Interventions to promote oral care regimen adherence in the critical care setting: A systematic review.

BACKGROUND: Oral care is a fundamental nurse-led intervention in the critical care setting that provides patient comfort and prevents adverse outcomes in critically ill patients. To date, there has been minimal focus on nurse-focused interventions to improve adherence to oral care regimens in the adult intensive care unit setting. OBJECTIVES: The objectives of this study were to (i) identify types and characteristics of interventions to improve oral care adherence amongst critical care nurses and intervention core components, (ii) evaluate the effectiveness of interventions to improve adherence of oral care regimens, and (iii) identify the types of outcome measures used to assess oral care regimen adherence. DESIGN: This is a systematic review in alignment with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. DATA SOURCES: Key bibliographic databases and platforms, including Scopus, Cochrane, MEDLINE, CINAHL, Embase, PsycINFO, ProQuest, and Web of Science, were searched for studies published before July 2020. The Joanna Briggs Institute's quality appraisal tool was used to assess risk of bias in included studies. RESULTS: A total of 21 original research studies were identified, of which 18 studies used multifaceted interventions. In accordance with the Joanna Briggs Institute's quality appraisal tools, four of the 20 quasi-experimental studies were rated as high quality. The one randomised control trial was of moderate quality. Outcome measures included oral care adherence behaviours, oral care knowledge, self-reported adherence, and documentation. Improved effectiveness in oral care adherence was reported in 20 studies. CONCLUSIONS: Review findings confirm interventions to change behaviours improve oral care adherence. The most effective interventional approach could not be determined owing to heterogeneity in intervention design and outcome measures. Oral care in the intensive care unit is a vital, nurse-led activity that reduces the risk of hospital-acquired infection. It is recommended that future research adopt implementation science methods to ensure stakeholder engagement and feasibility. SYSTEMATIC REVIEW REGISTRATION NUMBER: This review was submitted and subsequently registered on PROSPERO, the International Perspective Register of Systematic Reviews PROSPERO 2019 CRD42019123142.

Development of Covalent Ligands for G Protein-Coupled Receptors: A Case for the Human Adenosine A3 Receptor.

The development of covalent ligands for G protein-coupled receptors (GPCRs) is not a trivial process. Here, we report a streamlined workflow thereto from synthesis to validation, exemplified by the discovery of a covalent antagonist for the human adenosine A3 receptor (hA3AR). Based on the 1 H,3 H-pyrido[2,1- f]purine-2,4-dione scaffold, a series of ligands bearing a fluorosulfonyl warhead and a varying linker was synthesized. This series was subjected to an affinity screen, revealing compound 17b as the most potent antagonist. In addition, a nonreactive methylsulfonyl derivative 19 was developed as a reversible control compound. A series of assays, comprising time-dependent affinity determination, washout experiments, and [35S]GTPγS binding assays, then validated 17b as the covalent antagonist. A combined in silico hA3AR-homology model and site-directed mutagenesis study was performed to demonstrate that amino acid residue Y2657.36 was the unique anchor point of the covalent interaction. This workflow might be applied to other GPCRs to guide the discovery of covalent ligands.

Structure-Affinity Relationships and Structure-Kinetics Relationships of Pyrido[2,1-f]purine-2,4-dione Derivatives as Human Adenosine A3 Receptor Antagonists.

We expanded on a series of pyrido[2,1-f]purine-2,4-dione derivatives as human adenosine A3 receptor (hA3R) antagonists to determine their kinetic profiles and affinities. Many compounds showed high affinities and a diverse range of kinetic profiles. We found hA3R antagonists with very short residence time (RT) at the receptor (2.2 min for 5) and much longer RTs (e.g., 376 min for 27 or 391 min for 31). Two representative antagonists (5 and 27) were tested in [35S]GTPγS binding assays, and their RTs appeared correlated to their (in)surmountable antagonism. From a kon-koff-KD kinetic map, we divided the antagonists into three subgroups, providing a possible direction for the further development of hA3R antagonists. Additionally, we performed a computational modeling study that sheds light on the crucial receptor interactions, dictating the compounds' binding kinetics. Knowledge of target binding kinetics appears useful for developing and triaging new hA3R antagonists in the early phase of drug discovery.

