False-negative real-time polymerase chain reaction tests in COVID-19 patients: an epidemiological analysis of 302 patients.

OBJECTIVES: Patients who arrive at the emergency department (ED) with COVID-19, who test negative at the first real-time polymerase chain reaction (RT-PCR), represent a clinical challenge. This study aimed to evaluate if the clinical manifestation at presentation, the laboratory and imaging results, and the prognosis of COVID-19 differ in patients who tested negative at the first RT-PCR compared with those who tested positive and also to evaluate if comorbid conditions patient-related or the period of arrival are associated with negative testing. STUDY DESIGN: We retrospectively collected clinical data of patients who accessed the ED from March 1 to May 15, 2020. METHODS: We compared clinical variables, comorbid conditions, and clinical outcomes in the two groups by univariate analysis and logistic regression. RESULTS: Patients who tested negative at the first RT-PCR showed a higher prevalence of cardiopathy, immunosuppression, and diabetes, as well as a higher leukocyte and lower lymphocyte counts compared with patients who tested positive. A bilateral interstitial syndrome and a typical pattern at computed tomography scan were prevalent in the test-negative group. Test-negative patients were more likely to be admitted to the hospital but less likely to need admission in a high level of care ward. The false-negative rate increased from March to May. CONCLUSION: False-negative RT-PCR COVID-19 patients present a similar spectrum of symptoms compared with positive cohort, but more comorbidities. Imaging helps to identify them. True positives had a higher risk of serious complications.

Recombinant tissue plasminogen activator to restore catheter patency: efficacy and safety analysis from a multihospital NICU system.

OBJECTIVE: In 2001, the US Food and Drug Administration approved recombinant tissue plasminogen activator (alteplase, Cathflo Activase) to reestablish patency of central catheters occluded, presumably, by a fibrin clot. We conducted a multicenter quality improvement study to determine the value of this procedure in our Neonatal Intensive Care Unit (NICUs), including analyses of efficacy, safety and costs. STUDY DESIGN: We conducted a retrospective quality analysis of neonates in level III NICUs, who received alteplase for the purpose of reestablishing patency of occluded central catheters. RESULTS: Alteplase was administered to 169 neonates, each given one to four doses, totaling 205 episodes of administration. The most common type of catheter where alteplase was used was percutaneously inserted central catheter (PICC) lines (78% of uses), 8% were umbilical venous catheters (UVCs), 6% arterial lines, 5% chest tubes and 3% other catheters. Postnatal age at first dose ranged from 0 to 132 days (median, 12); dosed patients were 22 to 41 weeks gestation at birth (median, 31). Fifty-eight percentage of administrations restored catheter function. Success was more likely at younger postnatal age (10±2 days old in successful vs 14±1 days in unsuccessful treatments; P=0.023). Seventy-two percentage of the re-canalized catheters remained functional until they were no longer needed (2 to 30 days later). Nine percentage of episodes were treated with a second dose 1 to 17 days later for re-occlusion and 50% of those were successful. Bleeding consequences were identified in only one case, where three separate lines were treated (chest tube, PICC and UVC) within a 6-h period. Costs to the health system of doses, minus savings to the system by not needing to replace lines, averaged a net of $34 per dose. CONCLUSIONS: The apparent safety and favorable value analysis prompted us to develop a consistent approach to alteplase usage in the Intermountain Healthcare NICUs, using the data in this report to standardize the guidelines across our health system.

Coping with challenging behaviours of children with autism: effectiveness of brief training workshop for frontline staff in special education settings.

BACKGROUND: The present study examined the effectiveness of three staff training elements: psychoeducation (PE) on autism, introduction of functional behavioural analysis (FBA) and emotional management (EM), on the reaction of challenging behaviours for frontline staff towards children with autism in Hong Kong special education settings. METHODS: A sample of 311 frontline staff in educational settings was recruited to one of the three conditions: control, PE-FBA and PE-FBA-EM groups. A total of 175 participants completed all three sets of questionnaires during pre-training, immediate post-training and 1-month follow-up. RESULTS: Findings showed that the one-session staff training workshop increased staff knowledge of autism and perceived efficacy but decrease helping behavioural intention. CONCLUSIONS: In spite of the limited effectiveness of a one-session staff training workshop, continued staff training is still necessary for the improvement of service quality. Further exploration on how to change emotion response of staff is important.

Expired nitric oxide as a marker for childhood asthma.

