The Use of Bi-Nasal Prongs for Delivery of Non-Invasive Ventilation to Foals.

Non-invasive ventilation (NIV) is a method of providing respiratory support without the need for airway intubation. The current study was undertaken to assess tolerance to bi-nasal prongs and NIV in healthy, standing, lightly sedated foals. Bi-nasal prongs were well tolerated by foals, remaining in place for the allocated five minutes in four of six unsedated foals and, subsequently, in five of six lightly sedated foals. All foals tolerated NIV through bi-nasal prongs, although increasing airway pressures were associated with increases in inspiratory volume, duration of inspiration and air leakage in most foals. These changes preceded discontinuation/intolerance of NIV on the basis of behaviour changes consistent with discomfort. Increased circuit leakage was associated with reduced return of expired air to the ventilator and increasing disparity between inspiratory and expiratory times and tidal volumes. The study results suggest that bi-nasal prongs might be suitable for NIV but that design or fitting requires further optimization and that behaviour and ventilator variables should be monitored to assess patient tolerance of the procedure.

Depressive Symptoms and Its Correlates in Undergraduates during the COVID-19 Pandemic.

INTRODUCTION: This study aims to investigate depressive symptoms and its association with resilience, pessimistic bias of COVID-19, lifestyle changes, and family conflicts among undergraduates in a Hong Kong university. METHODS: 1020 undergraduates in The University of Hong Kong completed the online survey between May and August 2020. Severity of depressive symptoms was assessed using the Patient Health Questionnaire-9. Resilience was assessed using the Connor-Davidson Resilience Scale. Pessimistic bias was assessed using two questions on the perceived risks of contracting COVID-19 and of dying from COVID-19. Changes in lifestyles and the presence of family conflicts were measured. Multivariable and mediation analyses were performed to examine association of depressive symptoms with other variables. RESULTS: 61.7% of the respondents reported having mild to severe depressive symptoms. 18.5% of the variance in depressive symptoms was explained by resilience, pessimistic bias, changes in the frequency of sleep, studying at home, and family conflict. Pessimistic bias partially mediated the association between resilience and depressive symptoms. CONCLUSION: The proportion of undergraduates with mild to severe depressive symptoms during the pandemic was high. Measures to reduce family conflict, maintain healthy daily habits, adjust pessimistic bias, and enhance resilience may help to improve the mental well-being of undergraduates during the pandemic.

Mental Health Youth Ambassador Programme for Anti-Stigma Among Secondary Students in Hong Kong: a Pilot Study.

OBJECTIVES: To evaluate the Mental Health Youth Ambassador Programme between 2016 and 2019 in terms of participants' improvement in attitudes towards individuals with depression or psychosis. METHODS: This anti-stigma programme was provided to secondary students (form 3 and above) and comprised three levels. Level 1 involved attending lectures about mental health; level 2 and level 3 involved social contact with persons-in-recovery. Students' attitudes towards those with depression and those with psychosis were assessed at baseline and after completion of each level of programme using the Chinese version of the Social Distance Scale. RESULTS: Only 25 students who were assessed at all four time points were included in analysis. The mean Social Distance Scale scores for attitudes towards depression and psychosis improved significantly across all time points. Specifically, significant improvement occurred after completion of level 2 and level 2 but not after completion of level 1. CONCLUSION: Social contact with people with mental illness (rather than attending lectures about mental health) contributed significantly to the improvement in students' attitude towards depression and psychosis. With the positive preliminary results, the Mental Health Youth Ambassador Programme should be extended to more students.

Development of a NanoBRET assay to validate inhibitors of Sirt2-mediated lysine deacetylation and defatty-acylation that block prostate cancer cell migration.

