Adapting the modified barium swallow: modifications to improve safety in the setting of airborne respiratory illnesses like COVID-19.

No guidance exists on how to safely perform modified barium swallows (MBS) in the midst of the COVID-19 pandemic or other communicable airborne respiratory infections (C-ARI). MBS has the potential to become an aerosol generating procedure (AGP) as it may trigger a cough or necessitate suctioning which may result in transmission of C-ARI putting patients and health care workers at risk. Regulations and best practices from international and US governmental and commercial agencies were reviewed. This review led to the multidisciplinary development of best practices of the safety measures and structural requirements to avoid transmission of SARS-CoV-2 or other C-ARIs when performing MBS. Implementation of these best practices resulted in structural changes to the fluoroscopy suite and protocol workflows. This enabled patients with COVID-19 to undergo MBS while maintaining patient and staff safety including mitigation of potential risk of onward transmission of SARS-CoV-2 to other patients. With proper modifications, MBS can be safely performed on patients with C-ARI such as COVID-19 while maintaining patient and health care worker (HCW) safety.

Searching for cognitive enhancement in the Morris water maze: better and worse performance in D-amino acid oxidase knockout (Dao(-/-)) mice.

A common strategy when searching for cognitive-enhancing drugs has been to target the N-methyl-d-aspartate receptor (NMDAR), given its putative role in synaptic plasticity and learning. Evidence in favour of this approach has come primarily from studies with rodents using behavioural assays like the Morris water maze. D-amino acid oxidase (DAO) degrades neutral D-amino acids such as D-serine, the primary endogenous co-agonist acting at the glycine site of the synaptic NMDAR. Inhibiting DAO could therefore provide an effective and viable means of enhancing cognition, particularly in disorders like schizophrenia, in which NMDAR hypofunction is implicated. Indirect support for this notion comes from the enhanced hippocampal long-term potentiation and facilitated water maze acquisition of ddY/Dao(-) mice, which lack DAO activity due to a point mutation in the gene. Here, in Dao knockout (Dao(-/-) ) mice, we report both better and worse water maze performance, depending on the radial distance of the hidden platform from the side wall of the pool. Dao(-/-) mice displayed an increased innate preference for swimming in the periphery of the maze (possibly due to heightened anxiety), which facilitated the discovery of a peripherally located platform, but delayed the discovery of a centrally located platform. By contrast, Dao(-/-) mice exhibited normal performance in two alternative assays of long-term spatial memory: the appetitive and aversive Y-maze reference memory tasks. Taken together, these results question the proposed relationship between DAO inactivation and enhanced long-term associative spatial memory. They also have generic implications for how Morris water maze studies are performed and interpreted.

Alterations in spatial memory and anxiety in the MAM E17 rat model of hippocampal pathology in schizophrenia.

Adult rats exposed to methylazoxymethanol acetate (MAM) at embryonic day 17 (E17) display robust pathological alterations in the hippocampus. However, discrepancies exist in the literature regarding the behavioural effects of this pre-natal manipulation. Therefore, a systematic assessment of MAM E17-induced behavioural alterations was conducted using a battery of dorsal and ventral hippocampus-dependent tests. Compared to saline controls, MAM E17-treated rats displayed deficits in spatial reference memory in both the aversive hidden platform watermaze task and an appetitive Y-maze task. Deficits in the spatial reference memory watermaze task were replicated across three different cohorts and two laboratories. In contrast, there was little, or no, effect on the non-spatial, visible platform watermaze task or an appetitive, non-spatial, visual discrimination task, respectively. MAM rats were also impaired in the spatial novelty preference task which assesses short-term memory, and displayed reduced anxiety levels in the elevated plus maze task. Thus, MAM E17 administration resulted in abnormal spatial information processing and reduced anxiety in a number of hippocampus-dependent behavioural tests, paralleling the effects of dorsal and ventral hippocampal lesions, respectively. These findings corroborate recent pathological and physiological studies, further highlighting the usefulness of MAM E17 as a model of hippocampal dysfunction in at least some aspects of schizophrenia.

Dissociations within short-term memory in GluA1 AMPA receptor subunit knockout mice.

GluA1 AMPA receptor subunit knockout mice display a selective impairment on short-term recognition memory tasks. In this study we tested whether GluA1 is important for short-term memory that is necessary for bridging the discontiguity between cues in trace conditioning. GluA1 knockout mice were not impaired at using short-term memory traces of T-maze floor inserts, made of different materials, to bridge the temporal gap between conditioned stimuli and reinforcement during appetitive discrimination tasks. Thus, different aspects of short-term memory are differentially sensitive to GluA1 deletion. This dissociation may reflect processing of qualitatively different short-term memory traces. Memory that results in performance of short-term recognition (e.g. for objects or places) may be different from the memory required for associative learning in trace conditioning.

Pre-existing major depression predicts in-hospital cardiac complications after acute myocardial infarction.

BACKGROUND: Depression (MDD) and anxiety have been associated with negative long-term outcomes among patients with acute myocardial infarction (MI). OBJECTIVE: The objective of the study was to determine whether MDD and anxiety preceding MI were associated with in-hospital post-MI cardiac complications. METHOD: Subjects (N=129) underwent psychiatric interviews within 72 hours of MI and were evaluated for five in-hospital cardiac complications (recurrent ischemia, ventricular arrhythmia, ventricular arrhythmia requiring intervention, congestive heart failure, and reinfarction). RESULTS: Current (pre-MI) MDD was a significant and independent predictor of all complications except recurrent ischemia on multivariate regression analysis. In contrast, pre-MI anxiety was not associated with complications. CONCLUSION: These findings underscore the importance of identifying and treating MDD in post-MI patients and those at risk for MI.