Expression of the inflammatory isoform of the enzyme nitric oxide synthase (NOS) is increased in airway-lining cells of patients with asthma. The NOS product nitric oxide (NO.) was measured in the expired gas of children with asthma. Vital capacity expirates from 21 control subjects and 13 subjects with asthma were assayed by chemiluminescence. Measurements were highly reproducible (coefficient of variation, 2.6% +/- 1.1%) and did not vary with age, sex, height, or weight. Patients with asthma had mean NO. levels (16.3 parts per billion) that were more than threefold higher than those of control subjects (5.05 ppb; p < 0.001). Expired NO. decreased as airflow obstruction improved during corticosteroid treatment (r2 = 0.77; n = 7; p < 0.001) but remained higher than normal (13.5 ppb; n = 5; p < 0.01) even after airflow obstruction resolved. We demonstrate the use of a reproducible test for asthma in children that is independent of measures of airflow obstruction. We speculate that expired NO assays may prove to be a more sensitive measure of childhood asthma than spirometry.

Contribution of neurons born during embryonic, juvenile, and adult life to the brain of adult canaries: regional specificity and delayed birth of neurons in the song-control nuclei.

Neurogenesis occurs in adult song birds, which suggests that neurons born after hatching may contribute to histogenesis and plasticity of the avian brain. However, little is known about the overall contribution to the mature brain of neurons born in juveniles and adults, and how this process affects different regions of the avian brain. In fact, studies of the histogenesis of the avian forebrain have made the classical assumption that neuronal birth ends before hatching. Here we determined the contribution of neurons born before and after hatching to different regions throughout the adult canary brain. Male canaries were injected with [3H]-thymidine at different times during embryonic, juvenile, and adult life. The position of labeled neurons was mapped in parasagittal brain sections. Because all birds were killed as adults, results indicate the time of birth of neurons that survived to adulthood in different structures of the avian brain. Injection at embryonic day (E) 5 or E9 resulted in labeled neurons in all regions of the neuroaxis. The vast majority of neurons outside of the telencephalon were born before E9. One exception was a discrete region in the dorsal thalamus, a part of the song-control circuit, where neurons continued to be born after E9. Most regions of the telencephalon had a high proportion of its neurons labeled by the embryonic injections. In particular, archistriatum, anterior neostriatum, and the hippocampus had most of their neurons labeled before hatching. This indicates that many of the telencephalic neurons born in the embryo are long lived and are not replaced by other neurons that continue to be added to the telencephalon after hatching. Neurons labeled by [3H]-thymidine injections after hatching were restricted to the telencephalon and contributed importantly to many regions. In particular, the avian striatum (lobus parolfactorius, LPO) received a large number of its neurons during the first 20 days of life, but continued to incorporate new neurons throughout juvenile and adult life. Neurons continued to be added to the telencephalon of adults (even in 4-year-old birds). The distribution of labeled neurons after [3H]-thymidine injections in adults was similar to that observed in latter stages of juvenile development. The contribution of neurons born at different ages from embryonic development to adulthood varied among different anatomical subdivisions of the canary brain. this could, in part, explain differences in the cytoarchitecture and plasticity between brain regions. Neurogenesis after hatching may allow the modification of selected brain circuits as the bird matures and ages.

High vocal center growth and its relation to neurogenesis, neuronal replacement and song acquisition in juvenile canaries.

It is generally thought that most circuits of the adult central nervous system (CNS) are sculpted, in part at least, by selective elimination of some of the neurons present in an initial overabundant set. In this scenario, the birth of neurons precedes the period when brain functions, such as learning, first occur. In contrast to this form of brain assembly, we describe here the delayed development of the high vocal center (HVC) and one of its efferent pathways in canaries. The retrograde tracer Fluoro-Gold (FG) was injected into one of HVC's two efferent targets, the nucleus robustus archistriatalis (RA), to define the boundaries of HVC. The HVC grows markedly between 1 and 4 months, invading neighboring territories of the caudal telencephalon. During this same period, 0.43%-0.64% of the HVC neurons present at 1 year of age are labeled per day of [3H]-thymidine injection. [3H]-Thymidine labeling is a marker of cell birth, and during the first 4 months HVC neuron number increases, probably accounting for part of the HVC growth observed. Thereafter, the number of HVC neurons remains constant, but neuronal birth persists. We infer from this that neuronal replacement starts as early as 4 months after hatching and perhaps before then. About half of the neurons born after posthatching day 10 grow an axon to RA to form the main efferent pathway exiting from HVC. HVC growth, neurogenesis, axogenesis, and the observed replacement of neurons happen during the period of juvenile vocal learning. However, the recruitment of neurons that are still present at 1 year shows no particular inflections corresponding to the various stages in song learning, and continues at essentially the same rate after the more stereotyped adult song has been acquired. We suggest that a combination of neurogenesis and neuronal replacement provides unique advantages for learning.