Migration of myeloid cells during inflammation is differentially regulated by the cell surface receptors Slamf1 and Slamf8.

Previous studies have demonstrated that the cell surface receptor Slamf1 (CD150) is requisite for optimal NADPH-oxidase (Nox2) dependent reactive oxygen species (ROS) production by phagocytes in response to Gram- bacteria. By contrast, Slamf8 (CD353) is a negative regulator of ROS in response to Gram+ and Gram- bacteria. Employing in vivo migration after skin sensitization, induction of peritonitis, and repopulation of the small intestine demonstrates that in vivo migration of Slamf1-/- dendritic cells and macrophages is reduced, as compared to wt mice. By contrast, in vivo migration of Slamf8-/- dendritic cells, macrophages and neutrophils is accelerated. These opposing effects of Slamf1 and Slamf8 are cell-intrinsic as judged by in vitro migration in transwell chambers in response to CCL19, CCL21 or CSF-1. Importantly, inhibiting ROS production of Slamf8-/- macrophages by diphenyleneiodonium chloride blocks this in vitro migration. We conclude that Slamf1 and Slamf8 govern ROS-dependent innate immune responses of myeloid cells, thus modulating migration of these cells during inflammation in an opposing manner.

The treatment of eyelid malposition following septal reset blepharoplasty.

The authors have developed a systematic approach to treating eyelid malposition secondary to septal reset blepharoplasty. A key treatment factor is appropriate timing of interventions, which includes initiating treatment with nonsurgical interventions. Although patients who are unresponsive to nonsurgical measures may express a strong desire to surgically correct the eyelid malposition early on, surgical interventions before 3 to 6 months after the initial surgery can, in many instances, worsen the result.

Three-dimensional tomography of composite fracture surfaces.

The goal of this project was to image the three-dimensional fracture interface of a dental composite with the use of X-ray tomography. With the use of the Advanced Photon Source (APS) at Argonne National Laboratory, three-dimensional images were obtained of the crack interface of a dental composite material that had been subjected to three different treatments: a control, cycled in air, and cycled in a 50/50 mixture by volume of ethanol and distilled water. The cycle-loaded treatments were for 100,000 cycles at a load between 80 and 100 N at 5 Hz. The crack interface extended over 28 slices for the control, 96 for the air-cycled specimen, and 83 slices for the 50/50 solution cycle specimen. It would appear that the fatiguing of the specimens allowed for an increase in the crack interface as demonstrated by the 3D tomographical analysis. This volume increase in the crack interface is attributed to a separation of the filler fiber from the resin matrix. Three-dimensional tomography provides an excellent method to observe crack interfaces of dental composites subjected to different types of mechanical and environmental conditions.

Fracture surface examination of dental ceramics using fractal analysis.

OBJECTIVE: The purpose of this study was to measure the fractal dimensional increment of the fracture surface of six dental ceramics, and to measure the correlation of the fractal dimensional increment with fracture toughness. The six dental ceramics investigated were: a traditional porcelain (Finesse[F], Ceramco, Burlington, NJ, USA), four leucite reinforced pressable ceramics (Finesse Pressable [FP], Ceramco; Empress [E], Ivoclar; New Albany, NY, USA and two shades of OPC [OA2 and OI40], Jeneric-Pentron, MA, USA), and a lithium disilicate containing pressable ceramic ([LD] Ceramco). METHODS: The fracture surfaces examined and the measured fracture toughness (K(IC)) values are from a previous study . An impression was taken of the fracture surface, poured up in epoxy, coated with gold, a second layer of epoxy added, and then the surface polished at an angle to the fracture surface. This fracture interface (slit island) was observed in an optical microscope with an imaging system from which an image of the fracture line was digitized. The slit island perimeter was then measured using five different length rulers. The fractal dimensional increment (D*) was determined using a Richardson technique. A second experiment on three ceramics investigated whether there was a correlation between fracture toughness and the values of D* measured by an alternative technique using a confocal microscope. RESULTS AND SIGNIFICANCE: Fracture toughness was well correlated with D* using either technique.

