACT
Objective: To compare clinical documentation of skin warmth to patient report and quantitative skin surface temperatures of patients diagnosed with cellulitis in the emergency department (ED). Methods: Adult patients (≥18 years) presenting to the ED with an acute complaint involving visible erythema of the lower extremity were prospectively enrolled. Those diagnosed with cellulitis were included in this analysis. Participant report of skin warmth was recorded and skin surface temperature values were obtained from the affected and corresponding unaffected area of skin using thermal cameras. Average temperature (Tavg) was extracted from each image and the difference in Tavg between the affected and unaffected limb was calculated (Tgradient). Clinical documentation of skin warmth was compared to patient report and measured skin warmth (Tgradient >0°C). Results: Among 126 participants diagnosed with cellulitis, 110 (87%) exhibited objective warmth (Tgradient >0°C) and 58 (53%) of these cases had warmth documented in the physical examination. Of those with objective warmth, 86 (78%) self-reported warmth and 7 (6%) had warmth documented in their history of present illness (HPI) (difference = 72%, 95% confidence interval [CI]: 62%-82%; P < 0.001). A significant difference was observed for Tavg affected when warmth was documented (32.1°C) versus not documented (31.0°C) in the physical examination (difference = 1.1°C, 95% CI: 0.29-1.94; P = 0.0083). No association was found between Tgradient and patient-reported or HPI-documented warmth. Conclusions: The majority of ED-diagnosed cellulitis exhibited objective warmth, yet significant discordance was observed between patient-reported, clinician-documented, and measured warmth. This raises concerns over inadequate documentation practices and/or the poor sensitivity of touch as a reliable means to assess skin surface temperature. Introduction of objective temperature measurement tools could reduce subjectivity in the assessment of warmth in patients with suspected cellulitis.
ABSTRACT
A highly efficient, cost-effective, and environmentally friendly protocol is reported for the C5-selective alkylation of hydantoins under phase-transfer catalysis. The reactions are scalable and only require a catalytic amount of tetrabutylammonium bromide (TBAB) to achieve high yields under mild reaction conditions. Moreover, the method is applicable to a wide range of electrophiles, including alkyl-, allyl-, propargyl-, and benzyl halides, as well as acrylates and dibromoalkanes, but also to virtually any hydantoin precursor. We also highlight the potential for an enantioselective adaptation using a chiral phase-transfer catalyst.
ABSTRACT
Lipedematous alopecia is a rare, non-androgenic form of alopecia that is challenging to diagnose, often requiring clinical-pathological correlation. The condition has been reported predominantly in African-American females, but more recently has been described in a broader demographic [1,2]. We describe a rare case of a young Caucasian man with isolated lipedematous alopecia who presented with a boggy, erythematous plaque with alopecia of the occipital scalp and subcutaneous thickening with lymphocytic dermal infiltrate and decreased anagen hairs on histology.
Subject(s)
Adipose Tissue/pathology , Alopecia/pathology , Scalp/pathology , Adult , Humans , Lymphocytes , Male , Subcutaneous Tissue/pathology , White PeopleABSTRACT
Intralesional corticosteroids are associated with various, uncommon, local adverse events [1]. Atrophy and hypopigmentation most commonlyremain localized to sites of injection. However, outward radiation in a linear, streaky pattern has been reported and is termed "perilesional/perilymphatic hypopigmentation or atrophy [2]." We report a case of this rare adverse event.
Subject(s)
Glucocorticoids/adverse effects , Hypopigmentation/chemically induced , Skin/pathology , Triamcinolone Acetonide/adverse effects , Aged , Atrophy/chemically induced , Glucocorticoids/administration & dosage , Humans , Injections, Intralesional/adverse effects , Male , Tennis Elbow/drug therapy , Triamcinolone Acetonide/administration & dosageABSTRACT
The authors present the case of a patient who developed an Aspergillosis flavus (A flavus) superficial cutaneous infection which was identified at the time of cast removal, 2 weeks after immobilization of a closed distal third humerus fracture. Clinical and microbiological findings, as well as the treatment of this patient, are reported. An otherwise healthy 27-year-old male presented to the orthopaedic surgery clinic 2 weeks after a closed distal humerus fracture, which was initially immobilized with a functional removable brace. Upon cast removal, the patient was noted to have significant brown hyperkeratotic patches and plaques, studded with pustules in an annular configuration on his left posterior and lateral arm. Fungal culture later grew A flavus. The patient was started on both oral and topical antifungals and operative management of the displaced fracture was delayed until skin lesions resolved. Once clinical examination and negative repeat bedside potassium hydroxide were confirmed, open reduction and internal fixation was performed. The fracture healed uneventfully, and the patient did not develop any signs or symptoms of postoperative infection.
