Lowering mortality risk in CR-HvKP infection in intestinal immunohistological and microbiota restoration.

Gut damage during carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-HvKP) infection is associated with a death risk. Understanding the mechanisms by which CR-HvKP causes intestinal damage and gut microbiota alteration, and the impact on immunity, is crucial for developing therapeutic strategies. This study investigated if gastrointestinal tract damage and disruption of gut microbiota induced by CR-HvKP infection undermined host immunity and facilitated multi-organ invasion of CR-HvKP; whether the therapeutic value of the rifampicin (RIF) and zidovudine (ZDV) combination was attributed to their ability to repair damages and restore host immunity was determined. A sepsis model was utilized to assess the intestinal pathological changes. Metagenomic analysis was performed to characterize the alteration of gut microbiota. The effects of the RIF and ZDV on suppressing inflammatory responses and improving immune functions and gut microbiota were evaluated by immunopathological and transcriptomic analyses. Rapid colonic damage occurred upon activation of the inflammation signaling pathways during lethal infections. Gut inflammation compromised host innate immunity and led to a significant decrease in probiotics abundance, including Bifidobacterium and Lactobacillus. Treatment with combination drugs significantly attenuated the inflammatory response, up-regulated immune cell differentiation signaling pathways, and promoted the abundance of Bifidobacterium (33.40 %). Consistently, supplementation of Bifidobacterium alone delayed the death in sepsis model. Gut inflammation and disrupted microbiota are key disease features of CR-HvKP infection but can be reversed by the RIF and ZDV drug combination. The finding that these drugs can restore host immunity through multiple mechanisms is novel and deserves further investigation of their clinical application potential.

Fragment-based drug discovery for disorders of the central nervous system: designing better drugs piece by piece.

Fragment-based drug discovery (FBDD) has emerged as a powerful strategy to confront the challenges faced by conventional drug development approaches, particularly in the context of central nervous system (CNS) disorders. FBDD involves the screening of libraries that comprise thousands of small molecular fragments, each no greater than 300 Da in size. Unlike the generally larger molecules from high-throughput screening that limit customisation, fragments offer a more strategic starting point. These fragments are inherently compact, providing a strong foundation with good binding affinity for the development of drug candidates. The minimal elaboration required to transition the hit into a drug-like molecule is not only accelerated, but also it allows for precise modifications to enhance both their activity and pharmacokinetic properties. This shift towards a fragment-centric approach has seen commercial success and holds considerable promise in the continued streamlining of the drug discovery and development process. In this review, we highlight how FBDD can be integrated into the CNS drug discovery process to enhance the exploration of a target. Furthermore, we provide recent examples where FBDD has been an integral component in CNS drug discovery programs, enabling the improvement of pharmacokinetic properties that have previously proven challenging. The FBDD optimisation process provides a systematic approach to explore this vast chemical space, facilitating the discovery and design of compounds piece by piece that are capable of modulating crucial CNS targets.

Molecular epidemiology and clinical impact of Klebsiella spp. causing bloodstream infections in Hong Kong.

BACKGROUND: The epidemiological features of the Klebsiella pneumoniae causing bloodstream infections in Hong Kong and their potential threats to human health remained unknown. METHODS: K. pneumoniae strains collected from four hospitals in Hong Kong during the period of 2009-2018 were subjected to molecular typing, string test, antimicrobial susceptibility testing, whole genome sequencing and analysis. Clinical data of patients from whom these strains were isolated were analyzed retrospectively using univariate and multivariate logistic regression approaches. FINDINGS: The 240 Klebsiella spp. strains belonged to 123 different STs and 63 different capsule loci (KLs), with KL1 and KL2 being the major type. 86 out of 212 BSI-KP (40.6%) carried at least one of the virulence genes iuc, iro, rmpA or rmpA2. Virulence plasmid correlated well with the string test positive result, yet 8 strains without rmp genes were also hypermucoviscous, which was due to wzc mutation. The mortality rate of bloodstream infection patients was 43.0%. Univariant analysis showed that factors including renal replacement therapy (FDR adjusted p = 0.0007), mechanical ventilation (FDR adjusted p < 0.0001) and respiratory sepsis (FDR adjusted p < 0.0001) were found to pose the highest risk of death upon infection by Klebsiella spp. INTERPRETATION: This study revealed the high mortality rate and risk factors associated with bloodstream infections caused by K. pneumoniae in Hong Kong, which warrants immediate action to develop effective solution to tackle this problem. FUNDING: Theme Based Research Scheme (T11-104/22-R), Research Impact Fund (R5011-18 F) and Postdoctoral Fellowship (PDFS2223-1S09).