Characteristics of period doubling in the human cone flicker electroretinogram.

Electroretinogram (ERG) responses of the cone system to a flickering stimulus can exhibit a cyclic variation in amplitude. This phenomenon of synchronous period doubling has been attributed to a nonlinear feedback mechanism within the retina that alters response gain. The aim of the present study was to investigate intersubject variability in period doubling in the ERG of the human cone system, and to assess the implications of this variability for signal processing within the retina. Period doubling was examined in a group of 12 visually normal subjects, using sinusoidal full-field flicker and harmonic analysis of the ERG waveforms. For all subjects, the ERG responses to 32-Hz flicker (a frequency commonly used clinically) were characterized by a harmonic component at the stimulus frequency and at higher harmonics that were integral multiples of the stimulus frequency, as expected. In addition, six of the subjects showed period doubling at 32 Hz, characterized by harmonic components at integer multiples of a frequency that was half the stimulus frequency (the subharmonic). However, the subharmonic itself did not exceed the noise level. These findings suggest that the subharmonic is generated prior to or at the site that produces the nonlinear higher harmonics of the ERG response, and that a subsequent band-pass filter attenuates this subharmonic. Examination of harmonic components of the subjects' ERG waveforms at other stimulus frequencies, as well as a cycle-by-cycle analysis of the ERG waveforms, suggested that individual differences in period doubling may be due to intersubject variation in the strength of the hypothesized feedback signal and/or the time constant of its decay.

Toxicity and dose-response studies of 1alpha-hydroxyvitamin D2 in a retinoblastoma xenograft model.

BACKGROUND: Although calcitriol (1,25-dihydroxycholecalciferol) and vitamin D(2) inhibit retinoblastoma growth in the athymic (nude) mouse xenograft (Y-79 cell line) model of retinoblastoma, they can cause severe toxicity. OBJECTIVE: To examine the toxicity of and dose-dependent response for the inhibition of tumor growth for 1alpha-hydroxyvitamin D(2) (1alpha-OH-D(2)), an analogue with reduced systemic toxicity, in the athymic Y-79 mouse model. METHODS: Mice were randomized into treatment and control groups for 5-week toxicity and dose-response studies. Treatment was via oral gavage 5 times per week. Dose-response studies measured tumor inhibition and drug serum levels. Tumor size and body weight were measured weekly together with various criteria for toxicity. Animals were euthanized at the end of the treatment period. Tumors and kidneys were harvested, and serum was analyzed for calcium and drug levels. RESULTS: Doses of 0.1 to 1.2 microg/d were selected on the basis of toxicity studies for the dose-response trial. Tumor weight and volume in the 0.2-microg and 0.3-microg doses were significantly lower than in controls. Mortality rates and kidney calcification in mice treated with doses of 0.1 to 0.3 microg were lower than those observed in studies of calcitriol and vitamin D(2). CONCLUSION: A vitamin D analogue, 1alpha-OH-D(2), inhibits tumor growth in this xenograft model of retinoblastoma with less toxicity than calcitriol and vitamin D(2).

Tumor-related epilepsy in children.