Use of the Health Care for the Homeless Program services and other health care services by homeless adults.

This study examined factors associated with the use of the Health Care for the Homeless Program and other health care services by homeless adults. A total of 941 homeless adults were identified in 52 soup kitchens in U.S. communities. Descriptive statistics and logistic regression models were applied. Among homeless adults, having dental problems was the most robust factor associated with their use of Health Care for the Homeless Program services (odds ratio [OR] = 2.50, 95 percent confidence interval [CI] = 1.44-4.32). Among homeless adults who did not visit Health Care for the Homeless Program services during last six months, the number of emergency room visits was the most powerful factor associated with their use of other health care services (OR = 1.15, 95 percent CI = 1.05-1.26). The results of the study can help health care providers better serve homeless adults to meet their health needs.

Fatal aspiration pneumonia during transition from donepezil to rivastigmine.

OBJECTIVE: To report a case of fatal aspiration pneumonia in a patient shortly after initiation of rivastigmine and discontinuation of donepezil, with no washout period between therapies. CASE SUMMARY: An 83-year-old white man presented to the emergency department in respiratory distress (O2 saturation 70%; RR 44 breaths/min) secondary to aspiration. He had started rivastigmine 1.5 mg twice daily that same day. The patient had been previously treated with donepezil 10 mg/d, and there was no washout period. He was intubated due to worsening respiratory status and was transferred to the cardiac care unit. He then became hypotensive and required dopamine and fluid support. Brief bronchoscopy revealed food particles in the lower airways and bile-stained secretions. Intubation was notable for the large amount of secretions. The patient died approximately 27 hours after presentation to the emergency department. Blood and sputum cultures were subsequently positive for Haemophilus influenzae. DISCUSSION: Cholinesterase (ChE) inhibitors approved for treatment of Alzheimer disease are associated with nausea and vomiting in a sizable percentage of patients, ranging from 5% to 31% in clinical trials. Most of these adverse events occur during the initiation/titration phase of therapy. An additive risk of adverse events may be expected with coadministration of ChE inhibitors or cholinergic agents or, potentially, with an inadequate washout period between such agents. Review of MEDLINE (1966-July 2002) and International Pharmaceutical Abstracts (1970-July 2002) failed to identify any previous reports of aspiration with rivastigmine or donepezil. CONCLUSIONS: A washout period should be considered when switching between ChE inhibitors to minimize the risk of vomiting and aspiration.

Development of Contamination-Free Restriction Fragment Length Polymorphism Probes for the Obligate Biotroph Peronospora tabacina, an Oomycete Causing Blue Mold of Tobacco.

ABSTRACT Peronospora tabacina is an obligately parasitic oomycete that causes blue mold, a devastating disease of tobacco. Genetic studies of this pathogen have been hampered by the lack of molecular markers. We generated a set of molecular markers for P. tabacina by collecting sporangiospores from infected tobacco leaves, extracting spore DNA, and cloning it in a plasmid vector. The resulting clones were then used to probe DNA from a collection of P. tabacina isolates to survey for polymorphisms. Most probes gave unexpected hybridization patterns with signal intensities that varied significantly from one DNA sample to another or between different DNA preparations of the same isolate. These results indicated that certain DNA preparations contained DNA from a source other than P. tabacina, which in turn suggested that some probes might have been derived from contaminating organisms present in the spore suspensions. Therefore, we characterized the inserts of several recombinant plasmids to determine their origins. Sequence analysis revealed that several of the inserts encoded peptides with similarity to bacterial proteins, suggesting that they were derived from bacterial contaminants. Of the remaining clones, five exhibited similarity to retroelements, one resembled eukaryotic helicase genes, and nine had no similarity to sequences in the databases. These were postulated to be true P. tabacina DNA clones. Verification of the origin of each probe was achieved by filtering a spore suspension, extracting DNA from the retentate and filtrate, and probing Southern blots of these DNA samples. These experiments confirmed the probe origins predicted by sequence analysis, resulting in the generation of 20 different restriction fragment length polymorphism probes that are specific for P. tabacina DNA. These probes should enable identification of reliable genetic markers for population studies of the blue mold organism.

Genetic Uniformity Among Isolates of Peronospora tabacina, the Tobacco Blue Mold Pathogen.

ABSTRACT As a first step toward analysis of genetic variation and population structure in Peronospora tabacina, we used a collection of random genomic DNA fragments to survey for restriction fragment length polymorphisms (RFLPs) in DNA from a collection of isolates from Kentucky and other tobacco-growing regions of the United States. Also included in the study were isolates from the wild tobacco species, Nicotiana repanda, and from ornamental tobacco, N. alata. In a preliminary survey using DNA from 10 pathogen isolates, no polymorphisms were detected at six single-copy DNA loci using 22 probe-enzyme combinations. Moderately repetitive and highly repetitive regions of the genome were also remarkably similar between isolates, with only 6 of 15 different probes identifying genetic differences. Some of the polymorphic probes were then used to analyze a larger collection of isolates, most of which were from Kentucky. This resulted in the identification of very few additional polymorphisms, indicating that the population of P. tabacina that infects the Kentucky tobacco crop is genetically very homogeneous. The low level of polymorphism detected in this study overall, suggests that genetic variability may be lacking in P. tabacina populations throughout the United States. Two of the RFLP markers gave hybridization patterns that were consistent with P. tabacina being diploid. Frequencies of alleles at these loci and linkage disequilibrium between different marker loci indicated that genetic recombination does not occur frequently in the pathogen population. DNA polymorphisms that were identified in this study enabled us to differentiate the pathogen population into at least 10 haplotypes. One isolate was analyzed in detail and was shown to be genetically stable through several rounds of single-spore isolation and through several pathogenic cycles.