A longitudinal environmental surveillance study for SARS-CoV-2 from the emergency department of a teaching hospital in Hong Kong.

BACKGROUND: Understanding factors associated with SARS-CoV-2 exposure risk in the hospital setting may help improve infection control measures for prevention. AIM: To monitor SARS-CoV-2 exposure risk among healthcare workers and to identify risk factors associated with SARS-CoV-2 detection. METHODS: Surface and air samples were collected longitudinally over 14 months spanning 2020-2022 at the Emergency Department (ED) of a teaching hospital in Hong Kong. SARS-CoV-2 viral RNA was detected by real-time reverse-transcription polymerase chain reaction. Ecological factors associated with SARS-CoV-2 detection were analysed by logistic regression. A sero-epidemiological study was conducted in January-April 2021 to monitor SARS-CoV-2 seroprevalence. A questionnaire was used to collect information on job nature and use of personal protective equipment (PPE) of the participants. FINDINGS: SARS-CoV-2 RNA was detected at low frequencies from surfaces (0.7%, N = 2562) and air samples (1.6%, N = 128). Crowding was identified as the main risk factor, as weekly ED attendance (OR = 1.002, P=0.04) and sampling after peak-hours of ED attendance (OR = 5.216, P=0.03) were associated with the detection of SARS-CoV-2 viral RNA from surfaces. The low exposure risk was corroborated by the zero seropositive rate among 281 participants by April 2021. CONCLUSION: Crowding may introduce SARS-CoV-2 into the ED through increased attendances. Multiple factors may have contributed to the low contamination of SARS-CoV-2 in the ED, including hospital infection control measures for screening ED attendees, high PPE compliance among healthcare workers, and various public health and social measures implemented to reduce community transmission in Hong Kong where a dynamic zero COVID-19 policy was adopted.

Influence of dietary carbohydrate level on endocrine status and hepatic carbohydrate metabolism in the marine fish Sparus sarba.

Silver sea bream, Sparus sarba, were fed two diets of different carbohydrate levels (2 and 20% dextrin) for 4 weeks, and the effects on organ indices, liver composition, serum metabolite and hormone levels and gene expression profile of key enzymes of carbohydrate metabolism in the liver were investigated. By using real-time PCR, mRNA expression levels of carbohydrate metabolic enzymes including glucokinase (GK, glycolysis), glucose-6-phosphatase (G6Pase, gluconeogenesis), glycogen synthase (GS, glycogenesis), glycogen phosphorylase (GP, glycogenolysis) and glucose-6-phosphate dehydrogenase (G6PDH, pentose phosphate pathway) in liver of sea bream have been examined, and it was found that high dietary carbohydrate level increased mRNA level of GK but decreased mRNA levels of G6Pase and GP. However, mRNA levels of GS and G6PDH were not significantly influenced by dietary carbohydrate. Silver sea bream fed high dietary carbohydrate had higher hepatosomatic index (HSI), liver glycogen and protein, but there were no significant changes in gonadosomatic index (GSI), serum glucose and protein level, as well as liver lipid and moisture level. Pituitary growth hormone (GH) and hepatic insulin-like growth factor I (IGF-I) transcript abundance were assayed by real-time PCR, and it was found that both parameters remained unchanged in fish fed different dietary carbohydrate levels. Serum triiodothyronine (T(3)) and thyroxine (T(4)) were not significantly affected by dietary carbohydrate levels, but lower serum cortisol level was found in fish fed high dietary carbohydrate level. These results suggest that silver sea bream is able to adapt to a diet with high carbohydrate content (up to 20% dextrin), the consumption of which would lead to fundamental re-organization of carbohydrate metabolism resulting in hepatic glycogen deposition.

Effects of growth hormone, insulin-like growth factor I, triiodothyronine, thyroxine, and cortisol on gene expression of carbohydrate metabolic enzymes in sea bream hepatocytes.