A Longitudinal Study of Physical Activity and Personality in the Wellbeing of Older Adults.

Objective: This study examines the interactions of physical activity and personality traits in the subjective wellbeing (SWB) of older adults. Methods: 520 Scottish participants (262 male; 258 female) completed self-reported surveys measuring their level of physical activity, personality, and SWB in 2011-2013 (mean age = 76.23 ± .68) and in 2014-2016 (mean age = 79.31 ± .62). Results: While all of the Big Five personality traits predicted SWB across the 3-year period in the expected direction, neither physical activity nor its joint effect with any of the personality traits was a significant predictor of subsequent SWB. Discussion: Further research on older adults with higher variation in age, exercise level, and cultural background is needed to disentangle how physical activity and personality influence SWB.

Factors associated with latino sexual minority men's likelihood and motivation for obtaining a COVID-19 vaccine: a mixed-methods study.

Minoritized communities are underreached by biomedical interventions, such as the COVID-19 vaccine. This mixed-methods study identified factors associated with vaccine likelihood (VL) and uptake (VU) among 187 Latino sexual minority men (LSMM) in South Florida. Regression models with LASSO variable selection and Classification and Regression Trees (CART) assessed determinants of VL and VU while open-ended questions were evaluated using thematic content analysis. VL (range 1-7; M = 6.00, SD = 1.84) and VU (63.6%) was high. LASSO modeling identified being insured, worrying about others, fear of transmitting COVID-19, and financial stress as the most influential factors for VL; working remotely from home was important for VU. Time (weeks) since addition of COVID-19 vaccination-related questions (December 2nd, 2020) was associated with both outcomes across both modeling techniques. Convergence between data suggests capitalizing on altruistic motivations and improving accessibility to vaccine campaigns are valuable assets to increase LSMM's vaccine confidence.

A Siderophore-Encoding Plasmid Encodes High-Level Virulence in Escherichia coli.

A plasmid that harbored the virulence factors highly like those of the virulence plasmid commonly found in clinical hypervirulent Klebsiella pneumoniae strains was detected in a foodborne Escherichia coli strain EC1108 and designated p1108-IncFIB. This virulent-like plasmid was found to be common in E. coli from various sources. To understand the contribution of this plasmid to the virulence of E. coli, plasmid p1108-IncFIB in strain EC1108 was first cured to generate strain EC1108-PC. The virulence plasmid p15WZ-82_Vir in Klebsiella pneumoniae strain 15WZ-82 was then transmitted to EC1108-PC to produce the transconjugant, EC1108-PC-TC to assess the contribution of this virulence plasmid to the virulence level of E. coli. During the process of conjugation, p15WZ-82_Vir was found to be evolved into p15WZ-82_int, which underwent homologous recombination with a plasmid encoding a carbapenemase gene, blaNDM-1, p1108-NDM, in EC1108-PC. Comparison between the level of virulence in the EC1108, EC1108-PC-TC, and EC1108-PC through serum and macrophage resistance assay, as well as animal experiments, confirmed that plasmid p1108-IncFIB encoded a high level of virulence in E. coli, yet the fusion plasmid derived from p15WZ-82_Vir did not encode virulence but instead imposed a high fitness cost in the E. coli strain EC1108-PC-TC. These findings indicate that E. coli strains carrying the virulence plasmid p1108-IncFIB in multidrug-resistant (MDR) strains may also impose serious public health threats like that of hypervirulent Klebsiella pneumoniae strains harboring the p15WZ-82_Vir plasmid. IMPORTANCE Acquisition of pLVPK-like virulence plasmid by Klebsiella pneumoniae converts it to hypervirulent K. pneumoniae (HvKP), which has become one of the most important clinical bacterial pathogens. The potential of transmission of this virulence plasmid and its contribution to the virulence of other Enterobacteriaceae, such as E. coli, are not clear yet. In this study, we showed that pLVPK-like virulence plasmid exhibited fitness costs and did not contribute to the virulence in E. coli. However, we identified a novel virulence plasmid, p1108-IncFIB, that encodes similar siderophore genes as those of pLVPK from a foodborne E. coli strain and showed that p1108-IncFIB encoded a high level of virulence in E. coli. BLAST of E. coli genomes from GenBank showed that these siderophore genes were widespread in clinical E. coli strains. Further studies are warranted to understand the impact of this plasmid in the control of clinical infections caused by E. coli.