A 10-year retrospective review of 15 children with cerebral tumors and seizures was conducted to study the factors responsible for delay in the diagnosis of tumors and to assess outcome following surgery. Mean duration of seizures prior to surgery was 37 months. Ninety-three percent had no focal neurologic deficits. Head computed tomography was abnormal in 64%, whereas magnetic resonance imaging was abnormal in all patients. Electroencephalography showed focal abnormalities ipsilateral to the tumor in 73%. There was no surgical mortality. Eighty percent were seizure free or had rare seizures following surgery. Factors contributing to a delayed diagnosis of the brain tumor included a nonfocal neurologic examination and delay in obtaining an appropriate neuroimaging study. We believe that head magnetic resonance imaging should be the investigation of choice in partial epilepsies.

Perceptual organization of two-dimensional patterns.

The perceptual organization of image patterns is considered from 2 standpoints. First, a theoretical framework is presented from which computational models of perceptual organization can be constructed and tested. Second, a specific computational model for perceptual organization of line images is described. In this model, input images are first processed by a dense array of neurons that have properties consistent with recent analyses of single-neuron responses in primary visual cortex. Then, complex image structure is discovered by interleaved pattern-matching and grouping processes constrained by a generalized uniqueness principle. A series of 3-pattern grouping experiments was performed to test a restricted version of the model and to estimate critical parameters. Using the estimated parameters, an extended version of the model was tested by generating predictions for a series of "textbook" perceptual organization demonstrations.

Phase II evaluation of interferon-alpha-2a for progressive or recurrent craniopharyngiomas.

OBJECT: Craniopharyngiomas originate from the same cells as squamous cell skin carcinoma, which can be treated successfully with interferon-alpha (IFNalpha)-2a. The authors evaluated the activity and toxicity of systemic IFN in young patients with craniopharyngiomas. METHODS: Fifteen patients between the ages of 4.2 and 19.8 years who had progressive or recurrent craniopharyngiomas were enrolled in this study. Nine of these patients had never received external-beam radiation therapy. Therapy consisted of 8,000,000 U/m2 IFNalpha-2a administered daily for 16 weeks (induction phase) followed by the same dose three times per week for an additional 32 weeks (maintenance phase). Of the 12 patients who could be evaluated, radiological studies demonstrated a response to treatment in three with predominantly cystic tumors (one minor response, one partial response, and one complete response); one of these patients also showed improvement in visual fields. The size of the cystic component of the tumors often increased temporarily during the first several months of therapy. Three patients met the criteria for progressive disease during therapy. The median time to progression was 25 months. The need for radiation therapy in patients treated with IFN was delayed for 18 to 35 months (median 25 months) in six patients. All patients developed transient flulike symptoms shortly after receiving the first dose of IFN. Other toxicities (predominantly hepatic, neurological, and cutaneous) were seen in nine (60%) of the 15 patients during the first 8 weeks of treatment but resolved after temporary discontinuation and/or dose reduction. CONCLUSIONS: Interferon-alpha-2a is active against some childhood craniopharyngiomas; its toxicity precludes administration of high daily doses, and the optimum dose level and schedule remain to be defined.

Hydrocephalus in children: neurosurgical and neuroimaging concerns.

The neuroimaging of hydrocephalus from the perspective of the pediatric neurosurgeon is discussed. Processes with new developments in therapy and imaging are described, including congenital causes of hydrocephalus, unilateral hydrocephalus, trapped fourth ventricle, and benign external hydrocephalus.

Chiari III malformation treated with CSF diversion and delayed surgical closure.

Chiari III malformations are extremely rare hindbrain malformations that are associated with a high early mortality rate, or severe neurologic deficits in the survivors. The preferred treatment is early operative closure and CSF shunting. We report a case of a newborn infant with a Chiari III malformation with displacement of the brainstem and cerebellum into the cervical encephalocele which precluded immediate operative closure of the defect. Instead, a ventriculoperitoneal shunt was placed and the patient was followed with serial imaging studies. The child survived. The shunt allowed the brainstem and cerebellum to regress into the cervical spinal canal as the dilated cerebral aqueduct and fourth ventricle decompressed. A delayed closure of the cervical encephalocele was performed at 30 months of age. Cerebrospinal fluid diversion with delayed closure may be an option for large lesions.