The present study investigated the regulatory effects of growth hormone (GH), human insulin-like growth factor I (hIGF-I), thyroxine (T(4)), triiodothyronine (T(3)) and cortisol, on mRNA expression of key enzymes involved in carbohydrate metabolism, including glucokinase (GK), glucose-6-phosphatase (G6Pase), glycogen synthase (GS), glycogen phosphorylase (GP) and glucose-6-phosphate dehydrogenase (G6PDH) in hepatocytes isolated from silver sea bream. Genes encoding GK, G6Pase, GS and GP were partially cloned and characterized from silver sea bream liver and real-time PCR assays were developed for the quantification of the mRNA expression profiles of these genes in order to evaluate the potential of these carbohydrate metabolic pathways. GK mRNA level was elevated by GH and hIGF-I, implying that GH-induced stimulation of GK expression may be mediated via IGF-I. GH was found to elevate GS and G6Pase expression, but reduce G6PDH mRNA expression. However, hIGF-I did not affect mRNA levels of GS, G6Pase and G6PDH, suggesting that GH-induced modulation of GS, G6Pase and G6PDH expression levels is direct, and occurs independently of the action of IGF-I. T(3) and T(4) directly upregulated transcript abundance of GK, G6Pase, GS and GP. Cortisol significantly increased transcript amounts of G6Pase and GS but markedly decreased transcript abundance of GK and G6PDH. These changes in transcript abundance indicate that (1) the potential of glycolysis is stimulated by GH and thyroid hormones, but attenuated by cortisol, (2) gluconeogenic and glycogenic potential are augmented by GH, thyroid hormones and cortisol, (3) glycogenolytic potential is upregulated by thyroid hormones but not affected by GH or cortisol, and (4) the potential of the pentose phosphate pathway is attenuated by GH and cortisol but unaffected by thyroid hormones.

Effect of extracellular osmolality and ionic levels on pituitary prolactin release in euryhaline silver sea bream (Sparus sarba).

In many euryhaline fish, prolactin (PRL) plays a key role in freshwater adaptation. Consistent with this function, the present study showed a remarkable reduction in pituitary PRL content of silver sea bream abruptly transferred to low salinity (6ppt). This reduction in pituitary PRL content followed closely the temporal changes in serum osmolality and ion levels. Serum osmolality, Na(+) and Cl(-) levels of silver sea bream abruptly transferred to hyposmotic salinity (6ppt) were markedly reduced 2h after the transfer. The decline in pituitary PRL content lagged behind the serum changes implying that reduction in pituitary PRL content is a response to the drop in serum ion levels and osmotic pressure. Silver sea bream pituitary cells were dispersed and exposed to a medium with reduced ion levels and osmolality in vitro, and PRL released from pituitary cells was significantly elevated. In hyposmotic exposed anterior pituitary cells, cell volume exhibited a 20% increase when exposed to a medium with a 20% decrease in osmolality. The enlarged pituitary cells did not shrink until the surrounding hyposmotic medium was replaced, a phenomenon suggesting an osmosensing ability of silver sea bream PRL cells for PRL secretion in response to a change in extracellular osmotic pressure. The decrease in pituitary PRL content in vivo and stimulated pituitary PRL release in vitro under reduced osmolality together suggest hyposmotic exposure triggers PRL release from the pituitary.

Trajectory of functional outcome and health status after moderate-to-major trauma in Hong Kong: A prospective 5 year cohort study.