ABSTRACT
It is known that eosinophilic fasciitis can be associated with monoclonal gammopathy. There is clinical similarity between eosinophilic fasciitis and morphea profunda, but it is unclear whether morphea profunda might be associated with monoclonal gammopathy. The temporal quantification of gammopathy in morphea profunda has not been well characterized. We describe four patients with morphea profunda that were associated with monoclonal gammopathy. Three were associated with monoclonal IgG protein and one with IgM. No patients in our series developed myeloma. In conclusion, the association of monoclonal gammopathy is not unique to eosinophilic fasciitis and scleromyxedema. Further studies are necessary to characterize further the relationship between the two conditions.
Subject(s)
Monoclonal Gammopathy of Undetermined Significance/complications , Scleroderma, Localized/complications , Adult , Aged , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Male , Middle Aged , Monoclonal Gammopathy of Undetermined Significance/immunology , Scleroderma, Localized/pathology , Skin/pathologyABSTRACT
We present an air knife design for creating a heated air curtain to protect optical infrared access windows in high-temperature, condensing, and corrosive stack environments. The design uses the Coanda effect to turn the air curtain and to attach the air curtain to the window surface. The design was tested and verified on our 24 m stack and used extensively over a 6 yr period on several release stacks. During testing and subsequent use no detrimental changes to access window materials have been noted. This design allows stack monitoring without significantly affecting the stack flow profile or chemical concentration.
ABSTRACT
Investigation of biochemical cues in isolation or in combinations in cell culture systems is crucial for unraveling the mechanisms that govern neural development and repair. The most widely used experimental paradigms that elicit axon guidance in vitro utilize as the source of the gradient a pulsatile pipette, transfected cells, or a loaded gel, producing time-varying gradients of poor reproducibility which are not well suited for studying slow-growing mammalian cells. Although microfluidic device design have allowed for generating stable, complex gradients of diffusible molecules, the flow-induced shear forces in a microchannel has made it impossible to maintain viable mammalian neuronal cultures for sufficiently long times. In this paper, we describe axonal responses of mouse cortical neurons in a "neuron-benign" gradient-generator device based on an open chamber that can establish highly stable gradients of diffusible molecules for at least 6 h with negligible shear stress, and also allows the neurons to thrive for at least 2 weeks. Except for the period when the gradient is on, the cells in the gradient are under the same conditions as the cells on the control surfaces, which ensure a consistent set of micro-environmental variables. The gradient stability and uniformity over the cell culture surface achieved by the device, together with our software platform for acquiring, post-processing and quantitatively analyzing the large number of images allowed us to extract valuable information even from small datasets. We report a directed response of primary mammalian neurons (from E14 embryonic mice cortex) to a diffusible gradient of netrin in vitro. We infer from our studies that a large majority (â¼73%) of the neurons that extend axons during the gradient application grow towards the netrin source, and our data analysis also indicates that netrin acts as a growth factor for this same population of neurons.