Sirtuin2 (Sirt2) with its NAD+-dependent deacetylase and defatty-acylase activities plays a central role in the regulation of specific cellular functions. Dysregulation of Sirt2 activity has been associated with the pathogenesis of many diseases, thus making Sirt2 a promising target for pharmaceutical intervention. Herein, we present new high affinity Sirt2 selective Sirtuin-Rearranging Ligands (SirReals) that inhibit both Sirt2-dependent deacetylation and defatty-acylation in vitro and in cells. We show that simultaneous inhibition of both Sirt2 activities results in strongly reduced levels of the oncoprotein c-Myc and an inhibition of cancer cell migration. Furthermore, we describe the development of a NanoBRET-based assay for Sirt2, thereby providing a method to study cellular target engagement for Sirt2 in a straightforward and accurately quantifiable manner. Applying this assay, we could confirm cellular Sirt2 binding of our new Sirt2 inhibitors and correlate their anticancer effects with their cellular target engagement.

Cognition and cerebrovascular function in primary hyperparathyroidism before and after parathyroidectomy.

PURPOSE: There are cognitive changes in primary hyperparathyroidism (PHPT) that improve with parathyroidectomy, but the mechanism of cognitive dysfunction has not been delineated. We assessed if cerebrovascular function is impaired in PHPT, improves post-parathyroidectomy and is associated with PTH level and cognitive dysfunction. METHODS: This is an observational study of 43 patients with mild hypercalcemic or normocalcemic PHPT or goiter. At baseline, cerebrovascular function (dynamic cerebral autoregulation and vasomotor reactivity) by transcranial Doppler and neuropsychological function were compared between all three groups. A subset underwent parathyroidectomy or thyroidectomy, and was compared 6 months post-operatively. RESULTS: Mean cerebrovascular and neuropsychological function was normal and no worse in PHPT compared to controls preoperatively. Higher PTH was associated with worse intracerebral autoregulation (r = - 0.43, p = 0.02) and worse cognitive performance on some tests. Post-parathyroidectomy, mood improved significantly, but changes did not differ compared to those having thyroidectomy (p = 0.84). There was no consistent improvement in cognition or change in vascular function in either surgical group. CONCLUSIONS: Although higher PTH was associated with worse intracerebral autoregulation, cerebrovascular function, cognition and mood were normal in mild PHPT. PTX did not improve vascular or cognitive function. The observed improvement in mood cannot be clearly attributed to PTX. Notwithstanding the small sample size, the results do not support changing current criteria for parathyroidectomy to include cognitive complaints. However, the associations between PTH, cognition and cerebral autoregulation merit future studies in those with more severe hyperparathyroidism.

Investigation of the antibacterial activity of Ag-NPs conjugated with a specific antibody against Staphylococcus aureus after photoactivation.

AIM: This work reports a new method for the use of lasers for the selective killing of bacteria targeted using light-absorbing Silver nanoparticles (Ag-NPs) conjugated with a specific antibody against the Gram-positive bacterium Staphylococcus aureus (S. aureus). METHODS AND RESULTS: Ag-NPs were synthesized using a chemical reduction method and characterized with respect to their surface plasmon resonance, surface morphology via transmission electron microscopy (TEM) and dynamic light scattering (DLS). The bacterial surface was targeted using 20 nm Ag-NPs conjugated with an anti-protein A antibody. Labelled bacteria were irradiated with blue visible laser at 2·04 W/cm2 . The antibacterial activity of functionalized Ag-NPs was investigated by fluorescence microscopy after irradiation, and morphological changes in S. aureus after laser treatment were assessed using scanning electron microscopy (SEM). The laser-irradiated, functionalized Ag-NPs exhibited significant bactericidal activity, and laser-induced bacterial damage was observed after 10 min of laser irradiation against S. aureus. The fluorescence microscopic analysis results supported that bacterial cell death occurred in the presence of the functionalized Ag-NPs. CONCLUSIONS: The results of this study suggest that a novel method for the preparation of functionalized nanoparticles has potential as a potent antibacterial agent for the selective killing of resistant disease-causing bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that Ag-NPs functionalized with a specific antibody, could be used in combination with laser radiation as a novel treatment to target resistant bacterial and fungal pathogens with minimal impact on normal microflora.

Using a checklist to assess if a child undergoing MRI needs general anaesthesia.