BACKGROUND: Trauma care systems in Asia have been developing in recent years, but there has been little long-term outcome data from injured survivors. This study aims to evaluate the trajectory of functional outcome and health status up to five years after moderate to major trauma in Hong Kong. METHODS: We report the five year follow up results of a multicentre, prospective cohort from the trauma registries of three regional trauma centres in Hong Kong. The original cohort recruited 400 adult trauma patients with ISS ≥ 9. Telephone follow up was conducted longitudinally at seven time points, and the extended Glasgow Outcome Scale (GOSE) and Short-Form 36 (SF36) were tracked. RESULTS: 119 out of 309 surviving patients (39%) completed follow up after 5 years. The trajectory of GOSE, PCS and MCS showed gradual improvements over the seven time points. 56/119 (47.1%) patients reported a GOSE = 8 (upper good recovery), and the mean PCS and MCS was 47.8 (95% CI 45.8, 49.9) and 55.8 (95% CI 54.1, 57.5) respectively at five years. Univariate logistic regression showed change in PCS - baseline to 1 year and 1 year to 2 years, and change in MCS - baseline to 1 year were associated with GOSE = 8 at 5 years. Linear mixed effects model showed differences in PCS and MCS were greatest between 1-month and 6-month follow up. CONCLUSIONS: After injury, the most rapid improvement in PCS and MCS occurred in the first six to 12 months, but further recovery was still evident for MCS in patients aged under 65 years for up to five years.

Direct actions of cortisol, thyroxine and growth hormone on IGF-I mRNA expression in sea bream hepatocytes.

The present study aims to investigate potential regulatory effect of different growth-related hormones including growth hormone (GH), human insulin-like growth factor-I (hIGF-I), thyroxine (T(4)), triiodothyronine (T(3)) and cortisol, on insulin-like growth factor-I (IGF-I) mRNA expression of hepatocytes isolated from silver sea bream. By using real-time PCR, IGF-I mRNA expression profiles of hepatocytes in response to individual hormones were determined in vitro. Hepatocytes incubated with GH at concentrations of 10-1000 ng/mL showed significantly higher IGF-I expression, but the elevation was attenuated at high concentration of GH (1000 ng/mL). IGF-I expression remained unchanged in hepatocytes after incubation with hIGF-I. Hepatocytes incubated with T(4) at concentration of 1000 ng/mL exhibited a significant elevation in IGF-I expression, whereas no difference in IGF-I expression was demonstrated in hepatocytes after incubation with T(3). Upon incubation with cortisol (1-1000 ng/mL), IGF-I expression was significantly decreased in hepatocytes in a dose-dependent manner. Our study demonstrated that GH, T(4), and cortisol had direct modulatory effects on IGF-I expression in fish hepatocytes in vitro.

Circulating human leucine-rich α-2-glycoprotein 1 mRNA and protein levels to detect acute appendicitis in patients with acute abdominal pain.

BACKGROUND: Elevated levels of circulating plasma and urine leucine-rich-2-glycoprotein-1 (LRG1) protein has been found in patients with acute appendicitis (AA) and may be useful for diagnosis. This study aimed to investigate whether combined tests including circulating LRG1 mRNA levels improve the early diagnosis of AA. METHODS: Between December 2011 and October 2012, a prospective study was conducted on patients aged 18years or older presenting to the ED with acute abdominal pain (<7days of symptom onset). Levels of whole blood LRG1 mRNA and plasma LRG1 protein taken from these patients within 24h of arrival (mean 12.4h) were analyzed. The primary outcome was AA. RESULTS: Eighty-four patients (40 (47.6%) with AA and 44 (52.4%) without AA; mean age 35years; 41.6% males) were recruited. Median whole blood LRG1 mRNA and plasma LRG1 levels were higher in AA patients than in non-AA. Of 40 AA patients, 13 (32.5%) were diagnosed as complicated AA. In ROC analysis of LRG1 mRNA (normalized to GAPDH), LRG1 protein and Alvarado score for discriminating AA and non-AA, the areas under the curve (AUC) were 0.723, 0.742 and 0.805 respectively. The AUC of combination of normalized LRG1 mRNA, LRG1 protein and Alvarado score was 0.845. CONCLUSION: A combination of modified whole blood LRG1 mRNA levels, plasma LRG1 protein and Alvarado score at the ED may be useful to diagnose simple and complicated AA from other causes of abdominal pain.

Comparative pharmacology in the rat of ketamine and its two principal metabolites, norketamine and (Z)-6-hydroxynorketamine.