Subject(s)
Microfluidic Analytical Techniques/instrumentation , Neurons/physiology , Animals , Axons/drug effects , Axons/physiology , Cell Culture Techniques , Cell Tracking , Equipment Design , Female , Mice , Nerve Growth Factors/pharmacology , Netrin-1 , Neurogenesis , Neurons/drug effects , Pregnancy , Signal Transduction , Tumor Suppressor Proteins/pharmacologyABSTRACT
Human neural progenitors are increasingly being employed in drug screens and emerging cell therapies targeted towards neurological disorders where neurogenesis is thought to play a key role including developmental disorders, Alzheimer's disease, and depression. Key to the success of these applications is understanding the mechanisms by which neurons arise. Our understanding of development can provide some guidance but since little is known about the specifics of human neural development and the requirement that cultures be expanded in vitro prior to use, it is unclear whether neural progenitors obey the same developmental mechanisms that exist in vivo. In previous studies we have shown that progenitors derived from fetal cortex can be cultured for many weeks in vitro as undifferentiated neurospheres and then induced to undergo neurogenesis by removing mitogens and exposing them to supportive substrates. Here we use live time lapse imaging and immunocytochemical analysis to show that neural progenitors use developmental mechanisms to generate neurons. Cells with morphologies and marker profiles consistent with radial glia and recently described outer radial glia divide asymmetrically and symmetrically to generate multipolar intermediate progenitors, a portion of which express ASCL1. These multipolar intermediate progenitors subsequently divide symmetrically to produce CTIP2(+) neurons. This 3-cell neurogenic scheme echoes observations in rodents in vivo and in human fetal slice cultures in vitro, providing evidence that hNPCs represent a renewable and robust in vitro assay system to explore mechanisms of human neurogenesis without the continual need for fresh primary human fetal tissue. Knowledge provided by this and future explorations of human neural progenitor neurogenesis will help maximize the safety and efficacy of new stem cell therapies by providing an understanding of how to generate physiologically-relevant cell types that maintain their identities when placed in diagnostic or transplantation environments.
Subject(s)
Neurogenesis , Stem Cells/cytology , Cells, Cultured , Green Fluorescent Proteins/genetics , Humans , Immunohistochemistry , Lentivirus/genetics , Microscopy/methods , Stem Cells/metabolismABSTRACT
During inflammation neutrophils rapidly migrate to the site of tissue damage or infection by following complex gradients of bacterial peptides and host-derived chemokines. The efficiency and speed of neutrophil migration is critically dependent upon the ability of neutrophils to sense new gradients and utilize only those that provide the most direct path to the damaged or infected site. Receptor desensitization plays an important role in migration efficiency and is most commonly studied using bath application of chemotactic factor solutions instead of presenting cells with gradients analogous to those they would experience in vivo. Here we describe a new method for examining gradient-induced neutrophil desensitization using a previously-developed open-chamber microfluidic gradient generator.
Subject(s)
Chemotactic Factors/chemistry , Chemotaxis/physiology , Microfluidic Analytical Techniques/methods , Neutrophil Infiltration/physiology , Neutrophils/cytology , Cells, Cultured , Fluorescent Dyes/chemistry , Humans , Microfluidic Analytical Techniques/instrumentation , Neutrophils/physiologyABSTRACT
Biomolecule gradients have been shown to play roles in a wide range of biological processes including development, inflammation, wound healing, and cancer metastasis. Elucidation of these phenomena requires the ability to expose cells to biomolecule gradients that are quantifiable, controllable, and mimic those that are present in vivo. Here we review the major biological phenomena in which biomolecule gradients are employed, traditional in vitro gradient-generating methods developed over the past 50 years, and new microfluidic devices for generating gradients. Microfluidic gradient generators offer greater levels of precision, quantitation, and spatiotemporal gradient control than traditional methods, and may greatly enhance our understanding of many biological phenomena. For each method, we outline the salient features, capabilities, and applications.
Subject(s)
Biological Factors/metabolism , Biological Factors/pharmacology , Cell Culture Techniques/methods , Cell Physiological Phenomena/drug effects , Animals , Cell Culture Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Substrate Specificity , Time FactorsABSTRACT
This study compared the psychological and physical functioning of 12 children in each of three groups: mothers with chronic pain, fathers with chronic pain and a control, pain-free parents. Parents completed a number of questionnaires including the RAND-36 Health Status Inventory, a child health scale and the Child Behavior Checklist. Children completed the Revised Child Manifest Anxiety Scale and a scale measuring pain and sickness behaviour. Children of mothers with chronic pain reported the most physical and psychological problems, followed by children of fathers with chronic pain and children from the control group. Pain reports between children and parents with chronic pain were significantly correlated, suggesting support for a familial pain model. Social learning may explain the concordance between parent and child health in families experiencing parental chronic pain.