AIM: To assess if a child-assessment checklist covering tasks children are expected to perform during magnetic resonance imaging (MRI) can determine whether the child requires general anaesthesia (GA) during MRI. MATERIALS AND METHODS: In this institute review board approved study, children who underwent MRI from September 2016 to June 2017 at KK Women's and Children's Hospital were assessed using a checklist by a research assistant before their examination. During this project, the checklist had no influence on whether the MRI was performed under GA or not. The checklist consisted of five items rated on a binary scale assessing the child's behaviour. Binary logistic regression was performed separately on the overall sample and for a subset of younger children to identify variables associated with the requirement for GA. RESULTS: The mean age of the overall sample (798 children) and the subset of children <8 years (124 children) were 11.7±3.7 and 5.5±1.3 years, respectively. In both groups, children who required GA were significantly younger than those who did not (p<0.001). No gender differences were observed. Children who required GA scored higher on the checklist compared to those who did not in both groups (p<0.001). The diagnostic accuracy of the checklist was found to be good (area under the curve [AUC]=0.97 for both groups), with a suggested cut-off score of 4. Intraclass correlation coefficient of the ratings by two independent individuals was 0.78. CONCLUSION: The child assessment checklist was useful in identifying GA requirement in children undergoing MRI and can be administered by non-medical staff with good inter-rater reliability.

Progression from selective to general involvement of hippocampal subfields in schizophrenia.

Volume deficits of the hippocampus in schizophrenia have been consistently reported. However, the hippocampus is anatomically heterogeneous; it remains unclear whether certain portions of the hippocampus are affected more than others in schizophrenia. In this study, we aimed to determine whether volume deficits in schizophrenia are confined to specific subfields of the hippocampus and to measure the subfield volume trajectories over the course of the illness. Magnetic resonance imaging scans were obtained from Data set 1: 155 patients with schizophrenia (mean duration of illness of 7 years) and 79 healthy controls, and Data set 2: an independent cohort of 46 schizophrenia patients (mean duration of illness of 18 years) and 46 healthy controls. In addition, follow-up scans were collected for a subset of Data set 1. A novel, automated method based on an atlas constructed from ultra-high resolution, post-mortem hippocampal tissue was used to label seven hippocampal subfields. Significant cross-sectional volume deficits in the CA1, but not of the other subfields, were found in the schizophrenia patients of Data set 1. However, diffuse cross-sectional volume deficits across all subfields were found in the more chronic and ill schizophrenia patients of Data set 2. Consistent with this pattern, the longitudinal analysis of Data set 1 revealed progressive illness-related volume loss (~2-6% per year) that extended beyond CA1 to all of the other subfields. This decline in volume correlated with symptomatic worsening. Overall, these findings provide converging evidence for early atrophy of CA1 in schizophrenia, with extension to other hippocampal subfields and accompanying clinical sequelae over time.

Impact of duration of untreated psychosis and premorbid intelligence on cognitive functioning in patients with first-episode schizophrenia.

BACKGROUND: The neurotoxic hypothesis suggests that psychosis is toxic to the brain leading to clinical consequences. In this study, we hypothesized that a longer duration of untreated psychosis (DUP) in first episode schizophrenia (FES) patients is associated with poorer cognitive functioning, and that higher premorbid intelligence buffers against DUP-related cognitive impairment. METHOD: Eighty-one FES patients completed a neuropsychological battery, the Brief Assessment of Cognition in Schizophrenia (BACS). Composite scores of the BACS, which were normalized to a matched healthy control of seventy-three subjects, were used as an index of general cognition. A median split using the Wide Range Achievement Test-Reading Test scores was used to divide the patients into low versus high premorbid IQ groups. Hierarchical linear regression was performed to examine predictors of general cognition, including DUP. RESULTS: Longer DUP was found to be a significant predictor of poorer general cognition. In addition, DUP predicted general cognition in the low premorbid IQ group but not in the high premorbid IQ group. CONCLUSIONS: Our findings demonstrate that longer DUP in FES patients is associated with worse cognitive scores, and that this association is more pronounced in a subgroup of patients who have lower premorbid intelligence. Our results suggest the importance of earlier identification and management of patients with low premorbid IQ, given that their cognition may be more vulnerable to the toxicity of psychosis.

Informed consent for human genetic and genomic studies: a systematic review.