(Z)-6-Hydroxynorketamine (3), a secondary metabolite of the dissociative anesthetic agent ketamine (1), was synthesized, and its central nervous system (CNS) properties were compared to those of the parent drug and the primary metabolite, norketamine (2). Administration of compounds 1 and 2 to rats (40 mg/kg iv) produced general anesthesia and also led to marked increases in spontaneous locomotor activity during the postanesthetic recovery phase. These effects were of significantly longer duration with 1 than with 2. In contrast, the same dose of 3 produced neither general anesthesia nor CNS excitation, despite the fact that 3 entered brain tissue readily from the systemic circulation. It is concluded that the CNS effects of 1 are attenuated by metabolism to 2 and are abolished by subsequent hydroxylation to produce 3. Moreover, the results suggest that the desirable anesthetic properties of 1 and related arylcyclohexylamines may be inseparable from their ability to produce adverse postanesthetic emergence reactions.

A randomized, placebo-controlled trial of granulocyte colony-stimulating factor administration to newborn infants with neutropenia and clinical signs of early-onset sepsis.

OBJECTIVE: To determine whether recombinant human granulocyte colony-stimulating factor (G-CSF) administration: 1) accelerates production of neutrophils; 2) increases bone marrow stored and precursor neutrophils; and 3) is safe in newborn infants with neutropenia and clinical signs of early-onset sepsis. STUDY DESIGN: We randomized 20 infants with neutropenia and clinical signs of early-onset sepsis in the first 3 days of life to receive G-CSF (10 microg/kg/d) or placebo for 3 days. Entry criteria included neutropenia as defined by Manroe criteria, an elevated immature to total neutrophil ratio [(I/T) >/=0.25], and a requirement for ventilatory support. Cultures were obtained and antibiotics initiated on all study infants. Circulating absolute neutrophil count (ANC), I/T ratio, bone marrow neutrophil storage pool (NSP) and neutrophil proliferative pool (NPP), and plasma G-CSF concentrations were evaluated. Also, severity of illness as determined using the Score for Neonatal Acute Physiology (SNAP), morbidity, and mortality were recorded. RESULTS: Circulating ANC increased in both G-CSF and placebo recipients by day 1. Also, the I/T neutrophil ratio decreased in both G-CSF and placebo recipients. There were no significant differences in the ANC or I/T ratio between the two groups during the study period. Similarly, bone marrow NSP and NPP did not differ between G-CSF and placebo recipients at study entry or day 2. No differences were observed in the secondary outcome measures including severity of illness, morbidity, and mortality. CONCLUSIONS: Administration of recombinant G-CSF to infants with neutropenia and clinical signs of early-onset sepsis did not increase circulating ANC, or bone marrow NSP and NPP compared with placebo. No differences were observed between G-CSF and placebo recipients in severity of illness, morbidity, or mortality. No adverse effects of G-CSF administrations were noted.

Studies on the biotransformation of ketamine. II--Quantitative significance of the N-demethylation pathway in rats in vivo determined by a novel stable isotope technique.

In order to determine the fraction of an intravenous bolus dose of ketamine which is metabolized in vivo to the corresponding N-desmethyl compound, norketamine, a novel stable isotope technique was developed and applied to a study in rats. Co-injection of equimolar amounts of deuterium-labeled ketamine and unlabeled norketamine to four animals, followed by gas chromatographic/mass spectrometric analysis of both the administered compounds and deuterium-labeled norketamine in plasma, yielded pharmacokinetic data from which the fraction of the parent drug subjected to N-demethylation (fm) was calculated from AUC data to be 36.8 +/- 2.4%. It is concluded that this stable isotope co-administration technique represents a powerful approach to the determination of fm, in that the pharmacokinetics of the metabolite of interest, given as the preformed compound and generated in vivo, are determined simultaneously. This experimental design thus obviates the influence of time-dependent changes in metabolite clearance which may complicate the interpretation of studies performed using the classical cross-over design.

C-formylation in the presence of rat brain mitochondria of the 2,3,4,5-tetrahydropyridinium metabolite derived from the psychotomimetic drug phencyclidine.