Subject(s)
Father-Child Relations , Mental Health , Mother-Child Relations , Pain/psychology , Psychology, Child , Adult , Case-Control Studies , Child , Female , Humans , Male , Parenting/psychology , Pilot Projects , Sex Factors , Statistics, NonparametricABSTRACT
AIM: There is limited research examining the functioning of children living with parental chronic pain and illness. The aim of this study was to examine the psychosocial adjustment and physical health of children living with a mother experiencing chronic pain. METHODS: One-hundred and three children aged 6-12 years served as participants, with approximately equal numbers of children in maternal chronic pain (n=55) and control groups (n=48). Children completed self-reports about their internalising behaviour, health and attachment security. Mothers, fathers and teachers completed questionnaires relating to children's internalising and externalising behaviour, social behaviour and physical health. RESULTS: Reports from children, mothers and fathers indicated significantly more internalising, externalising, insecure attachment and social and health problems for children in the maternal chronic pain group compared with control children. Teachers reported decreased social skills and increased pain complaints for children in the maternal chronic pain group. Boys in the maternal chronic pain group appear to be affected more than girls. Boys reported more anxiety and insecure attachment, while mothers reported greater social problems and increased illness behaviour for boys. Characteristics of the mother's pain condition, such as, severity, length and frequency were generally unrelated to child functioning. CONCLUSIONS: The study demonstrates the importance of maternal and family variables to child outcomes. The results are discussed in terms of maternal chronic pain comprising a considerable, yet rarely studied, influence in the lives of young children.
Subject(s)
Adaptation, Psychological , Child of Impaired Parents/psychology , Mothers , Pain , Child , Female , Humans , Male , New Zealand , Surveys and QuestionnairesABSTRACT
The potential for the use of woody biomass in poly-beta-hydroxyalkanoate (PHA) biosynthesis is reviewed. Based on previously cited work indicating incorporation of xylose or levulinic acid (LA) into PHAs by several bacterial strains, we have initiated a study for exploring bioconversion of forest resources to technically relevant copolymers. Initially, PHA was synthesized in shake-flask cultures of Burkholderia cepacia grown on 2.2% (w/v) xylose, periodically amended with varying concentrations of levulinic acid [0.07-0.67% (w/v)]. Yields of poly(beta-hydroxybutyrate-co-beta-hydroxyvalerate) [P(3HB-co-3HV)] from 1.3 to 4.2 g/l were obtained and could be modulated to contain from 1.0 to 61 mol% 3-hydroxyvalerate (3HV), as determined by 1H and 13C NMR analyses. No evidence for either the 3HB or 4HV monomers was found. Characterization of these P(3HB-co-3HV) samples, which ranged in molecular mass (viscometric, Mv) from 511-919 kDa, by differential scanning calorimetry and thermogravimetric analyses (TGA) provided data which were in agreement for previously reported P(3HB-co-3HV) copolymers. For these samples, it was noted that melting temperature (Tm) and glass transition temperature (Tg) decreased as a function of 3HVcontent, with Tm demonstrating a pseudoeutectic profile as a function of mol% 3HV content. In order to extend these findings to the use of hemicellulosic process streams as an inexpensive carbon source, a detoxification procedure involving sequential overliming and activated charcoal treatments was developed. Two such detoxified process hydrolysates (NREL CF: aspen and CESF: maple) were each fermented with appropriate LA supplementation. For the NREL CF hydrolysate-based cultures amended with 0.25-0.5% LA, P(3HB-co-3HV) yields, PHA contents (PHA as percent of dry biomass), and mol% 3HV compositions of 2.0 g/l, 40% (w/w), and 16-52 mol% were obtained, respectively. Similarly, the CESF hydrolysate-based shake-flask cultures yielded 1.6 g/l PHA, 39% (w/w) PHA contents, and 4-67 mol% 3HV compositions. These data are comparable to copolymer yields and cellular contents reported for hexose plus levulinic acid-based shake-flask cultures, as reported using Alcaligenes eutrophus and Pseudomonas putida. However, our findings presage a conceivable alternative, forestry-based biorefinery approach for the production of value-added biodegradable PHA polymers. Specifically, this review describes the current and potential utilization of lignocellulosic process streams as platform precursors to PHA polymers including hemicellulosic hydrolysates, residual cellulose-derived levulinic acid, tall oil fatty acids (Kraft pulping residual), and lignin-derived aromatics.