Spontaneous spinal epidural hematoma in children.

Spontaneous spinal epidural hematoma is rare in children. It is usually confined to the dorsal epidural space. Ventral spontaneous spinal epidural hematoma (SSEH) is rarer, with only two previous reports. The authors present three children, two with dorsal and one with ventral spinal epidural hematoma, and review the literature. No etiology of the hematoma was found in the authors' patients and there was no history of trauma. A review of 24 patients of children younger than 18 years of age reported in the literature and the authors' three patients revealed that the cervicothoracic region was the most common site of SSEH, the mode of onset was frequently subacute, and there was no male preponderance as has been reported in adults. We found that the initial symptoms were often nonspecific, leading to a delay in diagnosis, especially in younger children. Follow-up data revealed that 15 of the 27 patients recovered completely, 11 had residual neurologic deficits, and one patient died. Irritability and neck pain with restricted movements of the cervical spine in an afebrile child may be early signs of SSEH and often precede onset of neurologic deficits by several hours to days. These signs should alert the clinician to consider spinal epidural hematoma and the need for urgent magnetic resonance imaging (MRI) of the spine for early diagnosis and treatment to minimize morbidity.

Cranio-orbital-temporal neurofibromatosis: are we treating the whole problem?

Cranio-orbital-temporal neurofibromatosis is an uncommon subtype of neurofibromatosis 1 characterized by pulsatile exophthalmos, orbital neurofibromas, sphenoid wing dysplasia, expansion of the temporal fossa, and herniation of the temporal lobe into the orbit. The cause of the sphenoid wing dysplasia is uncertain. Reconstruction of the sphenoid defect, separating the orbit and cranial vault, has been problematic because of resorption of bone grafts. This reports illustrates one potential cause of the sphenoid defect and a possible cause of the bone graft resorption.

Chiari I malformation: association with hypophosphatemic rickets and MR imaging appearance.

PURPOSE: To evaluate for an association between familial hypophosphatemic rickets (FHR) and Chiari I malformation (CM1). MATERIALS AND METHODS: Sixteen patients with FHR underwent magnetic resonance (MR) imaging of the cervicomedullary junction. Images were analyzed by three radiologists for cerebellar tonsillar ectopia, syringohydromyelia, calvarial bone thickening, a flat posterior fossa, and cervical spinal stenosis. Final diagnoses were made by means of consensus. Tonsillar ectopia of 4 mm indicated CM1. Subjects underwent neurologic examination and completed a questionnaire. Medical records were retrospectively reviewed. A two-sided Fisher exact test was used to test for independence between CM1 and bone thickening or ventriculomegaly. RESULTS: Seven subjects (44%) had CM1. The more severe the bone thickening, the more likely that a CM1 was present. Four subjects (25%) had cervical spinal stenosis. CONCLUSION: Findings indicate that CM1 is associated with FHR and that the primary abnormality in patients with CM1 is a small posterior fossa caused by a bony malformation.

Primary central nervous system malignant rhabdoid tumor: CT and MR appearance simulates a primitive neuroectodermal tumor.

Malignant rhabdoid tumor was originally described and is most commonly reported in the kidney [1-5]. A case of primary central nervous system malignant rhabdoid tumor is presented. The clinical and pathologic findings are presented and the computed tomography and magnetic resonance imaging findings are described.

Magnetic resonance imaging diagnosis of a cerebral aneurysm in an infant. Case report and review of the literature.

A posterior cerebral artery aneurysm presented as a seizure disorder in a 7-week-old infant. A small hemorrhage in the posterior thalamus was seen on CT scan. However, magnetic resonance imaging (MRI study) demonstrated an aneurysm and appropriate therapy was carried out. The incidence, natural history, etiology, and surgical treatment of these lesions are reviewed, and the usefulness of MRI in their diagnosis is emphasized.