As genetic and genomic studies grow in scale, there are ethical concerns related to the collection and use of genetic information. The emergence of large public databases potentially redefine the terms of participation in genetic and genomic research, and suggests the changing application of traditional ethical principles such as privacy or consent. For this study, we wanted to see whether such developments are reflected in the informed consent processes in human genetic and genomic studies. Therefore, we performed a systematic review of the empirical studies that examined informed consent involving large genetic databases in human genetic and genomic studies, grouped the identified issues related to the different stakeholders (including subjects, researchers, and institutional review boards) and discussed the limitations and implications of these findings. Major themes related to the place of bioethical considerations, procured tissues, people involved, process of informed consent and study procedures. Frequently raised issues included confidentiality of participants, documentation of informed consent, public attitudes, future use of participant samples or data, and disclosure of results. Awareness and attention to these bioethical issues as well as assiduousness in managing these concerns in genetic/genomic research would further strengthen and safeguard the rights, safety and well-being of genetic research participants.

Increased body mass index makes an impact on brain white-matter integrity in adults with remitted first-episode mania.

BACKGROUND: Obesity is increasingly prevalent in bipolar disorder (BD) but data about the impact of elevated body mass index (BMI) on brain white-matter integrity in BD are sparse. Based on extant literature largely from structural magnetic resonance imaging (MRI) studies, we hypothesize that increased BMI is associated with decreased fractional anisotropy (FA) in the frontal, temporal, parietal and occipital brain regions early in the course of BD. METHOD: A total of 26 euthymic adults (12 normal weight and 14 overweight/obese) with remitted first-episode mania (FEM) and 28 controls (13 normal weight and 15 overweight/obese) matched for age, handedness and years of education underwent structural MRI and diffusion tensor imaging scans. RESULTS: There are significant effects of diagnosis by BMI interactions observed especially in the right parietal lobe (adjusted F(1,48) = 5.02, p = 0.030), occipital lobe (adjusted F(1,48) = 10.30, p = 0.002) and temporal lobe (adjusted F(1,48) = 7.92, p = 0.007). Specifically, decreased FA is found in the right parietal (F(1,48) = 5.864, p = 0.023) and occipital lobes (F(1,48) = 4.397, p = 0.047) within overweight/obese patients compared with normal-weight patients with FEM. Compared with overweight/obese controls, decreased FA is observed in right parietal (F(1,48) = 6.708, p = 0.015), temporal (F(1,48) = 10.751, p = 0.003) and occipital (F(1,48) = 9.531, p = 0.005) regions in overweight/obese patients with FEM. CONCLUSIONS: Our findings suggest that increased BMI affects temporo-parietal-occipital brain white-matter integrity in FEM. This highlights the need to further elucidate the relationship between obesity and other neural substrates (including subcortical changes) in BD which may clarify brain circuits subserving the association between obesity and clinical outcomes in BD.

Performance of nurses in the Department of Health as service providers for a cervical screening programme.

A territory-wide cervical screening programme was launched in Hong Kong in March 2004. Since 2002, 160 nurses from the Department of Health's Maternal and Child Health Centres have completed the training necessary to carry out the screening procedures. A clinical audit of their performance was carried out between 2002 and 2004. A customer satisfaction survey revealed that 94% of respondents agreed or strongly agreed that they were satisfied with the cervical smear procedure performed by nurses. Since January 2003, all routine cervical screening tests at Maternal and Child Health Centres have been performed by nurses. The mean time required to complete a test is 7 minutes. The mean unsatisfactory smear rate for the year 2003 was 1.3%, well below the benchmark of 5% set by the Working Party on Quality Assurance of the Cervical Screening Task Force. The results of this survey confirm that nurses at Maternal and Child Health Centres are highly effective and efficient at taking smears and that this is well accepted by clients.

NMR studies of a novel calcium, phosphate and fluoride delivery vehicle-alpha(S1)-casein(59-79) by stabilized amorphous calcium fluoride phosphate nanocomplexes.