The 1-(1-phenylcyclohexyl)-2,3,4,5-tetrahydropyridinium metabolite derived from the psychotomimetic agent phencyclidine [1-(1-phenylcyclohexyl)piperidine] is converted to 1-(phenylcyclohexyl)-1,2,3,4-tetrahydropyridine-5-carboxaldehyde in the presence of rat brain and liver mitochondria. The C-5 formylation of synthetic 1-(1-phenylcyclohexyl)-2,3,4,5-tetrahydropyridinium perchlorate by N5-formyltetrahydrofolic acid (folinic acid) suggests that this biotransformation is mediated by a transformylation process involving this N5- or the corresponding N10-formyltetrahydrofolic acid.

Chondroblastoma of the lumbar vertebra.

Chondroblastoma of the vertebra is a very rare condition. To our knowledge fewer than 20 cases have been reported in the world literature. We report a 54-year-old man with chondroblastoma of the fifth lumbar vertebra. The clinical and radiological aspects of the tumor are discussed, emphasizing the presence of an extraosseous mass suggestive of locally aggressive behavior.

Pharmacokinetic and deuterium isotope effect studies on the metabolism of formaldehyde and formate to carbon dioxide in rats in vivo.

The effect of deuterium substitution on the metabolism of formaldehyde and formate to carbon dioxide in vivo was examined. Four groups of male Sprague-Dawley rats were injected ip with carbon-14-labeled formaldehyde, formaldehyde-d2, sodium formate, or sodium formate-d at doses of 0.67 mmol/kg. Similar rates of labeled carbon dioxide exhalation were observed for the four groups of animals, the cumulative excretion of 14CO2 in breath reaching 68-71% of the theoretical value 12 hr after injection in all cases. Plots of amount remaining to be excreted showed that the metabolism was biexponential, with half-lives of approximately 0.4 and 3 hr for the two phases for each of the four compounds. Competitive experiments in which equimolar mixtures of CH2O with CD2O or HCO2- with DCO2- were injected also failed to reveal a substantial isotope effect, although the cumulative conversion of formate to carbon dioxide was significantly higher than that of its deuterated analog at four time points in the middle of the 8-hr mixed-isotope experiment. The data indicate that deuterium substitution has little or no effect on the rates and extents of in vivo oxidation of these 1-carbon species to carbon dioxide, although a small decrease of up to 10% in reactivity under the conditions employed cannot be excluded. The results support the use of carbon dioxide exhalation data in the measurement of deuterium isotope effects on oxidative demethylation reactions such as those that occur in the activation of the carcinogen, N-nitrosodimethylamine.

Nodular fasciitis: MRI appearance and literature review.

OBJECTIVE: To describe the MRI features of nodular fasciitis and to review the clinical, MRI and histologic aspects of the tumor. DESIGN AND PATIENTS: Three patients with biopsy-proven nodular fasciitis were selected for a retrospective study. A literature review was also carried out. RESULTS AND CONCLUSIONS: All the lesions appeared slightly hyperintense to skeletal muscle on T1-weighted images, and hyperintense on T2-weighted images with fat saturation [either frequency saturation or Short TI Inversion Recovery (STIR) sequences]. Two enhanced homogeneously after intravenous gadolinium, whereas the third showed heterogeneous enhancement with a nonenhancing area. Despite the difference in enhancing patterns, the histologic appearances of these lesions were similar. Our study shows that the MRI appearance of nodular fasciitis may not be related to the location of lesion. It is thought that the age of nodular fasciitis may reflect its gross morphology, and it is possible that the MRI and histologic appearances could correlate with the age of the lesion, but it would require a larger series to evaluate this concept.

Ruptured adrenocortical carcinoma as a cause of paediatric acute abdomen.

Adrenocortical carcinoma (ACC) is rare in children. Its presentation is usually related to hormonal activity of the tumour. We report a case of childhood ACC that presented as an acute abdomen due to tumour rupture. This is the first reported case of a ruptured ACC as a cause of paediatric acute abdomen.