Transcriptional Regulation and Functional Characterization of the Plasmid-Borne oqxAB Genes in Salmonella Typhimurium.

Coexistence of oqxAB and aac(6')-Ib-cr is often associated with the expression of fluoroquinolone resistance in Salmonella. The actual role of the plasmid-borne oqxAB gene and its regulatory mechanism compared to its chromosomally encoded counterpart in Klebsiella pneumoniae remain unclear We found that cloning of oqxAB gene only or chromosomally encoded oqxABR (ABRc) locus did not lead to an increase of ciprofloxacin (CIP) minimum inhibitory concentration (MIC) in S. Typhimurium, while cloning of the plasmid-encoded oqxABR (ABRp) locus led to a 4-fold increase in CIP MIC, reaching 0.0065 µg/mL. The co-carriage of these constructs with aac(6')-Ib-cr further increased the CIP MIC to 0.25 µg/mL in S. Typhimurium carrying aac(6')-Ib-cr and ABRp. Analysis of the transcription start site sequences showed that the expression level of suppressor protein gene, oqxR, in strains carrying ABRp was lower than that of its chromosomal counterpart due to the truncated promoter region in ABRp. The lower expression of OqxR in ABRp led to the overexpression of OqxAB, which elevated CIP MIC and exhibited a synergistic antimicrobial effect with the aac(6')-Ib-cr gene product to confer intermediate CIP (MIC = 0.25 µg/mL) in S. Typhimurium. Global transcriptional regulators in S. Typhimurium did not seem to play a role in regulating the plasmid-borne oqxAB genes. In conclusion, findings in this work showed that neither aac(6')-Ib-cr nor oqxABRp, but the combination of both genes, could mediate intermediated resistance to fluoroquinolone in Salmonella. The truncated promoter region in the oqxR gene of the plasmid-encoded locus led to the constituted expression of oqxAB genes. IMPORTANCE The transferable mechanisms of quinolone resistance (TMQR) gene, oqxAB, has been widely detected in Salmonella and is commonly associated with aac(6')-Ib-cr. It is thought to be associated with fluoroquinolone resistance, while its ancestor gene from K. pneumoniae is not. This study evaluated the actual role of the plasmid-borne oqxAB genes in Salmonella and showed that it was not able to mediate intermediated resistance to fluoroquinolone and only did so when it coexisted with aac(6')-Ib-cr. Chromosomally encoded oqxABRc from K. pneumoniae was not able to mediate enhanced CIP MIC due to tight regulation by the suppressor oqxR. However, plasmid-encoded oqxABRp enabled oqxAB to be expressed constitutionally due to the truncated promoter region of oqxR, leading to lower expression of the suppressor oqxR. This study clarified the roles of oqxAB and aac(6')-Ib-cr in mediating fluoroquinolone resistance in Salmonella and provides insights into the regulation of plasmid-encoded TMQR determinant, oqxAB.

A longitudinal examination of tablet self-management technology acceptance by patients with chronic diseases: Integrating perceived hand function, perceived visual function, and perceived home space adequacy with the TAM and TPB.