The repair of early tooth enamel lesions has been recently demonstrated by tryptic phosphopeptides derived from milk caseins that associate with amorphous calcium phosphate (ACP) forming stable complexes. These casein phosphopeptides (CPP), containing the cluster sequence-Ser(P)-Ser(P)-Ser(P)-Glu-Glu-, form calcium phosphate delivery vehicles that retard enamel demineralization and promote remineralization. Recently, we have shown that these peptides also stabilize calcium fluoride phosphate as soluble complexes. These complexes designated CPP-ACFP, have the potential to provide superior clinical efficacy in preventing dental caries and treating and repairing early stages of disease. In an approach to determine the ultrastructure of the casein phosphopeptide-amorphous calcium fluoride phosphate complexes, we have studied the structure of the predominant peptide alpha(S1)-CN(59-79) bound to ACFP using nuclear magnetic resonance (NMR) spectroscopy and X-ray diffraction. The alpha(S1)-CN(59-79) peptide stabilized calcium fluoride phosphate as amorphous nanocomplexes with a hydrodynamic radius of 2.12+/-0.26 nm. The nanocomplexes exhibited stoichiometry of one peptide to 15 calcium, nine phosphate and three fluoride ions. Sequence-specific resonance assignments were determined for the peptide alpha(S1)-CN(59-79) complexed to the ACFP. The secondary structure of the peptide alpha(S1)-CN(59-79) was characterized by sequential (i, i+1), medium-range (i, i+2) nOes and H alpha chemical shifts. The spectral data were compared with that of the peptide alpha(S1)-CN(59-79) bound to calcium ions, revealing that the structurally significant secondary NH and alpha-chemical shifts were similar.

Modular subdivisions of dolphin insular cortex: does evolutionary history repeat itself?

The structural organization of the insular cortex in the bottlenose dolphin was investigated by examining Nissl- and myelin-stained tissue that was sectioned coronally and tangentially. An uneven distribution of cell clusters that coincided with myelin-light zones was observed in layer II. When the present observations were compared to descriptions of modules in other animals, we found that the range of module size is restricted, while the size of the brain, particularly the neocortex, varies dramatically. Indeed, despite the tremendous expansion of the cetacean neocortex, the size of the modules in the insular cortex is similar to that described for small-brained mammals like the mouse, suggesting that module size is evolutionarily stable across species. Selection for optimal-size processing units, in terms of the lengths of connections within and between them, is a likely source of this stability.

Beneficial hemodynamic effects of intravenous terbutaline in patients with severe heart failure.

The hemodynamic effects of terbutaline infusion at rates of 0.15, 0.3, and 0.45 micrograms/kg/min were studied and compared in eight patients with severe heart failure. Terbutaline infusion at 0.15 micrograms/kg/min infusion produced insignificant effects at 30 minutes. At 0.3 micrograms/kg/min infusion highly significant beneficial hemodynamic effects were observed: at 60 minutes cardiac index increased from 1.79 +/- 0.38 to 3.60 +/- 0.96 (mean +/- SD) L/min/m2 (p less than 0.0001) and stroke volume index increased from 20.1 +/- 6.2 to 36.7 +/- 13.1 ml/beat/m2 (p less than 0.0001); mean pulmonary artery wedge pressure fell from 27.5 +/0- 5.5 to 18.5 +/- 5.7 mm Hg (p less than 0.0001); systemic vascular resistance fell from 2624 +/- 586 to 1455 +/- 500 dynes . sec . cm-5/m2 (p less than 0.0001); and pulmonary vascular resistance fell from 248 +/- 84 to 150 +/- 70 dynes . sec . cm-5/m2 (p less than 0.0005). Mean arterial pressure and O2 uptake did not change significantly; however, mean heart rate increased from 93.4 +/- 22 to 103.1 +/- 26 bpm (p less than 0.005) and plasma potassium fell from 3.86 +/- 0.14 to 3.12 +/ 0.23 mEq/L (p less than 0.05). The 0.45 micrograms/kg/min infusion at 30 minutes produced no greater hemodynamic changes than that from 0.3 micrograms/kg/min. Our study suggests that intravenous terbutaline produces beneficial effects and may be useful in the acute management of severe heart failure.