Cresyl violet: a red fluorescent Nissl stain.

Cresyl violet is widely used by neurobiologists to visualize Nissl substance in bright-field microscopy. Here we describe a method for using this dye as a red fluorescent Nissl stain. Unlike the bright-field staining technique, fluorescent cresyl is compatible with other fluorescent dyes and tracers, such as fluorescein, Fluoro-Gold and Fast Blue. The procedure requires only minor modifications of routine bright-field cresyl staining, the most significant being dilution of the stain. Thus, fluorescent red cresyl violet is simple to implement and may be of general use in fluorescence microscopy.

Song learning in birds: the relation between perception and production.

The vocal control system of oscine songbirds has some perplexing properties--e.g. laterality, adult neurogenesis, neuronal replacement--that are not predicted by common views of how vocal learning takes place. Similarly, we do not understand the relation between the direct pathway for the control of learned song and the recursive pathway necessary for song learning. Some of the paradoxes of the vocal system of birds may disappear once the relation between the perception and production of learned vocalizations is better understood. To some extent, perception and production may be two closely related states of a same system.

Monoclonal antibodies specific for human IgE and their clinical applications.

By applying the hybridoma technique, two mouse anti-human Immunoglobulin E (IgE) monoclonal antibodies, designated as E17-58 and E20-62, were generated and characterized. E17-58 was a murine IgG2b with an affinity constant of 4 x 10(8)l/mole. E20-62 was a murine IgG1 with an affinity constant of 1 x 10(8) l/mole. These two antibodies recognized different antigenic determinants specific to the IgE molecule. They were used in combination to quantify the total serum IgE level of forty-nine persons. Data obtained correlated highly with that obtained by using the Pharmacia PRIST Kit (r = 0.91). E17-58 was also used to detect the anti-Aspergillus specific IgE of twenty-one atopic patients by a radioimmunosorbent test. The positive rate detected correlated very well with the skin test (p less than 0.05). In addition, in the Western blot system, these monoclonal antibodies were capable of identifying IgE binding components of crude allergen extracts. Extracts from pollens of Bermuda grass were evaluated, and a new major allergenic component with a molecular weight of 40 kd was identified.

[A preliminary study for cellular, albumin and immunoglobulin components of bronchoalveolar lavage fluid in normal control, pulmonary T.B. and malignant lung diseases].

Bronchoalveolar lavage (BAL) is a new diagnostic tool which could be applied repeatedly to investigate the nature of lesion in pulmonary diseases. To evaluate the clinical significance of the difference in immunoglobulin content for the differential diagnosis between benign and malignant pulmonary diseases, we performed bronchoalveolar lavage for 64 patients. They included 12 patients with bronchogenic carcinoma, 12 patients with pulmonary tuberculosis, 20 patients with benign non-specific bronchopulmonary diseases (these including 6 patients with pneumoconiosis, 6 patients with bronchietasis, 2 patients with paraquate intoxication, 6 patients with pneumonia) and 20 healthy persons as of the control group. We analyzed the following items: (1) cell count (2) differential count (3) protein content (4) immunoglobulin content. The results showed that there were increase in PMN cells in paraquate intoxication, pnuenmonia and bronchiectasis. While there was lymphocytosis in pulmonary tuberculosis. In comparison with the control group, there was elevation of statistical significance in the IgA/Albumin ratio in bronchogenic carcinoma and pulmonary tuberculosis. Although the IgG/Albumin ratio would be elevated with statistical significance among a variety of pulmonary diseases, it was particularly high in pulmonary tuberculosis. In contrast, the IgA/IgG ratio was significantly increased only in bronchogenic carcinoma. In conclusion, there were differences in the cell number, differential cell count, protein content and immunoglobulin content among various pulmonary diseases. It may be useful in making differential diagnosis between benign and malignant pulmonary disease and the prediction of prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)