BACKGROUND: Health information technologies (HITs) are increasingly being used to support the self-management of chronic diseases. However, patients' initial or continued acceptance of such technologies is not always achieved. OBJECTIVE: The aim of this study was to develop a theory-driven HIT acceptance model to examine factors affecting acceptance of HIT (measured by behavioral intention; BI) for disease self-management among patients with chronic diseases, in which we also focused on three additional, previously unexplored factors related to perceived hand function (PHF), perceived visual function (PVF), and perceived space adequacy (PSA) and a longitudinal scrutinization of changes in the effects of these factors on acceptance over time. METHODS: The theoretical basis of our acceptance model was drawn from the technology acceptance model and the theory of planned behavior. The model was further extended by including patients' PHF, PVF (related to patients with chronic diseases who are mostly elderly), and PSA (related to the patients' home environment). The model was tested in the context of type 2 diabetes and hypertension self-management via a touchscreen tablet-based system over a 24-week period. A questionnaire was administered at four time points (baseline and 8, 16, and 24 weeks after implementation) to collect data from 151 patients with coexisting type 2 diabetes and hypertension. We tested the model at each time point using partial least squares structural equation modeling. RESULTS: Perceived usefulness of the self-management system influenced BI directly at 8 and 24 weeks and indirectly at 8, 16, and 24 weeks. Perceived ease of use indirectly affected BI at 8, 16, and 24 weeks. Attitude directly affected BI at 8, 16, and 24 weeks. Perceived behavioral control directly influenced BI at baseline and 8 and 16 weeks. Subjective norms indirectly influenced BI at 8, 16, and 24 weeks. PHF and PVF indirectly influenced BI over the entire study period. PSA influenced BI directly at 16 weeks and indirectly at 8, 16, and 24 weeks. CONCLUSION: The effects of the proposed factors in our model on patient-focused HIT acceptance changed over a longer time period, emphasizing the importance of further investigation of the longitudinal mechanisms influencing technology acceptance behavior. It is recommended that healthcare practitioners consider such changes when implementing comparable technologies. Moreover, beyond technology attributes, the characteristics, needs, and limitations of older adults and elderly patient users and their home environments should also be considered in the design and implementation of patient-focused HIT systems for chronic disease self-management at home.

RUVBL1/2 Complex Regulates Pro-Inflammatory Responses in Macrophages via Regulating Histone H3K4 Trimethylation.

Macrophages play an important role in the host defense mechanism. In response to infection, macrophages activate a genetic program of pro-inflammatory response to kill any invading pathogen, and initiate an adaptive immune response. We have identified RUVBL2 - an ATP-binding protein belonging to the AAA+ (ATPase associated with diverse cellular activities) superfamily of ATPases - as a novel regulator in pro-inflammatory response of macrophages. Gene knockdown of Ruvbl2, or pharmacological inhibition of RUVBL1/2 activity, compromises type-2 nitric oxide synthase (Nos2) gene expression, nitric oxide production and anti-bacterial activity of mouse macrophages in response to lipopolysaccharides (LPS). RUVBL1/2 inhibitor similarly inhibits pro-inflammatory response in human monocytes, suggesting functional conservation of RUVBL1/2 in humans. Transcriptome analysis further revealed that major LPS-induced pro-inflammatory pathways in macrophages are regulated in a RUVBL1/2-dependent manner. Furthermore, RUVBL1/2 inhibition significantly reduced the level of histone H3K4me3 at the promoter region of Nos2 and Il6, two prototypical pro-inflammatory genes, and diminished the recruitment of NF-kappaB to the corresponding enhancers. Our study reveals RUVBL1/2 as an integral component of macrophage pro-inflammatory responses through epigenetic regulations, and the therapeutic potentials of RUVBL1/2 inhibitors in the treatment of diseases caused by aberrant activation of pro-inflammatory pathways.

Randomised controlled trial: Can topical timolol maleate prevent complications for small superficial infantile haemangiomata in high-risk areas?

BACKGROUND: To define the role of topical timolol maleate (TTM) in the treatment of infantile haemangiomata (IH). METHODS: In this single-centre randomised controlled trial, we included all <1-year-old infants within a 13-month period presenting with small (<2 cm) superficial IH located at high-risk areas (i.e. tip of ears, tip of nose, eyelids, acral areas, facial areas, scalp, neck, buttocks, perineum and axilla). Patients either received 12 months of 0.5% TTM solution (study group) or watchful waiting (control group). The primary outcome was IH with development of complications that required additional interventions. The secondary outcomes included side effects of TTM and change in IH size. RESULTS: Forty-two children were eligible to the study. Patients who received TTM were noted to have significantly fewer complications than the control group (4.2% versus 29%, odds ratio 9.58 [95% confidence interval: 1.01-91.62], p = 0.04). Mean IH volume percentage reduction was significantly more for the TTM group and no-TTM group at 3, 6 and 12 months. CONCLUSIONS: TTM is an effective and safe treatment option to reduce complications, IH volume and the need for further intervention for infants with small superficial IH located at high-risk areas. IMPACT: There is a lack of reliable signs to predict ulceration, disfigurement and other complications for high-risk IH. Treatment options range from watchful waiting to early systemic treatment, with TTM a novel and promising treatment. The exact role of TTM remains unanswered due to a lack of evidence-based research. TTM is effective and safe for infants with superficial IH of <2 cm in high-risk areas. Early TTM use on IH can reduce complications, IH volume and the need for further treatment.

Over-Expression of ISAba1-Linked Intrinsic and Exogenously Acquired OXA Type Carbapenem-Hydrolyzing-Class D-ß-Lactamase-Encoding Genes Is Key Mechanism Underlying Carbapenem Resistance in Acinetobacter baumannii.

Acinetobacter baumannii is an important clinical pathogen which often causes fatal infections among seriously ill patients. Treatment options for managing infections caused by this organism have become limited as a result of emergence of carbapenem resistant strains. In the current study, whole genome sequencing, gene expression studies and enzyme kinetics analyses were performed to investigate the underlying carbapenem resistance mechanisms in fourteen clinical A. baumannii strains isolated from two hospitals, one each in Hong Kong and Henan Province, People's Republic of China. A large majority of the A. baumannii strains (11/14) were found to belong to the International Clone II (IC-II), among which six were ST208. Twelve of these strains were carbapenem resistant and found to either harbor bla OXA- 23/bla OXA- 72, or exhibit over-expression of the bla OXA- 51 gene upon ISAba1 insertion. Enzymatic assay confirmed that the OXA variants, including those of bla OXA - 51, exhibited strong carbapenem-degrading activities. In terms of other intrinsic mechanisms, a weak correlation was observed between reduced production of outer membrane porin CarO/expression resistance-nodulation-division (RND) efflux AdeB and phenotypic resistance. This finding implied that over-production of carbapenem-hydrolyzing-class D-ß-lactamases (CHDLs), including the intrinsic bla OXA- 51 gene and the acquired bla OXA- 23 and bla OXA- 24 elements, is the key mechanism of carbapenem resistance in A. baumannii. This view is confirmed by testing the effect of NaCl, a known bla OXA inhibitor, which was found to cause reduction in carbapenem MIC by twofolds to eightfolds, suggesting that inhibiting OXA type carbapenemases represents the most effective strategy to control phenotypic carbapenem resistance in A. baumannii.

Accurate Age Determination for Adolescents Using Magnetic Resonance Imaging of the Hand and Wrist with an Artificial Neural Network-Based Approach.

This study proposes an accurate method in assessing chronological age of the adolescents using a machine learning approach using MRI images. We also examined the value of MRI with Tanner-Whitehouse 3 (TW3) method in assessing skeletal maturity. Seventy-nine 12-17-year-old healthy Hong Kong Chinese adolescents were recruited. The left hand and wrist region were scanned by a dedicated skeletal MRI scanner. T1-weighted three-dimensional coronal view images for the left hand and wrist region were acquired. Independent maturity indicators such as subject body height, body weight, bone marrow composition intensity quantified by MRI, and TW3 skeletal age were included for artificial neural network (ANN) analysis. Our results indicated that the skeletal age was generally underestimated using TW3 method, and significant difference (p < 0.05) was noted for skeletal age with chronological age for female category and at later stage of adolescence (15 to 17 years old) in both genders. In our proposed machine learning approach, ages determined by ANN method agreed well with chronological age (p > 0.05).The machine learning approach using ANN method was about 10-fold more accurate than the TW3 method using MRI alone. It offers a more objective and accurate solution for prospective chronological maturity assessment for adolescents.

Interaction of Physical Activity and Personality in the Subjective Wellbeing of Older Adults in Hong Kong and the United Kingdom.

Subjective wellbeing (SWB) has been widely accepted as one of the most important elements of successful ageing. The present study explores the impact of two well-established correlates of SWB: physical activity and personality. Physical activity and each of the Big Five personality traits are consistent predictors of SWB, but there has been little research on whether certain personality traits enhance or hinder the psychological benefits of physical activity in older adults. This study examines the interactions of leisure-time physical activity and personality traits on SWB, and whether such interactions vary between older adults in Hong Kong (HK) and older adults in the United Kingdom (UK). Altogether, 349 participants (178 HK, 171 UK; 157 males, 192 female) aged 50 years or above (mean age = 61.84 ± 8.46 years old) completed an online assessment of: (1) leisure-time physical activity (Godin⁻Shephard Leisure-Time Physical Activity Questionnaire); (2) personality traits (Big Five Inventory); and (3) SWB (Satisfaction with Life Scale, Positive and Negative Affect Schedule). Results showed that agreeableness, conscientiousness, extraversion, neuroticism, openness to experience, and physical activity were all significantly related to SWB in the expected direction. The relationship between physical activity and SWB was moderated by extraversion and by openness to experience: higher levels of these two traits significantly enhanced the relationship. None of the interactions varied between the HK and UK samples. The expected negative relationship between neuroticism and SWB, however, was significantly stronger in the UK sample than in the HK sample. The findings of the present study indicate that personality needs to be considered when promoting and providing physical activity for older adults, although more research is needed to further explore how this can work effectively.

Increase in Weight in Low Birth Weight and Very Low Birth Weight Infants Fed Fortified Breast Milk versus Formula Milk: A Retrospective Cohort Study.

There has been a dramatic rise in preterm births in developed countries owing to changes in clinical practices and greater use of assisted reproductive techniques. However, few studies have examined the growth and outcomes of preterm infants according to the type of feeding (with fortified breast milk or formula). The purpose of this study was to examine the effect of breast milk feedings and formula on the growth and short-term outcomes of preterm infants in Hong Kong. In a single-center retrospective cohort study, we included 642 preterm infants at gestational age <37 weeks with birth weights <2200 g. According to World Health Organization criteria, 466 were classified as low birth weight (LBW) infants (≥1500 g and <2200 g) and 176 were classified as very low birth weight (VLBW) infants (<1500 g). The mothers of approximately 80% of VLBW infants and 60% LBW infants initiated breast milk feeding. When compared with no breast milk intake, LBW infants that received breast milk were significantly more likely to have growth z-scores closer to the median of the reference population on admission and experienced slower weight gain from birth to discharge. When breast milk was categorized by percent of total enteral intake, significant differences were seen among LBW infants, with lower percentages of small-for-gestational-age (SGA) status at discharge with increased proportions of breast milk intake. Our results suggest that LBW infants fed breast milk had better growth z-scores and lower SGA status at discharge compared with those predominately fed preterm formula.

Thermal stability and kinetic constants for 129 variants of a family 1 glycoside hydrolase reveal that enzyme activity and stability can be separately designed.

Accurate modeling of enzyme activity and stability is an important goal of the protein engineering community. However, studies seeking to evaluate current progress are limited by small data sets of quantitative kinetic constants and thermal stability measurements. Here, we report quantitative measurements of soluble protein expression in E. coli, thermal stability, and Michaelis-Menten constants (kcat, KM, and kcat/KM) for 129 designed mutants of a glycoside hydrolase. Statistical analyses reveal that functional Tm is independent of kcat, KM, and kcat/KM in this system, illustrating that an individual mutation can modulate these functional parameters independently. In addition, this data set is used to evaluate computational predictions of protein stability using the established Rosetta and FoldX algorithms. Predictions for both are found to correlate only weakly with experimental measurements, suggesting improvements are needed in the underlying algorithms.

The neonatal resuscitation algorithm organized cart is more efficient than the airway-breathing-circulation organized drawer: a crossover randomized control trial.

INTRODUCTION: Although there is consensus on the resuscitation of newborns, there is no standardization on how resuscitation equipment should be organized. This might lead to difficulty and inefficiency in retrieval of the right equipment during resuscitation. The neonatal resuscitation carts organized in accordance with the American Academy of Pediatrics (AAP) Neonatal Resuscitation Program (NRP) algorithm might result in more efficient retrieval of resuscitation equipment. OBJECTIVES: To compare user preference and lengths of time required to retrieve standard resuscitation equipment from an NRP Cart versus a generic storage drawer. STUDY DESIGN: A prospective, randomized, controlled, and crossover trial was conducted during simulation-based NRP provider courses in the Accident & Emergency Training Centre from September to October 2013. The mean time of accurate equipment retrieval and ease of use, which was rated by the participants using a five-point Likert scale (1=most difficult, 5=easiest to use), were compared using the Wilcoxon signed-rank test because of right skew. RESULTS: A total of 55 individuals participated in this study. The mean length of time required for equipment retrieval from the NRP Cart was significantly less than that from the drawer (Z=-3.90, P<0.01, median=36.23 s, interquartile range=97 s). In general, the NRP Cart was 32% faster than the drawer when extensive resuscitation equipment was required. All the participants rated the NRP Cart as easier to use than the drawer, with a median score of 4 for NRP Cart and 3 for the drawer (Z=-4.10, P<0.01, interquartile range=2). CONCLUSION: The NRP Cart was superior to the generic drawer in terms of the speed of equipment retrieval and user acceptability.

A home-based program of transcutaneous electrical nerve stimulation and task-related trunk training improves trunk control in patients with stroke: a randomized controlled clinical trial.

BACKGROUND: Impaired trunk motor control is common after stroke. Combining transcutaneous electrical nerve stimulation (TENS) with task-related trunk training (TRTT) has been shown to enhance the recovery of lower limb motor function. OBJECTIVE: This study investigated whether combining TENS with TRTT would enhance trunk control after stroke. Methods. Thirty-seven subjects with stroke were recruited into a randomized controlled clinical trial. Subjects were randomly assigned to any one of the three 6-week home-based training groups: (1) TENS + TRTT, (2) placebo TENS + TRTT, or (3) control without active training. The outcome measures included isometric peak trunk flexion torque and extension torque; forward seated and lateral seated reaching distance to the affected and unaffected side; and Trunk Impairment Scale (TIS) scores. All outcome measures were assessed at baseline, after 3 and 6 weeks of training, and 4 weeks after training ended at follow-up. RESULTS: Both the TENS + TRTT and the placebo-TENS + TRTT groups had significantly greater improvements in isometric peak trunk flexion torque and extension torque, lateral seated reaching distance to affected and unaffected side, and TIS score than the control group after 3 weeks of training. The TENS + TRTT group had significantly greater and earlier improvement in its mean TIS score than the other 2 groups. CONCLUSIONS: Home-based TRTT is effective for improving trunk muscle strength, sitting functional reach and trunk motor control after stroke in subjects without somatosensory deficits. The addition of TENS to the trunk augments the effectiveness of the exercise in terms of TIS scores within the first 3 weeks of training.

Dermoscopy for common skin problems in Chinese children using a novel Hong Kong-made dermoscope.

OBJECTIVE: To evaluate the dermoscopic features of common skin problems in Chinese children. DESIGN: A case series with retrospective qualitative analysis of dermoscopic features of common skin problems in Chinese children. SETTING: A regional hospital in Hong Kong. PARTICIPANTS: Dermoscopic image database, from 1 May 2013 to 31 October 2013, of 185 Chinese children (aged 0 to 18 years). RESULTS: Dermoscopic features of common paediatric skin problems in Chinese children were identified. These features corresponded with the known dermoscopic features reported in the western medical literature. New dermoscopic features were identified in café-au-lait macules. CONCLUSION: Dermoscopic features of common skin problems in Chinese children were consistent with those reported in western medical literature. Dermoscopy has a role in managing children with skin problems.

Therapeutic cloning in individual parkinsonian mice.

Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. 'Therapeutic cloning' is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response.